C661DEC5EFCA0F83910449083B33AEF8
Standards Survey of New Drugs, Medicines, Vaccines, and Diagnostic Tests Involving Human Beings - Resolution CNS No. 251/97
http://conselho.saude.gov.br/resolucoes/1997/Res251_en.pdf
http://leaux.net/URLS/ConvertAPI Text Files/95DF7A91B0002D90A04954E9E3308BD7.en.txt
Examining the file media/Synopses/95DF7A91B0002D90A04954E9E3308BD7.html:
This file was generated: 2020-04-11 02:06:37
| 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
Health / Cognitive Impairment
Searching for indicator impaired:
(return to top)
p.(None): h – Communicate the occurrence of serious adverse events to CONEP and the SVS/MS.
p.(None): i – Communicate to the Institution the occurrence or existence of administrative responsibility problems
p.(None): that may interfere with the ethical conduction of the research; report to CONEP and the SVS/MS immediately and, as the
p.(None): case may be, to the Regional Councils.
p.(None):
p.(None): V.2 – The National Health Council hereby delegates to the CEP authority to approve, from the point of view of ethics,
p.(None): research projects involving new pharmaceutical products, medicines and diagnostic tests, with the provision that the
p.(None): following documents be submitted to CONEP and the SVS/MS:
p.(None): a – a copy of the consolidated report approving the research project, together with a completed header page,
p.(None): b – official conclusion on the partial and final reports on the research and
p.(None): c – other documents required by CEP, CONEP or the SVS.
p.(None): V.3 – In research that includes patients submitted to emergency or urgency situations, the CEP must previously
p.(None): approve the conditions or limits for obtaining free and informed consent; in addition, the researcher must
p.(None): inform the research subject, on a timely basis, about his/her participation in the project.
p.(None):
p.(None): V.4 – Assess whether all adequate measures are being implemented in the case of research with human beings whose
p.(None): capability for self-determination is impaired or limited.
p.(None):
p.(None):
p.(None): VI - OPERATIONALIZATION
p.(None):
p.(None): VI.1 - CONEP will exercise its competencies in the terms of Resolution 196/96, with emphasis on the following
p.(None): activities:
p.(None): a – organizing an information and follow up system (item VIII.9.g of Resolution 196/96) on the basis of the data
p.(None): supplied by the CEPs (consolidated approval report, duly completed header page, partial and final reports, etc.);
p.(None): b – organizing a system to evaluate and follow up the activities of the CEPs. The system should enable peers, i.e.
p.(None): members of the various CEPs, to exchange information and experience, with reports to CONEP. It should also
p.(None): comply with the specific regulations issued by CONEP;
p.(None): c – informing the appropriate authorities, particularly the Health Surveillance Secretariat of the Ministry of Health,
p.(None): with a view to appropriate action, proven violations of the ethical standards in the execution of research projects;
p.(None): and
p.(None): d – supplying the various bodies of the Ministry of Health, particularly the Health Surveillance Secretariat,
p.(None): the information required to fully exercise their respective competencies as regards the research covered in this
p.(None): Resolution.
p.(None):
p.(None): VI.2 – The Health Surveillance Secretariat/MS shall exercise its attributions in the terms of Resolution
p.(None): 196/96, with especial emphasis on the following activities.
...
Health / Drug Dependence
Searching for indicator dependency:
(return to top)
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
p.(None): subject, even when not fully capable (for example, the elderly) or not fully developed (for example, children).
p.(None): r – In the case of research on psychiatric patients, whenever possible consent should be obtained from
p.(None): the patient him/herself. It is mandatory that the level of capability to express free and informed consent of each
p.(None): psychiatric patient be established by a psychiatrist other than the researcher involved in the project.
p.(None): In the case of drugs with psychopharmacological action, a critical analysis must be made of the possible risks of
p.(None): causing dependency.
p.(None):
p.(None): IV.2 – Including healthy subjects in research.
p.(None): a – Justifying the need to include healthy subject in the research project. Critical analysis of the risks involved.
p.(None): b – Description of how the recruitment will take place; no dependency situation should exist.
p.(None): c – In the case of drugs with psychopharmacological action, a critical analysis of the risk of causing
p.(None): dependency is necessary.
p.(None):
p.(None):
p.(None): V – ATTRIBUTIONS OF THE CEP
p.(None):
p.(None): V.1 – The CEP and the researcher will be jointly responsible for maintaining ethically correct conducts
p.(None): throughout the project and during the implementation of the research. In addition, they should take the following
p.(None): actions.
p.(None): a – Issue a consolidated report explaining the scientific basis of the research project and its relation
p.(None): with the studies in prior phases, including the preclinical phase, with emphasis on safety, toxicity,
p.(None): adverse reactions or effects, effectiveness, and results.
p.(None): b – Approve the justification of the use of a placebo and washout.
p.(None): c – Request partial and final reports from the main researcher establishing the schedule (on a six-monthly basis at
p.(None): least) according to the characteristics of the research. Copies of the reports must be forwarded to the
p.(None): SVS/MS.
p.(None): d – If announcements in the media are to be used to recruit research subjects, such advertising must be authorized by
p.(None): the CEP. No indication may be given, whether implicitly or explicitly, that the product being investigated is effective
p.(None): and/or safe, or that it is equivalent to or better than other existing products.
p.(None): e – Convene the research subjects for follow up and evaluation.
p.(None): f – Require that the top management of the institution start an inquiry, suspend or interrupt the research and
p.(None): communicate the fact to CONEP and the SVS/MS.
p.(None): g – Any infringement of ethical principles or evidence of fraud of any nature should lead the CEP to request the
p.(None): creation of an Inquiry Committee and to communicate the results[of such inquiry] to CONEP, SVS/MS and other agencies
...
Health / Drug Usage
Searching for indicator substance:
(return to top)
p.(None): keeping in abeyance until the matter is appreciated by the CEP, except in urgent cases to safeguard the
p.(None): safety of research subjects; in the latter case, the CEP should be notified immediately afterwards;
p.(None): f – making available to CEP, CONEP and the SVS/MS all duly required information;
p.(None): g – continuously analyzing the findings, throughout the research, for the purpose of detecting, as soon as possible,
p.(None): the advantages of one treatment over another or preventing adverse effects on research subjects;
p.(None): h – submitting regular reports within the time periods established by the CEP, with at least one report every six
p.(None): months and one final report;
p.(None): i – providing the patient‟s physician and the patient him/herself access to the results of tests and treatment whenever
p.(None): requested and/or indicated; and
p.(None): j – recommending that no individual be selected as research subject before a year has passed from his/her participation
p.(None): in another research, unless that individual were to directly benefit from it.
p.(None):
p.(None):
p.(None): IV – RESEARCH PROTOCOL
p.(None):
p.(None): IV.1 – The protocol must include all items stipulated in Chapter VI of Resolution 196/96, in addition
p.(None): to the basic pharmacological information appropriate to the phase of the research project, in compliance
p.(None): with Res. GMC 129/96 - Mercosul – including the following.
p.(None): a – Specifications and rationale of the clinical research phase in which the study is to be carried out, demonstrating
p.(None): that prior phases have been concluded.
