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Monday, March 12, 2012
8.4.2. DOCUMENTATION ON THE DESTRUCTION OF THE TESTED PRODUCT
8.4.3. LISTA SA
respondents, how much was returned to the sponsor Document destruction
unused tested products at the testing center or sponsored
Enable
X (if X
destroyed at the site of the test)
X
tests performed on humans. Complying with these standards gives the public confidence that they are
the rights, safety and well-being of the respondents are protected and in accordance with the principles arising from the Declaration of Helsinki, and
that the information obtained from the clinical trial is credible.
The aim of these Good Clinical Practice Guidelines is to provide a single standard for the European Union
(EU), Japan and the United States to facilitate the mutual acceptance of clinical data by
by the competent authorities of those
IDENTIFICATION IDENTIFICATION
countries.
CODE OF RESPONDENTS
of all respondents who participated in the examination for the purpose of monitoring them. The list should be kept confidential at
the agreed time period
The guidelines have been developed taking into account the applicable principles of good clinical practice in the European Union, Japan and
The United States, but also Australia, Canada, the Nordic countries, and the World Health Organization (WHO).
These guidelines should be followed when analyzing clinical trial data at the time of submission
requests to the competent authorities.
The principles set out in these Guidelines may also apply
8.4.4. WITNESS CERTIFICATE Document that X
(where available)
8.4.5. FINAL
is odit performed Document yes
in other clinical trials that may affect safety
X and respondent welfare.
MONITOR REPORT are all activities in
1. DEFINITIONS
ABOUT TESTING COMPLETION
8.4.6. THERAPY GROUPS AND DECISION DOCUMENTATION
8.4.7. FINAL REPORT OF THE RESEARCHER TO THE ETHICAL COMMITTEE AND / OR THE COMPETENT AUTHORITIES
8.4.8. CLINICAL TESTING FINAL REPORT
9. PUBLISHING
examination completed, and copies of basic documents kept in appropriate records
Returns to the sponsor to document any decryption procedures
Document completion of testing
Document test results and interpretation
X
X
X X
(if necessary)
1.1. Adverse drug reaction
Any adverse and unintentionally induced drug reaction that may occur at a therapeutic dose, or
administration of the usual dose for prophylactic, diagnostic or therapeutic purposes, or for modifying physiological
function (see "ICH" Clinical Safety Information Management Guidelines: Definitions and Standards for Emergency
reporting).
The term & quot; drug reaction & quot; means that there is a cause and effect relationship between the drug and the undesired
to act at least as a possibility, ie. that it cannot be ruled out.
1.2. Adverse event
Any adverse medical event in a clinical trial in a patient or subject
who has received a pharmaceutical product and for which there is no need for a cause and effect relationship with the administration of the product
to be proved. An adverse event represents any adverse and adverse event (including
deviation in laboratory findings), symptom or disease associated with the use of (investigated)
product, whether or not it is the cause (see "ICH" Clinical Data Management Guidelines
security:
These Guidelines shall enter into force on the day of their adoption and shall be published in the Official Gazette of BiH.
Chairman of the Expert Council
Definitions and standards for emergency reporting).
1.3. Amendments to the Protocol
Amendments to the Protocol or formal explanation of the Protocol.
No. 10-07.2-1174-1 / 12
February 27, 2012
Cf. mr ph.
Ivan Prlic, s. r.
1.4. Legislation in force (s)
Law (s) and regulation (s) relating to the conduct of clinical trials of medicinal products / medical devices.
1.5. Approval (Refers to Ethics Committee)
Pursuant to Article 47, paragraph (3) of the Law on Medicines and Medical Devices of Bosnia and Herzegovina
(Official Gazette of BiH, No. 58/08), Expert Council of the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina
Herzegovina, at the 13th session held on 17.11.2011. at the proposal of the Director of the Agency for Medicinal Products and
medical devices of Bosnia and Herzegovina, brings
GUIDELINES
GOOD CLINICAL PRACTICES IN CLINICAL TESTING
INTRODUCTION
Good clinical practice (GCP) represents international ethical and scientific
quality standards for planning, implementing, monitoring and reporting on
Positive decision of the Ethics Committee on clinical trial that it can be conducted at the trial center in accordance with
provisions of this committee, institution, Good Clinical Practice and applicable law.
1.6. Odit
Systematic and independent review of clinical trial activities and documents to determine if
examination conducted, data entered and analyzed and reported in accordance with the Protocol,
sponsor standard operating procedures (SOPs), Good Clinical Practice and applicable legal requirements.
1.7. Certificate of Completion
A statement confirming that the odit was performed.
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1.8. Departure report
Auditor's written report on the results of the audit.
1.9. The documentation is gone
Documentation allowing monitoring of the course of the clinical trial.
1.10. Clinical trial blindness / masking
A process to ensure that one or more parties participating in a clinical trial do not have insight into
the respondents' belonging to the treatment groups. A single blind examination means that the respondent,
that is, respondents have no insight into belonging to treatment groups, and double-blind to insight into belonging
The treatment groups do not have a respondent, ie respondents, a researcher, a monitor, and in some cases, an analyst
data.
1.11. Test list
Printed, optical or electronic document intended to record all data required by the Protocol
a clinical trial reporting the sponsor to each subject.
1.12. Clinical trial
Any human test intended to detect or confirm clinical, pharmacological and / or
pharmacodynamic effects of the test product and / or adverse reaction identification and / or testing
resorption, distribution, metabolism and excretion, with the aim of determining safety and / or efficacy
of the tested product.
1.13. Clinical trial report
Document a complete clinical trial of any therapeutic, prophylactic or diagnostic efficacy
of the drug, which summarizes clinically and statistically significant data, findings and analyzes obtained
test results. (see "ICH" Guidelines for the Structure and Content of the Clinical Report
examination).
1.14. Comparative product
Tested or marketed product (i.e. active control) or placebo to compare drug / medical
the product being clinically tested.
1.15. Compliance with the adopted clinical trial plan
Compliance with all clinical trial requirements, Good Clinical Practice and applicable legal requirements.
1.16. Confidentiality
Preventing the disclosure of proprietary information owned by the sponsor or disclosing the identity of the respondents,
except for authorized ones.
1.17. The contract
A written, dated and signed contract between two or more parties involved in determining the assignments,
delegation and allocation of tasks and responsibilities, and financial matters if necessary. The contract may be based on
Protocol.
1.18. Coordination committee
A sponsor-based committee to conduct a multicenter clinical trial in concert.
1.19. Researcher Coordinator
Researcher responsible for coordinating researchers at different participating multicenter centers
examination.
1.20. Contract Research Organization (CRO)
A legal or natural person who contracts with a sponsor of a clinical trial based on which of the sponsors
assumes all or part of the authorization in the clinical trial.
1.21. Direct access to data
Permission to view, analyze, verify and transmit all data and reports relevant to clinical evaluation
testing.
Any party having direct access to the documentation (eg domestic or foreign authorities, monitors and
auditors) is obliged to take all reasonable precautions within the applicable legal provisions in order to preserve
the secrecy of the identity of the respondents and the data owned by the sponsor
1.22. Clinical trial documentation
All data in any format (including written, electronic, magnetic and optical records and
recordings, x-rays, electrocardiograms, etc.) describing or recording methods, and conducting and / or
the results of the clinical trial, the factors affecting it, and the measures taken.
1.23. Basic documentation
Documents that, individually or together, provide an assessment of the conduct of the clinical trial and the quality
the data obtained (see 8. Basic documents for conducting the clinical trial).
1.24. Good clinical practice
Good Clinical Practice (GCP) is an international ethical and scientific system
the quality of planning, performing, recording, monitoring and reporting on clinical trial at
people, which enables the credibility of the information obtained during the examination and protection of rights
and the safety of the respondent in accordance with the Declaration of Helsinki on the Protection of Patients' Rights (u
(hereinafter referred to as the Declaration of Helsinki).
