79C3C34C52B45572883A05D425EB0F82
Research Involving Human Subjects
https://www.bioethics-singapore.org/files/publications/reports/research-involving-human-subjects-guideline-for-irbs-full-report.pdf
http://leaux.net/URLS/ConvertAPI Text Files/698E0557CF6EA11EFA38FDF7333E287E.en.txt
Examining the file media/Synopses/698E0557CF6EA11EFA38FDF7333E287E.html:
This file was generated: 2020-12-01 07:47:25
| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Political / political affiliation
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p.000018:
p.000018: 3.15. In general, we suggest that categories for Exempted Review should be drawn from categories of
p.000018: Indirect Human Biomedical Research. By way of illustration, the following categories of Indirect Human
p.000018: Biomedical Research could be considered for Exempted Review, taking into account current practice:
p.000018:
p.000018: (a) Writing up or reporting of individual patients’ clinical results by the patients’ doctors, provided that the
p.000018: patients’ consent for procedures and interventions in clinical management have been obtained and the patients’ privacy
p.000018: protected, for example, the review of a clinical programme that includes demographic, clinical and
p.000018: outcome parameters, which are useful in the audit of the programme; or the review of a procedure or
p.000018: treatment (a surgical technique or drug treatment outcome) by a physician or surgeon, where the choice of the
p.000018: drug or technique is based on the clinical judgment of the physician or surgeon and on best
p.000018: practices and not on any randomisation procedure. Researchers who are not the attending physicians in
p.000018: the programme but wish to have access to such information should send their proposals to the IRB in
p.000018: the usual way;
p.000018:
p.000018: (b) Research using appropriately designed data escrow or other arrangements in which personal or
p.000018: other identity information is securely withheld from researchers by a third party provider of information,
p.000018: there being no possibility of researchers by themselves being able to trace or reconstruct significant
p.000018: information on the identity of subject donor;
p.000018:
p.000018: (c) Research using established commercially available cell lines or commercially available anonymous
p.000018: DNAs, RNAs and fixed tissues; and
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p.000019: HUMAN
p.000019: BIOMEDICAL RESEARCH
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p.000019: (d) The development of diagnostic tests using existing samples for test validation purposes provided
p.000019: that the necessary consent for the taking and use of the samples has been obtained.
p.000019:
p.000019: Expedited Review
p.000019:
p.000019: 3.16. Some categories of research programmes may be permitted a less formal process of review than that of a
p.000019: standard full review. For example, the Chairperson or other IRB delegate(s) (the reviewer) may be empowered to
p.000019: conduct Expedited Review.
p.000019:
p.000019: 3.17. The same principles and general considerations set out above in relation to the categories of Human Biomedical
p.000019: Research that qualifies for Exempted Review also apply to IRBs’ determination of categories permitted
p.000019: Expedited Review. Research qualifying for Expedited Review should present no more than minimal risks to research
p.000019: subjects.
p.000019:
p.000019: 3.18. By way of illustration, the following categories of Human Biomedical Research could be considered
p.000019: for Expedited Review, taking into account current practice:
p.000019:
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p.000040: ETHICS GOVERNANCE
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p.000040: Human Biomedical Research that could qualify for Exempted Review or Expedited Review, it should draw up a
p.000040: set of standard operating procedures to provide for these categories.
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p.000040: 5.79. Instead of requiring consideration by the entire IRB, the standard operating procedures may allow the
p.000040: Chairperson or his delegate(s) to make decisions on applications that qualify for Expedited Review.
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p.000041: ETHICS GOVERNANCE
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p.000041: SECTION VI: RESEARCHERS
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p.000041: 6. Researchers
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p.000041: The General Responsibilities of Researchers
p.000041:
p.000041: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethics governance of Human
p.000041: Biomedical Research. More than any other party or parties in the ethics review and governance
p.000041: process, researchers have the fullest access to the facts on which ethical judgments are to be made.
p.000041:
p.000041: 6.2. Researchers are responsible for making the threshold decisions in conceiving, designing and
p.000041: putting together a proposed research project. In these decisions, they have the most freedom to shape
p.000041: the proposed research project in a way that gives fullest consideration and respect to ethical
p.000041: considerations, always cognizant of the fact that it is the human subjects whom they study who make
p.000041: their research possible, and are therefore under an obligation to respect and to protect the subjects.
p.000041:
p.000041: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000041: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000041: judgments.
p.000041:
p.000041: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000041: aspects of the Human Biomedical Research rests with the researchers. IRBs bear the responsibility for the
p.000041: overall ethics review and approval of Human Biomedical Research programmes.
p.000041:
p.000041: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000041: responsibility that cannot be transferred or delegated to an IRB or to any party in the ethics review and
p.000041: governance process merely through the approval of a research proposal by an IRB.
p.000041:
p.000041: 6.6. By the same token, researchers remain entirely responsible for ensuring that their research complies
p.000041: with all relevant laws and legal or regulatory obligations and requirements. Ethics approval given by an IRB is not to
p.000041: be taken as an assurance or representation by the IRB of such compliance, or as an assumption of legal liabilities
p.000041: arising out of the proposed research by the IRB. In short, it is unethical for researchers to treat IRBs
p.000041: and the review process merely as “lega l insurers” or as “legal insurance”.
p.000041:
p.000041: 6.7. Researchers are primarily and ultimately responsible for making the first judgment as to whether, in
p.000041: their own professional judgment, the proposed research is ethical.
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p.000042: ETHICS GOVERNANCE
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p.000042: 6.8. Researchers should only submit to IRBs proposals that they are objectively and professionally satisfied
p.000042: are entirely ethical in all aspects and are prepared to defend them as such.
p.000042:
p.000042: 6.9. By submitting a research proposal to an IRB, researchers indicate to all involved parties that the
p.000042: proposed research is, in the researchers’ objective and professional judgement, ethical in all aspects.
p.000042:
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p.000042: researchers themselves feel that they need ethical guidance.
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p.000043: ETHICS GOVERNANCE
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p.000043: 6.14. It is important that researchers take special care to avoid any form of conflicts of interest,
p.000043: whether actual, potential, or merely an appearance of conflict as such. Where such actual, potential or apparent
p.000043: conflict arises, researchers have a duty to make a declaration of the conflict, to give full disclosure of the facts
p.000043: giving rise to such conflict and to detail the steps proposed or taken to minimise or avoid the actual or
p.000043: potential conflict of interest or the appearance of such a conflict of interest.
p.000043:
p.000043: 6.15. Researchers should not be involved in, or give the appearance of being involved in, the ethics
p.000043: review and approval process of any research project in which he or she is involved. For instance, a researcher who is a
p.000043: me mber of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000043: personally involved and make a declaration of such an interest to the IRB.
p.000043:
p.000043: 6.16. In submitting a proposal for ethics review, every researcher involved in the research project should be named
p.000043: as a party and applicant in the proposal.
p.000043:
p.000043: 6.17. For the purposes of this Section, we exclude from the definition of researcher, persons acting
p.000043: only in an administrative or support capacity and who have no independent control over the conduct of
p.000043: the research. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000043: in clinical duties.
p.000043:
p.000043:
p.000043: Principal Investigators
p.000043:
p.000043: 6.18. Where a research project involves more than one researcher, the term “investigator” refers to any
p.000043: one of the researchers generally, while the term “Principal Investigator” specifically refers to the researcher who has
p.000043: been designated to undertake the role of Principal Investigator (PI) of that research project.
p.000043:
p.000043: 6.19. If a single researcher is carrying out a research project, then he or she shall be the PI. If multiple
p.000043: researchers are carrying out a research project, then the researchers must among themselves designate a PI. The
p.000043: PI is the researcher who shall be regarded as the lead res earcher of the research project.
p.000043:
p.000043: 6.20. A research application by a group of collaborating researchers should be submitted in the name of a
p.000043: single PI and his or her collaborating researchers.
p.000043:
p.000043: 6.21. It is permissible for a research project to have more than one PI, especially for large projects, projects
p.000043: with different parts or different (but related)
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p.000044: 44
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p.000056: B-93
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p.000056: ANNEXE B
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p.000056: 5.73. It is desirable that the IRB should have the ultimate authority and responsibility for
p.000056: the ethical clearance of access to patient medical information within the institution, so that no
p.000056: patient medical information may be released for research purposes without clearance by the IRB. Such authority
p.000056: should by necessity also extend over the administrative custodians of patient medical information.
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p.000056: B-94
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p.000056: ANNEXE B
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p.000056:
p.000056: SECTION VI: RESEARCHERS
p.000056:
p.000056: 6. The Responsibilities of Researchers
p.000056:
p.000056: The general responsibilities of researchers
p.000056:
p.000056: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethical governance of clinical
p.000056: research. More than any other party or parties in the ethical review and governance process, they are in
p.000056: the position of having the fullest access to the facts on which ethical judgments are to be made.
p.000056:
p.000056: 6.2. They are responsible for making the threshold decisions in conceiving, designing and putting
p.000056: together a proposed research project. In these decisions, they have the most freedom to shape the
p.000056: proposed research project in a way that gives fullest consideration and respect to ethical considerations,
p.000056: always cognizant of the fact that it is the human subjects whom they study who make their research
p.000056: possible, and are therefore under an obligation to respect and to protect.
p.000056:
p.000056: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000056: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000056: judgments.
p.000056:
p.000056: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000056: aspects of the clinical research in question which involves human subjects rests with the
p.000056: researchers. IRBs bear the responsibility for the overall ethical review and approval of
p.000056: clinical research programmes, as explained in Recommendation 4.
p.000056:
p.000056: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000056: responsibility which is not and cannot be transferred or delegated to an IRB or any party in the ethics
p.000056: review and governance process merely through the approval of a research proposal by an IRB.
p.000056:
p.000056: 6.6. By the same token, researchers remain entirely responsible to ensure that their research complies with all
p.000056: relevant laws as well as legal or regulatory obligations and requirements. Ethical approval given by an IRB is not to
p.000056: be taken as an assurance or representation by the IRB of such compliance, or as an assumption of legal liabilities
p.000056: arising out of the proposed research by the IRB. In short, it is unethical for resear chers to treat ethical review
p.000056: boards and the review process merely as “legal insurers”, or as “legal insurance”.
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p.000056: B-95
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p.000056: ANNEXE B
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p.000056: 6.7. Researchers are primarily and ultimately responsible for making the first judgment as to whether in
p.000056: their own professional judgment, the proposed research is ethical.
p.000056:
p.000056: 6.8. Researchers should only submit to ethical review boards proposals for research which they are
p.000056: objectively and professionally satisfied are entirely ethical in all aspects, and are prepared to defend them as such.
p.000056:
p.000056: 6.9. Submission of a research proposal to an IRB by researchers amounts to a representation by the researchers to
p.000056: the IRB and to all parties involved in the ethical review and governance process that, in the
p.000056: objective professional judgment of the researchers, the proposed res earch is ethical in all aspects.
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p.000056: there is no objection to researchers submitting in good faith for
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p.000056: B-96
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p.000056: ANNEXE B
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p.000056: ethical review a research proposal that the researchers themselves feel that they need ethical guidance.
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p.000056: 6.14. As for IRBs and members of IRBs, it is important that researchers take special care to avoid
p.000056: any form of conflicts of interest, whether actual, potential, or merely an appearance of conflict as such.
p.000056: Where such actual, potential or apparent conflicts arise, researchers have a duty to make a declaration of
p.000056: the conflict, give full disclosure of the facts giving rise to such conflict, and detail the steps proposed
p.000056: or taken to minimise or avoid the actual or potential conflict of interest, or the appearance of such a
p.000056: conflict of interest.
p.000056:
p.000056: 6.15. In no case should any researcher be involved in, or give the appearance of being involved in, the ethics
p.000056: review and approval process of any research project in which he or she is involved in. For instance, a researcher who
p.000056: is a member of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000056: personally involved, and make a declaration of such an interest to the IRB.
p.000056:
p.000056: 6.16. In submitting a proposal for ethical review, every researcher involved in the research project should be
p.000056: named as a party and applicant in the proposal.
p.000056:
p.000056: 6.17. For the purposes of this Section, we exclude from the definition of researcher persons acting
p.000056: only in an administrative or support capacity, and who are under the direct supervis ion and control of
p.000056: a researcher. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000056: in clinical duties.
p.000056:
p.000056: Principal Investigators
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p.000056: 6.18. It has been the practice in the past to informally refer to all researchers invo lved in a
p.000056: research project as “Principal Investigators” or “PIs”. We think, however, that this practice causes
p.000056: confusion, especially if a large number of researchers are involved in a research project.
p.000056:
p.000056: 6.19. Where a research project involves more than one researcher, we prefer to use the term “investigator” to refer
p.000056: to any one of the researchers generally, and the term “Principal Investigator” to specifically refer to
p.000056: the investigator who has been elected (and who has accepted) the role of Principal Investigator of that
p.000056: research project.
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p.000056: 6.20. Where a research project is to be carried out by a single researcher, that researcher is the Principal
p.000056: Investigator. Where a research project is to be carried out by more than one researcher, then the
p.000056: researchers must elect
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p.000056: B-97
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p.000056: ANNEXE B
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p.000056:
p.000056: BAC: Certain research proposals may be subject to expedited review and thus a decision need not be made at
p.000056: a face-to- face meeting.
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p.000056: Special IRBs
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p.000056: IRB: In some countries, IRBs are removed from the auspices of institutions and yet some other institutions, such as
p.000056: the UK National Health Services, share IRBs. The motive is to secure the independence of IRBs from their
p.000056: appointing institutions and thereby avoid conflict of interest.
p.000056:
p.000056: However, it is the institution’s responsibility to ensure that its appointment of IRB members will not result in any
p.000056: conflict of interest. If an IRB is separated from an institution, it will not be able to familiarise itself with the
p.000056: operations of that institution. Hence, the two-tier approach is a good one.
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p.000056: E-155
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p.000056: ANNEXE E
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p.000056: However, there are commercial IRBs in the US that are independent of an institution. These IRBs have
p.000056: been mentioned in the Paper. They can be an option for us. The members of commercial IRBs are recruited
p.000056: from a large range of institutions. They do not serve on the IRB full-time and are paid about US$200 per
p.000056: protocol reviewed.
p.000056:
p.000056: BAC: A reason for the acceptance of commercial IRBs in the US is that they provide a liability shield for research
p.000056: institutions, as these IRBs are adequately insured. The concept of commercial IRBs is culturally new to Singapore and
p.000056: may not be applicable within the local context.
p.000056:
p.000056: In a small nation like Singapore, IRBs operating outside an institution will not solve issues of conflict of interest.
p.000056: Nonetheless, the BAC welcomes the idea of shared IRBs or domain-specific IRBs, which have been described in the Paper.
p.000056:
p.000056: IRB: Domain-specificity is advantageous as there will be a need for IRB members with the suitable expertise for
p.000056: evaluating specialty research protocols. Another potential problem to note with respect to the small size of
p.000056: the local medical community is the ‘rubber-stamping’ of one another’s research protocol, because most of
p.000056: members of the community recognise one another’s field of work.
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p.000056: Conclusion
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p.000056: BAC: The BAC will consider all suggestions that have been made and will try to address as many of the
p.000056: issues that have been raised. Some of the provisions in the Paper may have been misinterpreted as excessive. These
p.000056: provisions will be clarified by the BAC in its recommendations to the Government. It is
p.000056: emphasised that the provisions and recommendations issued by the BAC are only intended as general guidelines. The BAC
p.000056: thanks all participants for their time and valuable input.
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p.000056: –––––––––––––––––––––
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p.000056: E-156
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p.000056: ANNEXE F
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p.000056: SELECT REFERENCES
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p.000056: International
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Political / vulnerable
Searching for indicator vulnerable:
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p.000026: parties involved in the process of ethics governance to consider taking these ethical principles into
p.000026: account.
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p.000026: 4.17. Such principles, in addition to or in elaboration of those identified by the NMEC, include:
p.000026:
p.000026: (a) Respect for the human body, welfare and safety, and for religious and cultural perspectives and
p.000026: traditions of human subjects. We elaborated on this principle in our Human Tissue Research Report. In the
p.000026: context of a diverse society such as Singapore, researchers have an especial obligation to be sensitive
p.000026: to religious and cultural perspectives and traditions of their human subjects.
p.000026:
p.000026: (b) Respect for free and informed consent. This principle is discussed at length in our Human Stem Cell Report, our
p.000026: Human Tissue Research Report and the NMEC Report (Section 2.5). In addition, the Medicines (Clinical
p.000026: Trials) Regulations and the SGGCP recommend strict requirements regarding consent.
p.000026:
p.000026: (c) Respect for privacy and confidentiality. This is treated in detail in Section 2.6 of the NMEC Guidelines
p.000026: and again in our Human Tissue Research Report.
p.000026:
p.000026: (d) Respect for vulnerable persons. This is discussed in Sections 2.5.5 and 2.5.6 of the NMEC
p.000026: Guidelines. In essence, the ethics governance process must pay especial attention to the protection of
p.000026: persons who may not be competent to give consent themselves, or whose ability to give free and full consent
p.000026: may be compromised by physical conditions or other circumstances, such as being in a dependent
p.000026: relationship.
p.000026:
p.000026: (e) Avoidance of conflicts of interest or the appearance of conflicts of interest. We further elaborate on
p.000026: this principle below in our discussion of the roles and responsibilities of researchers and IRBs.
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p.000027: ETHICS GOVERNANCE
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p.000027: SECTION V: INSTITUTIONAL REVIEW BOARDS
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p.000027: 5. Institutional Review Boards The Role of Institutional Review Boards
p.000027: 5.1. Ethics review bodies having the first responsibility for ethics review in the ethics review and governance
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p.000056: governance consider taking these ethical principles into account.
p.000056:
p.000056: 4.19. Such principles, in addition to or in elaboration of those identified by the NMEC, might include:
p.000056:
p.000056: • Respect for the human body, welfare and safety, and for religious and cultural perspectives and traditions of
p.000056: human subjects. We elaborated on this principle in our Human Tissue Research Report. In the context of a diverse
p.000056: society such as Singapore, researchers have an especial obligation to be sensitive to religious and
p.000056: cultural perspectives and traditions of their human subjects.
p.000056:
p.000056: • Respect for free and informed consent. Again, this principle is discussed at length in our
p.000056: Human Stem Cell Report, and our Human Tissue Research Report. A detailed discussion of the requirements of consent is
p.000056: also set out at section 2.5 of the NMEC Report, and we note also the strict requirements with regards to consent
p.000056: laid down by the Clinical Trials Regulations and the SGGCP.
p.000056:
p.000056: • Respect for privacy and confidentiality. This is treated in detail in section 2.6 of the NMEC
p.000056: Guidelines, and again in our Human Tissue Research Report.
p.000056:
p.000056: • Respect for vulnerable persons. This is discussed in paragraphs 2.5.5 to 2.5.6 of the NMEC Guidelines. In
p.000056: essence, the ethics governance
p.000056:
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p.000056: B-78
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p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: process must pay especial attention to the protection of persons who may not be competent to give consent
p.000056: themselves, or whose ability to give free and full consent may be compromised by reason of their physical
p.000056: condition or other circumstances, such as being in a dependent relationship.
p.000056:
p.000056: • Avoidance of conflicts of interest, or the appearance of conflicts of interest. We further elaborate
p.000056: on this principle below in our discussion of the roles and responsibilities of investigators and institutional review
p.000056: boards.
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p.000056: B-79
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p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION V: INSTITUTIONAL REVIEW BOARDS
...
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p.000009: Singapore, the need for ethics committees or IRBs and the requirement for the ethics review of research
p.000009: proposals involving human subjects have long been an accepted and integral part of biomedical research in the
p.000009: institutional setting.
p.000009:
p.000009: 2.7. The principle s of the Declaration of Helsinki today find expression in regulatory standards and
p.000009: practice guidelines governing various aspects of clinical research such as those contained in the Medicines (Clinical
p.000009: Trials) Regulations, promulgated pursuant to Section 74 of the Medicines Act (Cap. 176), the “Singapore
p.000009: Guideline for Good Clinical Practice” (SGGCP) and the “Ethical Guidelines on Research Involving Human
p.000009: Subjects” (NMEC Guidelines) issued in August 1997 by the National Medical Ethics Committee (NMEC).
p.000009: We discuss these regulatory standards and practice guidelines in detail below.
p.000009:
p.000009:
p.000009: Pharmaceutical Trials in Singapore
p.000009:
p.000009: 2.8. In Singapore, pharmaceutical trials involving the testing of drugs on human subjects are regulated by the
p.000009: Health Sciences Authority (HSA). The HSA regulates the conduct of pharmaceutical trials under the Medicines Act and the
p.000009: Medicines (Clinical Trials) Regulations (2000, Revised Edition). Under the Medicines Act, these
p.000009: pharmaceutical or drug trials are known as “clinical trials”.
p.000009:
p.000009: 2.9. The system of regulation requires that sponsors and researchers conducting pharmaceutical trials obtain
p.000009: both ethics and regulatory approval before initiating a study.
p.000009:
p.000009: 2.10. The current approval system is sequential. Approval from the HSA is sought only after the
p.000009: relevant hospital ethics committee has approved an application. Regulatory approval is provided in the form
p.000009: of a Clinical Trial Certificate issued by the HSA to the applicant.
p.000009:
p.000009: 2.11. The HSA, in deciding the regulatory approval for a pharmaceutical trial, consults an expert
p.000009: advisory committee known as the Medical Clinical Research Committee (MCRC). The MCRC is an
p.000009: “independent body constituted of medical members, whose responsibility is to ensure the
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: INTRODUCTION AND CURRENT
p.000010: FRAMEWORK
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: protection of the rights, safety and well- being of human subjects involved in a trial ... and documenting
p.000010: informed consent of the trial subjects” (Section 1.37 of the SGGCP). It currently comprises five members, all of
p.000010: whom are clinical specialists.
p.000010:
p.000010: 2.12. In this way, pharmaceutical trials are subject to ethics review at more than one level.
p.000010:
...
p.000011: 4 Ibid.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012: INTRODUCTION AND CURRENT
p.000012: FRAMEWORK
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2.24. Several sets of ethics guidelines were issued by the NMEC and adopted by the MOH. In the sphere of
p.000012: ethics governance of human biomedical research, the most significant of these ethics guidelines is the
p.000012: NMEC Guidelines.
p.000012:
p.000012: 2.25. In a written directive dated 25 June 1998 (Directive), the MOH required all government and restructured
p.000012: hospitals to set up hospital ethics committees (if they had not already done so) for the ethics governance
p.000012: of research involving human subjects. Before 1998, the practice of reviewing research proposals involving human
p.000012: subjects by hospital and medical institution ethics committees in Singapore was not governed by any
p.000012: formal rules or directives.
p.000012:
p.000012: 2.26. We quote from the Directive:
p.000012:
p.000012: “The National Medical Ethics Committee has recommended that:
p.000012:
p.000012: (i) hospital ethics committees vet for ethical considerations, all research protocols that involve
p.000012: • human experimentation be they clinical trials or drug trials, trials of new medical devices, new procedures
p.000012: and any other forms of clinical studies that require the participation of human subjects or the use of human tissues
p.000012: and organs
p.000012: ...
p.000012: (ii) a senior nursing representative be included as a member of hospital ethics committee.
p.000012:
p.000012: The Ministry has accepted these recommendations.”
p.000012:
p.000012: 2.27. The NMEC Guidelines set out in detail suggested principles of the ethics governance of research involving
p.000012: human subjects, the constitution of ethics committees and the implementation of the framework for the ethics
p.000012: governance of biomedical research. These NMEC Guidelines represent the principal controlling document governing
p.000012: research involving human subjects in Singapore today, but despite this they remain non-directive in
p.000012: nature.
p.000012:
p.000012: 2.28. In developing the Guidelines, the NMEC drew exte nsively from similar guidelines published in other
p.000012: technologically advanced countries, notably those issued by the Canadian Medical Research Council and the
p.000012: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with internationally
p.000012: accepted approaches to, and norms of, ethics governance of biomedical research involving human subjects at that
p.000012: time.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: INTRODUCTION AND CURRENT
...
p.000013: subject to the regulatory jurisdiction of the MOH. Such entit ies include companies and other
p.000013: commercial entities in the biomedical industry, research institutes and statutory agencies with an interest
p.000013: in the biomedical industry.
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: INTRODUCTION AND CURRENT
p.000014: FRAMEWORK
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014: 2.34. The vast majority of these new players in the field of human biomedical research in Singapore
p.000014: are keenly aware of the need for proper ethics governance. Most researchers are anxious to conform to
p.000014: internationally accepted standards for ethics governance. In many cases, researchers are involved as
p.000014: collaborators in multinational or multi-centre (or both) biomedical research projects.
p.000014:
p.000014: 2.35. With the development of the biomedical sector in Singapore, new avenues of biomedical inquiry are rapidly
p.000014: emerging. The traditional categorisation of research for ethics governance, which separates research
p.000014: into pharmaceutical trials and non-pharmaceutical trials, is becoming irrelevant and obsolete. Some new kinds of
p.000014: research may blur the border between these two categories. New kinds of biomedical research include trials of medical
p.000014: devices, experimental therapeutic procedures (which may or may not involve drugs), new modes of non-drug treatment and
p.000014: new diagnostic methods. Other increasingly important research includes epidemiological or population studies
p.000014: (which may or may not require invasive interaction with human subjects), genetic screening, genetic research and
p.000014: research that involves no direct interaction with human subjects but only access to their medical, personal or genetic
p.000014: information.
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
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p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000015: 15
p.000015:
p.000015: HUMAN
p.000015: BIOMEDICAL RESEARCH
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: PART B: HUMAN BIOMEDICAL RESEARCH
p.000015: SECTION III: HUMAN BIOMEDICAL RESEARCH
p.000015:
p.000015: 3. Human Biomedical Research Defining Human Biomedical Research
p.000015: 3.1. In this section, we consider what kinds of human biomedical research ought to be subject to
p.000015: the framework of ethics go vernance that we recommend in these Guidelines.
p.000015:
p.000015: 3.2. In keeping with our terms of reference, we consider only such human biomedical research that
p.000015: involves an interaction (whether direct or otherwise) with a human subject or human biological
p.000015: material, and therefore exclude any human biomedical research in relation to:
p.000015:
p.000015: (a) Genetically modified organisms;
...
p.000016: largely on cell lines, tissues or other bodily samples given by human donors, and on medical information
p.000016: derived from patients and other human subjects.
p.000016:
p.000016: 3.6. Increasingly, it is the case that there is no direct physical contact at all between the
p.000016: researchers and the human subjects. In such circumstances, there is no possibility of physical injury or harm
p.000016: befalling the human research subjects. In these situations, the ethical, le gal and social concerns centre not on
p.000016: the possibility of physical injury or harm but on the larger penumbra of indirect harms to the patient or
p.000016: donor such as the breach of the patient’s or donor’s expectation of confidentiality of his medical
p.000016: information, or his expectation that his tissue should not be used for research without his consent.
p.000016:
p.000016: 3.7. It is therefore appropriate that a fundamental distinction be made between:
p.000016:
p.000016: (a) Direct Human Biomedical Research. This comprises any kind of human biomedical research that
p.000016: involves any direct interference or interaction with the physical body of a human subject, and that
p.000016: involves a concomitant risk of physical injury or harm, however remote or minor. A research
p.000016: programme which involves the administration of any drug (whether it is for the purpose of testing the
p.000016: effects or efficacy of the drug, or whether it is a means for establishing any other objective of the
p.000016: research programme), the trial or use of a medical device on a human subject, or any test of a human subject’s
p.000016: physiological, emotional or mental responses (not being tests conducted for diagnostic purposes with a view to
p.000016: the therapeutic management of a patient) all qualify as Direct Human Biomedical Research; and
p.000016:
p.000016: (b) Indirect Human Biomedical Research. This comprises any research (not qualifying as Direct Human
p.000016: Biomedical Research) involving human subjects, human tissue, or medical, personal or genetic
p.000016: information relating to both identifiable and anonymous individuals, undertaken with a view to generating data about
p.000016: medical, genetic or biological processes, diseases or conditions in human subjects, or of human physiology or about the
p.000016: safety, efficacy, effect or function of any device, drug, diagnostic, surgical or therapeutic procedure
p.000016: (whether invasive, observational or otherwise) in human subjects whether as one of the objectives or the sole
p.000016: objective, of the research study, trial or activity, and which research, study, trial or activity has
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: HUMAN
p.000017: BIOMEDICAL RESEARCH
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: the potential to affect the safety, health, welfare, dignity or privacy of the human subjects involved in the study, or
p.000017: of the donors of human tissue or information used in the research, or of the family members of any of the human
p.000017: subjects or donors thereof, or to which such medical, personal or genetic information relates.
p.000017:
p.000017: 3.8. For the purposes of these Guidelines, we define Human Biomedical Research as Direct Human
p.000017: Biomedical Research and Indirect Human Biomedical Research taken together.
p.000017:
p.000017:
p.000017: Ethics Review of Direct Human Biomedical Research
p.000017:
p.000017: 3.9. Every research programme involving Direct Human Biomedical Research should be reviewed and approved
p.000017: by a properly constituted ethics committee or IRB.
p.000017:
p.000017:
p.000017: Ethics Review of Indirect Human Biomedical Research
p.000017:
p.000017: 3.10. There is currently no international consensus on what kind of Indirect Human Biomedical Research
...
p.000018: 3.13. Exempted Review should in general only be permitted for categories that are widely accepted by the
p.000018: community as being eligible for Exempted Review.
p.000018:
p.000018: 3.14. There can be no hard and fast rule dictating which categories of Human Biomedical Research ought
p.000018: to be allowed exemption from review, and which categories ought to undergo full review. Each institution
p.000018: should determine for itself, after due deliberation and consultation with its IRB, the categories of Human
p.000018: Biomedical Research that could be exempted from ethics review. The most important consideration is that there
p.000018: should be no likelihood of harm to the research subject.
p.000018:
p.000018: 3.15. In general, we suggest that categories for Exempted Review should be drawn from categories of
p.000018: Indirect Human Biomedical Research. By way of illustration, the following categories of Indirect Human
p.000018: Biomedical Research could be considered for Exempted Review, taking into account current practice:
p.000018:
p.000018: (a) Writing up or reporting of individual patients’ clinical results by the patients’ doctors, provided that the
p.000018: patients’ consent for procedures and interventions in clinical management have been obtained and the patients’ privacy
p.000018: protected, for example, the review of a clinical programme that includes demographic, clinical and
p.000018: outcome parameters, which are useful in the audit of the programme; or the review of a procedure or
p.000018: treatment (a surgical technique or drug treatment outcome) by a physician or surgeon, where the choice of the
p.000018: drug or technique is based on the clinical judgment of the physician or surgeon and on best
p.000018: practices and not on any randomisation procedure. Researchers who are not the attending physicians in
p.000018: the programme but wish to have access to such information should send their proposals to the IRB in
p.000018: the usual way;
p.000018:
p.000018: (b) Research using appropriately designed data escrow or other arrangements in which personal or
p.000018: other identity information is securely withheld from researchers by a third party provider of information,
p.000018: there being no possibility of researchers by themselves being able to trace or reconstruct significant
p.000018: information on the identity of subject donor;
p.000018:
p.000018: (c) Research using established commercially available cell lines or commercially available anonymous
p.000018: DNAs, RNAs and fixed tissues; and
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019: HUMAN
p.000019: BIOMEDICAL RESEARCH
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: (d) The development of diagnostic tests using existing samples for test validation purposes provided
p.000019: that the necessary consent for the taking and use of the samples has been obtained.
p.000019:
p.000019: Expedited Review
p.000019:
p.000019: 3.16. Some categories of research programmes may be permitted a less formal process of review than that of a
p.000019: standard full review. For example, the Chairperson or other IRB delegate(s) (the reviewer) may be empowered to
...
p.000048: with informing and discussing with the attending physicians of their subjects;
p.000048:
p.000048: (b) In the case of research that involves access to patients’ medical records but with minimal levels of
p.000048: clinical interaction (e.g. the taking of blood or urine samples) or only social interaction (e.g.
p.000048: interviewing the subject-patient for a history), the IRB may in its discretion make formal contact and
p.000048: discussion a condition of ethics approval if it takes the view that the proposed interaction is relevant to the
p.000048: continued medical treatment and management of the subject- patient. Otherwise, researchers may in such
p.000048: cases dispense with contacting the attending physicians; and
p.000048:
p.000048: (c) In the case of research that involves access to and a study of patients’ medical records without any kind of
p.000048: contact between researchers and the patients, researchers need not inform or discuss with the
p.000048:
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049:
p.000049: ETHICS GOVERNANCE
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049: attending physicians (on the assumption, of course, that they have complied with all other applicable
p.000049: requirements).
p.000049:
p.000049: 6.44. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000049: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the subjects
p.000049: without first seeking and obtaining the approval of both the attending physicians and the IRB.
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
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p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000050: 50
p.000050:
p.000050:
p.000050: ETHICS GOVERNANCE
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION VII: INSTITUTIONS
p.000050:
p.000050: 7. Institutions
p.000050:
p.000050: The Responsibilities of Appointing Institutions
p.000050:
p.000050: 7.1. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical Research and
p.000050: the protection of human subjects in all Human Biomedical Research carried out on their premises or facilities, or by
p.000050: their employees, or on their patients, or involving access to or use of human tissue collections in their custody, or
p.000050: involving access to or use of medical records or other personal information in their custody.
p.000050:
...
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: submitted to an independent et hical review committee for “consideration, comment, guidance, and where appropriate,
p.000056: approval”.
p.000056:
p.000056: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000056: medical community in Singapore, as with other medical communities in the great majority of nations.
p.000056: The need for ethics committees or institutional review boards and the requirement for the ethical
p.000056: review of research proposals involving human subjects have long been an accepted and integral part of medical
p.000056: research in the institutional setting in Singapore. The principles of the Declaration of Helsinki today find
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
p.000056: as those contained in the Medicines (Clinical Trials) Re gulations, promulgated pursuant to s.74 of the
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
p.000056: Regulations and its parent Act (the Medicines Act, Cap. 176) has a special meaning. As defined in
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
p.000056: instead use the term “drug trials” in this Consultation Paper when referring to “clinical trials” in the legal sense of
p.000056: that term, as used in the Clinical Trials Regulations and the Medicines Act.
p.000056:
p.000056: 2.13. In keeping with the principles enunciated in the Declaration of Helsinki, an important component of
p.000056: the requirements of the Clinical Trials Regulations is that the researchers must ensure that the free
p.000056: consent of the proposed research subject must be obtained, and that researchers are under a duty to give full
p.000056: explanation and information of (among others) the risks and objectives of the proposed drug trial.
p.000056:
p.000056: The Singapore Guideline for Good Clinical Practice
p.000056:
p.000056: 2.14. In 1998, the Ministry of Health released the Singapore Guideline for Good Clinical Practice (SGGCP), which is
p.000056: a set of guidelines adapted from the Good Clinical Practice Guidelines of the International Conference on
p.000056: Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
p.000056: Accordingly, the SGGCP reflects best international practice in its approach to the governance of drug trials.
p.000056: Since 1998, the SGGCP has been incorporated by reference in the Clinical Trials Regulations, and sponsors and
p.000056: researchers in drug trials are required by law to comply with the SGGCP unless specifically exempted under the Clinical
p.000056: Trials Regulations.
p.000056:
p.000056: 2.15. The SGGCP sets out in detail a framework for the ethical governance of drug trials. The SGGCP begins its
p.000056: statement of applicable principles by declaring that drug trials “should be conducted in accordance with the
p.000056: ethical principles that have their origin in the Declaration of Helsinki”.
p.000056:
p.000056: 2.16. Article 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000056: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000056: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000056: investigational product(s), and/or to identify any adverse reactions to an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-64
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: investigational product(s), and /or to study absorption, distribution, metabolism, and excretion of an
p.000056: investigational product(s) with the object of ascertaining its safety and/or efficacy”.
p.000056:
p.000056: 2.17. The SGGCP sets out detailed guidelines as to the roles and duties of researchers and sponsors in
p.000056: a pharmaceutical drug trial, and lays down the requirements such as monitoring procedures, audits and the matters to be
p.000056: included in trial protocols.
p.000056:
p.000056: 2.18. Of relevance to this Consultation Paper are the provisions in Part 3 of the SGGCP requiring all drug
p.000056: trials to be reviewed and approved by the Medical Clinical Research Committee (MCRC) of the Health
p.000056: Sciences Authority (“HSA”) and hospital’s “ethics committees” before an application may be made
p.000056: for a clinical trial certificate from the HSA. The responsibilities, composition, functions and operations of the
p.000056: MCRC are set out in detail in Article 3.1 of the SGGCP, while the responsibilities, composition, functions
p.000056: and operations of ethics committee are detailed in Article 3.2.
p.000056:
p.000056: The Current Approval Process for a Proposed Pharmaceutical Drug Trial
p.000056:
p.000056: 2.19. It may be useful to summarise the current approval process for a proposed pharmaceutical drug trial under the
p.000056: current regulatory regime. Researchers seeking a clinical trial certificate under the Medicines Act are required to
p.000056: submit their trial protocol and application first to their hospital ethics committee or IRB for
p.000056: review and approval. If the proposed pharmaceutical drug trial is a multi-centre trial (where
p.000056: the trial is carried out at more than one institution or centre), the application is submitted to the Clinical Trials
p.000056: Coordinating Committee (CTCC) instead for review and approval. The CTCC was established in 1999 by the Ministry of
p.000056: Health to coordinate the ethical governance of multi-centre drug trials in Singapore.
p.000056:
p.000056: 2.20. If the protocol and application are approved by the hospital ethics committees (and the
p.000056: CTCC, if the application is for a multi- centre trial), they are then submitted to the Centre for Pharmaceutical
p.000056: Administration (CPA) of the HSA for review and approval.
p.000056:
p.000056: 2.21. The CPA is aided in its task by the MCRC. The MCRC is an advisory committee appointed by the
p.000056: Ministry of Health to review applications for drug trials in Singapore. It is an “independent body constituted of
p.000056: medical members, whose responsibility is to ensure the protection of the rights, safety and well-being
p.000056: of human subjects involved in a trial ... and documenting informed consent of the trial subjects”
p.000056: (Article 1.37 of the SGGCP). The MCRC currently comprises five members, all of whom are clinical specialists.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-65
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.22. The current formal regulatory regime for drug trials as constituted under the Medicines Act, the
p.000056: Clinical Trials Regulations and the SGGCP has worked very well, and the standards of ethical governance in
p.000056: Singapore for drug trials conform to the highest internationally agreed standards of ethical governance for
p.000056: drug trials.
p.000056:
p.000056: 2.23. We understand that the rules are being examined with a view to procedural changes in the interests of
p.000056: streamlining processes, emphasising a risk- based approach and perhaps also for the inclusion of the trial
p.000056: of medical devices to be included within the ambit of the current regulatory regime. We agree with these moves, and
p.000056: they do not detract from or alter the core principles for ethical governance currently in place for drug trials.
p.000056:
p.000056:
p.000056: Non-Drug Trials
p.000056:
p.000056: The NMEC Guidelines on Research Involving Human Subjects
p.000056:
p.000056: 2.24. While the ethical governance of drug trials in Singapore is comprehensively and
p.000056: appropriately regulated by statutory rules and practice guidelines, the picture for the ethical
p.000056: governance of clinical research other than for drug trials is less clear.
p.000056:
p.000056: 2.25. Currently, there is no statutory scheme for the ethical governance of clinical research apart
p.000056: from drug trials. We expand on the definition of “clinical research” in Section III below.
p.000056:
p.000056: 2.26. Indirectly, however, the Ministry of Health has long exercised jurisdiction over, and given informal ethical
p.000056: guidance on, clinical research carried out in hospitals, clinics and clinical laboratories in its role as a
p.000056: statutory regulator under the Private Hospitals and Medical Clinics Act.
p.000056:
p.000056: 2.27. In January 1994, the Ministry of Health set up a national- level policy advisory body, the National
p.000056: Medical Ethics Committee (NMEC) to “assist the medical profession in addressing ethical issues in medical practice and
p.000056: to ensure a high standard of ethical practice in Singapore”.
p.000056:
p.000056: 2.28. One of the objectives of establishing the NMEC was to “identify and study ethical issues relating to medical
p.000056: practice and research in Singapore and to provide an ethical framework for medical practitioners to carry out
p.000056: their duties and responsibilities”.
p.000056:
p.000056: 2.29. Several sets of Ethical Guidelines were issued by the NMEC and adopted by the Ministry of Health. In the
p.000056: sphere of ethical governance of clinical
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-66
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: research, the most significant of these Ethical Guidelines is the Ethical Guidelines on Research Involving
p.000056: Human Subjects issued by the NMEC in August 1997 (“the NMEC Guidelines”).
p.000056:
p.000056: 2.30. The NMEC Guidelines were accepted and adopted by the Ministry of Health, and copies of these
p.000056: Guidelines were circulated to all hospital ethics committees for their adoption and implementation.
p.000056:
p.000056: 2.31. In 1998, the previously informal practice of hospitals and medical institutions in Singapore
p.000056: of having ethics committees (sometimes on an ad hoc basis) to review research proposals involving human
p.000056: subjects was formalised by a written direction dated 25 June 1998 from the Ministry of Health to all government and
p.000056: restructured hospitals to set up hospital ethics committees (if they had not already done so) for the ethical
p.000056: governance of research involving human subjects.
p.000056:
p.000056: 2.32. We quote from the written direction:
p.000056:
p.000056: “The National Medical Ethics Committee has recommended that:
p.000056:
p.000056: (i) hospital ethics committees vet for ethical considerations, all research protocols that involve
p.000056: • human experimentation be they drug trials, trials of new medical devices, new procedures and any
p.000056: other forms of clinical studies that require the participation of human subjects or the use of human tissues
p.000056: and organs
p.000056: ...
p.000056: (ii) a senior nursing representative be included as a member of hospital ethics committee.
p.000056:
p.000056: The Ministry has accepted these recommendations”.
p.000056:
p.000056: 2.33. The NMEC Guidelines set out in detail suggested principles of the ethical governance of research involving
p.000056: human subjects, the constitution of ethics committees and the implementation of the framework for the ethical
p.000056: governance of biomedical research. These Guidelines represent the principal controlling document
p.000056: governing research involving human subjects in Singapore today, but despite this they rema ins non-directive in
p.000056: nature,
p.000056:
p.000056: 2.34. In developing the Guidelines, the NMEC drew extensively from similar guidelines published in other
p.000056: technologically-advanced countries, notably those issued by the Canadian Medical Research Council, and the
p.000056: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with
p.000056: internationally-accepted approaches to, and norms of,
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-67
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical governance of biomedical research involving human subjects at that time.
p.000056:
p.000056: 2.35. We have reviewed the NMEC Guidelines. We have no hesitation in using the NMEC Guidelines as the
p.000056: starting point of the larger enquiry in this Consultation Paper. Although it was formulated in the
p.000056: restricted context of the governance of biomedical research on human subjects by the medical professions
p.000056: (as appropriate and in keeping with the NMEC’s terms of reference), the principles expressed in it and the
p.000056: framework which it recommended for the ethical governance of clinical research are entirely sound and are universally
p.000056: accepted within the medical professions.
p.000056:
p.000056: 2.36. We therefore are of the view that the principles and the framework for ethical governance of
p.000056: biomedical research on human subjects set out in the NMEC Guidelines are an appropriate foundation for our
p.000056: proposals for a scheme of ethical governance of all clinical research on human subjects in Singapore, whether or not
p.000056: such research is carried out by members of the medical professions, and whether or not such research is carried out in
p.000056: an institution under the direct jurisdiction of the Ministry of Health pursuant to the Private Hospitals and Medical
p.000056: Clinics Act.
p.000056:
p.000056: Limitations of the Current Regulatory Regime
p.000056:
p.000056: 2.37. The evolution of regimes for the ethical governance of clinical research and drug trials must be
p.000056: seen in the context of the history of clinical research and drug trials in Singapore. At the time when the
p.000056: Clinical Trials Regulations were first enacted, drug trials were the most common kind of clinical research trial.
p.000056: As such, it was entirely appropriate to enact the Clinical Trials Regulations as subsidiary legislation
p.000056: under the Medicines Act, which deals principally with medicines.
p.000056:
p.000056: 2.38. Likewise, until recently, the vast majority of clinical research (whether drug trials or non-drug
p.000056: trials) were carried out by researchers who were medical practitioners registered under the Medical Registration
p.000056: Act (Cap. 174), or in Government medical institutions directly controlled by the Ministry of Health, or in
p.000056: hospitals and medical clinics licensed under the Private Hospitals and Medical Clinics Act. In all of these
p.000056: cases, the competent supervisory authority was the Ministry of Health.
p.000056:
p.000056: 2.39. In recent years, however, the development of the biomedical industry in Singapore has led to an
p.000056: increasing proportion of non-drug trials. For example, in 2002, hospital ethics committees of the five main
p.000056: restructured hospitals in Singapore reviewed nearly three times as many applications for non-drug trials as
p.000056: they did for drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-68
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.40. Clinical research tends increasingly to be institutionally-driven, rather than being researcher-driven (the
p.000056: traditional model assumed in the current regulatory regime). Company-driven drug trials received by the HSA now
p.000056: outnumber researcher-driven drug trials.
p.000056:
p.000056: 2.41. Concomitantly, an increasing proportion of clinical research trials are now also being carried out outside
p.000056: the traditional paradigm assumed by the current regulatory environment: many trials are now led by
p.000056: researchers, who although being qualified and competent for the trials proposed by them, are not
p.000056: medical practitioners registered under the Medical Registration Act, or by researchers who work in or for
p.000056: entities not subject to the regulatory jurisdiction of the Ministry of Health. Such entities include
p.000056: companies and other commercial entities in the biomedical industry, research institutes and statutory
p.000056: agencies with an interest in the biomedical industry.
p.000056:
p.000056: 2.42. The vast majority of these new players in the field of clinical research in Singapore are keenly aware of
p.000056: the need for proper ethical governance. Most researchers are anxious to conform to
p.000056: internationally-accepted standards for ethical governance. In many cases, researchers are involved as collaborators
p.000056: in multi- jurisdictional or multi-centred (or both) clinical research projects.
p.000056:
p.000056: 2.43. With the development of the biomedical industry in Singapore, new avenues of biomedical inquiry
p.000056: are rapidly emerging, and the traditional categorisation of research trials into drug trials and non-drug trials
p.000056: for the purposes of ethical governance is rapidly becoming irrelevant and obsolete. Some new kinds of
p.000056: research may blur the border between drug and non-drug trials. For example, the first use of a new drug
p.000056: already approved elsewhere on the local population: in this situation, is the trial one for the drug, or a
p.000056: trial to observe and determine the responses of the local population to the drug? New kinds of research trials
p.000056: include trials of medical devices, experimental therapy procedures (which may or may not involve drugs), new modes
p.000056: of non-drug treatment and new diagnostic methods. Other increasingly important research include
p.000056: epidemiological or population studies (which may or may not require invasive interaction with human subjects),
p.000056: genetic screening, genetic research and research which involve no direct interaction with human subjects but only
p.000056: access to their personal medical or genetic information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-69
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.44. In summary:
p.000056:
p.000056: • The most comprehensive formal framework for the ethical governance of clinical research trials at the moment is
p.000056: limited largely to drug trials, or “clinical trials” as defined in the Medicines Act. The principal
p.000056: documents setting out this framework of ethical governance are the Medicines Act, the Clinical Trials
p.000056: Regulations, and the SGGCP. In this framework, the HSA is the principal regulatory agency.
p.000056:
p.000056: • For clinical research other than drug tr ials, the Ministry of Health exercises indirect control over
p.000056: hospitals and medical clinics under the Private Hospitals and Medical Clinics Act. The Ministry of Health has directed
p.000056: that hospitals establish ethics committees to review and approve applications for both drug and
p.000056: non-drug trials.
p.000056:
p.000056: • For clinical research other than drug trials, the main document spelling out a framework for ethical governance is
p.000056: the NMEC Guidelines.
p.000056:
p.000056: • There is some uncertainty as to whether the jurisdiction of the Ministry of Health under the Private Hospitals and
p.000056: Medical Clinics Act extends to clinical research entities or institutions which are not hospitals or clinics
p.000056: liable to be licensed under the Act.
p.000056:
p.000056: • Non-drug trials have in recent years surpassed drug trials in number, and new kinds of clinical research
p.000056: projects not contemplated when the current controlling documents were drafted have since emerged. New types of
p.000056: clinical research have evolved, blurring and making irrelevant the traditional distinction between drug trials and
p.000056: non-drug trials.
p.000056:
p.000056: 2.45. The current framework for ethical governance of clinical research has evolved incrementally and
p.000056: cautiously. In our view, this evolutionary approach was an entirely appropriate response to specific
p.000056: needs and technological advances as they developed over the years.
p.000056:
p.000056: 2.46. At a time when the bulk of medical research was centred about drug trials carried out by the medical
p.000056: professions, it was entirely appropriate to provide for a scheme of ethical governance within the
p.000056: framework of the Medicines Act. But the present and future of clinical research on human subjects embraces a
p.000056: diversity of research inquiry which can no longer be accommodated within the current framework. Accordingly, we think
p.000056: that it is now the appropriate time to undertake a global review of the current rules and framework for the ethical
p.000056: governance of clinical research, and a new, unified framework be created for the ethical governance of all
p.000056: research involving human subjects whether involving drug or non-drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-70
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.47. The principles and ethical governance framework expressed in the Clinical Trials Regulations, the SGGCP and
p.000056: the NMEC Guidelines have served us well in their restricted contexts, and are universally accepted. We take the view
p.000056: that these remain sound guides, and should wherever possible be applied and extended as appropriate to all
p.000056: other forms of clinical research involving human subjects. To this end, the current provisions relating to drug
p.000056: trials should be substantively retained insofar as drug trials are concerned, subject to the procedural
p.000056: changes currently being proposed by the HSA.
p.000056:
p.000056: 2.48. In the sections that follow, we will consider the elements of the proposed new unified framework for
p.000056: ethical governance of clinical research involving human subjects.
p.000056:
p.000056:
p.000056: Recommenda tion 1:
p.000056:
p.000056: A new national framework for the ethical governance of all clinical research involving human subjects should be
p.000056: established.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-71
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART B: CLINICAL RESEARCH
p.000056:
p.000056: SECTION III: CLINICAL RESEARCH
p.000056:
p.000056: 3. Defining Clinical Research
p.000056:
p.000056: 3.1. In this section, we attempt a definition of what kinds of clinical research ought to be subject to the
p.000056: framework of ethical governance that we recommend in this Consultation Paper.
p.000056:
p.000056: 3.2. Clinical research is a term capable of a very broad definition. In our review of the
p.000056: approaches taken by national ethical bodies or agencies in other countries, we have found that there is considerable
p.000056: variation in what is to be included in the definition of clinical research coming within the purview of
...
p.000056: 3.5. The NMEC also went on to consider the relationship and distinction between research and therapy.
p.000056: They held that when “an activity is undertaken with the sole intention of benefiting the patient,
p.000056: the activity may be considered to be part of “therapy”. The progressive modification of methods of diagnosis and
p.000056: treatment in the light of experience is a normal feature of medical practice and should not be
p.000056: considered as research. There could be potential conflicts between research (intended to generate new information)
p.000056: and therapy (intended to benefit the individual patient directly). Their resolution rests on the integrity of the
p.000056: physician / researcher. The patient is always entitled to the best clinical management, and research considerations
p.000056: must never override this”. We agree with these statements of the NMEC, and likewise adopt them. In keeping
p.000056: with the spirit of this definition, we therefore exclude therapeutic activities undertaken with the sole
p.000056: intention of benefiting the patient from our definition of clinical research.
p.000056:
p.000056: 3.6. Subject to the preceding qualifications, we propose to define clinical research in the following
p.000056: terms:
p.000056:
p.000056: Any research study, trial or activity involving human subjects, human tissue, or medical, personal or
p.000056: genetic information relating to both identifiable and anonymous individuals, undertaken with a
p.000056: view to generating data about medical, genetic or biological processes, diseases or conditions in human subjects, or
p.000056: of human physiology or about the safety, efficacy, effect or function of any device, drug, diagnostic,
p.000056: surgical or therapeutic procedure (whether invasive, observational or otherwise) in human subjects whether as
p.000056: one of the objectives or the sole objective, of the research study, trial or activity
p.000056:
p.000056: and
p.000056:
p.000056: which research study, trial or activity has the potential to affect the safety, health, welfare, dignity or privacy of
p.000056: the human subjects involved in the study, or of the donors of human tissue or information used in the research, or of
p.000056: the family members of any of the human subjects or donors thereof, or to which such medical, personal or genetic
p.000056: information relates.
p.000056:
p.000056: Savings
p.000056:
p.000056: 3.7. We make clear that nothing in this Consultation Paper is intended to supplant the recommendations
p.000056: that we have made in the Human Stem Cell Report and the Human Tissue Research Report, and tha t
p.000056: the recommendations contained in this Consultation Paper are intended to supplement those advanced in our
p.000056: first two Reports.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-73
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Exceptional Situations
p.000056:
p.000056: 3.8. We note that there may be some exceptional circumstances in which it may be ethically acceptable
p.000056: to abbreviate or temporarily suspend the usual ethics review procedures and requirements, provided that all the
p.000056: applicable legislative and regulatory requirements are satisfied. We have in mind situations of national
p.000056: security or emergency health situations, in w hich urgent research may have to be carried out to avert
p.000056: harm to national security or for the urgent protection or treatment of whole populations at risk. In such cases, we
p.000056: think that it is permissible for institutional review boards in consultation with the proper authorities to
p.000056: formulate and lay down written guidelines for the exemption or expedited review of defined classes or types of
p.000056: such emergency or urgent research in the national interest.
p.000056:
p.000056: 3.9. We therefore recommend that all clinical research as defined in this section be statutorily subject to
p.000056: review and approval by and to the continued supervision of an institutional review board in
p.000056: accordance with the principles discussed below.
p.000056:
p.000056:
p.000056: Recommendation 2:
p.000056:
p.000056: • The current statutory requirement for review and approval by an institutional review board in
p.000056: drug trials should be extended to all kinds of clinical research involving human subjects, as defined in this section.
p.000056:
p.000056: • All clinical research proposed to be carried out in Singapore must be submitted to and approved by a
p.000056: properly constituted institutional review board.
p.000056:
p.000056: • No programme of clinical research may be commenced or carried out without the approval of such an
p.000056: institutional review board, or other than on terms as set out by such an institutional review board.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-74
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART C: ETHICAL GOVERNANCE
p.000056:
p.000056: SECTION IV: PRINCIPLES OF ETHICAL GOVERNANCE
p.000056:
p.000056: 4. Principles of Ethical Governance The Purpose of Ethical Governance
p.000056: 4.1. Article 5 of the Helsinki Declaration states that in “medical research on human subjects, considerations
p.000056: related to the well-being of the human subject should take precedence over the interests of science and society”.
p.000056: At Article 8, the Declaration states that “[m]edical research is subject to ethical standards that
p.000056: promote respect for all human beings and protect their health and rights”.
p.000056:
p.000056: 4.2. Continuing biomedical human research is fundamental to improving our understanding of biological
...
p.000056: to be submitted to other IRBs in other jurisdictions, information on these applications, and on their
p.000056: outcome, should be provided to the local IRB as well.
p.000056:
p.000056: 5.38. The local IRB may then elect to give expedited approval of such applications after
p.000056: reviewing the documentation, and the reasons for the decision of the leading ethical review board. In general,
p.000056: local IRBs should consider a full ethics review if a substantial portion of the research project is to be carried
p.000056: out in Singapore. Similarly, local IRBs should be concerned to ask for evidence of approval by IRBs
p.000056: in the jurisdiction in which the major part of the research project will be carried out.
p.000056:
p.000056:
p.000056: Recommendation 5:
p.000056:
p.000056: The local portion of a proposed multinational research programme should be subject to review by the institutional
p.000056: review board(s) of the local partner institution or institutions.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-88
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Multi-Centre Research Projects
p.000056:
p.000056: 5.39. Currently, the situation is that ethics review is required by the ethics committees of every
p.000056: institution which will be involved in the proposed research programme. Except for drug trials, there is
p.000056: no mechanism or requirement that any one of the ethics committees involved should act as a principal or
p.000056: coordinating ethics committee (in drug trials, this function is currently carried out by the CTCC).
p.000056:
p.000056: 5.40. We recommend that a “lead” IRB be designated from among the IRBs of the participating institutions. The
p.000056: researchers may be asked to propose a lead IRB. On reviewing the proposal, the proposed lead IRB may then
p.000056: decide to accept nomination as the lead IRB, and if not, to give reasons why other IRBs may be more
p.000056: appropriate. If the proposal is accepted by the proposed lead IRB, the first application for review should be made
p.000056: to that lead IRB. The choice of the lead IRB should be dictated by considerations such as the
p.000056: principal institution of affiliation of the principal investigator, the location where the greater part of
p.000056: the research is carried out, the expertise of the constituted IRB, or the location where the largest number of subjects
p.000056: is located.
p.000056:
p.000056: 5.41. The primary ethical and scientific assessment should be made by the lead IRB, and copies of its decision sho
p.000056: uld be sent to the other institutions or organizations involved. Each of the IRBs of the other institutions may still
p.000056: give further consideration to ethical and administrative aspects of the research which are specific to their
p.000056: own institutions or organisations.
p.000056:
p.000056: 5.42. Researchers should distinguish between core elements of their research (those components of
p.000056: their research that cannot be altered without invalidating the pooling of data from the
p.000056: participating institutions) and non-core elements (those that can be altered to comply with local IRB
p.000056: requirements without invalidating the research proposal).
p.000056:
p.000056: 5.43. Researchers should:
p.000056:
...
p.000056: for ethical review are directed at a completely different end to that of proposals submitted for funding
p.000056: purposes.
p.000056:
p.000056: 5.51. The requirements of impartiality, fair review, and documentation of decisions should apply
p.000056: equally to IRBs engaged in the continuing review, supervision or audit of a research program.
p.000056:
p.000056: 5.52. Conflicts of interest. IRBs and members of IRBs should take especial care to avoid conflicts of interest,
p.000056: whether actual conflict, potential conflict, or only the appearance of conflict as such.
p.000056:
p.000056: 5.53. A situation of real, potential or apparent conflict of interest amounts to circumstances which
p.000056: adversely affect the impartiality, objectivity and independence of the IRB or of its members as described above.
p.000056:
p.000056: 5.54. In the event that a member of the IRB has a personal interest in the research under review, that
p.000056: member should recuse himself or herself from any consideration of the case by the IRB, a nd he or she should refrain
p.000056: from offering his or her opinion to the board on the particular research under review.
p.000056:
p.000056: 5.55. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000056: the board.
p.000056:
p.000056: 5.56. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000056: obtaining of free and informed consent of subjects in drug trials be in principle extended to all other kinds of
p.000056: clinical research with appropriate modifications.
p.000056:
p.000056: 5.57. Both researchers and IRBs should take especial care to ensure that the proposed human subjects will
p.000056: be able to understand and assess the risks of participation, and that the consent -taking procedure and the
p.000056: documentation are properly designed to achieve this end.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-91
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.58. Both researchers and IRBs should ensure that the participants of research projects are aware that they have
p.000056: the right to withdraw from the research programme at any time.
p.000056:
p.000056: 5.59. We recommend that IRBs and institutions formalise arrangements which allow participants a one-stop direct
p.000056: access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000056: quality service standards and control. In this way, participants in research trials can have access to independent
p.000056: officers in order to give feedback on the trial, or to express their concerns.
p.000056:
p.000056: 5.60. In the same vein, we further recommend that researchers consider (and IRBs should consider making it
p.000056: a condition of approval) appointing one of their number (who should be a registered med ical practitioner or a senior
p.000056: member of the research team) as a one-stop participant contact in all cases where the research programme involves any
...
p.000056: interaction for the purposes of obtaining more information (for instance, interviewing the subject
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-101
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: patient for a history), researchers should still be encouraged to contact and inform the attending physicians,
p.000056: and the IRB may in its discretion make such formal contact and information a condition of ethics approval.
p.000056:
p.000056: 6.39.3. In the case of research which involves access to and a study of patient medical records without
p.000056: any kind of contact at all between the researchers and the subject patients, the IRB need not require
p.000056: researchers to formally contact or inform the attending physicians (on the assumption, of course, that they have
p.000056: complied with all other applicable requirements).
p.000056:
p.000056: 6.39.4. We take the view that efforts to contact and inform the attending physician(s), or the consultant or
p.000056: senior person in charge of the department or clinic concerned, should be made before
p.000056: commencement of the research project. Whe re this is not possible, such contact must be made as immediately after
p.000056: commencement of the research project as may be practicable, or as the IRB may direct.
p.000056:
p.000056: 6.40. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000056: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the
p.000056: subject patients, without first seeking and obtaining the approval of both the attending physicians and the
p.000056: IRB.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-102
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART D:
p.000056: THE NATIONAL ORGANISATION, ENFORCEMENT AND PROTECTION OF ETHICAL GOVERNANCE
p.000056:
p.000056:
p.000056: SECTION VII:
p.000056: THE NATIONAL ORGANIZATION OF ETHICAL GOVERNANCE
p.000056:
p.000056: 7. The National Organization Of Ethical Governance
p.000056:
p.000056: 7.1. The current regulatory regime governing the review and approval of drug trials (which we described in
p.000056: Section II above) provide for a system in which applications for drug trials are first screened by IRBs
p.000056: at the local institutional level before being forwarded to a national regulatory agency (the CPA of the HSA) for
p.000056: approval. This system has served us well. It is well- understood by all parties involved in the process. We
p.000056: recommend that this system continue to apply in the case of drug trials.
p.000056:
p.000056: 7.2. In the case of clinical research other than drug trials there is currently no national agency or regulatory
p.000056: body fulfilling a function equivalent to that of the HSA. The exception is the Ministry of Health, but the Ministry
p.000056: only has jurisdiction over hospitals, private clinics and other institutions falling within its purview under the
p.000056: Private Hospitals and Medical Clinics Act.
p.000056:
p.000056: 7.3. The Ministry of Health provides guidance from time to time to IRBs falling within its
p.000056: jurisdiction. For example, it has directed all IRBs to adopt and apply the NMEC Guidelines.
p.000056: From time to time, other directions are issued. Some of these are on the advice of the NMEC.
p.000056:
p.000056: 7.4. The role of the NMEC, however, is to advise the Ministry of Health on ethical issues arising in the practice
p.000056: of medicine. It does not advise IRB directly, and does not function as a higher- level appeal or advisory body to
p.000056: IRBs.
p.000056:
p.000056: 7.5. Apart from complying with the directives issued by the Ministry of Health (including the NMEC
p.000056: Guidelines), IRBs in institutions under the jurisdiction of the Ministry are free to adopt such
p.000056: procedures, formulate their own Standard Operating Procedures, and determine their constitution, operating principles
p.000056: and other administrative practices.
p.000056:
p.000056: 7.6. As a result, there is considerable diversity in the constitution, procedures and practice among IRBs. On the
p.000056: informal feedback that we have received on this point, there is considerable support in favour of there
p.000056: being an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-103
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: agreed standard model or set of guidelines for all IRBs to follow and apply.
p.000056:
p.000056: 7.7. We support this view, as we think that a national standard model or set of guidelines for standard operating
p.000056: procedures for all IRBs is desirable in the interests of promoting consistency and fairness in the decisions,
p.000056: especially in the case of multi- centre research programmes. We think, too, that having a national standard
p.000056: model or set of guidelines will also serve as a quality of service benchmark for all IRBs to judge themselves.
p.000056:
p.000056: 7.8. Such a national standard model or set of guidelines can consist of a set of documents issued by a national
p.000056: body or agency. These documents can be modelled on documents such as the SGGCP. The NMEC Guidelines itself is
p.000056: already such a document, but for the fact that it was intended only for the direction of hospitals and
p.000056: institutions falling under the jurisdiction of the Ministry of Health.
p.000056:
p.000056: 7.9. Likewise, we think that it would be desirab le for all clinical research in Singapore to come under
p.000056: the formal statutory jurisdiction of a national government agency or ministry, as drug trials currently do. We
p.000056: suggest that this government agency could be the Ministry of Health, or the HSA, or the statutory agency proposed
p.000056: for the oversight of human stem cell search, cloning research and human tissue research as announced by
p.000056: the Government.
p.000056:
p.000056: 7.10. In addition to coordinating and promoting national standards for IRBs, such a national supervisory
p.000056: agency could also function as the accrediting agency for IRBs. No IRB should be permitted to operate without
p.000056: obtaining such accreditation.
p.000056:
p.000056: 7.11. The national supervisory agency should be empowered to conduct audit and investigations into
p.000056: complaints (including complaints from research subjects), and should have the power to appoint external
p.000056: auditors and investigators at the cost of the institution being audited as part of the accreditation check
p.000056: or as a matter of routine audit for compliance.
p.000056:
p.000056: 7.12. The national supervisory agency should be empowered to appoint committees of inquiry to
p.000056: investigate complaints arising from research programmes (including complaints from research subjects) and
p.000056: should have powers to compel the testimony of witnesses and the production of documents (in this, the statutory powers
p.000056: of the Singapore Medical Council in disciplinary proceedings may be used as an example).
p.000056:
p.000056: 7.13. The national supervisory agency should also be empowered to work towards developing a code of
p.000056: ethics and principles for the governance of
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-104
p.000056:
...
p.000056:
p.000056: IRB: This is not feasible. Some IRBs are currently overloaded with protocols for review (200-400 per
p.000056: year). It is not only difficult for IRBs to find time for the added audit responsibilities, but is also difficult for
p.000056: IRBs to find people with the time and capability to perform independent audits on their behalf. In addition,
p.000056: certain IRBs have difficulty coping with a large number of annual reports.
p.000056:
p.000056: BAC: Institutions should provide their IRBs with adequate resources to enable them to discharge their
p.000056: responsibilities.
p.000056:
p.000056: In addition, institutions should be the ones to select the independent auditors. The main requirement of audit is to
p.000056: assess ethical merits, not scientific merits.
p.000056:
p.000056: IRB: Although not officially or legally empowered, one impression is that IRBs have the power to
p.000056: investigate ethics violations even after the protocol has been approved. Do the recommendations require more of IRB
p.000056: than what is already being done?
p.000056:
p.000056:
p.000056:
p.000056: E-153
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: BAC: IRBs will need to report to a national supervisory body.
p.000056:
p.000056: IRB: The Singapore Guideline for Good Clinical Practice (SGGCP) has clearly delineated the roles of
p.000056: monitors, sponsors and auditors. The Paper should follow the SGGCP’s framework so that the IRB’s responsibility
p.000056: is clearly and primarily confined to a review of documents.
p.000056:
p.000056: BAC: One of the purposes of this Paper is to extend the rules in the SGCCP on clinical drug trials to
p.000056: non-drug trials. An IRB is not the enforcer of these rules and these provisions should not lead to unnecessary
p.000056: bureaucracy that stifles research.
p.000056:
p.000056: IRB: There are situations where IRB members find it difficult to confront researchers who are
p.000056: very senior in rank. In fact, many researchers in certain countries who have flouted ethics rules were highly
p.000056: regarded PIs.
p.000056:
p.000056: There is a huge gap between the recommended standards and what IRBs can achieve. While the responsibilities spelt
p.000056: out are probably appropriate, IRBs currently do not have the capacity to take on all of them.
p.000056:
p.000056: BAC: In the UK, IRBs are not the ones who conduct investigation at the research level. It is important
p.000056: for IRBs to have the power to require that an audit be performed. Such controls will reassure the public
p.000056: that adequate protection is in place.
p.000056:
p.000056: IRB: The responsibilities of IRBs in reviewing, supervising and auditing, as well as the means of discharging
p.000056: these responsibilities, need to be more clearly defined. Often, the problem lies not with the lack of regulations
p.000056: (because these are present), but with the lack of people to implement them. Monitoring and auditing of research
p.000056: protocols should be conducted at two levels: at the institution- level, at which independent inspectors
p.000056: are authorised to examine any records at random and report their findings to the IRB; and at the level of the
p.000056: accreditation body, which can mandate that research institutions submit reports.
p.000056:
...