p.(None): b – Description of the pharmacological substance or product being investigated, including its chemical
p.(None): formula and/or structure, in addition to a brief summary of relevant physical, chemical and pharmaceutical
p.(None): properties. Any structural similarity to other known chemical compounds should also be mentioned.
p.(None): c – Detailed preclinical information is required to justify the phase of the project, including a report
p.(None): on the experimental studies (materials and methods, animals used, laboratory tests,
p.(None): pharmacodynamics data, margin of safety, therapeutic margin, pharmacokinetics, and toxicology, in the case of drugs,
p.(None): medicines, or vaccines). The preclinical results must be accompanied by a discussion of the relevance of
p.(None): the findings in connection with the expected therapeutic effects and possible undesirable effects in human beings.
p.(None): d – The preclinical toxicology data should include the study of acute toxicology, subacute toxicology with
p.(None): repeated doses and chronic toxicity (repeated doses).
p.(None): e – The toxicology studies should be performed in at least three animal species, one of which must be a non-rodent
p.(None): mammal; both sexes must be included in the studies.
p.(None): f – In studying acute toxicity, two paths of administration must be used, one of which must be related to that
p.(None): recommended for the therapeutic use being proposed and the other must be a path that will ensure the absorption of the
p.(None): pharmaceutical product.
p.(None): g - In subacute toxicity, repeated dose and chronic toxicity studies the path of administration should be
p.(None): related to the proposed therapeutic use and the experiment should last at least 24 weeks.
...
Health / Health
Searching for indicator health:
(return to top)
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None):
p.(None): NATIONAL HEALTH COUNCIL
p.(None):
p.(None):
p.(None): RESOLUTION Nº 251, DATED 7 AUGUST 1997
p.(None):
p.(None):
p.(None):
p.(None): Plenary of the National Health Council in its 15th Special Meeting, held on 5 August 1997, in the
p.(None): exercise of its competencies, as set forth in its by-laws, and the attributions in Law 8.080 and Law
p.(None): 8.142, respectively dated 19 September 1990 and 28 December 1990, Resolves:
p.(None):
p.(None): To approve the following norms of research involving human beings in the thematic area of research with new
p.(None): pharmaceutical products, medicines, vaccines, and diagnostic tests:
p.(None):
p.(None): I - PREAMBLE
p.(None):
p.(None): I.1 – This Resolution incorporates all provisions contained in Resolution 196/96 of the National Health Council on
p.(None): Guidelines and Norms Regulating Research Involving Human Beings, which this Resolution complements in the specific
p.(None): thematic area of research with new pharmaceutical products, medicines, vaccines, and diagnostic tests.
p.(None):
p.(None): I.2 – It also refers to the Resolution on the Common Market Group (GMC) Nº 129/96, signed by Brazil, which establishes
p.(None): the technical regulations for ascertaining [the implementation of] good practices in clinical research.
p.(None):
p.(None): I.3 – The norms, resolutions and regulations issued by the Health Surveillance Secretariat of the Ministry of Health
p.(None): (SVS/MS) should be fully complied with, and SVS/MS authorization is required to execute and subsequently follow up and
p.(None): control the technical development of research projects in [the area of] Clinical Pharmacology (Phases I, II, III, and
p.(None): IV of products not yet registered in the country) and Bioavailability and Bioequivalence. Research projects in this
p.(None): area should comply with the provisions of Law 6.360 (23 September 1976), regulated by Decree Nº 79.094 (5 January
p.(None): 1977).
p.(None):
p.(None): I.4 – In any clinical essay and particularly when there are conflicts of interests associated with new products, the
p.(None): dignity and well-being of the research subject must prevail over any other interests, whether economic, scientific, or
p.(None): of the community.
p.(None):
p.(None): I.5 – It is essential that all research in this thematic area be founded on recognized scientific norms and
p.(None): on knowledge based on in vitro laboratory experiments and pertinent literature.
p.(None):
p.(None): I.6 – It is necessary that the investigation of new products be justified and that such products actually result in
p.(None): significant progress when compared with existing products.
p.(None):
p.(None):
p.(None): II - TERMS AND DEFINITIONS
p.(None):
p.(None): II.1 – Research of new pharmaceutical products, medicines, vaccines or diagnostic tests. It refers to
p.(None): Phase I, II or III research with these types of products or with products not yet registered in the
p.(None): country, even in Phase IV, when the research focuses on their use with modalities, indications, dosages, or paths of
p.(None): administration different from those established at the time registration was authorized, including their use in
...
p.(None): standpoint, it is the study of the biochemical and physiological effects of medicines and their action
p.(None): mechanisms.
p.(None): g – Margin of Safety
p.(None): It is the pharmacodynamics indicator that expresses the difference between the toxic dose (for example, the DL 50) and
p.(None): the effective dose (for example, the DE 50).
p.(None): h – Therapeutic Margin
p.(None): It is the ratio of the maximum tolerated dose, also toxic dose, to the therapeutic dose (toxic
p.(None): dose/therapeutic dose). In clinical pharmacology, the therapeutic margin is used as equivalent of the
p.(None): Therapeutic Indicator.
p.(None):
p.(None):
p.(None): III – RESPONSIBILITY OF THE RESEARCHER
p.(None):
p.(None): III.1 – The unremittable and untrasferable responsibility of the researcher to [comply with] the terms of
p.(None): Resolution 196/96 is hereby reaffirmed. All obligations provided for in said Resolution are equally reaffirmed,
p.(None): particularly the guarantee of conditions [required] to care for research subjects.
p.(None):
p.(None): III.2 – The researcher shall be responsible for:
p.(None): a – submitting a complete research project to the Research Ethics Committee (CEP), in the terms of
p.(None): Resolution 196/96 and this Resolution;
p.(None): b – maintaining a file for each research subject, for a period of five years, after the end of the research, due
p.(None): compliance being given to the confidentiality and secrecy of the records;
p.(None):
p.(None): c – submitting a detailed report as requested or established by the CEP, the National Research Ethics Committee
p.(None): (CONEP), or the Health Surveillance Secretariat (SVS/MS);
p.(None): d – informing the CEP of any occurrence of collateral effects and/or unexpected adverse
p.(None): reactions;
p.(None): e – communicating also any proposed changes in the project and/or justification of interruptions,
p.(None): keeping in abeyance until the matter is appreciated by the CEP, except in urgent cases to safeguard the
p.(None): safety of research subjects; in the latter case, the CEP should be notified immediately afterwards;
p.(None): f – making available to CEP, CONEP and the SVS/MS all duly required information;
p.(None): g – continuously analyzing the findings, throughout the research, for the purpose of detecting, as soon as possible,
p.(None): the advantages of one treatment over another or preventing adverse effects on research subjects;
p.(None): h – submitting regular reports within the time periods established by the CEP, with at least one report every six
p.(None): months and one final report;
p.(None): i – providing the patient‟s physician and the patient him/herself access to the results of tests and treatment whenever
p.(None): requested and/or indicated; and
p.(None): j – recommending that no individual be selected as research subject before a year has passed from his/her participation
p.(None): in another research, unless that individual were to directly benefit from it.
p.(None):
p.(None):
p.(None): IV – RESEARCH PROTOCOL
p.(None):
p.(None): IV.1 – The protocol must include all items stipulated in Chapter VI of Resolution 196/96, in addition
p.(None): to the basic pharmacological information appropriate to the phase of the research project, in compliance
p.(None): with Res. GMC 129/96 - Mercosul – including the following.