1.25. Independent Data Monitoring Committee
An independent data monitoring committee may establish a sponsor in order to conduct a periodic assessment of the clinical course
tests, safety data and key performance conclusions, and which he recommends
sponsor continuation, modification, or termination of clinical trial.
1.26. An impartial witness
A person independent of the clinical trial who cannot be influenced by the people involved in the clinical trial,
which is present in the process of giving informed consent if the respondent or his legal representative does not
can read, and who reads to the respondent any written notice for the respondent.
1.27. Ethics Committee
An independent advisory body responsible for evaluating the validity of a clinical trial,
as well as the ability to conduct a clinical trial according to the principles of Good Clinical Practice, and all
this to ensure and protect the rights, safety and well-being of the subjects involved in the clinical
examination.
The legal status, composition, activities and regulations of the Ethics Committees may vary from country to country,
but they must certainly allow the Ethics Committee to act in accordance with the Good Clinical Practice described in these
guidelines.
1.28. Informed consent
The process by which the respondent voluntarily confirms his / her willingness to participate in a particular clinical
examination, having previously been informed of all aspects of the clinical trial that may be affected
to the decision to participate. The informed consent of the informed respondent shall be documented by written,
signed and dated patient informed consent form.
1.29. Inspection
Procedure by the competent authorities to carry out an official review of documents, institutions, files and all
other information that authorities believe is related to the clinical trial and can be found at the site of the study
clinical trial, with sponsors and / or contracting research organizations, or others
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Monday, March 12, 2012
institutions that the competent authorities deem appropriate for assessment.
1.30. Institution (medical)
One or more healthcare facilities where the clinical trial is being conducted.
1.31. Institutional Ethics Committee
An independent body made up of medical, scientific or non-scientific members whose responsibility is insurance
protection of the rights, safety and well-being of the subjects involved in the clinical trial, among others
controlling, approving and ensuring ongoing review of the Clinical Trial Protocol and its annexes,
as well as the method for obtaining and documenting the consent of the respondents.
1.32. Clinical trial progress report
Report on the results of the clinical trial and their evaluation based on the analysis conducted for
a specific period of time during the clinical trial.
1.33. Tested product
The pharmaceutical form of the active substance being tested or the placebo with which the test substance is compared,
including a product that has a marketing authorization if its use or method (form
or packaging) different from the approved one, or, if applicable for an indication that is not approved,
or used to obtain new information on an approved application.
1.34. Explorer
The person responsible for conducting the clinical trial at the place where it is conducted. If testing on someone
The site is run by a research team, the researcher responsible for conducting the clinical trial is
principal investigator.
1.35. Researcher / Institution
The term "researcher and / or institution" is used if required by applicable regulations.
1.36. Brochure for the researcher
A set of clinical and preclinical data on a test product relevant to its testing in humans
(see
7. Researcher Brochure).
1.37. Legal representative
An individual or a legal or other body empowered by applicable law to give consent on behalf of respondents
participation in a clinical trial.
1.38. Monitoring
The process of monitoring the clinical trial process and confirming that implementation, documentation, and
reporting in accordance with the Clinical Trial Protocol, standard operating procedures, Good
clinical practice and applicable law.
1.39. Monitoring report
A written report that the monitor submits to the sponsor after each visit to the examination center, as well as a report on
any new knowledge regarding testing in accordance with the sponsor's standard operating procedures.
1.40. Multicenter clinical trial
A clinical trial conducted in accordance with the unique clinical trial protocol in
multiple centers and is conducted by multiple researchers, whether the test centers are in the same or
different countries.
1.41. Preclinical research
Non-human biomedical research.
1.42. Opinion of the Independent Ethics Committee
Advice and / or recommendation of the Independent Ethics Committee.
1.43. Original health information
See Original data.
1.44. Clinical trial protocol
Document describing the objectives, plan, test methodology, method of statistical data processing and
organization of testing. The protocol usually contains either an introduction and a rational basis for testing or this may
be described by a protocol amendment.
1.45. Changes and additions to the Clinical Trial Protocol
Description of the modification of the Clinical Trial Protocol in writing, or its official explanation.
1.46. Quality assurance
All planned and systematic activities aimed at ensuring consistency of implementation
clinical trial, documenting results and reporting with Good Clinical Practice and applicable law
regulations.
1.47. Quality control
Operational techniques and quality assurance activities aimed at verifying that they are
all the quality requirements related to the test are met.
1.48. Randomization
The process of randomly selecting (classifying) subjects into a therapeutic or control group, thereby reducing it
researcher bias.
1.49. Competent authorities
Bodies competent for the adoption of legislation. For the purposes of these guidelines, the term competent authorities includes bodies which
have the regulatory power to legislate including review a submitted clinical
documentation and inspection (see 1.29).
1.50. Serious adverse event or serious adverse reaction
Any undesirable medical phenomenon related to the health of the subjects causing at any dose:
- death,
- Immediate threat to life,
- requires or extends existing hospitalization,
- permanent or significant disability or disability,
- congenital anomalies, that is, a birth defect.
1.51. Original data
Original medical records from original documents and certified copies of original clinical and laboratory records
findings or other results of activities performed during the clinical trial that are required for
evaluation of test results.
The original information is contained in the original documentation (as originals or certified copies).
1.52. Original documentation
Source documents, data and records (e.g., medical history, clinical and administrative records,
laboratory findings, memos, subjects' diaries or test lists, drug dispensing records, recorded
automated device data, copies and transcripts verified after authentication, negatives,
microfilms and magnetic recordings, x-rays, pharmacy records, laboratories and
medical-technical services involved in the clinical trial).
1.53. Sponsor
Individual or legal entity responsible for initiating, conducting and / or financing a clinical
testing.
1.54. Sponsor - Researcher
An individual who initiates and conducts a clinical trial, alone or with others, and under whose immediate supervision
the test product is prescribed, dispensed, or applied by the respondent. This one
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the term is restricted to natural persons (ie does not include legal persons such as corporations or agencies).
The duties of sponsor - researcher are combined the duties of sponsor and researcher
1.55. Standard Operating Procedures ("SOPs")
Detailed written instructions for achieving uniformity in performing all clinical procedures
testing.
1.56. Podistraživač
Each individual member of the clinical trial team is appointed and supervised by
investigator at the test center to perform key activities in the clinical trial and / or for
clinical trial decision making (eg associates, specialists, research associates).
1.57. Respondent
The person participating in the clinical trial, whether receiving the test product or
participates to control drug administration.
1.58. Respondent's identification code
The unique identification code assigned by the researcher to each respondent to protect the respondent's identity,
which is used instead of the name of the respondent when the researcher reports adverse reactions and / or others
clinical trial data.
1.59. Testing Center
The place or institution where the activities related to the clinical trial are conducted.
1.60. An unexpected side effect
Reaction to a medicine whose nature, severity or outcome are not known or are not described in the Product Brochure
researcher or in the summary of product characteristics, which cannot be expected based on known pharmacological properties
drug.
1.61. Vulnerable subjects
Individuals whose willingness to participate in a clinical trial may be unjustifiably influenced by expectations,
justified or not, that participation will bring them certain benefits, that is, otherwise they will be
threaten the elderly or superiors in the event that they refuse to participate. Examples are members
hierarchical groups such as medical, pharmacy or dental students, hospital and laboratory
personnel, employees of the pharmaceutical industry, members of the military and police forces and prisoners.
Among these respondents are patients with incurable diseases, residents of homes for
powerless, unemployed and poor people, patients in urgent conditions, ethnic minorities, homeless people,
nomads, refugees, minors and persons incapable of giving their consent.