Health / Motherhood/Family
Searching for indicator family:
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p.000016: research programme), the trial or use of a medical device on a human subject, or any test of a human subject’s
p.000016: physiological, emotional or mental responses (not being tests conducted for diagnostic purposes with a view to
p.000016: the therapeutic management of a patient) all qualify as Direct Human Biomedical Research; and
p.000016:
p.000016: (b) Indirect Human Biomedical Research. This comprises any research (not qualifying as Direct Human
p.000016: Biomedical Research) involving human subjects, human tissue, or medical, personal or genetic
p.000016: information relating to both identifiable and anonymous individuals, undertaken with a view to generating data about
p.000016: medical, genetic or biological processes, diseases or conditions in human subjects, or of human physiology or about the
p.000016: safety, efficacy, effect or function of any device, drug, diagnostic, surgical or therapeutic procedure
p.000016: (whether invasive, observational or otherwise) in human subjects whether as one of the objectives or the sole
p.000016: objective, of the research study, trial or activity, and which research, study, trial or activity has
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: HUMAN
p.000017: BIOMEDICAL RESEARCH
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: the potential to affect the safety, health, welfare, dignity or privacy of the human subjects involved in the study, or
p.000017: of the donors of human tissue or information used in the research, or of the family members of any of the human
p.000017: subjects or donors thereof, or to which such medical, personal or genetic information relates.
p.000017:
p.000017: 3.8. For the purposes of these Guidelines, we define Human Biomedical Research as Direct Human
p.000017: Biomedical Research and Indirect Human Biomedical Research taken together.
p.000017:
p.000017:
p.000017: Ethics Review of Direct Human Biomedical Research
p.000017:
p.000017: 3.9. Every research programme involving Direct Human Biomedical Research should be reviewed and approved
p.000017: by a properly constituted ethics committee or IRB.
p.000017:
p.000017:
p.000017: Ethics Review of Indirect Human Biomedical Research
p.000017:
p.000017: 3.10. There is currently no international consensus on what kind of Indirect Human Biomedical Research
p.000017: needs to be formally reviewed by an IRB. Laws, social attitudes and concerns, and ethical formulations vary
p.000017: from jurisdiction to jurisdiction.
p.000017:
p.000017: 3.11. Subject to the recommendations set out in our earlier Reports (the Human Stem Cell Report and the Human Tissue
p.000017: Research Report), we recommend that every research institute have clear policies for the ethics review (full, exempted
p.000017: or expedited review) of all categories of research involving Indirect Human Biomedical Research, as set out
p.000017: below.
p.000017:
p.000017:
p.000017: Exempted Review and Expedited Review of Human Biomedical Research
p.000017:
p.000017: 3.12. Not every proposed programme of Human Biomedical Research requires a full review. In some cases,
...
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: ANNEXES
p.000055:
p.000055:
p.000055: Annexe A: The Human Genetics Subcommittee
p.000055:
p.000055: Annexe B: Consultation Paper entitled “Advancing the Framework of Ethics Governance for Human Research”
p.000055:
p.000055: Annexe C: Distribution List
p.000055:
p.000055: Annexe D: Responses to the Consultation Paper Annexe E: Summary of the Dialogue Session Annexe F:
p.000055: Select References
p.000055: Annexe G: List of Abbreviations
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: ANNEXE A
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: HUMAN GENETICS SUBCOMMITTEE
p.000056:
p.000056:
p.000056: Chairman
p.000056:
p.000056: Associate Professor Terry Kaan Sheung-Hung Faculty of Law
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey Chan Wah Teck
p.000056: Principal Senior State Counsel (Civil) Attorney-General’s Chambers
p.000056:
p.000056: Associate Professor Samuel Chong Department of Paediatrics
p.000056: National University of Singapore
p.000056:
p.000056: Professor Yap Hui Kim
p.000056: Senior Consultant, National University Hospital Professor in Paediatrics, National University of Singapore
p.000056:
p.000056: Associate Professor Chia Kee Seng (from September 2004) Department of Community, Occupational and Family Medicine
p.000056: Faculty of Medicine
p.000056: National University of Singapore
p.000056:
p.000056: Dr Denise Goh Li Meng (from September 2004) Consultant
p.000056: The Children's Medical Institute National University Hospital
p.000056:
p.000056: Dr Lee Soo Chin (from September 2004) Consultant
p.000056: Department of Haematology-Oncology National University Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: A-57
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH
p.000056:
p.000056: A CONSULTATION PAPER
p.000056:
p.000056:
p.000056:
p.000056: THE BIOETHICS ADVISORY COMMITTEE SINGAPORE
p.000056:
p.000056:
p.000056:
p.000056: 16 September 2003
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-58
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: THE BIOETHICS ADVISORY COMMITTEE
p.000056: Chairman
p.000056:
p.000056: Professor Lim Pin
p.000056: University Professor
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey Chan Wah Teck
p.000056: Principal Senior State Counsel, Civil Division, Attorney -General’s Chambers
p.000056:
p.000056: Mr Cheong Yip Seng
p.000056: Editor-in-Chief, English/Malay Newspapers Division, Singapore Press Holdings
p.000056:
p.000056: Associate Professor John Elliott
...
p.000056: physician / researcher. The patient is always entitled to the best clinical management, and research considerations
p.000056: must never override this”. We agree with these statements of the NMEC, and likewise adopt them. In keeping
p.000056: with the spirit of this definition, we therefore exclude therapeutic activities undertaken with the sole
p.000056: intention of benefiting the patient from our definition of clinical research.
p.000056:
p.000056: 3.6. Subject to the preceding qualifications, we propose to define clinical research in the following
p.000056: terms:
p.000056:
p.000056: Any research study, trial or activity involving human subjects, human tissue, or medical, personal or
p.000056: genetic information relating to both identifiable and anonymous individuals, undertaken with a
p.000056: view to generating data about medical, genetic or biological processes, diseases or conditions in human subjects, or
p.000056: of human physiology or about the safety, efficacy, effect or function of any device, drug, diagnostic,
p.000056: surgical or therapeutic procedure (whether invasive, observational or otherwise) in human subjects whether as
p.000056: one of the objectives or the sole objective, of the research study, trial or activity
p.000056:
p.000056: and
p.000056:
p.000056: which research study, trial or activity has the potential to affect the safety, health, welfare, dignity or privacy of
p.000056: the human subjects involved in the study, or of the donors of human tissue or information used in the research, or of
p.000056: the family members of any of the human subjects or donors thereof, or to which such medical, personal or genetic
p.000056: information relates.
p.000056:
p.000056: Savings
p.000056:
p.000056: 3.7. We make clear that nothing in this Consultation Paper is intended to supplant the recommendations
p.000056: that we have made in the Human Stem Cell Report and the Human Tissue Research Report, and tha t
p.000056: the recommendations contained in this Consultation Paper are intended to supplement those advanced in our
p.000056: first two Reports.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-73
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Exceptional Situations
p.000056:
p.000056: 3.8. We note that there may be some exceptional circumstances in which it may be ethically acceptable
p.000056: to abbreviate or temporarily suspend the usual ethics review procedures and requirements, provided that all the
p.000056: applicable legislative and regulatory requirements are satisfied. We have in mind situations of national
p.000056: security or emergency health situations, in w hich urgent research may have to be carried out to avert
p.000056: harm to national security or for the urgent protection or treatment of whole populations at risk. In such cases, we
p.000056: think that it is permissible for institutional review boards in consultation with the proper authorities to
...
Social / Access to Social Goods
Searching for indicator access:
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p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: INTRODUCTION AND CURRENT
p.000014: FRAMEWORK
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014: 2.34. The vast majority of these new players in the field of human biomedical research in Singapore
p.000014: are keenly aware of the need for proper ethics governance. Most researchers are anxious to conform to
p.000014: internationally accepted standards for ethics governance. In many cases, researchers are involved as
p.000014: collaborators in multinational or multi-centre (or both) biomedical research projects.
p.000014:
p.000014: 2.35. With the development of the biomedical sector in Singapore, new avenues of biomedical inquiry are rapidly
p.000014: emerging. The traditional categorisation of research for ethics governance, which separates research
p.000014: into pharmaceutical trials and non-pharmaceutical trials, is becoming irrelevant and obsolete. Some new kinds of
p.000014: research may blur the border between these two categories. New kinds of biomedical research include trials of medical
p.000014: devices, experimental therapeutic procedures (which may or may not involve drugs), new modes of non-drug treatment and
p.000014: new diagnostic methods. Other increasingly important research includes epidemiological or population studies
p.000014: (which may or may not require invasive interaction with human subjects), genetic screening, genetic research and
p.000014: research that involves no direct interaction with human subjects but only access to their medical, personal or genetic
p.000014: information.
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000015: 15
p.000015:
p.000015: HUMAN
p.000015: BIOMEDICAL RESEARCH
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: PART B: HUMAN BIOMEDICAL RESEARCH
p.000015: SECTION III: HUMAN BIOMEDICAL RESEARCH
p.000015:
p.000015: 3. Human Biomedical Research Defining Human Biomedical Research
p.000015: 3.1. In this section, we consider what kinds of human biomedical research ought to be subject to
p.000015: the framework of ethics go vernance that we recommend in these Guidelines.
p.000015:
p.000015: 3.2. In keeping with our terms of reference, we consider only such human biomedical research that
p.000015: involves an interaction (whether direct or otherwise) with a human subject or human biological
p.000015: material, and therefore exclude any human biomedical research in relation to:
p.000015:
p.000015: (a) Genetically modified organisms;
p.000015: (b) Animals and their treatment; and
p.000015: (c) Economic, sociological and other studies in the disciplines of the humanities and social sciences.
p.000015:
p.000015: 3.3. Human biomedical research is a term capable of a very broad definition. In our review of the approaches
...
p.000018: Biomedical Research that could be exempted from ethics review. The most important consideration is that there
p.000018: should be no likelihood of harm to the research subject.
p.000018:
p.000018: 3.15. In general, we suggest that categories for Exempted Review should be drawn from categories of
p.000018: Indirect Human Biomedical Research. By way of illustration, the following categories of Indirect Human
p.000018: Biomedical Research could be considered for Exempted Review, taking into account current practice:
p.000018:
p.000018: (a) Writing up or reporting of individual patients’ clinical results by the patients’ doctors, provided that the
p.000018: patients’ consent for procedures and interventions in clinical management have been obtained and the patients’ privacy
p.000018: protected, for example, the review of a clinical programme that includes demographic, clinical and
p.000018: outcome parameters, which are useful in the audit of the programme; or the review of a procedure or
p.000018: treatment (a surgical technique or drug treatment outcome) by a physician or surgeon, where the choice of the
p.000018: drug or technique is based on the clinical judgment of the physician or surgeon and on best
p.000018: practices and not on any randomisation procedure. Researchers who are not the attending physicians in
p.000018: the programme but wish to have access to such information should send their proposals to the IRB in
p.000018: the usual way;
p.000018:
p.000018: (b) Research using appropriately designed data escrow or other arrangements in which personal or
p.000018: other identity information is securely withheld from researchers by a third party provider of information,
p.000018: there being no possibility of researchers by themselves being able to trace or reconstruct significant
p.000018: information on the identity of subject donor;
p.000018:
p.000018: (c) Research using established commercially available cell lines or commercially available anonymous
p.000018: DNAs, RNAs and fixed tissues; and
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019: HUMAN
p.000019: BIOMEDICAL RESEARCH
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: (d) The development of diagnostic tests using existing samples for test validation purposes provided
p.000019: that the necessary consent for the taking and use of the samples has been obtained.
p.000019:
p.000019: Expedited Review
p.000019:
p.000019: 3.16. Some categories of research programmes may be permitted a less formal process of review than that of a
p.000019: standard full review. For example, the Chairperson or other IRB delegate(s) (the reviewer) may be empowered to
p.000019: conduct Expedited Review.
p.000019:
p.000019: 3.17. The same principles and general considerations set out above in relation to the categories of Human Biomedical
p.000019: Research that qualifies for Exempted Review also apply to IRBs’ determination of categories permitted
p.000019: Expedited Review. Research qualifying for Expedited Review should present no more than minimal risks to research
p.000019: subjects.
p.000019:
p.000019: 3.18. By way of illustration, the following categories of Human Biomedical Research could be considered
p.000019: for Expedited Review, taking into account current practice:
p.000019:
p.000019: (a) Minor changes to previously approved research;
p.000019:
p.000019: (b) Annual reviews of previously approved research in which there has been little or no change in the on- going
p.000019: research;
p.000019:
p.000019: (c) The analysis of patients’ information without interacting with the patients. Researchers may be
p.000019: allowed access to medical records only if the IRB is satisfied that there is potential scientific / medical
p.000019: benefit of the research and that the researchers will take appropriate measures to protect the privacy of the
p.000019: individuals;
p.000019:
p.000019: (d) The local portion (at the level of specific institutions) of a multi- centre or multinational researc
p.000019: h programme that has already received a full review and approval by the lead IRB (as elaborated
p.000019: in paragraphs 5.49 to 5.56 of this Report); and
p.000019:
p.000019: (e) Research involving human tissues from tissue banks. IRBs must be satisfied that the tissues are obtained from
p.000019: a reliable source in which consent has been obtained for the tissues to be used for research and that the donor's
p.000019: privacy is protected.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: HUMAN
p.000020: BIOMEDICAL RESEARCH
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020: Stem Cell Lines
p.000020:
p.000020: 3.19. We make clear that all research involving the use of human embryonic stem cell lines or the creatio
p.000020: n of such human stem cell lines requires full ethics review.
p.000020:
p.000020:
p.000020: Cadaveric, Foetal and Legacy Tissues
p.000020:
p.000020: 3.20. We reiterate that nothing in these Guidelines is intended to displace the recommendations we
p.000020: advance in our Human Tissue Research Report. We take the view that human biomedical research to be conducted on
...
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028:
p.000028: ETHICS GOVERNANCE
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028: appropriate hospitals or other medical institutions. This approach could also be applied to biomedical
p.000028: researchers who are not registered medical practitioners. In any event, the requirements for appropriate ethics
p.000028: review as defined in these guidelines should apply regardless of the institutional affiliation of researchers.
p.000028:
p.000028: 5.6. There is universal agreement in all developed countries that IRBs are central to a proper framework
p.000028: of ethics governance of human research and that the primary objective of an IRB is to protect and assure
p.000028: the safety, health, dignity, welfare and well-being of human research subjects, in keeping with the
p.000028: principles outlined above.
p.000028:
p.000028: 5.7. Increasingly, collaborative research programmes are carried out across international borders (in
p.000028: multinational research programmes) or by researchers in several institutions (in multi-centre research
p.000028: programmes), or even a combination of both. It is usually a condition of such research programmes that the
p.000028: proposed or prospective researchers secure the approval of a properly constituted IRB in their own country or
p.000028: institution. Without a properly constituted IRB or access to such an IRB, an institution engaging in human
p.000028: research cannot hope to participate in such multinational or multi-centre collaboration research
p.000028: programmes.
p.000028:
p.000028: 5.8. From this viewpoint, the harmonisation of our national ethics governance framework with that in
p.000028: leading research jurisdictions is of national strategic importance.
p.000028:
p.000028: 5.9. The ultimate responsibility fo r the ethics compliance of human biomedical research rests with the
p.000028: researchers who carry out the research, and with the institution that sanctions the research or in which research is
p.000028: carried out.
p.000028:
p.000028: 5.10. The IRB is the vehicle through which such institutions ac t to implement a proper system of ethics
p.000028: governance of research carried out in such institutions.
p.000028:
p.000028: 5.11. We accordingly recommend that every institution that conducts Human Biomedical Research, or allows
p.000028: such research to be carried out on its premises, or on its patients, or involving access to or use of human
p.000028: tissue collections in its custody, or involving access to or use of medical records or other personal information in
p.000028: its custody, should establish and maintain an effective IRB.
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029:
p.000029: ETHICS GOVERNANCE
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Shared and Domain Institutional Review Boards
p.000029:
p.000029: 5.12. Where by reason of the small size of the institution or the small number of research proposals it is
p.000029: impractical to establish and maintain a standing IRB of its own, such institutions should make clear
p.000029: arrangements with other institutions which maintain IRBs for research proposals to be considered by
p.000029: the IRBs of larger institutions.
p.000029:
p.000029: 5.13. Alternatively, it is permissible for several such institutions to jointly appoint a shared IRB.
p.000029:
p.000029: 5.14. Even in cases of institutions that already have their own IRBs, these institutions may prefer or
p.000029: wish to refer some kinds of research applications (for example, a proposal for research in a specialist area)
p.000029: to a specialist IRB or a domain IRB that has the technical capacity to assess research in that specialised area.
p.000029: Again, several institutions could jointly appoint and share in the expertise of such an IRB in situations where such
p.000029: expertise is limited. Such a specialist IRB has the advantage of delivering consistent decisions, special
p.000029: competence and knowled ge in their field of specialisation.
p.000029:
...
p.000038: purposes.
p.000038:
p.000038: 5.69. The requirements of impartiality, fair review and documentation of decisions should apply
p.000038: equally to IRBs engaged in the continuing review or supervision of a research programme.
p.000038:
p.000038: 5.70. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000038: obtaining of free and informed consent of subjects in pharmaceutical trials should be applied to all other
p.000038: kinds of human biomedical research with appropriate modifications.
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039:
p.000039: ETHICS GOVERNANCE
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 5.71. Both researchers and IRBs should take especial care to ensure that potential research
p.000039: subjects will be able to understand and assess the risks of participation, and that the consent-taking
p.000039: procedure and the documentation are properly designed to achieve this end.
p.000039:
p.000039: 5.72. Both researchers and IRBs should ensure that research participants are aware that they have the right
p.000039: to withdraw from the research programme at any time.
p.000039:
p.000039: 5.73. We recommend that IRBs and institutions formalise arrangements that allow participants a one-stop
p.000039: direct access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000039: quality service standards and control. In this way, research participants can have access to independent officers
p.000039: in order to give feedback on the research, or to express their concerns.
p.000039:
p.000039: 5.74. For related reasons, we further recommend that researchers consider appointing a member
p.000039: of their research team to serve as a one-stop participant contact. This contact person should be
p.000039: a registered medical practitioner or a senior member of the research team. It will be the responsibility
p.000039: of this person to handle initial contact in all cases in which a research programme involves any level of
p.000039: clinical intervention or interaction with the participants, and in cases where the interaction with
p.000039: participants is delegated to support and field workers or assistants (for example, the collation of medical
p.000039: histories or physical examination). We also recommend that IRBs make the appointment of a contact person a
p.000039: condition of approval.
p.000039:
p.000039: 5.75. A copy of every document signed by research subjects or given to them to read, including the consent
p.000039: documentation, should be retained by the research subjects.
p.000039:
p.000039: 5.76. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000039: Research Report apply to the use of human biological materials in Human Biomedical Research.
p.000039:
p.000039: 5.77. Meetings. IRBs should have regular, formal, face-to- face meetings with a defined quorum. The work of the
p.000039: board should not be conducted routinely via circulation of documents. Applications that raise novel, unusual
...
p.000040: Human Biomedical Research that could qualify for Exempted Review or Expedited Review, it should draw up a
p.000040: set of standard operating procedures to provide for these categories.
p.000040:
p.000040: 5.79. Instead of requiring consideration by the entire IRB, the standard operating procedures may allow the
p.000040: Chairperson or his delegate(s) to make decisions on applications that qualify for Expedited Review.
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041:
p.000041: ETHICS GOVERNANCE
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: SECTION VI: RESEARCHERS
p.000041:
p.000041: 6. Researchers
p.000041:
p.000041: The General Responsibilities of Researchers
p.000041:
p.000041: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethics governance of Human
p.000041: Biomedical Research. More than any other party or parties in the ethics review and governance
p.000041: process, researchers have the fullest access to the facts on which ethical judgments are to be made.
p.000041:
p.000041: 6.2. Researchers are responsible for making the threshold decisions in conceiving, designing and
p.000041: putting together a proposed research project. In these decisions, they have the most freedom to shape
p.000041: the proposed research project in a way that gives fullest consideration and respect to ethical
p.000041: considerations, always cognizant of the fact that it is the human subjects whom they study who make
p.000041: their research possible, and are therefore under an obligation to respect and to protect the subjects.
p.000041:
p.000041: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000041: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000041: judgments.
p.000041:
p.000041: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000041: aspects of the Human Biomedical Research rests with the researchers. IRBs bear the responsibility for the
p.000041: overall ethics review and approval of Human Biomedical Research programmes.
p.000041:
p.000041: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000041: responsibility that cannot be transferred or delegated to an IRB or to any party in the ethics review and
p.000041: governance process merely through the approval of a research proposal by an IRB.
p.000041:
...
p.000044: areas requiring supervision or direction by a member of a team. Such statements outlining the roles and
p.000044: responsibilities of each of the researchers in a team should be included in the submission to the IRB.
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045:
p.000045: ETHICS GOVERNANCE
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 6.26. The PI shall be responsible for settling, coordinating and formalising the distribution of roles and
p.000045: responsibilities among the researchers in a research programme.
p.000045:
p.000045:
p.000045: Continuing Responsibilities, Deviation and Variation
p.000045:
p.000045: 6.27. The ethical responsibilities of researchers outlined in this section are continuing
p.000045: responsibilities that apply at least for the lifetime of the research project, which is defined
p.000045: as the time the research project is submitted to the IRB for ethics review until the time the research project is
p.000045: deemed to have concluded or been terminated.
p.000045:
p.000045: 6.28. When an IRB approves a research application, its judgment is based on the facts and proposals disclosed to it
p.000045: by the researchers in their application. Most significantly, the ethical judgment has to be made before the research
p.000045: project begins. Once the project is approved and the research is underway, researchers may find that varia
p.000045: tions or departures from the original proposal may be dictated by such considerations as budget,
p.000045: access to subjects, unexpected clinical results and other factors. A research project may also expand in scope, in
p.000045: its objectives, or in the researchers involved. Some researchers may, for example, resign or take a less active role,
p.000045: while other researchers may be recruited. There are other situations in which deviation may occur. A
p.000045: proposed course of action may be found to pose greater risks for the proposed subject population than originally
p.000045: assessed, or that the research has resulted in greater harm (whether of degree or of incidence) than originally
p.000045: contemplated. Or it may be discovered in the course of the research that some part of the original protocol as
p.000045: proposed in the ethics review application has not been strictly adhered to, although such departure may have been
p.000045: made in good faith, by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000045:
p.000045: 6.29. As part of his continuing responsibilities, the PI in particular is under a strict obligation
p.000045: to immediately and in writing seek approval for any changes where such changes have not yet been made, or
p.000045: otherwise report any changes where such changes have already been made, to the IRB by which the initial research
p.000045: application was considered and approved. The PI shall in his request or report detail the changes, giving
p.000045: his objective assessment of any impact and consequences (both from the clinical and ethical points of view)
p.000045: of the changes.
p.000045:
...
p.000048: the consent of the attending physicians.
p.000048:
p.000048: 6.42. The existence of attending physicians (or the likelihood of the existence of such attending physicians) should
p.000048: be disclosed to the IRB by the PI at the time that the research application is being made.
p.000048:
p.000048: 6.43. The IRB may then consider whether informing and discussing with the attending physicians should
p.000048: be made a formal requirement of ethics approval. Such a requirement should be made upon
p.000048: considerations that include, but are not limited to, the following:
p.000048:
p.000048: (a) In the case of research that involves any level of clinical interaction with patients being treated or
p.000048: managed for medical conditions relevant to the proposed programme of research, researchers should be required
p.000048: to contact and inform the attending physicians. The IRB should decide on the facts of each case whether or
p.000048: not there is a sufficient connection between the proposed programme of research and the clinical treatment and
p.000048: management of the subject-patients, bearing in mind the interests of ensuring the safety, health, dignity, welfare
p.000048: and privacy of the subject-patients. Where the IRB is satisfied that there is no reasonable connection
p.000048: between the research programme and the treatment and management of the subject-patient, the researchers may dispense
p.000048: with informing and discussing with the attending physicians of their subjects;
p.000048:
p.000048: (b) In the case of research that involves access to patients’ medical records but with minimal levels of
p.000048: clinical interaction (e.g. the taking of blood or urine samples) or only social interaction (e.g.
p.000048: interviewing the subject-patient for a history), the IRB may in its discretion make formal contact and
p.000048: discussion a condition of ethics approval if it takes the view that the proposed interaction is relevant to the
p.000048: continued medical treatment and management of the subject- patient. Otherwise, researchers may in such
p.000048: cases dispense with contacting the attending physicians; and
p.000048:
p.000048: (c) In the case of research that involves access to and a study of patients’ medical records without any kind of
p.000048: contact between researchers and the patients, researchers need not inform or discuss with the
p.000048:
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049:
p.000049: ETHICS GOVERNANCE
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049: attending physicians (on the assumption, of course, that they have complied with all other applicable
p.000049: requirements).
p.000049:
p.000049: 6.44. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000049: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the subjects
p.000049: without first seeking and obtaining the approval of both the attending physicians and the IRB.
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000050: 50
p.000050:
p.000050:
p.000050: ETHICS GOVERNANCE
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION VII: INSTITUTIONS
p.000050:
p.000050: 7. Institutions
p.000050:
p.000050: The Responsibilities of Appointing Institutions
p.000050:
p.000050: 7.1. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical Research and
p.000050: the protection of human subjects in all Human Biomedical Research carried out on their premises or facilities, or by
p.000050: their employees, or on their patients, or involving access to or use of human tissue collections in their custody, or
p.000050: involving access to or use of medical records or other personal information in their custody.
p.000050:
p.000050: 7.2. Every institution involved in Human Biomedical Research as defined in these Guidelines should
p.000050: establish and maintain an effective IRB. The IRB is accountable to the appointing institution, which must
p.000050: accept legal responsibility for the decisions of its IRB.
p.000050:
p.000050: 7.3. Institutions should lay policies for the composition of IRBs and the formal appointment of IRB members in
p.000050: accordance with the general principles and guidance presented in these Guidelines and, in particular, those set
p.000050: out under “Specific Operating Procedures for Institutional Review Boards” in Section V.
p.000050:
p.000050: 7.4. It is the responsibility of institutions to provide adequate resources and administrative support
p.000050: so as to enable IRBs to discharge their duties and responsibilities in an effective and timely manner.
p.000050:
p.000050: 7.5. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of
p.000050: their work and IRBs should likewise ensure that their workload does not compromise the quality of their
p.000050: review. If this is likely, the institution is obliged to establish additional IRBs, to enlarge the
p.000050: membership of the IRB or to make formal arrangements for other IRBs to provide an opinion.
p.000050:
p.000050: 7.6. Institutions are obliged to ensure that IRBs receive adequate administrative support that is commensurate
p.000050: with the central role of the IRB in the ethics governance process. In this respect, the institution may take
...
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051:
p.000051: ETHICS GOVERNANCE
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: 7.7. Such full-time administrative support should be sufficient to allow the IRB to:
p.000051:
p.000051: (a) Ensure continuity and consistency in the work of the IRBs;
p.000051:
p.000051: (b) Discharge any continuing review and supervisory obligations, outcome assessment and reporting
p.000051: duties;
p.000051:
p.000051: (c) Ensure that the IRB's decisions are made with regard to previously established precedents and
p.000051: decisions tha t they and their predecessors have made; and
p.000051:
p.000051: (d) Ensure that proposals are reviewed and dealt with in a timely manner within the target time frames set by the
p.000051: institution.
p.000051:
p.000051: 7.8. The core members of the IRB should be able to devote sufficient and protected time commensurate
p.000051: with the workload of the IRB.
p.000051:
p.000051: 7.9. Institutions are also responsible for providing their IRB members with a full indemnity as set
p.000051: out in paragraphs 7.17 to 7.22 and this should be reflected in their letters of appointment.
p.000051:
p.000051: 7.10. Institutions providing care should retain responsibility for the quality of all aspects of care afforded to
p.000051: human subjects whether or not some aspects of care are part of a research study.
p.000051:
p.000051: 7.11. Medical Records and Patient Information. We recognise that the issues arising from access to the
p.000051: use of and the custody of medical records and other patient information are becoming increasingly complex. In this
p.000051: area, the ethical issues are inextricably interwoven with legal considerations, and the impact of the existing
p.000051: law is currently unclear in many situations. We hope to explore these issues in a separate subsequent report.
p.000051:
p.000051: 7.12. In the context of institutions such as hospitals with centralised patient records and databases,
p.000051: we recommend that appointing institutions take steps to determine who within the administrative structure should
p.000051: be the proper administrative custodians responsible for patients’ medical information in the
p.000051: institution, and to advise their IRBs accordingly.
p.000051:
p.000051: 7.13. In situations where any of the researchers are also the administrative custodian of patients’
p.000051: medical information within the institution, procedures should be established to address actual,
p.000051: potential or apparent conflicts of interest.
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
...
p.000056: in multi- jurisdictional or multi-centred (or both) clinical research projects.
p.000056:
p.000056: 2.43. With the development of the biomedical industry in Singapore, new avenues of biomedical inquiry
p.000056: are rapidly emerging, and the traditional categorisation of research trials into drug trials and non-drug trials
p.000056: for the purposes of ethical governance is rapidly becoming irrelevant and obsolete. Some new kinds of
p.000056: research may blur the border between drug and non-drug trials. For example, the first use of a new drug
p.000056: already approved elsewhere on the local population: in this situation, is the trial one for the drug, or a
p.000056: trial to observe and determine the responses of the local population to the drug? New kinds of research trials
p.000056: include trials of medical devices, experimental therapy procedures (which may or may not involve drugs), new modes
p.000056: of non-drug treatment and new diagnostic methods. Other increasingly important research include
p.000056: epidemiological or population studies (which may or may not require invasive interaction with human subjects),
p.000056: genetic screening, genetic research and research which involve no direct interaction with human subjects but only
p.000056: access to their personal medical or genetic information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-69
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.44. In summary:
p.000056:
p.000056: • The most comprehensive formal framework for the ethical governance of clinical research trials at the moment is
p.000056: limited largely to drug trials, or “clinical trials” as defined in the Medicines Act. The principal
p.000056: documents setting out this framework of ethical governance are the Medicines Act, the Clinical Trials
p.000056: Regulations, and the SGGCP. In this framework, the HSA is the principal regulatory agency.
p.000056:
p.000056: • For clinical research other than drug tr ials, the Ministry of Health exercises indirect control over
p.000056: hospitals and medical clinics under the Private Hospitals and Medical Clinics Act. The Ministry of Health has directed
p.000056: that hospitals establish ethics committees to review and approve applications for both drug and
p.000056: non-drug trials.
p.000056:
p.000056: • For clinical research other than drug trials, the main document spelling out a framework for ethical governance is
p.000056: the NMEC Guidelines.
p.000056:
p.000056: • There is some uncertainty as to whether the jurisdiction of the Ministry of Health under the Private Hospitals and
...
p.000056: level as medical boards, and that the institutional review board should report directly to the highest level of
p.000056: management of the hospital. We believe that the term “institutional review board” (“IRB”) best reflects this
p.000056: role.
p.000056:
p.000056: 5.3. We differentiate here between IRBs which review, approve and monitor clinical research involving
p.000056: humans, and hospital ethics committees that address medical practice issues. For the avoidance of
p.000056: doubt, the recommendations in this paper cover only IRBs which review, approve and monitor clinical
p.000056: research involving human beings.
p.000056:
p.000056: 5.4. There is universal agreement in all developed countries that IRBs are central to a proper
p.000056: framework of ethical governance of human research, and that the primary objective of an IRB is the protection and
p.000056: assurance of the safety, health, dignity, welfare and well-being of human research subjects, in keeping with
p.000056: the principles outlined above.
p.000056:
p.000056: 5.5. Increasingly, collaborative research programmes are ca rried out across international borders (in
p.000056: multi- national research programmes) or by researchers in several institutions (in multi-centre research
p.000056: programmes), or even a combination of both. It is usually a condition of such research programmes that the
p.000056: proposed or prospective researchers secure the approval of a properly constituted IRB in their own country or
p.000056: institution. Without a proper constituted IRB or access to such an IRB, an institution engaging in human research
p.000056: cannot hope to participate in suc h multi- national or multi-centre collaboration research programmes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-80
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.6. From this viewpoint, the harmonisation of our national ethical governance framework with that in
p.000056: leading research jurisdictions is of national strategic importance.
p.000056:
p.000056: 5.7. The ultimate respons ibility for the ethical compliance of clinical research rests with the researchers who
p.000056: propose and carry out the research, and with the institution which sanctions the research or in which research is
p.000056: carried out.
p.000056:
p.000056: 5.8. The IRB is the vehicle through which such institutions act to implement a proper system of ethical
p.000056: governance of research carried out in such institutions.
p.000056:
p.000056: 5.9. Every institution that conducts research, or allows research to be carried out on its premises, or
p.000056: on its patients, or on or involving acces s to or use of human tissue collections in its custody, or on or involving
p.000056: access to or use of medical records or other personal information in its custody, should have an effective
p.000056: and properly constituted IRB.
p.000056:
p.000056:
p.000056: Recommendation 3:
p.000056:
p.000056: The current requirement that every hospital have an institutional review board should be statutorily
p.000056: formalised, and extended to all institutions that carry out clinical research. Every institution that
p.000056: conducts research, or allows research to be carried out on its premises, or on its patients, or on or involving
p.000056: access to or use of human tissue collections in its custody, or on or involving access to or use of medical records or
p.000056: other personal information in its custody should have an effective institutional review board.
p.000056:
p.000056:
p.000056: Shared, “Domain” and Other Special Institutional Review Boards
p.000056:
p.000056: 5.10. Where by reason of the small size of the institution or the small number of research proposals it is
p.000056: impractical to establish and maintain a standing IRB of its own, such institutions should make clear
p.000056: arrangements with other institutions which maintain IRBs, to be supervised and audited by the IRBs of these other
p.000056: institutions.
p.000056:
p.000056: 5.11. Alternatively, it is permissible for several such institutions to jointly appoint a shared IRB.
p.000056:
p.000056: 5.12. Even in cases of institutions who already have their own IRBs, these institutions may prefer or
p.000056: wish to refer some kinds of research applications
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-81
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: (for example, a proposal for research in a specialist area) to a specialist IRB or a domain IRB which has
p.000056: the technical capacity to assess research in that specialised area. Again, several institutions could jointly appoint
p.000056: and share in the expertise of such an IRB in situations where such expertise is limited. Such a specialist IRB has
p.000056: the advantage of delivering consistent decisions, and special competent and knowledge in their field
p.000056: of specialisation. It is also acceptable that a cluster of hospitals cooperate in developing a panel of IRBs to cover
p.000056: all reasonable disciplines.
...
p.000056: member should recuse himself or herself from any consideration of the case by the IRB, a nd he or she should refrain
p.000056: from offering his or her opinion to the board on the particular research under review.
p.000056:
p.000056: 5.55. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000056: the board.
p.000056:
p.000056: 5.56. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000056: obtaining of free and informed consent of subjects in drug trials be in principle extended to all other kinds of
p.000056: clinical research with appropriate modifications.
p.000056:
p.000056: 5.57. Both researchers and IRBs should take especial care to ensure that the proposed human subjects will
p.000056: be able to understand and assess the risks of participation, and that the consent -taking procedure and the
p.000056: documentation are properly designed to achieve this end.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-91
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.58. Both researchers and IRBs should ensure that the participants of research projects are aware that they have
p.000056: the right to withdraw from the research programme at any time.
p.000056:
p.000056: 5.59. We recommend that IRBs and institutions formalise arrangements which allow participants a one-stop direct
p.000056: access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000056: quality service standards and control. In this way, participants in research trials can have access to independent
p.000056: officers in order to give feedback on the trial, or to express their concerns.
p.000056:
p.000056: 5.60. In the same vein, we further recommend that researchers consider (and IRBs should consider making it
p.000056: a condition of approval) appointing one of their number (who should be a registered med ical practitioner or a senior
p.000056: member of the research team) as a one-stop participant contact in all cases where the research programme involves any
p.000056: level of clinical intervention or interaction with the participants, and in cases where the interaction (for example,
p.000056: the collation of medical histories, or physical examination) with participants is delegated to support and field
p.000056: workers or assistants.
p.000056:
p.000056: 5.61. A copy of every document signed by research subjects or given to them to read, including the consent
p.000056: documentation, should be given to and retained by the research subjects.
p.000056:
p.000056: 5.62. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000056: Research Report apply to the use of human biological materials in clinical research.
p.000056:
p.000056: 5.63. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of its
p.000056: work, and IRB should likewise ensure that its workload does not compromise the quality of its review. Where
p.000056: this is likely, it is the obligation of the institution to establish additional IRBs, or to enlarge the
p.000056: membership of the IRB, or make formal arrangements for other IRBs to provide an opinion.
p.000056:
...
p.000056: of research proposals, in a properly-
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-92
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: deliberated and written set of Standard Operating Procedures for the work of the board.
p.000056:
p.000056: 5.66. Such expedited or exempted review should be allowed only for classes of research programmes which involve
p.000056: minimal or no risk to the safety, health, welfare and well-being of the participants and which are
p.000056: widely accepted in the research community as being eligible for exempted or expedited review.
p.000056:
p.000056: 5.67. The Standard Operating Procedures may allow decisions on applications qualifying for expedited or
p.000056: exempted review to be decided by the chairperson of the IRB or his delegate(s) instead of
p.000056: having to be considered by the whole board.
p.000056:
p.000056: 5.68. Examples of cases in which an exemption from review or an expedited review may be permitted are
p.000056: the analysis and publication of the clinical results of a regime of therapy given by a registered medical
p.000056: practitioner to his or her patients in which the regime of therapy is given purely for therapeutic
p.000056: objectives, or the analysis of patient information without any interaction with the patients themselves.
p.000056:
p.000056: 5.69. Medical Records and Patient Information. The BAC recognises that the issues arising from access to the
p.000056: use of and the custody of medical records and other patient information is becoming increasingly complex. In
p.000056: this area, the ethical issues are inextricably interwoven with legal considerations, and the
p.000056: impact of the existing law is currently unclear in many situations. We hope to explore these issues in a
p.000056: separate subsequent report.
p.000056:
p.000056: 5.70. In the context of institutions such as hospitals with centralised patient records databases, we
p.000056: recommend that IRBs should take steps to determine who should be the proper administrative custodians responsible for
p.000056: patient medical information in the institution, and to establish a system through which the custodians
p.000056: would inform the attending physicians before releasing patients’ medical information for the
p.000056: purposes of medical research.
p.000056:
p.000056: 5.71. In situations where any of the researchers are also the administrative custodian of patient medical
p.000056: information within the institution, procedures should be established to address potential or apparent conflicts of
p.000056: interest.
p.000056:
p.000056: 5.72. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000056: kinds of patient and medical information, and should formulate these procedures in consultation with their
p.000056: ethics committees.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-93
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.73. It is desirable that the IRB should have the ultimate authority and responsibility for
p.000056: the ethical clearance of access to patient medical information within the institution, so that no
p.000056: patient medical information may be released for research purposes without clearance by the IRB. Such authority
p.000056: should by necessity also extend over the administrative custodians of patient medical information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-94
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VI: RESEARCHERS
p.000056:
p.000056: 6. The Responsibilities of Researchers
p.000056:
p.000056: The general responsibilities of researchers
p.000056:
p.000056: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethical governance of clinical
p.000056: research. More than any other party or parties in the ethical review and governance process, they are in
p.000056: the position of having the fullest access to the facts on which ethical judgments are to be made.
p.000056:
p.000056: 6.2. They are responsible for making the threshold decisions in conceiving, designing and putting
p.000056: together a proposed research project. In these decisions, they have the most freedom to shape the
p.000056: proposed research project in a way that gives fullest consideration and respect to ethical considerations,
p.000056: always cognizant of the fact that it is the human subjects whom they study who make their research
p.000056: possible, and are therefore under an obligation to respect and to protect.
p.000056:
p.000056: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000056: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000056: judgments.
p.000056:
p.000056: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000056: aspects of the clinical research in question which involves human subjects rests with the
p.000056: researchers. IRBs bear the responsibility for the overall ethical review and approval of
p.000056: clinical research programmes, as explained in Recommendation 4.
p.000056:
p.000056: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000056: responsibility which is not and cannot be transferred or delegated to an IRB or any party in the ethics
p.000056: review and governance process merely through the approval of a research proposal by an IRB.
...
p.000056: statements outlining the roles
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-98
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: and responsibilities of each of the researchers in a team should be included in the submission to the ethics committee.
p.000056:
p.000056: 6.26. The Principal Investigator(s) shall be responsible for settling, coordinating and formalising the
p.000056: distribution of roles and responsibilities among the researchers in a research programme.
p.000056:
p.000056: Continuing Responsibilities, Deviation and Variation
p.000056:
p.000056: 6.27. The ethical responsibilities of researchers outlined in this section are continuing responsibilities
p.000056: which apply at least for the lifetime of the research project, that is, from the time the research project is
p.000056: submitted by the researchers to the IRB for ethics review, until such time as the research project is deemed to have
p.000056: concluded or been terminated.
p.000056:
p.000056: 6.28. When an IRB grants its approval on a research application, it can only make its judgment as to
p.000056: whether approval should be granted to the research application based on the facts and proposals disclosed to it
p.000056: by the researchers in their application. Most significantly, the ethical judgment has to be made before the
p.000056: research project begins. Once the project is approved, and the research is underway, researchers
p.000056: often find that variations or departures from the original proposal may be dictated by suc h considerations as
p.000056: budget, access to subjects, unexpected clinical results and other factors. A research project may also
p.000056: expand in scope, in its objectives, or in the researchers involved – some researchers may resign, or decide to
p.000056: take a less active ro le, while other researchers may be recruited. Or it may be discovered that a proposed
p.000056: course of action poses greater risks for the proposed subject population than originally assessed, or that the trial
p.000056: has resulted in greater harm (whether of degree or o f incidence) then originally contemplated. Or it
p.000056: may be discovered in the course of the trial that some part of the original protocol as proposed in the ethics
p.000056: review application has not been strictly adhered to, although such departure may have been made in good faith
p.000056: by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000056:
p.000056: 6.29. As part of their continuing responsibilities, the Principal Investigator(s) in particular is under a
p.000056: strict obligation to immediately and in writing seek approval for any changes where such changes have not yet been
p.000056: made, or otherwise report any changes where such changes have already been made, to the IRB by which initial
p.000056: research application was considered and approved. The Principal Investigator(s) shall in their request or
p.000056: report detail the changes, giving their objective assessment of any impact and consequences (both from
p.000056: the clinical and ethical points of view) of the changes.
p.000056:
p.000056:
p.000056:
p.000056:
...
p.000056: 6.37. We further take the view that where researchers are aware that the proposed research subjects are
p.000056: currently receiving treatment or otherwise being attended to by physicians, reasonable efforts should be made on an
p.000056: informal basis by the researchers to contact and inform the attending physicians of the proposed research
p.000056: progr amme. If the research subjects customarily attend at a hospital or clinic, and are attended to by different
p.000056: physicians on their visits, reasonable efforts should be made on an informal basis to contact
p.000056: and inform the institution concerned, and the consultant or senior person having charge of the department
p.000056: or clinic concerned.
p.000056:
p.000056: 6.38. The existence of attending physicians (or the likelihood of the existence of such attending physicians) should
p.000056: be disclosed to the IRB by the Principal Investigator(s), at the time that the research application is being made.
p.000056:
p.000056: 6.39. The IRB may then consider whether contacting the attending physicians should be made a formal
p.000056: requirement of ethics approval, upon considerations which should include, but not be limited to, the
p.000056: following:
p.000056:
p.000056: 6.39.1. In the case of research which involves any level of clinical interaction with patients,
p.000056: researchers should be formally required to contact and inform the attending physicians, in the interests of
p.000056: ensuring the safety, health, welfare and well-being of the subject patients.
p.000056:
p.000056: 6.39.2. In the case of research which involves access to patient medical records, but with minimal levels of
p.000056: interaction for the purposes of obtaining more information (for instance, interviewing the subject
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-101
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: patient for a history), researchers should still be encouraged to contact and inform the attending physicians,
p.000056: and the IRB may in its discretion make such formal contact and information a condition of ethics approval.
p.000056:
p.000056: 6.39.3. In the case of research which involves access to and a study of patient medical records without
p.000056: any kind of contact at all between the researchers and the subject patients, the IRB need not require
p.000056: researchers to formally contact or inform the attending physicians (on the assumption, of course, that they have
p.000056: complied with all other applicable requirements).
p.000056:
p.000056: 6.39.4. We take the view that efforts to contact and inform the attending physician(s), or the consultant or
p.000056: senior person in charge of the department or clinic concerned, should be made before
p.000056: commencement of the research project. Whe re this is not possible, such contact must be made as immediately after
p.000056: commencement of the research project as may be practicable, or as the IRB may direct.
p.000056:
p.000056: 6.40. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000056: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the
p.000056: subject patients, without first seeking and obtaining the approval of both the attending physicians and the
p.000056: IRB.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-102
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART D:
p.000056: THE NATIONAL ORGANISATION, ENFORCEMENT AND PROTECTION OF ETHICAL GOVERNANCE
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p.000056: require amendments or modifications to research proposals at any time, and to make such amendments or
p.000056: modifications a condition of approval for the conduct of the research programme.
p.000056:
p.000056: 5.15.3. Outcome Assessment, Reporting and Feedback. In this responsibility, IRBs (especially
p.000056: those in large institutions with a large number of research programmes) undertake the monitoring and
p.000056: collation of adverse event reports, the outcomes of the research programmes, an evaluation of the actual versus
p.000056: the anticipated outcome or results, and the reporting of outcomes and trends to the relevant authorities and to
p.000056: the institutions that they are appointed by and to whom they are responsible. Another major aspect of this role
p.000056: is the role of IRBs in providing feedback and maintaining a dialogue on applicable standards with its
p.000056: constituent researchers. In the discharge of their role, IRBs can and should also act as the key institutional
p.000056: agency which receives, acts upon and reports to the relevant authorities on concerns and feedback expressed by the
p.000056: human subjects of the research programmes.
p.000056:
p.000056: 5.16. Additionally, IRBs may (but not necessarily or invariably, according to the terms of their constitution
p.000056: and appointment) also under take responsibility for:
p.000056:
p.000056: 5.16.1. Review of Scientific Merits. In this responsibility, IRBs carry out peer or expert assessments of the
p.000056: scientific merits and soundness of proposed research programmes. In view of the present system requiring the
p.000056: grant funding age ncy to conduct scientific review of the research, we clarify that the extent of the IRBs
p.000056: responsibility for scientific review may be delineated by the particular institution to which it belongs. By way
p.000056: of illustration, where the institution possesses the necessary expertise needed or where the research
p.000056: project is not subject to grant funding, the IRB may conduct scientific review; where the institution
p.000056: does not possess the necessary expertise, a summary of the scientific review conducted by the grant funding
p.000056: agency should be submitted to the IRB as one of the documents required for approval by the IRB. In all cases, we think
p.000056: it is important that clear standard operating procedures in this area are established by the particular
p.000056: institution. The fact that a particular proposed programme of research is judged to be of sufficient
p.000056: scientific merit does not necessarily mean that it satisfies ethical considerations, although in many
p.000056: cases, these two
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-83
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: considerations are linked, especially in the assessment of harms versus benefits.
p.000056:
p.000056: 5.17. It is the responsibility of all institutions to ensure that a proper review of the scientific merits of all
p.000056: clinical research proposals is carried out.
p.000056:
p.000056: 5.18. Institutions also have the responsibility for establishing clear standard operating procedures for
p.000056: the review of the scientific merits of all clinical research proposals, and whether this is to be done by a separate
...
p.000056: application. We believe that such full and frank account of reasons for rejection is an important key to
p.000056: helping
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-106
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: researchers understand their ethical obligations, and in helping them to redesign programmes for ethical
p.000056: compliance. Likewise, protection for members would also encourage earlier reporting of negative outcomes or
p.000056: suspicious trends to the authorities for investigation.
p.000056:
p.000056: 8.7. Legal protection for members of IRBs acting in good faith would also encourage the best and
p.000056: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000056: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000056: fields.
p.000056:
p.000056: 8.8. Statutory protection may be especially important in encouraging participation by lay
p.000056: non- medical persons to become members of IRBs.
p.000056:
p.000056: 8.9. The same protection should also be extended to ethics assurance auditors, ethics investigators or members of
p.000056: committees of inquiry appointed by the national supervisory age ncy.
p.000056:
p.000056:
p.000056: Recommendation 8:
p.000056:
p.000056: Members of institutional review boards should be fully protected by the law in the discharge of their duties, provided
p.000056: that they do so in good faith, against any liability arising out of their actions. Such protection should
p.000056: extend to immunity from liability in tort arising from any claim by human subjects, and to a defence of
p.000056: qualified privilege to any claim in defamation. The same protection should also be extended to ethics assurance
p.000056: auditors, ethics investigators or members of committees of inquiry appointed by the national supervisory agency.
p.000056:
p.000056: Appointing institutions should nonetheless be required to give members of institutional review boards,
p.000056: ethics assurance auditors, and ethics investigators a full indemnity.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-107
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Annexe A
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: The Human Genetics Subcommittee
p.000056:
p.000056:
p.000056:
p.000056: Chairman
p.000056:
p.000056: Associate Professor Terry KAAN Sheung Hung
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p.000055:
p.000055: Annexe C: Distribution List
p.000055:
p.000055: Annexe D: Responses to the Consultation Paper Annexe E: Summary of the Dialogue Session Annexe F:
p.000055: Select References
p.000055: Annexe G: List of Abbreviations
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: ANNEXE A
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: HUMAN GENETICS SUBCOMMITTEE
p.000056:
p.000056:
p.000056: Chairman
p.000056:
p.000056: Associate Professor Terry Kaan Sheung-Hung Faculty of Law
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey Chan Wah Teck
p.000056: Principal Senior State Counsel (Civil) Attorney-General’s Chambers
p.000056:
p.000056: Associate Professor Samuel Chong Department of Paediatrics
p.000056: National University of Singapore
p.000056:
p.000056: Professor Yap Hui Kim
p.000056: Senior Consultant, National University Hospital Professor in Paediatrics, National University of Singapore
p.000056:
p.000056: Associate Professor Chia Kee Seng (from September 2004) Department of Community, Occupational and Family Medicine
p.000056: Faculty of Medicine
p.000056: National University of Singapore
p.000056:
p.000056: Dr Denise Goh Li Meng (from September 2004) Consultant
p.000056: The Children's Medical Institute National University Hospital
p.000056:
p.000056: Dr Lee Soo Chin (from September 2004) Consultant
p.000056: Department of Haematology-Oncology National University Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: A-57
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH
p.000056:
p.000056: A CONSULTATION PAPER
p.000056:
p.000056:
p.000056:
p.000056: THE BIOETHICS ADVISORY COMMITTEE SINGAPORE
p.000056:
p.000056:
p.000056:
p.000056: 16 September 2003
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-58
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: THE BIOETHICS ADVISORY COMMITTEE
p.000056: Chairman
p.000056:
p.000056: Professor Lim Pin
p.000056: University Professor
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey Chan Wah Teck
p.000056: Principal Senior State Counsel, Civil Division, Attorney -General’s Chambers
p.000056:
p.000056: Mr Cheong Yip Seng
p.000056: Editor-in-Chief, English/Malay Newspapers Division, Singapore Press Holdings
p.000056:
p.000056: Associate Professor John Elliott
p.000056: Department of Social Work & Psychology, National University of Singapore
p.000056:
p.000056: Associate Professor Terry Kaan Sheung Hung
p.000056: Faculty of Law, National University of Singapore
p.000056:
p.000056: Ms Lim Soo Hoon
...
p.000056: Sciences National University of Singapore
p.000056: 7 Dr Ronnie Tan General Manager East Shore Hospita
p.000056:
p.000056: 8 Prof John Wong Dean Faculty of Medicine
p.000056: National University of Singapore
p.000056: 9 Prof Edison Liu Executive Director Genome Institute of Singapore
p.000056:
p.000056:
p.000056: 10 Dr Khoo Chong Yew Chairman
p.000056: Parkway Independent Ethics Committee
p.000056: Gleneagles Hospital
p.000056: 11 Mr Art Oullette Chief Executive Officer HMI Balestier Hospita
p.000056:
p.000056: 12 Prof. Jackie Yi-Ru Ying Executive Director Institute of Bioengineering and
p.000056: Nanotechnology
p.000056:
p.000056:
p.000056: 13 A/Prof Chong Siow Ann Chairman
p.000056: Research and Ethics Committee
p.000056: Institute of Mental Health/ Woodbridge Hospital
p.000056: 14 Prof Hong Wan-Jin Deputy Director Institute of Molecular & Cell
p.000056: Biology
p.000056: National University of Singapore
p.000056: 15 Dr Alex Chang Chief Executive Officer John-Hopkins-NUH International
p.000056: Medical Centre
p.000056:
p.000056:
p.000056: 16 Dr Chay Oh Moh Chairman
p.000056: Research Committee
p.000056: KK Women’s and Children’s Hospital
p.000056: 17 Mr Thomas E. Lee Chief Executive Officer Mount Alvernia Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-109
p.000056:
p.000056:
p.000056: ANNEXE C
p.000056:
p.000056:
p.000056: Name Designation Organisation
p.000056: 18 Mrs Nellie Tang General Manager Mount Elizabeth Hospital
p.000056:
p.000056: 19 Prof Soo Khee Chee Director National Cancer Centre
p.000056:
p.000056: 20 Dr Kwa Chong Teck Executive Director National Dental Centre
p.000056:
p.000056: 21 A/Prof Koh Tian Hai Medical Director National Heart Centre
p.000056:
p.000056: 22 Mr Tan Tee How Group Chief Executive Officer National Healthcare Group
p.000056:
p.000056:
p.000056: 23 Dr Yee Woon Chee Deputy Director
p.000056: Research
p.000056: 24 Prof Goh Chee Leok Chairman
p.000056: Research Ethics Committee
p.000056: 25 Prof Lee Kok Onn Chairman
p.000056: Institutional Review Board
p.000056: National Neuroscience Institute National Skin Centre
p.000056: National University Hospital
p.000056: 26 Prof Yap Hui Kim Director NUMI Directorate
p.000056: National University of Singapore
p.000056: 27 Prof John Wong Director Office of Life Sciences
p.000056: National University of Singapore
p.000056:
p.000056:
...
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056:
p.000056: DIALOGUE SESSION ON THE CONSULTATION PAPER “ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH”
p.000056:
p.000056:
p.000056: 20 Chairpersons and Representatives of the hospital ethics committees or institutional review boards (IRBs) of 17
p.000056: organisations met with seven members of the Bioethics Advisory Committee (BAC) on 7 November 2003. This Annexe
p.000056: provides a summary of the comments and concerns raised at the dialogue session between the parties.
p.000056:
p.000056:
p.000056: Organisation Represented:
p.000056:
p.000056: 1. Alexandra Hospital
p.000056:
p.000056: 2. Changi General Hospital
p.000056:
p.000056: 3. Health Promotion Board
p.000056:
p.000056: 4. Institute of Mental Health/Woodbridge Hospital
p.000056:
p.000056: 5. Institute of Molecular and Cell Biology
p.000056:
p.000056: 6. KK Women’s and Children’s Hospital
p.000056:
p.000056: 7. National Cancer Centre
p.000056:
p.000056: 8. National Dental Centre
p.000056:
p.000056: 9. National Healthcare Group
p.000056:
p.000056: 10. National Heart Centre
p.000056:
p.000056: 11. National Medical Ethics Committee
p.000056:
p.000056: 12. National Neuroscience Institute
p.000056:
p.000056: 13. National University Hospital
p.000056:
p.000056: 14. National University of Singapore
p.000056:
p.000056: 15. Parkway Group Healthcare Pte Ltd
p.000056:
p.000056: 16. Singapore Tissue Network
p.000056:
p.000056: 17. Tan Tock Seng Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-151
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: Summary of Comments and Concerns Raised at the Dialogue Session
p.000056:
p.000056: Intention of the Consultation Paper
p.000056:
p.000056: IRB: Rules set for the industry quickly become obsolete given the speed of progression in
p.000056: biomedical sciences.
p.000056:
p.000056: BAC: The preliminary Recommendations advanced in the Consultation Paper (Paper) are not meant to be
p.000056: cast in iron but will be reviewed as and when the need arises. This is to be expected not only with the advancement of
p.000056: science, but also as values and laws of the society evolve over time. The intention behind the Paper is to
p.000056: establish a framework for the Government to consider when to implement appropriate policies on the ethics
p.000056: governance of human research. One of the main motivations of the Recommendations is to harmonise
p.000056: the ethical standards for all research institutions and their IR Bs. Such standards, as prescribed in the
...
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p.000012:
p.000012: The Ministry has accepted these recommendations.”
p.000012:
p.000012: 2.27. The NMEC Guidelines set out in detail suggested principles of the ethics governance of research involving
p.000012: human subjects, the constitution of ethics committees and the implementation of the framework for the ethics
p.000012: governance of biomedical research. These NMEC Guidelines represent the principal controlling document governing
p.000012: research involving human subjects in Singapore today, but despite this they remain non-directive in
p.000012: nature.
p.000012:
p.000012: 2.28. In developing the Guidelines, the NMEC drew exte nsively from similar guidelines published in other
p.000012: technologically advanced countries, notably those issued by the Canadian Medical Research Council and the
p.000012: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with internationally
p.000012: accepted approaches to, and norms of, ethics governance of biomedical research involving human subjects at that
p.000012: time.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: INTRODUCTION AND CURRENT
p.000013: FRAMEWORK
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 2.29. We have reviewed the NMEC Guidelines and have no hesitation in using them as a basic framework for these
p.000013: BAC Guidelines. Although the NMEC Guidelines were formulated in the restricted context of research
p.000013: carried out by the medical profession, we are of the view that the principles they espouse are
p.000013: appropriate for all human biomedical research, whether such research is carried out by the medical profession
p.000013: or by others. We also take the view that the same principles should apply to all human biomedical research wherever
p.000013: such research may be carried out in Singapore, and whether or not such research is carried out in an institution under
p.000013: the direct jurisdiction of the MOH pursuant to the Private Hospitals and Medical Clinics Act.
p.000013:
p.000013: The Future of Human Biomedical Research
p.000013:
p.000013: 2.30. Until recently, the vast majority of human biomedical research (whether pharmaceutical trials or
p.000013: research other than pharmaceutical trials) were carried out by researchers who were medical practitioners
p.000013: registered under the Medical Registration Act (Cap. 174), in government medical institutions directly
p.000013: controlled by the MOH or in hospitals and medical clinics licensed under the Private Hospitals and Medical
p.000013: Clinics Act. In all of these cases, the competent supervisory authority was the MOH.
p.000013:
p.000013: 2.31. In recent years, however, the development of the biomedical industry in Singapore has led to
p.000013: an increasing proportion of human biomedical research other than pharmaceutical trials. In 2002, for
p.000013: example, hospital ethics committees of the five main restructured hospitals reviewed nearly three times as many
p.000013: applications for such research as they did for pharmaceutical trials.
p.000013:
...
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
p.000056: Regulations and its parent Act (the Medicines Act, Cap. 176) has a special meaning. As defined in
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
p.000056: instead use the term “drug trials” in this Consultation Paper when referring to “clinical trials” in the legal sense of
p.000056: that term, as used in the Clinical Trials Regulations and the Medicines Act.
p.000056:
p.000056: 2.13. In keeping with the principles enunciated in the Declaration of Helsinki, an important component of
p.000056: the requirements of the Clinical Trials Regulations is that the researchers must ensure that the free
...
p.000056: (ii) a senior nursing representative be included as a member of hospital ethics committee.
p.000056:
p.000056: The Ministry has accepted these recommendations”.
p.000056:
p.000056: 2.33. The NMEC Guidelines set out in detail suggested principles of the ethical governance of research involving
p.000056: human subjects, the constitution of ethics committees and the implementation of the framework for the ethical
p.000056: governance of biomedical research. These Guidelines represent the principal controlling document
p.000056: governing research involving human subjects in Singapore today, but despite this they rema ins non-directive in
p.000056: nature,
p.000056:
p.000056: 2.34. In developing the Guidelines, the NMEC drew extensively from similar guidelines published in other
p.000056: technologically-advanced countries, notably those issued by the Canadian Medical Research Council, and the
p.000056: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with
p.000056: internationally-accepted approaches to, and norms of,
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-67
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical governance of biomedical research involving human subjects at that time.
p.000056:
p.000056: 2.35. We have reviewed the NMEC Guidelines. We have no hesitation in using the NMEC Guidelines as the
p.000056: starting point of the larger enquiry in this Consultation Paper. Although it was formulated in the
p.000056: restricted context of the governance of biomedical research on human subjects by the medical professions
p.000056: (as appropriate and in keeping with the NMEC’s terms of reference), the principles expressed in it and the
p.000056: framework which it recommended for the ethical governance of clinical research are entirely sound and are universally
p.000056: accepted within the medical professions.
p.000056:
p.000056: 2.36. We therefore are of the view that the principles and the framework for ethical governance of
p.000056: biomedical research on human subjects set out in the NMEC Guidelines are an appropriate foundation for our
p.000056: proposals for a scheme of ethical governance of all clinical research on human subjects in Singapore, whether or not
p.000056: such research is carried out by members of the medical professions, and whether or not such research is carried out in
p.000056: an institution under the direct jurisdiction of the Ministry of Health pursuant to the Private Hospitals and Medical
p.000056: Clinics Act.
p.000056:
p.000056: Limitations of the Current Regulatory Regime
p.000056:
p.000056: 2.37. The evolution of regimes for the ethical governance of clinical research and drug trials must be
p.000056: seen in the context of the history of clinical research and drug trials in Singapore. At the time when the
p.000056: Clinical Trials Regulations were first enacted, drug trials were the most common kind of clinical research trial.
p.000056: As such, it was entirely appropriate to enact the Clinical Trials Regulations as subsidiary legislation
p.000056: under the Medicines Act, which deals principally with medicines.
p.000056:
...
p.000056: non-drug trials.
p.000056:
p.000056: 2.45. The current framework for ethical governance of clinical research has evolved incrementally and
p.000056: cautiously. In our view, this evolutionary approach was an entirely appropriate response to specific
p.000056: needs and technological advances as they developed over the years.
p.000056:
p.000056: 2.46. At a time when the bulk of medical research was centred about drug trials carried out by the medical
p.000056: professions, it was entirely appropriate to provide for a scheme of ethical governance within the
p.000056: framework of the Medicines Act. But the present and future of clinical research on human subjects embraces a
p.000056: diversity of research inquiry which can no longer be accommodated within the current framework. Accordingly, we think
p.000056: that it is now the appropriate time to undertake a global review of the current rules and framework for the ethical
p.000056: governance of clinical research, and a new, unified framework be created for the ethical governance of all
p.000056: research involving human subjects whether involving drug or non-drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-70
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.47. The principles and ethical governance framework expressed in the Clinical Trials Regulations, the SGGCP and
p.000056: the NMEC Guidelines have served us well in their restricted contexts, and are universally accepted. We take the view
p.000056: that these remain sound guides, and should wherever possible be applied and extended as appropriate to all
p.000056: other forms of clinical research involving human subjects. To this end, the current provisions relating to drug
p.000056: trials should be substantively retained insofar as drug trials are concerned, subject to the procedural
p.000056: changes currently being proposed by the HSA.
p.000056:
p.000056: 2.48. In the sections that follow, we will consider the elements of the proposed new unified framework for
p.000056: ethical governance of clinical research involving human subjects.
p.000056:
p.000056:
p.000056: Recommenda tion 1:
p.000056:
p.000056: A new national framework for the ethical governance of all clinical research involving human subjects should be
p.000056: established.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-71
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART B: CLINICAL RESEARCH
p.000056:
p.000056: SECTION III: CLINICAL RESEARCH
p.000056:
p.000056: 3. Defining Clinical Research
p.000056:
p.000056: 3.1. In this section, we attempt a definition of what kinds of clinical research ought to be subject to the
...
p.000056: previously-established precedents and decisions made by themselves and their predecessors.
p.000056:
p.000056: 5.25. Institutions should also ensure that IRBs have sufficient administrative support so as to ensure
p.000056: that proposals are reviewed and dealt with in a timely manner within the target time- frames set by the
p.000056: institution.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-85
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Composition
p.000056:
p.000056: 5.26. We are of the opinion that the SGGCP, in particular paragraph 3.2.3, and the NMEC Guidelines, in particular
p.000056: paragraph 3.2.2, lay out appropriate and comprehensive guidelines regarding the composition of an ethics
p.000056: committee. We endorse these requirements, and propose that they be similarly used to form the framework for
p.000056: the composition of an IRB.
p.000056:
p.000056: 5.27. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000056:
p.000056: 5.27.1 Given the importance of the IRB, it is important that the core members of IRB should be appointed
p.000056: from among the institutions’ most senior, most respected and scientifically competent officers, researchers or
p.000056: consultants, who possess the appropriate experience and training.
p.000056:
p.000056: 5.27.2 The core members of the IRB should be able to devote sufficient time commensurate to the workload of
p.000056: the IRB.
p.000056:
p.000056: 5.27.3 Representation on an IRB should not be restricted to members of the institution, but should include
p.000056: external and lay representation.
p.000056:
p.000056: 5.27.4 External representation may be in the form of specialists of reputation from other
p.000056: institutions: the objective here is to lend impartiality and objectivity to the work of the IRB, and to ensure
p.000056: that the decisions of the board are carried out in accordance with scientific thinking accepted within the community.
p.000056:
p.000056: 5.27.5 IRBs should also have lay, non-scientific or non-medical representation. Where pract
p.000056: ical, and where the size and volume of the workload of the IRB permits, lay representation may include
p.000056: respected lay members of the community, experts in philosophy, ethics, psychology, sociology or the law.
p.000056: The IRB may consult representative religious leaders on an ad hoc basis where it feels that such a need
p.000056: exists.
p.000056:
p.000056: 5.27.6 As far as possible, the core membership of an IRB should be representative of the particular fields
p.000056: of research carried out in the institution, such that for every research proposal received by the board, there
p.000056: will be at least one specialist or expert (and preferably more) on the IRB that is competent to assess that proposal.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-86
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Institutional Conflicts of Interest
p.000056:
...
Social / Laboratory Staff
Searching for indicator research staff:
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p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
...
Social / Marital Status
Searching for indicator single:
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p.000043: potential conflict of interest or the appearance of such a conflict of interest.
p.000043:
p.000043: 6.15. Researchers should not be involved in, or give the appearance of being involved in, the ethics
p.000043: review and approval process of any research project in which he or she is involved. For instance, a researcher who is a
p.000043: me mber of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000043: personally involved and make a declaration of such an interest to the IRB.
p.000043:
p.000043: 6.16. In submitting a proposal for ethics review, every researcher involved in the research project should be named
p.000043: as a party and applicant in the proposal.
p.000043:
p.000043: 6.17. For the purposes of this Section, we exclude from the definition of researcher, persons acting
p.000043: only in an administrative or support capacity and who have no independent control over the conduct of
p.000043: the research. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000043: in clinical duties.
p.000043:
p.000043:
p.000043: Principal Investigators
p.000043:
p.000043: 6.18. Where a research project involves more than one researcher, the term “investigator” refers to any
p.000043: one of the researchers generally, while the term “Principal Investigator” specifically refers to the researcher who has
p.000043: been designated to undertake the role of Principal Investigator (PI) of that research project.
p.000043:
p.000043: 6.19. If a single researcher is carrying out a research project, then he or she shall be the PI. If multiple
p.000043: researchers are carrying out a research project, then the researchers must among themselves designate a PI. The
p.000043: PI is the researcher who shall be regarded as the lead res earcher of the research project.
p.000043:
p.000043: 6.20. A research application by a group of collaborating researchers should be submitted in the name of a
p.000043: single PI and his or her collaborating researchers.
p.000043:
p.000043: 6.21. It is permissible for a research project to have more than one PI, especially for large projects, projects
p.000043: with different parts or different (but related)
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044:
p.000044: ETHICS GOVERNANCE
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044: objectives and projects in which the research is to be carried out at many locations (multi-centre research). Where
p.000044: more than one PI is involved, then each and every one of the PIs shall be held jointly and severally
p.000044: responsible as PIs.
p.000044:
p.000044: 6.22. PIs have special additional responsibilities over and above that of ordinary researchers.
p.000044:
p.000044: The MOH has recently proposed a definition of “Principal Investigator” and of a PI's roles and
p.000044: responsibilities:
p.000044:
p.000044: “The Principal Investigator (PI) is the individual responsible and accountable for the design, conduct,
p.000044: monitoring, analyses and reporting of the protocol. The PI assumes full responsibility for the evaluation,
p.000044: analyses and integrity of the research data. The PI must assure that the protocol is followed and the data collected
p.000044: promptly and accurately. The PI assumes specific responsibilities to include: writing the protocol
p.000044: document, assuring that necessary approvals are obtained, monit oring the protocol during its execution, ensure
p.000044: that the protocol is conducted in accordance to the ethical guidelines, and to ensure that all participating
...
p.000056: is a member of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000056: personally involved, and make a declaration of such an interest to the IRB.
p.000056:
p.000056: 6.16. In submitting a proposal for ethical review, every researcher involved in the research project should be
p.000056: named as a party and applicant in the proposal.
p.000056:
p.000056: 6.17. For the purposes of this Section, we exclude from the definition of researcher persons acting
p.000056: only in an administrative or support capacity, and who are under the direct supervis ion and control of
p.000056: a researcher. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000056: in clinical duties.
p.000056:
p.000056: Principal Investigators
p.000056:
p.000056: 6.18. It has been the practice in the past to informally refer to all researchers invo lved in a
p.000056: research project as “Principal Investigators” or “PIs”. We think, however, that this practice causes
p.000056: confusion, especially if a large number of researchers are involved in a research project.
p.000056:
p.000056: 6.19. Where a research project involves more than one researcher, we prefer to use the term “investigator” to refer
p.000056: to any one of the researchers generally, and the term “Principal Investigator” to specifically refer to
p.000056: the investigator who has been elected (and who has accepted) the role of Principal Investigator of that
p.000056: research project.
p.000056:
p.000056: 6.20. Where a research project is to be carried out by a single researcher, that researcher is the Principal
p.000056: Investigator. Where a research project is to be carried out by more than one researcher, then the
p.000056: researchers must elect
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-97
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: one of themselves to be designated as the Principal Investigator. The Principal Investigator is the
p.000056: researcher who shall be regarded as the lead researcher of the research project.
p.000056:
p.000056: 6.21. A research application by a group of researchers working in collaboration with each other should therefore
p.000056: ordinarily be submitted by the researchers in the name of a single Principal Investigator and his or her collaborating
p.000056: Investigators.
p.000056:
p.000056: 6.22. It is permissible for a research project to have more than one Principal Investigator. This is
p.000056: especially in a large project, or one with different parts or different (but related) objectives, or one in
p.000056: which the research is to be carried out at many places or trial locations (multi-centre trials). Where more than one
p.000056: Principal Investigator is contemplated, then each and every one of the Principal Investigators shall be held
p.000056: jointly and severally responsible as Principal Investigators.
p.000056:
p.000056: 6.23. Principal Investigators have special additional responsibilities over and above that of ordinary
p.000056: researchers.
p.000056:
p.000056: A definition of the term “Principal Investigator”, and of the role and responsibilities of a Principal
p.000056: Investigator has recently been proposed:
p.000056:
p.000056: “The Principal Investigator (PI) is the individual responsible and accountable for the design, conduct,
p.000056: monitoring, analyses and reporting of the protocol. The PI assumes full responsibility for the evaluation,
p.000056: analyses and integrity of the research data. The PI must assure that the protocol is followed and the data collected
p.000056: promptly and accurately. The PI assumes specific responsibilities to include: writing the protocol
p.000056: document, assuring that necessary approvals are obtained, monitoring the protocol during its execution, ensure
p.000056: that the protocol is conducted in accordance to the ethical guidelines, and to ensure that all participating
p.000056: investigators on the research teams, involved in implementing the protocol are adequately informed about the protocol
...