...
p.(None): adverse reactions or effects, effectiveness, and results.
p.(None): b – Approve the justification of the use of a placebo and washout.
p.(None): c – Request partial and final reports from the main researcher establishing the schedule (on a six-monthly basis at
p.(None): least) according to the characteristics of the research. Copies of the reports must be forwarded to the
p.(None): SVS/MS.
p.(None): d – If announcements in the media are to be used to recruit research subjects, such advertising must be authorized by
p.(None): the CEP. No indication may be given, whether implicitly or explicitly, that the product being investigated is effective
p.(None): and/or safe, or that it is equivalent to or better than other existing products.
p.(None): e – Convene the research subjects for follow up and evaluation.
p.(None): f – Require that the top management of the institution start an inquiry, suspend or interrupt the research and
p.(None): communicate the fact to CONEP and the SVS/MS.
p.(None): g – Any infringement of ethical principles or evidence of fraud of any nature should lead the CEP to request the
p.(None): creation of an Inquiry Committee and to communicate the results[of such inquiry] to CONEP, SVS/MS and other agencies
p.(None): (top management of the Institution, pertinent Regional Councils).
p.(None): h – Communicate the occurrence of serious adverse events to CONEP and the SVS/MS.
p.(None): i – Communicate to the Institution the occurrence or existence of administrative responsibility problems
p.(None): that may interfere with the ethical conduction of the research; report to CONEP and the SVS/MS immediately and, as the
p.(None): case may be, to the Regional Councils.
p.(None):
p.(None): V.2 – The National Health Council hereby delegates to the CEP authority to approve, from the point of view of ethics,
p.(None): research projects involving new pharmaceutical products, medicines and diagnostic tests, with the provision that the
p.(None): following documents be submitted to CONEP and the SVS/MS:
p.(None): a – a copy of the consolidated report approving the research project, together with a completed header page,
p.(None): b – official conclusion on the partial and final reports on the research and
p.(None): c – other documents required by CEP, CONEP or the SVS.
p.(None): V.3 – In research that includes patients submitted to emergency or urgency situations, the CEP must previously
p.(None): approve the conditions or limits for obtaining free and informed consent; in addition, the researcher must
p.(None): inform the research subject, on a timely basis, about his/her participation in the project.
p.(None):
p.(None): V.4 – Assess whether all adequate measures are being implemented in the case of research with human beings whose
p.(None): capability for self-determination is impaired or limited.
p.(None):
p.(None):
p.(None): VI - OPERATIONALIZATION
p.(None):
p.(None): VI.1 - CONEP will exercise its competencies in the terms of Resolution 196/96, with emphasis on the following
p.(None): activities:
p.(None): a – organizing an information and follow up system (item VIII.9.g of Resolution 196/96) on the basis of the data
p.(None): supplied by the CEPs (consolidated approval report, duly completed header page, partial and final reports, etc.);
p.(None): b – organizing a system to evaluate and follow up the activities of the CEPs. The system should enable peers, i.e.
p.(None): members of the various CEPs, to exchange information and experience, with reports to CONEP. It should also
p.(None): comply with the specific regulations issued by CONEP;
...
...
Health / healthy volunteers
Searching for indicator healthy volunteers:
(return to top)
p.(None): area should comply with the provisions of Law 6.360 (23 September 1976), regulated by Decree Nº 79.094 (5 January
p.(None): 1977).
p.(None):
p.(None): I.4 – In any clinical essay and particularly when there are conflicts of interests associated with new products, the
p.(None): dignity and well-being of the research subject must prevail over any other interests, whether economic, scientific, or
p.(None): of the community.
p.(None):
p.(None): I.5 – It is essential that all research in this thematic area be founded on recognized scientific norms and
p.(None): on knowledge based on in vitro laboratory experiments and pertinent literature.
p.(None):
p.(None): I.6 – It is necessary that the investigation of new products be justified and that such products actually result in
p.(None): significant progress when compared with existing products.
p.(None):
p.(None):
p.(None): II - TERMS AND DEFINITIONS
p.(None):
p.(None): II.1 – Research of new pharmaceutical products, medicines, vaccines or diagnostic tests. It refers to
p.(None): Phase I, II or III research with these types of products or with products not yet registered in the
p.(None): country, even in Phase IV, when the research focuses on their use with modalities, indications, dosages, or paths of
p.(None): administration different from those established at the time registration was authorized, including their use in
p.(None): combinations, as well as bioavailability and bioequivalence studies.
p.(None):
p.(None): II.2 – The terms listed below, which are part of the Common Market Group Resolution (GMC Nº 129/96), are hereby
p.(None): incorporated into this Resolution.
p.(None):
p.(None): a – Phase I
p.(None): It is the first study with human beings, in small groups of usually healthy volunteers, of a new active principle or
p.(None): a new formulation, usually investigated using human volunteers. The purpose of such research is to establish
p.(None): a preliminary notion of the safety and pharmacokinetic profile, and, if possible, the phamacodynamics profile [of the
p.(None): product].
p.(None): b – Phase II
p.(None): (Pilot-Scale Therapeutic Study)
p.(None): The objectives of the Pilot-Scale Therapeutic Study are to demonstrate the activity [of the product] and
p.(None): to ascertain the short-term safety of the active principle in patients affected by a given disease or pathological
p.(None): condition. The research is carried out on a limited (small) number of individuals and is frequently followed by an
p.(None): administration study. It should also be possible to establish the dose/response ratio for the purpose of
p.(None): obtaining sound background for the description of the extended therapeutic studies (Phase III).
p.(None): c – Phase III
p.(None): Extended Therapeutic Study
p.(None): These studies are performed on a large and varied number of patients, for the purpose of
p.(None):
p.(None): determining:
p.(None):
p.(None): • the result of short-term and long-term risks/benefits of the active principle formulations and
p.(None): • in a global (general) manner, the relative therapeutic value.
p.(None): In this phase, the type and profile of the most frequent adverse reactions are studied, as well as
p.(None): the especial characteristics of the medication and/or therapeutic specialty, for example, clinically
p.(None): relevant interactions, main factors that modify the effect, such as age, etc.
p.(None): d – Phase IV
...