1.62. Respondent safety
Physical and mental integrity of the participant in the clinical trial.
2. PRINCIPLES OF GOOD CLINICAL PRACTICE IN CLINICAL TESTING
2.1. Clinical trials should be conducted in accordance with the ethical principles of Helsinki
declarations, Good Clinical Practices and applicable legislation.
2.2. Before starting the clinical trial, the risks and disruptions to
expected benefits for respondents and society. Clinical trials should only be initiated and conducted if
the expected benefit justifies the risk.
2.3. The rights, safety and well-being of the respondents must be above the interests of science and society.
2.4. The intended clinical trial should be supported by appropriate available preclinical and clinical data on
test product.
2.5. The clinical trial should be scientifically based, and clearly and thoroughly presented in the Protocol.
2.6. Clinical trials should be conducted in accordance with the Ethics-approved Protocol / Positive Opinion
board.
2.7. Nursing care and treatment decisions should always be a responsibility
researchers.
2.8. All persons participating in the examination must have the appropriate education, expertise and skills
experience to perform their tasks.
2.9. Prior to enrolling in a clinical trial, each subject should voluntarily consent to participate in a clinical trial
examination.
2.10. All clinical trial information should be documented and documented and stored on file
a way that enables accurate reporting, interpretation and verification.
2.11. Information that can reveal the identity of respondents should be protected in accordance with the principles of privacy and
confidentiality in accordance with applicable law.
2.12. The production, handling and storage / storage of tested products must be in accordance with the applicable regulations
Good manufacturing practice. They should be used in accordance with the approved Protocol.
2.13. Procedures should be established to ensure the quality of all aspects of the clinical trial.
3. ETHICAL COMMITTEE
3.1. Responsibilities
3.1.1. The Ethics Committee protects the rights, safety and well-being of all respondents, especially sensitive patients.
3.1.2. The ethics committee should have the following documents: Clinical trial protocol and amendments thereto
and Appendices, Forms for Informed Consent of the Respondents, and their Amendments that the Researcher intends to use
in the examination, the procedure for engaging respondents (e.g., advertisements), written information intended
respondents, Researcher Brochure, security information available, payment information and reimbursements
for respondents, the researcher's current biography and / or other documents attesting to his or her own
qualifications and other documentation at the request of the Ethics Committee. The Ethics Committee should consider and evaluate
reviewed clinical trial within a reasonable timeframe and to provide its opinion in writing clearly
identifying the clinical trial as well as the documents and dates considered for the following:
- approval / positive opinion;
- necessary modifications to the test prior to approval / positive opinion;
- rejection / negative opinion;
- Permanent or temporary revocation of any earlier opinion.
3.1.3. The Ethics Committee should consider the qualifications of the researcher for the proposed examination at
on the basis of the biography or other relevant documentation requested by the Ethics Committee.
3.1.4. The Ethics Committee should conduct continuous monitoring of each ongoing examination, in periods
which are appropriate for the risk assessment of the respondents and at least once a year.
3.1.5. The Ethics Committee has the right to request that the respondent be provided with more information than the one indicated in
of items 4.8.10. when, in the opinion of the Ethics Committee, such supplementary information
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can significantly contribute to the protection of the rights, safety and / or well-being of respondents.
3.1.6. When should a non-therapeutic clinical trial be conducted for which legal consent is required
(see 4.8.12, 4.8.14), the Ethics Committee should determine whether they are in the proposed Testing Protocol
and / or other documentation sufficiently considered ethical issues and whether they meet current legal requirements
regulations for such tests.
3.1.7. When the Examination Protocol indicates that it is not possible to obtain the consent of the subjects in a timely manner or
of his legal representative (ie in an emergency, see 4.8.15), the Ethics Committee should determine whether
the proposed Testing Protocol and / or other documentation sufficiently considered ethical issues and whether
meet the applicable legal requirements for such tests.
3.1.8. The Ethics Committee considers the amount and method of payment of reimbursement to respondents to remove
the potential for forcible or inappropriate influence on the respondents. Payment of compensation is required
distribute in installments, not the full amount upon completion of respondent's participation in
examination.
3.1.9. The Ethics Committee should provide payment information to the respondents, including manner, amount and schedule
payments, to be defined in the respondent's written consent form, as well as in any other written notice
for the respondents. The method of payment in proportionate installments should be indicated.
3.2. Composition, functions and procedures
3.2.1. The ethics committee should be composed of persons who have the appropriate qualifications and experience required for
consideration and evaluation of the scientific, medical and ethical aspects of the proposed test. It is recommended that Ethical
committee:
a) has at least five members;
b) at least one member whose sphere of interest is unscientific;
c) at least one member independent of the institution or the place where the examination is conducted.
To prevent conflicts of interest, only those Ethics Committee members who are not researchers and are independent of
sponsors can vote, or give their opinion on clinical trial issues. Member list
The Ethics Committee and their qualifications should be separately kept and regularly updated.
3.2.2. The Ethics Committee should perform its function in accordance with written standard operating procedures,
document their work and make minutes of their meetings, and the Good Clinical should be adhered to
practices and applicable laws.
3.2.3. The Ethics Committee should make its decisions at the pre-announced meetings, at least attended
a quorum, in accordance with written operating procedures.
3.2.4. Only members of the Ethics Committee shall have the right to vote or to express opinions and / or recommendations
committees involved in the deliberation and discussion.
3.2.5. Researchers may be required to provide the Ethics Committee with information on any aspect of the examination,
but he may not participate in the deliberations or decisions of the Ethics Committee.
3.2.6. The Ethics Committee may seek the assistance of experts in specific areas other than its members.
3.3. Procedures
The Ethics Committee should define, document and follow its procedures in writing, which should include:
3.3.1. Determining the composition of the Ethics Committee (names and qualifications of members) and the legislative form by which
Ethics committee established.
3.3.2. Plan meetings, lead them, and notify members.
3.3.3. Conducting initial and continuous review of tests.
3.3.4. Determining the frequency of audits as needed.
3.3.5. In accordance with the applicable legal regulations, the definition of carrying out expedited review and
granting approval / positive opinion on minor changes to ongoing testing already received previously
approval / positive opinion from the Ethics Committee.
3.3.6. Note that no interviewee may be included in the examination before it is taken
approved by the Ethics Committee.
3.3.7. Note that no deviation from the Test Protocol or its amendment without
the prior written approval / positive opinion of the Ethics Committee, except when promptly removed
imminent danger to the respondent, that is, when the amendments relate exclusively to logistical or
administrative aspects of testing (eg change of monitor telephone number) (see 4.5.2).
3.3.8. Note that the researcher is obliged to immediately inform the Ethics Committee of:
a) deviations or amendments to the Test Protocol in order to remove the immediate one
hazards per respondent (see 3.3.7., 4.5.2., 4.5.4.);
b) amendments that increase the risk to the respondent and / or significantly affect the implementation
tests (see 4.10.2.);
c) any serious and unexpected adverse reactions;
d) new knowledge that may adversely affect the safety of the interviewee or the conduct of the examination.
3.3.9. Ensures that the Ethics Committee promptly, in writing, notifies the researcher / institution of:
a) their decisions / opinions regarding the examination;
b) the reasons for such a decision / opinion;
c) the procedures for appealing the decision / opinion.
3.4. Documentation
The Ethics Committee should keep all relevant documentation (eg written procedures, a list of members with their members)
occupations, documents received, meeting minutes and correspondence) from
at least three years after completion of the tests and to make them available at the request of the competent authorities.
Researchers, sponsors or authorities may request the Ethics Committee to submit their procedures and list
members.