Social / Occupation
Searching for indicator job:
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p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
p.000053: ETHICS GOVERNANCE
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 7.20. We take the view that IRB members should be fully protected in the discharge of their duties,
p.000053: provided that they do so in good faith, against any liability arising from their actions. Appointing
p.000053: institutions should give IRB members a full indemnity and arrange for the necessary insurance.
p.000053:
p.000053: 7.21. Legal protection for IRB members acting in good faith would also encourage the best and
p.000053: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000053: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000053: fields.
p.000053:
p.000053: 7.22. Because IRBs act as their appointing institutions’ officers and agents, institutions remain liable
p.000053: to human subjects from any claim in tort and should be required to take out appropriate insurance coverage
p.000053: against the variety of claims that may arise in the course of the work of the IRB (for example, in relation to the
p.000053: approval of multi-centre or multinational research).
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
...
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VIII: PROTECTION
p.000056:
p.000056: 8. The Protection Of Institutional Review Boards
p.000056:
p.000056: 8.1. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000056: difficulties in attracting members of its choice in that some of the most qualified potential candidates for
p.000056: membership decline the invitation to serve. These candidates may do so out of a fear of legal liability in the event
p.000056: of a contested decision, or a decision which has an unexpectedly adverse impact on human subjects. Few such
p.000056: candidates have any legal training, and the ir reluctance on this ground is understandable.
p.000056:
p.000056: 8.2. On this point, we note that the NMEC Guidelines suggests that IRBs should look to the
p.000056: authority appointing them to give them formal indemnity against the cost of any legal
p.000056: representation, and any compensation ultimately awarded to human subjects. The NMEC Guidelines
p.000056: further recommend that such an indemnity should be given in the letter of appointments of the members.
p.000056:
p.000056: 8.3. Members of IRBs discharge an important office in the public interest in the protection of human subjects.
p.000056: Often they do so for minimal or token remuneration, or none at all. Their only motivation being a call to
p.000056: duty, and their only reward being the satisfaction of a job well done.
p.000056:
p.000056: 8.4. We take the view that members of IRBs should be fully protected by the law in their discharge of their
p.000056: duties, provided that they do so in good faith, against any liability arising from their actions. Such
p.000056: protection should extend to immunity from liability in tort arising from any claim by human subjects, and to a
p.000056: defence of qualified privilege to any claim in defamation.
p.000056:
p.000056: 8.5. Appointing institutions should nonetheless be required to give members of IRBs a full indemnity. Such
p.000056: institutions should remain liable to human subjects from any claim in tort, and should be required to
p.000056: take out appropriate insurance coverage against the variety of claims which may arise in the course of the
p.000056: work of the IRB. For example, in relation to the approval of multi- centre or multinational trials.
p.000056:
p.000056: 8.6. We note that such protection would also promote frankness and transparency by the IRB in
p.000056: the discharge of their duties: members would be able to state their opinion frankly without fear of being
p.000056: sued for defamation, and would be able to give researchers a full and frank account of their reasons for rejecting an
p.000056: application. We believe that such full and frank account of reasons for rejection is an important key to
p.000056: helping
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-106
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
...
Social / Police Officer
Searching for indicator officer:
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p.000032: proposed Human Biomedical Research programmes on behalf of their appointing institutions. This should
p.000032: take into account the scientific merits of the proposed research.
p.000032:
p.000032: 5.29. Additionally, as institutional resources may permit, and on the mutual agreement of IRBs and
p.000032: their appointing institutions, IRBs may also be given authority by their appointing institutions for:
p.000032:
p.000032: (a) The continuing review and supervision (including evaluation of feedback from research
p.000032: subjects) of Human Biomedical Research programmes approved by them;
p.000032:
p.000032: (b) The receiving of feedback from research subjects and the providing of feedback to researchers; and
p.000032:
p.000032: (c) The reporting of unusual or unexpected events arising from the Human Biomedical Research programmes
p.000032: carried out under the auspices of its appointing institution to the management of that institution.
p.000032:
p.000032:
p.000032: The Constitution of Institutional Review Boards
p.000032:
p.000032: 5.30. IRBs should be established at the highest administrative level of the institutions. They
p.000032: should be appropriately resourced relative to the research activity of the institution and, where this is
p.000032: substantial, should be regarded as one of the key full- time management offices within the organisation of
p.000032: institutions, and not merely as honorary or ad hoc committees.
p.000032:
p.000032: 5.31. The IRB should be appointed by and report to at least an authority at the level of the Chief Executive
p.000032: Officer (as recommended by the NMEC Guidelines in the case of hospitals falling under the jurisdiction
p.000032: of the MOH pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000032:
p.000032: 5.32. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000032: although it is acceptable for institutions
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033: ETHICS GOVERNANCE
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: with standing IRBs to appoint special ad hoc committees in consultation with their standing IRBs to
p.000033: consider special research proposals. We prefer, in such cases, that the institutions work with their standing
p.000033: IRBs to appoint special subcommittees co-opting experts or reviewers to assist the standing IRBs in the particular
p.000033: project concerned. For example, an IRB may receive a research proposal involving an area of research with which no
p.000033: member of the IRB is familiar. In such a case, the institution may work with the IRB to identify and co-opt ad
p.000033: hoc experts or reviewers to assist the IRB in its assessment and review of the proposal. The co-opted ad hoc experts
p.000033: or reviewers sit as a subcommittee of the IRB.
p.000033:
p.000033:
p.000033: Composition
p.000033:
p.000033: 5.33. We are of the opinion that the SGGCP (in particular Section 3.2.3) and the NMEC Guidelines (in particular
p.000033: Section 3.2.2) lay out appropriate and comprehensive guidelines regarding the composition of an
...
p.000038: purposes.
p.000038:
p.000038: 5.69. The requirements of impartiality, fair review and documentation of decisions should apply
p.000038: equally to IRBs engaged in the continuing review or supervision of a research programme.
p.000038:
p.000038: 5.70. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000038: obtaining of free and informed consent of subjects in pharmaceutical trials should be applied to all other
p.000038: kinds of human biomedical research with appropriate modifications.
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039:
p.000039: ETHICS GOVERNANCE
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 5.71. Both researchers and IRBs should take especial care to ensure that potential research
p.000039: subjects will be able to understand and assess the risks of participation, and that the consent-taking
p.000039: procedure and the documentation are properly designed to achieve this end.
p.000039:
p.000039: 5.72. Both researchers and IRBs should ensure that research participants are aware that they have the right
p.000039: to withdraw from the research programme at any time.
p.000039:
p.000039: 5.73. We recommend that IRBs and institutions formalise arrangements that allow participants a one-stop
p.000039: direct access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000039: quality service standards and control. In this way, research participants can have access to independent officers
p.000039: in order to give feedback on the research, or to express their concerns.
p.000039:
p.000039: 5.74. For related reasons, we further recommend that researchers consider appointing a member
p.000039: of their research team to serve as a one-stop participant contact. This contact person should be
p.000039: a registered medical practitioner or a senior member of the research team. It will be the responsibility
p.000039: of this person to handle initial contact in all cases in which a research programme involves any level of
p.000039: clinical intervention or interaction with the participants, and in cases where the interaction with
p.000039: participants is delegated to support and field workers or assistants (for example, the collation of medical
p.000039: histories or physical examination). We also recommend that IRBs make the appointment of a contact person a
p.000039: condition of approval.
p.000039:
p.000039: 5.75. A copy of every document signed by research subjects or given to them to read, including the consent
p.000039: documentation, should be retained by the research subjects.
p.000039:
p.000039: 5.76. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000039: Research Report apply to the use of human biological materials in Human Biomedical Research.
p.000039:
...
p.000056: to proper authorities and to their appointing institutions and to principal investigators of the research
p.000056: programmes;
p.000056:
p.000056: • Reporting on the clinical research programmes and in particular the results of the programme approved by
p.000056: them to the proper authorities and to their appointing institutions, feedback to the constituent researchers of the
p.000056: institutional review board, and monitoring feedback from research subjects.
p.000056:
p.000056: • Additionally, and provided that this responsibility and jurisdiction is clearly set out by the terms
p.000056: of its constitution and appointment by the appointing institution, institutional review boards may
p.000056: also have responsibility for the review of the scientific merits of proposed clinical research programmes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-84
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: The Constitution of Institutional Review Boards
p.000056:
p.000056: 5.20. IRBs should be established and appointed by and at the highest administrative levels of
p.000056: the institutions. They should be appropriately resourced relative to the research activity of the institution
p.000056: and, where this is substantial, should be regarded as one of the key full- time management offices within the
p.000056: organisation of institutions, and not merely as honorary or ad hoc committees.
p.000056:
p.000056: 5.21. The IRB should be appointed and report to at least an authority at the level of the Chief Executive Officer
p.000056: (as required by the NMEC guidelines in the case of hospitals falling under the jurisdiction of the Ministry of Health
p.000056: pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000056:
p.000056: 5.22. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000056: although it is acceptable for institutions with standing IRBs to appoint special ad hoc committees in
p.000056: consultation with their standing IRBs to consider special research proposals. We prefer, in such cases, that
p.000056: the institution works with their standing IRB to appoint special subcommittees co-opting experts or reviewers to assist
p.000056: the standing IRB in the particular project concerned. For example, an IRB may receive a research proposal
p.000056: involving an area of research with which no member of the IRB is familiar. In such a case, the institution may work
p.000056: with the IRB to identify and co-opt ad hoc experts or reviewers to assist the IRB in its assessment and review
p.000056: of the proposal. The co-opted ad hoc experts or reviewers sit as a subcommittee of the IRB.
p.000056:
p.000056: 5.23. Institutions have an obligation to ensure that IRBs receive adequate administrative support
p.000056: that is commensurate with their central role in the ethical governance process.
p.000056:
p.000056: 5.24. IRBs should have sufficient full-time administrative support so as to ensure continuity and
p.000056: consistency in the work of the IRBs, to discharge its continuing review, supervision and audit obligations,
p.000056: its outcome assessment and reporting duties, and to ensure that their decisions are made with regard to
p.000056: previously-established precedents and decisions made by themselves and their predecessors.
...
p.000056: from offering his or her opinion to the board on the particular research under review.
p.000056:
p.000056: 5.55. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000056: the board.
p.000056:
p.000056: 5.56. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000056: obtaining of free and informed consent of subjects in drug trials be in principle extended to all other kinds of
p.000056: clinical research with appropriate modifications.
p.000056:
p.000056: 5.57. Both researchers and IRBs should take especial care to ensure that the proposed human subjects will
p.000056: be able to understand and assess the risks of participation, and that the consent -taking procedure and the
p.000056: documentation are properly designed to achieve this end.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-91
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.58. Both researchers and IRBs should ensure that the participants of research projects are aware that they have
p.000056: the right to withdraw from the research programme at any time.
p.000056:
p.000056: 5.59. We recommend that IRBs and institutions formalise arrangements which allow participants a one-stop direct
p.000056: access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000056: quality service standards and control. In this way, participants in research trials can have access to independent
p.000056: officers in order to give feedback on the trial, or to express their concerns.
p.000056:
p.000056: 5.60. In the same vein, we further recommend that researchers consider (and IRBs should consider making it
p.000056: a condition of approval) appointing one of their number (who should be a registered med ical practitioner or a senior
p.000056: member of the research team) as a one-stop participant contact in all cases where the research programme involves any
p.000056: level of clinical intervention or interaction with the participants, and in cases where the interaction (for example,
p.000056: the collation of medical histories, or physical examination) with participants is delegated to support and field
p.000056: workers or assistants.
p.000056:
p.000056: 5.61. A copy of every document signed by research subjects or given to them to read, including the consent
p.000056: documentation, should be given to and retained by the research subjects.
p.000056:
p.000056: 5.62. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000056: Research Report apply to the use of human biological materials in clinical research.
p.000056:
p.000056: 5.63. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of its
p.000056: work, and IRB should likewise ensure that its workload does not compromise the quality of its review. Where
...
p.000056:
p.000056: Name Designation Organisation
p.000056:
p.000056: 1 Dr Ng Swee Cheng Chairman
p.000056: Research & Ethics Committee
p.000056: Alexandra Hospital
p.000056:
p.000056: 2 Dr Gunaretnam Rajagopa Acting Executive Director Bioinformatics Institute
p.000056:
p.000056: 3 Prof Miranda Yap Director Bioprocessing Technology
p.000056: Centre
p.000056:
p.000056:
p.000056: 4 Dr Khoo Teng Kew Chairman
p.000056: Medical Ethics Committee
p.000056: Changi General Hospital
p.000056:
p.000056: 5 A/Prof Lionel Lee Director Defence Medical &
p.000056: Environmental Research Institute
p.000056: DSO National Laboratories
p.000056: 6 Prof Hew Choy Leong Head Department of Biological
p.000056: Sciences National University of Singapore
p.000056: 7 Dr Ronnie Tan General Manager East Shore Hospita
p.000056:
p.000056: 8 Prof John Wong Dean Faculty of Medicine
p.000056: National University of Singapore
p.000056: 9 Prof Edison Liu Executive Director Genome Institute of Singapore
p.000056:
p.000056:
p.000056: 10 Dr Khoo Chong Yew Chairman
p.000056: Parkway Independent Ethics Committee
p.000056: Gleneagles Hospital
p.000056: 11 Mr Art Oullette Chief Executive Officer HMI Balestier Hospita
p.000056:
p.000056: 12 Prof. Jackie Yi-Ru Ying Executive Director Institute of Bioengineering and
p.000056: Nanotechnology
p.000056:
p.000056:
p.000056: 13 A/Prof Chong Siow Ann Chairman
p.000056: Research and Ethics Committee
p.000056: Institute of Mental Health/ Woodbridge Hospital
p.000056: 14 Prof Hong Wan-Jin Deputy Director Institute of Molecular & Cell
p.000056: Biology
p.000056: National University of Singapore
p.000056: 15 Dr Alex Chang Chief Executive Officer John-Hopkins-NUH International
p.000056: Medical Centre
p.000056:
p.000056:
p.000056: 16 Dr Chay Oh Moh Chairman
p.000056: Research Committee
p.000056: KK Women’s and Children’s Hospital
p.000056: 17 Mr Thomas E. Lee Chief Executive Officer Mount Alvernia Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-109
p.000056:
p.000056:
p.000056: ANNEXE C
p.000056:
p.000056:
p.000056: Name Designation Organisation
p.000056: 18 Mrs Nellie Tang General Manager Mount Elizabeth Hospital
p.000056:
p.000056: 19 Prof Soo Khee Chee Director National Cancer Centre
p.000056:
p.000056: 20 Dr Kwa Chong Teck Executive Director National Dental Centre
p.000056:
p.000056: 21 A/Prof Koh Tian Hai Medical Director National Heart Centre
p.000056:
p.000056: 22 Mr Tan Tee How Group Chief Executive Officer National Healthcare Group
p.000056:
p.000056:
p.000056: 23 Dr Yee Woon Chee Deputy Director
p.000056: Research
p.000056: 24 Prof Goh Chee Leok Chairman
p.000056: Research Ethics Committee
p.000056: 25 Prof Lee Kok Onn Chairman
p.000056: Institutional Review Board
p.000056: National Neuroscience Institute National Skin Centre
p.000056: National University Hospital
p.000056: 26 Prof Yap Hui Kim Director NUMI Directorate
p.000056: National University of Singapore
p.000056: 27 Prof John Wong Director Office of Life Sciences
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: 28 Dr James J Murugasu Chairman
p.000056: Ethics Committee
p.000056: Raffles Hospital
p.000056: 29 Prof James P. Tam Dean School of Biological Sciences
p.000056: Nanyang Technological University
p.000056: 30 A/Prof Donald Tan Director Singapore Eye Research
p.000056: Institute
p.000056:
p.000056:
p.000056: 31 Dr Aw Swee Eng Chairman
p.000056: Ethics Committee
p.000056: Singapore General Hospital
p.000056:
p.000056: 32 Dr Ang Chong Lye Director Singapore National Eye Centre
p.000056:
p.000056:
p.000056: 33 Ms Theresa Chow Pui Fun
p.000056: Deputy Director Singapore Tissue Network
p.000056:
p.000056: 34 Prof Low Yin Peng Chairman
p.000056: Ethics Committee
p.000056: Tan Tock Seng Hospital
p.000056:
p.000056: 35 Mr Allan Yeo Chief Group Executive Thomson Medical Centre
p.000056:
p.000056: 36 Prof Tan Ser Kiat Group Chief Executive Officer Singapore Health Services
p.000056:
p.000056: 37 Dr Predeebha Kannan Secretariat National Medical Ethics Committee
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-110
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
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p.000056:
p.000056:
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p.000056:
p.000056:
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p.000056:
p.000056:
p.000056:
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p.000056:
p.000056:
p.000056:
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p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056:
p.000056: DIALOGUE SESSION ON THE CONSULTATION PAPER “ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH”
p.000056:
p.000056:
p.000056: 20 Chairpersons and Representatives of the hospital ethics committees or institutional review boards (IRBs) of 17
p.000056: organisations met with seven members of the Bioethics Advisory Committee (BAC) on 7 November 2003. This Annexe
...
p.000056: Sciences and Humanities Research Council, Canada
p.000056:
p.000056: 4. Governance arrangements for NHS Research Ethics Committees (July 2001) Department of Health, United Kingdom
p.000056:
p.000056: 5. Research Governance Framework for Health and Social Care, 2nd edition draft (April 2003) Department of Health,
p.000056: United Kingdom
p.000056:
p.000056: 6. Code of Federal Regulations Title 45 Public Welfare – Part 46: Protection of Human Subjects (2001)
p.000056: Office for Protection from Research Risks, National Institutes of Health, Department of Health and Human Services,
p.000056: U.S.A.
p.000056:
p.000056: 7. Ethical and Policy Issues in Research Involving Human Participants (August 2001) National Bioethics Advisory
p.000056: Commissio n, U.S.A.
p.000056:
p.000056: 8. The Belmont Report (1979)
p.000056: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, U.S.A.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: F-158
p.000056:
p.000056:
p.000056: ANNEXE G
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: LIST OF ABBREVIATIONS
p.000056:
p.000056: BAC Bioethics Advisory Committee (Singapore)
p.000056: CEO Chief Executive Officer
p.000056: DNA Deoxyribonucleic acid
p.000056: EC Ethics committee
p.000056: GCP Good Clinical Practice
p.000056: HGS Human Genetics Subcommittee
p.000056: HSA Health Sciences Authority (Singapore)
p.000056: ICH International Conference on Harmonisation
p.000056: IRB Institutional Review Board
p.000056: MCRC Medical Clinical Research Committee
p.000056: MOH Ministry of Health (Singapore)
p.000056: NHG National Healthcare Group (Singapore)
p.000056: NMEC National Medical Ethics Committee (Sin gapore) NUH National University
p.000056: Hospital
p.000056: PI Principal Investigator
p.000056: RNA Ribonucleic acid
p.000056: SGGCP Singapore Guideline for Good Clinical Practice SOP Standard Operating
p.000056: Procedure
p.000056: UNESCO United Nations Education, Scientific and Cultural Organization
p.000056: WHO World Health Organization
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
...
Social / Racial Minority
Searching for indicator race:
(return to top)
p.000007:
p.000007: Objectives
p.000007:
p.000007: 1.6. Our objectives in advancing these Guidelines are:
p.000007:
p.000007: (a) To review the current system of ethics governance of human biomedical research in
p.000007: Singapore, with particular focus on the processes and procedures;
p.000007:
p.000007: (b) To advance recommendations and operational guidelines on the constitution and role of ethics committees
p.000007: or IRBs in the process of ethics governance of human biomedical research; and
p.000007:
p.000007: (c) To provide guidance in Singapore for the promotion of ethically responsible human biomedical
p.000007: research conforming to the best international standards and practice.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: INTRODUCTION AND CURRENT
p.000008: FRAMEWORK
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: SECTION II: THE CURRENT FRAMEWORK
p.000008:
p.000008: 2. The Current Framework The Background
p.000008: 2.1. In Singapore and other technologically advanced societies, advances in biomedical technology and
p.000008: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000008: of life of the general population. These advances represent some of the principal achievements in the modern
p.000008: history of the human race. In the main, such advances in biomedical knowledge have been beneficial and
p.000008: are considered to be research conducted in good faith for the benefit of humankind.
p.000008:
p.000008: 2.2. Events during World War II, however, gave rise to concerns that research conducted on human subjects should
p.000008: be subject to agreed ethical norms. The Nuremberg Code1 was born out of these concerns and represents the first
p.000008: universally accepted code spelling out the minimum content of the ethical norms governing the conduct of
p.000008: research on human subjects.
p.000008:
p.000008: 2.3. These ethical norms were given full consideration and description in the World Medical
p.000008: Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Huma n Subjects,2 which
p.000008: since its adoption by the 18th World Medical Association General Assembly at Helsinki, Finland, has become
p.000008: universally accepted as the core body of ethical norms governing human research.
p.000008:
p.000008: 2.4. The principal theme of the Helsinki Declaratio n is that the life, health, privacy and dignity of
p.000008: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000008: Declaration advocates safeguards such as the principle of freely given informed consent of the
...
p.000056: we made in the earlier two Reports in relation to human embryonic stem cell research, on human cloning, and
p.000056: on human tissue research should control.
p.000056:
p.000056: Objectives
p.000056:
p.000056: 1.7. Our objectives in this Consultation Paper and in the proposed Report are:
p.000056:
p.000056: • To review the current system of ethical governance of clinical research in Singapore, with particular focus on the
p.000056: processes and procedures of ethical governance of clinical research;
p.000056: • To advance recommendations on the constitution and role of ethics committees or institutional review
p.000056: boards in the process of ethical governance of clinical research;
p.000056: • To make recommendations for the future development of the national framework for the ethical governance of
p.000056: clinical researc h in Singapore; and
p.000056: • To advance recommendations for an unified framework of common processes and procedures to be applied
p.000056: in the ethical governance of clinical research in Singapore.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-61
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION II: THE CURRENT FRAMEWORK
p.000056:
p.000056: 2. The Background
p.000056:
p.000056: 2.1. In Singapore and other technologically-advanced societies, advances in biomedical technology and
p.000056: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000056: of life of the general population. These advances represent one of the principal achievements in the
p.000056: modern history of the human race. In the main, such advances in biomedical knowledge have been beneficial, and
p.000056: research conducted in good faith for the benefit of humankind.
p.000056:
p.000056: 2.2. The events of World War II however, gave rise to concerns that biomedical research
p.000056: conducted on human subjects should be subject to agreed ethical norms. The Nuremberg Code 1 was born
p.000056: out of these concerns, and represents the first universally-accepted code spelling out the minimum content
p.000056: of the ethical norms governing the conduct of biomedical research on human subjects.
p.000056:
p.000056: 2.3. These ethical norms were fleshed out and received fuller treatment and consideration in the World
p.000056: Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects2, which since its adoption by the 18th World Medical Association General Assembly at Helsinki,
p.000056: Finland, has become universally accepted as the core body of ethical norms governing human research.
p.000056:
p.000056: 2.4. The principal theme of the Helsinki Declaration is that the life, health, privacy and dignity of
p.000056: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000056: Declaration advocates safeguards such as the principle of freely given informed consent of the
...
Social / Religion
Searching for indicator faith:
(return to top)
p.000007: Singapore, with particular focus on the processes and procedures;
p.000007:
p.000007: (b) To advance recommendations and operational guidelines on the constitution and role of ethics committees
p.000007: or IRBs in the process of ethics governance of human biomedical research; and
p.000007:
p.000007: (c) To provide guidance in Singapore for the promotion of ethically responsible human biomedical
p.000007: research conforming to the best international standards and practice.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: INTRODUCTION AND CURRENT
p.000008: FRAMEWORK
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: SECTION II: THE CURRENT FRAMEWORK
p.000008:
p.000008: 2. The Current Framework The Background
p.000008: 2.1. In Singapore and other technologically advanced societies, advances in biomedical technology and
p.000008: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000008: of life of the general population. These advances represent some of the principal achievements in the modern
p.000008: history of the human race. In the main, such advances in biomedical knowledge have been beneficial and
p.000008: are considered to be research conducted in good faith for the benefit of humankind.
p.000008:
p.000008: 2.2. Events during World War II, however, gave rise to concerns that research conducted on human subjects should
p.000008: be subject to agreed ethical norms. The Nuremberg Code1 was born out of these concerns and represents the first
p.000008: universally accepted code spelling out the minimum content of the ethical norms governing the conduct of
p.000008: research on human subjects.
p.000008:
p.000008: 2.3. These ethical norms were given full consideration and description in the World Medical
p.000008: Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Huma n Subjects,2 which
p.000008: since its adoption by the 18th World Medical Association General Assembly at Helsinki, Finland, has become
p.000008: universally accepted as the core body of ethical norms governing human research.
p.000008:
p.000008: 2.4. The principal theme of the Helsinki Declaratio n is that the life, health, privacy and dignity of
p.000008: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000008: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000008: human subject and the need for rigorous scientific assessment of the risks to the human subject
p.000008: in relation to the benefit sought to be gained from the research.
p.000008:
...
p.000042: are entirely ethical in all aspects and are prepared to defend them as such.
p.000042:
p.000042: 6.9. By submitting a research proposal to an IRB, researchers indicate to all involved parties that the
p.000042: proposed research is, in the researchers’ objective and professional judgement, ethical in all aspects.
p.000042:
p.000042: 6.10. Researchers should not submit to IRBs the same or substantially the same documents for ethics review that
p.000042: they submitted to prospective funding agencies, unless these documents focus on or evaluate the potential impact of
p.000042: the research on the safety, health, dignity, welfare and privacy of the subject in addition to solely describing the
p.000042: scientific merits of the research. However, we nonetheless prefer researchers submit a separate document for
p.000042: ethics review. Researchers should be aware that research proposals submitted for ethics review and research
p.000042: proposals submitted for funding purposes are directed at completely different ends and should be drafted accordingly.
p.000042:
p.000042: 6.11. In no circumstances should researchers use IRBs and the ethics review process as a means of gaining
p.000042: ethics approval for research projects that the researchers themselves entertain doubts or uncertainties about
p.000042: from the ethical point of view.
p.000042:
p.000042: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000042: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000042: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000042: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000042:
p.000042: 6.13. In such cases, we take the view that if researchers believe, in good faith, that the proposed
p.000042: research is ethical, the n such proposed research may be submitted for ethics review provided that the researchers
p.000042: fully disclose all such differing opinions and potential ethical difficulties or controversies known to them;
p.000042: that the researchers fully disclose the ethical reservations or doubts they hold; and that researchers fully disclose
p.000042: all other material facts and issues that might help the IRB carry out an impartial and objective review.
p.000042: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to
p.000042: explore all potential ethical issues, and to carry out an impartial and objective review of a novel
p.000042: situation, there is no objection to researchers submitting in good faith for ethics review a research proposal that the
p.000042: researchers themselves feel that they need ethical guidance.
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043:
p.000043: ETHICS GOVERNANCE
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: 6.14. It is important that researchers take special care to avoid any form of conflicts of interest,
p.000043: whether actual, potential, or merely an appearance of conflict as such. Where such actual, potential or apparent
p.000043: conflict arises, researchers have a duty to make a declaration of the conflict, to give full disclosure of the facts
p.000043: giving rise to such conflict and to detail the steps proposed or taken to minimise or avoid the actual or
p.000043: potential conflict of interest or the appearance of such a conflict of interest.
p.000043:
p.000043: 6.15. Researchers should not be involved in, or give the appearance of being involved in, the ethics
p.000043: review and approval process of any research project in which he or she is involved. For instance, a researcher who is a
p.000043: me mber of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000043: personally involved and make a declaration of such an interest to the IRB.
p.000043:
p.000043: 6.16. In submitting a proposal for ethics review, every researcher involved in the research project should be named
p.000043: as a party and applicant in the proposal.
p.000043:
...
p.000045: as the time the research project is submitted to the IRB for ethics review until the time the research project is
p.000045: deemed to have concluded or been terminated.
p.000045:
p.000045: 6.28. When an IRB approves a research application, its judgment is based on the facts and proposals disclosed to it
p.000045: by the researchers in their application. Most significantly, the ethical judgment has to be made before the research
p.000045: project begins. Once the project is approved and the research is underway, researchers may find that varia
p.000045: tions or departures from the original proposal may be dictated by such considerations as budget,
p.000045: access to subjects, unexpected clinical results and other factors. A research project may also expand in scope, in
p.000045: its objectives, or in the researchers involved. Some researchers may, for example, resign or take a less active role,
p.000045: while other researchers may be recruited. There are other situations in which deviation may occur. A
p.000045: proposed course of action may be found to pose greater risks for the proposed subject population than originally
p.000045: assessed, or that the research has resulted in greater harm (whether of degree or of incidence) than originally
p.000045: contemplated. Or it may be discovered in the course of the research that some part of the original protocol as
p.000045: proposed in the ethics review application has not been strictly adhered to, although such departure may have been
p.000045: made in good faith, by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000045:
p.000045: 6.29. As part of his continuing responsibilities, the PI in particular is under a strict obligation
p.000045: to immediately and in writing seek approval for any changes where such changes have not yet been made, or
p.000045: otherwise report any changes where such changes have already been made, to the IRB by which the initial research
p.000045: application was considered and approved. The PI shall in his request or report detail the changes, giving
p.000045: his objective assessment of any impact and consequences (both from the clinical and ethical points of view)
p.000045: of the changes.
p.000045:
p.000045: 6.30. This continuing obligation of researchers is clearly referred to in the NMEC Guidelines (Section
p.000045: 3.2.5). The NMEC Guidelines state that investigators are “bound to act in exact accordance with the details”
p.000045: of the protocol submitted for ethics review and that investigators are “obliged to
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046:
p.000046: ETHICS GOVERNANCE
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: report to the [IRB] any adverse events and apparent risks beyond those predicted in the original
p.000046: submission. The investigator should also immediately inform the [IRB] of any new information that might alter
p.000046: the ethical basis of the research programme. The [IRB] should also be notified if the study is terminated prematurely.”
p.000046: We agree entirely with the NMEC in these statements and adopt them.
p.000046:
...
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
p.000053: ETHICS GOVERNANCE
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 7.20. We take the view that IRB members should be fully protected in the discharge of their duties,
p.000053: provided that they do so in good faith, against any liability arising from their actions. Appointing
p.000053: institutions should give IRB members a full indemnity and arrange for the necessary insurance.
p.000053:
p.000053: 7.21. Legal protection for IRB members acting in good faith would also encourage the best and
p.000053: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000053: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000053: fields.
p.000053:
p.000053: 7.22. Because IRBs act as their appointing institutions’ officers and agents, institutions remain liable
p.000053: to human subjects from any claim in tort and should be required to take out appropriate insurance coverage
p.000053: against the variety of claims that may arise in the course of the work of the IRB (for example, in relation to the
p.000053: approval of multi-centre or multinational research).
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000054: 54
p.000054:
p.000054:
p.000054: ETHICS GOVERNANCE
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054: SECTION VIII: ACCREDITATION
p.000054:
p.000054: 8. Accreditation
p.000054:
p.000054: The Accreditation of Institutional Review Boards
p.000054:
p.000054: 8.1. The current regulatory regime governing the review and approval of pharmaceutical trials (which
p.000054: we described in Section II) provides for a system in which applications for pharma ceutical trials are
...
p.000056: Objectives
p.000056:
p.000056: 1.7. Our objectives in this Consultation Paper and in the proposed Report are:
p.000056:
p.000056: • To review the current system of ethical governance of clinical research in Singapore, with particular focus on the
p.000056: processes and procedures of ethical governance of clinical research;
p.000056: • To advance recommendations on the constitution and role of ethics committees or institutional review
p.000056: boards in the process of ethical governance of clinical research;
p.000056: • To make recommendations for the future development of the national framework for the ethical governance of
p.000056: clinical researc h in Singapore; and
p.000056: • To advance recommendations for an unified framework of common processes and procedures to be applied
p.000056: in the ethical governance of clinical research in Singapore.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-61
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION II: THE CURRENT FRAMEWORK
p.000056:
p.000056: 2. The Background
p.000056:
p.000056: 2.1. In Singapore and other technologically-advanced societies, advances in biomedical technology and
p.000056: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000056: of life of the general population. These advances represent one of the principal achievements in the
p.000056: modern history of the human race. In the main, such advances in biomedical knowledge have been beneficial, and
p.000056: research conducted in good faith for the benefit of humankind.
p.000056:
p.000056: 2.2. The events of World War II however, gave rise to concerns that biomedical research
p.000056: conducted on human subjects should be subject to agreed ethical norms. The Nuremberg Code 1 was born
p.000056: out of these concerns, and represents the first universally-accepted code spelling out the minimum content
p.000056: of the ethical norms governing the conduct of biomedical research on human subjects.
p.000056:
p.000056: 2.3. These ethical norms were fleshed out and received fuller treatment and consideration in the World
p.000056: Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects2, which since its adoption by the 18th World Medical Association General Assembly at Helsinki,
p.000056: Finland, has become universally accepted as the core body of ethical norms governing human research.
p.000056:
p.000056: 2.4. The principal theme of the Helsinki Declaration is that the life, health, privacy and dignity of
p.000056: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000056: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000056: human subject, and the need for rigorous scientific assessment of the risks to the human subject
p.000056: in relation to the benefit sought to be gained from the research.
p.000056:
...
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 6.7. Researchers are primarily and ultimately responsible for making the first judgment as to whether in
p.000056: their own professional judgment, the proposed research is ethical.
p.000056:
p.000056: 6.8. Researchers should only submit to ethical review boards proposals for research which they are
p.000056: objectively and professionally satisfied are entirely ethical in all aspects, and are prepared to defend them as such.
p.000056:
p.000056: 6.9. Submission of a research proposal to an IRB by researchers amounts to a representation by the researchers to
p.000056: the IRB and to all parties involved in the ethical review and governance process that, in the
p.000056: objective professional judgment of the researchers, the proposed res earch is ethical in all aspects.
p.000056:
p.000056: 6.10. Researchers should not submit the same or substantially the same documents submitted to IRBs
p.000056: for ethical review as that submitted by them to prospective funding agencies for funding. Researchers should
p.000056: bear in mind that research proposals submitted for ethical review are directed at a completely different end to
p.000056: that of proposals submitted for funding purposes, and should draft them accordingly.
p.000056:
p.000056: 6.11. Accordingly, in no circumstances should researchers use IRBs and the ethical review process as a
p.000056: means of gaining ethical approval for research projects that the researchers themselves entertain doubts or
p.000056: uncertainties about from the ethical point of view.
p.000056:
p.000056: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000056: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000056: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000056: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000056:
p.000056: 6.13. In such cases, we take the view that so long as the researchers in good faith are of the belief that the
p.000056: proposed research is ethical, then such proposed research may be submitted for ethics review provided that the
p.000056: researchers make full disclosure of all such differing opinions known to them, and any potential ethical difficulties
p.000056: or controversies known to them or ethical reservations or doubts held by them, and make disclosure of
p.000056: all other material facts and issues that would help the IRB carry out an impartial and objective review.
p.000056: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to explore
p.000056: all potential ethical issues, and to carry out an impartial and objective review of a novel situation,
p.000056: there is no objection to researchers submitting in good faith for
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-96
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical review a research proposal that the researchers themselves feel that they need ethical guidance.
p.000056:
p.000056: 6.14. As for IRBs and members of IRBs, it is important that researchers take special care to avoid
p.000056: any form of conflicts of interest, whether actual, potential, or merely an appearance of conflict as such.
p.000056: Where such actual, potential or apparent conflicts arise, researchers have a duty to make a declaration of
p.000056: the conflict, give full disclosure of the facts giving rise to such conflict, and detail the steps proposed
p.000056: or taken to minimise or avoid the actual or potential conflict of interest, or the appearance of such a
p.000056: conflict of interest.
p.000056:
p.000056: 6.15. In no case should any researcher be involved in, or give the appearance of being involved in, the ethics
p.000056: review and approval process of any research project in which he or she is involved in. For instance, a researcher who
p.000056: is a member of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000056: personally involved, and make a declaration of such an interest to the IRB.
p.000056:
p.000056: 6.16. In submitting a proposal for ethical review, every researcher involved in the research project should be
p.000056: named as a party and applicant in the proposal.
p.000056:
p.000056: 6.17. For the purposes of this Section, we exclude from the definition of researcher persons acting
...
p.000056: concluded or been terminated.
p.000056:
p.000056: 6.28. When an IRB grants its approval on a research application, it can only make its judgment as to
p.000056: whether approval should be granted to the research application based on the facts and proposals disclosed to it
p.000056: by the researchers in their application. Most significantly, the ethical judgment has to be made before the
p.000056: research project begins. Once the project is approved, and the research is underway, researchers
p.000056: often find that variations or departures from the original proposal may be dictated by suc h considerations as
p.000056: budget, access to subjects, unexpected clinical results and other factors. A research project may also
p.000056: expand in scope, in its objectives, or in the researchers involved – some researchers may resign, or decide to
p.000056: take a less active ro le, while other researchers may be recruited. Or it may be discovered that a proposed
p.000056: course of action poses greater risks for the proposed subject population than originally assessed, or that the trial
p.000056: has resulted in greater harm (whether of degree or o f incidence) then originally contemplated. Or it
p.000056: may be discovered in the course of the trial that some part of the original protocol as proposed in the ethics
p.000056: review application has not been strictly adhered to, although such departure may have been made in good faith
p.000056: by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000056:
p.000056: 6.29. As part of their continuing responsibilities, the Principal Investigator(s) in particular is under a
p.000056: strict obligation to immediately and in writing seek approval for any changes where such changes have not yet been
p.000056: made, or otherwise report any changes where such changes have already been made, to the IRB by which initial
p.000056: research application was considered and approved. The Principal Investigator(s) shall in their request or
p.000056: report detail the changes, giving their objective assessment of any impact and consequences (both from
p.000056: the clinical and ethical points of view) of the changes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-99
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 6.30. This continuing obligation of researchers is clearly referred to in the NMEC Guidelines (at
p.000056: paragraph 3.2.5). The Guidelines state that investigators are “bound to act in exact accordance with the
p.000056: details” of the protocol submitted for ethics review, and that investigators are “obliged to report to the [IRB]
p.000056: any adverse events and apparent risks beyond those predicted in the original submission. The
p.000056: investigator should also immediately inform the [IRB] of any new information that might alter the ethical basis of
p.000056: the research programme. The [IRB] should also be notified if the study is terminated prematurely”. We agree entirely
p.000056: with the NMEC in these statements, and adopt them.
p.000056:
...
p.000056:
p.000056: 8.1. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000056: difficulties in attracting members of its choice in that some of the most qualified potential candidates for
p.000056: membership decline the invitation to serve. These candidates may do so out of a fear of legal liability in the event
p.000056: of a contested decision, or a decision which has an unexpectedly adverse impact on human subjects. Few such
p.000056: candidates have any legal training, and the ir reluctance on this ground is understandable.
p.000056:
p.000056: 8.2. On this point, we note that the NMEC Guidelines suggests that IRBs should look to the
p.000056: authority appointing them to give them formal indemnity against the cost of any legal
p.000056: representation, and any compensation ultimately awarded to human subjects. The NMEC Guidelines
p.000056: further recommend that such an indemnity should be given in the letter of appointments of the members.
p.000056:
p.000056: 8.3. Members of IRBs discharge an important office in the public interest in the protection of human subjects.
p.000056: Often they do so for minimal or token remuneration, or none at all. Their only motivation being a call to
p.000056: duty, and their only reward being the satisfaction of a job well done.
p.000056:
p.000056: 8.4. We take the view that members of IRBs should be fully protected by the law in their discharge of their
p.000056: duties, provided that they do so in good faith, against any liability arising from their actions. Such
p.000056: protection should extend to immunity from liability in tort arising from any claim by human subjects, and to a
p.000056: defence of qualified privilege to any claim in defamation.
p.000056:
p.000056: 8.5. Appointing institutions should nonetheless be required to give members of IRBs a full indemnity. Such
p.000056: institutions should remain liable to human subjects from any claim in tort, and should be required to
p.000056: take out appropriate insurance coverage against the variety of claims which may arise in the course of the
p.000056: work of the IRB. For example, in relation to the approval of multi- centre or multinational trials.
p.000056:
p.000056: 8.6. We note that such protection would also promote frankness and transparency by the IRB in
p.000056: the discharge of their duties: members would be able to state their opinion frankly without fear of being
p.000056: sued for defamation, and would be able to give researchers a full and frank account of their reasons for rejecting an
p.000056: application. We believe that such full and frank account of reasons for rejection is an important key to
p.000056: helping
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-106
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: researchers understand their ethical obligations, and in helping them to redesign programmes for ethical
p.000056: compliance. Likewise, protection for members would also encourage earlier reporting of negative outcomes or
p.000056: suspicious trends to the authorities for investigation.
p.000056:
p.000056: 8.7. Legal protection for members of IRBs acting in good faith would also encourage the best and
p.000056: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000056: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000056: fields.
p.000056:
p.000056: 8.8. Statutory protection may be especially important in encouraging participation by lay
p.000056: non- medical persons to become members of IRBs.
p.000056:
p.000056: 8.9. The same protection should also be extended to ethics assurance auditors, ethics investigators or members of
p.000056: committees of inquiry appointed by the national supervisory age ncy.
p.000056:
p.000056:
p.000056: Recommendation 8:
p.000056:
p.000056: Members of institutional review boards should be fully protected by the law in the discharge of their duties, provided
p.000056: that they do so in good faith, against any liability arising out of their actions. Such protection should
p.000056: extend to immunity from liability in tort arising from any claim by human subjects, and to a defence of
p.000056: qualified privilege to any claim in defamation. The same protection should also be extended to ethics assurance
p.000056: auditors, ethics investigators or members of committees of inquiry appointed by the national supervisory agency.
p.000056:
p.000056: Appointing institutions should nonetheless be required to give members of institutional review boards,
p.000056: ethics assurance auditors, and ethics investigators a full indemnity.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-107
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Annexe A
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: The Human Genetics Subcommittee
p.000056:
p.000056:
p.000056:
p.000056: Chairman
p.000056:
p.000056: Associate Professor Terry KAAN Sheung Hung
p.000056: Faculty of Law, National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey CHAN Wah Teck
p.000056: Principal Senior State Counsel, Civil Division, Attorney-General’s Chambers
p.000056:
p.000056: Professor YAP Hui Kim
...
Searching for indicator belief:
(return to top)
p.000056:
p.000056: 6.10. Researchers should not submit the same or substantially the same documents submitted to IRBs
p.000056: for ethical review as that submitted by them to prospective funding agencies for funding. Researchers should
p.000056: bear in mind that research proposals submitted for ethical review are directed at a completely different end to
p.000056: that of proposals submitted for funding purposes, and should draft them accordingly.
p.000056:
p.000056: 6.11. Accordingly, in no circumstances should researchers use IRBs and the ethical review process as a
p.000056: means of gaining ethical approval for research projects that the researchers themselves entertain doubts or
p.000056: uncertainties about from the ethical point of view.
p.000056:
p.000056: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000056: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000056: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000056: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000056:
p.000056: 6.13. In such cases, we take the view that so long as the researchers in good faith are of the belief that the
p.000056: proposed research is ethical, then such proposed research may be submitted for ethics review provided that the
p.000056: researchers make full disclosure of all such differing opinions known to them, and any potential ethical difficulties
p.000056: or controversies known to them or ethical reservations or doubts held by them, and make disclosure of
p.000056: all other material facts and issues that would help the IRB carry out an impartial and objective review.
p.000056: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to explore
p.000056: all potential ethical issues, and to carry out an impartial and objective review of a novel situation,
p.000056: there is no objection to researchers submitting in good faith for
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-96
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical review a research proposal that the researchers themselves feel that they need ethical guidance.
p.000056:
p.000056: 6.14. As for IRBs and members of IRBs, it is important that researchers take special care to avoid
p.000056: any form of conflicts of interest, whether actual, potential, or merely an appearance of conflict as such.
p.000056: Where such actual, potential or apparent conflicts arise, researchers have a duty to make a declaration of
p.000056: the conflict, give full disclosure of the facts giving rise to such conflict, and detail the steps proposed
...
Searching for indicator religious:
(return to top)
p.000025: the applicable body of ethics be reviewed and assessed from time to time to keep it relevant to and
p.000025: reflective of community values and the needs of research.
p.000025:
p.000025: 4.15. We emphasise that it is not the intention of this document to prescribe the specific ethical principles to
p.000025: be applied by IRBs and researchers in the process of ethics governance. We believe that these are
p.000025: professional
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026:
p.000026: ETHICS GOVERNANCE
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: judgments that are appropriately and properly left to members of IRBs, researchers and other parties involved
p.000026: in the process of ethics governance.
p.000026:
p.000026: 4.16. We note, however, that certain broad ethical principles are universally accepted and applied in
p.000026: all the leading research jurisdictions. We find it appropriate and desirable for IRBs, researchers and other
p.000026: parties involved in the process of ethics governance to consider taking these ethical principles into
p.000026: account.
p.000026:
p.000026: 4.17. Such principles, in addition to or in elaboration of those identified by the NMEC, include:
p.000026:
p.000026: (a) Respect for the human body, welfare and safety, and for religious and cultural perspectives and
p.000026: traditions of human subjects. We elaborated on this principle in our Human Tissue Research Report. In the
p.000026: context of a diverse society such as Singapore, researchers have an especial obligation to be sensitive
p.000026: to religious and cultural perspectives and traditions of their human subjects.
p.000026:
p.000026: (b) Respect for free and informed consent. This principle is discussed at length in our Human Stem Cell Report, our
p.000026: Human Tissue Research Report and the NMEC Report (Section 2.5). In addition, the Medicines (Clinical
p.000026: Trials) Regulations and the SGGCP recommend strict requirements regarding consent.
p.000026:
p.000026: (c) Respect for privacy and confidentiality. This is treated in detail in Section 2.6 of the NMEC Guidelines
p.000026: and again in our Human Tissue Research Report.
p.000026:
p.000026: (d) Respect for vulnerable persons. This is discussed in Sections 2.5.5 and 2.5.6 of the NMEC
p.000026: Guidelines. In essence, the ethics governance process must pay especial attention to the protection of
p.000026: persons who may not be competent to give consent themselves, or whose ability to give free and full consent
p.000026: may be compromised by physical conditions or other circumstances, such as being in a dependent
p.000026: relationship.
p.000026:
p.000026: (e) Avoidance of conflicts of interest or the appearance of conflicts of interest. We further elaborate on
p.000026: this principle below in our discussion of the roles and responsibilities of researchers and IRBs.
p.000026:
p.000026:
...
p.000033: members to IRBs. An IRB should be carefully composed in order that there can be no room for any public perception
p.000033: that it is not independent of those who are required to submit to its review;
p.000033:
p.000033: (b) Where a majority of the IRB members are drawn from within the appointing institutions, these persons
p.000033: should be the institutions’ most senior, most respected and scientifically competent officers,
p.000033: researche rs or consultants, who possess the appropriate experience and training;
p.000033:
p.000033: (c) An IRB should include non- medical and/or non-scientific persons (lay representation) who are not members
p.000033: of or otherwise associated with the appointing institution of the IRB. Their inclusion is to reinforce the
p.000033: impartiality and objectivity of the work of the IRB;
p.000033:
p.000033: (d) To further reinforce the independence of the IRB and to ensure that the decisions of the board are
p.000033: carried out in accordance with scientific thinking accepted within the community, external
p.000033: representation may include specialists of favorable reputation from other institutions; and
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034:
p.000034: ETHICS GOVERNANCE
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: (e) Lay representation may include respected lay members of the community and experts in
p.000034: philosophy, ethics, psychology, sociology or the law. The IRB may consult representative religious leaders on an ad
p.000034: hoc basis where it feels that such a need exists.
p.000034:
p.000034: 5.35. As far as possible, the core membership of an IRB should be representative of the particular fields of
p.000034: research carried out in the institution, such that for every research proposal received by the IRB, there will
p.000034: be at least one specialist or expert (and preferably more) on the IRB who may give a specialist viewpoint
p.000034: as needed.
p.000034:
p.000034:
p.000034: Institutional Conflicts of Interest
p.000034:
p.000034: 5.36. In the relationship between an institution and its IRB, the fundamental underlying principles are
p.000034: the independence of the IRB in the exercise of its powers and duties, and its ethical integrity.
p.000034:
p.000034: 5.37. The research programmes that IRBs are asked to review are often of considerable financial or
p.000034: other benefit (potential or otherwise) to the appointing institutions. In the review of these research
p.000034: programmes, both IRBs and institutions alike must be aware of any potential or apparent conflict of
p.000034: interest involved and take reasonable steps to avoid and minimise the conflict.
p.000034:
p.000034: 5.38. It is for this reason, among others, that we have recommended that IRBs report directly to the highest level
p.000034: of management of their institutions.
p.000034:
p.000034: 5.39. At minimum, all communications in relation to the review of the research programme in question should be fully
p.000034: documented in writing. Informal communication between the institution and its officers and the individual members of
p.000034: the IRB in connection with such research programmes should be strongly discouraged.
p.000034:
...
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: below. Likewise, the draft of such a code, and the revisions thereto, should be sponsored and led by such
p.000056: a national agency.
p.000056:
p.000056: 4.16. We take the view that it is part of the function of a responsive and dynamic system of ethical
p.000056: governance that the applicable body of ethics be reviewed and assessed from time to time to keep
p.000056: it relevant to and reflective of community values and the needs of research.
p.000056:
p.000056: 4.17. We emphasize that it is not the intention of this document to prescribe the specific ethical principles to be
p.000056: applied by institutional review boards and researchers in the process of ethical governance. We believe that these are
p.000056: professional judgments which are appropriately and properly left to members of institutional review
p.000056: boards, researchers and other parties involved in the process of ethical governance.
p.000056:
p.000056: 4.18. We note, however, that there are broad ethical principles which are universally accepted and
p.000056: applied in all the leading research jurisdictions, and we take the view that it would be appropriate
p.000056: and desirable if institutional review boards, researchers and other parties involved in the process of ethical
p.000056: governance consider taking these ethical principles into account.
p.000056:
p.000056: 4.19. Such principles, in addition to or in elaboration of those identified by the NMEC, might include:
p.000056:
p.000056: • Respect for the human body, welfare and safety, and for religious and cultural perspectives and traditions of
p.000056: human subjects. We elaborated on this principle in our Human Tissue Research Report. In the context of a diverse
p.000056: society such as Singapore, researchers have an especial obligation to be sensitive to religious and
p.000056: cultural perspectives and traditions of their human subjects.
p.000056:
p.000056: • Respect for free and informed consent. Again, this principle is discussed at length in our
p.000056: Human Stem Cell Report, and our Human Tissue Research Report. A detailed discussion of the requirements of consent is
p.000056: also set out at section 2.5 of the NMEC Report, and we note also the strict requirements with regards to consent
p.000056: laid down by the Clinical Trials Regulations and the SGGCP.
p.000056:
p.000056: • Respect for privacy and confidentiality. This is treated in detail in section 2.6 of the NMEC
p.000056: Guidelines, and again in our Human Tissue Research Report.
p.000056:
p.000056: • Respect for vulnerable persons. This is discussed in paragraphs 2.5.5 to 2.5.6 of the NMEC Guidelines. In
p.000056: essence, the ethics governance
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-78
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: process must pay especial attention to the protection of persons who may not be competent to give consent
p.000056: themselves, or whose ability to give free and full consent may be compromised by reason of their physical
...
p.000056: the composition of an IRB.
p.000056:
p.000056: 5.27. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000056:
p.000056: 5.27.1 Given the importance of the IRB, it is important that the core members of IRB should be appointed
p.000056: from among the institutions’ most senior, most respected and scientifically competent officers, researchers or
p.000056: consultants, who possess the appropriate experience and training.
p.000056:
p.000056: 5.27.2 The core members of the IRB should be able to devote sufficient time commensurate to the workload of
p.000056: the IRB.
p.000056:
p.000056: 5.27.3 Representation on an IRB should not be restricted to members of the institution, but should include
p.000056: external and lay representation.
p.000056:
p.000056: 5.27.4 External representation may be in the form of specialists of reputation from other
p.000056: institutions: the objective here is to lend impartiality and objectivity to the work of the IRB, and to ensure
p.000056: that the decisions of the board are carried out in accordance with scientific thinking accepted within the community.
p.000056:
p.000056: 5.27.5 IRBs should also have lay, non-scientific or non-medical representation. Where pract
p.000056: ical, and where the size and volume of the workload of the IRB permits, lay representation may include
p.000056: respected lay members of the community, experts in philosophy, ethics, psychology, sociology or the law.
p.000056: The IRB may consult representative religious leaders on an ad hoc basis where it feels that such a need
p.000056: exists.
p.000056:
p.000056: 5.27.6 As far as possible, the core membership of an IRB should be representative of the particular fields
p.000056: of research carried out in the institution, such that for every research proposal received by the board, there
p.000056: will be at least one specialist or expert (and preferably more) on the IRB that is competent to assess that proposal.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-86
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Institutional Conflicts of Interest
p.000056:
p.000056: 5.28. In the relationship between an institution and the IRB, the fundamental underlying principles are
p.000056: the independence of the IRB in the exercise of its powers and duties, and its ethical integrity.
p.000056:
p.000056: 5.29. The research programmes which IRBs are asked to review are often of considerable financial or
p.000056: other benefit (potential or otherwise) to the appointing institutions. In the review of these research
p.000056: programmes, both IRBs and institutions alike must be aware of the potential conflict of interest involved
p.000056: and take reasonable steps to minimise conflict.
p.000056:
p.000056: 5.30. It is for this reason, among others, that we have recommended that IRBs report directly to the highest
p.000056: levels of governance in an institution. In the case of hospitals and other similar medical institutions, the IRB
p.000056: should not report to the medical board of that institution.
p.000056:
p.000056: 5.31. At minimum, all communications in relation to the review of the research programme in question should be
...
Social / Soldier
Searching for indicator military:
(return to top)
p.000008: universally accepted code spelling out the minimum content of the ethical norms governing the conduct of
p.000008: research on human subjects.
p.000008:
p.000008: 2.3. These ethical norms were given full consideration and description in the World Medical
p.000008: Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Huma n Subjects,2 which
p.000008: since its adoption by the 18th World Medical Association General Assembly at Helsinki, Finland, has become
p.000008: universally accepted as the core body of ethical norms governing human research.
p.000008:
p.000008: 2.4. The principal theme of the Helsinki Declaratio n is that the life, health, privacy and dignity of
p.000008: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000008: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000008: human subject and the need for rigorous scientific assessment of the risks to the human subject
p.000008: in relation to the benefit sought to be gained from the research.
p.000008:
p.000008: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000008: This provides that the “design and performance of
p.000008:
p.000008: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol.
p.000008: 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000008: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects
p.000008: adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most recently
p.000008: amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: INTRODUCTION AND CURRENT
p.000009: FRAMEWORK
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: each experimental procedure involving human subjects should be clearly formulated in an experimental protocol” and that
p.000009: this protocol should be submitted to an independent ethics review committee for “consideration, comment,
p.000009: guidance, and where appropriate, approval.”
p.000009:
p.000009: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000009: medical community in Singapore and by other medical communities in the great majority of nations. In
p.000009: Singapore, the need for ethics committees or IRBs and the requirement for the ethics review of research
p.000009: proposals involving human subjects have long been an accepted and integral part of biomedical research in the
p.000009: institutional setting.
p.000009:
...
p.000056: 2.3. These ethical norms were fleshed out and received fuller treatment and consideration in the World
p.000056: Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects2, which since its adoption by the 18th World Medical Association General Assembly at Helsinki,
p.000056: Finland, has become universally accepted as the core body of ethical norms governing human research.
p.000056:
p.000056: 2.4. The principal theme of the Helsinki Declaration is that the life, health, privacy and dignity of
p.000056: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000056: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000056: human subject, and the need for rigorous scientific assessment of the risks to the human subject
p.000056: in relation to the benefit sought to be gained from the research.
p.000056:
p.000056: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000056: This provides that the “design and performance of each experimental procedure involving human subjects should be
p.000056: clearly formulated in an experimental protocol”, and that this protocol should be
p.000056:
p.000056: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under
p.000056: Control Council Law No. 10, Vol. 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000056: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most
p.000056: recently amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-62
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: submitted to an independent et hical review committee for “consideration, comment, guidance, and where appropriate,
p.000056: approval”.
p.000056:
p.000056: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000056: medical community in Singapore, as with other medical communities in the great majority of nations.
p.000056: The need for ethics committees or institutional review boards and the requirement for the ethical
p.000056: review of research proposals involving human subjects have long been an accepted and integral part of medical
p.000056: research in the institutional setting in Singapore. The principles of the Declaration of Helsinki today find
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
...
p.000056:
p.000056: Conclusion
p.000056:
p.000056: BAC: The BAC will consider all suggestions that have been made and will try to address as many of the
p.000056: issues that have been raised. Some of the provisions in the Paper may have been misinterpreted as excessive. These
p.000056: provisions will be clarified by the BAC in its recommendations to the Government. It is
p.000056: emphasised that the provisions and recommendations issued by the BAC are only intended as general guidelines. The BAC
p.000056: thanks all participants for their time and valuable input.
p.000056:
p.000056:
p.000056: –––––––––––––––––––––
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-156
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SELECT REFERENCES
p.000056:
p.000056: International
p.000056:
p.000056: 1. Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (2000)
p.000056: World Medical Association
p.000056:
p.000056: 2. ICH Topic E6 - Guideline For Good Clinical Practice (1996)
p.000056: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
p.000056:
p.000056: 3. International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) Council for International
p.000056: Organizations of Medical Sciences
p.000056:
p.000056: 4. Nuremberg Code (1949)
p.000056: Trials of War Criminals before the Nuremberg Military Tribunals under Control Council
p.000056: U.S. Government Printing Office, Washington D.C. Law No. 10, Vol. 2:181-182
p.000056: 5. Operational Guidelines for Ethics Committees that Review Biomedical Research (20 00) World Health Organization
p.000056:
p.000056: 6. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services (1998)
p.000056: World Health Organization
p.000056:
p.000056: 7. Universal Declaration on the Human Genome and Human Rights (1997) United Nations Educational, Scientific and
p.000056: Cultural Organization
p.000056:
p.000056:
p.000056: Singapore
p.000056:
p.000056: 1. Ethical, Legal and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning (June 2002)
p.000056: Bioethics Advisory Committee
p.000056:
p.000056: 2. Human Tissue Research (November 2002) Bioethics Advisory Committee
p.000056:
p.000056: 3. National Medical Ethics Committee: A Review of Activities, 1994-1997 (1998) National Medical Ethics Committee,
p.000056: Ministry of Health
p.000056:
p.000056: 4. Singapore Guideline for Good Clinical Practice (1998) Ministry of Health
p.000056:
p.000056:
p.000056:
p.000056: F-157
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056: Other Countries
p.000056:
p.000056: 1. National Statement on Ethical Conduct in Research Involving Humans (1999) National Health and Medical Research
p.000056: Council, Australia
p.000056:
p.000056: 2. Human Research Ethics Handbook (2001)
...
Social / Women
Searching for indicator women:
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p.000056: 6 Prof Hew Choy Leong Head Department of Biological
p.000056: Sciences National University of Singapore
p.000056: 7 Dr Ronnie Tan General Manager East Shore Hospita
p.000056:
p.000056: 8 Prof John Wong Dean Faculty of Medicine
p.000056: National University of Singapore
p.000056: 9 Prof Edison Liu Executive Director Genome Institute of Singapore
p.000056:
p.000056:
p.000056: 10 Dr Khoo Chong Yew Chairman
p.000056: Parkway Independent Ethics Committee
p.000056: Gleneagles Hospital
p.000056: 11 Mr Art Oullette Chief Executive Officer HMI Balestier Hospita
p.000056:
p.000056: 12 Prof. Jackie Yi-Ru Ying Executive Director Institute of Bioengineering and
p.000056: Nanotechnology
p.000056:
p.000056:
p.000056: 13 A/Prof Chong Siow Ann Chairman
p.000056: Research and Ethics Committee
p.000056: Institute of Mental Health/ Woodbridge Hospital
p.000056: 14 Prof Hong Wan-Jin Deputy Director Institute of Molecular & Cell
p.000056: Biology
p.000056: National University of Singapore
p.000056: 15 Dr Alex Chang Chief Executive Officer John-Hopkins-NUH International
p.000056: Medical Centre
p.000056:
p.000056:
p.000056: 16 Dr Chay Oh Moh Chairman
p.000056: Research Committee
p.000056: KK Women’s and Children’s Hospital
p.000056: 17 Mr Thomas E. Lee Chief Executive Officer Mount Alvernia Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-109
p.000056:
p.000056:
p.000056: ANNEXE C
p.000056:
p.000056:
p.000056: Name Designation Organisation
p.000056: 18 Mrs Nellie Tang General Manager Mount Elizabeth Hospital
p.000056:
p.000056: 19 Prof Soo Khee Chee Director National Cancer Centre
p.000056:
p.000056: 20 Dr Kwa Chong Teck Executive Director National Dental Centre
p.000056:
p.000056: 21 A/Prof Koh Tian Hai Medical Director National Heart Centre
p.000056:
p.000056: 22 Mr Tan Tee How Group Chief Executive Officer National Healthcare Group
p.000056:
p.000056:
p.000056: 23 Dr Yee Woon Chee Deputy Director
p.000056: Research
p.000056: 24 Prof Goh Chee Leok Chairman
p.000056: Research Ethics Committee
p.000056: 25 Prof Lee Kok Onn Chairman
p.000056: Institutional Review Board
p.000056: National Neuroscience Institute National Skin Centre
p.000056: National University Hospital
p.000056: 26 Prof Yap Hui Kim Director NUMI Directorate
p.000056: National University of Singapore
p.000056: 27 Prof John Wong Director Office of Life Sciences
...
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056:
p.000056: DIALOGUE SESSION ON THE CONSULTATION PAPER “ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH”
p.000056:
p.000056:
p.000056: 20 Chairpersons and Representatives of the hospital ethics committees or institutional review boards (IRBs) of 17
p.000056: organisations met with seven members of the Bioethics Advisory Committee (BAC) on 7 November 2003. This Annexe
p.000056: provides a summary of the comments and concerns raised at the dialogue session between the parties.
p.000056:
p.000056:
p.000056: Organisation Represented:
p.000056:
p.000056: 1. Alexandra Hospital
p.000056:
p.000056: 2. Changi General Hospital
p.000056:
p.000056: 3. Health Promotion Board
p.000056:
p.000056: 4. Institute of Mental Health/Woodbridge Hospital
p.000056:
p.000056: 5. Institute of Molecular and Cell Biology
p.000056:
p.000056: 6. KK Women’s and Children’s Hospital
p.000056:
p.000056: 7. National Cancer Centre
p.000056:
p.000056: 8. National Dental Centre
p.000056:
p.000056: 9. National Healthcare Group
p.000056:
p.000056: 10. National Heart Centre
p.000056:
p.000056: 11. National Medical Ethics Committee
p.000056:
p.000056: 12. National Neuroscience Institute
p.000056:
p.000056: 13. National University Hospital
p.000056:
p.000056: 14. National University of Singapore
p.000056:
p.000056: 15. Parkway Group Healthcare Pte Ltd
p.000056:
p.000056: 16. Singapore Tissue Network
p.000056:
p.000056: 17. Tan Tock Seng Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-151
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: Summary of Comments and Concerns Raised at the Dialogue Session
p.000056:
p.000056: Intention of the Consultation Paper
p.000056:
p.000056: IRB: Rules set for the industry quickly become obsolete given the speed of progression in
p.000056: biomedical sciences.
p.000056:
p.000056: BAC: The preliminary Recommendations advanced in the Consultation Paper (Paper) are not meant to be
p.000056: cast in iron but will be reviewed as and when the need arises. This is to be expected not only with the advancement of
p.000056: science, but also as values and laws of the society evolve over time. The intention behind the Paper is to
p.000056: establish a framework for the Government to consider when to implement appropriate policies on the ethics
p.000056: governance of human research. One of the main motivations of the Recommendations is to harmonise
...