Health / volunteers
Searching for indicator volunteers:
(return to top)
p.(None): dignity and well-being of the research subject must prevail over any other interests, whether economic, scientific, or
p.(None): of the community.
p.(None):
p.(None): I.5 – It is essential that all research in this thematic area be founded on recognized scientific norms and
p.(None): on knowledge based on in vitro laboratory experiments and pertinent literature.
p.(None):
p.(None): I.6 – It is necessary that the investigation of new products be justified and that such products actually result in
p.(None): significant progress when compared with existing products.
p.(None):
p.(None):
p.(None): II - TERMS AND DEFINITIONS
p.(None):
p.(None): II.1 – Research of new pharmaceutical products, medicines, vaccines or diagnostic tests. It refers to
p.(None): Phase I, II or III research with these types of products or with products not yet registered in the
p.(None): country, even in Phase IV, when the research focuses on their use with modalities, indications, dosages, or paths of
p.(None): administration different from those established at the time registration was authorized, including their use in
p.(None): combinations, as well as bioavailability and bioequivalence studies.
p.(None):
p.(None): II.2 – The terms listed below, which are part of the Common Market Group Resolution (GMC Nº 129/96), are hereby
p.(None): incorporated into this Resolution.
p.(None):
p.(None): a – Phase I
p.(None): It is the first study with human beings, in small groups of usually healthy volunteers, of a new active principle or
p.(None): a new formulation, usually investigated using human volunteers. The purpose of such research is to establish
p.(None): a preliminary notion of the safety and pharmacokinetic profile, and, if possible, the phamacodynamics profile [of the
p.(None): product].
p.(None): b – Phase II
p.(None): (Pilot-Scale Therapeutic Study)
p.(None): The objectives of the Pilot-Scale Therapeutic Study are to demonstrate the activity [of the product] and
p.(None): to ascertain the short-term safety of the active principle in patients affected by a given disease or pathological
p.(None): condition. The research is carried out on a limited (small) number of individuals and is frequently followed by an
p.(None): administration study. It should also be possible to establish the dose/response ratio for the purpose of
p.(None): obtaining sound background for the description of the extended therapeutic studies (Phase III).
p.(None): c – Phase III
p.(None): Extended Therapeutic Study
p.(None): These studies are performed on a large and varied number of patients, for the purpose of
p.(None):
p.(None): determining:
p.(None):
p.(None): • the result of short-term and long-term risks/benefits of the active principle formulations and
p.(None): • in a global (general) manner, the relative therapeutic value.
p.(None): In this phase, the type and profile of the most frequent adverse reactions are studied, as well as
p.(None): the especial characteristics of the medication and/or therapeutic specialty, for example, clinically
p.(None): relevant interactions, main factors that modify the effect, such as age, etc.
p.(None): d – Phase IV
p.(None): This is research performed when the product and/or therapeutic specialty is commercially
p.(None): available.
p.(None): This research is based on the characteristics under which the medicine and/or therapeutic
...
p.(None): repeated doses and chronic toxicity (repeated doses).
p.(None): e – The toxicology studies should be performed in at least three animal species, one of which must be a non-rodent
p.(None): mammal; both sexes must be included in the studies.
p.(None): f – In studying acute toxicity, two paths of administration must be used, one of which must be related to that
p.(None): recommended for the therapeutic use being proposed and the other must be a path that will ensure the absorption of the
p.(None): pharmaceutical product.
p.(None): g - In subacute toxicity, repeated dose and chronic toxicity studies the path of administration should be
p.(None): related to the proposed therapeutic use and the experiment should last at least 24 weeks.
p.(None): h – In the preclinical phase, the toxicity studies should also include an analysis of the effects on fertility,
p.(None): embryo-toxicity, mutagenicity, oncogenic (carcinogenic) potential, and other studies, according to the nature of the
p.(None): pharmaceutical product and the therapeutic proposal.
p.(None): i – Depending on the importance of the project, in view of the lack of time and in the absence of other therapeutic
p.(None): methods, the CEP may approve projects that have not fulfilled all clinical pharmacology phases; in this
p.(None): case, approval must also be obtained from CONEP and the SVS/MS.
p.(None): j – Information about the status of the research and product registration in the country of origin.
p.(None): k – The detailed clinical information obtained during the prior phases, as regards safety,
p.(None): pharmacodynamics, effectiveness, and dose-response observed in studies using human beings, whether healthy
p.(None): volunteers or patients. If possible, there should be a separate summary of each essay, with a
p.(None): description of the objectives, design, method, results (safety and effectiveness), and conclusions. In the case of a
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
...
Social / Access to Social Goods
Searching for indicator access:
(return to top)
p.(None):
p.(None): III.2 – The researcher shall be responsible for:
p.(None): a – submitting a complete research project to the Research Ethics Committee (CEP), in the terms of
p.(None): Resolution 196/96 and this Resolution;
p.(None): b – maintaining a file for each research subject, for a period of five years, after the end of the research, due
p.(None): compliance being given to the confidentiality and secrecy of the records;
p.(None):
p.(None): c – submitting a detailed report as requested or established by the CEP, the National Research Ethics Committee
p.(None): (CONEP), or the Health Surveillance Secretariat (SVS/MS);
p.(None): d – informing the CEP of any occurrence of collateral effects and/or unexpected adverse
p.(None): reactions;
p.(None): e – communicating also any proposed changes in the project and/or justification of interruptions,
p.(None): keeping in abeyance until the matter is appreciated by the CEP, except in urgent cases to safeguard the
p.(None): safety of research subjects; in the latter case, the CEP should be notified immediately afterwards;
p.(None): f – making available to CEP, CONEP and the SVS/MS all duly required information;
p.(None): g – continuously analyzing the findings, throughout the research, for the purpose of detecting, as soon as possible,
p.(None): the advantages of one treatment over another or preventing adverse effects on research subjects;
p.(None): h – submitting regular reports within the time periods established by the CEP, with at least one report every six
p.(None): months and one final report;
p.(None): i – providing the patient‟s physician and the patient him/herself access to the results of tests and treatment whenever
p.(None): requested and/or indicated; and
p.(None): j – recommending that no individual be selected as research subject before a year has passed from his/her participation
p.(None): in another research, unless that individual were to directly benefit from it.
p.(None):
p.(None):
p.(None): IV – RESEARCH PROTOCOL
p.(None):
p.(None): IV.1 – The protocol must include all items stipulated in Chapter VI of Resolution 196/96, in addition
p.(None): to the basic pharmacological information appropriate to the phase of the research project, in compliance
p.(None): with Res. GMC 129/96 - Mercosul – including the following.
p.(None): a – Specifications and rationale of the clinical research phase in which the study is to be carried out, demonstrating
p.(None): that prior phases have been concluded.
p.(None): b – Description of the pharmacological substance or product being investigated, including its chemical
p.(None): formula and/or structure, in addition to a brief summary of relevant physical, chemical and pharmaceutical
p.(None): properties. Any structural similarity to other known chemical compounds should also be mentioned.
p.(None): c – Detailed preclinical information is required to justify the phase of the project, including a report
p.(None): on the experimental studies (materials and methods, animals used, laboratory tests,
p.(None): pharmacodynamics data, margin of safety, therapeutic margin, pharmacokinetics, and toxicology, in the case of drugs,
p.(None): medicines, or vaccines). The preclinical results must be accompanied by a discussion of the relevance of
p.(None): the findings in connection with the expected therapeutic effects and possible undesirable effects in human beings.