4. RESEARCHER
4.1. Researcher qualifications
4.1.1. In order to take on the duties of conducting the examination properly, the researcher should be qualified
in terms of education, training and experience, the qualifications should meet current legal requirements
regulations and should provide evidence of their qualifications through an updated CV and / or other relevant
the documentation requested by the sponsor, the Ethics Committee and / or the competent authorities.
4.1.2. The researcher must be familiar with the proper application of the product under test as described in
Protocol, Brochure
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for the researcher, product information, and other sources of information provided by the sponsor.
4.1.3. The researcher must be familiar with and adhere to Good Clinical Practice and applicable law.
4.1.4. The researcher / institution should allow the sponsor to monitor and leave, as well as inspection by the competent
bodies.
4.1.5. The researcher should draw up a list of appropriately qualified persons to whom he or she has been assigned
significant testing obligations.
4.2. Appropriate options
4.2.1. The researcher should document (eg retrospective data) the potential for recruitment
the required number of appropriate respondents in the agreed period.
4.2.2. The researcher should have sufficient time to properly conduct and complete the examination within the agreed time
deadline.
4.2.3. For the test to be conducted properly and safely, the researcher should have a sufficient number
qualified personnel and appropriate facilities and equipment requirements.
4.2.4. The researcher must ensure that the personnel involved in the examination are properly informed of
The protocol, the product being tested and its obligations and functions related to the testing.
4.3. Medical care of respondents
4.3.1. Qualified Doctor of Medicine, or if necessary Doctor of Dentistry, who
the researcher or investigator in the clinical trial should be responsible for bringing all medical
testing decisions.
4.3.2. During and after the participation of the respondents in the examination, the researcher / institution should ensure that it is appropriate
medical care to respondents in the event of any adverse event related to the trial,
including clinically relevant laboratory findings. Does the researcher / institution find that
the respondent, meanwhile, was ill with some illness, should be informed of the need for his treatment.
4.3.3. It is recommended that the researcher inform the respondent's family doctor of his
participation in the examination, if the respondent has it and agrees.
4.3.4. Although the respondent is not required to explain the reasons for his or her early withdrawal from the examination, the investigator does
reasonable efforts should be made to determine the reasons, with full respect for the rights of the respondents.
4.4. Communication with the Ethics Committee
4.4.1. Prior to the start of the test, the researcher / institution should have written and dated approval / positive
opinion of the Ethics Committee on the Testing Protocol, the written consent form and its amendments, the procedure for
the recruitment of respondents (eg through advertisements) and any other written information intended for the respondents.
4.4.2. An integral part of the written request submitted by the researcher / institution to Ethics
the board is also the current version of the Researcher Brochure. If there is an amendment to the Brochure for
researchers during the examination, the researcher / institution is obliged to submit to the Ethics Committee
updated Brochures.
4.4.3. During the examination, the researcher / institution shall submit to the Ethics Committee all documents that are
subject to change.
4.5. Protocol Compliance
4.5.1. The investigator / institution should carry out the test in accordance with the Test Protocol
approved by sponsors, competent authorities and the Ethics Committee. For confirmation
Under the agreement, the researcher / institution and sponsor sign a Protocol or other agreement.
4.5.2. The researcher does not need to deviate from the Protocol, that is, to amend it without agreeing with the sponsor,
as well as without the prior written approval / positive opinion of the Ethics Committee, except when necessary to prevent
imminent danger to the respondents, or when the changes relate exclusively to logistical or
administrative aspects of testing (eg changing the phone number of the monitor).
4.5.3. The researcher or the person designated by the researcher should document and explain any deviation from
of the approved Protocol.
4.5.4. The researcher may deviate from the Protocol or change it without prior approval / positive
opinions of the Ethics Committee solely to eliminate imminent danger to respondents. Deviations from
The Protocol, that is, its amendments, the reasons for their introduction and the proposed amendments
The protocol should be delivered as soon as possible:
a) Ethics Committee for evaluation and approval / positive opinion,
b) the sponsor for consent,
c) the competent authorities.
4.6. Tested product
4.6.1. The researcher / institution is responsible for recording the inputs and outputs of the test product at the center
testing.
4.6.2. When permitted, or necessary, the researcher / institution needs all or part of it
the obligation to record the inputs and outputs of the test product at the test center is transferred to
pharmacist or other appropriate person under the supervision of the researcher / institution.
4.6.3. Researcher / institution and / or pharmacist or other appropriate person appointed by
the researcher / institution should properly record the delivery of the product and its condition at the test center, list
use for each respondent, and returning it to the sponsor or otherwise removing the unused product.
Records should include dates, quantities, serial numbers, shelf life (where appropriate) and
a unique identification code linking the product being tested and the respondent. The researcher needs to be neat
record whether the subjects received the doses indicated in the Test Protocol and agree on all the quantities tested
product obtained from the sponsor.
4.6.4. The test product should be stored in accordance with the sponsor's instructions (see 5.13.2. I
5.14.3.) And applicable legal regulations.
4.6.5. The researcher should ensure that the test product is used only in accordance with the approved one
Test protocol.
4.6.6. The researcher / person appointed by the researcher / institution should explain the correct one
the application of the test product to each respondent and that from time to time, in periods appropriate to the individual
clinical trial, checks that each subject adheres to the instructions given.
4.7. Randomization and decryption procedures
The researcher should adhere to the random selection procedures (if provided for testing) and should
ensure that decryption takes place solely in accordance with the Protocol. If the test is blind,
the researcher should promptly provide the sponsor with documentation and reasons for any early disclosure of the code that
connects the respondent and the product under investigation (eg accidentally or due to a serious adverse event).
4.8. Consent of respondents
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Monday, March 12, 2012
4.8.1. In the process of obtaining and recording the consent of the respondents, the researcher should adhere to the valid ones
legislation, good clinical practice and ethical principles stemming from the Declaration of Helsinki. Before you begin
examinations, the researcher should have the written approval / positive opinion of the Ethics Committee on the written form
consent to other written notices intended for the respondents.
4.8.2. The written consent form of the respondents and all other written information intended for the respondents should be provided
amendments after each new information that might affect the consent of the respondents. Before application,
Amended respondent consent form and other written notice intended
respondents should be approved / approved by the Ethics Committee. Respondent respectively his / her legal
the deputy should be informed in good time of any new information that may influence the decision
respondents to continue participation in the examination. Information on this shall be kept in writing.
4.8.3. Neither the researcher nor the staff participating in the test shall coerce or inappropriately influence
respondents to participate in, or continue to participate in, the examination.
4.8.4. None of the oral and written examination-related information, including consent form
respondents should not be written in a language that would deprive the respondent or his legal representative
any legal right, or by which the researcher, institution, sponsor or his representative would be exonerated
liability for negligence.
4.8.5. The researcher or the person designated by the researcher should inform the respondent, that is, his / her legal
if the respondent is not competent to give consent, on all aspects of the examination, including written notices
for which approval / positive opinion of the Ethics Committee has been obtained.
4.8.6. Language used in oral and written examination notices, including
the respondent's consent form should not contain expert terminology but should be understandable to the respondent
that is, his legal representative and impartial witness.
4.8.7. Before obtaining consent, the researcher or the person appointed by the researcher should provide
respondent or his / her legal representative sufficient time and opportunity to find out details about
examination to decide whether or not to participate in it. All questions related to the examination should
to answer until the respondent or his legal representative is satisfied with them.
4.8.8. The written consent form must be signed and dated before the interviewee is included in the examination
by the respondent or his legal representative, also signed by the person who
interviewed the respondent / legal representative.
4.8.9. If the respondent or his legal representative cannot read, there must be throughout the interview
an impartial witness present. After the respondent or his legal representative is read
a written consent form and other written notice intended for the respondents, and after the respondent
or his legal representative orally consent to the respondent's participation in the examination, the respondent personally
sign and date a written consent form, if capable, and also an impartial witness.