Social / Youth/Minors
Searching for indicator minor:
(return to top)
p.000016: direct physical interference or interaction with human subjects themselves, towards research conducted
p.000016: largely on cell lines, tissues or other bodily samples given by human donors, and on medical information
p.000016: derived from patients and other human subjects.
p.000016:
p.000016: 3.6. Increasingly, it is the case that there is no direct physical contact at all between the
p.000016: researchers and the human subjects. In such circumstances, there is no possibility of physical injury or harm
p.000016: befalling the human research subjects. In these situations, the ethical, le gal and social concerns centre not on
p.000016: the possibility of physical injury or harm but on the larger penumbra of indirect harms to the patient or
p.000016: donor such as the breach of the patient’s or donor’s expectation of confidentiality of his medical
p.000016: information, or his expectation that his tissue should not be used for research without his consent.
p.000016:
p.000016: 3.7. It is therefore appropriate that a fundamental distinction be made between:
p.000016:
p.000016: (a) Direct Human Biomedical Research. This comprises any kind of human biomedical research that
p.000016: involves any direct interference or interaction with the physical body of a human subject, and that
p.000016: involves a concomitant risk of physical injury or harm, however remote or minor. A research
p.000016: programme which involves the administration of any drug (whether it is for the purpose of testing the
p.000016: effects or efficacy of the drug, or whether it is a means for establishing any other objective of the
p.000016: research programme), the trial or use of a medical device on a human subject, or any test of a human subject’s
p.000016: physiological, emotional or mental responses (not being tests conducted for diagnostic purposes with a view to
p.000016: the therapeutic management of a patient) all qualify as Direct Human Biomedical Research; and
p.000016:
p.000016: (b) Indirect Human Biomedical Research. This comprises any research (not qualifying as Direct Human
p.000016: Biomedical Research) involving human subjects, human tissue, or medical, personal or genetic
p.000016: information relating to both identifiable and anonymous individuals, undertaken with a view to generating data about
p.000016: medical, genetic or biological processes, diseases or conditions in human subjects, or of human physiology or about the
p.000016: safety, efficacy, effect or function of any device, drug, diagnostic, surgical or therapeutic procedure
p.000016: (whether invasive, observational or otherwise) in human subjects whether as one of the objectives or the sole
p.000016: objective, of the research study, trial or activity, and which research, study, trial or activity has
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: HUMAN
p.000017: BIOMEDICAL RESEARCH
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
...
p.000018: there being no possibility of researchers by themselves being able to trace or reconstruct significant
p.000018: information on the identity of subject donor;
p.000018:
p.000018: (c) Research using established commercially available cell lines or commercially available anonymous
p.000018: DNAs, RNAs and fixed tissues; and
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019: HUMAN
p.000019: BIOMEDICAL RESEARCH
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: (d) The development of diagnostic tests using existing samples for test validation purposes provided
p.000019: that the necessary consent for the taking and use of the samples has been obtained.
p.000019:
p.000019: Expedited Review
p.000019:
p.000019: 3.16. Some categories of research programmes may be permitted a less formal process of review than that of a
p.000019: standard full review. For example, the Chairperson or other IRB delegate(s) (the reviewer) may be empowered to
p.000019: conduct Expedited Review.
p.000019:
p.000019: 3.17. The same principles and general considerations set out above in relation to the categories of Human Biomedical
p.000019: Research that qualifies for Exempted Review also apply to IRBs’ determination of categories permitted
p.000019: Expedited Review. Research qualifying for Expedited Review should present no more than minimal risks to research
p.000019: subjects.
p.000019:
p.000019: 3.18. By way of illustration, the following categories of Human Biomedical Research could be considered
p.000019: for Expedited Review, taking into account current practice:
p.000019:
p.000019: (a) Minor changes to previously approved research;
p.000019:
p.000019: (b) Annual reviews of previously approved research in which there has been little or no change in the on- going
p.000019: research;
p.000019:
p.000019: (c) The analysis of patients’ information without interacting with the patients. Researchers may be
p.000019: allowed access to medical records only if the IRB is satisfied that there is potential scientific / medical
p.000019: benefit of the research and that the researchers will take appropriate measures to protect the privacy of the
p.000019: individuals;
p.000019:
p.000019: (d) The local portion (at the level of specific institutions) of a multi- centre or multinational researc
p.000019: h programme that has already received a full review and approval by the lead IRB (as elaborated
p.000019: in paragraphs 5.49 to 5.56 of this Report); and
p.000019:
p.000019: (e) Research involving human tissues from tissue banks. IRBs must be satisfied that the tissues are obtained from
p.000019: a reliable source in which consent has been obtained for the tissues to be used for research and that the donor's
p.000019: privacy is protected.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: HUMAN
p.000020: BIOMEDICAL RESEARCH
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020: Stem Cell Lines
p.000020:
p.000020: 3.19. We make clear that all research involving the use of human embryonic stem cell lines or the creatio
p.000020: n of such human stem cell lines requires full ethics review.
...
p.000045: 3.2.5). The NMEC Guidelines state that investigators are “bound to act in exact accordance with the details”
p.000045: of the protocol submitted for ethics review and that investigators are “obliged to
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046:
p.000046: ETHICS GOVERNANCE
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: report to the [IRB] any adverse events and apparent risks beyond those predicted in the original
p.000046: submission. The investigator should also immediately inform the [IRB] of any new information that might alter
p.000046: the ethical basis of the research programme. The [IRB] should also be notified if the study is terminated prematurely.”
p.000046: We agree entirely with the NMEC in these statements and adopt them.
p.000046:
p.000046: 6.31. The submission of a protocol operates as a representation and agreement by each researcher who signs the
p.000046: application that the research programme will be carried out strictly in accordance with the submitted protocol.
p.000046:
p.000046: 6.32. Researchers are obliged to suspend their research immediately, pending their report to the IRB,
p.000046: if deviations or changes to the original project submitted are substantial. Researchers are under the
p.000046: same obligation if deviations and changes have resulted or will likely result in greater harm or greater likelihood
p.000046: of harm (whether of degree or incidence) to the sub jects involved.
p.000046:
p.000046: 6.33. Minor changes intended solely for the greater safety, health, welfare and well-being of the
p.000046: human subjects taken after consultation with all researchers involved in the research need not be
p.000046: immediately reported to the IRB. For example, if it appears to a researcher that a particular research
p.000046: subject is not altogether comfortable with one of the planned procedures, that procedure may be stopped
p.000046: and the research programme varied to such extent, without the need for immediate reporting. Reporting of such
p.000046: changes by the PI to the relevant IRB should however take place within a time frame that shall be decided by
p.000046: the IRB. We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000046: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of
p.000046: the research or for meeting its objectives, do not fall within this category and should be immediately
p.000046: reported.
p.000046:
p.000046: 6.34. PIs have an obligation to submit regular reports to IRBs regarding the status of their research
p.000046: programmes. These reports are intended to aid the IRBs in its role of continuing review and supervision.
p.000046:
p.000046:
p.000046: Researchers and Attending Physicians
p.000046:
p.000046: 6.35. Human subjects for research projects are often recruited from patients who are already receiving treatment
p.000046: from physicians.
p.000046:
p.000046: 6.36. Where a proposed researcher is the attending physician, the researcher- physician should be aware of
p.000046: a potential conflict of interest and of the fact
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047: ETHICS GOVERNANCE
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of Helsinki,
p.000047: which states that:
p.000047:
p.000047: “When obtaining informed consent for the research project the physician should be particularly cautious if the subject
p.000047: is in a dependent relationship with the physician or may consent under duress. In that case the informed consent
...
p.000056: B-99
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 6.30. This continuing obligation of researchers is clearly referred to in the NMEC Guidelines (at
p.000056: paragraph 3.2.5). The Guidelines state that investigators are “bound to act in exact accordance with the
p.000056: details” of the protocol submitted for ethics review, and that investigators are “obliged to report to the [IRB]
p.000056: any adverse events and apparent risks beyond those predicted in the original submission. The
p.000056: investigator should also immediately inform the [IRB] of any new information that might alter the ethical basis of
p.000056: the research programme. The [IRB] should also be notified if the study is terminated prematurely”. We agree entirely
p.000056: with the NMEC in these statements, and adopt them.
p.000056:
p.000056: 6.31. The submission of a protocol operates as a representation and agreement by each and every researcher who signs
p.000056: the application that the research programme will be carried out strictly in accordance with the submitted
p.000056: protocol.
p.000056:
p.000056: 6.32. Where deviations or changes are substantial, or in every case where the deviations and changes from the
p.000056: original proposal submitted to the IRB has resulted or is likely to result in greater harm or a greater likelihood
p.000056: of harm (whether of degree or incidence) to the subjects involved, the researchers are under a duty to
p.000056: suspend the research immediately, pending their report to the IRB.
p.000056:
p.000056: 6.33. Minor changes intended solely for the greater safety, health, welfare and well-being of the human
p.000056: subjects taken after consultation with all researchers involved in the trial need not be immediately
p.000056: reported to the IRB. For example, if it appears to a researcher that a particular research subject is not
p.000056: altogether comfortable with one of the planned procedures, that procedure may be dropped and the research programme
p.000056: varied to such extent, without the need for immediate reporting. Reporting of such changes by the Principal
p.000056: Investigator to the relevant IRB should however take place within a set time frame that shall be decided by the IRB.
p.000056: We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000056: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of the
p.000056: trial or of its objectives do not fall within this category and should be immediately reported.
p.000056:
p.000056: Researchers and Attending Physicians
p.000056:
p.000056: 6.34. Human subjects for research projects are often recruited from patie nts who are already receiving treatment
p.000056: from physicians.
p.000056:
p.000056: 6.35. Where a proposed researcher is the attending physician, the researcher / physician should be aware
p.000056: of a potential conflict of interest, and of the fact
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-100
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of
p.000056: Helsinki, which states that “[w]hen obtaining informed consent for the research project the physician
p.000056: should be particularly cautious if the subject is in a dependent relationship with the physician or may
p.000056: consent under duress. In that case the informed consent should be obtained by a well- informed
p.000056: physician who is not engaged in the investigation and who is completely independent of this relationship”.
p.000056:
p.000056: 6.36. In our view, however, this does not app ly to situations where clinicians wish to write up or publish
...
Searching for indicator youth:
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p.000001: in the consultation process and took time to consider and provide thoughtful feedback. We are pleased to
p.000001: append to this Report a complete record of the representations received. The BAC also sought the views of several
p.000001: local and international experts during its deliberations.
p.000001:
p.000001: Finally, I would like to thank my fellow Committee members, especially the Chairman of the HGS, Associate
p.000001: Professor Terry Kaan, as well as the members of his Subcommittee, for their commitment and dedication to
p.000001: the project and for ensuring that these recommendations remain a considered, fair and sensitive response to the
p.000001: many difficult issues relating to the ethical conduct of research involving human subjects.
p.000001:
p.000001:
p.000001: Professor Lim Pin Chairman
p.000001: Bioethics Advisory Committee November 2004
p.000001:
p.000001: THE BIOETHICS ADVISORY COMMITTEE
p.000001: Chairman
p.000001:
p.000001: Professor Lim Pin
p.000001: University Professor
p.000001: National University of Singapore
p.000001:
p.000001:
p.000001: Members
p.000001:
p.000001: Mr Jeffrey Chan Wah Teck
p.000001: Principal Senior State Counsel (Civil), Attorney-General’s Chambers
p.000001:
p.000001: Mr Cheong Yip Seng
p.000001: Editor-in-Chief, English/Malay Newspapers Division, Singapore Press Holdings
p.000001:
p.000001: Associate Professor John Elliott
p.000001: Department of Social Work & Psychology, National University of Singapore
p.000001:
p.000001: Associate Professor Terry Kaan Sheung-Hung
p.000001: Faculty of Law, National University of Singapore
p.000001:
p.000001: Ms Lim Soo Hoon
p.000001: Permanent Secretary, Ministry of Community Development, Youth and Sports
p.000001:
p.000001: Professor Edison Liu
p.000001: Executive Director, Genome Institute of Singapore
p.000001:
p.000001: Mr Richard Magnus
p.000001: Senior District Judge, Subordinate Courts of Singapore
p.000001:
p.000001: Professor Ong Yong Yau
p.000001: Emeritus Consultant, Singapore General Hospital
p.000001:
p.000001: Professor Kandiah Satkunanantham
p.000001: Director of Medical Services, Ministry of Health
p.000001:
p.000001: Professor Tan Chorh Chuan
p.000001: Provost, National University of Singapore
p.000001:
p.000001: Mr Zainul Abidin Rasheed
p.000001: Mayor, North East Community Development Council
p.000001:
p.000001: About the Bioethics Advisory Committee
p.000001: The Bioethics Advisory Committee (BAC) was appointed by the Singapore Cabinet in December 2000. The BAC was directed
p.000001: to
p.000001: „examine the legal, ethical and social issues arising from research on human biology and behaviour and its
p.000001: applications“ and to
p.000001: „develop and recommend policies ... on legal, ethical and social issues, with the aim to protect the
p.000001: rights and welfare of individuals, while allowing the Life Sciences to develop and realise their full potential for
p.000001: the benefit of mankind“.
p.000001:
p.000001: The BAC reports to the Ministerial Committee for Life Sciences. For further information about the BAC and its work,
p.000001: please visit http://www.bioethics-singapore.org
p.000001:
p.000001: Contacting the Bioethics Advisory Committee
p.000001: The BAC welcomes views, comments, suggestions and other feedback on the issues raised in this report and on any
p.000001: bioethical issues within the BAC’s remit. All feedback should be addressed to:
p.000001:
p.000001: Bioethics Advisory Committee
...
Social / education
Searching for indicator education:
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p.000004: research involves interfering with the subjects’ medical management.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005: EXECUTIVE SUMMARY
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: Institutions
p.000005:
p.000005: 31. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical
p.000005: Research carried out by their employees on their premises.
p.000005:
p.000005: 32. Every institution involved in Human Biomedica l Research as defined in these Guidelines should establish
p.000005: and maintain an effective IRB. The institution must accept legal responsibility for the decisions of its
p.000005: IRB. IRBs may be shared by more than one institution. They could also be domain specific, providing
p.000005: more focused and specialised ethics review.
p.000005:
p.000005: 33. Each institution must set up clear policies for the establishment and operation of its IRB. The institution
p.000005: will determine the composition and constitution of the IRB, the specific operating procedures for ethics review and
p.000005: categories of research for Exempted Review and Expedited Review.
p.000005:
p.000005: 34. Institutions are responsible for providing their IRB members with full indemnity.
p.000005:
p.000005: 35. Institutions, in particular those with sizeable research programmes, should have in place
p.000005: programmes for the training and education of their IRB members.
p.000005:
p.000005: 36. Institutions should, in consultation with their IRBs, ensure that clear formal procedures are
p.000005: laid down for the release of all kinds of patients’ medical information.
p.000005:
p.000005: 37. Institutions should also ensure that there are adequate resources to enable their IRBs to discharge their
p.000005: duties and responsibilities in an effective and timely manner.
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: INTRODUCTION AND CURRENT
p.000006: FRAMEWORK
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006: RESEARCH INVOLVING HUMAN SUBJECTS
p.000006: GUIDELINES FOR IRBS
p.000006:
p.000006:
p.000006: PART A:
p.000006: INTRODUCTION AND CURRENT FRAMEWORK
p.000006:
p.000006: SECTION I: INTRODUCTION
p.000006:
p.000006: 1. Introduction About these Guidelines
p.000006: 1.1. The Bioethics Advisory Committee (BAC) was appointed by the Cabinet to examine the potential ethical,
p.000006: legal and social issues arising from research in the biomedical sciences in Singapore, and to recommend
p.000006: policies to the Life Sciences Ministerial Committee.
p.000006:
p.000006: 1.2. These Guidelines are issued by the BAC and were prepared by the Human Genetics Subcommittee (HGS). The
p.000006: members of the HGS are detailed in Annexe A.
p.000006:
p.000006: 1.3. These Guidelines are the third of a series of recommendations submitted to the Government by the BAC. The
...
p.000019: h programme that has already received a full review and approval by the lead IRB (as elaborated
p.000019: in paragraphs 5.49 to 5.56 of this Report); and
p.000019:
p.000019: (e) Research involving human tissues from tissue banks. IRBs must be satisfied that the tissues are obtained from
p.000019: a reliable source in which consent has been obtained for the tissues to be used for research and that the donor's
p.000019: privacy is protected.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: HUMAN
p.000020: BIOMEDICAL RESEARCH
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020: Stem Cell Lines
p.000020:
p.000020: 3.19. We make clear that all research involving the use of human embryonic stem cell lines or the creatio
p.000020: n of such human stem cell lines requires full ethics review.
p.000020:
p.000020:
p.000020: Cadaveric, Foetal and Legacy Tissues
p.000020:
p.000020: 3.20. We reiterate that nothing in these Guidelines is intended to displace the recommendations we
p.000020: advance in our Human Tissue Research Report. We take the view that human biomedical research to be conducted on
p.000020: legacy tissue as defined in our Human Tissue Research Report should always be subject to full review. In the
p.000020: case of other tissues donated with the free and informed consent of living donors, or of cadave ric or
p.000020: foetal tissue donated under the Medical (Therapy, Education and Research) Act, review should be considered, but
p.000020: Expedited Review may be allowed as appropriate, provided always that the use of the tissue concerned is
p.000020: within the terms of the gift of the tissue.
p.000020:
p.000020:
p.000020: Therapy versus Research
p.000020:
p.000020: 3.21. In Section 2.2.1 of the NMEC Guidelines, it is stated that:
p.000020:
p.000020: “Human research can be broadly defined as studies which generate data about human subjects which go beyond what is
p.000020: needed for the individual’s well-being. The primary purpose of research activity is the generation of new information
p.000020: or the testing of a hypothesis. The fact that some benefit may result from the activity does not alter its
p.000020: status as “research”. Defined in this manner, human research includes not only studies which involve human
p.000020: subjects directly, but also epidemiological surveys and reviews of patient records, for purposes not
p.000020: related to the patient’s immediate health care needs”.
p.000020:
p.000020: 3.22. In its Guidelines, the NMEC also considered the relationship and distinction between
p.000020: research and therapy. It held that when “an activity is undertaken with the sole intention of benefiting the
p.000020: patient, the activity may be considered to be part of “therapy”. The progressive modification of methods of
p.000020: diagnosis and treatment in the light of experience is a normal feature of medical practice and should
p.000020: not be considered as research. There could be potential conflicts between research (intended to generate new
p.000020: information) and therapy (intended to benefit the individual patient directly). Their resolution rests on the
p.000020: integrity of the physician /
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
...
p.000051: 7.12. In the context of institutions such as hospitals with centralised patient records and databases,
p.000051: we recommend that appointing institutions take steps to determine who within the administrative structure should
p.000051: be the proper administrative custodians responsible for patients’ medical information in the
p.000051: institution, and to advise their IRBs accordingly.
p.000051:
p.000051: 7.13. In situations where any of the researchers are also the administrative custodian of patients’
p.000051: medical information within the institution, procedures should be established to address actual,
p.000051: potential or apparent conflicts of interest.
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
...
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: F-158
p.000056:
p.000056:
p.000056: ANNEXE G
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: LIST OF ABBREVIATIONS
p.000056:
p.000056: BAC Bioethics Advisory Committee (Singapore)
p.000056: CEO Chief Executive Officer
p.000056: DNA Deoxyribonucleic acid
p.000056: EC Ethics committee
p.000056: GCP Good Clinical Practice
p.000056: HGS Human Genetics Subcommittee
p.000056: HSA Health Sciences Authority (Singapore)
p.000056: ICH International Conference on Harmonisation
p.000056: IRB Institutional Review Board
p.000056: MCRC Medical Clinical Research Committee
p.000056: MOH Ministry of Health (Singapore)
p.000056: NHG National Healthcare Group (Singapore)
p.000056: NMEC National Medical Ethics Committee (Sin gapore) NUH National University
p.000056: Hospital
p.000056: PI Principal Investigator
p.000056: RNA Ribonucleic acid
p.000056: SGGCP Singapore Guideline for Good Clinical Practice SOP Standard Operating
p.000056: Procedure
p.000056: UNESCO United Nations Education, Scientific and Cultural Organization
p.000056: WHO World Health Organization
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
...
Searching for indicator educational:
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p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
...
p.000056:
p.000056:
p.000056: –––––––––––––––––––––
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-156
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SELECT REFERENCES
p.000056:
p.000056: International
p.000056:
p.000056: 1. Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (2000)
p.000056: World Medical Association
p.000056:
p.000056: 2. ICH Topic E6 - Guideline For Good Clinical Practice (1996)
p.000056: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
p.000056:
p.000056: 3. International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) Council for International
p.000056: Organizations of Medical Sciences
p.000056:
p.000056: 4. Nuremberg Code (1949)
p.000056: Trials of War Criminals before the Nuremberg Military Tribunals under Control Council
p.000056: U.S. Government Printing Office, Washington D.C. Law No. 10, Vol. 2:181-182
p.000056: 5. Operational Guidelines for Ethics Committees that Review Biomedical Research (20 00) World Health Organization
p.000056:
p.000056: 6. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services (1998)
p.000056: World Health Organization
p.000056:
p.000056: 7. Universal Declaration on the Human Genome and Human Rights (1997) United Nations Educational, Scientific and
p.000056: Cultural Organization
p.000056:
p.000056:
p.000056: Singapore
p.000056:
p.000056: 1. Ethical, Legal and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning (June 2002)
p.000056: Bioethics Advisory Committee
p.000056:
p.000056: 2. Human Tissue Research (November 2002) Bioethics Advisory Committee
p.000056:
p.000056: 3. National Medical Ethics Committee: A Review of Activities, 1994-1997 (1998) National Medical Ethics Committee,
p.000056: Ministry of Health
p.000056:
p.000056: 4. Singapore Guideline for Good Clinical Practice (1998) Ministry of Health
p.000056:
p.000056:
p.000056:
p.000056: F-157
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056: Other Countries
p.000056:
p.000056: 1. National Statement on Ethical Conduct in Research Involving Humans (1999) National Health and Medical Research
p.000056: Council, Australia
p.000056:
p.000056: 2. Human Research Ethics Handbook (2001)
p.000056: National Health and Medical Research Council, Australia
p.000056:
p.000056: 3. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (1998, with 2000, 2002, 2003 updates)
p.000056: Medical Research Council, Natural Sciences and Engineering Research Council, and Social
p.000056: Sciences and Humanities Research Council, Canada
p.000056:
p.000056: 4. Governance arrangements for NHS Research Ethics Committees (July 2001) Department of Health, United Kingdom
p.000056:
...
Social / employees
Searching for indicator employees:
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p.000004: research programme and in keeping other participating IRBs informed of any decisions and amendments made during the
p.000004: whole research period. The local portion of a multinational research programme should be subject to review by
p.000004: the local IRB.
p.000004:
p.000004: Researchers
p.000004:
p.000004: 26. Researchers must comply with all the conditions laid down by the IRB that approved their project.
p.000004:
p.000004: 27. Researchers are also responsible for ensuring that their research complies with all relevant laws and other
p.000004: regulatory obligations and requirements.
p.000004:
p.000004: 28. Researchers are required to inform and seek approval from their IRBs for any proposed variations from the
p.000004: terms of approval of the projects before such variations can be implemented.
p.000004:
p.000004: 29. Researchers should submit annual (or more frequent) progress reports as required by their IRBs,
p.000004: as well as project completion reports and reports of adverse events.
p.000004:
p.000004: 30. Researchers should inform and discuss with the research subjects’ attending physicians if the
p.000004: research involves interfering with the subjects’ medical management.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005: EXECUTIVE SUMMARY
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: Institutions
p.000005:
p.000005: 31. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical
p.000005: Research carried out by their employees on their premises.
p.000005:
p.000005: 32. Every institution involved in Human Biomedica l Research as defined in these Guidelines should establish
p.000005: and maintain an effective IRB. The institution must accept legal responsibility for the decisions of its
p.000005: IRB. IRBs may be shared by more than one institution. They could also be domain specific, providing
p.000005: more focused and specialised ethics review.
p.000005:
p.000005: 33. Each institution must set up clear policies for the establishment and operation of its IRB. The institution
p.000005: will determine the composition and constitution of the IRB, the specific operating procedures for ethics review and
p.000005: categories of research for Exempted Review and Expedited Review.
p.000005:
p.000005: 34. Institutions are responsible for providing their IRB members with full indemnity.
p.000005:
p.000005: 35. Institutions, in particular those with sizeable research programmes, should have in place
p.000005: programmes for the training and education of their IRB members.
p.000005:
p.000005: 36. Institutions should, in consultation with their IRBs, ensure that clear formal procedures are
p.000005: laid down for the release of all kinds of patients’ medical information.
p.000005:
p.000005: 37. Institutions should also ensure that there are adequate resources to enable their IRBs to discharge their
p.000005: duties and responsibilities in an effective and timely manner.
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
...
p.000027: highest level of management of the hospital. We believe that the term “institutional review board” best reflects
p.000027: this role.
p.000027:
p.000027: 5.3. We differentiate here between IRBs that review, approve and supervise biomedical research involving
p.000027: humans, and hospital ethics committees that address issues arising out of clinical practice (clinical practice
p.000027: ethics committees). For the avoidance of doubt, we make clear that our recommendations in these
p.000027: Guidelines cover only IRBs that review, approve and supervise Human Biomedical Research, and are no t
p.000027: intended to apply to clinical practice ethics committees.
p.000027:
p.000027: 5.4. We further clarify that the term "institution" is not limited to hospitals or medical clinics, but also
p.000027: includes any organisation or entity that carries out Human Biomedical Research as defined in these Guidelines. This
p.000027: includes commercial entities and government agencies.
p.000027:
p.000027: 5.5. We recognise that valuable Human Biomedical Research is also carried out by biomedical
p.000027: researchers who have no formal affiliation with IRB- guided institutions. Such biomedical
p.000027: researchers include medical practitioners in private practice (such as specialist consultants and general
p.000027: practitioners), and biomedical researchers who are employed by or who are affiliated with institutions that do not have
p.000027: and do not propose to constit ute an IRB because of the low volume of Human Biomedical Research carried out by their
p.000027: employees or affiliates. In the case of registered medical practitioners and specialists in private practice,
p.000027: we suggest that they seek ethics approval for the conduct of their proposed research from the IRBs of
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028:
p.000028: ETHICS GOVERNANCE
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028: appropriate hospitals or other medical institutions. This approach could also be applied to biomedical
p.000028: researchers who are not registered medical practitioners. In any event, the requirements for appropriate ethics
p.000028: review as defined in these guidelines should apply regardless of the institutional affiliation of researchers.
p.000028:
p.000028: 5.6. There is universal agreement in all developed countries that IRBs are central to a proper framework
p.000028: of ethics governance of human research and that the primary objective of an IRB is to protect and assure
p.000028: the safety, health, dignity, welfare and well-being of human research subjects, in keeping with the
p.000028: principles outlined above.
p.000028:
p.000028: 5.7. Increasingly, collaborative research programmes are carried out across international borders (in
p.000028: multinational research programmes) or by researchers in several institutions (in multi-centre research
p.000028: programmes), or even a combination of both. It is usually a condition of such research programmes that the
...
p.000049:
p.000049:
p.000049:
p.000049: attending physicians (on the assumption, of course, that they have complied with all other applicable
p.000049: requirements).
p.000049:
p.000049: 6.44. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000049: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the subjects
p.000049: without first seeking and obtaining the approval of both the attending physicians and the IRB.
p.000049:
p.000049:
p.000049:
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p.000049:
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p.000049:
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p.000049:
p.000049:
p.000049:
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p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
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p.000049:
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p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000050: 50
p.000050:
p.000050:
p.000050: ETHICS GOVERNANCE
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION VII: INSTITUTIONS
p.000050:
p.000050: 7. Institutions
p.000050:
p.000050: The Responsibilities of Appointing Institutions
p.000050:
p.000050: 7.1. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical Research and
p.000050: the protection of human subjects in all Human Biomedical Research carried out on their premises or facilities, or by
p.000050: their employees, or on their patients, or involving access to or use of human tissue collections in their custody, or
p.000050: involving access to or use of medical records or other personal information in their custody.
p.000050:
p.000050: 7.2. Every institution involved in Human Biomedical Research as defined in these Guidelines should
p.000050: establish and maintain an effective IRB. The IRB is accountable to the appointing institution, which must
p.000050: accept legal responsibility for the decisions of its IRB.
p.000050:
p.000050: 7.3. Institutions should lay policies for the composition of IRBs and the formal appointment of IRB members in
p.000050: accordance with the general principles and guidance presented in these Guidelines and, in particular, those set
p.000050: out under “Specific Operating Procedures for Institutional Review Boards” in Section V.
p.000050:
p.000050: 7.4. It is the responsibility of institutions to provide adequate resources and administrative support
p.000050: so as to enable IRBs to discharge their duties and responsibilities in an effective and timely manner.
p.000050:
p.000050: 7.5. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of
p.000050: their work and IRBs should likewise ensure that their workload does not compromise the quality of their
p.000050: review. If this is likely, the institution is obliged to establish additional IRBs, to enlarge the
p.000050: membership of the IRB or to make formal arrangements for other IRBs to provide an opinion.
p.000050:
...
Social / parents
Searching for indicator parent:
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p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Shared and Domain Institutional Review Boards
p.000029:
p.000029: 5.12. Where by reason of the small size of the institution or the small number of research proposals it is
p.000029: impractical to establish and maintain a standing IRB of its own, such institutions should make clear
p.000029: arrangements with other institutions which maintain IRBs for research proposals to be considered by
p.000029: the IRBs of larger institutions.
p.000029:
p.000029: 5.13. Alternatively, it is permissible for several such institutions to jointly appoint a shared IRB.
p.000029:
p.000029: 5.14. Even in cases of institutions that already have their own IRBs, these institutions may prefer or
p.000029: wish to refer some kinds of research applications (for example, a proposal for research in a specialist area)
p.000029: to a specialist IRB or a domain IRB that has the technical capacity to assess research in that specialised area.
p.000029: Again, several institutions could jointly appoint and share in the expertise of such an IRB in situations where such
p.000029: expertise is limited. Such a specialist IRB has the advantage of delivering consistent decisions, special
p.000029: competence and knowled ge in their field of specialisation.
p.000029:
p.000029: 5.15. We note that some hospitals and institutions in Singapore have set up domain specific IRBs with
p.000029: the intention of providing more focused and specialised ethics review. For example, sister or subsidiary
p.000029: institutions under the direction and control of a parent institution may choose to organise IRBs along
p.000029: domain lines, which can be shared by all the related institutions within the group. Such an arrangement is acceptable
p.000029: to us, as it is entirely in keeping with the ethical principles we have set out. Under this arrangement, the
p.000029: parent institution for all the hospitals and other institutions within the group will be responsible
p.000029: for constituting the necessary IRBs for all its constituent institutions and arranging for the
p.000029: accreditation of the IRBs.
p.000029:
p.000029: 5.16. We have no objections to other groups of research institutions adopting such a similar approach,
p.000029: provided that the terms of the arrangement between the institutions are clearly spelt out.
p.000029:
p.000029: 5.17. We therefore recommend that related institutions under the direction and control of a parent institution
p.000029: should be permitted to share an IRB or IRBs constituted by the parent institution.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030:
p.000030: ETHICS GOVERNANCE
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: The Responsibilities of Institutional Review Boards
p.000030:
p.000030: 5.18. In its acts and decisions, and in the exercise and discharge of its duties and responsibilities, an IRB acts
p.000030: on the behalf of the institution that appoints it and exercises on its behalf the authority and powers of
p.000030: that institution in matters within the terms of reference of the IRB.
p.000030:
p.000030: 5.19. Accordingly, we emphasise that the institution is responsible for the acts and decisions of the
p.000030: IRB(s) that it appoints.
p.000030:
p.000030: 5.20. Ethics Review Gateway. The fundamental responsibility of an IRB is to act as an ethics review gateway
p.000030: for all Human Biomedical Research carried out under the auspices of its appointing institution, with the
p.000030: primary objectives of the protection and assurance of the safety, health, dignity, welfare and well-being of
p.000030: human research subjects. An IRB has a duty to ensure that all Human Biomedical Research carried out under the auspices
p.000030: of its appointing institution are ethically acceptable, and to comply with the principles outlined in Section
p.000030: IV.
p.000030:
...
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
p.000056: as those contained in the Medicines (Clinical Trials) Re gulations, promulgated pursuant to s.74 of the
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
p.000056: Regulations and its parent Act (the Medicines Act, Cap. 176) has a special meaning. As defined in
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
p.000056: instead use the term “drug trials” in this Consultation Paper when referring to “clinical trials” in the legal sense of
p.000056: that term, as used in the Clinical Trials Regulations and the Medicines Act.
p.000056:
p.000056: 2.13. In keeping with the principles enunciated in the Declaration of Helsinki, an important component of
p.000056: the requirements of the Clinical Trials Regulations is that the researchers must ensure that the free
p.000056: consent of the proposed research subject must be obtained, and that researchers are under a duty to give full
p.000056: explanation and information of (among others) the risks and objectives of the proposed drug trial.
p.000056:
p.000056: The Singapore Guideline for Good Clinical Practice
p.000056:
p.000056: 2.14. In 1998, the Ministry of Health released the Singapore Guideline for Good Clinical Practice (SGGCP), which is
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.000032:
p.000032: 5.31. The IRB should be appointed by and report to at least an authority at the level of the Chief Executive
p.000032: Officer (as recommended by the NMEC Guidelines in the case of hospitals falling under the jurisdiction
p.000032: of the MOH pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000032:
p.000032: 5.32. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000032: although it is acceptable for institutions
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033: ETHICS GOVERNANCE
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: with standing IRBs to appoint special ad hoc committees in consultation with their standing IRBs to
p.000033: consider special research proposals. We prefer, in such cases, that the institutions work with their standing
p.000033: IRBs to appoint special subcommittees co-opting experts or reviewers to assist the standing IRBs in the particular
p.000033: project concerned. For example, an IRB may receive a research proposal involving an area of research with which no
p.000033: member of the IRB is familiar. In such a case, the institution may work with the IRB to identify and co-opt ad
p.000033: hoc experts or reviewers to assist the IRB in its assessment and review of the proposal. The co-opted ad hoc experts
p.000033: or reviewers sit as a subcommittee of the IRB.
p.000033:
p.000033:
p.000033: Composition
p.000033:
p.000033: 5.33. We are of the opinion that the SGGCP (in particular Section 3.2.3) and the NMEC Guidelines (in particular
p.000033: Section 3.2.2) lay out appropriate and comprehensive guidelines regarding the composition of an
p.000033: ethics committee. We endorse these requirements and propose that they be similarly used to form the
p.000033: framework for the composition of an IRB.
p.000033:
p.000033: 5.34. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000033:
p.000033: (a) Impartiality and objectivity are fundamental principles to be observed in the appointment of
p.000033: members to IRBs. An IRB should be carefully composed in order that there can be no room for any public perception
p.000033: that it is not independent of those who are required to submit to its review;
p.000033:
p.000033: (b) Where a majority of the IRB members are drawn from within the appointing institutions, these persons
p.000033: should be the institutions’ most senior, most respected and scientifically competent officers,
p.000033: researche rs or consultants, who possess the appropriate experience and training;
p.000033:
p.000033: (c) An IRB should include non- medical and/or non-scientific persons (lay representation) who are not members
p.000033: of or otherwise associated with the appointing institution of the IRB. Their inclusion is to reinforce the
p.000033: impartiality and objectivity of the work of the IRB;
p.000033:
p.000033: (d) To further reinforce the independence of the IRB and to ensure that the decisions of the board are
p.000033: carried out in accordance with scientific thinking accepted within the community, external
...
p.000037: owe a public and professional duty to act with total impartiality, objectivity and independence in the
p.000037: discharge of their duties.
p.000037:
p.000037: 5.59. If for any reason a member of an IRB or the IRB itself should be of the view that there exist
p.000037: circumstances or considerations that might impair, adversely affect or make impossible the impartial,
p.000037: objective and independent discharge of duties, the member or IRB concerned should decline to review or
p.000037: process the research proposal or proposals in question and immediately report such concerns to the highest level of
p.000037: management of the institution.
p.000037:
p.000037: 5.60. Conflicts of interest. IRBs and members of IRBs should take especial care to avoid conflicts of interes t,
p.000037: whether actual conflict, potential conflict, or only the appearance of conflict as such.
p.000037:
p.000037: 5.61. A situation of real, potential or apparent conflict of interest amounts to circumstances that
p.000037: adversely affects the impartiality, objectivity and independence of the IRB or of its members as described
p.000037: above.
p.000037:
p.000037: 5.62. In the event that a member of the IRB has a personal interest in the research under review, that
p.000037: member should recuse himself or herself from
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038:
p.000038: ETHICS GOVERNANCE
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038: any consideration of the case by the IRB, and he or she should refra in from offering his or her opinion to the
p.000038: IRB on the particular research under review.
p.000038:
p.000038: 5.63. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000038: the IRB.
p.000038:
p.000038: 5.64. Fair review and documentation of decisions. IRBs should provide a fair hearing to those involved. Where
p.000038: there exist any doubts or difficulties with particular aspects of proposals, IRBs should clarify these
p.000038: in writing with the researchers, or in a minuted face-to- face meeting between the IRB and the researchers.
p.000038:
p.000038: 5.65. All discussions of the IRB should be appropriately minuted and all opinions recorded. The decisions
p.000038: of the IRB should be provided in written form and, where appropriate, a fair and frank account of the
p.000038: reasons for those decisions should be provided.
p.000038:
p.000038: 5.66. Ethics review by an IRB should be based upon fully detailed research proposals or, where
p.000038: applicable, the most up -to-date progress reports. The proposals or progress reports on which ethics review is
p.000038: based should be drawn up specifically for the purposes of submission for ethics review.
p.000038:
p.000038: 5.67. IRBs may also require the submission of a lay summary of the research proposal, where this may aid
p.000038: the lay members of the IRB in the conduct of ethics review. This summary should set out concisely the salient fea
p.000038: tures of the research proposal. In certain cases, it may also be useful to have a lay summary of the scientific
p.000038: review.
p.000038:
...
p.000042:
p.000042: 6.10. Researchers should not submit to IRBs the same or substantially the same documents for ethics review that
p.000042: they submitted to prospective funding agencies, unless these documents focus on or evaluate the potential impact of
p.000042: the research on the safety, health, dignity, welfare and privacy of the subject in addition to solely describing the
p.000042: scientific merits of the research. However, we nonetheless prefer researchers submit a separate document for
p.000042: ethics review. Researchers should be aware that research proposals submitted for ethics review and research
p.000042: proposals submitted for funding purposes are directed at completely different ends and should be drafted accordingly.
p.000042:
p.000042: 6.11. In no circumstances should researchers use IRBs and the ethics review process as a means of gaining
p.000042: ethics approval for research projects that the researchers themselves entertain doubts or uncertainties about
p.000042: from the ethical point of view.
p.000042:
p.000042: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000042: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000042: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000042: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000042:
p.000042: 6.13. In such cases, we take the view that if researchers believe, in good faith, that the proposed
p.000042: research is ethical, the n such proposed research may be submitted for ethics review provided that the researchers
p.000042: fully disclose all such differing opinions and potential ethical difficulties or controversies known to them;
p.000042: that the researchers fully disclose the ethical reservations or doubts they hold; and that researchers fully disclose
p.000042: all other material facts and issues that might help the IRB carry out an impartial and objective review.
p.000042: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to
p.000042: explore all potential ethical issues, and to carry out an impartial and objective review of a novel
p.000042: situation, there is no objection to researchers submitting in good faith for ethics review a research proposal that the
p.000042: researchers themselves feel that they need ethical guidance.
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043:
p.000043: ETHICS GOVERNANCE
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: 6.14. It is important that researchers take special care to avoid any form of conflicts of interest,
...
p.000050: their employees, or on their patients, or involving access to or use of human tissue collections in their custody, or
p.000050: involving access to or use of medical records or other personal information in their custody.
p.000050:
p.000050: 7.2. Every institution involved in Human Biomedical Research as defined in these Guidelines should
p.000050: establish and maintain an effective IRB. The IRB is accountable to the appointing institution, which must
p.000050: accept legal responsibility for the decisions of its IRB.
p.000050:
p.000050: 7.3. Institutions should lay policies for the composition of IRBs and the formal appointment of IRB members in
p.000050: accordance with the general principles and guidance presented in these Guidelines and, in particular, those set
p.000050: out under “Specific Operating Procedures for Institutional Review Boards” in Section V.
p.000050:
p.000050: 7.4. It is the responsibility of institutions to provide adequate resources and administrative support
p.000050: so as to enable IRBs to discharge their duties and responsibilities in an effective and timely manner.
p.000050:
p.000050: 7.5. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of
p.000050: their work and IRBs should likewise ensure that their workload does not compromise the quality of their
p.000050: review. If this is likely, the institution is obliged to establish additional IRBs, to enlarge the
p.000050: membership of the IRB or to make formal arrangements for other IRBs to provide an opinion.
p.000050:
p.000050: 7.6. Institutions are obliged to ensure that IRBs receive adequate administrative support that is commensurate
p.000050: with the central role of the IRB in the ethics governance process. In this respect, the institution may take
p.000050: steps to lighten the workload of IRBs by delegating review in specific areas to a subcommittee, or by
p.000050: delegating some of its administrative or supervisory tasks to a separate well-staffed administrative body.
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051:
p.000051: ETHICS GOVERNANCE
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: 7.7. Such full-time administrative support should be sufficient to allow the IRB to:
p.000051:
p.000051: (a) Ensure continuity and consistency in the work of the IRBs;
p.000051:
p.000051: (b) Discharge any continuing review and supervisory obligations, outcome assessment and reporting
p.000051: duties;
p.000051:
p.000051: (c) Ensure that the IRB's decisions are made with regard to previously established precedents and
p.000051: decisions tha t they and their predecessors have made; and
p.000051:
p.000051: (d) Ensure that proposals are reviewed and dealt with in a timely manner within the target time frames set by the
p.000051: institution.
p.000051:
p.000051: 7.8. The core members of the IRB should be able to devote sufficient and protected time commensurate
p.000051: with the workload of the IRB.
p.000051:
p.000051: 7.9. Institutions are also responsible for providing their IRB members with a full indemnity as set
...
p.000056: the institution works with their standing IRB to appoint special subcommittees co-opting experts or reviewers to assist
p.000056: the standing IRB in the particular project concerned. For example, an IRB may receive a research proposal
p.000056: involving an area of research with which no member of the IRB is familiar. In such a case, the institution may work
p.000056: with the IRB to identify and co-opt ad hoc experts or reviewers to assist the IRB in its assessment and review
p.000056: of the proposal. The co-opted ad hoc experts or reviewers sit as a subcommittee of the IRB.
p.000056:
p.000056: 5.23. Institutions have an obligation to ensure that IRBs receive adequate administrative support
p.000056: that is commensurate with their central role in the ethical governance process.
p.000056:
p.000056: 5.24. IRBs should have sufficient full-time administrative support so as to ensure continuity and
p.000056: consistency in the work of the IRBs, to discharge its continuing review, supervision and audit obligations,
p.000056: its outcome assessment and reporting duties, and to ensure that their decisions are made with regard to
p.000056: previously-established precedents and decisions made by themselves and their predecessors.
p.000056:
p.000056: 5.25. Institutions should also ensure that IRBs have sufficient administrative support so as to ensure
p.000056: that proposals are reviewed and dealt with in a timely manner within the target time- frames set by the
p.000056: institution.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-85
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Composition
p.000056:
p.000056: 5.26. We are of the opinion that the SGGCP, in particular paragraph 3.2.3, and the NMEC Guidelines, in particular
p.000056: paragraph 3.2.2, lay out appropriate and comprehensive guidelines regarding the composition of an ethics
p.000056: committee. We endorse these requirements, and propose that they be similarly used to form the framework for
p.000056: the composition of an IRB.
p.000056:
p.000056: 5.27. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000056:
p.000056: 5.27.1 Given the importance of the IRB, it is important that the core members of IRB should be appointed
p.000056: from among the institutions’ most senior, most respected and scientifically competent officers, researchers or
p.000056: consultants, who possess the appropriate experience and training.
p.000056:
p.000056: 5.27.2 The core members of the IRB should be able to devote sufficient time commensurate to the workload of
p.000056: the IRB.
p.000056:
p.000056: 5.27.3 Representation on an IRB should not be restricted to members of the institution, but should include
p.000056: external and lay representation.
p.000056:
p.000056: 5.27.4 External representation may be in the form of specialists of reputation from other
p.000056: institutions: the objective here is to lend impartiality and objectivity to the work of the IRB, and to ensure
p.000056: that the decisions of the board are carried out in accordance with scientific thinking accepted within the community.
p.000056:
p.000056: 5.27.5 IRBs should also have lay, non-scientific or non-medical representation. Where pract
...
p.000056: applicable, the most up -to-date progress reports. The proposals or progress reports on which ethics review is
p.000056: based should be drawn up specifically for the purposes of submission for ethical review.
p.000056:
p.000056: 5.50. Research proposals should not consist of the same or substantially the same documents submitted by
p.000056: the researchers for the purpose of a proposal for funding. IRBs should bear in mind that research proposals submitted
p.000056: for ethical review are directed at a completely different end to that of proposals submitted for funding
p.000056: purposes.
p.000056:
p.000056: 5.51. The requirements of impartiality, fair review, and documentation of decisions should apply
p.000056: equally to IRBs engaged in the continuing review, supervision or audit of a research program.
p.000056:
p.000056: 5.52. Conflicts of interest. IRBs and members of IRBs should take especial care to avoid conflicts of interest,
p.000056: whether actual conflict, potential conflict, or only the appearance of conflict as such.
p.000056:
p.000056: 5.53. A situation of real, potential or apparent conflict of interest amounts to circumstances which
p.000056: adversely affect the impartiality, objectivity and independence of the IRB or of its members as described above.
p.000056:
p.000056: 5.54. In the event that a member of the IRB has a personal interest in the research under review, that
p.000056: member should recuse himself or herself from any consideration of the case by the IRB, a nd he or she should refrain
p.000056: from offering his or her opinion to the board on the particular research under review.
p.000056:
p.000056: 5.55. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000056: the board.
p.000056:
p.000056: 5.56. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000056: obtaining of free and informed consent of subjects in drug trials be in principle extended to all other kinds of
p.000056: clinical research with appropriate modifications.
p.000056:
p.000056: 5.57. Both researchers and IRBs should take especial care to ensure that the proposed human subjects will
p.000056: be able to understand and assess the risks of participation, and that the consent -taking procedure and the
p.000056: documentation are properly designed to achieve this end.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-91
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.58. Both researchers and IRBs should ensure that the participants of research projects are aware that they have
p.000056: the right to withdraw from the research programme at any time.
p.000056:
p.000056: 5.59. We recommend that IRBs and institutions formalise arrangements which allow participants a one-stop direct
p.000056: access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
...
p.000056: officers in order to give feedback on the trial, or to express their concerns.
p.000056:
p.000056: 5.60. In the same vein, we further recommend that researchers consider (and IRBs should consider making it
p.000056: a condition of approval) appointing one of their number (who should be a registered med ical practitioner or a senior
p.000056: member of the research team) as a one-stop participant contact in all cases where the research programme involves any
p.000056: level of clinical intervention or interaction with the participants, and in cases where the interaction (for example,
p.000056: the collation of medical histories, or physical examination) with participants is delegated to support and field
p.000056: workers or assistants.
p.000056:
p.000056: 5.61. A copy of every document signed by research subjects or given to them to read, including the consent
p.000056: documentation, should be given to and retained by the research subjects.
p.000056:
p.000056: 5.62. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000056: Research Report apply to the use of human biological materials in clinical research.
p.000056:
p.000056: 5.63. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of its
p.000056: work, and IRB should likewise ensure that its workload does not compromise the quality of its review. Where
p.000056: this is likely, it is the obligation of the institution to establish additional IRBs, or to enlarge the
p.000056: membership of the IRB, or make formal arrangements for other IRBs to provide an opinion.
p.000056:
p.000056: 5.64. Meetings. IRBs should have regular and frequent formal face-to-face meetings with a defined quorum.
p.000056: The work of the board should not be conducted routinely via circulation of documents. Applications that
p.000056: raise novel, unusual or difficult issues (from the ethical or scientific merit perspectives) or those which
p.000056: present significant risk to partic ipants should be debated and discussed in face-to- face meetings.
p.000056:
p.000056: 5.65. Exempted and Expedited Review. IRBs may draw up and provide for exempted or expedited review
p.000056: of research proposals, in a properly-
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-92
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: deliberated and written set of Standard Operating Procedures for the work of the board.
p.000056:
p.000056: 5.66. Such expedited or exempted review should be allowed only for classes of research programmes which involve
p.000056: minimal or no risk to the safety, health, welfare and well-being of the participants and which are
p.000056: widely accepted in the research community as being eligible for exempted or expedited review.
p.000056:
p.000056: 5.67. The Standard Operating Procedures may allow decisions on applications qualifying for expedited or
p.000056: exempted review to be decided by the chairperson of the IRB or his delegate(s) instead of
p.000056: having to be considered by the whole board.
p.000056:
...
p.000056: objectively and professionally satisfied are entirely ethical in all aspects, and are prepared to defend them as such.
p.000056:
p.000056: 6.9. Submission of a research proposal to an IRB by researchers amounts to a representation by the researchers to
p.000056: the IRB and to all parties involved in the ethical review and governance process that, in the
p.000056: objective professional judgment of the researchers, the proposed res earch is ethical in all aspects.
p.000056:
p.000056: 6.10. Researchers should not submit the same or substantially the same documents submitted to IRBs
p.000056: for ethical review as that submitted by them to prospective funding agencies for funding. Researchers should
p.000056: bear in mind that research proposals submitted for ethical review are directed at a completely different end to
p.000056: that of proposals submitted for funding purposes, and should draft them accordingly.
p.000056:
p.000056: 6.11. Accordingly, in no circumstances should researchers use IRBs and the ethical review process as a
p.000056: means of gaining ethical approval for research projects that the researchers themselves entertain doubts or
p.000056: uncertainties about from the ethical point of view.
p.000056:
p.000056: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000056: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000056: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000056: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000056:
p.000056: 6.13. In such cases, we take the view that so long as the researchers in good faith are of the belief that the
p.000056: proposed research is ethical, then such proposed research may be submitted for ethics review provided that the
p.000056: researchers make full disclosure of all such differing opinions known to them, and any potential ethical difficulties
p.000056: or controversies known to them or ethical reservations or doubts held by them, and make disclosure of
p.000056: all other material facts and issues that would help the IRB carry out an impartial and objective review.
p.000056: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to explore
p.000056: all potential ethical issues, and to carry out an impartial and objective review of a novel situation,
p.000056: there is no objection to researchers submitting in good faith for
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-96
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical review a research proposal that the researchers themselves feel that they need ethical guidance.
p.000056:
p.000056: 6.14. As for IRBs and members of IRBs, it is important that researchers take special care to avoid
...
p.000056:
p.000056: 8.3. Members of IRBs discharge an important office in the public interest in the protection of human subjects.
p.000056: Often they do so for minimal or token remuneration, or none at all. Their only motivation being a call to
p.000056: duty, and their only reward being the satisfaction of a job well done.
p.000056:
p.000056: 8.4. We take the view that members of IRBs should be fully protected by the law in their discharge of their
p.000056: duties, provided that they do so in good faith, against any liability arising from their actions. Such
p.000056: protection should extend to immunity from liability in tort arising from any claim by human subjects, and to a
p.000056: defence of qualified privilege to any claim in defamation.
p.000056:
p.000056: 8.5. Appointing institutions should nonetheless be required to give members of IRBs a full indemnity. Such
p.000056: institutions should remain liable to human subjects from any claim in tort, and should be required to
p.000056: take out appropriate insurance coverage against the variety of claims which may arise in the course of the
p.000056: work of the IRB. For example, in relation to the approval of multi- centre or multinational trials.
p.000056:
p.000056: 8.6. We note that such protection would also promote frankness and transparency by the IRB in
p.000056: the discharge of their duties: members would be able to state their opinion frankly without fear of being
p.000056: sued for defamation, and would be able to give researchers a full and frank account of their reasons for rejecting an
p.000056: application. We believe that such full and frank account of reasons for rejection is an important key to
p.000056: helping
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-106
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: researchers understand their ethical obligations, and in helping them to redesign programmes for ethical
p.000056: compliance. Likewise, protection for members would also encourage earlier reporting of negative outcomes or
p.000056: suspicious trends to the authorities for investigation.
p.000056:
p.000056: 8.7. Legal protection for members of IRBs acting in good faith would also encourage the best and
p.000056: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000056: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000056: fields.
p.000056:
p.000056: 8.8. Statutory protection may be especially important in encouraging participation by lay
p.000056: non- medical persons to become members of IRBs.
p.000056:
p.000056: 8.9. The same protection should also be extended to ethics assurance auditors, ethics investigators or members of
...
Searching for indicator philosophy:
(return to top)
p.000033:
p.000033: (a) Impartiality and objectivity are fundamental principles to be observed in the appointment of
p.000033: members to IRBs. An IRB should be carefully composed in order that there can be no room for any public perception
p.000033: that it is not independent of those who are required to submit to its review;
p.000033:
p.000033: (b) Where a majority of the IRB members are drawn from within the appointing institutions, these persons
p.000033: should be the institutions’ most senior, most respected and scientifically competent officers,
p.000033: researche rs or consultants, who possess the appropriate experience and training;
p.000033:
p.000033: (c) An IRB should include non- medical and/or non-scientific persons (lay representation) who are not members
p.000033: of or otherwise associated with the appointing institution of the IRB. Their inclusion is to reinforce the
p.000033: impartiality and objectivity of the work of the IRB;
p.000033:
p.000033: (d) To further reinforce the independence of the IRB and to ensure that the decisions of the board are
p.000033: carried out in accordance with scientific thinking accepted within the community, external
p.000033: representation may include specialists of favorable reputation from other institutions; and
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034:
p.000034: ETHICS GOVERNANCE
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: (e) Lay representation may include respected lay members of the community and experts in
p.000034: philosophy, ethics, psychology, sociology or the law. The IRB may consult representative religious leaders on an ad
p.000034: hoc basis where it feels that such a need exists.
p.000034:
p.000034: 5.35. As far as possible, the core membership of an IRB should be representative of the particular fields of
p.000034: research carried out in the institution, such that for every research proposal received by the IRB, there will
p.000034: be at least one specialist or expert (and preferably more) on the IRB who may give a specialist viewpoint
p.000034: as needed.
p.000034:
p.000034:
p.000034: Institutional Conflicts of Interest
p.000034:
p.000034: 5.36. In the relationship between an institution and its IRB, the fundamental underlying principles are
p.000034: the independence of the IRB in the exercise of its powers and duties, and its ethical integrity.
p.000034:
p.000034: 5.37. The research programmes that IRBs are asked to review are often of considerable financial or
p.000034: other benefit (potential or otherwise) to the appointing institutions. In the review of these research
p.000034: programmes, both IRBs and institutions alike must be aware of any potential or apparent conflict of
p.000034: interest involved and take reasonable steps to avoid and minimise the conflict.
p.000034:
p.000034: 5.38. It is for this reason, among others, that we have recommended that IRBs report directly to the highest level
p.000034: of management of their institutions.
p.000034:
p.000034: 5.39. At minimum, all communications in relation to the review of the research programme in question should be fully
...
p.000056: committee. We endorse these requirements, and propose that they be similarly used to form the framework for
p.000056: the composition of an IRB.
p.000056:
p.000056: 5.27. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000056:
p.000056: 5.27.1 Given the importance of the IRB, it is important that the core members of IRB should be appointed
p.000056: from among the institutions’ most senior, most respected and scientifically competent officers, researchers or
p.000056: consultants, who possess the appropriate experience and training.
p.000056:
p.000056: 5.27.2 The core members of the IRB should be able to devote sufficient time commensurate to the workload of
p.000056: the IRB.
p.000056:
p.000056: 5.27.3 Representation on an IRB should not be restricted to members of the institution, but should include
p.000056: external and lay representation.
p.000056:
p.000056: 5.27.4 External representation may be in the form of specialists of reputation from other
p.000056: institutions: the objective here is to lend impartiality and objectivity to the work of the IRB, and to ensure
p.000056: that the decisions of the board are carried out in accordance with scientific thinking accepted within the community.
p.000056:
p.000056: 5.27.5 IRBs should also have lay, non-scientific or non-medical representation. Where pract
p.000056: ical, and where the size and volume of the workload of the IRB permits, lay representation may include
p.000056: respected lay members of the community, experts in philosophy, ethics, psychology, sociology or the law.
p.000056: The IRB may consult representative religious leaders on an ad hoc basis where it feels that such a need
p.000056: exists.
p.000056:
p.000056: 5.27.6 As far as possible, the core membership of an IRB should be representative of the particular fields
p.000056: of research carried out in the institution, such that for every research proposal received by the board, there
p.000056: will be at least one specialist or expert (and preferably more) on the IRB that is competent to assess that proposal.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-86
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Institutional Conflicts of Interest
p.000056:
p.000056: 5.28. In the relationship between an institution and the IRB, the fundamental underlying principles are
p.000056: the independence of the IRB in the exercise of its powers and duties, and its ethical integrity.
p.000056:
p.000056: 5.29. The research programmes which IRBs are asked to review are often of considerable financial or
p.000056: other benefit (potential or otherwise) to the appointing institutions. In the review of these research
p.000056: programmes, both IRBs and institutions alike must be aware of the potential conflict of interest involved
p.000056: and take reasonable steps to minimise conflict.
p.000056:
p.000056: 5.30. It is for this reason, among others, that we have recommended that IRBs report directly to the highest
p.000056: levels of governance in an institution. In the case of hospitals and other similar medical institutions, the IRB
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.000026: context of a diverse society such as Singapore, researchers have an especial obligation to be sensitive
p.000026: to religious and cultural perspectives and traditions of their human subjects.
p.000026:
p.000026: (b) Respect for free and informed consent. This principle is discussed at length in our Human Stem Cell Report, our
p.000026: Human Tissue Research Report and the NMEC Report (Section 2.5). In addition, the Medicines (Clinical
p.000026: Trials) Regulations and the SGGCP recommend strict requirements regarding consent.
p.000026:
p.000026: (c) Respect for privacy and confidentiality. This is treated in detail in Section 2.6 of the NMEC Guidelines
p.000026: and again in our Human Tissue Research Report.
p.000026:
p.000026: (d) Respect for vulnerable persons. This is discussed in Sections 2.5.5 and 2.5.6 of the NMEC
p.000026: Guidelines. In essence, the ethics governance process must pay especial attention to the protection of
p.000026: persons who may not be competent to give consent themselves, or whose ability to give free and full consent
p.000026: may be compromised by physical conditions or other circumstances, such as being in a dependent
p.000026: relationship.
p.000026:
p.000026: (e) Avoidance of conflicts of interest or the appearance of conflicts of interest. We further elaborate on
p.000026: this principle below in our discussion of the roles and responsibilities of researchers and IRBs.
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027: ETHICS GOVERNANCE
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: SECTION V: INSTITUTIONAL REVIEW BOARDS
p.000027:
p.000027: 5. Institutional Review Boards The Role of Institutional Review Boards
p.000027: 5.1. Ethics review bodies having the first responsibility for ethics review in the ethics review and governance
p.000027: process are variously known as “ethics committees”, “research ethics committees” or “institutional
p.000027: review boards”. In the context of Singapore, the term “ethics committees” is most commonly used.
p.000027:
p.000027: 5.2. We prefer instead the term “Institutional Review Board” (IRB). Our main reason for doing so is
p.000027: our desire to see institutional review boards established as full- time permanent supervisory bodies
p.000027: organised at and integral to the function of the highest administrative level in all institut ions in which research
...
p.000046: the IRB. We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000046: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of
p.000046: the research or for meeting its objectives, do not fall within this category and should be immediately
p.000046: reported.
p.000046:
p.000046: 6.34. PIs have an obligation to submit regular reports to IRBs regarding the status of their research
p.000046: programmes. These reports are intended to aid the IRBs in its role of continuing review and supervision.
p.000046:
p.000046:
p.000046: Researchers and Attending Physicians
p.000046:
p.000046: 6.35. Human subjects for research projects are often recruited from patients who are already receiving treatment
p.000046: from physicians.
p.000046:
p.000046: 6.36. Where a proposed researcher is the attending physician, the researcher- physician should be aware of
p.000046: a potential conflict of interest and of the fact
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047: ETHICS GOVERNANCE
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of Helsinki,
p.000047: which states that:
p.000047:
p.000047: “When obtaining informed consent for the research project the physician should be particularly cautious if the subject
p.000047: is in a dependent relationship with the physician or may consent under duress. In that case the informed consent
p.000047: should be obtained by a well -informed physician who is not engaged in the investigation and who is
p.000047: completely independent of this relationship.”
p.000047:
p.000047: 6.37. In our view, ho wever, this does not apply to situations where physicians wish to write up or
p.000047: publish summaries or analyses of the results of their therapeutic interventions or treatment of their patients,
p.000047: provided that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000047: diagnostic purposes and in the interests of the patients and without regard to any consideration for research
p.000047: objectives or for the subsequent publication of the results.
p.000047:
p.000047: 6.38. In some circumstances, it may be difficult or impractical for researcher- physicians to comply
p.000047: with the letter of Article 23 of the Declaration of Helsinki. Such a situation might arise, for example,
p.000047: where the patient and prospective research subject is receiving specialist treatment at a centre or institution at
p.000047: which a majority of the attending physicians are also actively involved in institution- level research programmes. Or
p.000047: it may be that there is only one relevant specialist at the given institution, and that specialist is at the same time
p.000047: the treating physician as well as the proposed researcher. We recommend that in such cases, the IRB may give
...
p.000056:
p.000056: • Respect for free and informed consent. Again, this principle is discussed at length in our
p.000056: Human Stem Cell Report, and our Human Tissue Research Report. A detailed discussion of the requirements of consent is
p.000056: also set out at section 2.5 of the NMEC Report, and we note also the strict requirements with regards to consent
p.000056: laid down by the Clinical Trials Regulations and the SGGCP.
p.000056:
p.000056: • Respect for privacy and confidentiality. This is treated in detail in section 2.6 of the NMEC
p.000056: Guidelines, and again in our Human Tissue Research Report.
p.000056:
p.000056: • Respect for vulnerable persons. This is discussed in paragraphs 2.5.5 to 2.5.6 of the NMEC Guidelines. In
p.000056: essence, the ethics governance
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-78
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: process must pay especial attention to the protection of persons who may not be competent to give consent
p.000056: themselves, or whose ability to give free and full consent may be compromised by reason of their physical
p.000056: condition or other circumstances, such as being in a dependent relationship.
p.000056:
p.000056: • Avoidance of conflicts of interest, or the appearance of conflicts of interest. We further elaborate
p.000056: on this principle below in our discussion of the roles and responsibilities of investigators and institutional review
p.000056: boards.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-79
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION V: INSTITUTIONAL REVIEW BOARDS
p.000056:
p.000056: 5. Institutional Review Boards
p.000056:
p.000056: The Role of Institutional Review Boards
p.000056:
p.000056: Nomenclature
p.000056:
p.000056: 5.1. Ethical review bodies having the first responsibility for ethical review in the ethical review and
p.000056: governance process are variously known as “ethics committees”, “research ethics committees” or “institutional
p.000056: review boards”. In the context of Singapore, the term “ethics committees” is presently most commonly
p.000056: used.
p.000056:
p.000056: 5.2. We prefer instead the term “institutional review boards”. Our main reason for doing so is our desire to see
...
p.000056: varied to such extent, without the need for immediate reporting. Reporting of such changes by the Principal
p.000056: Investigator to the relevant IRB should however take place within a set time frame that shall be decided by the IRB.
p.000056: We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000056: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of the
p.000056: trial or of its objectives do not fall within this category and should be immediately reported.
p.000056:
p.000056: Researchers and Attending Physicians
p.000056:
p.000056: 6.34. Human subjects for research projects are often recruited from patie nts who are already receiving treatment
p.000056: from physicians.
p.000056:
p.000056: 6.35. Where a proposed researcher is the attending physician, the researcher / physician should be aware
p.000056: of a potential conflict of interest, and of the fact
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-100
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of
p.000056: Helsinki, which states that “[w]hen obtaining informed consent for the research project the physician
p.000056: should be particularly cautious if the subject is in a dependent relationship with the physician or may
p.000056: consent under duress. In that case the informed consent should be obtained by a well- informed
p.000056: physician who is not engaged in the investigation and who is completely independent of this relationship”.
p.000056:
p.000056: 6.36. In our view, however, this does not app ly to situations where clinicians wish to write up or publish
p.000056: summaries or analyses of the results of their therapeutic interventions or treatment of patients, provided
p.000056: that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000056: diagnostic purposes and in the interests of the patients, and without regard to any consideration for research
p.000056: objectives, or for the subsequent publication of the results.
p.000056:
p.000056: 6.37. We further take the view that where researchers are aware that the proposed research subjects are
p.000056: currently receiving treatment or otherwise being attended to by physicians, reasonable efforts should be made on an
p.000056: informal basis by the researchers to contact and inform the attending physicians of the proposed research
p.000056: progr amme. If the research subjects customarily attend at a hospital or clinic, and are attended to by different
p.000056: physicians on their visits, reasonable efforts should be made on an informal basis to contact
p.000056: and inform the institution concerned, and the consultant or senior person having charge of the department
p.000056: or clinic concerned.
p.000056:
p.000056: 6.38. The existence of attending physicians (or the likelihood of the existence of such attending physicians) should
...
General/Other / Impaired Autonomy
Searching for indicator autonomy:
(return to top)
p.000024: public confidence in human biomedical research by ensuring that all forms of human biomedical research conform
p.000024: to the accepted body of ethical values of the community.
p.000024:
p.000024: 4.8. These fundamental ethical values are expressed and repeated in international
p.000024: documents such as the Declaration of Helsinki, the Nuremberg Code, the Belmont Report (“Ethical
p.000024: Principles and Guidelines for the Protection of Human Subjects of Research”, 1976), the UNESCO’s “Universal Declaration
p.000024: on the Human Genome and Human Rights” (1997) and the WHO’s “Proposed International Guidelines on Ethical Issues
p.000024: in Medical Genetics and Genetic Services” (1998).
p.000024:
p.000024: 4.9. In Singapore, these same principles are found or reflected in regulatio ns such as the Medicines
p.000024: (Clinical Trials) Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already
p.000024: addressed some of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000024:
p.000024: 4.10. These core principles are expressed, restated and elaborated upon in many ways. For example, the NMEC
p.000024: expresses some of these fundamental principles as follows:
p.000024:
p.000024: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000024: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000024: risks of participating in research. Justice relates to the fair distribution of risks in research in relation
p.000024: to the anticipated benefits for research subjects. Autonomy refers to the right of individuals to decide for
p.000024: themselves what is good for them.
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025:
p.000025: ETHICS GOVERNANCE
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: 2.3.2 With respect to beneficence, the benefits and risks of research must always be carefully assessed.
p.000025: Research on human subjects should only be undertaken if the potential benefits arising from the expected new
p.000025: knowledge are of sufficient importance to outweigh any risk or harm inherent in the research, bearing in mind that
p.000025: risks and benefits may not be measurable on the same scale.
p.000025:
p.000025: 2.3.3 …Justice must be exercised in the allocation of the anticipated risks and the anticipated benefits…
p.000025:
p.000025: 2.3.4 A corollary of autonomy is that any research procedure must have, as far as possible, the
p.000025: free and informed consent of the experimental subject. Similarly, respect for the individual implies
p.000025: that safeguards should be provided to protect the experimental subject from physical and
p.000025: emotional harm including provisions for confidentiality.”
p.000025:
p.000025: 4.11. Despite some uncertainty at the edges, a core of universally accepted principles and ethical
p.000025: values lie at the heart of most societies in their application to the protection of human research subjects.
p.000025:
p.000025: 4.12. In the interests of consistency and fairness of the judgments of IRBs, a code of applicable
p.000025: principles for ethics governance should eventually be formulated for the common guidance of IRBs,
p.000025: research institutions, researchers, the human research subjects and all other parties involved in human research.
p.000025:
p.000025: 4.13. We do not attempt, and it is beyond the scope of this document to attempt, to list all these fundamental
p.000025: principles. In our view, the applicable principles of the proposed code are best settled in an
p.000025: incremental and evolutionary manner through dialogue and discussion between IRBs and the other parties in
p.000025: the research governance process. This process of dialogue and discussion should be informed by and have
p.000025: reference to the experiences of the parties involved.
p.000025:
...
p.000056: defined for all time, but evolves in response to advances in knowledge, technology, changes in social mores,
p.000056: and community dialogue and debate.
p.000056:
p.000056: 4.9. These fundamental principles are expressed and repeated in international documents such as the Declaration
p.000056: of Helsinki, the Nuremberg Code, the Belmont Report (Ethical Principles and Guidelines for the Protection of
p.000056: Human Subjects of Research, 1976), the UNESCO Universal Declaration on the Human Genome and Human Rights 1997, and the
p.000056: WHO’s Proposed Guidelines on Ethical Issues in Medical Genetics and Genetic Services 1997 (as updated 2001).
p.000056:
p.000056: 4.10. In Singapore, these same principles are found or reflected in regulations such as the Clinical
p.000056: Trials Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already addressed some
p.000056: of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000056:
p.000056: 4.11. These core principles are exp ressed, restated and elaborated upon in many ways. For example, the NMEC
p.000056: expresses some of these fundamental principles as follows:
p.000056:
p.000056: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000056: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000056: risks of participating in research. Justice relates to
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-76
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: the fair distribution of risks in research in relation to the anticipated benefits for research subjects.
p.000056: Autonomy refers to the right of individuals to decide for themselves what is good for them.
p.000056:
p.000056: 2.3.2 With respect to beneficence, the benefits and risks of research must always be carefully assessed.
p.000056: Research on human subjects should only be undertaken if the potential benefits arising from the expected new
p.000056: knowledge are of sufficient importance to outweigh any risk or harm inherent in the research, bearing in mind that
p.000056: risks and benefits may not be measurable on the same scale.
p.000056:
p.000056: 2.3.3 …Justice must be exercised in the allocation of the anticipated risks and the anticipated benefits…
p.000056:
p.000056: 2.3.4 A corollary of autonomy is that any research procedure must have, as far as possible, the
p.000056: free and informed consent of the experimental subject. Similarly, respect for the individual implies
p.000056: that safeguards should be provided to protect the experimental subject form physical and
p.000056: emotional harm including provisions for confidentiality.”
p.000056:
p.000056: 4.12. Despite some uncertainty at the edges, a core of universally accepted principles and ethical
p.000056: values lie at the heart of most societies in their application to the protection of human research subjects.
p.000056:
p.000056: 4.13. It is desirable that a code of applicable principles for ethical governance be eventually formulated for
p.000056: the common guidance alike of ethics committees, institutional review boards, research institutions,
p.000056: researchers, the human subjects of research and all other parties involved in human research, in the
p.000056: interests of consistency and fairness of the judgments of institutional review boards.
p.000056:
p.000056: 4.14. We do not attempt, and it is beyond the scope of this document, to attempt to list all these
p.000056: fundamental principles. In our view, the applicable principles of the proposed code are best settled
p.000056: in an incremental and evolutionary manner through dialogue and discussion between inst itutional review boards
p.000056: and the other parties in the research governance process. This process of dialogue and discussion should be
...