...
p.(None): related to the proposed therapeutic use and the experiment should last at least 24 weeks.
p.(None): h – In the preclinical phase, the toxicity studies should also include an analysis of the effects on fertility,
p.(None): embryo-toxicity, mutagenicity, oncogenic (carcinogenic) potential, and other studies, according to the nature of the
p.(None): pharmaceutical product and the therapeutic proposal.
p.(None): i – Depending on the importance of the project, in view of the lack of time and in the absence of other therapeutic
p.(None): methods, the CEP may approve projects that have not fulfilled all clinical pharmacology phases; in this
p.(None): case, approval must also be obtained from CONEP and the SVS/MS.
p.(None): j – Information about the status of the research and product registration in the country of origin.
p.(None): k – The detailed clinical information obtained during the prior phases, as regards safety,
p.(None): pharmacodynamics, effectiveness, and dose-response observed in studies using human beings, whether healthy
p.(None): volunteers or patients. If possible, there should be a separate summary of each essay, with a
p.(None): description of the objectives, design, method, results (safety and effectiveness), and conclusions. In the case of a
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
p.(None): subject, even when not fully capable (for example, the elderly) or not fully developed (for example, children).
p.(None): r – In the case of research on psychiatric patients, whenever possible consent should be obtained from
p.(None): the patient him/herself. It is mandatory that the level of capability to express free and informed consent of each
...
Social / Age
Searching for indicator age:
(return to top)
p.(None): a new formulation, usually investigated using human volunteers. The purpose of such research is to establish
p.(None): a preliminary notion of the safety and pharmacokinetic profile, and, if possible, the phamacodynamics profile [of the
p.(None): product].
p.(None): b – Phase II
p.(None): (Pilot-Scale Therapeutic Study)
p.(None): The objectives of the Pilot-Scale Therapeutic Study are to demonstrate the activity [of the product] and
p.(None): to ascertain the short-term safety of the active principle in patients affected by a given disease or pathological
p.(None): condition. The research is carried out on a limited (small) number of individuals and is frequently followed by an
p.(None): administration study. It should also be possible to establish the dose/response ratio for the purpose of
p.(None): obtaining sound background for the description of the extended therapeutic studies (Phase III).
p.(None): c – Phase III
p.(None): Extended Therapeutic Study
p.(None): These studies are performed on a large and varied number of patients, for the purpose of
p.(None):
p.(None): determining:
p.(None):
p.(None): • the result of short-term and long-term risks/benefits of the active principle formulations and
p.(None): • in a global (general) manner, the relative therapeutic value.
p.(None): In this phase, the type and profile of the most frequent adverse reactions are studied, as well as
p.(None): the especial characteristics of the medication and/or therapeutic specialty, for example, clinically
p.(None): relevant interactions, main factors that modify the effect, such as age, etc.
p.(None): d – Phase IV
p.(None): This is research performed when the product and/or therapeutic specialty is commercially
p.(None): available.
p.(None): This research is based on the characteristics under which the medicine and/or therapeutic
p.(None): specialty was authorized. These are usually post-commercialization surveillance studies that aim
p.(None): at establishing the therapeutic value, [verifying] the emergence of new adverse reactions and/or confirming the
p.(None): frequency of known adverse reactions, as well as the treatment strategies.
p.(None): The same ethical and scientific norms applied in the research in the previous phases should be used in Phase IV
p.(None): research.
p.(None): Once a medicine and/or therapeutic specialty is already commercially available, the clinical research
p.(None): performed to explore new indications, new methods of administration, or new combinations (associations),
p.(None): etc. shall be considered research of a new medicine and/or therapeutic specialty.
p.(None): e – Pharmacokinetics
p.(None): As a rule, it is all the modifications a biological system causes on an active principle.
p.(None): In operational terms, it is the study of kinetics (quantitative relation between the independent variable
p.(None): „time‟ and the dependent variable „concentration‟) of the absorption, distribution, biotransformation, and excretion
p.(None): of medicines (active principle and/or its metabolites).
p.(None): f – Pharmacodynamics
p.(None): It is all the modifications an active principle causes in a biological system. From a practical
p.(None): standpoint, it is the study of the biochemical and physiological effects of medicines and their action
p.(None): mechanisms.
p.(None): g – Margin of Safety
...
Social / Child
Searching for indicator children:
(return to top)
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
p.(None): subject, even when not fully capable (for example, the elderly) or not fully developed (for example, children).
p.(None): r – In the case of research on psychiatric patients, whenever possible consent should be obtained from
p.(None): the patient him/herself. It is mandatory that the level of capability to express free and informed consent of each
p.(None): psychiatric patient be established by a psychiatrist other than the researcher involved in the project.
p.(None): In the case of drugs with psychopharmacological action, a critical analysis must be made of the possible risks of
p.(None): causing dependency.
p.(None):
p.(None): IV.2 – Including healthy subjects in research.
p.(None): a – Justifying the need to include healthy subject in the research project. Critical analysis of the risks involved.
p.(None): b – Description of how the recruitment will take place; no dependency situation should exist.
p.(None): c – In the case of drugs with psychopharmacological action, a critical analysis of the risk of causing
p.(None): dependency is necessary.
p.(None):
p.(None):
p.(None): V – ATTRIBUTIONS OF THE CEP
p.(None):
p.(None): V.1 – The CEP and the researcher will be jointly responsible for maintaining ethically correct conducts
p.(None): throughout the project and during the implementation of the research. In addition, they should take the following
p.(None): actions.
p.(None): a – Issue a consolidated report explaining the scientific basis of the research project and its relation
p.(None): with the studies in prior phases, including the preclinical phase, with emphasis on safety, toxicity,
...
Social / Elderly
Searching for indicator elderly:
(return to top)
p.(None): description of the objectives, design, method, results (safety and effectiveness), and conclusions. In the case of a
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
p.(None): subject, even when not fully capable (for example, the elderly) or not fully developed (for example, children).
p.(None): r – In the case of research on psychiatric patients, whenever possible consent should be obtained from
p.(None): the patient him/herself. It is mandatory that the level of capability to express free and informed consent of each
p.(None): psychiatric patient be established by a psychiatrist other than the researcher involved in the project.
p.(None): In the case of drugs with psychopharmacological action, a critical analysis must be made of the possible risks of
p.(None): causing dependency.
p.(None):
p.(None): IV.2 – Including healthy subjects in research.
p.(None): a – Justifying the need to include healthy subject in the research project. Critical analysis of the risks involved.
p.(None): b – Description of how the recruitment will take place; no dependency situation should exist.
p.(None): c – In the case of drugs with psychopharmacological action, a critical analysis of the risk of causing
p.(None): dependency is necessary.
p.(None):
p.(None):
p.(None): V – ATTRIBUTIONS OF THE CEP
p.(None):
p.(None): V.1 – The CEP and the researcher will be jointly responsible for maintaining ethically correct conducts
p.(None): throughout the project and during the implementation of the research. In addition, they should take the following
p.(None): actions.
p.(None): a – Issue a consolidated report explaining the scientific basis of the research project and its relation
...