By signing the written consent form, the witness confirms that the information on the form and other information is correct
explained to the respondent or his legal representative that they were clear and that according to his
assessment, the respondent or his legal representative understood and voluntarily gave his or her consent.
4.8.10. Consent interview, consent form and other written notices intended
respondents should include the following explanations:
a) the clinical trial is of a research nature;
b) the objective of the examination;
c) the therapy being tested and the possibility of accidental inclusion in one of the treatment groups;
d) the procedures provided for in the test, including invasive procedures;
e) Respondents' duties;
f) experimental aspects of testing;
g) the foreseeable risks and inconveniences for the respondent, ie embryo, fetus or infant;
h) benefits that can be expected. When no clinical benefit is expected for the respondent,
he must be warned;
i) alternative therapeutic procedures and / or treatment options available to the respondent at
the availability and their potential risks and benefits;
j) compensation and / or treatment provided to the respondent in case of injury caused by the examination;
k) the estimated schedule of payment of installments of any compensation to the respondents for participation in the examination;
l) any other costs foreseen for the respondent to participate in the examination;
m) that the respondent's participation in the examination is voluntary and that the respondent may leave at any time
that is, to interrupt the examination without suffering any consequences of its decision;
n) that the monitor, the auditor, the Ethics Committee and the competent authorities will have direct access to the original healthcare
the data of the subjects for the purpose of verifying the procedures, ie obtained data in the clinical trial, with full protection
secrecy of the respondent's identity within the limits of the applicable laws and regulations, as well as that of the respondent or his
the legal representative permits such access to the data by signing informed consent;
o) that the personal data of the respondents will be confidential and that, within the limits of the applicable laws and / or
regulations, will not be available to the public. If the test results are published, the identities of the respondents will remain
in secret;
p) that the respondent or his legal representative will be informed in a timely manner of new ones
insights that could influence the respondent's decision to continue participating in the examination;
r) contact person information for questioning information and interviewee rights as well as o
contacting the person for possible injury arising from participation in the examination;
s) the foreseeable circumstances and / or reasons why the respondent participates in the examination
can end;
t) the expected duration of the respondent's participation in the examination;
u) the indicative number of respondents envisaged for the examination.
4.8.11. The respondent or his / her legal representative should receive a copy before entering the examination
signed and dated written consent form as well as other written notice intended
to the respondents. While participating in the examination, the respondent or his legal representative should
receive signed and dated copies of the updated consent form as well as copies of changes and
supplement to information intended for respondents.
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4.8.12. When a clinical trial (whether therapeutic action is expected or not) involves subjects for
whose participation requires the consent of a legal representative (eg minors or patients with severe
dementia), such respondents should be introduced to the examination in accordance with their ability to understand and from those
who are able to obtain a signed and dated written consent form.
4.8.13. In addition to the one described under 4.8.14, non-therapeutic testing (ie a non-
expects a direct clinical benefit for the respondent) should be conducted on subjects who give their personal consent and
who sign and date the consent form.
4.8.14. Non-therapeutic testing may also be conducted on subjects with assured consent
their legal representatives, if the following conditions are met:
a) the examination cannot be conducted on subjects who can give their personal consent;
b) the foreseeable risks for the respondents are small;
c) the negative impact on the well-being of the respondents is minimal and low;
d) the examination is not prohibited by law;
e) The approval / positive opinion of the Ethics Committee on inclusion has been explicitly sought and obtained
of these respondents.
With justifiable exceptions, these tests should be performed in patients whose disease or
condition is the test product intended. Respondents should be closely monitored and excluded from testing,
unless there is doubt about the discomfort caused by the examination.
4.8.15. In urgent cases where it is not possible to obtain the prior consent of the respondents, it should
ask the respondent's legal representative. When it is not possible to obtain the prior consent of the respondents, a
his legal representative is not available, the inclusion of respondents requires the measures described in the Protocol, in addition
the approval of the Ethics Committee, in order to protect the rights, safety and welfare of the respondents and with respect
applicable legislation. The respondent or his legal representative needs as soon as possible
to notify the examination and request their consent to continue the examination or others
appropriate consent (see 4.8.10.)
4.9 Record keeping and reporting
4.9.1. The researcher should ensure that the data reported is accurate, complete, legible and up-to-date
to the sponsor in the test lists and other required reports.
4.9.2. The information given in the test lists of the respondents taken from the original documentation should be
according to the original documentation, and any differences should be explained.
4.9.3. Any changes or corrections to the test list should be dated, initialed and (where necessary)
explained and the original information should not be deleted or overlaid (ie, the traceability of the changes should be enabled)
and correction). This also applies to changes and corrections in written and electronic documents (see
5.18.4.). The sponsor is required to provide guidance to the researcher and / or his designated associates for
making these updates. The sponsor should have written procedures to ensure that the changes or
test list corrections made by the named sponsor agent be
documented, initialed and supported by the researcher. The researcher should keep a record of all changes and
correction.
4.9.4. The investigator / institution should keep the examination documentation as specified in the Basic Documents section
for conducting a clinical trial (see 8.), as well as with applicable legal regulations.
The researcher / institution should take measures to prevent the accidental or early destruction of these
of documents.
4.9.5. The basic documents should be kept for at least two years after the last approval was obtained
of the marketing request in the "ICH" countries of the region as well as as long as there are unresolved or considered
license applications in the "ICH" countries of the region, or at least two years after the official
cessation of clinical development of the investigational product. These documents should be kept for a longer period of time
period, if required by applicable law, or an agreement with the sponsor. He is a sponsor
obliged to inform the researcher / institution when it is no longer necessary to keep this documentation (see 5.5.12).
4.9.6. The financial aspects of the test should be documented by a contract between the sponsor and the researcher / institution.
4.9.7. At the request of the monitor, the auditor, the Ethics Committee or the competent authorities, the investigator / institution is obliged to make it possible
direct access to all documents related to the examination.
4.10. Test progress reports
4.10.1. The researcher should submit a written summary of the examination status to the Ethics Committee once a year or
more often, at the request of the Ethics Committee.
4.10.2. The researcher should promptly submit a written report to the sponsor, the Ethics Committee (see 3.3.8) and, where
to the healthcare institution, on changes that significantly affect the conduct of the examination and / or
increase the risk for respondents.
4.11. Security reporting
4.11.1. All serious adverse events in the clinical trial should be reported to the sponsor immediately,
except those which are not stated in the Protocol or other document (eg the Researcher's Brochure)
should be reported immediately. A detailed event report should be written immediately after the application. That report
instead of the respondent's name, unique identification number and / or address, the respondent should be identified
predominantly by the original code number assigned to the respondent. The researcher should also adhere to the applicable ones
legal regulations concerning reporting to the competent authorities and the Ethics Committee on unexpected serious
adverse reactions to the drug.
4.11.2. Adverse events and / or unusual laboratory findings identified by the Protocol as critical to
the safety assessment should be reported to the sponsor in accordance with established reporting rules and timed
the period specified by the sponsor in the Protocol.
4.11.3. When reporting a death, the investigator should provide everything to the sponsor and the Ethics Committee
additional information requested (eg autopsy findings and final medical report).
4.12. Premature completion or delay of clinical trial
If for any reason the test is terminated or postponed early, the investigator / institution shall do so
inform the respondents immediately, ensure their proper treatment and follow-up, and inform the competent
bodies in accordance with applicable legal regulations. Besides:
4.12.1. If the researcher interrupts or postpones the examination without the prior consent of the sponsor, he shall be obliged to do so
inform the institution and the investigator / institution should immediately inform the sponsor and the Ethics Committee and
provide them with a detailed written explanation of the interruption or adjournment.