General/Other / Natural Hazards
Searching for indicator hazard:
(return to top)
p.000034:
p.000034:
p.000035: 35
p.000035:
p.000035:
p.000035: ETHICS GOVERNANCE
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: Multinational and Multi-Centre Research Projects
p.000035:
p.000035: 5.42. As we have previously pointed out, biomedical research projects increasingly involve
p.000035: collaborators in more than one country. Indeed, one of the hallmarks of current leading edge research is the
p.000035: multinational and multi-centre collaborative nature of the research effort, which often involves a very
p.000035: large number of researchers based in many institutions in different countries.
p.000035:
p.000035: Multinational Research Projects
p.000035:
p.000035: 5.43. Guidance has been sought from us as to whether ethics review should be required for the portion of
p.000035: multinational research projects carried out in Singapore. We take the view that ethics review should indeed be
p.000035: required for any portion of a research project carried out in Singapore; or involving human tissue or medical,
p.000035: personal or genetic information collected in Singapore or derived from donors in Singapore; or which
p.000035: involves the export or transmission abroad of any human tissue or medical, personal or genetic information collected
p.000035: in Singapore or derived from donors in Singapore.
p.000035:
p.000035: 5.44. This conclusion is based on Singapore law and Singapore ethical standards and rules, which are not necessarily
p.000035: the same as those of other countries. This approach is supported in other jurisdictions. Without this approach a moral
p.000035: hazard would exist in the temptation of researchers to pick as their ethical jurisdiction of choice the
p.000035: jurisdiction with the perceived most liberal regime.
p.000035:
p.000035: 5.45. Nonetheless, we envisage that expedited review may be permissible in certain circumstances. For
p.000035: example, where human tissues from an IRB- approved study conducted in another country comes to Singapore
p.000035: for analysis, and the Singaporean institution does not have direct contact with the patient but merely performs tests
p.000035: on patient samples.
p.000035:
p.000035: 5.46. To avoid unnecessary bureaucracy, local research collaborators should be encouraged to provide their local
p.000035: IRBs with full documentation of ethics review applications made to the lead IRB (defined in paragraph
p.000035: 5.50 ), together with copies of all relevant queries and rulings of that IRB. If applications have been
p.000035: submitted or are proposed to be submitted to other IRBs in other jurisdictions, information on these applications and
p.000035: on their outcome, should be provided to the local IRB as well.
p.000035:
p.000035: 5.47. The local IRB may then elect to grant expedited approval of such applications after
p.000035: reviewing the documentation, and the reasons for the decision of the lead IRB. In general, local IRBs
p.000035: should consider a full
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036:
p.000036: ETHICS GOVERNANCE
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
...
p.000056:
p.000056: 5.33. As we have previously pointed out, research projects or trials increasingly involve collaborators in more one
p.000056: country. Indeed, o ne of the hallmarks of current leading-edge research are the multinational and
p.000056: multi-centre collaborative nature of the research effort, which often involves a very large number of
p.000056: researchers based in many institutions in different countries.
p.000056:
p.000056: Multinational Research Projects
p.000056:
p.000056: 5.34. Guidance has been sought from us as to whether ethics review should be required for the portion of
p.000056: multinational research projects carried out in Singapore. We take the view that ethics review should indeed be
p.000056: required for any portio n of a research project or trial carried out in Singapore, or involving human tissue, or
p.000056: medical, personal or genetic information
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-87
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: collected in Singapore or derived from donors in Singapore, or which involves the export or
p.000056: transmission abroad of any human tissue, or medical, personal or genetic information collected in Singapore
p.000056: or derived from donors in Singapore.
p.000056:
p.000056: 5.35. This is on the basis that Singapore law and Singapore ethical standards and rules are not necessarily the same
p.000056: as that in other countries. This approach is supported in other jurisdictions. Otherwise there would be a
p.000056: moral hazard in the temptation of researchers picking the jurisdiction perceived to have the most liberal regime as
p.000056: their ethical jurisdiction of choice.
p.000056:
p.000056: 5.36. Nonetheless, we envisage that expedited review may be permissible in certain circumstances. For
p.000056: example, where patient tissues from an IRB approved study conducted in another country comes to
p.000056: Singapore for analysis, and the Singaporean institution does not have direct contact with the patient but merely
p.000056: performs tests on patient samples.
p.000056:
p.000056: 5.37. To avoid unnecessary bureaucracy, local research collaborators should be encouraged to provide their local
p.000056: IRBs with full documentation of ethics review applications made to the IRB of the lead jurisdiction, together
p.000056: with copies of all relevant queries and rulings of that IRB. If applications have been submitted or are proposed
p.000056: to be submitted to other IRBs in other jurisdictions, information on these applications, and on their
p.000056: outcome, should be provided to the local IRB as well.
p.000056:
p.000056: 5.38. The local IRB may then elect to give expedited approval of such applications after
p.000056: reviewing the documentation, and the reasons for the decision of the leading ethical review board. In general,
p.000056: local IRBs should consider a full ethics review if a substantial portion of the research project is to be carried
p.000056: out in Singapore. Similarly, local IRBs should be concerned to ask for evidence of approval by IRBs
p.000056: in the jurisdiction in which the major part of the research project will be carried out.
p.000056:
p.000056:
p.000056: Recommendation 5:
...
General/Other / Public Emergency
Searching for indicator emergency:
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p.000021: Guidelines or any other ethical or professional standards or guidelines does not guarantee compliance with the law, as
p.000021: the law may prescribe a different and higher standard in specific situations. The co nverse may also apply. At minimum,
p.000021: institutions should ensure that their decisions and actions are consistent with the law and do not
p.000021: infringe on the rights and protection afforded to human subjects and patients by the law.
p.000021:
p.000021: 3.26. Institutions should take into account not only ethical considerations, but also the requirements of the law
p.000021: and social attitudes.
p.000021:
p.000021:
p.000021: Savings
p.000021:
p.000021: 3.27. We make clear that nothing in these Guidelines is intended to supplant the recommendations that we have made
p.000021: in the Human Stem Cell Report and the Human Tissue Research Report, and that the recommendations
p.000021: contained in these Guidelines are intended to supplement those advanced in our first two Reports.
p.000021:
p.000021:
p.000021: Exceptional Situations
p.000021:
p.000021: 3.28. We note that there may be some exceptional circumstances in which it may be ethically acceptable to
p.000021: abbreviate or temporarily suspend the usual
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000022: HUMAN
p.000022: BIOMEDICAL RESEARCH
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: ethics review procedures and requirements, provided that all the applicable legislative and regulatory requirements
p.000022: are satisfied. We have in mind situations of national security or emergency health situations, in which
p.000022: urgent research may have to be carried out to avert harm to national security or for the urgent protection
p.000022: or treatment of whole populations at risk. In such cases, it should be permissible for IRBs in consultation with the
p.000022: proper authorities such as the MOH, to formulate and lay down written guidelines for the exemption or expedited
p.000022: review of defined classes or types of such emergency or urgent research in the national interest.
p.000022:
p.000022: 3.29. We also exclude from ethics review procedures and requirements all clinical audit and quality
p.000022: assurance activities, which require the institution to review patients' information and are conducted for the sole
p.000022: purpose of improving the quality of patient care within that institution.
p.000022:
p.000022: 3.30. We therefore recommend that all Human Biomedical Research as defined in this section, save for the
p.000022: exceptions expressly provided above, be subject to review and approval by and to the continued supervision of an
p.000022: IRB in accordance with the principles discussed in Section IV.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023: ETHICS GOVERNANCE
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: PART C: ETHICS GOVERNANCE
p.000023:
p.000023: SECTION IV: PRINCIPLES OF ETHICS GOVERNANCE
p.000023:
p.000023: 4. Principles of Ethics Governance The Purpose of Ethics Governance
...
p.000056: one of the objectives or the sole objective, of the research study, trial or activity
p.000056:
p.000056: and
p.000056:
p.000056: which research study, trial or activity has the potential to affect the safety, health, welfare, dignity or privacy of
p.000056: the human subjects involved in the study, or of the donors of human tissue or information used in the research, or of
p.000056: the family members of any of the human subjects or donors thereof, or to which such medical, personal or genetic
p.000056: information relates.
p.000056:
p.000056: Savings
p.000056:
p.000056: 3.7. We make clear that nothing in this Consultation Paper is intended to supplant the recommendations
p.000056: that we have made in the Human Stem Cell Report and the Human Tissue Research Report, and tha t
p.000056: the recommendations contained in this Consultation Paper are intended to supplement those advanced in our
p.000056: first two Reports.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-73
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Exceptional Situations
p.000056:
p.000056: 3.8. We note that there may be some exceptional circumstances in which it may be ethically acceptable
p.000056: to abbreviate or temporarily suspend the usual ethics review procedures and requirements, provided that all the
p.000056: applicable legislative and regulatory requirements are satisfied. We have in mind situations of national
p.000056: security or emergency health situations, in w hich urgent research may have to be carried out to avert
p.000056: harm to national security or for the urgent protection or treatment of whole populations at risk. In such cases, we
p.000056: think that it is permissible for institutional review boards in consultation with the proper authorities to
p.000056: formulate and lay down written guidelines for the exemption or expedited review of defined classes or types of
p.000056: such emergency or urgent research in the national interest.
p.000056:
p.000056: 3.9. We therefore recommend that all clinical research as defined in this section be statutorily subject to
p.000056: review and approval by and to the continued supervision of an institutional review board in
p.000056: accordance with the principles discussed below.
p.000056:
p.000056:
p.000056: Recommendation 2:
p.000056:
p.000056: • The current statutory requirement for review and approval by an institutional review board in
p.000056: drug trials should be extended to all kinds of clinical research involving human subjects, as defined in this section.
p.000056:
p.000056: • All clinical research proposed to be carried out in Singapore must be submitted to and approved by a
p.000056: properly constituted institutional review board.
p.000056:
p.000056: • No programme of clinical research may be commenced or carried out without the approval of such an
p.000056: institutional review board, or other than on terms as set out by such an institutional review board.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-74
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART C: ETHICAL GOVERNANCE
p.000056:
p.000056: SECTION IV: PRINCIPLES OF ETHICAL GOVERNANCE
p.000056:
p.000056: 4. Principles of Ethical Governance The Purpose of Ethical Governance
p.000056: 4.1. Article 5 of the Helsinki Declaration states that in “medical research on human subjects, considerations
...
General/Other / Relationship to Authority
Searching for indicator authority:
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p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: RESEARCH INVOLVING HUMAN SUBJECTS
p.000001: GUIDELINES FOR IRBS
p.000001:
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001: Principle
p.000001:
p.000001: 1. There is general agreement internationally that human biomedical research involving risk of harm
p.000001: to human subjects should be subject to independent ethics review.
p.000001:
p.000001: 2. This principle is reflected in international documents such as the Nuremberg Code of 1949, the
p.000001: Declaration of Helsinki of 1964 and the International Conference on Harmonisation’s “Guideline for Good Clinical
p.000001: Practice” (ICH GCP Guideline) of 1996.
p.000001:
p.000001:
p.000001: Pharmaceutical Trials
p.000001:
p.000001: 3. In Singapore, pharmaceutical trials are currently governed under the Medicines Act and the
p.000001: Medicines (Clinical Trials) Regulations. All proposals for pharmaceutical trials are required to undergo an
p.000001: independent ethics review process and to comply with the “Singapore Guideline for Good Clinical Practice”
p.000001: (SGGCP), which is based on the ICH GCP Guideline.
p.000001:
p.000001: 4. This independent review is carried out first at the institutional level by the institution’s
p.000001: ethics committee or institutional review board (IRB). If approved, the proposal is then submitted to the Health
p.000001: Sciences Authority (HSA), which is the licensing body for pharmaceutical trials. Clinical Trial Certificates will be
p.000001: issued for proposals approved by the HSA.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Human Biomedical Research other than Pharmaceutical Trials
p.000001:
p.000001: 5. Currently, there is no provision requiring human biomedical research other than pharmaceutical
p.000001: trials to be submitted for independent ethics review. This is so even if the proposed research programme
p.000001: entails a risk to the healt h, safety or welfare of the human subject.
p.000001:
p.000001: 6. Since 1998, the Ministry of Health (MOH) has required all government and restructured hospitals
p.000001: to establish ethics committees or IRBs. Hospitals are required to comply with the “Ethical
p.000001: Guidelines on Research Involving Human Subjects” (NMEC Guidelines) issued by the National Medical Ethics
p.000001: Committee (NMEC) in 1997.
p.000001:
p.000001: 7. The NMEC requires all research protocols that involve human experimentation, whether
p.000001: pharmaceutical trials, trials of new medical devices, new procedures or any other forms of clinical
p.000001: studies that require the participation of human subjects or the use of human tissues or organs, to
...
p.000009: guidance, and where appropriate, approval.”
p.000009:
p.000009: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000009: medical community in Singapore and by other medical communities in the great majority of nations. In
p.000009: Singapore, the need for ethics committees or IRBs and the requirement for the ethics review of research
p.000009: proposals involving human subjects have long been an accepted and integral part of biomedical research in the
p.000009: institutional setting.
p.000009:
p.000009: 2.7. The principle s of the Declaration of Helsinki today find expression in regulatory standards and
p.000009: practice guidelines governing various aspects of clinical research such as those contained in the Medicines (Clinical
p.000009: Trials) Regulations, promulgated pursuant to Section 74 of the Medicines Act (Cap. 176), the “Singapore
p.000009: Guideline for Good Clinical Practice” (SGGCP) and the “Ethical Guidelines on Research Involving Human
p.000009: Subjects” (NMEC Guidelines) issued in August 1997 by the National Medical Ethics Committee (NMEC).
p.000009: We discuss these regulatory standards and practice guidelines in detail below.
p.000009:
p.000009:
p.000009: Pharmaceutical Trials in Singapore
p.000009:
p.000009: 2.8. In Singapore, pharmaceutical trials involving the testing of drugs on human subjects are regulated by the
p.000009: Health Sciences Authority (HSA). The HSA regulates the conduct of pharmaceutical trials under the Medicines Act and the
p.000009: Medicines (Clinical Trials) Regulations (2000, Revised Edition). Under the Medicines Act, these
p.000009: pharmaceutical or drug trials are known as “clinical trials”.
p.000009:
p.000009: 2.9. The system of regulation requires that sponsors and researchers conducting pharmaceutical trials obtain
p.000009: both ethics and regulatory approval before initiating a study.
p.000009:
p.000009: 2.10. The current approval system is sequential. Approval from the HSA is sought only after the
p.000009: relevant hospital ethics committee has approved an application. Regulatory approval is provided in the form
p.000009: of a Clinical Trial Certificate issued by the HSA to the applicant.
p.000009:
p.000009: 2.11. The HSA, in deciding the regulatory approval for a pharmaceutical trial, consults an expert
p.000009: advisory committee known as the Medical Clinical Research Committee (MCRC). The MCRC is an
p.000009: “independent body constituted of medical members, whose responsibility is to ensure the
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: INTRODUCTION AND CURRENT
p.000010: FRAMEWORK
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: protection of the rights, safety and well- being of human subjects involved in a trial ... and documenting
p.000010: informed consent of the trial subjects” (Section 1.37 of the SGGCP). It currently comprises five members, all of
...
p.000012: time.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: INTRODUCTION AND CURRENT
p.000013: FRAMEWORK
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 2.29. We have reviewed the NMEC Guidelines and have no hesitation in using them as a basic framework for these
p.000013: BAC Guidelines. Although the NMEC Guidelines were formulated in the restricted context of research
p.000013: carried out by the medical profession, we are of the view that the principles they espouse are
p.000013: appropriate for all human biomedical research, whether such research is carried out by the medical profession
p.000013: or by others. We also take the view that the same principles should apply to all human biomedical research wherever
p.000013: such research may be carried out in Singapore, and whether or not such research is carried out in an institution under
p.000013: the direct jurisdiction of the MOH pursuant to the Private Hospitals and Medical Clinics Act.
p.000013:
p.000013: The Future of Human Biomedical Research
p.000013:
p.000013: 2.30. Until recently, the vast majority of human biomedical research (whether pharmaceutical trials or
p.000013: research other than pharmaceutical trials) were carried out by researchers who were medical practitioners
p.000013: registered under the Medical Registration Act (Cap. 174), in government medical institutions directly
p.000013: controlled by the MOH or in hospitals and medical clinics licensed under the Private Hospitals and Medical
p.000013: Clinics Act. In all of these cases, the competent supervisory authority was the MOH.
p.000013:
p.000013: 2.31. In recent years, however, the development of the biomedical industry in Singapore has led to
p.000013: an increasing proportion of human biomedical research other than pharmaceutical trials. In 2002, for
p.000013: example, hospital ethics committees of the five main restructured hospitals reviewed nearly three times as many
p.000013: applications for such research as they did for pharmaceutical trials.
p.000013:
p.000013: 2.32. Human biomedical research increasingly tends to be institution-driven, rather than being
p.000013: researcher-driven (the traditional model assumed in the current regulatory regime). Institution-driven
p.000013: pharmaceutical trials received by the HSA now outnumber researcher-driven pharmaceutical trials.
p.000013:
p.000013: 2.33. Concomitantly, an increasing proportion of human biomedical research is now conducted outside the
p.000013: traditional paradigm assumed by the current regulatory environment: many research projects are now led by
p.000013: researchers who, although being qualified and competent for the research proposed by them, are not medical
p.000013: practitioners registered under the Medical Registration Act, or by researchers who work in or for entities not
p.000013: subject to the regulatory jurisdiction of the MOH. Such entit ies include companies and other
p.000013: commercial entities in the biomedical industry, research institutes and statutory agencies with an interest
p.000013: in the biomedical industry.
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: INTRODUCTION AND CURRENT
p.000014: FRAMEWORK
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
...
p.000029: domain lines, which can be shared by all the related institutions within the group. Such an arrangement is acceptable
p.000029: to us, as it is entirely in keeping with the ethical principles we have set out. Under this arrangement, the
p.000029: parent institution for all the hospitals and other institutions within the group will be responsible
p.000029: for constituting the necessary IRBs for all its constituent institutions and arranging for the
p.000029: accreditation of the IRBs.
p.000029:
p.000029: 5.16. We have no objections to other groups of research institutions adopting such a similar approach,
p.000029: provided that the terms of the arrangement between the institutions are clearly spelt out.
p.000029:
p.000029: 5.17. We therefore recommend that related institutions under the direction and control of a parent institution
p.000029: should be permitted to share an IRB or IRBs constituted by the parent institution.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030:
p.000030: ETHICS GOVERNANCE
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: The Responsibilities of Institutional Review Boards
p.000030:
p.000030: 5.18. In its acts and decisions, and in the exercise and discharge of its duties and responsibilities, an IRB acts
p.000030: on the behalf of the institution that appoints it and exercises on its behalf the authority and powers of
p.000030: that institution in matters within the terms of reference of the IRB.
p.000030:
p.000030: 5.19. Accordingly, we emphasise that the institution is responsible for the acts and decisions of the
p.000030: IRB(s) that it appoints.
p.000030:
p.000030: 5.20. Ethics Review Gateway. The fundamental responsibility of an IRB is to act as an ethics review gateway
p.000030: for all Human Biomedical Research carried out under the auspices of its appointing institution, with the
p.000030: primary objectives of the protection and assurance of the safety, health, dignity, welfare and well-being of
p.000030: human research subjects. An IRB has a duty to ensure that all Human Biomedical Research carried out under the auspices
p.000030: of its appointing institution are ethically acceptable, and to comply with the principles outlined in Section
p.000030: IV.
p.000030:
p.000030: 5.21. Review of Scientific Merits. A review of the scientific merits of any proposed programme of Human
p.000030: Biomedical Re search is an integral part of a proper assessment of the ethical acceptability of the programme.
p.000030: A research programme with little or no scientific merit is ethically unacceptable.
p.000030:
p.000030: 5.22. In its assessment of the ethical acceptability of any proposed research programme, an IRB will need
p.000030: to be satisfied that an objective review of the scientific merits of the proposed programme of research has been
p.000030: carried out, and that there is sufficient evidence of scientific merit before the IRB makes a decision on the
...
p.000030: that the findings (whether positive or negative) of any review of scientific merit are made available and are fully
p.000030: disclosed to the IRB.
p.000030:
p.000030: 5.24. The review of scientific merits may be carried out by such committees, bodies or agencies as
p.000030: the IRB may in its judgment recognise as appropriate. Thus such reviews may be carried out by a
p.000030: scientific review committee constituted by the appointing institution or by the funding agency.
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031:
p.000031: ETHICS GOVERNANCE
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.25. We note that it is an accepted practice for the initial scientific review to be carried out by or for the
p.000031: agency that funds the research. When the grant funding agency is satisfied with the scientific merits of the
p.000031: proposed programme of research, it then gives in-principle approval on the condition (among others) that ethics
p.000031: approval is granted by the appropriate IRB. In such cases, IRBs may rely on the review of scientific merits carried
p.000031: out by or for the grant funding agency, on the proviso that IRBs must make their own determination as to the
p.000031: sufficiency and adequacy of the review of scientific merits that has been carried out. In these cases, IRBs
p.000031: should be empowered to require a more extensive or rigorous review of the scientific merits if deemed necessary.
p.000031:
p.000031: 5.26. In addition, appointing institutions may give IRBs authority for:
p.000031:
p.000031: (a) Continuing Review and Supervision. The institution has an overall duty to ensure that approved
p.000031: research programmes are conducted in accordance with the terms of the approval. We elaborate on this
p.000031: responsibility in Section VII. IRBs may assist the appointing institution in the discharge of this
p.000031: duty, but such delegation will have to be made clear in the terms of constitution of the IRB. Such
p.000031: delegation should only be made if the IRB is given sufficient resources to carry out such a
p.000031: responsibility. In this responsibility, IRBs will require Principal Investigators (PIs) to submit annual
p.000031: (or more frequent) progress reports and final reports within three months of completion of projects. PIs will
p.000031: also have to inform and seek approval from IRBs for any proposed deviations from the terms of approval
p.000031: of the projects before they can be implemented except when they are necessary to eliminate immediate hazards to
p.000031: participants, or when the changes involve only logistical or administrative aspects of research, in which case IRBs
p.000031: should be informed within seven days. IRBs may also direct or otherwise require amendments or
p.000031: modifications to research proposals at any time, and to make such amendments or modifications a condition of
p.000031: approval for the conduct or continuation of the research programme.
p.000031:
p.000031: (b) Reporting and Feedback. IRBs will require PIs to inform them of unusual or unexpected events within 15
p.000031: days of occurrence and report such events to the appointing institutions. Another major aspect of the role of IRBs
p.000031: is to provide feedback to and maintain dialogue about application standards with their constituent
p.000031: researchers. In the discharge of their role, IRBs can and should also act as the key institutional
p.000031: agency that receives and reports to their appointing institutions on concerns and feedback expressed by research
p.000031: subjects.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032:
p.000032: ETHICS GOVERNANCE
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.27. The implementation of a framework for the work of IRBs has been laid down and discussed
p.000032: extensively by the NMEC in Section 3 of the NMEC Guidelines. We agree generally with the principles of implementation
p.000032: laid down by the NMEC, and further elaborate on these principles in our discussion of the constitution of
p.000032: IRBs below.
p.000032:
p.000032: 5.28. We therefore recommend that IRBs should have responsibility for the ethics review and approval of
p.000032: proposed Human Biomedical Research programmes on behalf of their appointing institutions. This should
p.000032: take into account the scientific merits of the proposed research.
p.000032:
p.000032: 5.29. Additionally, as institutional resources may permit, and on the mutual agreement of IRBs and
p.000032: their appointing institutions, IRBs may also be given authority by their appointing institutions for:
p.000032:
p.000032: (a) The continuing review and supervision (including evaluation of feedback from research
p.000032: subjects) of Human Biomedical Research programmes approved by them;
p.000032:
p.000032: (b) The receiving of feedback from research subjects and the providing of feedback to researchers; and
p.000032:
p.000032: (c) The reporting of unusual or unexpected events arising from the Human Biomedical Research programmes
p.000032: carried out under the auspices of its appointing institution to the management of that institution.
p.000032:
p.000032:
p.000032: The Constitution of Institutional Review Boards
p.000032:
p.000032: 5.30. IRBs should be established at the highest administrative level of the institutions. They
p.000032: should be appropriately resourced relative to the research activity of the institution and, where this is
p.000032: substantial, should be regarded as one of the key full- time management offices within the organisation of
p.000032: institutions, and not merely as honorary or ad hoc committees.
p.000032:
p.000032: 5.31. The IRB should be appointed by and report to at least an authority at the level of the Chief Executive
p.000032: Officer (as recommended by the NMEC Guidelines in the case of hospitals falling under the jurisdiction
p.000032: of the MOH pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000032:
p.000032: 5.32. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000032: although it is acceptable for institutions
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033: ETHICS GOVERNANCE
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: with standing IRBs to appoint special ad hoc committees in consultation with their standing IRBs to
p.000033: consider special research proposals. We prefer, in such cases, that the institutions work with their standing
p.000033: IRBs to appoint special subcommittees co-opting experts or reviewers to assist the standing IRBs in the particular
p.000033: project concerned. For example, an IRB may receive a research proposal involving an area of research with which no
p.000033: member of the IRB is familiar. In such a case, the institution may work with the IRB to identify and co-opt ad
p.000033: hoc experts or reviewers to assist the IRB in its assessment and review of the proposal. The co-opted ad hoc experts
p.000033: or reviewers sit as a subcommittee of the IRB.
p.000033:
p.000033:
p.000033: Composition
p.000033:
p.000033: 5.33. We are of the opinion that the SGGCP (in particular Section 3.2.3) and the NMEC Guidelines (in particular
p.000033: Section 3.2.2) lay out appropriate and comprehensive guidelines regarding the composition of an
...
p.000051: use of and the custody of medical records and other patient information are becoming increasingly complex. In this
p.000051: area, the ethical issues are inextricably interwoven with legal considerations, and the impact of the existing
p.000051: law is currently unclear in many situations. We hope to explore these issues in a separate subsequent report.
p.000051:
p.000051: 7.12. In the context of institutions such as hospitals with centralised patient records and databases,
p.000051: we recommend that appointing institutions take steps to determine who within the administrative structure should
p.000051: be the proper administrative custodians responsible for patients’ medical information in the
p.000051: institution, and to advise their IRBs accordingly.
p.000051:
p.000051: 7.13. In situations where any of the researchers are also the administrative custodian of patients’
p.000051: medical information within the institution, procedures should be established to address actual,
p.000051: potential or apparent conflicts of interest.
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to research staff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
p.000053: ETHICS GOVERNANCE
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 7.20. We take the view that IRB members should be fully protected in the discharge of their duties,
p.000053: provided that they do so in good faith, against any liability arising from their actions. Appointing
p.000053: institutions should give IRB members a full indemnity and arrange for the necessary insurance.
p.000053:
p.000053: 7.21. Legal protection for IRB members acting in good faith would also encourage the best and
p.000053: most competent individuals (both within and outside the medical profession) to contribute their skill and
...
p.000056: review of research proposals involving human subjects have long been an accepted and integral part of medical
p.000056: research in the institutional setting in Singapore. The principles of the Declaration of Helsinki today find
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
p.000056: as those contained in the Medicines (Clinical Trials) Re gulations, promulgated pursuant to s.74 of the
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
p.000056: Regulations and its parent Act (the Medicines Act, Cap. 176) has a special meaning. As defined in
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
...
p.000056: ethical principles that have their origin in the Declaration of Helsinki”.
p.000056:
p.000056: 2.16. Article 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000056: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000056: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000056: investigational product(s), and/or to identify any adverse reactions to an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-64
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: investigational product(s), and /or to study absorption, distribution, metabolism, and excretion of an
p.000056: investigational product(s) with the object of ascertaining its safety and/or efficacy”.
p.000056:
p.000056: 2.17. The SGGCP sets out detailed guidelines as to the roles and duties of researchers and sponsors in
p.000056: a pharmaceutical drug trial, and lays down the requirements such as monitoring procedures, audits and the matters to be
p.000056: included in trial protocols.
p.000056:
p.000056: 2.18. Of relevance to this Consultation Paper are the provisions in Part 3 of the SGGCP requiring all drug
p.000056: trials to be reviewed and approved by the Medical Clinical Research Committee (MCRC) of the Health
p.000056: Sciences Authority (“HSA”) and hospital’s “ethics committees” before an application may be made
p.000056: for a clinical trial certificate from the HSA. The responsibilities, composition, functions and operations of the
p.000056: MCRC are set out in detail in Article 3.1 of the SGGCP, while the responsibilities, composition, functions
p.000056: and operations of ethics committee are detailed in Article 3.2.
p.000056:
p.000056: The Current Approval Process for a Proposed Pharmaceutical Drug Trial
p.000056:
p.000056: 2.19. It may be useful to summarise the current approval process for a proposed pharmaceutical drug trial under the
p.000056: current regulatory regime. Researchers seeking a clinical trial certificate under the Medicines Act are required to
p.000056: submit their trial protocol and application first to their hospital ethics committee or IRB for
p.000056: review and approval. If the proposed pharmaceutical drug trial is a multi-centre trial (where
p.000056: the trial is carried out at more than one institution or centre), the application is submitted to the Clinical Trials
p.000056: Coordinating Committee (CTCC) instead for review and approval. The CTCC was established in 1999 by the Ministry of
p.000056: Health to coordinate the ethical governance of multi-centre drug trials in Singapore.
p.000056:
...
p.000056: such research is carried out by members of the medical professions, and whether or not such research is carried out in
p.000056: an institution under the direct jurisdiction of the Ministry of Health pursuant to the Private Hospitals and Medical
p.000056: Clinics Act.
p.000056:
p.000056: Limitations of the Current Regulatory Regime
p.000056:
p.000056: 2.37. The evolution of regimes for the ethical governance of clinical research and drug trials must be
p.000056: seen in the context of the history of clinical research and drug trials in Singapore. At the time when the
p.000056: Clinical Trials Regulations were first enacted, drug trials were the most common kind of clinical research trial.
p.000056: As such, it was entirely appropriate to enact the Clinical Trials Regulations as subsidiary legislation
p.000056: under the Medicines Act, which deals principally with medicines.
p.000056:
p.000056: 2.38. Likewise, until recently, the vast majority of clinical research (whether drug trials or non-drug
p.000056: trials) were carried out by researchers who were medical practitioners registered under the Medical Registration
p.000056: Act (Cap. 174), or in Government medical institutions directly controlled by the Ministry of Health, or in
p.000056: hospitals and medical clinics licensed under the Private Hospitals and Medical Clinics Act. In all of these
p.000056: cases, the competent supervisory authority was the Ministry of Health.
p.000056:
p.000056: 2.39. In recent years, however, the development of the biomedical industry in Singapore has led to an
p.000056: increasing proportion of non-drug trials. For example, in 2002, hospital ethics committees of the five main
p.000056: restructured hospitals in Singapore reviewed nearly three times as many applications for non-drug trials as
p.000056: they did for drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-68
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.40. Clinical research tends increasingly to be institutionally-driven, rather than being researcher-driven (the
p.000056: traditional model assumed in the current regulatory regime). Company-driven drug trials received by the HSA now
p.000056: outnumber researcher-driven drug trials.
p.000056:
p.000056: 2.41. Concomitantly, an increasing proportion of clinical research trials are now also being carried out outside
p.000056: the traditional paradigm assumed by the current regulatory environment: many trials are now led by
p.000056: researchers, who although being qualified and competent for the trials proposed by them, are not
p.000056: medical practitioners registered under the Medical Registration Act, or by researchers who work in or for
p.000056: entities not subject to the regulatory jurisdiction of the Ministry of Health. Such entities include
...
p.000056: the technical capacity to assess research in that specialised area. Again, several institutions could jointly appoint
p.000056: and share in the expertise of such an IRB in situations where such expertise is limited. Such a specialist IRB has
p.000056: the advantage of delivering consistent decisions, and special competent and knowledge in their field
p.000056: of specialisation. It is also acceptable that a cluster of hospitals cooperate in developing a panel of IRBs to cover
p.000056: all reasonable disciplines.
p.000056:
p.000056: 5.13. To our knowledge, there are currently no commercial IR Bs in Singapore, in the sense of a board that offers
p.000056: ethics review on a commercial basis. In principle, we have no objection to such boards, provided that
p.000056: sufficient safeguards are taken against the obvious objections such as a lack of true independence, but will leave this
p.000056: issue to the national supervisory agency which we recommend in Section 7 below. In any event, we think
p.000056: that careful investigation and consideration by the national supervisory agency should be carried out before a
p.000056: commercial IRB is given accreditation as described in Section 7 below.
p.000056:
p.000056:
p.000056: The Responsibilities of Institutional Review Boards
p.000056:
p.000056: 5.14. In its acts and decisions, and in the exercise and discharge of its duties and responsibilities, an IRB acts
p.000056: on the behalf of the institution that appo ints it and exercises on its behalf the authority and powers of
p.000056: that institution in matters within the terms of reference of the IRB.
p.000056:
p.000056: 5.15. IRBs are required to carry out three distinct functions and responsibilities:
p.000056:
p.000056: 5.15.1. Ethical Review Gateway. In this responsibility, IRBs assume the role of an ethical review gateway through
p.000056: which all proposals for biomedical human research must be submitted and assessed for ethical acceptability
p.000056: and compliance, and for potential harms and benefits in accordance with the principles outlined in Section
p.000056: IV above. In this model of ethical governance, all proposed clinical research involving human subjects
p.000056: must be submitted for review and approval before the proposed research may be carried out. In the majority of
p.000056: developed countries, this is made a statutory or otherwise legal requirement. We recommend this
p.000056: model for adoption in Singapore.
p.000056:
p.000056: 5.15.2. Continuing Review, Supervision and Audit. In this responsibility, IRBs assume jurisdiction and
p.000056: authority for the continuing supervision and audit of approved research programmes upon their commencement. The
p.000056: IRB is also empowered to carry out audits of
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-82
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: research programmes, or to require such audits to be done, in order to ensure continued compliance with the
p.000056: terms of approval throughout the lifetime of the research programme. IRBs may also direct or otherwise
p.000056: require amendments or modifications to research proposals at any time, and to make such amendments or
p.000056: modifications a condition of approval for the conduct of the research programme.
p.000056:
p.000056: 5.15.3. Outcome Assessment, Reporting and Feedback. In this responsibility, IRBs (especially
p.000056: those in large institutions with a large number of research programmes) undertake the monitoring and
p.000056: collation of adverse event reports, the outcomes of the research programmes, an evaluation of the actual versus
p.000056: the anticipated outcome or results, and the reporting of outcomes and trends to the relevant authorities and to
p.000056: the institutions that they are appointed by and to whom they are responsible. Another major aspect of this role
p.000056: is the role of IRBs in providing feedback and maintaining a dialogue on applicable standards with its
p.000056: constituent researchers. In the discharge of their role, IRBs can and should also act as the key institutional
p.000056: agency which receives, acts upon and reports to the relevant authorities on concerns and feedback expressed by the
p.000056: human subjects of the research programmes.
p.000056:
...
p.000056: subjects) of clinical research programmes approved by them. Reporting of the outcomes of the review and audit
p.000056: to proper authorities and to their appointing institutions and to principal investigators of the research
p.000056: programmes;
p.000056:
p.000056: • Reporting on the clinical research programmes and in particular the results of the programme approved by
p.000056: them to the proper authorities and to their appointing institutions, feedback to the constituent researchers of the
p.000056: institutional review board, and monitoring feedback from research subjects.
p.000056:
p.000056: • Additionally, and provided that this responsibility and jurisdiction is clearly set out by the terms
p.000056: of its constitution and appointment by the appointing institution, institutional review boards may
p.000056: also have responsibility for the review of the scientific merits of proposed clinical research programmes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-84
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: The Constitution of Institutional Review Boards
p.000056:
p.000056: 5.20. IRBs should be established and appointed by and at the highest administrative levels of
p.000056: the institutions. They should be appropriately resourced relative to the research activity of the institution
p.000056: and, where this is substantial, should be regarded as one of the key full- time management offices within the
p.000056: organisation of institutions, and not merely as honorary or ad hoc committees.
p.000056:
p.000056: 5.21. The IRB should be appointed and report to at least an authority at the level of the Chief Executive Officer
p.000056: (as required by the NMEC guidelines in the case of hospitals falling under the jurisdiction of the Ministry of Health
p.000056: pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000056:
p.000056: 5.22. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000056: although it is acceptable for institutions with standing IRBs to appoint special ad hoc committees in
p.000056: consultation with their standing IRBs to consider special research proposals. We prefer, in such cases, that
p.000056: the institution works with their standing IRB to appoint special subcommittees co-opting experts or reviewers to assist
p.000056: the standing IRB in the particular project concerned. For example, an IRB may receive a research proposal
p.000056: involving an area of research with which no member of the IRB is familiar. In such a case, the institution may work
p.000056: with the IRB to identify and co-opt ad hoc experts or reviewers to assist the IRB in its assessment and review
p.000056: of the proposal. The co-opted ad hoc experts or reviewers sit as a subcommittee of the IRB.
p.000056:
p.000056: 5.23. Institutions have an obligation to ensure that IRBs receive adequate administrative support
p.000056: that is commensurate with their central role in the ethical governance process.
p.000056:
p.000056: 5.24. IRBs should have sufficient full-time administrative support so as to ensure continuity and
p.000056: consistency in the work of the IRBs, to discharge its continuing review, supervision and audit obligations,
p.000056: its outcome assessment and reporting duties, and to ensure that their decisions are made with regard to
...
p.000056: use of and the custody of medical records and other patient information is becoming increasingly complex. In
p.000056: this area, the ethical issues are inextricably interwoven with legal considerations, and the
p.000056: impact of the existing law is currently unclear in many situations. We hope to explore these issues in a
p.000056: separate subsequent report.
p.000056:
p.000056: 5.70. In the context of institutions such as hospitals with centralised patient records databases, we
p.000056: recommend that IRBs should take steps to determine who should be the proper administrative custodians responsible for
p.000056: patient medical information in the institution, and to establish a system through which the custodians
p.000056: would inform the attending physicians before releasing patients’ medical information for the
p.000056: purposes of medical research.
p.000056:
p.000056: 5.71. In situations where any of the researchers are also the administrative custodian of patient medical
p.000056: information within the institution, procedures should be established to address potential or apparent conflicts of
p.000056: interest.
p.000056:
p.000056: 5.72. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000056: kinds of patient and medical information, and should formulate these procedures in consultation with their
p.000056: ethics committees.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-93
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.73. It is desirable that the IRB should have the ultimate authority and responsibility for
p.000056: the ethical clearance of access to patient medical information within the institution, so that no
p.000056: patient medical information may be released for research purposes without clearance by the IRB. Such authority
p.000056: should by necessity also extend over the administrative custodians of patient medical information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-94
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VI: RESEARCHERS
p.000056:
p.000056: 6. The Responsibilities of Researchers
p.000056:
p.000056: The general responsibilities of researchers
p.000056:
p.000056: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethical governance of clinical
p.000056: research. More than any other party or parties in the ethical review and governance process, they are in
p.000056: the position of having the fullest access to the facts on which ethical judgments are to be made.
p.000056:
p.000056: 6.2. They are responsible for making the threshold decisions in conceiving, designing and putting
p.000056: together a proposed research project. In these decisions, they have the most freedom to shape the
p.000056: proposed research project in a way that gives fullest consideration and respect to ethical considerations,
...
p.000056:
p.000056: 7.11. The national supervisory agency should be empowered to conduct audit and investigations into
p.000056: complaints (including complaints from research subjects), and should have the power to appoint external
p.000056: auditors and investigators at the cost of the institution being audited as part of the accreditation check
p.000056: or as a matter of routine audit for compliance.
p.000056:
p.000056: 7.12. The national supervisory agency should be empowered to appoint committees of inquiry to
p.000056: investigate complaints arising from research programmes (including complaints from research subjects) and
p.000056: should have powers to compel the testimony of witnesses and the production of documents (in this, the statutory powers
p.000056: of the Singapore Medical Council in disciplinary proceedings may be used as an example).
p.000056:
p.000056: 7.13. The national supervisory agency should also be empowered to work towards developing a code of
p.000056: ethics and principles for the governance of
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-104
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: clinical research. This should be carried out by incremental and evolutionary development, through
p.000056: a process of dialogue and discussion between institutional review boards and the other parties in the
p.000056: research governance process, and having reference to the experiences of the parties involved.
p.000056:
p.000056:
p.000056: Recommendation 7:
p.000056:
p.000056: A national supervisory authority should be appointed for the statutory supervision, regulation, accreditation
p.000056: and audit of all IRBs in Singapore.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-105
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VIII: PROTECTION
p.000056:
p.000056: 8. The Protection Of Institutional Review Boards
p.000056:
p.000056: 8.1. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000056: difficulties in attracting members of its choice in that some of the most qualified potential candidates for
p.000056: membership decline the invitation to serve. These candidates may do so out of a fear of legal liability in the event
p.000056: of a contested decision, or a decision which has an unexpectedly adverse impact on human subjects. Few such
p.000056: candidates have any legal training, and the ir reluctance on this ground is understandable.
p.000056:
p.000056: 8.2. On this point, we note that the NMEC Guidelines suggests that IRBs should look to the
p.000056: authority appointing them to give them formal indemnity against the cost of any legal
p.000056: representation, and any compensation ultimately awarded to human subjects. The NMEC Guidelines
p.000056: further recommend that such an indemnity should be given in the letter of appointments of the members.
p.000056:
p.000056: 8.3. Members of IRBs discharge an important office in the public interest in the protection of human subjects.
p.000056: Often they do so for minimal or token remuneration, or none at all. Their only motivation being a call to
p.000056: duty, and their only reward being the satisfaction of a job well done.
p.000056:
p.000056: 8.4. We take the view that members of IRBs should be fully protected by the law in their discharge of their
p.000056: duties, provided that they do so in good faith, against any liability arising from their actions. Such
p.000056: protection should extend to immunity from liability in tort arising from any claim by human subjects, and to a
p.000056: defence of qualified privilege to any claim in defamation.
p.000056:
p.000056: 8.5. Appointing institutions should nonetheless be required to give members of IRBs a full indemnity. Such
p.000056: institutions should remain liable to human subjects from any claim in tort, and should be required to
p.000056: take out appropriate insurance coverage against the variety of claims which may arise in the course of the
p.000056: work of the IRB. For example, in relation to the approval of multi- centre or multinational trials.
p.000056:
...
p.000056: conduct, monitoring and analyses of the studies.
p.000056:
p.000056: BAC: This concern is noted and will be highlighted to the Ministry of Health (MOH).
p.000056:
p.000056: Requirements in Obtaining Informed Consent
p.000056:
p.000056: IRB: One of the provisions in the Paper is for a witness to be present at the consent- taking process (paragraph
p.000056: 5.57). Will the witness be required to observe the entire process or just the endorsement of the consent form?
p.000056:
p.000056: BAC: The purpose of that provision is to have an independent person ensure that the human subject understands what
p.000056: he/she is consenting to. This requirement does not entail any departure from normal medical procedures. As the
p.000056: Paper is meant to provide only a framework for ethics governance, the actual procedure for the procurement of consent
p.000056: will not be prescribed here.
p.000056:
p.000056: Role of a Supervisory Body for IRBs
p.000056:
p.000056: IRB: Will there be a central body to keep check on the standards of ethics governance of each
p.000056: institution? If so, some form of penalty needs to be prescribed for non-compliance so that the
p.000056: standards can be effectively maintained. Revocation of the accreditation of an IRB can be such a penalty.
p.000056:
p.000056: BAC: The BAC recommends that a central supervisory authority be established to either license each
p.000056: institution or grant an umbrella licence to a group o f institutions. This authority will be empowered
p.000056: to accredit and audit licensed institutions. A majority of the large hospitals will be licensed by their areas of
p.000056: competence. Licence can also be granted based on specific conditions. Such a
p.000056:
p.000056:
p.000056: E-152
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: supervisory authority will therefore impose two kinds of checks – licensing and accreditation.
p.000056:
p.000056: Role and Responsibilities of IRBs
p.000056:
p.000056: Continuing Review, Supervision and Audit
p.000056:
p.000056: IRB: Can the BAC clarify what it means by “continuing review” (paragraph 5.15.2)?
p.000056:
p.000056: BAC: The BAC has received several responses on this issue. By “continuing review”, the BAC
p.000056: intends to empower IRBs to carry out audits. This empowerment will change the mindset of some
p.000056: PIs who consider the IRB approval of research proposals as a one-off threshold clearance. IRBs should review on-
p.000056: going research even after it has given its initial approval for the research proposal. The Paper will be
p.000056: amended to clarify this issue.
p.000056:
p.000056: IRB: Can a separate body be assigned to conduct audit in order to alleviate the workload of IRBs?
p.000056:
p.000056: BAC: An IRB need not perform the audit itself but it has to have the means to monitor any deviations
p.000056: from the proposed research protocol. For example, the IRB can mandate an annual report and a completion report, or it
p.000056: can appoint independent auditors to carry out audits.
p.000056:
p.000056: However, it may be better for IRBs to carry out audits themselves, as appointing independent auditors
p.000056: may result in IRBs having to check on two parties. A research may have wide social impact and IRBs should
p.000056: ensure that the research is done in accordance with the approved protocol, with particular focus on the safety and
p.000056: privacy of human subjects. Other concerns, such as scientific validity of the research, are secondary.
p.000056:
...
p.000056: United Kingdom
p.000056:
p.000056: 6. Code of Federal Regulations Title 45 Public Welfare – Part 46: Protection of Human Subjects (2001)
p.000056: Office for Protection from Research Risks, National Institutes of Health, Department of Health and Human Services,
p.000056: U.S.A.
p.000056:
p.000056: 7. Ethical and Policy Issues in Research Involving Human Participants (August 2001) National Bioethics Advisory
p.000056: Commissio n, U.S.A.
p.000056:
p.000056: 8. The Belmont Report (1979)
p.000056: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, U.S.A.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: F-158
p.000056:
p.000056:
p.000056: ANNEXE G
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: LIST OF ABBREVIATIONS
p.000056:
p.000056: BAC Bioethics Advisory Committee (Singapore)
p.000056: CEO Chief Executive Officer
p.000056: DNA Deoxyribonucleic acid
p.000056: EC Ethics committee
p.000056: GCP Good Clinical Practice
p.000056: HGS Human Genetics Subcommittee
p.000056: HSA Health Sciences Authority (Singapore)
p.000056: ICH International Conference on Harmonisation
p.000056: IRB Institutional Review Board
p.000056: MCRC Medical Clinical Research Committee
p.000056: MOH Ministry of Health (Singapore)
p.000056: NHG National Healthcare Group (Singapore)
p.000056: NMEC National Medical Ethics Committee (Sin gapore) NUH National University
p.000056: Hospital
p.000056: PI Principal Investigator
p.000056: RNA Ribonucleic acid
p.000056: SGGCP Singapore Guideline for Good Clinical Practice SOP Standard Operating
p.000056: Procedure
p.000056: UNESCO United Nations Education, Scientific and Cultural Organization
p.000056: WHO World Health Organization
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
...
General/Other / belmont
Searching for indicator belmont:
(return to top)
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: involve some degree of risk of harm (however minimal or remote) to the human subject.
p.000024:
p.000024: 4.6. Ethical assessment and judgment therefore necessarily involve an assessment and balancing of
p.000024: the potential harms and benefits. In general, human biomedical research should be directed towards the minimisation
p.000024: of risks and the maximisation of benefits, always bearing in mind the overriding considerations of
p.000024: the safety, health, dignity, welfare and privacy of the human subject and the ethical standards of society at
p.000024: that point in time.
p.000024:
p.000024: 4.7. To this end, a system of ethics governance must ensure that there is a proper assessment and
p.000024: weighing of the potential harms against the potential benefits of all human biomedical research, in
p.000024: accordance with the ethical values of the community. A proper system of ethics governance serves to strengthen
p.000024: public confidence in human biomedical research by ensuring that all forms of human biomedical research conform
p.000024: to the accepted body of ethical values of the community.
p.000024:
p.000024: 4.8. These fundamental ethical values are expressed and repeated in international
p.000024: documents such as the Declaration of Helsinki, the Nuremberg Code, the Belmont Report (“Ethical
p.000024: Principles and Guidelines for the Protection of Human Subjects of Research”, 1976), the UNESCO’s “Universal Declaration
p.000024: on the Human Genome and Human Rights” (1997) and the WHO’s “Proposed International Guidelines on Ethical Issues
p.000024: in Medical Genetics and Genetic Services” (1998).
p.000024:
p.000024: 4.9. In Singapore, these same principles are found or reflected in regulatio ns such as the Medicines
p.000024: (Clinical Trials) Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already
p.000024: addressed some of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000024:
p.000024: 4.10. These core principles are expressed, restated and elaborated upon in many ways. For example, the NMEC
p.000024: expresses some of these fundamental principles as follows:
p.000024:
p.000024: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000024: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000024: risks of participating in research. Justice relates to the fair distribution of risks in research in relation
p.000024: to the anticipated benefits for research subjects. Autonomy refers to the right of individuals to decide for
p.000024: themselves what is good for them.
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025:
...
p.000056: the potential harms and benefits. In general, clinical research should be directed towards the minimisation of risks
p.000056: and the maximisation of benefits, always bearing in mind the overriding considerations of the safety, health,
p.000056: dignity, welfare and well-being of the human subject.
p.000056:
p.000056: 4.7. To this end, a system of ethical governance must ensure that there is a proper assessment
p.000056: and weighing of the potential harms against the potential benefits of all biomedical human research, in
p.000056: accordance with the ethical values of the community. A proper system of ethical governance serves to strengthen
p.000056: public confidence in biomedical human research by ensuring that all forms of biomedical human research conform
p.000056: to the accepted body of ethical values of the community.
p.000056:
p.000056: 4.8. We recognise, however, that there can be neither absolute certainty nor finality as to the precise
p.000056: content of the body of ethical values to be applied in such an assessment. This is so in Singapore, as it is
p.000056: everywhere else in the world. The body of ethics in any given society is neither fixed nor clearly
p.000056: defined for all time, but evolves in response to advances in knowledge, technology, changes in social mores,
p.000056: and community dialogue and debate.
p.000056:
p.000056: 4.9. These fundamental principles are expressed and repeated in international documents such as the Declaration
p.000056: of Helsinki, the Nuremberg Code, the Belmont Report (Ethical Principles and Guidelines for the Protection of
p.000056: Human Subjects of Research, 1976), the UNESCO Universal Declaration on the Human Genome and Human Rights 1997, and the
p.000056: WHO’s Proposed Guidelines on Ethical Issues in Medical Genetics and Genetic Services 1997 (as updated 2001).
p.000056:
p.000056: 4.10. In Singapore, these same principles are found or reflected in regulations such as the Clinical
p.000056: Trials Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already addressed some
p.000056: of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000056:
p.000056: 4.11. These core principles are exp ressed, restated and elaborated upon in many ways. For example, the NMEC
p.000056: expresses some of these fundamental principles as follows:
p.000056:
p.000056: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000056: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000056: risks of participating in research. Justice relates to
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-76
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: the fair distribution of risks in research in relation to the anticipated benefits for research subjects.
p.000056: Autonomy refers to the right of individuals to decide for themselves what is good for them.
...
p.000056:
p.000056:
p.000056:
p.000056: F-157
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056: Other Countries
p.000056:
p.000056: 1. National Statement on Ethical Conduct in Research Involving Humans (1999) National Health and Medical Research
p.000056: Council, Australia
p.000056:
p.000056: 2. Human Research Ethics Handbook (2001)
p.000056: National Health and Medical Research Council, Australia
p.000056:
p.000056: 3. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (1998, with 2000, 2002, 2003 updates)
p.000056: Medical Research Council, Natural Sciences and Engineering Research Council, and Social
p.000056: Sciences and Humanities Research Council, Canada
p.000056:
p.000056: 4. Governance arrangements for NHS Research Ethics Committees (July 2001) Department of Health, United Kingdom
p.000056:
p.000056: 5. Research Governance Framework for Health and Social Care, 2nd edition draft (April 2003) Department of Health,
p.000056: United Kingdom
p.000056:
p.000056: 6. Code of Federal Regulations Title 45 Public Welfare – Part 46: Protection of Human Subjects (2001)
p.000056: Office for Protection from Research Risks, National Institutes of Health, Department of Health and Human Services,
p.000056: U.S.A.
p.000056:
p.000056: 7. Ethical and Policy Issues in Research Involving Human Participants (August 2001) National Bioethics Advisory
p.000056: Commissio n, U.S.A.
p.000056:
p.000056: 8. The Belmont Report (1979)
p.000056: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, U.S.A.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: F-158
p.000056:
p.000056:
p.000056: ANNEXE G
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: LIST OF ABBREVIATIONS
p.000056:
p.000056: BAC Bioethics Advisory Committee (Singapore)
p.000056: CEO Chief Executive Officer
p.000056: DNA Deoxyribonucleic acid
p.000056: EC Ethics committee
p.000056: GCP Good Clinical Practice
p.000056: HGS Human Genetics Subcommittee
p.000056: HSA Health Sciences Authority (Singapore)
p.000056: ICH International Conference on Harmonisation
p.000056: IRB Institutional Review Board
p.000056: MCRC Medical Clinical Research Committee
p.000056: MOH Ministry of Health (Singapore)
p.000056: NHG National Healthcare Group (Singapore)
p.000056: NMEC National Medical Ethics Committee (Sin gapore) NUH National University
p.000056: Hospital
p.000056: PI Principal Investigator
p.000056: RNA Ribonucleic acid
...
General/Other / cultural difference
Searching for indicator culturally:
(return to top)
p.000056:
p.000056: IRB: There are international requirements, such as in the US, for IRB members to meet face to face. Singapore should
p.000056: conform to such international practices.
p.000056:
p.000056: BAC: Certain research proposals may be subject to expedited review and thus a decision need not be made at
p.000056: a face-to- face meeting.
p.000056:
p.000056: Special IRBs
p.000056:
p.000056: IRB: In some countries, IRBs are removed from the auspices of institutions and yet some other institutions, such as
p.000056: the UK National Health Services, share IRBs. The motive is to secure the independence of IRBs from their
p.000056: appointing institutions and thereby avoid conflict of interest.
p.000056:
p.000056: However, it is the institution’s responsibility to ensure that its appointment of IRB members will not result in any
p.000056: conflict of interest. If an IRB is separated from an institution, it will not be able to familiarise itself with the
p.000056: operations of that institution. Hence, the two-tier approach is a good one.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-155
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: However, there are commercial IRBs in the US that are independent of an institution. These IRBs have
p.000056: been mentioned in the Paper. They can be an option for us. The members of commercial IRBs are recruited
p.000056: from a large range of institutions. They do not serve on the IRB full-time and are paid about US$200 per
p.000056: protocol reviewed.
p.000056:
p.000056: BAC: A reason for the acceptance of commercial IRBs in the US is that they provide a liability shield for research
p.000056: institutions, as these IRBs are adequately insured. The concept of commercial IRBs is culturally new to Singapore and
p.000056: may not be applicable within the local context.
p.000056:
p.000056: In a small nation like Singapore, IRBs operating outside an institution will not solve issues of conflict of interest.
p.000056: Nonetheless, the BAC welcomes the idea of shared IRBs or domain-specific IRBs, which have been described in the Paper.
p.000056:
p.000056: IRB: Domain-specificity is advantageous as there will be a need for IRB members with the suitable expertise for
p.000056: evaluating specialty research protocols. Another potential problem to note with respect to the small size of
p.000056: the local medical community is the ‘rubber-stamping’ of one another’s research protocol, because most of
p.000056: members of the community recognise one another’s field of work.
p.000056:
p.000056: Conclusion
p.000056:
p.000056: BAC: The BAC will consider all suggestions that have been made and will try to address as many of the
p.000056: issues that have been raised. Some of the provisions in the Paper may have been misinterpreted as excessive. These
p.000056: provisions will be clarified by the BAC in its recommendations to the Government. It is
p.000056: emphasised that the provisions and recommendations issued by the BAC are only intended as general guidelines. The BAC
p.000056: thanks all participants for their time and valuable input.
p.000056:
p.000056:
p.000056: –––––––––––––––––––––
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-156
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SELECT REFERENCES
...
General/Other / declaration of helsinki
Searching for indicator helsinki:
(return to top)
p.000001:
p.000001:
p.000001:
p.000001: ANNEXES
p.000001:
p.000001:
p.000001: Annexe A: The Human Genetics Subcommittee A-57
p.000001:
p.000001: Annexe B: Consultation Paper entitled “Advancing the Framework B-58 of Ethics Governance for Human
p.000001: Research”
p.000001:
p.000001: Annexe C: Distribution List C-109
p.000001:
p.000001: Annexe D: Responses to the Consultation Paper D-111
p.000001:
p.000001: Annexe E: Summary of the Dialogue Session E-151
p.000001:
p.000001: Annexe F: Select References F-157
p.000001:
p.000001: Annexe G: List of Abbreviations G-159
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: RESEARCH INVOLVING HUMAN SUBJECTS
p.000001: GUIDELINES FOR IRBS
p.000001:
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001: Principle
p.000001:
p.000001: 1. There is general agreement internationally that human biomedical research involving risk of harm
p.000001: to human subjects should be subject to independent ethics review.
p.000001:
p.000001: 2. This principle is reflected in international documents such as the Nuremberg Code of 1949, the
p.000001: Declaration of Helsinki of 1964 and the International Conference on Harmonisation’s “Guideline for Good Clinical
p.000001: Practice” (ICH GCP Guideline) of 1996.
p.000001:
p.000001:
p.000001: Pharmaceutical Trials
p.000001:
p.000001: 3. In Singapore, pharmaceutical trials are currently governed under the Medicines Act and the
p.000001: Medicines (Clinical Trials) Regulations. All proposals for pharmaceutical trials are required to undergo an
p.000001: independent ethics review process and to comply with the “Singapore Guideline for Good Clinical Practice”
p.000001: (SGGCP), which is based on the ICH GCP Guideline.
p.000001:
p.000001: 4. This independent review is carried out first at the institutional level by the institution’s
p.000001: ethics committee or institutional review board (IRB). If approved, the proposal is then submitted to the Health
p.000001: Sciences Authority (HSA), which is the licensing body for pharmaceutical trials. Clinical Trial Certificates will be
p.000001: issued for proposals approved by the HSA.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Human Biomedical Research other than Pharmaceutical Trials
p.000001:
p.000001: 5. Currently, there is no provision requiring human biomedical research other than pharmaceutical
p.000001: trials to be submitted for independent ethics review. This is so even if the proposed research programme
...
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: INTRODUCTION AND CURRENT
p.000008: FRAMEWORK
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: SECTION II: THE CURRENT FRAMEWORK
p.000008:
p.000008: 2. The Current Framework The Background
p.000008: 2.1. In Singapore and other technologically advanced societies, advances in biomedical technology and
p.000008: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000008: of life of the general population. These advances represent some of the principal achievements in the modern
p.000008: history of the human race. In the main, such advances in biomedical knowledge have been beneficial and
p.000008: are considered to be research conducted in good faith for the benefit of humankind.
p.000008:
p.000008: 2.2. Events during World War II, however, gave rise to concerns that research conducted on human subjects should
p.000008: be subject to agreed ethical norms. The Nuremberg Code1 was born out of these concerns and represents the first
p.000008: universally accepted code spelling out the minimum content of the ethical norms governing the conduct of
p.000008: research on human subjects.
p.000008:
p.000008: 2.3. These ethical norms were given full consideration and description in the World Medical
p.000008: Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Huma n Subjects,2 which
p.000008: since its adoption by the 18th World Medical Association General Assembly at Helsinki, Finland, has become
p.000008: universally accepted as the core body of ethical norms governing human research.
p.000008:
p.000008: 2.4. The principal theme of the Helsinki Declaratio n is that the life, health, privacy and dignity of
p.000008: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000008: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000008: human subject and the need for rigorous scientific assessment of the risks to the human subject
p.000008: in relation to the benefit sought to be gained from the research.
p.000008:
p.000008: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000008: This provides that the “design and performance of
p.000008:
p.000008: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol.
p.000008: 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000008: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects
p.000008: adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most recently
p.000008: amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: INTRODUCTION AND CURRENT
p.000009: FRAMEWORK
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: each experimental procedure involving human subjects should be clearly formulated in an experimental protocol” and that
p.000009: this protocol should be submitted to an independent ethics review committee for “consideration, comment,
p.000009: guidance, and where appropriate, approval.”
p.000009:
p.000009: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000009: medical community in Singapore and by other medical communities in the great majority of nations. In
p.000009: Singapore, the need for ethics committees or IRBs and the requirement for the ethics review of research
p.000009: proposals involving human subjects have long been an accepted and integral part of biomedical research in the
p.000009: institutional setting.
p.000009:
p.000009: 2.7. The principle s of the Declaration of Helsinki today find expression in regulatory standards and
p.000009: practice guidelines governing various aspects of clinical research such as those contained in the Medicines (Clinical
p.000009: Trials) Regulations, promulgated pursuant to Section 74 of the Medicines Act (Cap. 176), the “Singapore
p.000009: Guideline for Good Clinical Practice” (SGGCP) and the “Ethical Guidelines on Research Involving Human
p.000009: Subjects” (NMEC Guidelines) issued in August 1997 by the National Medical Ethics Committee (NMEC).
p.000009: We discuss these regulatory standards and practice guidelines in detail below.
p.000009:
p.000009:
p.000009: Pharmaceutical Trials in Singapore
p.000009:
p.000009: 2.8. In Singapore, pharmaceutical trials involving the testing of drugs on human subjects are regulated by the
p.000009: Health Sciences Authority (HSA). The HSA regulates the conduct of pharmaceutical trials under the Medicines Act and the
p.000009: Medicines (Clinical Trials) Regulations (2000, Revised Edition). Under the Medicines Act, these
p.000009: pharmaceutical or drug trials are known as “clinical trials”.
p.000009:
p.000009: 2.9. The system of regulation requires that sponsors and researchers conducting pharmaceutical trials obtain
p.000009: both ethics and regulatory approval before initiating a study.
p.000009:
p.000009: 2.10. The current approval system is sequential. Approval from the HSA is sought only after the
p.000009: relevant hospital ethics committee has approved an application. Regulatory approval is provided in the form
...
p.000010: whom are clinical specialists.
p.000010:
p.000010: 2.12. In this way, pharmaceutical trials are subject to ethics review at more than one level.
p.000010:
p.000010: 2.13. Additionally, pharmaceutical trials are also required to conform to the SGGCP issued by the MOH in
p.000010: 1998. The SGGCP is a set of guidelines adapted from the 1996 “Guideline for Good Clinical Practice” of the
p.000010: International Conference on Harmonisa tion of Technical Requirements for Registration of Pharmaceuticals for Human
p.000010: Use (ICH GCP Guideline), which is the international gold standard for conduct of pharmaceutical trials.
p.000010: Accordingly, the SGGCP reflects best international practice in its approach to the governance of
p.000010: pharmaceutical trials. Since 1998, the SGGCP has been incorporated by reference in Regulation 21 of the
p.000010: Medicines (Clinical Trials) Regulations. Sponsors and researchers in pharmaceutical trials are
p.000010: required by law to comply with the SGGCP unless specifically exempted under the Medicines (Clinical
p.000010: Trials) Regulations.
p.000010:
p.000010: 2.14. The SGGCP sets out in detail a framework for the ethics governance of pharmaceutical trials.
p.000010: The SGGCP begins its statement of applicable principles by declaring that “[c]linical trials should be
p.000010: conducted in accordance with the ethical principles that have their origin in the Declaration of
p.000010: Helsinki” (Section 2.1).
p.000010:
p.000010: 2.15. Section 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000010: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000010: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000010: investigational product(s), and/or to identify any adverse reactions to an investigational product(s),
p.000010: and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the
p.000010: object of ascertaining its safety and/or efficacy.”
p.000010:
p.000010: 2.16. The SGGCP sets out detailed guidelines as to the roles and duties of researche rs and sponsors
p.000010: in a pharmaceutical trial, and lays down requirements such as monitoring procedures, audits and other
p.000010: matters to be included in trial protocols.
p.000010:
p.000010: 2.17. Of note are the provisions in Part 3 of the SGGCP requiring all pharmaceutical trials
p.000010: to be re viewed and approved by the hospital ethics committees concerned and the MCRC of the HSA before a Clinical
p.000010: Trial
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011: INTRODUCTION AND CURRENT
p.000011: FRAMEWORK
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: Certificate will be issued. The responsibilities, composition, functions and operations of the MCRC are set out in
p.000011: detail in Section 3.1 of the SGGCP, while those of the ethics committee are detailed in Section 3.2.
p.000011:
p.000011: 2.18. In keeping with the principles of the Declaration of Helsinki, the Medicines (Clinical
p.000011: Trials) Regulations require researchers to ensure that free and informed consent be obtained from the potential
p.000011: research subject and that researchers are under a duty to fully inform the subject by explaining, among
p.000011: other issues, the risks and objectives of the proposed pharmaceutical trial.
p.000011:
p.000011:
p.000011: Human Biomedical Research other than Pharmaceutical Trials
p.000011:
p.000011: The Ethics Governance of Human Biomedical Research other than Pharmaceutical Trials
p.000011:
p.000011: 2.19. While the ethics governance of pharmaceutical trials in Singapore is comprehensively and
p.000011: appropriately regulated by statutory rules and practice guidelines, the picture for the ethics
p.000011: governance of human biomedical research other than pharmaceutical trials is less clear.
p.000011:
p.000011: 2.20. Currently, there is no statutory scheme for the ethics governance of human biomedical research apart from
p.000011: pharmaceutical trials. In Section III, we define and explain “Human Biomedical Research”.
p.000011:
p.000011: 2.21. Indirectly, however, the MOH has long exercised jurisdiction over, and given informal ethical
p.000011: guidance on, human biomedical research carried out in hospitals, clinics and clinical laboratories in its role
p.000011: as the statutory regulator under the Private Hospitals and Medical Clinics Act.
p.000011:
...
p.000015:
p.000015: 3.3. Human biomedical research is a term capable of a very broad definition. In our review of the approaches
p.000015: taken by national ethics bodies or agencies in other countries, we have found that there is considerable
p.000015: variation in what is to be included in the definition of human biomedical research coming within the
p.000015: purview of institutional ethics review bodies. For example, in some jurisdictions, ethics committees are
p.000015: required to review proposals for sociological research or humanities-based research if they involve human
p.000015: subjects, while in other jurisdictions this requirement does not apply.
p.000015:
p.000015: 3.4. Currently, there is no international agreement on the exact scope of human biomedical research that should be
p.000015: subject to IRB review. But that is not to say that there is no agreement at all on what should be subject
p.000015: to IRB review. Clearly, there is universal and unanimous agreement in all reputable research
p.000015: communities that research involving direct physical interference or interaction with human subjects, and
p.000015: where such direct physical interference or interaction may result in death, injury or other physical or
p.000015: emotional harm to the research subject, must be subject to proper IRB review. These core values and
p.000015: principles are captured in international documents such as the Nuremberg Code, the Declaration of Helsinki and the
p.000015: ICH GCP Guideline.