Social / embryo
Searching for indicator embryo:
(return to top)
p.(None): properties. Any structural similarity to other known chemical compounds should also be mentioned.
p.(None): c – Detailed preclinical information is required to justify the phase of the project, including a report
p.(None): on the experimental studies (materials and methods, animals used, laboratory tests,
p.(None): pharmacodynamics data, margin of safety, therapeutic margin, pharmacokinetics, and toxicology, in the case of drugs,
p.(None): medicines, or vaccines). The preclinical results must be accompanied by a discussion of the relevance of
p.(None): the findings in connection with the expected therapeutic effects and possible undesirable effects in human beings.
p.(None): d – The preclinical toxicology data should include the study of acute toxicology, subacute toxicology with
p.(None): repeated doses and chronic toxicity (repeated doses).
p.(None): e – The toxicology studies should be performed in at least three animal species, one of which must be a non-rodent
p.(None): mammal; both sexes must be included in the studies.
p.(None): f – In studying acute toxicity, two paths of administration must be used, one of which must be related to that
p.(None): recommended for the therapeutic use being proposed and the other must be a path that will ensure the absorption of the
p.(None): pharmaceutical product.
p.(None): g - In subacute toxicity, repeated dose and chronic toxicity studies the path of administration should be
p.(None): related to the proposed therapeutic use and the experiment should last at least 24 weeks.
p.(None): h – In the preclinical phase, the toxicity studies should also include an analysis of the effects on fertility,
p.(None): embryo-toxicity, mutagenicity, oncogenic (carcinogenic) potential, and other studies, according to the nature of the
p.(None): pharmaceutical product and the therapeutic proposal.
p.(None): i – Depending on the importance of the project, in view of the lack of time and in the absence of other therapeutic
p.(None): methods, the CEP may approve projects that have not fulfilled all clinical pharmacology phases; in this
p.(None): case, approval must also be obtained from CONEP and the SVS/MS.
p.(None): j – Information about the status of the research and product registration in the country of origin.
p.(None): k – The detailed clinical information obtained during the prior phases, as regards safety,
p.(None): pharmacodynamics, effectiveness, and dose-response observed in studies using human beings, whether healthy
p.(None): volunteers or patients. If possible, there should be a separate summary of each essay, with a
p.(None): description of the objectives, design, method, results (safety and effectiveness), and conclusions. In the case of a
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
...
Economic / Economic/Poverty
Searching for indicator economic:
(return to top)
p.(None): pharmaceutical products, medicines, vaccines, and diagnostic tests:
p.(None):
p.(None): I - PREAMBLE
p.(None):
p.(None): I.1 – This Resolution incorporates all provisions contained in Resolution 196/96 of the National Health Council on
p.(None): Guidelines and Norms Regulating Research Involving Human Beings, which this Resolution complements in the specific
p.(None): thematic area of research with new pharmaceutical products, medicines, vaccines, and diagnostic tests.
p.(None):
p.(None): I.2 – It also refers to the Resolution on the Common Market Group (GMC) Nº 129/96, signed by Brazil, which establishes
p.(None): the technical regulations for ascertaining [the implementation of] good practices in clinical research.
p.(None):
p.(None): I.3 – The norms, resolutions and regulations issued by the Health Surveillance Secretariat of the Ministry of Health
p.(None): (SVS/MS) should be fully complied with, and SVS/MS authorization is required to execute and subsequently follow up and
p.(None): control the technical development of research projects in [the area of] Clinical Pharmacology (Phases I, II, III, and
p.(None): IV of products not yet registered in the country) and Bioavailability and Bioequivalence. Research projects in this
p.(None): area should comply with the provisions of Law 6.360 (23 September 1976), regulated by Decree Nº 79.094 (5 January
p.(None): 1977).
p.(None):
p.(None): I.4 – In any clinical essay and particularly when there are conflicts of interests associated with new products, the
p.(None): dignity and well-being of the research subject must prevail over any other interests, whether economic, scientific, or
p.(None): of the community.
p.(None):
p.(None): I.5 – It is essential that all research in this thematic area be founded on recognized scientific norms and
p.(None): on knowledge based on in vitro laboratory experiments and pertinent literature.
p.(None):
p.(None): I.6 – It is necessary that the investigation of new products be justified and that such products actually result in
p.(None): significant progress when compared with existing products.
p.(None):
p.(None):
p.(None): II - TERMS AND DEFINITIONS
p.(None):
p.(None): II.1 – Research of new pharmaceutical products, medicines, vaccines or diagnostic tests. It refers to
p.(None): Phase I, II or III research with these types of products or with products not yet registered in the
p.(None): country, even in Phase IV, when the research focuses on their use with modalities, indications, dosages, or paths of
p.(None): administration different from those established at the time registration was authorized, including their use in
p.(None): combinations, as well as bioavailability and bioequivalence studies.
p.(None):
p.(None): II.2 – The terms listed below, which are part of the Common Market Group Resolution (GMC Nº 129/96), are hereby
p.(None): incorporated into this Resolution.
p.(None):
p.(None): a – Phase I
p.(None): It is the first study with human beings, in small groups of usually healthy volunteers, of a new active principle or
p.(None): a new formulation, usually investigated using human volunteers. The purpose of such research is to establish
p.(None): a preliminary notion of the safety and pharmacokinetic profile, and, if possible, the phamacodynamics profile [of the
p.(None): product].
p.(None): b – Phase II
p.(None): (Pilot-Scale Therapeutic Study)
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.(None): • in a global (general) manner, the relative therapeutic value.
p.(None): In this phase, the type and profile of the most frequent adverse reactions are studied, as well as
p.(None): the especial characteristics of the medication and/or therapeutic specialty, for example, clinically
p.(None): relevant interactions, main factors that modify the effect, such as age, etc.
p.(None): d – Phase IV
p.(None): This is research performed when the product and/or therapeutic specialty is commercially
p.(None): available.
p.(None): This research is based on the characteristics under which the medicine and/or therapeutic
p.(None): specialty was authorized. These are usually post-commercialization surveillance studies that aim
p.(None): at establishing the therapeutic value, [verifying] the emergence of new adverse reactions and/or confirming the
p.(None): frequency of known adverse reactions, as well as the treatment strategies.
p.(None): The same ethical and scientific norms applied in the research in the previous phases should be used in Phase IV
p.(None): research.
p.(None): Once a medicine and/or therapeutic specialty is already commercially available, the clinical research
p.(None): performed to explore new indications, new methods of administration, or new combinations (associations),
p.(None): etc. shall be considered research of a new medicine and/or therapeutic specialty.
p.(None): e – Pharmacokinetics
p.(None): As a rule, it is all the modifications a biological system causes on an active principle.
p.(None): In operational terms, it is the study of kinetics (quantitative relation between the independent variable
p.(None): „time‟ and the dependent variable „concentration‟) of the absorption, distribution, biotransformation, and excretion
p.(None): of medicines (active principle and/or its metabolites).
p.(None): f – Pharmacodynamics
p.(None): It is all the modifications an active principle causes in a biological system. From a practical
p.(None): standpoint, it is the study of the biochemical and physiological effects of medicines and their action
p.(None): mechanisms.
p.(None): g – Margin of Safety
p.(None): It is the pharmacodynamics indicator that expresses the difference between the toxic dose (for example, the DL 50) and
p.(None): the effective dose (for example, the DE 50).