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4.12.2. If the sponsor interrupts or postpones the examination (see 5.21), the investigator should be informed immediately
institution and the researcher / institution should immediately inform the Ethics Committee and provide them in writing
explanation of interruption or delay.
4.12.3. If the Ethics Committee withdraws its approval / positive opinion on the examination
(see 3.1.2 and 3.3.9), the researcher is obliged to inform the institution and the researcher / institution should
immediately notify the sponsor and provide them with a detailed written explanation of the interruption or delay.
4.13. Final report from the researcher
Upon completion of the examination, the investigator should inform the institution that the examination has been completed;
the researcher / institution should submit to the Ethics Committee a summary of the test results and all to the competent authorities
required reports.
5. SPONSOR
5.1. Quality assurance and control
5.1.1. The sponsor is responsible for the implementation and quality assurance and quality control systems through
standard operating procedures, to ensure that conducting a clinical trial, obtaining
data, documentation and reporting are in accordance with the Protocol, Good Clinical Practice and applicable law
regulations.
5.1.2. The sponsor is responsible for contracting with all parties involved to ensure direct access
(see 1.21.) all test centers, original data / documents and
reports, for the purpose of monitoring and referral by the sponsor and domestic or foreign inspection.
5.1.3. Quality control should be carried out at all levels of data handling in order to ensure their quality
reliability and proper processing.
5.1.4. Contracts concluded between sponsors and researchers / institution and other parties
those involved in the clinical trial should be in writing as an integral part of the Protocol or as
special contract.
5.2. Contracting research organization
5.2.1. The sponsor may delegate all of its obligations or functions or part thereof to a contract research agent
organization, but the ultimate responsibility for the quality and integrity of the test results is always borne by the sponsor. Contractual
the research organization should meet the requirements of quality assurance and control.
5.2.2. Any obligation and function in connection with the examination, which is delegated and accepted by the contracting authority
research organizations, should be stated in writing.
5.2.3. Any examination obligation and function not specifically delegated and accepted by
contract research organization, retains sponsor.
5.2.4. Anything in these guidelines that applies to the sponsor applies to the contracting research organization in that sponsor
the extent to which the contracting research organization has assumed obligations and functions from the sponsor in relation to
by conducting a clinical trial.
5.3. Professional doctoral opinion
Medical professionals with appropriate qualifications should be identified, which will always be easy
available, to clarify medical issues and resolve test issues. If necessary,
the sponsor may also appoint external consultants for this purpose.
5.4. Test plan
5.4.1. The sponsor should, as appropriate, hire qualified persons (eg biostatistical, clinical)
pharmacologists and doctors) at all stages of testing, from the development of the Protocol and the test
list, through analysis planning, to analyzing and preparing interim and final clinical reports
testing.
5.4.2. Explanations regarding the Protocol and amendments to the Protocol are provided in Chapter 6, "ICH"
Guidelines for the structure and content of clinical trial reports and other "ICH" guidelines
related to test planning, protocol development and testing.
5.5. Test management, data handling and record keeping
5.5.1. The sponsor should appoint appropriately qualified staff to oversee the whole
conducting tests, for handling data, for validating data, for conducting statistical analysis
and preparing test reports.
5.5.2. The sponsor may set up independent monitoring committees to periodically evaluate progress
clinical trial, including safety data and critical conclusions on drug efficacy, and for recommendation
to the sponsor whether to continue, modify, or terminate the examination. An independent commission should have written documents
standard operating procedures and to keep written records of all its meetings.
5.5.3. When the test uses electronic data management, that is, a remote electronic system, the sponsor
should:
a) ensure and document the compliance of the electronic data processing system with the requirements
sponsors for completeness, accuracy, reliability and consistency of processing, ie. validation;
b) maintain standard operating procedures for the use of these systems;
c) Provide a system that enables the data to be modified in such a way that each change is recorded and
that there is no possibility of deleting the entered data (ie maintaining the transparency of the test data);
d) provide a security system that prevents unauthorized access to data;
e) maintain a list of persons authorized to change the information (see 4.1.5 and 4.9.3);
f) maintain adequate data protection;
g) Preserve masking, if any (eg when entering and processing data).
5.5.4. If data is transformed during its processing, it should always be left behind
ability to compare original data with transformed data.
5.5.5. Sponsor should use unambiguous code to identify respondents (see 1.58.)
which allows identification of all reported data for each respondent.
5.5.6. The sponsor or other data owners should keep all their basic documents concerning the sponsor in the
related to the trial (see 8. Basic documents for conducting the clinical trial).
5.5.7. These documents should be kept by the sponsor in accordance with the applicable laws of the countries in which they are located
a product approved for placing on the market and / or in the countries where it intends to apply for it
approval.
5.5.8. If the sponsor interrupts the clinical development of the product under study (ie for some or all indications, the route of administration
or dosage form) should retain all of its basic documents for at least two years from its formal termination
tests or in accordance with applicable legal regulations.
5.5.9. If the sponsor interrupts the clinical development of the product under investigation, everyone should be informed
researchers / institutions and all competent authorities.
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5.5.10. Any transfer of ownership of the data should be reported to the appropriate authorities, in accordance with the applicable ones
legal regulations.
5.5.11. The sponsor should keep the basic documents for at least two years after the last approval
of the request for placing the drug on the market in the "ICH" countries of the region, that is, as long as there is a request that
countries, or at least two years after the official discontinuation of testing. These documents
should be kept for a longer period if required by applicable law or
sponsor needs.
5.5.12. The sponsor should inform the researcher / institution in writing of the need for further safekeeping
data relating to the examination as well as the termination of the need to store them.
5.6. Choice of researcher
5.6.1. The sponsor is responsible for selecting the researcher / institution. To properly conduct the tests for which it is
selected, each researcher should be qualified with his or her knowledge and experience and should have appropriate
opportunities (see 4.1, 4.2). The sponsor is responsible for forming a coordination committee
examinations and / or the selection of coordinator-researchers required to organize multicenter trials.
5.6.2. Before concluding a test contract with the investigator / institution, the sponsor should
provide the researcher / institution with the Protocol, an updated Researcher's Brochure and should be given sufficient time to
study the Protocol and the documentation provided.
5.6.3. The sponsor should contract with the research-
what / institution that:
a) conduct the examination in accordance with Good Clinical Practice, applicable legal requirements
(see 4.1.3) and the Examination Protocol approved by the sponsor and the Ethics Committee (see 4.5.1);
b) comply with all data retention and reporting procedures;
c) facilitate monitoring, auditing and inspection (see 4.1.4);
d) keep all the basic documents relating to the examination until the sponsor is notified that they are no longer
there is a need to store them (see 4.9.4 and 5.5.12).
In agreement, the researcher / institution and sponsor sign a Protocol or alternative document.
5.7. Division of competencies
Prior to the start of the examination, the sponsor should define, determine and share all obligations and duties related to
examination.
5.8. Compensation to respondents and researchers
5.8.1. The sponsor should secure the researcher / institution (legal and material) from lawsuits arising from
examinations, ie to provide redress, except in the case of a malpractice lawsuit and / or negligence.
5.8.2. The sponsor, in its provisions and procedures, should determine the amount of treatment costs of the subjects in
in the case of injuries arising from his participation in the examination in accordance with the applicable legal provisions.
5.8.3. The procedure and manner of providing compensation to the respondent should be in accordance with the applicable legal regulations.
5.9. Financing
The financial aspects of the test should be documented by a contract between the sponsor and the researcher / institution.
5.10. Notification / submission of requests to competent authorities
Prior to the commencement of the clinical trial, the sponsor (or sponsor and investigator, if applicable)
regulations) should submit to the appropriate authorities the necessary requirements to begin testing on
assessment, acceptance and / or approval (in accordance with applicable legal regulations). Every application / request should
be dated and contain sufficient information to identify the Protocol.