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000016: HUMAN
p.000016: BIOMEDICAL RESEARCH
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: 3.5. At the edge of this core of certainty, however, international consensus is still in a state of
p.000016: development. Increasingly, human experimentation and human biomedical research have moved away from
p.000016: direct physical interference or interaction with human subjects themselves, towards research conducted
p.000016: largely on cell lines, tissues or other bodily samples given by human donors, and on medical information
p.000016: derived from patients and other human subjects.
p.000016:
p.000016: 3.6. Increasingly, it is the case that there is no direct physical contact at all between the
p.000016: researchers and the human subjects. In such circumstances, there is no possibility of physical injury or harm
p.000016: befalling the human research subjects. In these situations, the ethical, le gal and social concerns centre not on
p.000016: the possibility of physical injury or harm but on the larger penumbra of indirect harms to the patient or
p.000016: donor such as the breach of the patient’s or donor’s expectation of confidentiality of his medical
p.000016: information, or his expectation that his tissue should not be used for research without his consent.
p.000016:
p.000016: 3.7. It is therefore appropriate that a fundamental distinction be made between:
p.000016:
...
p.000022:
p.000022: 3.29. We also exclude from ethics review procedures and requirements all clinical audit and quality
p.000022: assurance activities, which require the institution to review patients' information and are conducted for the sole
p.000022: purpose of improving the quality of patient care within that institution.
p.000022:
p.000022: 3.30. We therefore recommend that all Human Biomedical Research as defined in this section, save for the
p.000022: exceptions expressly provided above, be subject to review and approval by and to the continued supervision of an
p.000022: IRB in accordance with the principles discussed in Section IV.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023: ETHICS GOVERNANCE
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: PART C: ETHICS GOVERNANCE
p.000023:
p.000023: SECTION IV: PRINCIPLES OF ETHICS GOVERNANCE
p.000023:
p.000023: 4. Principles of Ethics Governance The Purpose of Ethics Governance
p.000023: 4.1. Article 5 of the Helsinki Declaration states: "In medical research on human subjects, considerations
p.000023: related to the well-being of the human subject should take precedence over the interests of science and
p.000023: society.” Article 8 of the Declaration states: “Medical research is subject to ethical standards that promote respect
p.000023: for all human beings and protect their health and rights.”
p.000023:
p.000023: 4.2. Continuing human biomedical research is fundamental to improving our understanding of biological
p.000023: processes, and ultimately to the improvement of the health and welfare of humankind. Whereas diagnostic, prophylactic
p.000023: and therapeutic research have as their objective the immediate needs of individual patients, Human
p.000023: Biomedical Research has wider and longer- term objectives in the discovery of new knowledge that may
p.000023: lead to an improvement in the methods of diagnosis, prophylaxis and therapy of individuals, and to the
p.000023: health and welfare of society in general.
p.000023:
p.000023: 4.3. The experience of physicians in the management of patients often leads to new scientific insights,
p.000023: which when coupled with continuing human biomedical research leads to a virtuous circle that supports
p.000023: and advances biomedical knowledge to the benefit of both individuals and society at large. Article 4 of
p.000023: the Helsinki Declaration states: “Medical progress is based on research which ultimately must rest in
p.000023: part on experimentation involving human subjects.”
p.000023:
p.000023:
p.000023: Applicable Principles
p.000023:
p.000023: 4.4. The fundamental objective of having a system of ethics governance in relation to biomedical
p.000023: research is to ensure the protection and assurance of the safety, health, dignity, welfare and privacy of human
p.000023: research subjects and to safeguard against research practices and objectives that are not ethically
p.000023: acceptable to society at that point in time.
p.000023:
p.000023: 4.5. But as with most kinds of diagnostic, prophylactic or therapeutic interventions, most
p.000023: forms of human biomedical research unavoidably
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024:
p.000024: ETHICS GOVERNANCE
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: involve some degree of risk of harm (however minimal or remote) to the human subject.
p.000024:
p.000024: 4.6. Ethical assessment and judgment therefore necessarily involve an assessment and balancing of
p.000024: the potential harms and benefits. In general, human biomedical research should be directed towards the minimisation
p.000024: of risks and the maximisation of benefits, always bearing in mind the overriding considerations of
p.000024: the safety, health, dignity, welfare and privacy of the human subject and the ethical standards of society at
p.000024: that point in time.
p.000024:
p.000024: 4.7. To this end, a system of ethics governance must ensure that there is a proper assessment and
p.000024: weighing of the potential harms against the potential benefits of all human biomedical research, in
p.000024: accordance with the ethical values of the community. A proper system of ethics governance serves to strengthen
p.000024: public confidence in human biomedical research by ensuring that all forms of human biomedical research conform
p.000024: to the accepted body of ethical values of the community.
p.000024:
p.000024: 4.8. These fundamental ethical values are expressed and repeated in international
p.000024: documents such as the Declaration of Helsinki, the Nuremberg Code, the Belmont Report (“Ethical
p.000024: Principles and Guidelines for the Protection of Human Subjects of Research”, 1976), the UNESCO’s “Universal Declaration
p.000024: on the Human Genome and Human Rights” (1997) and the WHO’s “Proposed International Guidelines on Ethical Issues
p.000024: in Medical Genetics and Genetic Services” (1998).
p.000024:
p.000024: 4.9. In Singapore, these same principles are found or reflected in regulatio ns such as the Medicines
p.000024: (Clinical Trials) Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already
p.000024: addressed some of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000024:
p.000024: 4.10. These core principles are expressed, restated and elaborated upon in many ways. For example, the NMEC
p.000024: expresses some of these fundamental principles as follows:
p.000024:
p.000024: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000024: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000024: risks of participating in research. Justice relates to the fair distribution of risks in research in relation
p.000024: to the anticipated benefits for research subjects. Autonomy refers to the right of individuals to decide for
p.000024: themselves what is good for them.
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000025: 25
...
p.000046: and the research programme varied to such extent, without the need for immediate reporting. Reporting of such
p.000046: changes by the PI to the relevant IRB should however take place within a time frame that shall be decided by
p.000046: the IRB. We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000046: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of
p.000046: the research or for meeting its objectives, do not fall within this category and should be immediately
p.000046: reported.
p.000046:
p.000046: 6.34. PIs have an obligation to submit regular reports to IRBs regarding the status of their research
p.000046: programmes. These reports are intended to aid the IRBs in its role of continuing review and supervision.
p.000046:
p.000046:
p.000046: Researchers and Attending Physicians
p.000046:
p.000046: 6.35. Human subjects for research projects are often recruited from patients who are already receiving treatment
p.000046: from physicians.
p.000046:
p.000046: 6.36. Where a proposed researcher is the attending physician, the researcher- physician should be aware of
p.000046: a potential conflict of interest and of the fact
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047: ETHICS GOVERNANCE
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of Helsinki,
p.000047: which states that:
p.000047:
p.000047: “When obtaining informed consent for the research project the physician should be particularly cautious if the subject
p.000047: is in a dependent relationship with the physician or may consent under duress. In that case the informed consent
p.000047: should be obtained by a well -informed physician who is not engaged in the investigation and who is
p.000047: completely independent of this relationship.”
p.000047:
p.000047: 6.37. In our view, ho wever, this does not apply to situations where physicians wish to write up or
p.000047: publish summaries or analyses of the results of their therapeutic interventions or treatment of their patients,
p.000047: provided that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000047: diagnostic purposes and in the interests of the patients and without regard to any consideration for research
p.000047: objectives or for the subsequent publication of the results.
p.000047:
p.000047: 6.38. In some circumstances, it may be difficult or impractical for researcher- physicians to comply
p.000047: with the letter of Article 23 of the Declaration of Helsinki. Such a situation might arise, for example,
p.000047: where the patient and prospective research subject is receiving specialist treatment at a centre or institution at
p.000047: which a majority of the attending physicians are also actively involved in institution- level research programmes. Or
p.000047: it may be that there is only one relevant specialist at the given institution, and that specialist is at the same time
p.000047: the treating physician as well as the proposed researcher. We recommend that in such cases, the IRB may give
p.000047: directions for the consent to be taken by the researcher so long as safeguards are documented in the protocol.
p.000047:
p.000047: 6.39. In the conduct of research programmes involving any kind of clinical or social interaction with human
p.000047: subjects who are receiving treatment for medical conditions, researchers should be aware of the possibility,
p.000047: however remote, that such interaction may have the inadvertent effect of interfering with the therapeutic care of the
p.000047: subject-patient.
p.000047:
p.000047: 6.40. Subject to our specific recommendations in paragraph 6.44, we therefore recommend that where
p.000047: researchers are aware that the potential research subjects are currently receiving treatment or otherwise being
p.000047: attended to by physicians for a medical condition or disease relevant to the proposed programme of
p.000047: research, efforts should be made by the researchers to inform and discuss with the attending physicians. If
p.000047: the research subject customarily attends a hospital or clinic and is attended to by different physicians on
p.000047: each visit, efforts should be made to inform the institution
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
...
p.000056: • To advance recommendations for an unified framework of common processes and procedures to be applied
p.000056: in the ethical governance of clinical research in Singapore.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-61
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION II: THE CURRENT FRAMEWORK
p.000056:
p.000056: 2. The Background
p.000056:
p.000056: 2.1. In Singapore and other technologically-advanced societies, advances in biomedical technology and
p.000056: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000056: of life of the general population. These advances represent one of the principal achievements in the
p.000056: modern history of the human race. In the main, such advances in biomedical knowledge have been beneficial, and
p.000056: research conducted in good faith for the benefit of humankind.
p.000056:
p.000056: 2.2. The events of World War II however, gave rise to concerns that biomedical research
p.000056: conducted on human subjects should be subject to agreed ethical norms. The Nuremberg Code 1 was born
p.000056: out of these concerns, and represents the first universally-accepted code spelling out the minimum content
p.000056: of the ethical norms governing the conduct of biomedical research on human subjects.
p.000056:
p.000056: 2.3. These ethical norms were fleshed out and received fuller treatment and consideration in the World
p.000056: Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects2, which since its adoption by the 18th World Medical Association General Assembly at Helsinki,
p.000056: Finland, has become universally accepted as the core body of ethical norms governing human research.
p.000056:
p.000056: 2.4. The principal theme of the Helsinki Declaration is that the life, health, privacy and dignity of
p.000056: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000056: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000056: human subject, and the need for rigorous scientific assessment of the risks to the human subject
p.000056: in relation to the benefit sought to be gained from the research.
p.000056:
p.000056: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000056: This provides that the “design and performance of each experimental procedure involving human subjects should be
p.000056: clearly formulated in an experimental protocol”, and that this protocol should be
p.000056:
p.000056: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under
p.000056: Control Council Law No. 10, Vol. 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000056: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most
p.000056: recently amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-62
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: submitted to an independent et hical review committee for “consideration, comment, guidance, and where appropriate,
p.000056: approval”.
p.000056:
p.000056: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000056: medical community in Singapore, as with other medical communities in the great majority of nations.
p.000056: The need for ethics committees or institutional review boards and the requirement for the ethical
p.000056: review of research proposals involving human subjects have long been an accepted and integral part of medical
p.000056: research in the institutional setting in Singapore. The principles of the Declaration of Helsinki today find
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
p.000056: as those contained in the Medicines (Clinical Trials) Re gulations, promulgated pursuant to s.74 of the
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
...
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
p.000056: instead use the term “drug trials” in this Consultation Paper when referring to “clinical trials” in the legal sense of
p.000056: that term, as used in the Clinical Trials Regulations and the Medicines Act.
p.000056:
p.000056: 2.13. In keeping with the principles enunciated in the Declaration of Helsinki, an important component of
p.000056: the requirements of the Clinical Trials Regulations is that the researchers must ensure that the free
p.000056: consent of the proposed research subject must be obtained, and that researchers are under a duty to give full
p.000056: explanation and information of (among others) the risks and objectives of the proposed drug trial.
p.000056:
p.000056: The Singapore Guideline for Good Clinical Practice
p.000056:
p.000056: 2.14. In 1998, the Ministry of Health released the Singapore Guideline for Good Clinical Practice (SGGCP), which is
p.000056: a set of guidelines adapted from the Good Clinical Practice Guidelines of the International Conference on
p.000056: Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
p.000056: Accordingly, the SGGCP reflects best international practice in its approach to the governance of drug trials.
p.000056: Since 1998, the SGGCP has been incorporated by reference in the Clinical Trials Regulations, and sponsors and
p.000056: researchers in drug trials are required by law to comply with the SGGCP unless specifically exempted under the Clinical
p.000056: Trials Regulations.
p.000056:
p.000056: 2.15. The SGGCP sets out in detail a framework for the ethical governance of drug trials. The SGGCP begins its
p.000056: statement of applicable principles by declaring that drug trials “should be conducted in accordance with the
p.000056: ethical principles that have their origin in the Declaration of Helsinki”.
p.000056:
p.000056: 2.16. Article 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000056: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000056: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000056: investigational product(s), and/or to identify any adverse reactions to an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-64
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: investigational product(s), and /or to study absorption, distribution, metabolism, and excretion of an
p.000056: investigational product(s) with the object of ascertaining its safety and/or efficacy”.
p.000056:
p.000056: 2.17. The SGGCP sets out detailed guidelines as to the roles and duties of researchers and sponsors in
p.000056: a pharmaceutical drug trial, and lays down the requirements such as monitoring procedures, audits and the matters to be
p.000056: included in trial protocols.
p.000056:
p.000056: 2.18. Of relevance to this Consultation Paper are the provisions in Part 3 of the SGGCP requiring all drug
p.000056: trials to be reviewed and approved by the Medical Clinical Research Committee (MCRC) of the Health
p.000056: Sciences Authority (“HSA”) and hospital’s “ethics committees” before an application may be made
p.000056: for a clinical trial certificate from the HSA. The responsibilities, composition, functions and operations of the
...
p.000056: such emergency or urgent research in the national interest.
p.000056:
p.000056: 3.9. We therefore recommend that all clinical research as defined in this section be statutorily subject to
p.000056: review and approval by and to the continued supervision of an institutional review board in
p.000056: accordance with the principles discussed below.
p.000056:
p.000056:
p.000056: Recommendation 2:
p.000056:
p.000056: • The current statutory requirement for review and approval by an institutional review board in
p.000056: drug trials should be extended to all kinds of clinical research involving human subjects, as defined in this section.
p.000056:
p.000056: • All clinical research proposed to be carried out in Singapore must be submitted to and approved by a
p.000056: properly constituted institutional review board.
p.000056:
p.000056: • No programme of clinical research may be commenced or carried out without the approval of such an
p.000056: institutional review board, or other than on terms as set out by such an institutional review board.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-74
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART C: ETHICAL GOVERNANCE
p.000056:
p.000056: SECTION IV: PRINCIPLES OF ETHICAL GOVERNANCE
p.000056:
p.000056: 4. Principles of Ethical Governance The Purpose of Ethical Governance
p.000056: 4.1. Article 5 of the Helsinki Declaration states that in “medical research on human subjects, considerations
p.000056: related to the well-being of the human subject should take precedence over the interests of science and society”.
p.000056: At Article 8, the Declaration states that “[m]edical research is subject to ethical standards that
p.000056: promote respect for all human beings and protect their health and rights”.
p.000056:
p.000056: 4.2. Continuing biomedical human research is fundamental to improving our understanding of biological
p.000056: processes, and ultimately to the improvement of the health and welfare of humankind. Whereas diagnostic, prophylactic
p.000056: and the rapeutic research have as their objective the immediate needs of individual patients, biomedical
p.000056: human research have wider and longer- term objectives in the discovery of new knowledge that may lead
p.000056: to an improvement in the methods of diagnosis, prophylaxis and therapy of individuals, and to the health and
p.000056: welfare of society in general.
p.000056:
p.000056: 4.3. The experience of physicians in the management of patients often lead to new scientific insights, which when
p.000056: coupled with continuing biomedical human research leads to a virtuous circle that supports and advances
p.000056: biomedical knowledge to the benefit of both individuals and society at large. As Article 4 of the Helsinki
p.000056: Declaration states: “Medical progress is based on research which ultimately must rest in part on experimentation
p.000056: involving human subjects”.
p.000056:
p.000056:
p.000056: Applicable Principles
p.000056:
p.000056: 4.4. The fundamental objective of having a system of ethical governance is ultimately the protection
p.000056: and assurance of the safety, health, dignity, welfare and well-being of human research subjects.
p.000056:
p.000056: 4.5. But as with most kinds of diagnostic, prophylactic or therapeutic interventions, most
p.000056: forms of biomedical human research unavoidably involve some degree of risk of harm (however minimal or remote) to
p.000056: the human subject.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-75
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 4.6. Ethical assessment and judgment therefore necessarily involves an assessment and balancing of
p.000056: the potential harms and benefits. In general, clinical research should be directed towards the minimisation of risks
p.000056: and the maximisation of benefits, always bearing in mind the overriding considerations of the safety, health,
p.000056: dignity, welfare and well-being of the human subject.
p.000056:
p.000056: 4.7. To this end, a system of ethical governance must ensure that there is a proper assessment
p.000056: and weighing of the potential harms against the potential benefits of all biomedical human research, in
p.000056: accordance with the ethical values of the community. A proper system of ethical governance serves to strengthen
p.000056: public confidence in biomedical human research by ensuring that all forms of biomedical human research conform
p.000056: to the accepted body of ethical values of the community.
p.000056:
p.000056: 4.8. We recognise, however, that there can be neither absolute certainty nor finality as to the precise
p.000056: content of the body of ethical values to be applied in such an assessment. This is so in Singapore, as it is
p.000056: everywhere else in the world. The body of ethics in any given society is neither fixed nor clearly
p.000056: defined for all time, but evolves in response to advances in knowledge, technology, changes in social mores,
p.000056: and community dialogue and debate.
p.000056:
p.000056: 4.9. These fundamental principles are expressed and repeated in international documents such as the Declaration
p.000056: of Helsinki, the Nuremberg Code, the Belmont Report (Ethical Principles and Guidelines for the Protection of
p.000056: Human Subjects of Research, 1976), the UNESCO Universal Declaration on the Human Genome and Human Rights 1997, and the
p.000056: WHO’s Proposed Guidelines on Ethical Issues in Medical Genetics and Genetic Services 1997 (as updated 2001).
p.000056:
p.000056: 4.10. In Singapore, these same principles are found or reflected in regulations such as the Clinical
p.000056: Trials Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already addressed some
p.000056: of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000056:
p.000056: 4.11. These core principles are exp ressed, restated and elaborated upon in many ways. For example, the NMEC
p.000056: expresses some of these fundamental principles as follows:
p.000056:
p.000056: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000056: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000056: risks of participating in research. Justice relates to
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-76
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: the fair distribution of risks in research in relation to the anticipated benefits for research subjects.
...
p.000056: subjects taken after consultation with all researchers involved in the trial need not be immediately
p.000056: reported to the IRB. For example, if it appears to a researcher that a particular research subject is not
p.000056: altogether comfortable with one of the planned procedures, that procedure may be dropped and the research programme
p.000056: varied to such extent, without the need for immediate reporting. Reporting of such changes by the Principal
p.000056: Investigator to the relevant IRB should however take place within a set time frame that shall be decided by the IRB.
p.000056: We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000056: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of the
p.000056: trial or of its objectives do not fall within this category and should be immediately reported.
p.000056:
p.000056: Researchers and Attending Physicians
p.000056:
p.000056: 6.34. Human subjects for research projects are often recruited from patie nts who are already receiving treatment
p.000056: from physicians.
p.000056:
p.000056: 6.35. Where a proposed researcher is the attending physician, the researcher / physician should be aware
p.000056: of a potential conflict of interest, and of the fact
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-100
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of
p.000056: Helsinki, which states that “[w]hen obtaining informed consent for the research project the physician
p.000056: should be particularly cautious if the subject is in a dependent relationship with the physician or may
p.000056: consent under duress. In that case the informed consent should be obtained by a well- informed
p.000056: physician who is not engaged in the investigation and who is completely independent of this relationship”.
p.000056:
p.000056: 6.36. In our view, however, this does not app ly to situations where clinicians wish to write up or publish
p.000056: summaries or analyses of the results of their therapeutic interventions or treatment of patients, provided
p.000056: that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000056: diagnostic purposes and in the interests of the patients, and without regard to any consideration for research
p.000056: objectives, or for the subsequent publication of the results.
p.000056:
p.000056: 6.37. We further take the view that where researchers are aware that the proposed research subjects are
p.000056: currently receiving treatment or otherwise being attended to by physicians, reasonable efforts should be made on an
p.000056: informal basis by the researchers to contact and inform the attending physicians of the proposed research
p.000056: progr amme. If the research subjects customarily attend at a hospital or clinic, and are attended to by different
p.000056: physicians on their visits, reasonable efforts should be made on an informal basis to contact
...
p.000056: Nonetheless, the BAC welcomes the idea of shared IRBs or domain-specific IRBs, which have been described in the Paper.
p.000056:
p.000056: IRB: Domain-specificity is advantageous as there will be a need for IRB members with the suitable expertise for
p.000056: evaluating specialty research protocols. Another potential problem to note with respect to the small size of
p.000056: the local medical community is the ‘rubber-stamping’ of one another’s research protocol, because most of
p.000056: members of the community recognise one another’s field of work.
p.000056:
p.000056: Conclusion
p.000056:
p.000056: BAC: The BAC will consider all suggestions that have been made and will try to address as many of the
p.000056: issues that have been raised. Some of the provisions in the Paper may have been misinterpreted as excessive. These
p.000056: provisions will be clarified by the BAC in its recommendations to the Government. It is
p.000056: emphasised that the provisions and recommendations issued by the BAC are only intended as general guidelines. The BAC
p.000056: thanks all participants for their time and valuable input.
p.000056:
p.000056:
p.000056: –––––––––––––––––––––
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-156
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SELECT REFERENCES
p.000056:
p.000056: International
p.000056:
p.000056: 1. Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects (2000)
p.000056: World Medical Association
p.000056:
p.000056: 2. ICH Topic E6 - Guideline For Good Clinical Practice (1996)
p.000056: International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
p.000056:
p.000056: 3. International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) Council for International
p.000056: Organizations of Medical Sciences
p.000056:
p.000056: 4. Nuremberg Code (1949)
p.000056: Trials of War Criminals before the Nuremberg Military Tribunals under Control Council
p.000056: U.S. Government Printing Office, Washington D.C. Law No. 10, Vol. 2:181-182
p.000056: 5. Operational Guidelines for Ethics Committees that Review Biomedical Research (20 00) World Health Organization
p.000056:
p.000056: 6. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services (1998)
p.000056: World Health Organization
p.000056:
p.000056: 7. Universal Declaration on the Human Genome and Human Rights (1997) United Nations Educational, Scientific and
p.000056: Cultural Organization
p.000056:
p.000056:
p.000056: Singapore
p.000056:
p.000056: 1. Ethical, Legal and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning (June 2002)
p.000056: Bioethics Advisory Committee
p.000056:
p.000056: 2. Human Tissue Research (November 2002) Bioethics Advisory Committee
p.000056:
...
General/Other / tri-council policy statement
Searching for indicator tri-council:
(return to top)
p.000056: 5. Operational Guidelines for Ethics Committees that Review Biomedical Research (20 00) World Health Organization
p.000056:
p.000056: 6. Proposed International Guidelines on Ethical Issues in Medical Genetics and Genetic Services (1998)
p.000056: World Health Organization
p.000056:
p.000056: 7. Universal Declaration on the Human Genome and Human Rights (1997) United Nations Educational, Scientific and
p.000056: Cultural Organization
p.000056:
p.000056:
p.000056: Singapore
p.000056:
p.000056: 1. Ethical, Legal and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning (June 2002)
p.000056: Bioethics Advisory Committee
p.000056:
p.000056: 2. Human Tissue Research (November 2002) Bioethics Advisory Committee
p.000056:
p.000056: 3. National Medical Ethics Committee: A Review of Activities, 1994-1997 (1998) National Medical Ethics Committee,
p.000056: Ministry of Health
p.000056:
p.000056: 4. Singapore Guideline for Good Clinical Practice (1998) Ministry of Health
p.000056:
p.000056:
p.000056:
p.000056: F-157
p.000056:
p.000056:
p.000056: ANNEXE F
p.000056:
p.000056:
p.000056:
p.000056: Other Countries
p.000056:
p.000056: 1. National Statement on Ethical Conduct in Research Involving Humans (1999) National Health and Medical Research
p.000056: Council, Australia
p.000056:
p.000056: 2. Human Research Ethics Handbook (2001)
p.000056: National Health and Medical Research Council, Australia
p.000056:
p.000056: 3. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (1998, with 2000, 2002, 2003 updates)
p.000056: Medical Research Council, Natural Sciences and Engineering Research Council, and Social
p.000056: Sciences and Humanities Research Council, Canada
p.000056:
p.000056: 4. Governance arrangements for NHS Research Ethics Committees (July 2001) Department of Health, United Kingdom
p.000056:
p.000056: 5. Research Governance Framework for Health and Social Care, 2nd edition draft (April 2003) Department of Health,
p.000056: United Kingdom
p.000056:
p.000056: 6. Code of Federal Regulations Title 45 Public Welfare – Part 46: Protection of Human Subjects (2001)
p.000056: Office for Protection from Research Risks, National Institutes of Health, Department of Health and Human Services,
p.000056: U.S.A.
p.000056:
p.000056: 7. Ethical and Policy Issues in Research Involving Human Participants (August 2001) National Bioethics Advisory
p.000056: Commissio n, U.S.A.
p.000056:
p.000056: 8. The Belmont Report (1979)
p.000056: National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, U.S.A.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: F-158
p.000056:
p.000056:
p.000056: ANNEXE G
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: LIST OF ABBREVIATIONS
p.000056:
...
Orphaned Trigger Words
p.000001:
p.000001:
p.000001: Members
p.000001:
p.000001: Mr Jeffrey Chan Wah Teck
p.000001: Principal Senior State Counsel (Civil), Attorney-General’s Chambers
p.000001:
p.000001: Mr Cheong Yip Seng
p.000001: Editor-in-Chief, English/Malay Newspapers Division, Singapore Press Holdings
p.000001:
p.000001: Associate Professor John Elliott
p.000001: Department of Social Work & Psychology, National University of Singapore
p.000001:
p.000001: Associate Professor Terry Kaan Sheung-Hung
p.000001: Faculty of Law, National University of Singapore
p.000001:
p.000001: Ms Lim Soo Hoon
p.000001: Permanent Secretary, Ministry of Community Development, Youth and Sports
p.000001:
p.000001: Professor Edison Liu
p.000001: Executive Director, Genome Institute of Singapore
p.000001:
p.000001: Mr Richard Magnus
p.000001: Senior District Judge, Subordinate Courts of Singapore
p.000001:
p.000001: Professor Ong Yong Yau
p.000001: Emeritus Consultant, Singapore General Hospital
p.000001:
p.000001: Professor Kandiah Satkunanantham
p.000001: Director of Medical Services, Ministry of Health
p.000001:
p.000001: Professor Tan Chorh Chuan
p.000001: Provost, National University of Singapore
p.000001:
p.000001: Mr Zainul Abidin Rasheed
p.000001: Mayor, North East Community Development Council
p.000001:
p.000001: About the Bioethics Advisory Committee
p.000001: The Bioethics Advisory Committee (BAC) was appointed by the Singapore Cabinet in December 2000. The BAC was directed
p.000001: to
p.000001: „examine the legal, ethical and social issues arising from research on human biology and behaviour and its
p.000001: applications“ and to
p.000001: „develop and recommend policies ... on legal, ethical and social issues, with the aim to protect the
...
p.000001: Declaration of Helsinki of 1964 and the International Conference on Harmonisation’s “Guideline for Good Clinical
p.000001: Practice” (ICH GCP Guideline) of 1996.
p.000001:
p.000001:
p.000001: Pharmaceutical Trials
p.000001:
p.000001: 3. In Singapore, pharmaceutical trials are currently governed under the Medicines Act and the
p.000001: Medicines (Clinical Trials) Regulations. All proposals for pharmaceutical trials are required to undergo an
p.000001: independent ethics review process and to comply with the “Singapore Guideline for Good Clinical Practice”
p.000001: (SGGCP), which is based on the ICH GCP Guideline.
p.000001:
p.000001: 4. This independent review is carried out first at the institutional level by the institution’s
p.000001: ethics committee or institutional review board (IRB). If approved, the proposal is then submitted to the Health
p.000001: Sciences Authority (HSA), which is the licensing body for pharmaceutical trials. Clinical Trial Certificates will be
p.000001: issued for proposals approved by the HSA.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: 1
p.000001:
p.000001:
p.000001: EXECUTIVE SUMMARY
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Human Biomedical Research other than Pharmaceutical Trials
p.000001:
p.000001: 5. Currently, there is no provision requiring human biomedical research other than pharmaceutical
...
p.000004: research involves interfering with the subjects’ medical management.
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005: EXECUTIVE SUMMARY
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: Institutions
p.000005:
p.000005: 31. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical
p.000005: Research carried out by their employees on their premises.
p.000005:
p.000005: 32. Every institution involved in Human Biomedica l Research as defined in these Guidelines should establish
p.000005: and maintain an effective IRB. The institution must accept legal responsibility for the decisions of its
p.000005: IRB. IRBs may be shared by more than one institution. They could also be domain specific, providing
p.000005: more focused and specialised ethics review.
p.000005:
p.000005: 33. Each institution must set up clear policies for the establishment and operation of its IRB. The institution
p.000005: will determine the composition and constitution of the IRB, the specific operating procedures for ethics review and
p.000005: categories of research for Exempted Review and Expedited Review.
p.000005:
p.000005: 34. Institutions are responsible for providing their IRB members with full indemnity.
p.000005:
p.000005: 35. Institutions, in particular those with sizeable research programmes, should have in place
p.000005: programmes for the training and education of their IRB members.
p.000005:
p.000005: 36. Institutions should, in consultation with their IRBs, ensure that clear formal procedures are
p.000005: laid down for the release of all kinds of patients’ medical information.
p.000005:
p.000005: 37. Institutions should also ensure that there are adequate resources to enable their IRBs to discharge their
p.000005: duties and responsibilities in an effective and timely manner.
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000006: 6
p.000006:
p.000006: INTRODUCTION AND CURRENT
p.000006: FRAMEWORK
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
p.000006:
...
p.000008: 2.1. In Singapore and other technologically advanced societies, advances in biomedical technology and
p.000008: knowledge have been the main foundation for the vast improvement in health, life expectancy and the quality
p.000008: of life of the general population. These advances represent some of the principal achievements in the modern
p.000008: history of the human race. In the main, such advances in biomedical knowledge have been beneficial and
p.000008: are considered to be research conducted in good faith for the benefit of humankind.
p.000008:
p.000008: 2.2. Events during World War II, however, gave rise to concerns that research conducted on human subjects should
p.000008: be subject to agreed ethical norms. The Nuremberg Code1 was born out of these concerns and represents the first
p.000008: universally accepted code spelling out the minimum content of the ethical norms governing the conduct of
p.000008: research on human subjects.
p.000008:
p.000008: 2.3. These ethical norms were given full consideration and description in the World Medical
p.000008: Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Huma n Subjects,2 which
p.000008: since its adoption by the 18th World Medical Association General Assembly at Helsinki, Finland, has become
p.000008: universally accepted as the core body of ethical norms governing human research.
p.000008:
p.000008: 2.4. The principal theme of the Helsinki Declaratio n is that the life, health, privacy and dignity of
p.000008: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000008: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000008: human subject and the need for rigorous scientific assessment of the risks to the human subject
p.000008: in relation to the benefit sought to be gained from the research.
p.000008:
p.000008: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000008: This provides that the “design and performance of
p.000008:
p.000008: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10, Vol.
p.000008: 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000008: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects
p.000008: adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most recently
p.000008: amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: INTRODUCTION AND CURRENT
p.000009: FRAMEWORK
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: each experimental procedure involving human subjects should be clearly formulated in an experimental protocol” and that
p.000009: this protocol should be submitted to an independent ethics review committee for “consideration, comment,
p.000009: guidance, and where appropriate, approval.”
p.000009:
p.000009: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000009: medical community in Singapore and by other medical communities in the great majority of nations. In
p.000009: Singapore, the need for ethics committees or IRBs and the requirement for the ethics review of research
p.000009: proposals involving human subjects have long been an accepted and integral part of biomedical research in the
p.000009: institutional setting.
p.000009:
p.000009: 2.7. The principle s of the Declaration of Helsinki today find expression in regulatory standards and
p.000009: practice guidelines governing various aspects of clinical research such as those contained in the Medicines (Clinical
p.000009: Trials) Regulations, promulgated pursuant to Section 74 of the Medicines Act (Cap. 176), the “Singapore
p.000009: Guideline for Good Clinical Practice” (SGGCP) and the “Ethical Guidelines on Research Involving Human
p.000009: Subjects” (NMEC Guidelines) issued in August 1997 by the National Medical Ethics Committee (NMEC).
p.000009: We discuss these regulatory standards and practice guidelines in detail below.
p.000009:
p.000009:
p.000009: Pharmaceutical Trials in Singapore
p.000009:
p.000009: 2.8. In Singapore, pharmaceutical trials involving the testing of drugs on human subjects are regulated by the
p.000009: Health Sciences Authority (HSA). The HSA regulates the conduct of pharmaceutical trials under the Medicines Act and the
p.000009: Medicines (Clinical Trials) Regulations (2000, Revised Edition). Under the Medicines Act, these
p.000009: pharmaceutical or drug trials are known as “clinical trials”.
p.000009:
p.000009: 2.9. The system of regulation requires that sponsors and researchers conducting pharmaceutical trials obtain
p.000009: both ethics and regulatory approval before initiating a study.
p.000009:
p.000009: 2.10. The current approval system is sequential. Approval from the HSA is sought only after the
p.000009: relevant hospital ethics committee has approved an application. Regulatory approval is provided in the form
p.000009: of a Clinical Trial Certificate issued by the HSA to the applicant.
p.000009:
p.000009: 2.11. The HSA, in deciding the regulatory approval for a pharmaceutical trial, consults an expert
p.000009: advisory committee known as the Medical Clinical Research Committee (MCRC). The MCRC is an
p.000009: “independent body constituted of medical members, whose responsibility is to ensure the
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: INTRODUCTION AND CURRENT
p.000010: FRAMEWORK
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: protection of the rights, safety and well- being of human subjects involved in a trial ... and documenting
p.000010: informed consent of the trial subjects” (Section 1.37 of the SGGCP). It currently comprises five members, all of
p.000010: whom are clinical specialists.
p.000010:
p.000010: 2.12. In this way, pharmaceutical trials are subject to ethics review at more than one level.
p.000010:
p.000010: 2.13. Additionally, pharmaceutical trials are also required to conform to the SGGCP issued by the MOH in
p.000010: 1998. The SGGCP is a set of guidelines adapted from the 1996 “Guideline for Good Clinical Practice” of the
p.000010: International Conference on Harmonisa tion of Technical Requirements for Registration of Pharmaceuticals for Human
p.000010: Use (ICH GCP Guideline), which is the international gold standard for conduct of pharmaceutical trials.
p.000010: Accordingly, the SGGCP reflects best international practice in its approach to the governance of
p.000010: pharmaceutical trials. Since 1998, the SGGCP has been incorporated by reference in Regulation 21 of the
p.000010: Medicines (Clinical Trials) Regulations. Sponsors and researchers in pharmaceutical trials are
p.000010: required by law to comply with the SGGCP unless specifically exempted under the Medicines (Clinical
p.000010: Trials) Regulations.
p.000010:
p.000010: 2.14. The SGGCP sets out in detail a framework for the ethics governance of pharmaceutical trials.
p.000010: The SGGCP begins its statement of applicable principles by declaring that “[c]linical trials should be
p.000010: conducted in accordance with the ethical principles that have their origin in the Declaration of
p.000010: Helsinki” (Section 2.1).
p.000010:
p.000010: 2.15. Section 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000010: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000010: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000010: investigational product(s), and/or to identify any adverse reactions to an investigational product(s),
p.000010: and/or to study absorption, distribution, metabolism, and excretion of an investigational product(s) with the
p.000010: object of ascertaining its safety and/or efficacy.”
p.000010:
p.000010: 2.16. The SGGCP sets out detailed guidelines as to the roles and duties of researche rs and sponsors
p.000010: in a pharmaceutical trial, and lays down requirements such as monitoring procedures, audits and other
p.000010: matters to be included in trial protocols.
p.000010:
p.000010: 2.17. Of note are the provisions in Part 3 of the SGGCP requiring all pharmaceutical trials
p.000010: to be re viewed and approved by the hospital ethics committees concerned and the MCRC of the HSA before a Clinical
p.000010: Trial
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011: INTRODUCTION AND CURRENT
p.000011: FRAMEWORK
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: Certificate will be issued. The responsibilities, composition, functions and operations of the MCRC are set out in
p.000011: detail in Section 3.1 of the SGGCP, while those of the ethics committee are detailed in Section 3.2.
p.000011:
p.000011: 2.18. In keeping with the principles of the Declaration of Helsinki, the Medicines (Clinical
p.000011: Trials) Regulations require researchers to ensure that free and informed consent be obtained from the potential
p.000011: research subject and that researchers are under a duty to fully inform the subject by explaining, among
p.000011: other issues, the risks and objectives of the proposed pharmaceutical trial.
p.000011:
p.000011:
p.000011: Human Biomedical Research other than Pharmaceutical Trials
p.000011:
p.000011: The Ethics Governance of Human Biomedical Research other than Pharmaceutical Trials
p.000011:
p.000011: 2.19. While the ethics governance of pharmaceutical trials in Singapore is comprehensively and
p.000011: appropriately regulated by statutory rules and practice guidelines, the picture for the ethics
p.000011: governance of human biomedical research other than pharmaceutical trials is less clear.
p.000011:
p.000011: 2.20. Currently, there is no statutory scheme for the ethics governance of human biomedical research apart from
p.000011: pharmaceutical trials. In Section III, we define and explain “Human Biomedical Research”.
p.000011:
p.000011: 2.21. Indirectly, however, the MOH has long exercised jurisdiction over, and given informal ethical
p.000011: guidance on, human biomedical research carried out in hospitals, clinics and clinical laboratories in its role
p.000011: as the statutory regulator under the Private Hospitals and Medical Clinics Act.
p.000011:
p.000011: 2.22. In January 1994, the MOH set up the NMEC, a national- level policy advisory body, to “assist
p.000011: the medical profession in addressing ethical issues in medical practice and to ens ure a high standard of ethical
p.000011: practice in Singapore.”3
p.000011: 2.23. One of the objectives of establishing the NMEC was to “identify and study ethical issues relating to medical
p.000011: practice and research in Singapore and to provide an ethical framework for medical practit ioners to carry out
p.000011: their duties and responsibilities.”4
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: 3 “National Medical Ethics Committee: A Review of Activities, 1994-1997” published in 1998 , page 1
p.000011: 4 Ibid.
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000012: 12
p.000012:
p.000012: INTRODUCTION AND CURRENT
p.000012: FRAMEWORK
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: 2.24. Several sets of ethics guidelines were issued by the NMEC and adopted by the MOH. In the sphere of
p.000012: ethics governance of human biomedical research, the most significant of these ethics guidelines is the
p.000012: NMEC Guidelines.
p.000012:
p.000012: 2.25. In a written directive dated 25 June 1998 (Directive), the MOH required all government and restructured
p.000012: hospitals to set up hospital ethics committees (if they had not already done so) for the ethics governance
p.000012: of research involving human subjects. Before 1998, the practice of reviewing research proposals involving human
p.000012: subjects by hospital and medical institution ethics committees in Singapore was not governed by any
p.000012: formal rules or directives.
p.000012:
p.000012: 2.26. We quote from the Directive:
p.000012:
p.000012: “The National Medical Ethics Committee has recommended that:
p.000012:
p.000012: (i) hospital ethics committees vet for ethical considerations, all research protocols that involve
p.000012: • human experimentation be they clinical trials or drug trials, trials of new medical devices, new procedures
p.000012: and any other forms of clinical studies that require the participation of human subjects or the use of human tissues
p.000012: and organs
p.000012: ...
p.000012: (ii) a senior nursing representative be included as a member of hospital ethics committee.
p.000012:
p.000012: The Ministry has accepted these recommendations.”
p.000012:
p.000012: 2.27. The NMEC Guidelines set out in detail suggested principles of the ethics governance of research involving
p.000012: human subjects, the constitution of ethics committees and the implementation of the framework for the ethics
p.000012: governance of biomedical research. These NMEC Guidelines represent the principal controlling document governing
p.000012: research involving human subjects in Singapore today, but despite this they remain non-directive in
p.000012: nature.
p.000012:
p.000012: 2.28. In developing the Guidelines, the NMEC drew exte nsively from similar guidelines published in other
p.000012: technologically advanced countries, notably those issued by the Canadian Medical Research Council and the
p.000012: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with internationally
p.000012: accepted approaches to, and norms of, ethics governance of biomedical research involving human subjects at that
p.000012: time.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: INTRODUCTION AND CURRENT
p.000013: FRAMEWORK
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: 2.29. We have reviewed the NMEC Guidelines and have no hesitation in using them as a basic framework for these
p.000013: BAC Guidelines. Although the NMEC Guidelines were formulated in the restricted context of research
p.000013: carried out by the medical profession, we are of the view that the principles they espouse are
p.000013: appropriate for all human biomedical research, whether such research is carried out by the medical profession
p.000013: or by others. We also take the view that the same principles should apply to all human biomedical research wherever
p.000013: such research may be carried out in Singapore, and whether or not such research is carried out in an institution under
p.000013: the direct jurisdiction of the MOH pursuant to the Private Hospitals and Medical Clinics Act.
p.000013:
p.000013: The Future of Human Biomedical Research
p.000013:
p.000013: 2.30. Until recently, the vast majority of human biomedical research (whether pharmaceutical trials or
p.000013: research other than pharmaceutical trials) were carried out by researchers who were medical practitioners
p.000013: registered under the Medical Registration Act (Cap. 174), in government medical institutions directly
p.000013: controlled by the MOH or in hospitals and medical clinics licensed under the Private Hospitals and Medical
p.000013: Clinics Act. In all of these cases, the competent supervisory authority was the MOH.
p.000013:
p.000013: 2.31. In recent years, however, the development of the biomedical industry in Singapore has led to
p.000013: an increasing proportion of human biomedical research other than pharmaceutical trials. In 2002, for
p.000013: example, hospital ethics committees of the five main restructured hospitals reviewed nearly three times as many
p.000013: applications for such research as they did for pharmaceutical trials.
p.000013:
p.000013: 2.32. Human biomedical research increasingly tends to be institution-driven, rather than being
p.000013: researcher-driven (the traditional model assumed in the current regulatory regime). Institution-driven
p.000013: pharmaceutical trials received by the HSA now outnumber researcher-driven pharmaceutical trials.
p.000013:
p.000013: 2.33. Concomitantly, an increasing proportion of human biomedical research is now conducted outside the
p.000013: traditional paradigm assumed by the current regulatory environment: many research projects are now led by
p.000013: researchers who, although being qualified and competent for the research proposed by them, are not medical
p.000013: practitioners registered under the Medical Registration Act, or by researchers who work in or for entities not
p.000013: subject to the regulatory jurisdiction of the MOH. Such entit ies include companies and other
p.000013: commercial entities in the biomedical industry, research institutes and statutory agencies with an interest
p.000013: in the biomedical industry.
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: INTRODUCTION AND CURRENT
p.000014: FRAMEWORK
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014: 2.34. The vast majority of these new players in the field of human biomedical research in Singapore
p.000014: are keenly aware of the need for proper ethics governance. Most researchers are anxious to conform to
p.000014: internationally accepted standards for ethics governance. In many cases, researchers are involved as
p.000014: collaborators in multinational or multi-centre (or both) biomedical research projects.
p.000014:
p.000014: 2.35. With the development of the biomedical sector in Singapore, new avenues of biomedical inquiry are rapidly
p.000014: emerging. The traditional categorisation of research for ethics governance, which separates research
p.000014: into pharmaceutical trials and non-pharmaceutical trials, is becoming irrelevant and obsolete. Some new kinds of
p.000014: research may blur the border between these two categories. New kinds of biomedical research include trials of medical
p.000014: devices, experimental therapeutic procedures (which may or may not involve drugs), new modes of non-drug treatment and
p.000014: new diagnostic methods. Other increasingly important research includes epidemiological or population studies
p.000014: (which may or may not require invasive interaction with human subjects), genetic screening, genetic research and
p.000014: research that involves no direct interaction with human subjects but only access to their medical, personal or genetic
p.000014: information.
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000015: 15
p.000015:
p.000015: HUMAN
p.000015: BIOMEDICAL RESEARCH
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: PART B: HUMAN BIOMEDICAL RESEARCH
p.000015: SECTION III: HUMAN BIOMEDICAL RESEARCH
p.000015:
p.000015: 3. Human Biomedical Research Defining Human Biomedical Research
p.000015: 3.1. In this section, we consider what kinds of human biomedical research ought to be subject to
p.000015: the framework of ethics go vernance that we recommend in these Guidelines.
p.000015:
p.000015: 3.2. In keeping with our terms of reference, we consider only such human biomedical research that
p.000015: involves an interaction (whether direct or otherwise) with a human subject or human biological
p.000015: material, and therefore exclude any human biomedical research in relation to:
p.000015:
p.000015: (a) Genetically modified organisms;
p.000015: (b) Animals and their treatment; and
p.000015: (c) Economic, sociological and other studies in the disciplines of the humanities and social sciences.
p.000015:
p.000015: 3.3. Human biomedical research is a term capable of a very broad definition. In our review of the approaches
p.000015: taken by national ethics bodies or agencies in other countries, we have found that there is considerable
p.000015: variation in what is to be included in the definition of human biomedical research coming within the
p.000015: purview of institutional ethics review bodies. For example, in some jurisdictions, ethics committees are
p.000015: required to review proposals for sociological research or humanities-based research if they involve human
p.000015: subjects, while in other jurisdictions this requirement does not apply.
p.000015:
p.000015: 3.4. Currently, there is no international agreement on the exact scope of human biomedical research that should be
p.000015: subject to IRB review. But that is not to say that there is no agreement at all on what should be subject
p.000015: to IRB review. Clearly, there is universal and unanimous agreement in all reputable research
p.000015: communities that research involving direct physical interference or interaction with human subjects, and
p.000015: where such direct physical interference or interaction may result in death, injury or other physical or
p.000015: emotional harm to the research subject, must be subject to proper IRB review. These core values and
p.000015: principles are captured in international documents such as the Nuremberg Code, the Declaration of Helsinki and the
p.000015: ICH GCP Guideline.
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000016: 16
p.000016:
p.000016: HUMAN
p.000016: BIOMEDICAL RESEARCH
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: 3.5. At the edge of this core of certainty, however, international consensus is still in a state of
p.000016: development. Increasingly, human experimentation and human biomedical research have moved away from
p.000016: direct physical interference or interaction with human subjects themselves, towards research conducted
p.000016: largely on cell lines, tissues or other bodily samples given by human donors, and on medical information
p.000016: derived from patients and other human subjects.
p.000016:
p.000016: 3.6. Increasingly, it is the case that there is no direct physical contact at all between the
p.000016: researchers and the human subjects. In such circumstances, there is no possibility of physical injury or harm
p.000016: befalling the human research subjects. In these situations, the ethical, le gal and social concerns centre not on
p.000016: the possibility of physical injury or harm but on the larger penumbra of indirect harms to the patient or
p.000016: donor such as the breach of the patient’s or donor’s expectation of confidentiality of his medical
p.000016: information, or his expectation that his tissue should not be used for research without his consent.
p.000016:
p.000016: 3.7. It is therefore appropriate that a fundamental distinction be made between:
p.000016:
p.000016: (a) Direct Human Biomedical Research. This comprises any kind of human biomedical research that
p.000016: involves any direct interference or interaction with the physical body of a human subject, and that
p.000016: involves a concomitant risk of physical injury or harm, however remote or minor. A research
p.000016: programme which involves the administration of any drug (whether it is for the purpose of testing the
p.000016: effects or efficacy of the drug, or whether it is a means for establishing any other objective of the
p.000016: research programme), the trial or use of a medical device on a human subject, or any test of a human subject’s
p.000016: physiological, emotional or mental responses (not being tests conducted for diagnostic purposes with a view to
p.000016: the therapeutic management of a patient) all qualify as Direct Human Biomedical Research; and
p.000016:
p.000016: (b) Indirect Human Biomedical Research. This comprises any research (not qualifying as Direct Human
p.000016: Biomedical Research) involving human subjects, human tissue, or medical, personal or genetic
p.000016: information relating to both identifiable and anonymous individuals, undertaken with a view to generating data about
p.000016: medical, genetic or biological processes, diseases or conditions in human subjects, or of human physiology or about the
p.000016: safety, efficacy, effect or function of any device, drug, diagnostic, surgical or therapeutic procedure
p.000016: (whether invasive, observational or otherwise) in human subjects whether as one of the objectives or the sole
p.000016: objective, of the research study, trial or activity, and which research, study, trial or activity has
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000017: 17
p.000017:
p.000017: HUMAN
p.000017: BIOMEDICAL RESEARCH
p.000017:
p.000017:
p.000017:
p.000017:
p.000017:
p.000017: the potential to affect the safety, health, welfare, dignity or privacy of the human subjects involved in the study, or
p.000017: of the donors of human tissue or information used in the research, or of the family members of any of the human
p.000017: subjects or donors thereof, or to which such medical, personal or genetic information relates.
p.000017:
...
p.000018: patients’ consent for procedures and interventions in clinical management have been obtained and the patients’ privacy
p.000018: protected, for example, the review of a clinical programme that includes demographic, clinical and
p.000018: outcome parameters, which are useful in the audit of the programme; or the review of a procedure or
p.000018: treatment (a surgical technique or drug treatment outcome) by a physician or surgeon, where the choice of the
p.000018: drug or technique is based on the clinical judgment of the physician or surgeon and on best
p.000018: practices and not on any randomisation procedure. Researchers who are not the attending physicians in
p.000018: the programme but wish to have access to such information should send their proposals to the IRB in
p.000018: the usual way;
p.000018:
p.000018: (b) Research using appropriately designed data escrow or other arrangements in which personal or
p.000018: other identity information is securely withheld from researchers by a third party provider of information,
p.000018: there being no possibility of researchers by themselves being able to trace or reconstruct significant
p.000018: information on the identity of subject donor;
p.000018:
p.000018: (c) Research using established commercially available cell lines or commercially available anonymous
p.000018: DNAs, RNAs and fixed tissues; and
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019: HUMAN
p.000019: BIOMEDICAL RESEARCH
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: (d) The development of diagnostic tests using existing samples for test validation purposes provided
p.000019: that the necessary consent for the taking and use of the samples has been obtained.
p.000019:
p.000019: Expedited Review
p.000019:
p.000019: 3.16. Some categories of research programmes may be permitted a less formal process of review than that of a
p.000019: standard full review. For example, the Chairperson or other IRB delegate(s) (the reviewer) may be empowered to
p.000019: conduct Expedited Review.
p.000019:
p.000019: 3.17. The same principles and general considerations set out above in relation to the categories of Human Biomedical
p.000019: Research that qualifies for Exempted Review also apply to IRBs’ determination of categories permitted
p.000019: Expedited Review. Research qualifying for Expedited Review should present no more than minimal risks to research
p.000019: subjects.
p.000019:
p.000019: 3.18. By way of illustration, the following categories of Human Biomedical Research could be considered
p.000019: for Expedited Review, taking into account current practice:
p.000019:
p.000019: (a) Minor changes to previously approved research;
p.000019:
p.000019: (b) Annual reviews of previously approved research in which there has been little or no change in the on- going
p.000019: research;
p.000019:
p.000019: (c) The analysis of patients’ information without interacting with the patients. Researchers may be
p.000019: allowed access to medical records only if the IRB is satisfied that there is potential scientific / medical
p.000019: benefit of the research and that the researchers will take appropriate measures to protect the privacy of the
p.000019: individuals;
p.000019:
p.000019: (d) The local portion (at the level of specific institutions) of a multi- centre or multinational researc
p.000019: h programme that has already received a full review and approval by the lead IRB (as elaborated
p.000019: in paragraphs 5.49 to 5.56 of this Report); and
p.000019:
p.000019: (e) Research involving human tissues from tissue banks. IRBs must be satisfied that the tissues are obtained from
p.000019: a reliable source in which consent has been obtained for the tissues to be used for research and that the donor's
p.000019: privacy is protected.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: HUMAN
p.000020: BIOMEDICAL RESEARCH
p.000020:
p.000020:
p.000020:
p.000020:
p.000020:
p.000020: Stem Cell Lines
p.000020:
p.000020: 3.19. We make clear that all research involving the use of human embryonic stem cell lines or the creatio
p.000020: n of such human stem cell lines requires full ethics review.
p.000020:
p.000020:
p.000020: Cadaveric, Foetal and Legacy Tissues
p.000020:
p.000020: 3.20. We reiterate that nothing in these Guidelines is intended to displace the recommendations we
p.000020: advance in our Human Tissue Research Report. We take the view that human biomedical research to be conducted on
p.000020: legacy tissue as defined in our Human Tissue Research Report should always be subject to full review. In the
p.000020: case of other tissues donated with the free and informed consent of living donors, or of cadave ric or
p.000020: foetal tissue donated under the Medical (Therapy, Education and Research) Act, review should be considered, but
p.000020: Expedited Review may be allowed as appropriate, provided always that the use of the tissue concerned is
p.000020: within the terms of the gift of the tissue.
p.000020:
p.000020:
p.000020: Therapy versus Research
p.000020:
p.000020: 3.21. In Section 2.2.1 of the NMEC Guidelines, it is stated that:
p.000020:
p.000020: “Human research can be broadly defined as studies which generate data about human subjects which go beyond what is
p.000020: needed for the individual’s well-being. The primary purpose of research activity is the generation of new information
p.000020: or the testing of a hypothesis. The fact that some benefit may result from the activity does not alter its
p.000020: status as “research”. Defined in this manner, human research includes not only studies which involve human
p.000020: subjects directly, but also epidemiological surveys and reviews of patient records, for purposes not
...
p.000022: are satisfied. We have in mind situations of national security or emergency health situations, in which
p.000022: urgent research may have to be carried out to avert harm to national security or for the urgent protection
p.000022: or treatment of whole populations at risk. In such cases, it should be permissible for IRBs in consultation with the
p.000022: proper authorities such as the MOH, to formulate and lay down written guidelines for the exemption or expedited
p.000022: review of defined classes or types of such emergency or urgent research in the national interest.
p.000022:
p.000022: 3.29. We also exclude from ethics review procedures and requirements all clinical audit and quality
p.000022: assurance activities, which require the institution to review patients' information and are conducted for the sole
p.000022: purpose of improving the quality of patient care within that institution.
p.000022:
p.000022: 3.30. We therefore recommend that all Human Biomedical Research as defined in this section, save for the
p.000022: exceptions expressly provided above, be subject to review and approval by and to the continued supervision of an
p.000022: IRB in accordance with the principles discussed in Section IV.
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023:
p.000023: ETHICS GOVERNANCE
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: PART C: ETHICS GOVERNANCE
p.000023:
p.000023: SECTION IV: PRINCIPLES OF ETHICS GOVERNANCE
p.000023:
p.000023: 4. Principles of Ethics Governance The Purpose of Ethics Governance
p.000023: 4.1. Article 5 of the Helsinki Declaration states: "In medical research on human subjects, considerations
p.000023: related to the well-being of the human subject should take precedence over the interests of science and
p.000023: society.” Article 8 of the Declaration states: “Medical research is subject to ethical standards that promote respect
p.000023: for all human beings and protect their health and rights.”
p.000023:
p.000023: 4.2. Continuing human biomedical research is fundamental to improving our understanding of biological
p.000023: processes, and ultimately to the improvement of the health and welfare of humankind. Whereas diagnostic, prophylactic
p.000023: and therapeutic research have as their objective the immediate needs of individual patients, Human
p.000023: Biomedical Research has wider and longer- term objectives in the discovery of new knowledge that may
p.000023: lead to an improvement in the methods of diagnosis, prophylaxis and therapy of individuals, and to the
p.000023: health and welfare of society in general.
p.000023:
p.000023: 4.3. The experience of physicians in the management of patients often leads to new scientific insights,
p.000023: which when coupled with continuing human biomedical research leads to a virtuous circle that supports
p.000023: and advances biomedical knowledge to the benefit of both individuals and society at large. Article 4 of
p.000023: the Helsinki Declaration states: “Medical progress is based on research which ultimately must rest in
p.000023: part on experimentation involving human subjects.”
p.000023:
p.000023:
p.000023: Applicable Principles
p.000023:
p.000023: 4.4. The fundamental objective of having a system of ethics governance in relation to biomedical
p.000023: research is to ensure the protection and assurance of the safety, health, dignity, welfare and privacy of human
p.000023: research subjects and to safeguard against research practices and objectives that are not ethically
p.000023: acceptable to society at that point in time.
p.000023:
p.000023: 4.5. But as with most kinds of diagnostic, prophylactic or therapeutic interventions, most
p.000023: forms of human biomedical research unavoidably
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024:
p.000024: ETHICS GOVERNANCE
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000024: involve some degree of risk of harm (however minimal or remote) to the human subject.
p.000024:
p.000024: 4.6. Ethical assessment and judgment therefore necessarily involve an assessment and balancing of
p.000024: the potential harms and benefits. In general, human biomedical research should be directed towards the minimisation
p.000024: of risks and the maximisation of benefits, always bearing in mind the overriding considerations of
p.000024: the safety, health, dignity, welfare and privacy of the human subject and the ethical standards of society at
p.000024: that point in time.
p.000024:
p.000024: 4.7. To this end, a system of ethics governance must ensure that there is a proper assessment and
p.000024: weighing of the potential harms against the potential benefits of all human biomedical research, in
p.000024: accordance with the ethical values of the community. A proper system of ethics governance serves to strengthen
p.000024: public confidence in human biomedical research by ensuring that all forms of human biomedical research conform
p.000024: to the accepted body of ethical values of the community.
p.000024:
p.000024: 4.8. These fundamental ethical values are expressed and repeated in international
p.000024: documents such as the Declaration of Helsinki, the Nuremberg Code, the Belmont Report (“Ethical
p.000024: Principles and Guidelines for the Protection of Human Subjects of Research”, 1976), the UNESCO’s “Universal Declaration
p.000024: on the Human Genome and Human Rights” (1997) and the WHO’s “Proposed International Guidelines on Ethical Issues
p.000024: in Medical Genetics and Genetic Services” (1998).
p.000024:
p.000024: 4.9. In Singapore, these same principles are found or reflected in regulatio ns such as the Medicines
p.000024: (Clinical Trials) Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already
p.000024: addressed some of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000024:
p.000024: 4.10. These core principles are expressed, restated and elaborated upon in many ways. For example, the NMEC
p.000024: expresses some of these fundamental principles as follows:
p.000024:
p.000024: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000024: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000024: risks of participating in research. Justice relates to the fair distribution of risks in research in relation
p.000024: to the anticipated benefits for research subjects. Autonomy refers to the right of individuals to decide for
p.000024: themselves what is good for them.
p.000024:
p.000024:
p.000024:
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025:
p.000025: ETHICS GOVERNANCE
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: 2.3.2 With respect to beneficence, the benefits and risks of research must always be carefully assessed.
p.000025: Research on human subjects should only be undertaken if the potential benefits arising from the expected new
p.000025: knowledge are of sufficient importance to outweigh any risk or harm inherent in the research, bearing in mind that
p.000025: risks and benefits may not be measurable on the same scale.
p.000025:
p.000025: 2.3.3 …Justice must be exercised in the allocation of the anticipated risks and the anticipated benefits…
p.000025:
p.000025: 2.3.4 A corollary of autonomy is that any research procedure must have, as far as possible, the
p.000025: free and informed consent of the experimental subject. Similarly, respect for the individual implies
p.000025: that safeguards should be provided to protect the experimental subject from physical and
p.000025: emotional harm including provisions for confidentiality.”
p.000025:
p.000025: 4.11. Despite some uncertainty at the edges, a core of universally accepted principles and ethical
p.000025: values lie at the heart of most societies in their application to the protection of human research subjects.
p.000025:
p.000025: 4.12. In the interests of consistency and fairness of the judgments of IRBs, a code of applicable
p.000025: principles for ethics governance should eventually be formulated for the common guidance of IRBs,
p.000025: research institutions, researchers, the human research subjects and all other parties involved in human research.
p.000025:
p.000025: 4.13. We do not attempt, and it is beyond the scope of this document to attempt, to list all these fundamental
p.000025: principles. In our view, the applicable principles of the proposed code are best settled in an
p.000025: incremental and evolutionary manner through dialogue and discussion between IRBs and the other parties in
p.000025: the research governance process. This process of dialogue and discussion should be informed by and have
p.000025: reference to the experiences of the parties involved.
p.000025:
p.000025: 4.14. We take the view that it is part of the function of a responsive and dynamic system of ethics governance that
p.000025: the applicable body of ethics be reviewed and assessed from time to time to keep it relevant to and
p.000025: reflective of community values and the needs of research.
p.000025:
p.000025: 4.15. We emphasise that it is not the intention of this document to prescribe the specific ethical principles to
p.000025: be applied by IRBs and researchers in the process of ethics governance. We believe that these are
p.000025: professional
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026:
p.000026: ETHICS GOVERNANCE
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: judgments that are appropriately and properly left to members of IRBs, researchers and other parties involved
p.000026: in the process of ethics governance.
p.000026:
p.000026: 4.16. We note, however, that certain broad ethical principles are universally accepted and applied in
p.000026: all the leading research jurisdictions. We find it appropriate and desirable for IRBs, researchers and other
p.000026: parties involved in the process of ethics governance to consider taking these ethical principles into
p.000026: account.
p.000026:
p.000026: 4.17. Such principles, in addition to or in elaboration of those identified by the NMEC, include:
p.000026:
p.000026: (a) Respect for the human body, welfare and safety, and for religious and cultural perspectives and
p.000026: traditions of human subjects. We elaborated on this principle in our Human Tissue Research Report. In the
p.000026: context of a diverse society such as Singapore, researchers have an especial obligation to be sensitive
p.000026: to religious and cultural perspectives and traditions of their human subjects.
p.000026:
p.000026: (b) Respect for free and informed consent. This principle is discussed at length in our Human Stem Cell Report, our
p.000026: Human Tissue Research Report and the NMEC Report (Section 2.5). In addition, the Medicines (Clinical
p.000026: Trials) Regulations and the SGGCP recommend strict requirements regarding consent.
p.000026:
p.000026: (c) Respect for privacy and confidentiality. This is treated in detail in Section 2.6 of the NMEC Guidelines
p.000026: and again in our Human Tissue Research Report.
p.000026:
p.000026: (d) Respect for vulnerable persons. This is discussed in Sections 2.5.5 and 2.5.6 of the NMEC
p.000026: Guidelines. In essence, the ethics governance process must pay especial attention to the protection of
p.000026: persons who may not be competent to give consent themselves, or whose ability to give free and full consent
p.000026: may be compromised by physical conditions or other circumstances, such as being in a dependent
p.000026: relationship.
p.000026:
p.000026: (e) Avoidance of conflicts of interest or the appearance of conflicts of interest. We further elaborate on
p.000026: this principle below in our discussion of the roles and responsibilities of researchers and IRBs.
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027:
p.000027: ETHICS GOVERNANCE
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: SECTION V: INSTITUTIONAL REVIEW BOARDS
p.000027:
p.000027: 5. Institutional Review Boards The Role of Institutional Review Boards
p.000027: 5.1. Ethics review bodies having the first responsibility for ethics review in the ethics review and governance
p.000027: process are variously known as “ethics committees”, “research ethics committees” or “institutional
p.000027: review boards”. In the context of Singapore, the term “ethics committees” is most commonly used.
p.000027:
p.000027: 5.2. We prefer instead the term “Institutional Review Board” (IRB). Our main reason for doing so is
p.000027: our desire to see institutional review boards established as full- time permanent supervisory bodies
p.000027: organised at and integral to the function of the highest administrative level in all institut ions in which research
p.000027: is carried out. For instance, we think that institutional review boards in hospitals should be organised at
p.000027: the same level as medical boards, and that the institutional review board should report directly to the
p.000027: highest level of management of the hospital. We believe that the term “institutional review board” best reflects
p.000027: this role.
p.000027:
p.000027: 5.3. We differentiate here between IRBs that review, approve and supervise biomedical research involving
p.000027: humans, and hospital ethics committees that address issues arising out of clinical practice (clinical practice
p.000027: ethics committees). For the avoidance of doubt, we make clear that our recommendations in these
p.000027: Guidelines cover only IRBs that review, approve and supervise Human Biomedical Research, and are no t
p.000027: intended to apply to clinical practice ethics committees.
p.000027:
p.000027: 5.4. We further clarify that the term "institution" is not limited to hospitals or medical clinics, but also
p.000027: includes any organisation or entity that carries out Human Biomedical Research as defined in these Guidelines. This
p.000027: includes commercial entities and government agencies.
p.000027:
p.000027: 5.5. We recognise that valuable Human Biomedical Research is also carried out by biomedical
p.000027: researchers who have no formal affiliation with IRB- guided institutions. Such biomedical
p.000027: researchers include medical practitioners in private practice (such as specialist consultants and general
p.000027: practitioners), and biomedical researchers who are employed by or who are affiliated with institutions that do not have
p.000027: and do not propose to constit ute an IRB because of the low volume of Human Biomedical Research carried out by their
p.000027: employees or affiliates. In the case of registered medical practitioners and specialists in private practice,
p.000027: we suggest that they seek ethics approval for the conduct of their proposed research from the IRBs of
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028:
p.000028: ETHICS GOVERNANCE
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028: appropriate hospitals or other medical institutions. This approach could also be applied to biomedical
p.000028: researchers who are not registered medical practitioners. In any event, the requirements for appropriate ethics
p.000028: review as defined in these guidelines should apply regardless of the institutional affiliation of researchers.
p.000028:
p.000028: 5.6. There is universal agreement in all developed countries that IRBs are central to a proper framework
p.000028: of ethics governance of human research and that the primary objective of an IRB is to protect and assure
p.000028: the safety, health, dignity, welfare and well-being of human research subjects, in keeping with the
p.000028: principles outlined above.
p.000028:
p.000028: 5.7. Increasingly, collaborative research programmes are carried out across international borders (in
p.000028: multinational research programmes) or by researchers in several institutions (in multi-centre research
p.000028: programmes), or even a combination of both. It is usually a condition of such research programmes that the
p.000028: proposed or prospective researchers secure the approval of a properly constituted IRB in their own country or
p.000028: institution. Without a properly constituted IRB or access to such an IRB, an institution engaging in human
p.000028: research cannot hope to participate in such multinational or multi-centre collaboration research
p.000028: programmes.
p.000028:
p.000028: 5.8. From this viewpoint, the harmonisation of our national ethics governance framework with that in
p.000028: leading research jurisdictions is of national strategic importance.
p.000028:
p.000028: 5.9. The ultimate responsibility fo r the ethics compliance of human biomedical research rests with the
p.000028: researchers who carry out the research, and with the institution that sanctions the research or in which research is
p.000028: carried out.
p.000028:
p.000028: 5.10. The IRB is the vehicle through which such institutions ac t to implement a proper system of ethics
p.000028: governance of research carried out in such institutions.
p.000028:
p.000028: 5.11. We accordingly recommend that every institution that conducts Human Biomedical Research, or allows
p.000028: such research to be carried out on its premises, or on its patients, or involving access to or use of human
p.000028: tissue collections in its custody, or involving access to or use of medical records or other personal information in
p.000028: its custody, should establish and maintain an effective IRB.
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029:
p.000029: ETHICS GOVERNANCE
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: Shared and Domain Institutional Review Boards
p.000029:
p.000029: 5.12. Where by reason of the small size of the institution or the small number of research proposals it is
p.000029: impractical to establish and maintain a standing IRB of its own, such institutions should make clear
p.000029: arrangements with other institutions which maintain IRBs for research proposals to be considered by
p.000029: the IRBs of larger institutions.
p.000029:
p.000029: 5.13. Alternatively, it is permissible for several such institutions to jointly appoint a shared IRB.
p.000029:
p.000029: 5.14. Even in cases of institutions that already have their own IRBs, these institutions may prefer or
p.000029: wish to refer some kinds of research applications (for example, a proposal for research in a specialist area)
p.000029: to a specialist IRB or a domain IRB that has the technical capacity to assess research in that specialised area.
p.000029: Again, several institutions could jointly appoint and share in the expertise of such an IRB in situations where such
p.000029: expertise is limited. Such a specialist IRB has the advantage of delivering consistent decisions, special
p.000029: competence and knowled ge in their field of specialisation.
p.000029:
p.000029: 5.15. We note that some hospitals and institutions in Singapore have set up domain specific IRBs with
p.000029: the intention of providing more focused and specialised ethics review. For example, sister or subsidiary
p.000029: institutions under the direction and control of a parent institution may choose to organise IRBs along
p.000029: domain lines, which can be shared by all the related institutions within the group. Such an arrangement is acceptable
p.000029: to us, as it is entirely in keeping with the ethical principles we have set out. Under this arrangement, the
p.000029: parent institution for all the hospitals and other institutions within the group will be responsible
p.000029: for constituting the necessary IRBs for all its constituent institutions and arranging for the
p.000029: accreditation of the IRBs.
p.000029:
p.000029: 5.16. We have no objections to other groups of research institutions adopting such a similar approach,
p.000029: provided that the terms of the arrangement between the institutions are clearly spelt out.
p.000029:
p.000029: 5.17. We therefore recommend that related institutions under the direction and control of a parent institution
p.000029: should be permitted to share an IRB or IRBs constituted by the parent institution.