p.(None): h – Therapeutic Margin
p.(None): It is the ratio of the maximum tolerated dose, also toxic dose, to the therapeutic dose (toxic
p.(None): dose/therapeutic dose). In clinical pharmacology, the therapeutic margin is used as equivalent of the
p.(None): Therapeutic Indicator.
p.(None):
p.(None):
p.(None): III – RESPONSIBILITY OF THE RESEARCHER
p.(None):
p.(None): III.1 – The unremittable and untrasferable responsibility of the researcher to [comply with] the terms of
p.(None): Resolution 196/96 is hereby reaffirmed. All obligations provided for in said Resolution are equally reaffirmed,
p.(None): particularly the guarantee of conditions [required] to care for research subjects.
p.(None):
p.(None): III.2 – The researcher shall be responsible for:
p.(None): a – submitting a complete research project to the Research Ethics Committee (CEP), in the terms of
p.(None): Resolution 196/96 and this Resolution;
p.(None): b – maintaining a file for each research subject, for a period of five years, after the end of the research, due
p.(None): compliance being given to the confidentiality and secrecy of the records;
p.(None):
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.(None): e – Convene the research subjects for follow up and evaluation.
p.(None): f – Require that the top management of the institution start an inquiry, suspend or interrupt the research and
p.(None): communicate the fact to CONEP and the SVS/MS.
p.(None): g – Any infringement of ethical principles or evidence of fraud of any nature should lead the CEP to request the
p.(None): creation of an Inquiry Committee and to communicate the results[of such inquiry] to CONEP, SVS/MS and other agencies
p.(None): (top management of the Institution, pertinent Regional Councils).
p.(None): h – Communicate the occurrence of serious adverse events to CONEP and the SVS/MS.
p.(None): i – Communicate to the Institution the occurrence or existence of administrative responsibility problems
p.(None): that may interfere with the ethical conduction of the research; report to CONEP and the SVS/MS immediately and, as the
p.(None): case may be, to the Regional Councils.
p.(None):
p.(None): V.2 – The National Health Council hereby delegates to the CEP authority to approve, from the point of view of ethics,
p.(None): research projects involving new pharmaceutical products, medicines and diagnostic tests, with the provision that the
p.(None): following documents be submitted to CONEP and the SVS/MS:
p.(None): a – a copy of the consolidated report approving the research project, together with a completed header page,
p.(None): b – official conclusion on the partial and final reports on the research and
p.(None): c – other documents required by CEP, CONEP or the SVS.
p.(None): V.3 – In research that includes patients submitted to emergency or urgency situations, the CEP must previously
p.(None): approve the conditions or limits for obtaining free and informed consent; in addition, the researcher must
p.(None): inform the research subject, on a timely basis, about his/her participation in the project.
p.(None):
p.(None): V.4 – Assess whether all adequate measures are being implemented in the case of research with human beings whose
p.(None): capability for self-determination is impaired or limited.
p.(None):
p.(None):
p.(None): VI - OPERATIONALIZATION
p.(None):
p.(None): VI.1 - CONEP will exercise its competencies in the terms of Resolution 196/96, with emphasis on the following
p.(None): activities:
p.(None): a – organizing an information and follow up system (item VIII.9.g of Resolution 196/96) on the basis of the data
p.(None): supplied by the CEPs (consolidated approval report, duly completed header page, partial and final reports, etc.);
p.(None): b – organizing a system to evaluate and follow up the activities of the CEPs. The system should enable peers, i.e.
p.(None): members of the various CEPs, to exchange information and experience, with reports to CONEP. It should also
p.(None): comply with the specific regulations issued by CONEP;
p.(None): c – informing the appropriate authorities, particularly the Health Surveillance Secretariat of the Ministry of Health,
p.(None): with a view to appropriate action, proven violations of the ethical standards in the execution of research projects;
p.(None): and
p.(None): d – supplying the various bodies of the Ministry of Health, particularly the Health Surveillance Secretariat,
p.(None): the information required to fully exercise their respective competencies as regards the research covered in this
p.(None): Resolution.
p.(None):
p.(None): VI.2 – The Health Surveillance Secretariat/MS shall exercise its attributions in the terms of Resolution
p.(None): 196/96, with especial emphasis on the following activities.
p.(None): a – Reporting, in writing, to CONEP any indication of violation of ethics observed or detected during the
p.(None): execution of the research projects covered in this Resolution.
p.(None): b – Supply, upon request or when pertinent, the information required for the full exercise of the competencies of
p.(None): CONEP.
p.(None): c – In the case of research involving situations for which there is no recognized treatment
p.(None): (“humanitarian use” or “compassionately”), the release of the product may be authorized as an emergency measure, after
p.(None): CEP approval and ratification by CONEP and the SVS/MS.
p.(None): d – Standardizing its internal operational procedures with a view to exerting effective health control of
p.(None): the products object of clinical research.
p.(None):
p.(None):
p.(None):
p.(None):
p.(None): CARLOS CÉSAR S. DE ALBUQUERQUE
p.(None): President of the National Health Council
p.(None):
p.(None):
p.(None):
p.(None): I hereby ratify CNS Resolution Nº 251, dated 7 August 1997, in the terms of the Decree on the
p.(None): Delegation of Competency dated 12 November 1991.
p.(None):
p.(None):
p.(None):
p.(None):
p.(None): CARLOS CÉSAR S. DE ALBUQUERQUE
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.(None): b – Approve the justification of the use of a placebo and washout.
p.(None): c – Request partial and final reports from the main researcher establishing the schedule (on a six-monthly basis at
p.(None): least) according to the characteristics of the research. Copies of the reports must be forwarded to the
p.(None): SVS/MS.
p.(None): d – If announcements in the media are to be used to recruit research subjects, such advertising must be authorized by
p.(None): the CEP. No indication may be given, whether implicitly or explicitly, that the product being investigated is effective
p.(None): and/or safe, or that it is equivalent to or better than other existing products.
p.(None): e – Convene the research subjects for follow up and evaluation.
p.(None): f – Require that the top management of the institution start an inquiry, suspend or interrupt the research and
p.(None): communicate the fact to CONEP and the SVS/MS.
p.(None): g – Any infringement of ethical principles or evidence of fraud of any nature should lead the CEP to request the
p.(None): creation of an Inquiry Committee and to communicate the results[of such inquiry] to CONEP, SVS/MS and other agencies
p.(None): (top management of the Institution, pertinent Regional Councils).
p.(None): h – Communicate the occurrence of serious adverse events to CONEP and the SVS/MS.
p.(None): i – Communicate to the Institution the occurrence or existence of administrative responsibility problems
p.(None): that may interfere with the ethical conduction of the research; report to CONEP and the SVS/MS immediately and, as the
p.(None): case may be, to the Regional Councils.
p.(None):
p.(None): V.2 – The National Health Council hereby delegates to the CEP authority to approve, from the point of view of ethics,
p.(None): research projects involving new pharmaceutical products, medicines and diagnostic tests, with the provision that the
p.(None): following documents be submitted to CONEP and the SVS/MS:
p.(None): a – a copy of the consolidated report approving the research project, together with a completed header page,
p.(None): b – official conclusion on the partial and final reports on the research and
p.(None): c – other documents required by CEP, CONEP or the SVS.