5.11. Ethics Committee Decision
5.11.1. The sponsor from the researcher / institution should receive:
a) the name and address of the Ethics Committee of the institution;
b) a statement by the Ethics Committee that its composition and operation are in accordance with Good Clinical Practice and applicable laws; and
regulations;
c) a documented approval / positive opinion of the Ethics Committee and, if requested by the sponsor, a copy
current Protocol, respondent's written consent form, and any other written notice
intended for the respondents, their recruitment process, as well as documentation relating to compensation
respondents and other documents requested by the Ethics Committee.
5.11.2. If the Ethics Committee requires its approval / positive opinion to modify any aspect of the examination
such as amendments to the Protocol, respondent's written consent form, other written notices and / or
other procedures intended for respondents, the sponsor must receive a copy from the researcher / institution
amendments documents and date of approval / positive opinion of the Ethics Committee.
5.11.3. The sponsor should receive documentation and re-approval dates from the researcher / institution, respectively
reassessments with a positive decision of the Ethics Committee as well as withdrawal or delay of approval / positive
opinions.
5.12. Tested product data
5.12.1. When planning the test, the sponsor should provide sufficient safety information and
drug efficacy from preclinical and / or clinical trials that justify human exposure
the route of administration, the dosage, the length of the test and the appropriate population planned for the test.
5.12.2. When significant new information is available, the sponsor should update the Researcher Brochure (see
7.)
5.13. Production, packaging and labeling and coding of the product under test
5.13.1. The sponsor should ensure that the product under study (including, if necessary, a comparative drug)
and placebo) characterized according to the stage of its development, to have been produced in accordance with the Good
manufacturer's practice, and that it is encrypted and marked in a way that protects the blind process, if any. Besides,
labeling should be in accordance with applicable legal regulations.
5.13.2. The sponsor should indicate appropriate storage conditions for the drug such as temperature, protection against influences
light, storage time, drug reconstitution procedures and infusion agents as appropriate
planned. The sponsor should inform all parties involved (i.e. monitors, researchers,
pharmacists, warehouse managers).
5.13.3. The packaging of the test product should be such as to prevent its contamination and
unacceptable degree of damage during transport and storage.
5.13.4. In blind tests, the encryption system of the product under test should also contain
a mechanism that allows rapid identification of the drug in an emergency but which prevents it from becoming blind
interrupts unnoticed.
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5.13.5. If significant changes are made to the formulation of the test or comparative product during
clinical development, results of any additional formulated drug study (e.g., stability, degree of availability,
bioavailability) should be available before using the new formulation in a clinical trial to evaluate that
whether such changes would significantly alter the pharmacokinetic profile of the product.
5.14. Delivering and handling the tested product
5.14.1. The sponsor is responsible for delivering the test product to the researcher / institution.
5.14.2. The sponsor does not need to provide the investigator / institution with the product under test until he has all the necessary information
documentation (eg approval / positive opinion of the Ethics Committee and competent authorities).
5.14.3. The sponsor should ensure that the written procedures contain the instructions that the investigator / institution needs
Observe during testing, handling and storage of the product under test and related documentation. These
instructions should include proper and secure admission, handling, storage and dispensing of the subject
product, downloading unused test product from respondent and returning it to the sponsor (ie
another way to remove unused product if approved by the sponsor, in accordance with applicable law
regulations).
5.14.4. The sponsor should:
a) ensure timely delivery of the test product to the researcher;
b) keep records of the transport, receipt, disposal, return and destruction of the product under test (see
8. Basic documents for conducting the clinical trial);
c) provide for a system of return for the product under examination and for recording such a download (e.g.
for recall of defective products, returns upon completion of tests, refunds after expiration
duration);
d) maintains a system for withdrawing unused test product and recording it
withdrawals.
5.14.5. The sponsor should:
a) take the necessary measures to ensure the stability of the product under test during the period of use;
b) have sufficient quantities of the product under test for subsequent confirmation
its specifications, if necessary, and keeps the documentation of the analysis and
characteristics of the production batch sample. To the extent permitted by the stability of the drug, samples should be kept at or up to
completing the analysis of the test results or by the deadline prescribed by applicable law, if required
and a longer storage period.
5.15. Access to documentation
5.15.1. The sponsor should ensure that the Protocol or other written agreement states that
the researcher / institution must allow direct access to the original data / documents
for monitoring, audit, review by the Ethics Committee and inspection by the competent authorities.
5.15.2. The sponsor should determine that each respondent has given his / her written consent for direct access to his / her own
original health data for monitoring, audit, review by the Ethics Committee and inspection by
by the competent authorities.
5.16. Security information
5.16.1. The sponsor is responsible for the ongoing assessment of the safety of the product being tested.
5.16.2. The sponsor should promptly inform all researchers / institutions and competent authorities of
knowledge that may adversely affect the safety of the respondent, the conduct of the examination, or the modification
approval / positive opinion of the Ethics Committee.
5.17. Reporting adverse drug reactions
5.17.1. The sponsor should promptly inform all researchers / institutions, Ethics Committees (where applicable)
necessary) and the competent authorities of any serious and unexpected adverse reactions to the drug.
5.17.2. These emergency reports should comply with applicable laws and "ICH"
Clinical Safety Information Management Guidelines: Definitions and Standards for Urgent Reporting.
5.17.3. The sponsor should submit to the competent authorities all updated and periodic safety reports,
in accordance with applicable law.
5.18. Monitoring
5.18.1. Purpose
The purpose of monitoring the test is to confirm:
a) that the protection of the rights and welfare of the respondents is ensured;
b) the accuracy and completeness of the test data and compliance with the original documents;
c) the examination is carried out in accordance with the valid approved Protocol and its amendments
and amendments, with Good Clinical Practice and applicable legislation.
5.18.2. Monitor selection and qualifications
a) The sponsor should provide a monitor,
b) The monitor should have the appropriate qualifications and scientific and / or clinical knowledge to perform
appropriate monitoring of testing. Monitor qualifications should be documented,
c) The monitor should be fully familiar with the product being tested, the Protocol, the written form
consent and other written notices intended for respondents, with standard
operational procedures and applicable legal regulations.
5.18.3. Scope and nature of monitoring
The sponsor should ensure proper monitoring of the trials as well as determine the appropriate one
the extent and nature of monitoring. The determination of the extent and nature of monitoring should be based on facts such as
what are the objective, purpose, plan, complexity, blindness, size and conclusions of the examination. It is necessary that
the monitoring center shall be monitored before, during and after the end of the test. However, in the exceptional
In circumstances, the sponsor may designate central monitoring for procedures such as the training of researchers and experts
meetings, while detailed written instructions can ensure that the tests are conducted appropriately in accordance with
Good clinical practice. Statistically controlled sampling may be an acceptable method of data selection
to check.