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000030: 30
p.000030:
p.000030:
p.000030: ETHICS GOVERNANCE
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: The Responsibilities of Institutional Review Boards
p.000030:
p.000030: 5.18. In its acts and decisions, and in the exercise and discharge of its duties and responsibilities, an IRB acts
p.000030: on the behalf of the institution that appoints it and exercises on its behalf the authority and powers of
p.000030: that institution in matters within the terms of reference of the IRB.
p.000030:
p.000030: 5.19. Accordingly, we emphasise that the institution is responsible for the acts and decisions of the
p.000030: IRB(s) that it appoints.
p.000030:
p.000030: 5.20. Ethics Review Gateway. The fundamental responsibility of an IRB is to act as an ethics review gateway
p.000030: for all Human Biomedical Research carried out under the auspices of its appointing institution, with the
p.000030: primary objectives of the protection and assurance of the safety, health, dignity, welfare and well-being of
p.000030: human research subjects. An IRB has a duty to ensure that all Human Biomedical Research carried out under the auspices
p.000030: of its appointing institution are ethically acceptable, and to comply with the principles outlined in Section
p.000030: IV.
p.000030:
p.000030: 5.21. Review of Scientific Merits. A review of the scientific merits of any proposed programme of Human
p.000030: Biomedical Re search is an integral part of a proper assessment of the ethical acceptability of the programme.
p.000030: A research programme with little or no scientific merit is ethically unacceptable.
p.000030:
p.000030: 5.22. In its assessment of the ethical acceptability of any proposed research programme, an IRB will need
p.000030: to be satisfied that an objective review of the scientific merits of the proposed programme of research has been
p.000030: carried out, and that there is sufficient evidence of scientific merit before the IRB makes a decision on the
p.000030: ethical acceptability of the proposed research programme.
p.000030:
p.000030: 5.23. The IRB is not responsible for carrying out the scientific review of research proposals. It is for the
p.000030: researchers to satisfy the IRB that an objective review of scientific merit has been carried out, and
p.000030: that the findings (whether positive or negative) of any review of scientific merit are made available and are fully
p.000030: disclosed to the IRB.
p.000030:
p.000030: 5.24. The review of scientific merits may be carried out by such committees, bodies or agencies as
p.000030: the IRB may in its judgment recognise as appropriate. Thus such reviews may be carried out by a
p.000030: scientific review committee constituted by the appointing institution or by the funding agency.
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031:
p.000031: ETHICS GOVERNANCE
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: 5.25. We note that it is an accepted practice for the initial scientific review to be carried out by or for the
p.000031: agency that funds the research. When the grant funding agency is satisfied with the scientific merits of the
p.000031: proposed programme of research, it then gives in-principle approval on the condition (among others) that ethics
p.000031: approval is granted by the appropriate IRB. In such cases, IRBs may rely on the review of scientific merits carried
p.000031: out by or for the grant funding agency, on the proviso that IRBs must make their own determination as to the
p.000031: sufficiency and adequacy of the review of scientific merits that has been carried out. In these cases, IRBs
p.000031: should be empowered to require a more extensive or rigorous review of the scientific merits if deemed necessary.
p.000031:
p.000031: 5.26. In addition, appointing institutions may give IRBs authority for:
p.000031:
p.000031: (a) Continuing Review and Supervision. The institution has an overall duty to ensure that approved
p.000031: research programmes are conducted in accordance with the terms of the approval. We elaborate on this
p.000031: responsibility in Section VII. IRBs may assist the appointing institution in the discharge of this
p.000031: duty, but such delegation will have to be made clear in the terms of constitution of the IRB. Such
p.000031: delegation should only be made if the IRB is given sufficient resources to carry out such a
p.000031: responsibility. In this responsibility, IRBs will require Principal Investigators (PIs) to submit annual
p.000031: (or more frequent) progress reports and final reports within three months of completion of projects. PIs will
p.000031: also have to inform and seek approval from IRBs for any proposed deviations from the terms of approval
p.000031: of the projects before they can be implemented except when they are necessary to eliminate immediate hazards to
p.000031: participants, or when the changes involve only logistical or administrative aspects of research, in which case IRBs
p.000031: should be informed within seven days. IRBs may also direct or otherwise require amendments or
p.000031: modifications to research proposals at any time, and to make such amendments or modifications a condition of
p.000031: approval for the conduct or continuation of the research programme.
p.000031:
p.000031: (b) Reporting and Feedback. IRBs will require PIs to inform them of unusual or unexpected events within 15
p.000031: days of occurrence and report such events to the appointing institutions. Another major aspect of the role of IRBs
p.000031: is to provide feedback to and maintain dialogue about application standards with their constituent
p.000031: researchers. In the discharge of their role, IRBs can and should also act as the key institutional
p.000031: agency that receives and reports to their appointing institutions on concerns and feedback expressed by research
p.000031: subjects.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032:
p.000032: ETHICS GOVERNANCE
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032: 5.27. The implementation of a framework for the work of IRBs has been laid down and discussed
p.000032: extensively by the NMEC in Section 3 of the NMEC Guidelines. We agree generally with the principles of implementation
p.000032: laid down by the NMEC, and further elaborate on these principles in our discussion of the constitution of
p.000032: IRBs below.
p.000032:
p.000032: 5.28. We therefore recommend that IRBs should have responsibility for the ethics review and approval of
p.000032: proposed Human Biomedical Research programmes on behalf of their appointing institutions. This should
p.000032: take into account the scientific merits of the proposed research.
p.000032:
p.000032: 5.29. Additionally, as institutional resources may permit, and on the mutual agreement of IRBs and
p.000032: their appointing institutions, IRBs may also be given authority by their appointing institutions for:
p.000032:
p.000032: (a) The continuing review and supervision (including evaluation of feedback from research
p.000032: subjects) of Human Biomedical Research programmes approved by them;
p.000032:
p.000032: (b) The receiving of feedback from research subjects and the providing of feedback to researchers; and
p.000032:
p.000032: (c) The reporting of unusual or unexpected events arising from the Human Biomedical Research programmes
p.000032: carried out under the auspices of its appointing institution to the management of that institution.
p.000032:
p.000032:
p.000032: The Constitution of Institutional Review Boards
p.000032:
p.000032: 5.30. IRBs should be established at the highest administrative level of the institutions. They
p.000032: should be appropriately resourced relative to the research activity of the institution and, where this is
p.000032: substantial, should be regarded as one of the key full- time management offices within the organisation of
p.000032: institutions, and not merely as honorary or ad hoc committees.
p.000032:
p.000032: 5.31. The IRB should be appointed by and report to at least an authority at the level of the Chief Executive
p.000032: Officer (as recommended by the NMEC Guidelines in the case of hospitals falling under the jurisdiction
p.000032: of the MOH pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000032:
p.000032: 5.32. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000032: although it is acceptable for institutions
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033: ETHICS GOVERNANCE
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: with standing IRBs to appoint special ad hoc committees in consultation with their standing IRBs to
p.000033: consider special research proposals. We prefer, in such cases, that the institutions work with their standing
p.000033: IRBs to appoint special subcommittees co-opting experts or reviewers to assist the standing IRBs in the particular
p.000033: project concerned. For example, an IRB may receive a research proposal involving an area of research with which no
p.000033: member of the IRB is familiar. In such a case, the institution may work with the IRB to identify and co-opt ad
p.000033: hoc experts or reviewers to assist the IRB in its assessment and review of the proposal. The co-opted ad hoc experts
p.000033: or reviewers sit as a subcommittee of the IRB.
p.000033:
p.000033:
p.000033: Composition
p.000033:
p.000033: 5.33. We are of the opinion that the SGGCP (in particular Section 3.2.3) and the NMEC Guidelines (in particular
p.000033: Section 3.2.2) lay out appropriate and comprehensive guidelines regarding the composition of an
p.000033: ethics committee. We endorse these requirements and propose that they be similarly used to form the
p.000033: framework for the composition of an IRB.
p.000033:
p.000033: 5.34. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000033:
p.000033: (a) Impartiality and objectivity are fundamental principles to be observed in the appointment of
p.000033: members to IRBs. An IRB should be carefully composed in order that there can be no room for any public perception
p.000033: that it is not independent of those who are required to submit to its review;
p.000033:
p.000033: (b) Where a majority of the IRB members are drawn from within the appointing institutions, these persons
p.000033: should be the institutions’ most senior, most respected and scientifically competent officers,
p.000033: researche rs or consultants, who possess the appropriate experience and training;
p.000033:
p.000033: (c) An IRB should include non- medical and/or non-scientific persons (lay representation) who are not members
p.000033: of or otherwise associated with the appointing institution of the IRB. Their inclusion is to reinforce the
p.000033: impartiality and objectivity of the work of the IRB;
p.000033:
p.000033: (d) To further reinforce the independence of the IRB and to ensure that the decisions of the board are
p.000033: carried out in accordance with scientific thinking accepted within the community, external
p.000033: representation may include specialists of favorable reputation from other institutions; and
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000034: 34
p.000034:
p.000034:
p.000034: ETHICS GOVERNANCE
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: (e) Lay representation may include respected lay members of the community and experts in
p.000034: philosophy, ethics, psychology, sociology or the law. The IRB may consult representative religious leaders on an ad
...
p.000035: involves the export or transmission abroad of any human tissue or medical, personal or genetic information collected
p.000035: in Singapore or derived from donors in Singapore.
p.000035:
p.000035: 5.44. This conclusion is based on Singapore law and Singapore ethical standards and rules, which are not necessarily
p.000035: the same as those of other countries. This approach is supported in other jurisdictions. Without this approach a moral
p.000035: hazard would exist in the temptation of researchers to pick as their ethical jurisdiction of choice the
p.000035: jurisdiction with the perceived most liberal regime.
p.000035:
p.000035: 5.45. Nonetheless, we envisage that expedited review may be permissible in certain circumstances. For
p.000035: example, where human tissues from an IRB- approved study conducted in another country comes to Singapore
p.000035: for analysis, and the Singaporean institution does not have direct contact with the patient but merely performs tests
p.000035: on patient samples.
...
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038: any consideration of the case by the IRB, and he or she should refra in from offering his or her opinion to the
p.000038: IRB on the particular research under review.
p.000038:
p.000038: 5.63. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000038: the IRB.
p.000038:
p.000038: 5.64. Fair review and documentation of decisions. IRBs should provide a fair hearing to those involved. Where
p.000038: there exist any doubts or difficulties with particular aspects of proposals, IRBs should clarify these
p.000038: in writing with the researchers, or in a minuted face-to- face meeting between the IRB and the researchers.
p.000038:
p.000038: 5.65. All discussions of the IRB should be appropriately minuted and all opinions recorded. The decisions
p.000038: of the IRB should be provided in written form and, where appropriate, a fair and frank account of the
p.000038: reasons for those decisions should be provided.
p.000038:
p.000038: 5.66. Ethics review by an IRB should be based upon fully detailed research proposals or, where
p.000038: applicable, the most up -to-date progress reports. The proposals or progress reports on which ethics review is
p.000038: based should be drawn up specifically for the purposes of submission for ethics review.
p.000038:
p.000038: 5.67. IRBs may also require the submission of a lay summary of the research proposal, where this may aid
p.000038: the lay members of the IRB in the conduct of ethics review. This summary should set out concisely the salient fea
p.000038: tures of the research proposal. In certain cases, it may also be useful to have a lay summary of the scientific
p.000038: review.
p.000038:
p.000038: 5.68. Research proposals should not consist of the same or substantially the same documents submitted
p.000038: for the purpose of a proposal for fund ing. IRBs should bear in mind that research proposals submitted
p.000038: for ethics review are directed at a completely different end to that of proposals submitted for funding
p.000038: purposes.
p.000038:
p.000038: 5.69. The requirements of impartiality, fair review and documentation of decisions should apply
p.000038: equally to IRBs engaged in the continuing review or supervision of a research programme.
p.000038:
p.000038: 5.70. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000038: obtaining of free and informed consent of subjects in pharmaceutical trials should be applied to all other
p.000038: kinds of human biomedical research with appropriate modifications.
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039:
p.000039: ETHICS GOVERNANCE
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: 5.71. Both researchers and IRBs should take especial care to ensure that potential research
p.000039: subjects will be able to understand and assess the risks of participation, and that the consent-taking
p.000039: procedure and the documentation are properly designed to achieve this end.
p.000039:
p.000039: 5.72. Both researchers and IRBs should ensure that research participants are aware that they have the right
p.000039: to withdraw from the research programme at any time.
p.000039:
p.000039: 5.73. We recommend that IRBs and institutions formalise arrangements that allow participants a one-stop
p.000039: direct access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
...
p.000041:
p.000041: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethics governance of Human
p.000041: Biomedical Research. More than any other party or parties in the ethics review and governance
p.000041: process, researchers have the fullest access to the facts on which ethical judgments are to be made.
p.000041:
p.000041: 6.2. Researchers are responsible for making the threshold decisions in conceiving, designing and
p.000041: putting together a proposed research project. In these decisions, they have the most freedom to shape
p.000041: the proposed research project in a way that gives fullest consideration and respect to ethical
p.000041: considerations, always cognizant of the fact that it is the human subjects whom they study who make
p.000041: their research possible, and are therefore under an obligation to respect and to protect the subjects.
p.000041:
p.000041: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000041: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000041: judgments.
p.000041:
p.000041: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000041: aspects of the Human Biomedical Research rests with the researchers. IRBs bear the responsibility for the
p.000041: overall ethics review and approval of Human Biomedical Research programmes.
p.000041:
p.000041: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000041: responsibility that cannot be transferred or delegated to an IRB or to any party in the ethics review and
p.000041: governance process merely through the approval of a research proposal by an IRB.
p.000041:
p.000041: 6.6. By the same token, researchers remain entirely responsible for ensuring that their research complies
p.000041: with all relevant laws and legal or regulatory obligations and requirements. Ethics approval given by an IRB is not to
p.000041: be taken as an assurance or representation by the IRB of such compliance, or as an assumption of legal liabilities
p.000041: arising out of the proposed research by the IRB. In short, it is unethical for researchers to treat IRBs
p.000041: and the review process merely as “lega l insurers” or as “legal insurance”.
p.000041:
p.000041: 6.7. Researchers are primarily and ultimately responsible for making the first judgment as to whether, in
p.000041: their own professional judgment, the proposed research is ethical.
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000042: 42
p.000042:
p.000042:
p.000042: ETHICS GOVERNANCE
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042: 6.8. Researchers should only submit to IRBs proposals that they are objectively and professionally satisfied
p.000042: are entirely ethical in all aspects and are prepared to defend them as such.
p.000042:
p.000042: 6.9. By submitting a research proposal to an IRB, researchers indicate to all involved parties that the
p.000042: proposed research is, in the researchers’ objective and professional judgement, ethical in all aspects.
p.000042:
p.000042: 6.10. Researchers should not submit to IRBs the same or substantially the same documents for ethics review that
p.000042: they submitted to prospective funding agencies, unless these documents focus on or evaluate the potential impact of
p.000042: the research on the safety, health, dignity, welfare and privacy of the subject in addition to solely describing the
p.000042: scientific merits of the research. However, we nonetheless prefer researchers submit a separate document for
p.000042: ethics review. Researchers should be aware that research proposals submitted for ethics review and research
p.000042: proposals submitted for funding purposes are directed at completely different ends and should be drafted accordingly.
p.000042:
p.000042: 6.11. In no circumstances should researchers use IRBs and the ethics review process as a means of gaining
p.000042: ethics approval for research projects that the researchers themselves entertain doubts or uncertainties about
p.000042: from the ethical point of view.
p.000042:
p.000042: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000042: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000042: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000042: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000042:
p.000042: 6.13. In such cases, we take the view that if researchers believe, in good faith, that the proposed
p.000042: research is ethical, the n such proposed research may be submitted for ethics review provided that the researchers
p.000042: fully disclose all such differing opinions and potential ethical difficulties or controversies known to them;
p.000042: that the researchers fully disclose the ethical reservations or doubts they hold; and that researchers fully disclose
p.000042: all other material facts and issues that might help the IRB carry out an impartial and objective review.
p.000042: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to
p.000042: explore all potential ethical issues, and to carry out an impartial and objective review of a novel
p.000042: situation, there is no objection to researchers submitting in good faith for ethics review a research proposal that the
p.000042: researchers themselves feel that they need ethical guidance.
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043:
p.000043: ETHICS GOVERNANCE
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: 6.14. It is important that researchers take special care to avoid any form of conflicts of interest,
p.000043: whether actual, potential, or merely an appearance of conflict as such. Where such actual, potential or apparent
p.000043: conflict arises, researchers have a duty to make a declaration of the conflict, to give full disclosure of the facts
p.000043: giving rise to such conflict and to detail the steps proposed or taken to minimise or avoid the actual or
p.000043: potential conflict of interest or the appearance of such a conflict of interest.
p.000043:
p.000043: 6.15. Researchers should not be involved in, or give the appearance of being involved in, the ethics
p.000043: review and approval process of any research project in which he or she is involved. For instance, a researcher who is a
p.000043: me mber of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000043: personally involved and make a declaration of such an interest to the IRB.
p.000043:
p.000043: 6.16. In submitting a proposal for ethics review, every researcher involved in the research project should be named
p.000043: as a party and applicant in the proposal.
p.000043:
p.000043: 6.17. For the purposes of this Section, we exclude from the definition of researcher, persons acting
p.000043: only in an administrative or support capacity and who have no independent control over the conduct of
p.000043: the research. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000043: in clinical duties.
p.000043:
p.000043:
p.000043: Principal Investigators
p.000043:
p.000043: 6.18. Where a research project involves more than one researcher, the term “investigator” refers to any
p.000043: one of the researchers generally, while the term “Principal Investigator” specifically refers to the researcher who has
p.000043: been designated to undertake the role of Principal Investigator (PI) of that research project.
p.000043:
p.000043: 6.19. If a single researcher is carrying out a research project, then he or she shall be the PI. If multiple
p.000043: researchers are carrying out a research project, then the researchers must among themselves designate a PI. The
p.000043: PI is the researcher who shall be regarded as the lead res earcher of the research project.
p.000043:
p.000043: 6.20. A research application by a group of collaborating researchers should be submitted in the name of a
p.000043: single PI and his or her collaborating researchers.
p.000043:
p.000043: 6.21. It is permissible for a research project to have more than one PI, especially for large projects, projects
p.000043: with different parts or different (but related)
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044:
p.000044: ETHICS GOVERNANCE
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044: objectives and projects in which the research is to be carried out at many locations (multi-centre research). Where
p.000044: more than one PI is involved, then each and every one of the PIs shall be held jointly and severally
p.000044: responsible as PIs.
p.000044:
p.000044: 6.22. PIs have special additional responsibilities over and above that of ordinary researchers.
p.000044:
p.000044: The MOH has recently proposed a definition of “Principal Investigator” and of a PI's roles and
p.000044: responsibilities:
p.000044:
p.000044: “The Principal Investigator (PI) is the individual responsible and accountable for the design, conduct,
p.000044: monitoring, analyses and reporting of the protocol. The PI assumes full responsibility for the evaluation,
p.000044: analyses and integrity of the research data. The PI must assure that the protocol is followed and the data collected
p.000044: promptly and accurately. The PI assumes specific responsibilities to include: writing the protocol
p.000044: document, assuring that necessary approvals are obtained, monit oring the protocol during its execution, ensure
p.000044: that the protocol is conducted in accordance to the ethical guidelines, and to ensure that all participating
p.000044: investigators on the research teams, involved in implementing the protocol are adequately informed about the protocol
p.000044: and their responsibilities.”
p.000044:
p.000044: 6.23. We commend and adopt this definition and summary of the role and responsibilities of a PI, and
p.000044: extend it to all Human Biomedical Research as defined in these Guidelines.
p.000044:
p.000044: 6.24. We however also point out that in multi-centre, multinational trials of new drugs, there is often an
p.000044: international committee that designs and analyses the results of protocols. Thus, in the case of such pharmaceutical
p.000044: trials, the term “Principal Investigator” would apply to the appropriate and relevant person on that international
p.000044: committee, whether appointed to act as such or otherwise.
p.000044:
p.000044: 6.25. In large, multi-part, multi-centre or complex research programmes, it is especially critical that
p.000044: the exact roles and responsibilities of each of the researchers in a team should be made clear and reduced to
p.000044: writing. This makes clear to every researcher what each other’s responsibilities are, and helps identify overlooked
p.000044: areas requiring supervision or direction by a member of a team. Such statements outlining the roles and
p.000044: responsibilities of each of the researchers in a team should be included in the submission to the IRB.
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045:
p.000045: ETHICS GOVERNANCE
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: 6.26. The PI shall be responsible for settling, coordinating and formalising the distribution of roles and
p.000045: responsibilities among the researchers in a research programme.
p.000045:
p.000045:
p.000045: Continuing Responsibilities, Deviation and Variation
p.000045:
p.000045: 6.27. The ethical responsibilities of researchers outlined in this section are continuing
p.000045: responsibilities that apply at least for the lifetime of the research project, which is defined
p.000045: as the time the research project is submitted to the IRB for ethics review until the time the research project is
p.000045: deemed to have concluded or been terminated.
p.000045:
p.000045: 6.28. When an IRB approves a research application, its judgment is based on the facts and proposals disclosed to it
p.000045: by the researchers in their application. Most significantly, the ethical judgment has to be made before the research
p.000045: project begins. Once the project is approved and the research is underway, researchers may find that varia
p.000045: tions or departures from the original proposal may be dictated by such considerations as budget,
p.000045: access to subjects, unexpected clinical results and other factors. A research project may also expand in scope, in
p.000045: its objectives, or in the researchers involved. Some researchers may, for example, resign or take a less active role,
p.000045: while other researchers may be recruited. There are other situations in which deviation may occur. A
p.000045: proposed course of action may be found to pose greater risks for the proposed subject population than originally
p.000045: assessed, or that the research has resulted in greater harm (whether of degree or of incidence) than originally
p.000045: contemplated. Or it may be discovered in the course of the research that some part of the original protocol as
p.000045: proposed in the ethics review application has not been strictly adhered to, although such departure may have been
p.000045: made in good faith, by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000045:
p.000045: 6.29. As part of his continuing responsibilities, the PI in particular is under a strict obligation
p.000045: to immediately and in writing seek approval for any changes where such changes have not yet been made, or
p.000045: otherwise report any changes where such changes have already been made, to the IRB by which the initial research
p.000045: application was considered and approved. The PI shall in his request or report detail the changes, giving
p.000045: his objective assessment of any impact and consequences (both from the clinical and ethical points of view)
p.000045: of the changes.
p.000045:
p.000045: 6.30. This continuing obligation of researchers is clearly referred to in the NMEC Guidelines (Section
p.000045: 3.2.5). The NMEC Guidelines state that investigators are “bound to act in exact accordance with the details”
p.000045: of the protocol submitted for ethics review and that investigators are “obliged to
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046:
p.000046: ETHICS GOVERNANCE
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000046: report to the [IRB] any adverse events and apparent risks beyond those predicted in the original
p.000046: submission. The investigator should also immediately inform the [IRB] of any new information that might alter
p.000046: the ethical basis of the research programme. The [IRB] should also be notified if the study is terminated prematurely.”
p.000046: We agree entirely with the NMEC in these statements and adopt them.
p.000046:
p.000046: 6.31. The submission of a protocol operates as a representation and agreement by each researcher who signs the
p.000046: application that the research programme will be carried out strictly in accordance with the submitted protocol.
p.000046:
p.000046: 6.32. Researchers are obliged to suspend their research immediately, pending their report to the IRB,
p.000046: if deviations or changes to the original project submitted are substantial. Researchers are under the
p.000046: same obligation if deviations and changes have resulted or will likely result in greater harm or greater likelihood
p.000046: of harm (whether of degree or incidence) to the sub jects involved.
p.000046:
p.000046: 6.33. Minor changes intended solely for the greater safety, health, welfare and well-being of the
p.000046: human subjects taken after consultation with all researchers involved in the research need not be
p.000046: immediately reported to the IRB. For example, if it appears to a researcher that a particular research
p.000046: subject is not altogether comfortable with one of the planned procedures, that procedure may be stopped
p.000046: and the research programme varied to such extent, without the need for immediate reporting. Reporting of such
p.000046: changes by the PI to the relevant IRB should however take place within a time frame that shall be decided by
p.000046: the IRB. We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000046: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of
p.000046: the research or for meeting its objectives, do not fall within this category and should be immediately
p.000046: reported.
p.000046:
p.000046: 6.34. PIs have an obligation to submit regular reports to IRBs regarding the status of their research
p.000046: programmes. These reports are intended to aid the IRBs in its role of continuing review and supervision.
p.000046:
p.000046:
p.000046: Researchers and Attending Physicians
p.000046:
p.000046: 6.35. Human subjects for research projects are often recruited from patients who are already receiving treatment
p.000046: from physicians.
p.000046:
p.000046: 6.36. Where a proposed researcher is the attending physician, the researcher- physician should be aware of
p.000046: a potential conflict of interest and of the fact
p.000046:
p.000046:
p.000046:
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047:
p.000047: ETHICS GOVERNANCE
p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of Helsinki,
p.000047: which states that:
p.000047:
p.000047: “When obtaining informed consent for the research project the physician should be particularly cautious if the subject
p.000047: is in a dependent relationship with the physician or may consent under duress. In that case the informed consent
p.000047: should be obtained by a well -informed physician who is not engaged in the investigation and who is
p.000047: completely independent of this relationship.”
p.000047:
p.000047: 6.37. In our view, ho wever, this does not apply to situations where physicians wish to write up or
p.000047: publish summaries or analyses of the results of their therapeutic interventions or treatment of their patients,
p.000047: provided that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000047: diagnostic purposes and in the interests of the patients and without regard to any consideration for research
p.000047: objectives or for the subsequent publication of the results.
p.000047:
p.000047: 6.38. In some circumstances, it may be difficult or impractical for researcher- physicians to comply
...
p.000048: and privacy of the subject-patients. Where the IRB is satisfied that there is no reasonable connection
p.000048: between the research programme and the treatment and management of the subject-patient, the researchers may dispense
p.000048: with informing and discussing with the attending physicians of their subjects;
p.000048:
p.000048: (b) In the case of research that involves access to patients’ medical records but with minimal levels of
p.000048: clinical interaction (e.g. the taking of blood or urine samples) or only social interaction (e.g.
p.000048: interviewing the subject-patient for a history), the IRB may in its discretion make formal contact and
p.000048: discussion a condition of ethics approval if it takes the view that the proposed interaction is relevant to the
p.000048: continued medical treatment and management of the subject- patient. Otherwise, researchers may in such
p.000048: cases dispense with contacting the attending physicians; and
p.000048:
p.000048: (c) In the case of research that involves access to and a study of patients’ medical records without any kind of
p.000048: contact between researchers and the patients, researchers need not inform or discuss with the
p.000048:
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049:
p.000049: ETHICS GOVERNANCE
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049: attending physicians (on the assumption, of course, that they have complied with all other applicable
p.000049: requirements).
p.000049:
p.000049: 6.44. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000049: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the subjects
p.000049: without first seeking and obtaining the approval of both the attending physicians and the IRB.
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000050: 50
p.000050:
p.000050:
p.000050: ETHICS GOVERNANCE
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION VII: INSTITUTIONS
p.000050:
p.000050: 7. Institutions
p.000050:
p.000050: The Responsibilities of Appointing Institutions
p.000050:
p.000050: 7.1. Institutions have the overall responsibility of ensuring the proper conduct of Human Biomedical Research and
p.000050: the protection of human subjects in all Human Biomedical Research carried out on their premises or facilities, or by
p.000050: their employees, or on their patients, or involving access to or use of human tissue collections in their custody, or
p.000050: involving access to or use of medical records or other personal information in their custody.
p.000050:
p.000050: 7.2. Every institution involved in Human Biomedical Research as defined in these Guidelines should
p.000050: establish and maintain an effective IRB. The IRB is accountable to the appointing institution, which must
p.000050: accept legal responsibility for the decisions of its IRB.
p.000050:
p.000050: 7.3. Institutions should lay policies for the composition of IRBs and the formal appointment of IRB members in
p.000050: accordance with the general principles and guidance presented in these Guidelines and, in particular, those set
p.000050: out under “Specific Operating Procedures for Institutional Review Boards” in Section V.
p.000050:
p.000050: 7.4. It is the responsibility of institutions to provide adequate resources and administrative support
p.000050: so as to enable IRBs to discharge their duties and responsibilities in an effective and timely manner.
p.000050:
p.000050: 7.5. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of
p.000050: their work and IRBs should likewise ensure that their workload does not compromise the quality of their
p.000050: review. If this is likely, the institution is obliged to establish additional IRBs, to enlarge the
p.000050: membership of the IRB or to make formal arrangements for other IRBs to provide an opinion.
p.000050:
p.000050: 7.6. Institutions are obliged to ensure that IRBs receive adequate administrative support that is commensurate
p.000050: with the central role of the IRB in the ethics governance process. In this respect, the institution may take
p.000050: steps to lighten the workload of IRBs by delegating review in specific areas to a subcommittee, or by
p.000050: delegating some of its administrative or supervisory tasks to a separate well-staffed administrative body.
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051:
p.000051: ETHICS GOVERNANCE
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: 7.7. Such full-time administrative support should be sufficient to allow the IRB to:
p.000051:
p.000051: (a) Ensure continuity and consistency in the work of the IRBs;
p.000051:
p.000051: (b) Discharge any continuing review and supervisory obligations, outcome assessment and reporting
p.000051: duties;
p.000051:
p.000051: (c) Ensure that the IRB's decisions are made with regard to previously established precedents and
p.000051: decisions tha t they and their predecessors have made; and
p.000051:
p.000051: (d) Ensure that proposals are reviewed and dealt with in a timely manner within the target time frames set by the
p.000051: institution.
p.000051:
p.000051: 7.8. The core members of the IRB should be able to devote sufficient and protected time commensurate
p.000051: with the workload of the IRB.
p.000051:
p.000051: 7.9. Institutions are also responsible for providing their IRB members with a full indemnity as set
p.000051: out in paragraphs 7.17 to 7.22 and this should be reflected in their letters of appointment.
p.000051:
p.000051: 7.10. Institutions providing care should retain responsibility for the quality of all aspects of care afforded to
p.000051: human subjects whether or not some aspects of care are part of a research study.
p.000051:
p.000051: 7.11. Medical Records and Patient Information. We recognise that the issues arising from access to the
p.000051: use of and the custody of medical records and other patient information are becoming increasingly complex. In this
p.000051: area, the ethical issues are inextricably interwoven with legal considerations, and the impact of the existing
p.000051: law is currently unclear in many situations. We hope to explore these issues in a separate subsequent report.
p.000051:
p.000051: 7.12. In the context of institutions such as hospitals with centralised patient records and databases,
p.000051: we recommend that appointing institutions take steps to determine who within the administrative structure should
p.000051: be the proper administrative custodians responsible for patients’ medical information in the
p.000051: institution, and to advise their IRBs accordingly.
p.000051:
p.000051: 7.13. In situations where any of the researchers are also the administrative custodian of patients’
p.000051: medical information within the institution, procedures should be established to address actual,
p.000051: potential or apparent conflicts of interest.
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: ETHICS GOVERNANCE
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: 7.14. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000052: kinds of patients' medical information, and should formulate these procedures in consultation with their IRBs.
p.000052:
p.000052: 7.15. It is desirable that the IRB be given authority by its appointing institution for the ethical clearance of
p.000052: access to patients’ medical information for research within the institution, so that no patients’ medical
p.000052: information may be released for research purposes without clearance by the IRB except for cases of Exempted Reviews
p.000052: referred to in paragraph 3.15.
p.000052:
p.000052: 7.16. Training and Education for IRB me mbers. We recognise that training for IRB members can only be
p.000052: beneficial in the scheme of ethics governance of human research. We therefore recommend that institutions that
p.000052: conduct Human Biomedical Research and which are required in the context of these Guidelines to have IRBs,
p.000052: should also have in place programmes for the training and education of IRB members. Hospitals that have
p.000052: sizeable research programmes should in particular have such programmes. Such training and educational
p.000052: programmes should, where possible, also be provided to researchXstaff.
p.000052:
p.000052:
p.000052: The Protection of Institutional Review Boards
p.000052:
p.000052: 7.17. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000052: difficulties in attracting members of their choice in that some of the most qualified potential
p.000052: candidates for membership decline the invitation to serve. These candidates may do so out of a fear of legal
p.000052: liability in the event of a contested decision, or a decision that has an unexpectedly adverse impact on human
p.000052: subjects. Few such candidates have any legal training and their reluctance on this ground is understandable.
p.000052:
p.000052: 7.18. On this point, we note that the NMEC Guidelines recommend that IRBs should look to the authority
p.000052: appointing them to give IRB members formal indemnity “against the cost of any legal representation and
p.000052: any compensation ultimately awarded to human subjects” (Section 3.34). The NMEC Guidelines further recommend that such
p.000052: an indemnity be given in IRB members’ letters of appointment.
p.000052:
p.000052: 7.19. IRB members discharge an important office in the public interest in the protection of human
p.000052: subjects. Often they do so for minimal or token remuneration, or none at all. Their only motivation being a
p.000052: call to duty and their only reward being the satisfaction of a job well done.
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053:
p.000053: ETHICS GOVERNANCE
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: 7.20. We take the view that IRB members should be fully protected in the discharge of their duties,
p.000053: provided that they do so in good faith, against any liability arising from their actions. Appointing
p.000053: institutions should give IRB members a full indemnity and arrange for the necessary insurance.
p.000053:
p.000053: 7.21. Legal protection for IRB members acting in good faith would also encourage the best and
p.000053: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000053: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000053: fields.
p.000053:
p.000053: 7.22. Because IRBs act as their appointing institutions’ officers and agents, institutions remain liable
p.000053: to human subjects from any claim in tort and should be required to take out appropriate insurance coverage
p.000053: against the variety of claims that may arise in the course of the work of the IRB (for example, in relation to the
p.000053: approval of multi-centre or multinational research).
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
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p.000053:
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p.000053:
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p.000053:
p.000053:
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p.000053:
p.000053:
p.000053:
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p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000054: 54
p.000054:
p.000054:
p.000054: ETHICS GOVERNANCE
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054: SECTION VIII: ACCREDITATION
p.000054:
p.000054: 8. Accreditation
p.000054:
p.000054: The Accreditation of Institutional Review Boards
p.000054:
p.000054: 8.1. The current regulatory regime governing the review and approval of pharmaceutical trials (which
p.000054: we described in Section II) provides for a system in which applications for pharma ceutical trials are
p.000054: first screened by IRBs at the local institutional level before being forwarded to a national regulatory
p.000054: agency (the HSA) for approval. This system has served us well and is well understood by all parties
p.000054: involved in the process. It should continue to apply in the case of pharmaceutical trials.
p.000054:
p.000054: 8.2. In the case of Human Biomedical Research other than pharmaceutical trials there is currently no
p.000054: national agency or regulatory body fulfilling a function equivalent to that of the HSA. The exception is the MOH, but
p.000054: it only has jurisdiction over hospitals, private clinics and other institutions falling within its purview
p.000054: under the Private Hospitals and Medical Clinics Act.
p.000054:
p.000054: 8.3. The MOH provides guidance from time to time for IRBs falling within its jurisdiction. For example, the MOH
p.000054: has directed all IRBs to adopt and apply the NMEC Guidelines. From time to time, other directions are issued.
p.000054: Some of these are on the advice of the NMEC.
p.000054:
p.000054: 8.4. The role of the NMEC, however, is to advise the MOH on ethical issues arising in the practice of
p.000054: medicine. The NMEC does not advise IRBs directly and does not function as a higher level appeal or advisory body
p.000054: to IRBs.
p.000054:
p.000054: 8.5. Apart from complying with the directives issued by the MOH (including the NMEC Guidelines), IRBs in
p.000054: institutions under its jurisdiction are free to adopt such procedures, formulate their own standard
p.000054: operating procedures and determine their constitution, operating principles and other administrative practices.
p.000054:
p.000054: 8.6. We recommend that all IRBs be formally accredited by the MOH, which should be empowered to audit,
p.000054: to investigate complaints (including complaints from research subjects) and to appoint external auditors and
p.000054: investigators at the cost of the institution being audited as part of the accreditation check or as a
p.000054: matter of routine audit for compliance.
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055:
p.000055: ANNEXES
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: ANNEXES
p.000055:
p.000055:
p.000055: Annexe A: The Human Genetics Subcommittee
p.000055:
p.000055: Annexe B: Consultation Paper entitled “Advancing the Framework of Ethics Governance for Human Research”
p.000055:
p.000055: Annexe C: Distribution List
p.000055:
p.000055: Annexe D: Responses to the Consultation Paper Annexe E: Summary of the Dialogue Session Annexe F:
p.000055: Select References
p.000055: Annexe G: List of Abbreviations
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: ANNEXE A
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: HUMAN GENETICS SUBCOMMITTEE
p.000056:
p.000056:
p.000056: Chairman
p.000056:
p.000056: Associate Professor Terry Kaan Sheung-Hung Faculty of Law
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: Members
p.000056:
p.000056: Mr Jeffrey Chan Wah Teck
p.000056: Principal Senior State Counsel (Civil) Attorney-General’s Chambers
p.000056:
p.000056: Associate Professor Samuel Chong Department of Paediatrics
p.000056: National University of Singapore
p.000056:
p.000056: Professor Yap Hui Kim
p.000056: Senior Consultant, National University Hospital Professor in Paediatrics, National University of Singapore
p.000056:
p.000056: Associate Professor Chia Kee Seng (from September 2004) Department of Community, Occupational and Family Medicine
p.000056: Faculty of Medicine
p.000056: National University of Singapore
p.000056:
p.000056: Dr Denise Goh Li Meng (from September 2004) Consultant
p.000056: The Children's Medical Institute National University Hospital
p.000056:
p.000056: Dr Lee Soo Chin (from September 2004) Consultant
p.000056: Department of Haematology-Oncology National University Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
...
p.000056: of life of the general population. These advances represent one of the principal achievements in the
p.000056: modern history of the human race. In the main, such advances in biomedical knowledge have been beneficial, and
p.000056: research conducted in good faith for the benefit of humankind.
p.000056:
p.000056: 2.2. The events of World War II however, gave rise to concerns that biomedical research
p.000056: conducted on human subjects should be subject to agreed ethical norms. The Nuremberg Code 1 was born
p.000056: out of these concerns, and represents the first universally-accepted code spelling out the minimum content
p.000056: of the ethical norms governing the conduct of biomedical research on human subjects.
p.000056:
p.000056: 2.3. These ethical norms were fleshed out and received fuller treatment and consideration in the World
p.000056: Medical Association’s Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects2, which since its adoption by the 18th World Medical Association General Assembly at Helsinki,
p.000056: Finland, has become universally accepted as the core body of ethical norms governing human research.
p.000056:
p.000056: 2.4. The principal theme of the Helsinki Declaration is that the life, health, privacy and dignity of
p.000056: the human subject in biomedical research are the first considerations before all others. To this end, the Helsinki
p.000056: Declaration advocates safeguards such as the principle of freely given informed consent of the
p.000056: human subject, and the need for rigorous scientific assessment of the risks to the human subject
p.000056: in relation to the benefit sought to be gained from the research.
p.000056:
p.000056: 2.5. One of the basic principles enunciated in the Declaration of Helsinki is spelt out in Article 13.
p.000056: This provides that the “design and performance of each experimental procedure involving human subjects should be
p.000056: clearly formulated in an experimental protocol”, and that this protocol should be
p.000056:
p.000056: 1 Derived from Trials of War Criminals before the Nuremberg Military Tribunals under
p.000056: Control Council Law No. 10, Vol. 2 at pages 181-182 (Washington D.C.:U.S. Government Printing Office, 1949).
p.000056: 2 Declaration of Helsinki on Ethical Principles for Medical Research Involving Human
p.000056: Subjects adopted by the 18th World Medical Association General Assembly in Helsinki, Finland, in June 1964 and most
p.000056: recently amended by the 52nd World Medical Association General Assembly in Edinburgh, Scotland, in October 2000.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-62
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: submitted to an independent et hical review committee for “consideration, comment, guidance, and where appropriate,
p.000056: approval”.
p.000056:
p.000056: 2.6. The basic principles of the Declaration of Helsinki have been long accepted by the
p.000056: medical community in Singapore, as with other medical communities in the great majority of nations.
p.000056: The need for ethics committees or institutional review boards and the requirement for the ethical
p.000056: review of research proposals involving human subjects have long been an accepted and integral part of medical
p.000056: research in the institutional setting in Singapore. The principles of the Declaration of Helsinki today find
p.000056: expression in regulatory standards and practice guidelines governing various aspects of biomedical research such
p.000056: as those contained in the Medicines (Clinical Trials) Re gulations, promulgated pursuant to s.74 of the
p.000056: Medicines Act (Cap. 176), the Singapore Guideline for Good Clinical Practice, and the Ethical Guidelines on
p.000056: Research Involving Human Subjects of the National Medical Ethics Committee (NMEC). We discuss these regulatory
p.000056: standards and practice guidelines in detail below.
p.000056:
p.000056:
p.000056: The Ethical Governance of Clinical Trials in Singapore
p.000056:
p.000056: Clinical Trials
p.000056:
p.000056: 2.7. In this section, we summarise the current regulatory regime for the ethical governance of drug trials in
p.000056: Singapore.
p.000056:
p.000056: 2.8. Since 1978, the Medicines (Clinical Trials) Regulations (RG3 2000 Rev Ed) has statutorily regulated
p.000056: the conduct of clinical trials. These Regulations (“the Clinical Trials Regulations”) were made
p.000056: under the Medicines Act (Cap 176). The Clinical Trials Regulations set out the procedures and conditions
p.000056: which have to be satisfied before a licence for a clinical trial is issued by the competent authorities, which is
p.000056: currently the Health Sciences Authority (HSA).
p.000056:
p.000056: The Meaning of “Clinical Trials”
p.000056:
p.000056: 2.9. It is important to note, however, that the term “clinical trial” in the context of the Clinical Trials
p.000056: Regulations and its parent Act (the Medicines Act, Cap. 176) has a special meaning. As defined in
p.000056: the Clinical Trials Regulations and its parent Act, the term “clinical trial” is restricted essentially to
p.000056: pharmaceutical drug trials, in which the effect, safety and efficacy of new drugs (or new applications of
p.000056: existing drugs) are intended to be tested.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-63
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.10. As such, the Clinical Trials Regulations and its parent Act have no application to other research
p.000056: or trials involving human subjects or human biological materials.
p.000056:
p.000056: 2.11. The term “clinical trial” for example, does not cover observational trials or interventional trials (we
p.000056: further discuss these and other terms below) involving human subjects, even if such trials involve the
p.000056: administration of drugs (or control placebos), so long as the objectives of the research do not relate to the effect,
p.000056: safety and efficacy of the drugs concerned.
p.000056:
p.000056: 2.12. For this reason, and to avoid confusion, we avoid the use of the term “clinical trial”. We
p.000056: instead use the term “drug trials” in this Consultation Paper when referring to “clinical trials” in the legal sense of
p.000056: that term, as used in the Clinical Trials Regulations and the Medicines Act.
p.000056:
p.000056: 2.13. In keeping with the principles enunciated in the Declaration of Helsinki, an important component of
p.000056: the requirements of the Clinical Trials Regulations is that the researchers must ensure that the free
p.000056: consent of the proposed research subject must be obtained, and that researchers are under a duty to give full
p.000056: explanation and information of (among others) the risks and objectives of the proposed drug trial.
p.000056:
p.000056: The Singapore Guideline for Good Clinical Practice
p.000056:
p.000056: 2.14. In 1998, the Ministry of Health released the Singapore Guideline for Good Clinical Practice (SGGCP), which is
p.000056: a set of guidelines adapted from the Good Clinical Practice Guidelines of the International Conference on
p.000056: Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
p.000056: Accordingly, the SGGCP reflects best international practice in its approach to the governance of drug trials.
p.000056: Since 1998, the SGGCP has been incorporated by reference in the Clinical Trials Regulations, and sponsors and
p.000056: researchers in drug trials are required by law to comply with the SGGCP unless specifically exempted under the Clinical
p.000056: Trials Regulations.
p.000056:
p.000056: 2.15. The SGGCP sets out in detail a framework for the ethical governance of drug trials. The SGGCP begins its
p.000056: statement of applicable principles by declaring that drug trials “should be conducted in accordance with the
p.000056: ethical principles that have their origin in the Declaration of Helsinki”.
p.000056:
p.000056: 2.16. Article 1.12 of the SGGCP treats the terms “clinical trial” and “clinical study” as being
p.000056: synonymous, and defines them as being any “investigation in human subjects intended to discover or
p.000056: verify the clinical, pharmacological and/or other pharmacodynamic effects of an
p.000056: investigational product(s), and/or to identify any adverse reactions to an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-64
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: investigational product(s), and /or to study absorption, distribution, metabolism, and excretion of an
p.000056: investigational product(s) with the object of ascertaining its safety and/or efficacy”.
p.000056:
p.000056: 2.17. The SGGCP sets out detailed guidelines as to the roles and duties of researchers and sponsors in
p.000056: a pharmaceutical drug trial, and lays down the requirements such as monitoring procedures, audits and the matters to be
p.000056: included in trial protocols.
p.000056:
p.000056: 2.18. Of relevance to this Consultation Paper are the provisions in Part 3 of the SGGCP requiring all drug
p.000056: trials to be reviewed and approved by the Medical Clinical Research Committee (MCRC) of the Health
p.000056: Sciences Authority (“HSA”) and hospital’s “ethics committees” before an application may be made
p.000056: for a clinical trial certificate from the HSA. The responsibilities, composition, functions and operations of the
p.000056: MCRC are set out in detail in Article 3.1 of the SGGCP, while the responsibilities, composition, functions
p.000056: and operations of ethics committee are detailed in Article 3.2.
p.000056:
p.000056: The Current Approval Process for a Proposed Pharmaceutical Drug Trial
p.000056:
p.000056: 2.19. It may be useful to summarise the current approval process for a proposed pharmaceutical drug trial under the
p.000056: current regulatory regime. Researchers seeking a clinical trial certificate under the Medicines Act are required to
p.000056: submit their trial protocol and application first to their hospital ethics committee or IRB for
p.000056: review and approval. If the proposed pharmaceutical drug trial is a multi-centre trial (where
p.000056: the trial is carried out at more than one institution or centre), the application is submitted to the Clinical Trials
p.000056: Coordinating Committee (CTCC) instead for review and approval. The CTCC was established in 1999 by the Ministry of
p.000056: Health to coordinate the ethical governance of multi-centre drug trials in Singapore.
p.000056:
p.000056: 2.20. If the protocol and application are approved by the hospital ethics committees (and the
p.000056: CTCC, if the application is for a multi- centre trial), they are then submitted to the Centre for Pharmaceutical
p.000056: Administration (CPA) of the HSA for review and approval.
p.000056:
p.000056: 2.21. The CPA is aided in its task by the MCRC. The MCRC is an advisory committee appointed by the
p.000056: Ministry of Health to review applications for drug trials in Singapore. It is an “independent body constituted of
p.000056: medical members, whose responsibility is to ensure the protection of the rights, safety and well-being
p.000056: of human subjects involved in a trial ... and documenting informed consent of the trial subjects”
p.000056: (Article 1.37 of the SGGCP). The MCRC currently comprises five members, all of whom are clinical specialists.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-65
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.22. The current formal regulatory regime for drug trials as constituted under the Medicines Act, the
p.000056: Clinical Trials Regulations and the SGGCP has worked very well, and the standards of ethical governance in
p.000056: Singapore for drug trials conform to the highest internationally agreed standards of ethical governance for
p.000056: drug trials.
p.000056:
p.000056: 2.23. We understand that the rules are being examined with a view to procedural changes in the interests of
p.000056: streamlining processes, emphasising a risk- based approach and perhaps also for the inclusion of the trial
p.000056: of medical devices to be included within the ambit of the current regulatory regime. We agree with these moves, and
p.000056: they do not detract from or alter the core principles for ethical governance currently in place for drug trials.
p.000056:
p.000056:
p.000056: Non-Drug Trials
p.000056:
p.000056: The NMEC Guidelines on Research Involving Human Subjects
p.000056:
p.000056: 2.24. While the ethical governance of drug trials in Singapore is comprehensively and
p.000056: appropriately regulated by statutory rules and practice guidelines, the picture for the ethical
p.000056: governance of clinical research other than for drug trials is less clear.
p.000056:
p.000056: 2.25. Currently, there is no statutory scheme for the ethical governance of clinical research apart
p.000056: from drug trials. We expand on the definition of “clinical research” in Section III below.
p.000056:
p.000056: 2.26. Indirectly, however, the Ministry of Health has long exercised jurisdiction over, and given informal ethical
p.000056: guidance on, clinical research carried out in hospitals, clinics and clinical laboratories in its role as a
p.000056: statutory regulator under the Private Hospitals and Medical Clinics Act.
p.000056:
p.000056: 2.27. In January 1994, the Ministry of Health set up a national- level policy advisory body, the National
p.000056: Medical Ethics Committee (NMEC) to “assist the medical profession in addressing ethical issues in medical practice and
p.000056: to ensure a high standard of ethical practice in Singapore”.
p.000056:
p.000056: 2.28. One of the objectives of establishing the NMEC was to “identify and study ethical issues relating to medical
p.000056: practice and research in Singapore and to provide an ethical framework for medical practitioners to carry out
p.000056: their duties and responsibilities”.
p.000056:
p.000056: 2.29. Several sets of Ethical Guidelines were issued by the NMEC and adopted by the Ministry of Health. In the
p.000056: sphere of ethical governance of clinical
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-66
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: research, the most significant of these Ethical Guidelines is the Ethical Guidelines on Research Involving
p.000056: Human Subjects issued by the NMEC in August 1997 (“the NMEC Guidelines”).
p.000056:
p.000056: 2.30. The NMEC Guidelines were accepted and adopted by the Ministry of Health, and copies of these
p.000056: Guidelines were circulated to all hospital ethics committees for their adoption and implementation.
p.000056:
p.000056: 2.31. In 1998, the previously informal practice of hospitals and medical institutions in Singapore
p.000056: of having ethics committees (sometimes on an ad hoc basis) to review research proposals involving human
p.000056: subjects was formalised by a written direction dated 25 June 1998 from the Ministry of Health to all government and
p.000056: restructured hospitals to set up hospital ethics committees (if they had not already done so) for the ethical
p.000056: governance of research involving human subjects.
p.000056:
p.000056: 2.32. We quote from the written direction:
p.000056:
p.000056: “The National Medical Ethics Committee has recommended that:
p.000056:
p.000056: (i) hospital ethics committees vet for ethical considerations, all research protocols that involve
p.000056: • human experimentation be they drug trials, trials of new medical devices, new procedures and any
p.000056: other forms of clinical studies that require the participation of human subjects or the use of human tissues
p.000056: and organs
p.000056: ...
p.000056: (ii) a senior nursing representative be included as a member of hospital ethics committee.
p.000056:
p.000056: The Ministry has accepted these recommendations”.
p.000056:
p.000056: 2.33. The NMEC Guidelines set out in detail suggested principles of the ethical governance of research involving
p.000056: human subjects, the constitution of ethics committees and the implementation of the framework for the ethical
p.000056: governance of biomedical research. These Guidelines represent the principal controlling document
p.000056: governing research involving human subjects in Singapore today, but despite this they rema ins non-directive in
p.000056: nature,
p.000056:
p.000056: 2.34. In developing the Guidelines, the NMEC drew extensively from similar guidelines published in other
p.000056: technologically-advanced countries, notably those issued by the Canadian Medical Research Council, and the
p.000056: Royal College of Physicians, London. The NMEC Guidelines are therefore consistent with
p.000056: internationally-accepted approaches to, and norms of,
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-67
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical governance of biomedical research involving human subjects at that time.
p.000056:
p.000056: 2.35. We have reviewed the NMEC Guidelines. We have no hesitation in using the NMEC Guidelines as the
p.000056: starting point of the larger enquiry in this Consultation Paper. Although it was formulated in the
p.000056: restricted context of the governance of biomedical research on human subjects by the medical professions
p.000056: (as appropriate and in keeping with the NMEC’s terms of reference), the principles expressed in it and the
p.000056: framework which it recommended for the ethical governance of clinical research are entirely sound and are universally
p.000056: accepted within the medical professions.
p.000056:
p.000056: 2.36. We therefore are of the view that the principles and the framework for ethical governance of
p.000056: biomedical research on human subjects set out in the NMEC Guidelines are an appropriate foundation for our
p.000056: proposals for a scheme of ethical governance of all clinical research on human subjects in Singapore, whether or not
p.000056: such research is carried out by members of the medical professions, and whether or not such research is carried out in
p.000056: an institution under the direct jurisdiction of the Ministry of Health pursuant to the Private Hospitals and Medical
p.000056: Clinics Act.
p.000056:
p.000056: Limitations of the Current Regulatory Regime
p.000056:
p.000056: 2.37. The evolution of regimes for the ethical governance of clinical research and drug trials must be
p.000056: seen in the context of the history of clinical research and drug trials in Singapore. At the time when the
p.000056: Clinical Trials Regulations were first enacted, drug trials were the most common kind of clinical research trial.
p.000056: As such, it was entirely appropriate to enact the Clinical Trials Regulations as subsidiary legislation
p.000056: under the Medicines Act, which deals principally with medicines.
p.000056:
p.000056: 2.38. Likewise, until recently, the vast majority of clinical research (whether drug trials or non-drug
p.000056: trials) were carried out by researchers who were medical practitioners registered under the Medical Registration
p.000056: Act (Cap. 174), or in Government medical institutions directly controlled by the Ministry of Health, or in
p.000056: hospitals and medical clinics licensed under the Private Hospitals and Medical Clinics Act. In all of these
p.000056: cases, the competent supervisory authority was the Ministry of Health.
p.000056:
p.000056: 2.39. In recent years, however, the development of the biomedical industry in Singapore has led to an
p.000056: increasing proportion of non-drug trials. For example, in 2002, hospital ethics committees of the five main
p.000056: restructured hospitals in Singapore reviewed nearly three times as many applications for non-drug trials as
p.000056: they did for drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-68
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.40. Clinical research tends increasingly to be institutionally-driven, rather than being researcher-driven (the
p.000056: traditional model assumed in the current regulatory regime). Company-driven drug trials received by the HSA now
p.000056: outnumber researcher-driven drug trials.
p.000056:
p.000056: 2.41. Concomitantly, an increasing proportion of clinical research trials are now also being carried out outside
p.000056: the traditional paradigm assumed by the current regulatory environment: many trials are now led by
p.000056: researchers, who although being qualified and competent for the trials proposed by them, are not
p.000056: medical practitioners registered under the Medical Registration Act, or by researchers who work in or for
p.000056: entities not subject to the regulatory jurisdiction of the Ministry of Health. Such entities include
p.000056: companies and other commercial entities in the biomedical industry, research institutes and statutory
p.000056: agencies with an interest in the biomedical industry.
p.000056:
p.000056: 2.42. The vast majority of these new players in the field of clinical research in Singapore are keenly aware of
p.000056: the need for proper ethical governance. Most researchers are anxious to conform to
p.000056: internationally-accepted standards for ethical governance. In many cases, researchers are involved as collaborators
p.000056: in multi- jurisdictional or multi-centred (or both) clinical research projects.
p.000056:
p.000056: 2.43. With the development of the biomedical industry in Singapore, new avenues of biomedical inquiry
p.000056: are rapidly emerging, and the traditional categorisation of research trials into drug trials and non-drug trials
p.000056: for the purposes of ethical governance is rapidly becoming irrelevant and obsolete. Some new kinds of
p.000056: research may blur the border between drug and non-drug trials. For example, the first use of a new drug
p.000056: already approved elsewhere on the local population: in this situation, is the trial one for the drug, or a
p.000056: trial to observe and determine the responses of the local population to the drug? New kinds of research trials
p.000056: include trials of medical devices, experimental therapy procedures (which may or may not involve drugs), new modes
p.000056: of non-drug treatment and new diagnostic methods. Other increasingly important research include
p.000056: epidemiological or population studies (which may or may not require invasive interaction with human subjects),
p.000056: genetic screening, genetic research and research which involve no direct interaction with human subjects but only
p.000056: access to their personal medical or genetic information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-69
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.44. In summary:
p.000056:
p.000056: • The most comprehensive formal framework for the ethical governance of clinical research trials at the moment is
p.000056: limited largely to drug trials, or “clinical trials” as defined in the Medicines Act. The principal
p.000056: documents setting out this framework of ethical governance are the Medicines Act, the Clinical Trials
p.000056: Regulations, and the SGGCP. In this framework, the HSA is the principal regulatory agency.
p.000056:
p.000056: • For clinical research other than drug tr ials, the Ministry of Health exercises indirect control over
p.000056: hospitals and medical clinics under the Private Hospitals and Medical Clinics Act. The Ministry of Health has directed
p.000056: that hospitals establish ethics committees to review and approve applications for both drug and
p.000056: non-drug trials.
p.000056:
p.000056: • For clinical research other than drug trials, the main document spelling out a framework for ethical governance is
p.000056: the NMEC Guidelines.
p.000056:
p.000056: • There is some uncertainty as to whether the jurisdiction of the Ministry of Health under the Private Hospitals and
p.000056: Medical Clinics Act extends to clinical research entities or institutions which are not hospitals or clinics
p.000056: liable to be licensed under the Act.
p.000056:
p.000056: • Non-drug trials have in recent years surpassed drug trials in number, and new kinds of clinical research
p.000056: projects not contemplated when the current controlling documents were drafted have since emerged. New types of
p.000056: clinical research have evolved, blurring and making irrelevant the traditional distinction between drug trials and
p.000056: non-drug trials.
p.000056:
p.000056: 2.45. The current framework for ethical governance of clinical research has evolved incrementally and
p.000056: cautiously. In our view, this evolutionary approach was an entirely appropriate response to specific
p.000056: needs and technological advances as they developed over the years.
p.000056:
p.000056: 2.46. At a time when the bulk of medical research was centred about drug trials carried out by the medical
p.000056: professions, it was entirely appropriate to provide for a scheme of ethical governance within the
p.000056: framework of the Medicines Act. But the present and future of clinical research on human subjects embraces a
p.000056: diversity of research inquiry which can no longer be accommodated within the current framework. Accordingly, we think
p.000056: that it is now the appropriate time to undertake a global review of the current rules and framework for the ethical
p.000056: governance of clinical research, and a new, unified framework be created for the ethical governance of all
p.000056: research involving human subjects whether involving drug or non-drug trials.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-70
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 2.47. The principles and ethical governance framework expressed in the Clinical Trials Regulations, the SGGCP and
p.000056: the NMEC Guidelines have served us well in their restricted contexts, and are universally accepted. We take the view
p.000056: that these remain sound guides, and should wherever possible be applied and extended as appropriate to all
p.000056: other forms of clinical research involving human subjects. To this end, the current provisions relating to drug
p.000056: trials should be substantively retained insofar as drug trials are concerned, subject to the procedural
...
p.000056: must never override this”. We agree with these statements of the NMEC, and likewise adopt them. In keeping
p.000056: with the spirit of this definition, we therefore exclude therapeutic activities undertaken with the sole
p.000056: intention of benefiting the patient from our definition of clinical research.
p.000056:
p.000056: 3.6. Subject to the preceding qualifications, we propose to define clinical research in the following
p.000056: terms:
p.000056:
p.000056: Any research study, trial or activity involving human subjects, human tissue, or medical, personal or
p.000056: genetic information relating to both identifiable and anonymous individuals, undertaken with a
p.000056: view to generating data about medical, genetic or biological processes, diseases or conditions in human subjects, or
p.000056: of human physiology or about the safety, efficacy, effect or function of any device, drug, diagnostic,
p.000056: surgical or therapeutic procedure (whether invasive, observational or otherwise) in human subjects whether as
p.000056: one of the objectives or the sole objective, of the research study, trial or activity
p.000056:
p.000056: and
p.000056:
p.000056: which research study, trial or activity has the potential to affect the safety, health, welfare, dignity or privacy of
p.000056: the human subjects involved in the study, or of the donors of human tissue or information used in the research, or of
p.000056: the family members of any of the human subjects or donors thereof, or to which such medical, personal or genetic
p.000056: information relates.
p.000056:
p.000056: Savings
p.000056:
p.000056: 3.7. We make clear that nothing in this Consultation Paper is intended to supplant the recommendations
p.000056: that we have made in the Human Stem Cell Report and the Human Tissue Research Report, and tha t
p.000056: the recommendations contained in this Consultation Paper are intended to supplement those advanced in our
p.000056: first two Reports.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-73
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Exceptional Situations
p.000056:
p.000056: 3.8. We note that there may be some exceptional circumstances in which it may be ethically acceptable
p.000056: to abbreviate or temporarily suspend the usual ethics review procedures and requirements, provided that all the
p.000056: applicable legislative and regulatory requirements are satisfied. We have in mind situations of national
p.000056: security or emergency health situations, in w hich urgent research may have to be carried out to avert
p.000056: harm to national security or for the urgent protection or treatment of whole populations at risk. In such cases, we
p.000056: think that it is permissible for institutional review boards in consultation with the proper authorities to
p.000056: formulate and lay down written guidelines for the exemption or expedited review of defined classes or types of
p.000056: such emergency or urgent research in the national interest.
p.000056:
p.000056: 3.9. We therefore recommend that all clinical research as defined in this section be statutorily subject to
p.000056: review and approval by and to the continued supervision of an institutional review board in
p.000056: accordance with the principles discussed below.
p.000056:
p.000056:
p.000056: Recommendation 2:
p.000056:
p.000056: • The current statutory requirement for review and approval by an institutional review board in
p.000056: drug trials should be extended to all kinds of clinical research involving human subjects, as defined in this section.
p.000056:
p.000056: • All clinical research proposed to be carried out in Singapore must be submitted to and approved by a
p.000056: properly constituted institutional review board.
p.000056:
p.000056: • No programme of clinical research may be commenced or carried out without the approval of such an
p.000056: institutional review board, or other than on terms as set out by such an institutional review board.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-74
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART C: ETHICAL GOVERNANCE
p.000056:
p.000056: SECTION IV: PRINCIPLES OF ETHICAL GOVERNANCE
p.000056:
p.000056: 4. Principles of Ethical Governance The Purpose of Ethical Governance
p.000056: 4.1. Article 5 of the Helsinki Declaration states that in “medical research on human subjects, considerations
p.000056: related to the well-being of the human subject should take precedence over the interests of science and society”.
p.000056: At Article 8, the Declaration states that “[m]edical research is subject to ethical standards that
p.000056: promote respect for all human beings and protect their health and rights”.
p.000056:
p.000056: 4.2. Continuing biomedical human research is fundamental to improving our understanding of biological
p.000056: processes, and ultimately to the improvement of the health and welfare of humankind. Whereas diagnostic, prophylactic
p.000056: and the rapeutic research have as their objective the immediate needs of individual patients, biomedical
p.000056: human research have wider and longer- term objectives in the discovery of new knowledge that may lead
p.000056: to an improvement in the methods of diagnosis, prophylaxis and therapy of individuals, and to the health and
p.000056: welfare of society in general.
p.000056:
p.000056: 4.3. The experience of physicians in the management of patients often lead to new scientific insights, which when
p.000056: coupled with continuing biomedical human research leads to a virtuous circle that supports and advances
p.000056: biomedical knowledge to the benefit of both individuals and society at large. As Article 4 of the Helsinki
p.000056: Declaration states: “Medical progress is based on research which ultimately must rest in part on experimentation
p.000056: involving human subjects”.
p.000056:
p.000056:
p.000056: Applicable Principles
p.000056:
p.000056: 4.4. The fundamental objective of having a system of ethical governance is ultimately the protection
p.000056: and assurance of the safety, health, dignity, welfare and well-being of human research subjects.
p.000056:
p.000056: 4.5. But as with most kinds of diagnostic, prophylactic or therapeutic interventions, most
p.000056: forms of biomedical human research unavoidably involve some degree of risk of harm (however minimal or remote) to
p.000056: the human subject.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-75
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 4.6. Ethical assessment and judgment therefore necessarily involves an assessment and balancing of
p.000056: the potential harms and benefits. In general, clinical research should be directed towards the minimisation of risks
p.000056: and the maximisation of benefits, always bearing in mind the overriding considerations of the safety, health,
p.000056: dignity, welfare and well-being of the human subject.
p.000056:
p.000056: 4.7. To this end, a system of ethical governance must ensure that there is a proper assessment
p.000056: and weighing of the potential harms against the potential benefits of all biomedical human research, in
p.000056: accordance with the ethical values of the community. A proper system of ethical governance serves to strengthen
p.000056: public confidence in biomedical human research by ensuring that all forms of biomedical human research conform
p.000056: to the accepted body of ethical values of the community.
p.000056:
p.000056: 4.8. We recognise, however, that there can be neither absolute certainty nor finality as to the precise
p.000056: content of the body of ethical values to be applied in such an assessment. This is so in Singapore, as it is
p.000056: everywhere else in the world. The body of ethics in any given society is neither fixed nor clearly
p.000056: defined for all time, but evolves in response to advances in knowledge, technology, changes in social mores,
p.000056: and community dialogue and debate.
p.000056:
p.000056: 4.9. These fundamental principles are expressed and repeated in international documents such as the Declaration
p.000056: of Helsinki, the Nuremberg Code, the Belmont Report (Ethical Principles and Guidelines for the Protection of
p.000056: Human Subjects of Research, 1976), the UNESCO Universal Declaration on the Human Genome and Human Rights 1997, and the
p.000056: WHO’s Proposed Guidelines on Ethical Issues in Medical Genetics and Genetic Services 1997 (as updated 2001).
p.000056:
p.000056: 4.10. In Singapore, these same principles are found or reflected in regulations such as the Clinical
p.000056: Trials Regulations, and in documents such as the SGGCP and the NMEC Guidelines. We have already addressed some
p.000056: of these principles at length in the Human Stem Cell Report and the Human Tissue Research Report.
p.000056:
p.000056: 4.11. These core principles are exp ressed, restated and elaborated upon in many ways. For example, the NMEC
p.000056: expresses some of these fundamental principles as follows:
p.000056:
p.000056: “2.3.1 The fundamental principle of research involving human subjects is respect for life. From this
p.000056: principle, others follow: that of beneficence, justice, and autonomy. Beneficence concerns the benefits and
p.000056: risks of participating in research. Justice relates to
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-76
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: the fair distribution of risks in research in relation to the anticipated benefits for research subjects.
p.000056: Autonomy refers to the right of individuals to decide for themselves what is good for them.
p.000056:
p.000056: 2.3.2 With respect to beneficence, the benefits and risks of research must always be carefully assessed.
p.000056: Research on human subjects should only be undertaken if the potential benefits arising from the expected new
p.000056: knowledge are of sufficient importance to outweigh any risk or harm inherent in the research, bearing in mind that
p.000056: risks and benefits may not be measurable on the same scale.
p.000056:
p.000056: 2.3.3 …Justice must be exercised in the allocation of the anticipated risks and the anticipated benefits…
p.000056:
p.000056: 2.3.4 A corollary of autonomy is that any research procedure must have, as far as possible, the
p.000056: free and informed consent of the experimental subject. Similarly, respect for the individual implies
p.000056: that safeguards should be provided to protect the experimental subject form physical and
p.000056: emotional harm including provisions for confidentiality.”
p.000056:
p.000056: 4.12. Despite some uncertainty at the edges, a core of universally accepted principles and ethical
p.000056: values lie at the heart of most societies in their application to the protection of human research subjects.
p.000056:
p.000056: 4.13. It is desirable that a code of applicable principles for ethical governance be eventually formulated for
p.000056: the common guidance alike of ethics committees, institutional review boards, research institutions,
p.000056: researchers, the human subjects of research and all other parties involved in human research, in the
p.000056: interests of consistency and fairness of the judgments of institutional review boards.
p.000056:
p.000056: 4.14. We do not attempt, and it is beyond the scope of this document, to attempt to list all these
p.000056: fundamental principles. In our view, the applicable principles of the proposed code are best settled
p.000056: in an incremental and evolutionary manner through dialogue and discussion between inst itutional review boards
p.000056: and the other parties in the research governance process. This process of dialogue and discussion should be
p.000056: informed by and have reference to the experiences of the parties involved.