p.(None): V.3 – In research that includes patients submitted to emergency or urgency situations, the CEP must previously
p.(None): approve the conditions or limits for obtaining free and informed consent; in addition, the researcher must
p.(None): inform the research subject, on a timely basis, about his/her participation in the project.
p.(None):
p.(None): V.4 – Assess whether all adequate measures are being implemented in the case of research with human beings whose
p.(None): capability for self-determination is impaired or limited.
p.(None):
p.(None):
p.(None): VI - OPERATIONALIZATION
p.(None):
p.(None): VI.1 - CONEP will exercise its competencies in the terms of Resolution 196/96, with emphasis on the following
p.(None): activities:
p.(None): a – organizing an information and follow up system (item VIII.9.g of Resolution 196/96) on the basis of the data
p.(None): supplied by the CEPs (consolidated approval report, duly completed header page, partial and final reports, etc.);
p.(None): b – organizing a system to evaluate and follow up the activities of the CEPs. The system should enable peers, i.e.
...
General/Other / participants in a control group
Searching for indicator placebo:
(return to top)
p.(None): pharmaceutical product.
p.(None): g - In subacute toxicity, repeated dose and chronic toxicity studies the path of administration should be
p.(None): related to the proposed therapeutic use and the experiment should last at least 24 weeks.
p.(None): h – In the preclinical phase, the toxicity studies should also include an analysis of the effects on fertility,
p.(None): embryo-toxicity, mutagenicity, oncogenic (carcinogenic) potential, and other studies, according to the nature of the
p.(None): pharmaceutical product and the therapeutic proposal.
p.(None): i – Depending on the importance of the project, in view of the lack of time and in the absence of other therapeutic
p.(None): methods, the CEP may approve projects that have not fulfilled all clinical pharmacology phases; in this
p.(None): case, approval must also be obtained from CONEP and the SVS/MS.
p.(None): j – Information about the status of the research and product registration in the country of origin.
p.(None): k – The detailed clinical information obtained during the prior phases, as regards safety,
p.(None): pharmacodynamics, effectiveness, and dose-response observed in studies using human beings, whether healthy
p.(None): volunteers or patients. If possible, there should be a separate summary of each essay, with a
p.(None): description of the objectives, design, method, results (safety and effectiveness), and conclusions. In the case of a
p.(None): large number of studies, the summary must encompass groups by phase, in order to facilitate a discussion
p.(None): of the results and their implications.
p.(None): l – Justification for the use of a placebo and possible suspension of treatment (washout).
p.(None): m – Access to the medicine being tested must be assured by the sponsor or by the institution, researcher, or
p.(None): promoter, if there is no sponsor, in the event its superiority to the conventional treatment is proven.
p.(None):
p.(None): n – In multiple center studies the researcher must, to the extent possible, participate in the design of
p.(None): the project. If this is not possible, the researcher must formally state that he/she agrees with the existing design
p.(None): and that he/she will follow it.
p.(None): o – The sponsor must provide the researcher all data about the pharmaceutical product.
p.(None): p – Funding must not be tied to the per capita payment of the subjects effectively recruited.
p.(None): q – The protocol must be accompanied by the terms of consent. In the case of subjects not fully capable of
p.(None): self-determination, in addition to the consent from the individual legally responsible for the proposed
p.(None): research subject, it is necessary to take into account the expressed wishes of the proposed research
p.(None): subject, even when not fully capable (for example, the elderly) or not fully developed (for example, children).
p.(None): r – In the case of research on psychiatric patients, whenever possible consent should be obtained from
p.(None): the patient him/herself. It is mandatory that the level of capability to express free and informed consent of each
p.(None): psychiatric patient be established by a psychiatrist other than the researcher involved in the project.
p.(None): In the case of drugs with psychopharmacological action, a critical analysis must be made of the possible risks of
p.(None): causing dependency.
p.(None):
p.(None): IV.2 – Including healthy subjects in research.
p.(None): a – Justifying the need to include healthy subject in the research project. Critical analysis of the risks involved.
p.(None): b – Description of how the recruitment will take place; no dependency situation should exist.
p.(None): c – In the case of drugs with psychopharmacological action, a critical analysis of the risk of causing
p.(None): dependency is necessary.
p.(None):
p.(None):
p.(None): V – ATTRIBUTIONS OF THE CEP
p.(None):
p.(None): V.1 – The CEP and the researcher will be jointly responsible for maintaining ethically correct conducts
p.(None): throughout the project and during the implementation of the research. In addition, they should take the following
p.(None): actions.
p.(None): a – Issue a consolidated report explaining the scientific basis of the research project and its relation
p.(None): with the studies in prior phases, including the preclinical phase, with emphasis on safety, toxicity,
p.(None): adverse reactions or effects, effectiveness, and results.
p.(None): b – Approve the justification of the use of a placebo and washout.
p.(None): c – Request partial and final reports from the main researcher establishing the schedule (on a six-monthly basis at
p.(None): least) according to the characteristics of the research. Copies of the reports must be forwarded to the
p.(None): SVS/MS.
p.(None): d – If announcements in the media are to be used to recruit research subjects, such advertising must be authorized by
p.(None): the CEP. No indication may be given, whether implicitly or explicitly, that the product being investigated is effective
p.(None): and/or safe, or that it is equivalent to or better than other existing products.
p.(None): e – Convene the research subjects for follow up and evaluation.
p.(None): f – Require that the top management of the institution start an inquiry, suspend or interrupt the research and
p.(None): communicate the fact to CONEP and the SVS/MS.
p.(None): g – Any infringement of ethical principles or evidence of fraud of any nature should lead the CEP to request the
p.(None): creation of an Inquiry Committee and to communicate the results[of such inquiry] to CONEP, SVS/MS and other agencies
p.(None): (top management of the Institution, pertinent Regional Councils).
p.(None): h – Communicate the occurrence of serious adverse events to CONEP and the SVS/MS.
p.(None): i – Communicate to the Institution the occurrence or existence of administrative responsibility problems
p.(None): that may interfere with the ethical conduction of the research; report to CONEP and the SVS/MS immediately and, as the
p.(None): case may be, to the Regional Councils.
p.(None):
p.(None): V.2 – The National Health Council hereby delegates to the CEP authority to approve, from the point of view of ethics,
...
Orphaned Trigger Words
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| access | Access to Social Goods |
| age | Age |
| authority | Relationship to Authority |
| children | Child |
| dependency | Drug Dependence |
| dependent | Dependent |
| economic | Economic/Poverty |
| elderly | Elderly |
| embryo | embryo |
| emergency | Public Emergency |
| health | Health |
| healthy volunteers | healthy volunteers |
| impaired | Cognitive Impairment |
| placebo | participants in a control group |
| substance | Drug Usage |
| volunteers | volunteers |
Indicator Peers (Indicators in Same Vulnerability)
Trigger Words
consent
ethics
risk
self-determination
Applicable Type / Vulnerability / Indicator Overlay for this Input