p.000056:
p.000056: 4.15. We think that this process of dialogue and disc ussion is best sponsored or promoted through a national
p.000056: agency. We elaborate on this in our discussion on the national organisation of ethical governance
p.000056: in Part D
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-77
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: below. Likewise, the draft of such a code, and the revisions thereto, should be sponsored and led by such
p.000056: a national agency.
p.000056:
p.000056: 4.16. We take the view that it is part of the function of a responsive and dynamic system of ethical
p.000056: governance that the applicable body of ethics be reviewed and assessed from time to time to keep
p.000056: it relevant to and reflective of community values and the needs of research.
p.000056:
p.000056: 4.17. We emphasize that it is not the intention of this document to prescribe the specific ethical principles to be
p.000056: applied by institutional review boards and researchers in the process of ethical governance. We believe that these are
p.000056: professional judgments which are appropriately and properly left to members of institutional review
p.000056: boards, researchers and other parties involved in the process of ethical governance.
p.000056:
p.000056: 4.18. We note, however, that there are broad ethical principles which are universally accepted and
p.000056: applied in all the leading research jurisdictions, and we take the view that it would be appropriate
p.000056: and desirable if institutional review boards, researchers and other parties involved in the process of ethical
p.000056: governance consider taking these ethical principles into account.
p.000056:
p.000056: 4.19. Such principles, in addition to or in elaboration of those identified by the NMEC, might include:
p.000056:
p.000056: • Respect for the human body, welfare and safety, and for religious and cultural perspectives and traditions of
p.000056: human subjects. We elaborated on this principle in our Human Tissue Research Report. In the context of a diverse
p.000056: society such as Singapore, researchers have an especial obligation to be sensitive to religious and
p.000056: cultural perspectives and traditions of their human subjects.
p.000056:
p.000056: • Respect for free and informed consent. Again, this principle is discussed at length in our
p.000056: Human Stem Cell Report, and our Human Tissue Research Report. A detailed discussion of the requirements of consent is
p.000056: also set out at section 2.5 of the NMEC Report, and we note also the strict requirements with regards to consent
p.000056: laid down by the Clinical Trials Regulations and the SGGCP.
p.000056:
p.000056: • Respect for privacy and confidentiality. This is treated in detail in section 2.6 of the NMEC
p.000056: Guidelines, and again in our Human Tissue Research Report.
p.000056:
p.000056: • Respect for vulnerable persons. This is discussed in paragraphs 2.5.5 to 2.5.6 of the NMEC Guidelines. In
p.000056: essence, the ethics governance
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-78
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: process must pay especial attention to the protection of persons who may not be competent to give consent
p.000056: themselves, or whose ability to give free and full consent may be compromised by reason of their physical
p.000056: condition or other circumstances, such as being in a dependent relationship.
p.000056:
p.000056: • Avoidance of conflicts of interest, or the appearance of conflicts of interest. We further elaborate
p.000056: on this principle below in our discussion of the roles and responsibilities of investigators and institutional review
p.000056: boards.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-79
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION V: INSTITUTIONAL REVIEW BOARDS
p.000056:
p.000056: 5. Institutional Review Boards
p.000056:
p.000056: The Role of Institutional Review Boards
p.000056:
p.000056: Nomenclature
p.000056:
p.000056: 5.1. Ethical review bodies having the first responsibility for ethical review in the ethical review and
p.000056: governance process are variously known as “ethics committees”, “research ethics committees” or “institutional
p.000056: review boards”. In the context of Singapore, the term “ethics committees” is presently most commonly
p.000056: used.
p.000056:
p.000056: 5.2. We prefer instead the term “institutional review boards”. Our main reason for doing so is our desire to see
p.000056: institutional review boards established as full-time permanent supervisory bodies organised at and integral to
p.000056: the function of the highest administrative levels in all institutions in which research is carried out.
p.000056: For instance, we think that institutional review boards in hospitals should be organised at the same
p.000056: level as medical boards, and that the institutional review board should report directly to the highest level of
p.000056: management of the hospital. We believe that the term “institutional review board” (“IRB”) best reflects this
p.000056: role.
p.000056:
p.000056: 5.3. We differentiate here between IRBs which review, approve and monitor clinical research involving
p.000056: humans, and hospital ethics committees that address medical practice issues. For the avoidance of
p.000056: doubt, the recommendations in this paper cover only IRBs which review, approve and monitor clinical
p.000056: research involving human beings.
p.000056:
p.000056: 5.4. There is universal agreement in all developed countries that IRBs are central to a proper
p.000056: framework of ethical governance of human research, and that the primary objective of an IRB is the protection and
p.000056: assurance of the safety, health, dignity, welfare and well-being of human research subjects, in keeping with
p.000056: the principles outlined above.
p.000056:
p.000056: 5.5. Increasingly, collaborative research programmes are ca rried out across international borders (in
p.000056: multi- national research programmes) or by researchers in several institutions (in multi-centre research
p.000056: programmes), or even a combination of both. It is usually a condition of such research programmes that the
p.000056: proposed or prospective researchers secure the approval of a properly constituted IRB in their own country or
p.000056: institution. Without a proper constituted IRB or access to such an IRB, an institution engaging in human research
p.000056: cannot hope to participate in suc h multi- national or multi-centre collaboration research programmes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-80
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.6. From this viewpoint, the harmonisation of our national ethical governance framework with that in
p.000056: leading research jurisdictions is of national strategic importance.
p.000056:
p.000056: 5.7. The ultimate respons ibility for the ethical compliance of clinical research rests with the researchers who
p.000056: propose and carry out the research, and with the institution which sanctions the research or in which research is
p.000056: carried out.
p.000056:
p.000056: 5.8. The IRB is the vehicle through which such institutions act to implement a proper system of ethical
p.000056: governance of research carried out in such institutions.
p.000056:
p.000056: 5.9. Every institution that conducts research, or allows research to be carried out on its premises, or
p.000056: on its patients, or on or involving acces s to or use of human tissue collections in its custody, or on or involving
p.000056: access to or use of medical records or other personal information in its custody, should have an effective
p.000056: and properly constituted IRB.
p.000056:
p.000056:
p.000056: Recommendation 3:
p.000056:
p.000056: The current requirement that every hospital have an institutional review board should be statutorily
p.000056: formalised, and extended to all institutions that carry out clinical research. Every institution that
p.000056: conducts research, or allows research to be carried out on its premises, or on its patients, or on or involving
p.000056: access to or use of human tissue collections in its custody, or on or involving access to or use of medical records or
p.000056: other personal information in its custody should have an effective institutional review board.
p.000056:
p.000056:
p.000056: Shared, “Domain” and Other Special Institutional Review Boards
p.000056:
p.000056: 5.10. Where by reason of the small size of the institution or the small number of research proposals it is
p.000056: impractical to establish and maintain a standing IRB of its own, such institutions should make clear
p.000056: arrangements with other institutions which maintain IRBs, to be supervised and audited by the IRBs of these other
p.000056: institutions.
p.000056:
p.000056: 5.11. Alternatively, it is permissible for several such institutions to jointly appoint a shared IRB.
p.000056:
p.000056: 5.12. Even in cases of institutions who already have their own IRBs, these institutions may prefer or
p.000056: wish to refer some kinds of research applications
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-81
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: (for example, a proposal for research in a specialist area) to a specialist IRB or a domain IRB which has
p.000056: the technical capacity to assess research in that specialised area. Again, several institutions could jointly appoint
p.000056: and share in the expertise of such an IRB in situations where such expertise is limited. Such a specialist IRB has
p.000056: the advantage of delivering consistent decisions, and special competent and knowledge in their field
p.000056: of specialisation. It is also acceptable that a cluster of hospitals cooperate in developing a panel of IRBs to cover
p.000056: all reasonable disciplines.
p.000056:
p.000056: 5.13. To our knowledge, there are currently no commercial IR Bs in Singapore, in the sense of a board that offers
p.000056: ethics review on a commercial basis. In principle, we have no objection to such boards, provided that
p.000056: sufficient safeguards are taken against the obvious objections such as a lack of true independence, but will leave this
p.000056: issue to the national supervisory agency which we recommend in Section 7 below. In any event, we think
p.000056: that careful investigation and consideration by the national supervisory agency should be carried out before a
p.000056: commercial IRB is given accreditation as described in Section 7 below.
p.000056:
p.000056:
p.000056: The Responsibilities of Institutional Review Boards
p.000056:
p.000056: 5.14. In its acts and decisions, and in the exercise and discharge of its duties and responsibilities, an IRB acts
p.000056: on the behalf of the institution that appo ints it and exercises on its behalf the authority and powers of
p.000056: that institution in matters within the terms of reference of the IRB.
p.000056:
p.000056: 5.15. IRBs are required to carry out three distinct functions and responsibilities:
p.000056:
p.000056: 5.15.1. Ethical Review Gateway. In this responsibility, IRBs assume the role of an ethical review gateway through
p.000056: which all proposals for biomedical human research must be submitted and assessed for ethical acceptability
p.000056: and compliance, and for potential harms and benefits in accordance with the principles outlined in Section
p.000056: IV above. In this model of ethical governance, all proposed clinical research involving human subjects
p.000056: must be submitted for review and approval before the proposed research may be carried out. In the majority of
p.000056: developed countries, this is made a statutory or otherwise legal requirement. We recommend this
p.000056: model for adoption in Singapore.
p.000056:
p.000056: 5.15.2. Continuing Review, Supervision and Audit. In this responsibility, IRBs assume jurisdiction and
p.000056: authority for the continuing supervision and audit of approved research programmes upon their commencement. The
p.000056: IRB is also empowered to carry out audits of
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-82
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: research programmes, or to require such audits to be done, in order to ensure continued compliance with the
p.000056: terms of approval throughout the lifetime of the research programme. IRBs may also direct or otherwise
p.000056: require amendments or modifications to research proposals at any time, and to make such amendments or
p.000056: modifications a condition of approval for the conduct of the research programme.
p.000056:
p.000056: 5.15.3. Outcome Assessment, Reporting and Feedback. In this responsibility, IRBs (especially
p.000056: those in large institutions with a large number of research programmes) undertake the monitoring and
p.000056: collation of adverse event reports, the outcomes of the research programmes, an evaluation of the actual versus
p.000056: the anticipated outcome or results, and the reporting of outcomes and trends to the relevant authorities and to
p.000056: the institutions that they are appointed by and to whom they are responsible. Another major aspect of this role
p.000056: is the role of IRBs in providing feedback and maintaining a dialogue on applicable standards with its
p.000056: constituent researchers. In the discharge of their role, IRBs can and should also act as the key institutional
p.000056: agency which receives, acts upon and reports to the relevant authorities on concerns and feedback expressed by the
p.000056: human subjects of the research programmes.
p.000056:
p.000056: 5.16. Additionally, IRBs may (but not necessarily or invariably, according to the terms of their constitution
p.000056: and appointment) also under take responsibility for:
p.000056:
p.000056: 5.16.1. Review of Scientific Merits. In this responsibility, IRBs carry out peer or expert assessments of the
p.000056: scientific merits and soundness of proposed research programmes. In view of the present system requiring the
p.000056: grant funding age ncy to conduct scientific review of the research, we clarify that the extent of the IRBs
p.000056: responsibility for scientific review may be delineated by the particular institution to which it belongs. By way
p.000056: of illustration, where the institution possesses the necessary expertise needed or where the research
p.000056: project is not subject to grant funding, the IRB may conduct scientific review; where the institution
p.000056: does not possess the necessary expertise, a summary of the scientific review conducted by the grant funding
p.000056: agency should be submitted to the IRB as one of the documents required for approval by the IRB. In all cases, we think
p.000056: it is important that clear standard operating procedures in this area are established by the particular
p.000056: institution. The fact that a particular proposed programme of research is judged to be of sufficient
p.000056: scientific merit does not necessarily mean that it satisfies ethical considerations, although in many
p.000056: cases, these two
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-83
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: considerations are linked, especially in the assessment of harms versus benefits.
p.000056:
p.000056: 5.17. It is the responsibility of all institutions to ensure that a proper review of the scientific merits of all
p.000056: clinical research proposals is carried out.
p.000056:
p.000056: 5.18. Institutions also have the responsibility for establishing clear standard operating procedures for
p.000056: the review of the scientific merits of all clinical research proposals, and whether this is to be done by a separate
p.000056: agency or committee (whether internal or external), or whether it is to be done by the IRB. If the review of
p.000056: scientific merits is also to be conducted by the IRB, this must be made clear to, and accepted by, the IRB.
p.000056:
p.000056: 5.19. The implementation of a framework for the work of IRBs has been laid down and discussed
p.000056: extensively by the NMEC in section 3 of the NMEC Guidelines. We agree ge nerally with the principles of implementation
p.000056: laid down by the NMEC, and further elaborate on these principles in our discussion of the constitution of
p.000056: IRBs below.
p.000056:
p.000056:
p.000056: Recommendation 4:
p.000056:
p.000056: Institutional Review Boards should have responsibility for:
p.000056:
p.000056: • The ethical review and approval of proposed clinical research programmes. This should
p.000056: take into account the scientific merits of proposed clinical research programmes.;
p.000056:
p.000056: • The continuing review, supervision and audit (including monitoring feedback from research
p.000056: subjects) of clinical research programmes approved by them. Reporting of the outcomes of the review and audit
p.000056: to proper authorities and to their appointing institutions and to principal investigators of the research
p.000056: programmes;
p.000056:
p.000056: • Reporting on the clinical research programmes and in particular the results of the programme approved by
p.000056: them to the proper authorities and to their appointing institutions, feedback to the constituent researchers of the
p.000056: institutional review board, and monitoring feedback from research subjects.
p.000056:
p.000056: • Additionally, and provided that this responsibility and jurisdiction is clearly set out by the terms
p.000056: of its constitution and appointment by the appointing institution, institutional review boards may
p.000056: also have responsibility for the review of the scientific merits of proposed clinical research programmes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-84
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: The Constitution of Institutional Review Boards
p.000056:
p.000056: 5.20. IRBs should be established and appointed by and at the highest administrative levels of
p.000056: the institutions. They should be appropriately resourced relative to the research activity of the institution
p.000056: and, where this is substantial, should be regarded as one of the key full- time management offices within the
p.000056: organisation of institutions, and not merely as honorary or ad hoc committees.
p.000056:
p.000056: 5.21. The IRB should be appointed and report to at least an authority at the level of the Chief Executive Officer
p.000056: (as required by the NMEC guidelines in the case of hospitals falling under the jurisdiction of the Ministry of Health
p.000056: pursuant to the Private Hospitals and Medical Clinics Act) or senior management.
p.000056:
p.000056: 5.22. IRBs should not be appointed as ad hoc committees to consider research proposals as and when they arise,
p.000056: although it is acceptable for institutions with standing IRBs to appoint special ad hoc committees in
p.000056: consultation with their standing IRBs to consider special research proposals. We prefer, in such cases, that
p.000056: the institution works with their standing IRB to appoint special subcommittees co-opting experts or reviewers to assist
p.000056: the standing IRB in the particular project concerned. For example, an IRB may receive a research proposal
p.000056: involving an area of research with which no member of the IRB is familiar. In such a case, the institution may work
p.000056: with the IRB to identify and co-opt ad hoc experts or reviewers to assist the IRB in its assessment and review
p.000056: of the proposal. The co-opted ad hoc experts or reviewers sit as a subcommittee of the IRB.
p.000056:
p.000056: 5.23. Institutions have an obligation to ensure that IRBs receive adequate administrative support
p.000056: that is commensurate with their central role in the ethical governance process.
p.000056:
p.000056: 5.24. IRBs should have sufficient full-time administrative support so as to ensure continuity and
p.000056: consistency in the work of the IRBs, to discharge its continuing review, supervision and audit obligations,
p.000056: its outcome assessment and reporting duties, and to ensure that their decisions are made with regard to
p.000056: previously-established precedents and decisions made by themselves and their predecessors.
p.000056:
p.000056: 5.25. Institutions should also ensure that IRBs have sufficient administrative support so as to ensure
p.000056: that proposals are reviewed and dealt with in a timely manner within the target time- frames set by the
p.000056: institution.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-85
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Composition
p.000056:
p.000056: 5.26. We are of the opinion that the SGGCP, in particular paragraph 3.2.3, and the NMEC Guidelines, in particular
p.000056: paragraph 3.2.2, lay out appropriate and comprehensive guidelines regarding the composition of an ethics
p.000056: committee. We endorse these requirements, and propose that they be similarly used to form the framework for
p.000056: the composition of an IRB.
p.000056:
p.000056: 5.27. In addition, we propose to highlight certain general requirements for the composition of an IRB:
p.000056:
p.000056: 5.27.1 Given the importance of the IRB, it is important that the core members of IRB should be appointed
p.000056: from among the institutions’ most senior, most respected and scientifically competent officers, researchers or
p.000056: consultants, who possess the appropriate experience and training.
p.000056:
p.000056: 5.27.2 The core members of the IRB should be able to devote sufficient time commensurate to the workload of
p.000056: the IRB.
p.000056:
p.000056: 5.27.3 Representation on an IRB should not be restricted to members of the institution, but should include
p.000056: external and lay representation.
p.000056:
p.000056: 5.27.4 External representation may be in the form of specialists of reputation from other
p.000056: institutions: the objective here is to lend impartiality and objectivity to the work of the IRB, and to ensure
p.000056: that the decisions of the board are carried out in accordance with scientific thinking accepted within the community.
p.000056:
p.000056: 5.27.5 IRBs should also have lay, non-scientific or non-medical representation. Where pract
p.000056: ical, and where the size and volume of the workload of the IRB permits, lay representation may include
p.000056: respected lay members of the community, experts in philosophy, ethics, psychology, sociology or the law.
p.000056: The IRB may consult representative religious leaders on an ad hoc basis where it feels that such a need
p.000056: exists.
p.000056:
p.000056: 5.27.6 As far as possible, the core membership of an IRB should be representative of the particular fields
p.000056: of research carried out in the institution, such that for every research proposal received by the board, there
p.000056: will be at least one specialist or expert (and preferably more) on the IRB that is competent to assess that proposal.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-86
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Institutional Conflicts of Interest
p.000056:
p.000056: 5.28. In the relationship between an institution and the IRB, the fundamental underlying principles are
p.000056: the independence of the IRB in the exercise of its powers and duties, and its ethical integrity.
p.000056:
p.000056: 5.29. The research programmes which IRBs are asked to review are often of considerable financial or
p.000056: other benefit (potential or otherwise) to the appointing institutions. In the review of these research
p.000056: programmes, both IRBs and institutions alike must be aware of the potential conflict of interest involved
p.000056: and take reasonable steps to minimise conflict.
p.000056:
p.000056: 5.30. It is for this reason, among others, that we have recommended that IRBs report directly to the highest
p.000056: levels of governance in an institution. In the case of hospitals and other similar medical institutions, the IRB
p.000056: should not report to the medical board of that institution.
p.000056:
p.000056: 5.31. At minimum, all communications in relation to the review of the research programme in question should be
p.000056: fully documented in writing. Informal communication between the institution and its officers and the individual
p.000056: members of the IRB in connection with such research programmes should be strongly discouraged.
p.000056:
p.000056: 5.32. As part of its duty to make periodic reports, we recommend that IRBs include a special report on
p.000056: all reviews of research programmes in which there is or is potentially such a conflict of interest. This
p.000056: special report should be made directly to the board of directors of the institution.
p.000056:
p.000056:
p.000056: Multinational and Multi-Centre Research Projects
p.000056:
p.000056: 5.33. As we have previously pointed out, research projects or trials increasingly involve collaborators in more one
p.000056: country. Indeed, o ne of the hallmarks of current leading-edge research are the multinational and
p.000056: multi-centre collaborative nature of the research effort, which often involves a very large number of
p.000056: researchers based in many institutions in different countries.
p.000056:
p.000056: Multinational Research Projects
p.000056:
p.000056: 5.34. Guidance has been sought from us as to whether ethics review should be required for the portion of
p.000056: multinational research projects carried out in Singapore. We take the view that ethics review should indeed be
p.000056: required for any portio n of a research project or trial carried out in Singapore, or involving human tissue, or
p.000056: medical, personal or genetic information
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-87
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: collected in Singapore or derived from donors in Singapore, or which involves the export or
p.000056: transmission abroad of any human tissue, or medical, personal or genetic information collected in Singapore
p.000056: or derived from donors in Singapore.
p.000056:
p.000056: 5.35. This is on the basis that Singapore law and Singapore ethical standards and rules are not necessarily the same
p.000056: as that in other countries. This approach is supported in other jurisdictions. Otherwise there would be a
p.000056: moral hazard in the temptation of researchers picking the jurisdiction perceived to have the most liberal regime as
p.000056: their ethical jurisdiction of choice.
p.000056:
p.000056: 5.36. Nonetheless, we envisage that expedited review may be permissible in certain circumstances. For
p.000056: example, where patient tissues from an IRB approved study conducted in another country comes to
p.000056: Singapore for analysis, and the Singaporean institution does not have direct contact with the patient but merely
p.000056: performs tests on patient samples.
p.000056:
p.000056: 5.37. To avoid unnecessary bureaucracy, local research collaborators should be encouraged to provide their local
p.000056: IRBs with full documentation of ethics review applications made to the IRB of the lead jurisdiction, together
p.000056: with copies of all relevant queries and rulings of that IRB. If applications have been submitted or are proposed
p.000056: to be submitted to other IRBs in other jurisdictions, information on these applications, and on their
p.000056: outcome, should be provided to the local IRB as well.
p.000056:
p.000056: 5.38. The local IRB may then elect to give expedited approval of such applications after
p.000056: reviewing the documentation, and the reasons for the decision of the leading ethical review board. In general,
p.000056: local IRBs should consider a full ethics review if a substantial portion of the research project is to be carried
p.000056: out in Singapore. Similarly, local IRBs should be concerned to ask for evidence of approval by IRBs
p.000056: in the jurisdiction in which the major part of the research project will be carried out.
p.000056:
p.000056:
p.000056: Recommendation 5:
p.000056:
p.000056: The local portion of a proposed multinational research programme should be subject to review by the institutional
p.000056: review board(s) of the local partner institution or institutions.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-88
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Multi-Centre Research Projects
p.000056:
p.000056: 5.39. Currently, the situation is that ethics review is required by the ethics committees of every
p.000056: institution which will be involved in the proposed research programme. Except for drug trials, there is
p.000056: no mechanism or requirement that any one of the ethics committees involved should act as a principal or
p.000056: coordinating ethics committee (in drug trials, this function is currently carried out by the CTCC).
p.000056:
p.000056: 5.40. We recommend that a “lead” IRB be designated from among the IRBs of the participating institutions. The
p.000056: researchers may be asked to propose a lead IRB. On reviewing the proposal, the proposed lead IRB may then
p.000056: decide to accept nomination as the lead IRB, and if not, to give reasons why other IRBs may be more
p.000056: appropriate. If the proposal is accepted by the proposed lead IRB, the first application for review should be made
p.000056: to that lead IRB. The choice of the lead IRB should be dictated by considerations such as the
p.000056: principal institution of affiliation of the principal investigator, the location where the greater part of
p.000056: the research is carried out, the expertise of the constituted IRB, or the location where the largest number of subjects
p.000056: is located.
p.000056:
p.000056: 5.41. The primary ethical and scientific assessment should be made by the lead IRB, and copies of its decision sho
p.000056: uld be sent to the other institutions or organizations involved. Each of the IRBs of the other institutions may still
p.000056: give further consideration to ethical and administrative aspects of the research which are specific to their
p.000056: own institutions or organisations.
p.000056:
...
p.000056: applicable, the most up -to-date progress reports. The proposals or progress reports on which ethics review is
p.000056: based should be drawn up specifically for the purposes of submission for ethical review.
p.000056:
p.000056: 5.50. Research proposals should not consist of the same or substantially the same documents submitted by
p.000056: the researchers for the purpose of a proposal for funding. IRBs should bear in mind that research proposals submitted
p.000056: for ethical review are directed at a completely different end to that of proposals submitted for funding
p.000056: purposes.
p.000056:
p.000056: 5.51. The requirements of impartiality, fair review, and documentation of decisions should apply
p.000056: equally to IRBs engaged in the continuing review, supervision or audit of a research program.
p.000056:
p.000056: 5.52. Conflicts of interest. IRBs and members of IRBs should take especial care to avoid conflicts of interest,
p.000056: whether actual conflict, potential conflict, or only the appearance of conflict as such.
p.000056:
p.000056: 5.53. A situation of real, potential or apparent conflict of interest amounts to circumstances which
p.000056: adversely affect the impartiality, objectivity and independence of the IRB or of its members as described above.
p.000056:
p.000056: 5.54. In the event that a member of the IRB has a personal interest in the research under review, that
p.000056: member should recuse himself or herself from any consideration of the case by the IRB, a nd he or she should refrain
p.000056: from offering his or her opinion to the board on the particular research under review.
p.000056:
p.000056: 5.55. The IRB member should make full disclosure of such an actual, potential or apparent conflict of interest to
p.000056: the board.
p.000056:
p.000056: 5.56. Free and Informed Consent. We recommend that the current statutory and legal requirements relating to the
p.000056: obtaining of free and informed consent of subjects in drug trials be in principle extended to all other kinds of
p.000056: clinical research with appropriate modifications.
p.000056:
p.000056: 5.57. Both researchers and IRBs should take especial care to ensure that the proposed human subjects will
p.000056: be able to understand and assess the risks of participation, and that the consent -taking procedure and the
p.000056: documentation are properly designed to achieve this end.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-91
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.58. Both researchers and IRBs should ensure that the participants of research projects are aware that they have
p.000056: the right to withdraw from the research programme at any time.
p.000056:
p.000056: 5.59. We recommend that IRBs and institutions formalise arrangements which allow participants a one-stop direct
p.000056: access to the full-time secretariat of the IRB or to a senior officer of the institution charged with
p.000056: quality service standards and control. In this way, participants in research trials can have access to independent
p.000056: officers in order to give feedback on the trial, or to express their concerns.
p.000056:
p.000056: 5.60. In the same vein, we further recommend that researchers consider (and IRBs should consider making it
p.000056: a condition of approval) appointing one of their number (who should be a registered med ical practitioner or a senior
p.000056: member of the research team) as a one-stop participant contact in all cases where the research programme involves any
p.000056: level of clinical intervention or interaction with the participants, and in cases where the interaction (for example,
p.000056: the collation of medical histories, or physical examination) with participants is delegated to support and field
p.000056: workers or assistants.
p.000056:
p.000056: 5.61. A copy of every document signed by research subjects or given to them to read, including the consent
p.000056: documentation, should be given to and retained by the research subjects.
p.000056:
p.000056: 5.62. The requirements for free and informed consent as discussed in our Human Stem Cell Report and our Human Tissue
p.000056: Research Report apply to the use of human biological materials in clinical research.
p.000056:
p.000056: 5.63. Workload. Institutions should ensure that IRBs are not given a workload that compromises the quality of its
p.000056: work, and IRB should likewise ensure that its workload does not compromise the quality of its review. Where
p.000056: this is likely, it is the obligation of the institution to establish additional IRBs, or to enlarge the
p.000056: membership of the IRB, or make formal arrangements for other IRBs to provide an opinion.
p.000056:
p.000056: 5.64. Meetings. IRBs should have regular and frequent formal face-to-face meetings with a defined quorum.
p.000056: The work of the board should not be conducted routinely via circulation of documents. Applications that
p.000056: raise novel, unusual or difficult issues (from the ethical or scientific merit perspectives) or those which
p.000056: present significant risk to partic ipants should be debated and discussed in face-to- face meetings.
p.000056:
p.000056: 5.65. Exempted and Expedited Review. IRBs may draw up and provide for exempted or expedited review
p.000056: of research proposals, in a properly-
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-92
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: deliberated and written set of Standard Operating Procedures for the work of the board.
p.000056:
p.000056: 5.66. Such expedited or exempted review should be allowed only for classes of research programmes which involve
p.000056: minimal or no risk to the safety, health, welfare and well-being of the participants and which are
p.000056: widely accepted in the research community as being eligible for exempted or expedited review.
p.000056:
p.000056: 5.67. The Standard Operating Procedures may allow decisions on applications qualifying for expedited or
p.000056: exempted review to be decided by the chairperson of the IRB or his delegate(s) instead of
p.000056: having to be considered by the whole board.
p.000056:
p.000056: 5.68. Examples of cases in which an exemption from review or an expedited review may be permitted are
p.000056: the analysis and publication of the clinical results of a regime of therapy given by a registered medical
p.000056: practitioner to his or her patients in which the regime of therapy is given purely for therapeutic
p.000056: objectives, or the analysis of patient information without any interaction with the patients themselves.
p.000056:
p.000056: 5.69. Medical Records and Patient Information. The BAC recognises that the issues arising from access to the
p.000056: use of and the custody of medical records and other patient information is becoming increasingly complex. In
p.000056: this area, the ethical issues are inextricably interwoven with legal considerations, and the
p.000056: impact of the existing law is currently unclear in many situations. We hope to explore these issues in a
p.000056: separate subsequent report.
p.000056:
p.000056: 5.70. In the context of institutions such as hospitals with centralised patient records databases, we
p.000056: recommend that IRBs should take steps to determine who should be the proper administrative custodians responsible for
p.000056: patient medical information in the institution, and to establish a system through which the custodians
p.000056: would inform the attending physicians before releasing patients’ medical information for the
p.000056: purposes of medical research.
p.000056:
p.000056: 5.71. In situations where any of the researchers are also the administrative custodian of patient medical
p.000056: information within the institution, procedures should be established to address potential or apparent conflicts of
p.000056: interest.
p.000056:
p.000056: 5.72. Institutions should ensure that clear formal procedures are laid down for the release of all
p.000056: kinds of patient and medical information, and should formulate these procedures in consultation with their
p.000056: ethics committees.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-93
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 5.73. It is desirable that the IRB should have the ultimate authority and responsibility for
p.000056: the ethical clearance of access to patient medical information within the institution, so that no
p.000056: patient medical information may be released for research purposes without clearance by the IRB. Such authority
p.000056: should by necessity also extend over the administrative custodians of patient medical information.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-94
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VI: RESEARCHERS
p.000056:
p.000056: 6. The Responsibilities of Researchers
p.000056:
p.000056: The general responsibilities of researchers
p.000056:
p.000056: 6.1. Researchers share with institutions and IRBs a primary and central role in the ethical governance of clinical
p.000056: research. More than any other party or parties in the ethical review and governance process, they are in
p.000056: the position of having the fullest access to the facts on which ethical judgments are to be made.
p.000056:
p.000056: 6.2. They are responsible for making the threshold decisions in conceiving, designing and putting
p.000056: together a proposed research project. In these decisions, they have the most freedom to shape the
p.000056: proposed research project in a way that gives fullest consideration and respect to ethical considerations,
p.000056: always cognizant of the fact that it is the human subjects whom they study who make their research
p.000056: possible, and are therefore under an obligation to respect and to protect.
p.000056:
p.000056: 6.3. IRBs therefore have to depend on researchers to make full material disclosure and give as full
p.000056: an account of the relevant facts as to enable them to make objective, impartial and fully informed ethical
p.000056: judgments.
p.000056:
p.000056: 6.4. Accordingly, the primary and ultimate responsibility for the ethical compliance of all
p.000056: aspects of the clinical research in question which involves human subjects rests with the
p.000056: researchers. IRBs bear the responsibility for the overall ethical review and approval of
p.000056: clinical research programmes, as explained in Recommendation 4.
p.000056:
p.000056: 6.5. This responsibility of the researcher is a non-delegable and personal responsibility. It is a
p.000056: responsibility which is not and cannot be transferred or delegated to an IRB or any party in the ethics
p.000056: review and governance process merely through the approval of a research proposal by an IRB.
p.000056:
p.000056: 6.6. By the same token, researchers remain entirely responsible to ensure that their research complies with all
p.000056: relevant laws as well as legal or regulatory obligations and requirements. Ethical approval given by an IRB is not to
p.000056: be taken as an assurance or representation by the IRB of such compliance, or as an assumption of legal liabilities
p.000056: arising out of the proposed research by the IRB. In short, it is unethical for resear chers to treat ethical review
p.000056: boards and the review process merely as “legal insurers”, or as “legal insurance”.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-95
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 6.7. Researchers are primarily and ultimately responsible for making the first judgment as to whether in
p.000056: their own professional judgment, the proposed research is ethical.
p.000056:
p.000056: 6.8. Researchers should only submit to ethical review boards proposals for research which they are
p.000056: objectively and professionally satisfied are entirely ethical in all aspects, and are prepared to defend them as such.
p.000056:
p.000056: 6.9. Submission of a research proposal to an IRB by researchers amounts to a representation by the researchers to
p.000056: the IRB and to all parties involved in the ethical review and governance process that, in the
p.000056: objective professional judgment of the researchers, the proposed res earch is ethical in all aspects.
p.000056:
p.000056: 6.10. Researchers should not submit the same or substantially the same documents submitted to IRBs
p.000056: for ethical review as that submitted by them to prospective funding agencies for funding. Researchers should
p.000056: bear in mind that research proposals submitted for ethical review are directed at a completely different end to
p.000056: that of proposals submitted for funding purposes, and should draft them accordingly.
p.000056:
p.000056: 6.11. Accordingly, in no circumstances should researchers use IRBs and the ethical review process as a
p.000056: means of gaining ethical approval for research projects that the researchers themselves entertain doubts or
p.000056: uncertainties about from the ethical point of view.
p.000056:
p.000056: 6.12. We recognise that there may be circumstances in which researchers may in good faith hold the view that
p.000056: the proposed research is ethical, but are nonetheless aware of differing opinions held in good faith by
p.000056: competent peers or an established body of public opinion, or that the proposed research may pose novel risks
p.000056: or other factors whose ethical implications may not be readily quantifiable or ascertained by them.
p.000056:
p.000056: 6.13. In such cases, we take the view that so long as the researchers in good faith are of the belief that the
p.000056: proposed research is ethical, then such proposed research may be submitted for ethics review provided that the
p.000056: researchers make full disclosure of all such differing opinions known to them, and any potential ethical difficulties
p.000056: or controversies known to them or ethical reservations or doubts held by them, and make disclosure of
p.000056: all other material facts and issues that would help the IRB carry out an impartial and objective review.
p.000056: In such a process, where the researchers in good faith effectively assist the IRB in its attempt to explore
p.000056: all potential ethical issues, and to carry out an impartial and objective review of a novel situation,
p.000056: there is no objection to researchers submitting in good faith for
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-96
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ethical review a research proposal that the researchers themselves feel that they need ethical guidance.
p.000056:
p.000056: 6.14. As for IRBs and members of IRBs, it is important that researchers take special care to avoid
p.000056: any form of conflicts of interest, whether actual, potential, or merely an appearance of conflict as such.
p.000056: Where such actual, potential or apparent conflicts arise, researchers have a duty to make a declaration of
p.000056: the conflict, give full disclosure of the facts giving rise to such conflict, and detail the steps proposed
p.000056: or taken to minimise or avoid the actual or potential conflict of interest, or the appearance of such a
p.000056: conflict of interest.
p.000056:
p.000056: 6.15. In no case should any researcher be involved in, or give the appearance of being involved in, the ethics
p.000056: review and approval process of any research project in which he or she is involved in. For instance, a researcher who
p.000056: is a member of an IRB should recuse himself or herself from the review of any research project in which he or she is
p.000056: personally involved, and make a declaration of such an interest to the IRB.
p.000056:
p.000056: 6.16. In submitting a proposal for ethical review, every researcher involved in the research project should be
p.000056: named as a party and applicant in the proposal.
p.000056:
p.000056: 6.17. For the purposes of this Section, we exclude from the definition of researcher persons acting
p.000056: only in an administrative or support capacity, and who are under the direct supervis ion and control of
p.000056: a researcher. Examples of such research support personnel would be administrative clerks and nurses assisting
p.000056: in clinical duties.
p.000056:
p.000056: Principal Investigators
p.000056:
p.000056: 6.18. It has been the practice in the past to informally refer to all researchers invo lved in a
p.000056: research project as “Principal Investigators” or “PIs”. We think, however, that this practice causes
p.000056: confusion, especially if a large number of researchers are involved in a research project.
p.000056:
p.000056: 6.19. Where a research project involves more than one researcher, we prefer to use the term “investigator” to refer
p.000056: to any one of the researchers generally, and the term “Principal Investigator” to specifically refer to
p.000056: the investigator who has been elected (and who has accepted) the role of Principal Investigator of that
p.000056: research project.
p.000056:
p.000056: 6.20. Where a research project is to be carried out by a single researcher, that researcher is the Principal
p.000056: Investigator. Where a research project is to be carried out by more than one researcher, then the
p.000056: researchers must elect
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-97
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: one of themselves to be designated as the Principal Investigator. The Principal Investigator is the
p.000056: researcher who shall be regarded as the lead researcher of the research project.
p.000056:
p.000056: 6.21. A research application by a group of researchers working in collaboration with each other should therefore
p.000056: ordinarily be submitted by the researchers in the name of a single Principal Investigator and his or her collaborating
p.000056: Investigators.
p.000056:
p.000056: 6.22. It is permissible for a research project to have more than one Principal Investigator. This is
p.000056: especially in a large project, or one with different parts or different (but related) objectives, or one in
p.000056: which the research is to be carried out at many places or trial locations (multi-centre trials). Where more than one
p.000056: Principal Investigator is contemplated, then each and every one of the Principal Investigators shall be held
p.000056: jointly and severally responsible as Principal Investigators.
p.000056:
p.000056: 6.23. Principal Investigators have special additional responsibilities over and above that of ordinary
p.000056: researchers.
p.000056:
p.000056: A definition of the term “Principal Investigator”, and of the role and responsibilities of a Principal
p.000056: Investigator has recently been proposed:
p.000056:
p.000056: “The Principal Investigator (PI) is the individual responsible and accountable for the design, conduct,
p.000056: monitoring, analyses and reporting of the protocol. The PI assumes full responsibility for the evaluation,
p.000056: analyses and integrity of the research data. The PI must assure that the protocol is followed and the data collected
p.000056: promptly and accurately. The PI assumes specific responsibilities to include: writing the protocol
p.000056: document, assuring that necessary approvals are obtained, monitoring the protocol during its execution, ensure
p.000056: that the protocol is conducted in accordance to the ethical guidelines, and to ensure that all participating
p.000056: investigators on the research teams, involved in implementing the protocol are adequately informed about the protocol
p.000056: and their responsibilities.”
p.000056:
p.000056: 6.24. We commend and adopt this definition and summary of the role and responsib ilities of a
p.000056: Principal Investigator, and extend it to all clinical research as defined in this Consultation Paper.
p.000056:
p.000056: 6.25. In large multi-part or multi-centre or complex research programmes, it is especially critical that the
p.000056: exact roles and responsibilities of each of the researchers in the team should be made clear, and reduced to
p.000056: writing. This makes clear to every researcher what each other’s responsibilities are, and helps in the
p.000056: identification of overlooked areas requiring supervision or direction by a member of the team. Such
p.000056: statements outlining the roles
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-98
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: and responsibilities of each of the researchers in a team should be included in the submission to the ethics committee.
p.000056:
p.000056: 6.26. The Principal Investigator(s) shall be responsible for settling, coordinating and formalising the
p.000056: distribution of roles and responsibilities among the researchers in a research programme.
p.000056:
p.000056: Continuing Responsibilities, Deviation and Variation
p.000056:
p.000056: 6.27. The ethical responsibilities of researchers outlined in this section are continuing responsibilities
p.000056: which apply at least for the lifetime of the research project, that is, from the time the research project is
p.000056: submitted by the researchers to the IRB for ethics review, until such time as the research project is deemed to have
p.000056: concluded or been terminated.
p.000056:
p.000056: 6.28. When an IRB grants its approval on a research application, it can only make its judgment as to
p.000056: whether approval should be granted to the research application based on the facts and proposals disclosed to it
p.000056: by the researchers in their application. Most significantly, the ethical judgment has to be made before the
p.000056: research project begins. Once the project is approved, and the research is underway, researchers
p.000056: often find that variations or departures from the original proposal may be dictated by suc h considerations as
p.000056: budget, access to subjects, unexpected clinical results and other factors. A research project may also
p.000056: expand in scope, in its objectives, or in the researchers involved – some researchers may resign, or decide to
p.000056: take a less active ro le, while other researchers may be recruited. Or it may be discovered that a proposed
p.000056: course of action poses greater risks for the proposed subject population than originally assessed, or that the trial
p.000056: has resulted in greater harm (whether of degree or o f incidence) then originally contemplated. Or it
p.000056: may be discovered in the course of the trial that some part of the original protocol as proposed in the ethics
p.000056: review application has not been strictly adhered to, although such departure may have been made in good faith
p.000056: by mistake or by necessity, out of consideration for the welfare of the subjects.
p.000056:
p.000056: 6.29. As part of their continuing responsibilities, the Principal Investigator(s) in particular is under a
p.000056: strict obligation to immediately and in writing seek approval for any changes where such changes have not yet been
p.000056: made, or otherwise report any changes where such changes have already been made, to the IRB by which initial
p.000056: research application was considered and approved. The Principal Investigator(s) shall in their request or
p.000056: report detail the changes, giving their objective assessment of any impact and consequences (both from
p.000056: the clinical and ethical points of view) of the changes.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-99
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: 6.30. This continuing obligation of researchers is clearly referred to in the NMEC Guidelines (at
p.000056: paragraph 3.2.5). The Guidelines state that investigators are “bound to act in exact accordance with the
p.000056: details” of the protocol submitted for ethics review, and that investigators are “obliged to report to the [IRB]
p.000056: any adverse events and apparent risks beyond those predicted in the original submission. The
p.000056: investigator should also immediately inform the [IRB] of any new information that might alter the ethical basis of
p.000056: the research programme. The [IRB] should also be notified if the study is terminated prematurely”. We agree entirely
p.000056: with the NMEC in these statements, and adopt them.
p.000056:
p.000056: 6.31. The submission of a protocol operates as a representation and agreement by each and every researcher who signs
p.000056: the application that the research programme will be carried out strictly in accordance with the submitted
p.000056: protocol.
p.000056:
p.000056: 6.32. Where deviations or changes are substantial, or in every case where the deviations and changes from the
p.000056: original proposal submitted to the IRB has resulted or is likely to result in greater harm or a greater likelihood
p.000056: of harm (whether of degree or incidence) to the subjects involved, the researchers are under a duty to
p.000056: suspend the research immediately, pending their report to the IRB.
p.000056:
p.000056: 6.33. Minor changes intended solely for the greater safety, health, welfare and well-being of the human
p.000056: subjects taken after consultation with all researchers involved in the trial need not be immediately
p.000056: reported to the IRB. For example, if it appears to a researcher that a particular research subject is not
p.000056: altogether comfortable with one of the planned procedures, that procedure may be dropped and the research programme
p.000056: varied to such extent, without the need for immediate reporting. Reporting of such changes by the Principal
p.000056: Investigator to the relevant IRB should however take place within a set time frame that shall be decided by the IRB.
p.000056: We note, for example, that certain IRBs in institutions in the United States require such changes to be
p.000056: reported in annual updates. However, other changes, minor or otherwise, made for the greater effectiveness of the
p.000056: trial or of its objectives do not fall within this category and should be immediately reported.
p.000056:
p.000056: Researchers and Attending Physicians
p.000056:
p.000056: 6.34. Human subjects for research projects are often recruited from patie nts who are already receiving treatment
p.000056: from physicians.
p.000056:
p.000056: 6.35. Where a proposed researcher is the attending physician, the researcher / physician should be aware
p.000056: of a potential conflict of interest, and of the fact
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-100
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: that their patients may feel obliged to give consent. We repeat and endorse Article 23 of the Declaration of
p.000056: Helsinki, which states that “[w]hen obtaining informed consent for the research project the physician
p.000056: should be particularly cautious if the subject is in a dependent relationship with the physician or may
p.000056: consent under duress. In that case the informed consent should be obtained by a well- informed
p.000056: physician who is not engaged in the investigation and who is completely independent of this relationship”.
p.000056:
p.000056: 6.36. In our view, however, this does not app ly to situations where clinicians wish to write up or publish
p.000056: summaries or analyses of the results of their therapeutic interventions or treatment of patients, provided
p.000056: that such interventions and treatment were carried out in the first place purely for therapeutic or
p.000056: diagnostic purposes and in the interests of the patients, and without regard to any consideration for research
p.000056: objectives, or for the subsequent publication of the results.
p.000056:
p.000056: 6.37. We further take the view that where researchers are aware that the proposed research subjects are
p.000056: currently receiving treatment or otherwise being attended to by physicians, reasonable efforts should be made on an
p.000056: informal basis by the researchers to contact and inform the attending physicians of the proposed research
p.000056: progr amme. If the research subjects customarily attend at a hospital or clinic, and are attended to by different
p.000056: physicians on their visits, reasonable efforts should be made on an informal basis to contact
p.000056: and inform the institution concerned, and the consultant or senior person having charge of the department
p.000056: or clinic concerned.
p.000056:
p.000056: 6.38. The existence of attending physicians (or the likelihood of the existence of such attending physicians) should
p.000056: be disclosed to the IRB by the Principal Investigator(s), at the time that the research application is being made.
p.000056:
p.000056: 6.39. The IRB may then consider whether contacting the attending physicians should be made a formal
p.000056: requirement of ethics approval, upon considerations which should include, but not be limited to, the
p.000056: following:
p.000056:
p.000056: 6.39.1. In the case of research which involves any level of clinical interaction with patients,
p.000056: researchers should be formally required to contact and inform the attending physicians, in the interests of
p.000056: ensuring the safety, health, welfare and well-being of the subject patients.
p.000056:
p.000056: 6.39.2. In the case of research which involves access to patient medical records, but with minimal levels of
p.000056: interaction for the purposes of obtaining more information (for instance, interviewing the subject
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-101
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: patient for a history), researchers should still be encouraged to contact and inform the attending physicians,
p.000056: and the IRB may in its discretion make such formal contact and information a condition of ethics approval.
p.000056:
p.000056: 6.39.3. In the case of research which involves access to and a study of patient medical records without
p.000056: any kind of contact at all between the researchers and the subject patients, the IRB need not require
p.000056: researchers to formally contact or inform the attending physicians (on the assumption, of course, that they have
p.000056: complied with all other applicable requirements).
p.000056:
p.000056: 6.39.4. We take the view that efforts to contact and inform the attending physician(s), or the consultant or
p.000056: senior person in charge of the department or clinic concerned, should be made before
p.000056: commencement of the research project. Whe re this is not possible, such contact must be made as immediately after
p.000056: commencement of the research project as may be practicable, or as the IRB may direct.
p.000056:
p.000056: 6.40. In no circumstances should any researcher alter or modify in any way (whether in formulation,
p.000056: dosage or timing) any drug or other clinical regimen prescribed by the attending physicians of the
p.000056: subject patients, without first seeking and obtaining the approval of both the attending physicians and the
p.000056: IRB.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-102
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: PART D:
p.000056: THE NATIONAL ORGANISATION, ENFORCEMENT AND PROTECTION OF ETHICAL GOVERNANCE
p.000056:
p.000056:
p.000056: SECTION VII:
p.000056: THE NATIONAL ORGANIZATION OF ETHICAL GOVERNANCE
p.000056:
p.000056: 7. The National Organization Of Ethical Governance
p.000056:
p.000056: 7.1. The current regulatory regime governing the review and approval of drug trials (which we described in
p.000056: Section II above) provide for a system in which applications for drug trials are first screened by IRBs
p.000056: at the local institutional level before being forwarded to a national regulatory agency (the CPA of the HSA) for
p.000056: approval. This system has served us well. It is well- understood by all parties involved in the process. We
p.000056: recommend that this system continue to apply in the case of drug trials.
p.000056:
p.000056: 7.2. In the case of clinical research other than drug trials there is currently no national agency or regulatory
p.000056: body fulfilling a function equivalent to that of the HSA. The exception is the Ministry of Health, but the Ministry
p.000056: only has jurisdiction over hospitals, private clinics and other institutions falling within its purview under the
p.000056: Private Hospitals and Medical Clinics Act.
p.000056:
p.000056: 7.3. The Ministry of Health provides guidance from time to time to IRBs falling within its
p.000056: jurisdiction. For example, it has directed all IRBs to adopt and apply the NMEC Guidelines.
p.000056: From time to time, other directions are issued. Some of these are on the advice of the NMEC.
p.000056:
p.000056: 7.4. The role of the NMEC, however, is to advise the Ministry of Health on ethical issues arising in the practice
p.000056: of medicine. It does not advise IRB directly, and does not function as a higher- level appeal or advisory body to
p.000056: IRBs.
p.000056:
p.000056: 7.5. Apart from complying with the directives issued by the Ministry of Health (including the NMEC
p.000056: Guidelines), IRBs in institutions under the jurisdiction of the Ministry are free to adopt such
p.000056: procedures, formulate their own Standard Operating Procedures, and determine their constitution, operating principles
p.000056: and other administrative practices.
p.000056:
p.000056: 7.6. As a result, there is considerable diversity in the constitution, procedures and practice among IRBs. On the
p.000056: informal feedback that we have received on this point, there is considerable support in favour of there
p.000056: being an
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-103
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: agreed standard model or set of guidelines for all IRBs to follow and apply.
p.000056:
p.000056: 7.7. We support this view, as we think that a national standard model or set of guidelines for standard operating
p.000056: procedures for all IRBs is desirable in the interests of promoting consistency and fairness in the decisions,
p.000056: especially in the case of multi- centre research programmes. We think, too, that having a national standard
p.000056: model or set of guidelines will also serve as a quality of service benchmark for all IRBs to judge themselves.
p.000056:
p.000056: 7.8. Such a national standard model or set of guidelines can consist of a set of documents issued by a national
p.000056: body or agency. These documents can be modelled on documents such as the SGGCP. The NMEC Guidelines itself is
p.000056: already such a document, but for the fact that it was intended only for the direction of hospitals and
p.000056: institutions falling under the jurisdiction of the Ministry of Health.
p.000056:
p.000056: 7.9. Likewise, we think that it would be desirab le for all clinical research in Singapore to come under
p.000056: the formal statutory jurisdiction of a national government agency or ministry, as drug trials currently do. We
p.000056: suggest that this government agency could be the Ministry of Health, or the HSA, or the statutory agency proposed
p.000056: for the oversight of human stem cell search, cloning research and human tissue research as announced by
p.000056: the Government.
p.000056:
p.000056: 7.10. In addition to coordinating and promoting national standards for IRBs, such a national supervisory
p.000056: agency could also function as the accrediting agency for IRBs. No IRB should be permitted to operate without
p.000056: obtaining such accreditation.
p.000056:
p.000056: 7.11. The national supervisory agency should be empowered to conduct audit and investigations into
p.000056: complaints (including complaints from research subjects), and should have the power to appoint external
p.000056: auditors and investigators at the cost of the institution being audited as part of the accreditation check
p.000056: or as a matter of routine audit for compliance.
p.000056:
p.000056: 7.12. The national supervisory agency should be empowered to appoint committees of inquiry to
p.000056: investigate complaints arising from research programmes (including complaints from research subjects) and
p.000056: should have powers to compel the testimony of witnesses and the production of documents (in this, the statutory powers
p.000056: of the Singapore Medical Council in disciplinary proceedings may be used as an example).
p.000056:
p.000056: 7.13. The national supervisory agency should also be empowered to work towards developing a code of
p.000056: ethics and principles for the governance of
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-104
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: clinical research. This should be carried out by incremental and evolutionary development, through
p.000056: a process of dialogue and discussion between institutional review boards and the other parties in the
p.000056: research governance process, and having reference to the experiences of the parties involved.
p.000056:
p.000056:
p.000056: Recommendation 7:
p.000056:
p.000056: A national supervisory authority should be appointed for the statutory supervision, regulation, accreditation
p.000056: and audit of all IRBs in Singapore.
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-105
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: SECTION VIII: PROTECTION
p.000056:
p.000056: 8. The Protection Of Institutional Review Boards
p.000056:
p.000056: 8.1. Notwithstanding the important role played by IRBs in research institutions, IRBs sometimes experience
p.000056: difficulties in attracting members of its choice in that some of the most qualified potential candidates for
p.000056: membership decline the invitation to serve. These candidates may do so out of a fear of legal liability in the event
p.000056: of a contested decision, or a decision which has an unexpectedly adverse impact on human subjects. Few such
p.000056: candidates have any legal training, and the ir reluctance on this ground is understandable.
p.000056:
p.000056: 8.2. On this point, we note that the NMEC Guidelines suggests that IRBs should look to the
p.000056: authority appointing them to give them formal indemnity against the cost of any legal
p.000056: representation, and any compensation ultimately awarded to human subjects. The NMEC Guidelines
p.000056: further recommend that such an indemnity should be given in the letter of appointments of the members.
p.000056:
p.000056: 8.3. Members of IRBs discharge an important office in the public interest in the protection of human subjects.
p.000056: Often they do so for minimal or token remuneration, or none at all. Their only motivation being a call to
p.000056: duty, and their only reward being the satisfaction of a job well done.
p.000056:
p.000056: 8.4. We take the view that members of IRBs should be fully protected by the law in their discharge of their
p.000056: duties, provided that they do so in good faith, against any liability arising from their actions. Such
p.000056: protection should extend to immunity from liability in tort arising from any claim by human subjects, and to a
p.000056: defence of qualified privilege to any claim in defamation.
p.000056:
p.000056: 8.5. Appointing institutions should nonetheless be required to give members of IRBs a full indemnity. Such
p.000056: institutions should remain liable to human subjects from any claim in tort, and should be required to
p.000056: take out appropriate insurance coverage against the variety of claims which may arise in the course of the
p.000056: work of the IRB. For example, in relation to the approval of multi- centre or multinational trials.
p.000056:
p.000056: 8.6. We note that such protection would also promote frankness and transparency by the IRB in
p.000056: the discharge of their duties: members would be able to state their opinion frankly without fear of being
p.000056: sued for defamation, and would be able to give researchers a full and frank account of their reasons for rejecting an
p.000056: application. We believe that such full and frank account of reasons for rejection is an important key to
p.000056: helping
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: B-106
p.000056:
p.000056:
p.000056: ANNEXE B
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: researchers understand their ethical obligations, and in helping them to redesign programmes for ethical
p.000056: compliance. Likewise, protection for members would also encourage earlier reporting of negative outcomes or
p.000056: suspicious trends to the authorities for investigation.
p.000056:
p.000056: 8.7. Legal protection for members of IRBs acting in good faith would also encourage the best and
p.000056: most competent individuals (both within and outside the medical profession) to contribute their skill and
p.000056: expertise to the IRBs, and help ensure that members are selected from the best available experts in their
p.000056: fields.
p.000056:
p.000056: 8.8. Statutory protection may be especially important in encouraging participation by lay
p.000056: non- medical persons to become members of IRBs.
p.000056:
p.000056: 8.9. The same protection should also be extended to ethics assurance auditors, ethics investigators or members of
p.000056: committees of inquiry appointed by the national supervisory age ncy.
p.000056:
p.000056:
p.000056: Recommendation 8:
p.000056:
p.000056: Members of institutional review boards should be fully protected by the law in the discharge of their duties, provided
p.000056: that they do so in good faith, against any liability arising out of their actions. Such protection should
p.000056: extend to immunity from liability in tort arising from any claim by human subjects, and to a defence of
p.000056: qualified privilege to any claim in defamation. The same protection should also be extended to ethics assurance
p.000056: auditors, ethics investigators or members of committees of inquiry appointed by the national supervisory agency.
...
p.000056:
p.000056: 12 Prof. Jackie Yi-Ru Ying Executive Director Institute of Bioengineering and
p.000056: Nanotechnology
p.000056:
p.000056:
p.000056: 13 A/Prof Chong Siow Ann Chairman
p.000056: Research and Ethics Committee
p.000056: Institute of Mental Health/ Woodbridge Hospital
p.000056: 14 Prof Hong Wan-Jin Deputy Director Institute of Molecular & Cell
p.000056: Biology
p.000056: National University of Singapore
p.000056: 15 Dr Alex Chang Chief Executive Officer John-Hopkins-NUH International
p.000056: Medical Centre
p.000056:
p.000056:
p.000056: 16 Dr Chay Oh Moh Chairman
p.000056: Research Committee
p.000056: KK Women’s and Children’s Hospital
p.000056: 17 Mr Thomas E. Lee Chief Executive Officer Mount Alvernia Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-109
p.000056:
p.000056:
p.000056: ANNEXE C
p.000056:
p.000056:
p.000056: Name Designation Organisation
p.000056: 18 Mrs Nellie Tang General Manager Mount Elizabeth Hospital
p.000056:
p.000056: 19 Prof Soo Khee Chee Director National Cancer Centre
p.000056:
p.000056: 20 Dr Kwa Chong Teck Executive Director National Dental Centre
p.000056:
p.000056: 21 A/Prof Koh Tian Hai Medical Director National Heart Centre
p.000056:
p.000056: 22 Mr Tan Tee How Group Chief Executive Officer National Healthcare Group
p.000056:
p.000056:
p.000056: 23 Dr Yee Woon Chee Deputy Director
p.000056: Research
p.000056: 24 Prof Goh Chee Leok Chairman
p.000056: Research Ethics Committee
p.000056: 25 Prof Lee Kok Onn Chairman
p.000056: Institutional Review Board
p.000056: National Neuroscience Institute National Skin Centre
p.000056: National University Hospital
p.000056: 26 Prof Yap Hui Kim Director NUMI Directorate
p.000056: National University of Singapore
p.000056: 27 Prof John Wong Director Office of Life Sciences
p.000056: National University of Singapore
p.000056:
p.000056:
p.000056: 28 Dr James J Murugasu Chairman
p.000056: Ethics Committee
p.000056: Raffles Hospital
p.000056: 29 Prof James P. Tam Dean School of Biological Sciences
p.000056: Nanyang Technological University
p.000056: 30 A/Prof Donald Tan Director Singapore Eye Research
p.000056: Institute
p.000056:
p.000056:
p.000056: 31 Dr Aw Swee Eng Chairman
p.000056: Ethics Committee
p.000056: Singapore General Hospital
p.000056:
p.000056: 32 Dr Ang Chong Lye Director Singapore National Eye Centre
p.000056:
p.000056:
p.000056: 33 Ms Theresa Chow Pui Fun
p.000056: Deputy Director Singapore Tissue Network
p.000056:
p.000056: 34 Prof Low Yin Peng Chairman
p.000056: Ethics Committee
p.000056: Tan Tock Seng Hospital
p.000056:
p.000056: 35 Mr Allan Yeo Chief Group Executive Thomson Medical Centre
p.000056:
p.000056: 36 Prof Tan Ser Kiat Group Chief Executive Officer Singapore Health Services
p.000056:
p.000056: 37 Dr Predeebha Kannan Secretariat National Medical Ethics Committee
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: C-110
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
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p.000056:
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p.000056:
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p.000056:
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p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056:
p.000056: DIALOGUE SESSION ON THE CONSULTATION PAPER “ADVANCING THE FRAMEWORK OF ETHICS GOVERNANCE FOR HUMAN RESEARCH”
p.000056:
p.000056:
p.000056: 20 Chairpersons and Representatives of the hospital ethics committees or institutional review boards (IRBs) of 17
p.000056: organisations met with seven members of the Bioethics Advisory Committee (BAC) on 7 November 2003. This Annexe
p.000056: provides a summary of the comments and concerns raised at the dialogue session between the parties.
p.000056:
p.000056:
p.000056: Organisation Represented:
p.000056:
p.000056: 1. Alexandra Hospital
p.000056:
p.000056: 2. Changi General Hospital
p.000056:
p.000056: 3. Health Promotion Board
p.000056:
p.000056: 4. Institute of Mental Health/Woodbridge Hospital
p.000056:
p.000056: 5. Institute of Molecular and Cell Biology
p.000056:
p.000056: 6. KK Women’s and Children’s Hospital
p.000056:
p.000056: 7. National Cancer Centre
p.000056:
p.000056: 8. National Dental Centre
p.000056:
p.000056: 9. National Healthcare Group
p.000056:
p.000056: 10. National Heart Centre
p.000056:
p.000056: 11. National Medical Ethics Committee
p.000056:
p.000056: 12. National Neuroscience Institute
p.000056:
p.000056: 13. National University Hospital
p.000056:
p.000056: 14. National University of Singapore
p.000056:
p.000056: 15. Parkway Group Healthcare Pte Ltd
p.000056:
p.000056: 16. Singapore Tissue Network
p.000056:
p.000056: 17. Tan Tock Seng Hospital
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: E-151
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: Summary of Comments and Concerns Raised at the Dialogue Session
p.000056:
p.000056: Intention of the Consultation Paper
p.000056:
p.000056: IRB: Rules set for the industry quickly become obsolete given the speed of progression in
p.000056: biomedical sciences.
p.000056:
p.000056: BAC: The preliminary Recommendations advanced in the Consultation Paper (Paper) are not meant to be
p.000056: cast in iron but will be reviewed as and when the need arises. This is to be expected not only with the advancement of
p.000056: science, but also as values and laws of the society evolve over time. The intention behind the Paper is to
p.000056: establish a framework for the Government to consider when to implement appropriate policies on the ethics
p.000056: governance of human research. One of the main motivations of the Recommendations is to harmonise
p.000056: the ethical standards for all research institutions and their IR Bs. Such standards, as prescribed in the
p.000056: Paper, are universally accepted and hence would provide greater public assurance.
p.000056:
p.000056: Role of Principal Investigators
p.000056:
p.000056: IRB: In large multinational studies, a local principal investigator (PI) should have a greater role in the design,
p.000056: conduct, monitoring and analyses of the studies.
p.000056:
p.000056: BAC: This concern is noted and will be highlighted to the Ministry of Health (MOH).
p.000056:
p.000056: Requirements in Obtaining Informed Consent
p.000056:
p.000056: IRB: One of the provisions in the Paper is for a witness to be present at the consent- taking process (paragraph
p.000056: 5.57). Will the witness be required to observe the entire process or just the endorsement of the consent form?
p.000056:
p.000056: BAC: The purpose of that provision is to have an independent person ensure that the human subject understands what
p.000056: he/she is consenting to. This requirement does not entail any departure from normal medical procedures. As the
p.000056: Paper is meant to provide only a framework for ethics governance, the actual procedure for the procurement of consent
p.000056: will not be prescribed here.
p.000056:
p.000056: Role of a Supervisory Body for IRBs
p.000056:
p.000056: IRB: Will there be a central body to keep check on the standards of ethics governance of each
p.000056: institution? If so, some form of penalty needs to be prescribed for non-compliance so that the
p.000056: standards can be effectively maintained. Revocation of the accreditation of an IRB can be such a penalty.
p.000056:
p.000056: BAC: The BAC recommends that a central supervisory authority be established to either license each
p.000056: institution or grant an umbrella licence to a group o f institutions. This authority will be empowered
p.000056: to accredit and audit licensed institutions. A majority of the large hospitals will be licensed by their areas of
p.000056: competence. Licence can also be granted based on specific conditions. Such a
p.000056:
p.000056:
p.000056: E-152
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: supervisory authority will therefore impose two kinds of checks – licensing and accreditation.
p.000056:
p.000056: Role and Responsibilities of IRBs
p.000056:
p.000056: Continuing Review, Supervision and Audit
p.000056:
p.000056: IRB: Can the BAC clarify what it means by “continuing review” (paragraph 5.15.2)?
p.000056:
p.000056: BAC: The BAC has received several responses on this issue. By “continuing review”, the BAC
p.000056: intends to empower IRBs to carry out audits. This empowerment will change the mindset of some
p.000056: PIs who consider the IRB approval of research proposals as a one-off threshold clearance. IRBs should review on-
p.000056: going research even after it has given its initial approval for the research proposal. The Paper will be
p.000056: amended to clarify this issue.
p.000056:
p.000056: IRB: Can a separate body be assigned to conduct audit in order to alleviate the workload of IRBs?
p.000056:
p.000056: BAC: An IRB need not perform the audit itself but it has to have the means to monitor any deviations
p.000056: from the proposed research protocol. For example, the IRB can mandate an annual report and a completion report, or it
p.000056: can appoint independent auditors to carry out audits.
p.000056:
p.000056: However, it may be better for IRBs to carry out audits themselves, as appointing independent auditors
p.000056: may result in IRBs having to check on two parties. A research may have wide social impact and IRBs should
p.000056: ensure that the research is done in accordance with the approved protocol, with particular focus on the safety and
p.000056: privacy of human subjects. Other concerns, such as scientific validity of the research, are secondary.
p.000056:
p.000056: IRB: This is not feasible. Some IRBs are currently overloaded with protocols for review (200-400 per
p.000056: year). It is not only difficult for IRBs to find time for the added audit responsibilities, but is also difficult for
p.000056: IRBs to find people with the time and capability to perform independent audits on their behalf. In addition,
p.000056: certain IRBs have difficulty coping with a large number of annual reports.
p.000056:
p.000056: BAC: Institutions should provide their IRBs with adequate resources to enable them to discharge their
p.000056: responsibilities.
p.000056:
p.000056: In addition, institutions should be the ones to select the independent auditors. The main requirement of audit is to
p.000056: assess ethical merits, not scientific merits.
p.000056:
p.000056: IRB: Although not officially or legally empowered, one impression is that IRBs have the power to
p.000056: investigate ethics violations even after the protocol has been approved. Do the recommendations require more of IRB
p.000056: than what is already being done?
p.000056:
p.000056:
p.000056:
p.000056: E-153
p.000056:
p.000056:
p.000056: ANNEXE E
p.000056:
p.000056:
p.000056: BAC: IRBs will need to report to a national supervisory body.
p.000056:
p.000056: IRB: The Singapore Guideline for Good Clinical Practice (SGGCP) has clearly delineated the roles of
p.000056: monitors, sponsors and auditors. The Paper should follow the SGGCP’s framework so that the IRB’s responsibility
p.000056: is clearly and primarily confined to a review of documents.
p.000056:
p.000056: BAC: One of the purposes of this Paper is to extend the rules in the SGCCP on clinical drug trials to
p.000056: non-drug trials. An IRB is not the enforcer of these rules and these provisions should not lead to unnecessary
p.000056: bureaucracy that stifles research.
p.000056:
p.000056: IRB: There are situations where IRB members find it difficult to confront researchers who are
p.000056: very senior in rank. In fact, many researchers in certain countries who have flouted ethics rules were highly
p.000056: regarded PIs.
p.000056:
p.000056: There is a huge gap between the recommended standards and what IRBs can achieve. While the responsibilities spelt
p.000056: out are probably appropriate, IRBs currently do not have the capacity to take on all of them.
p.000056:
p.000056: BAC: In the UK, IRBs are not the ones who conduct investigation at the research level. It is important
p.000056: for IRBs to have the power to require that an audit be performed. Such controls will reassure the public
p.000056: that adequate protection is in place.
p.000056:
p.000056: IRB: The responsibilities of IRBs in reviewing, supervising and auditing, as well as the means of discharging
p.000056: these responsibilities, need to be more clearly defined. Often, the problem lies not with the lack of regulations
p.000056: (because these are present), but with the lack of people to implement them. Monitoring and auditing of research
...
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| age | Age |
| authority | Relationship to Authority |
| autonomy | Impaired Autonomy |
| belief | Religion |
| belmont | belmont |
| children | Child |
| culturally | cultural difference |
| dependent | Dependent |
| drug | Drug Usage |
| education | education |
| educational | education |
| emergency | Public Emergency |
| employees | employees |
| faith | Religion |
| family | Motherhood/Family |
| hazard | Natural Hazards |
| helsinki | declaration of helsinki |
| job | Occupation |
| military | Soldier |
| minor | Youth/Minors |
| nation | stateless persons |
| officer | Police Officer |
| opinion | philosophical differences/differences of opinion |
| parent | parents |
| party | political affiliation |
| philosophy | philosophical differences/differences of opinion |
| race | Racial Minority |
| religious | Religion |
| research staff | Laboratory Staff |
| restricted | Incarcerated |
| single | Marital Status |
| tri-council | tri-council policy statement |
| vulnerable | vulnerable |
| women | Women |
| youth | Youth/Minors |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| belief | ['faith', 'religious'] |
| education | ['educational'] |
| educational | ['education'] |
| faith | ['belief', 'religious'] |
| minor | ['youth'] |
| opinion | ['philosophy'] |
| philosophy | ['opinion'] |
| religious | ['faith', 'belief'] |
| youth | ['minor'] |
Trigger Words
capacity
consent
cultural
developing
ethics
harm
justice
protect
protection
risk
sensitive
welfare
Applicable Type / Vulnerability / Indicator Overlay for this Input