5.18.4. Duties of the monitor
In accordance with the requirements of the sponsor, the monitor should ensure that the test is properly conducted and documented in
the testing center, carrying out the following test-related activities or the testing center:
a) acts as the main line of communication between sponsors and researchers;
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b) confirm that the researcher has the appropriate qualifications and capabilities (see 4.1, 4.2;
5.6.), Which remain appropriate during the test and are appropriate for the premises, laboratories, equipment and personnel
requirements for the safe and proper conduct of the test during the test period;
c) certify for the product under test:
- that storage times and conditions are acceptable and that there is sufficient quantity to carry out
testing;
- the test product is given exclusively to test subjects and doses are administered
as defined in the Protocol;
- that the respondents were given appropriate instructions for proper administration, handling, storage and return
test product;
- that the download, use and return of the test product at the test site is controlled and
appropriately document;
- that the disposal of the unused test product at the test center is in accordance with
applicable laws and regulations of the sponsor;
d) Confirm that the researcher has complied with the approved Protocol and any approved amendments;
e) confirm that the written consent of the respondent was obtained before the respondent was included in the examination;
f) confirm that the researcher has received a valid Brochure for the researcher, all documentation as well as
other necessary for the proper conduct of the examination, in accordance with the applicable legal regulations;
g) ensure that the investigator and the research team are well informed of the examination;
h) confirm that the investigator and the research team carry out the specified testing functions in accordance with the Protocol
and other written agreement between the sponsor and the researcher / institution and that these functions
have not been transferred to unauthorized persons;
i) confirms that the researcher in the examination includes only those respondents who meet the criteria for
participation;
j) report on the degree of recruitment of respondents;
k) certify that the original documents and other test documentation are correct, complete,
and up to date;
l) Confirm that the researcher submits all necessary reports, notices and requests;
the accuracy, completeness, timeliness, legibility and date of this documentation, as well as their identification
testing;
m) checks the accuracy and completeness of completing the test sheets, original documentation and other records
regarding the examination. The monitor must confirm in particular that:
- the data in the test lists required by the Protocol are accurately recorded and in accordance with the data from
original documents;
- any dose / therapy change is properly documented for each subject;
- register adverse events, concomitant therapy and newly emerged illnesses in test lists in
in accordance with the Protocol;
- Absences of visits of the respondents, non-completed searches and examinations clearly state in the test lists;
- All exclusions and drop-outs of respondents are reported and explained in the test lists;
n) inform the researcher of any errors, omissions or illegibility of the data in the
test lists. The monitor should ensure that appropriate updates are made,
amend, delete, and delineate data (if necessary) and initiate researcher or
member of the research team authorized to make changes to the test list on behalf of the researcher. This authority should be
documented;
o) Determines whether adverse events are properly reported and within the timeframe required by Good Clinical
practice, Protocol, Ethics Committee, sponsor and applicable law;
p) determine the manner in which the basic documentation is kept by the researcher (see 8
conducting a clinical trial);
r) indicates to the researcher deviations from the Protocol, standard operating procedures, Good
clinical practice and applicable law and take appropriate measures to prevent the recurrence of those observed
deviations.
5.18.5. Monitoring procedures
The monitor should follow the sponsor's written standard operating procedures as well as those
procedures specifically established by the sponsor for monitoring the test.
5.18.6. Monitoring report
a) The monitor should submit a written report to the sponsor after each visit to the implementation center
testing or after any other form of communication related to testing,
b) The report should include the date, location, name of the monitor, and the name of the researcher or other person s
by which the monitor communicated,
c) The report should include a summary of what the monitor viewed and a statement
monitors important findings / findings, discrepancies or shortcomings, conclusions, and measures that
have been, or should be, taken and / or the measures recommended for the purpose of insurance
compliance,
d) Review and monitoring of test monitoring reports should be documented by an authorized representative
sponsors.
5.19. Odit
When conducting an audit, which is part of quality assurance, the sponsor should consider the following:
5.19.1. Purpose gone
The purpose of the sponsor's departure, which is independent and separate from routine monitoring and quality control,
should be an assessment of the conduct of testing and adherence to the Protocol, standard operating
procedures, Good Clinical Practices and applicable law.
5.19.2. Choice and qualifications of the auditor
a) The sponsor should appoint persons who are independent of the clinical trial, respectively, to conduct the audit
system.
b) The sponsor should ensure that the auditors are qualified by practice and experience for
conducting odits properly. Auditor qualifications should be documented.
5.19.3. Departure procedures
a) The sponsor should ensure that the clinical trial data and procedures are followed in accordance with
the sponsor's written procedures on what and how it should be monitored, how often and in what form and content
there should be surveillance reports.
b) The sponsor's plan and test procedures should be based on the importance of the test planned for
submission to the competent authorities, number of respondents, type and complexity of examination, level of risk for
respondents and any other perceived problems.
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c) Observer observations and findings should be documented.
d) In order to safeguard the independence and importance of the odit function, competent authorities need not routinely seek it
odita reports. Competent authorities may request access to the individual audit report
cases where there is evidence of a serious deviation from Good Clinical Practice, that is, during the trial
procedure.
e) When provided by applicable law or regulations, the sponsor is required to submit a certificate of completion
oditu.
5.20. Mismatch
5.20.1. In case of non-adherence to the Protocol, standard operating procedures, good clinical practice
and / or applicable legislation by the researcher / institution or member of the sponsor's team, the sponsor should
to take urgent measures to ensure compliance.
5.20.2. If the monitoring and / or departure process establishes a serious and / or permanent deviation from
plan by the researcher / institution, the sponsor should terminate his participation in the
examination. When the participation of the researcher / institution is terminated due to discrepancies, the sponsor shall do so
it must immediately inform the competent authorities.
5.21. Premature completion or delay of clinical trial
If the examination is interrupted or delayed, the sponsor should immediately inform the researcher / institution
and the competent authorities and give reasons for termination or delay. Also, sponsor or researcher / institution, depending on
current legislation, you should immediately notify the Ethics Committee and provide reasons for termination or adjournment.
5.22. Clinical trial reports
Whether the examination is completed or terminated, the sponsor should ensure that a report is prepared and submitted
clinical trial to competent authorities in accordance with applicable legal requirements. The sponsor should also provide
that clinical trial reports form an integral part of the application for marketing authorization
marketed drug, formed according to the "ICH" Guidelines for the Structure and Content of Clinical Trial Reports.
(NOTE: The "ICH" guidelines for the structure and content of clinical trial reports allow for abbreviated
reports in some cases).
5.23. Multicenter trials
For multicenter trials, the sponsor should ensure that:
5.23.1. That all researchers conduct the examination strictly in accordance with the Protocol agreed with
sponsored and approved by the competent authorities and, if requested, for which approval / positive opinion exists
Ethics Committee.
5.23.2. That the test list form allows you to view all the required information in each center
multicenter testing. Those researchers who collect additional data should submit a supplementary test
lists whose form also allows additional information to be recorded.
5.23.3. That the duties of the research coordinator and other researchers have been documented before the start of the examination.
5.23.4. That all researchers were given instructions on adhering to the Protocol, adherence to unique standards for
evaluation of clinical and laboratory results and completion of test lists.
5.23.5. Simplified communication between researchers.
6. CLINICAL TESTING PROTOCOL AND ITS AMENDMENTS AND APPENDICES
The clinical trial protocol should include the sections listed in this chapter. However, data related to
the test center may be indicated on the separate pages of the Protocol or laid down in a separate contract,
and some of the information below may be part of other documentation, such as the Explorer Booklet.
6.1. General information
6.1.1. The name, number and date of the Protocol. Amendments and additions to the Protocol should also be dated and dated.
6.1.2. Name and address of sponsor and monitor (if monitor address differs from sponsor).
6.1.3. Name and address of the person authorized to sign the Protocol and its amendments and additions on behalf of the sponsor.
6.1.4. Name, title, address and telephone number of sponsor medical expert (medical doctor)
or dentist) for examination.
6.1.5. Name and title of researcher responsible for conducting the test and address and telephone number of the test centers.
6.1.6. Name, title, address and telephone number of the qualified medical doctor (or dentist) responsible for
all health decisions related to testing (unless it is a researcher).
6.1.7. Name and address of clinical laboratories and other medical / technical departments and / or
institutions involved in the examination.
6.2. Basic information
6.2.1. Name and description of the product tested.
6.2.2. Summary of clinically relevant findings from preclinical studies and relevant clinical findings
testing.
6.2.3. Summary of known potential risks and benefits to respondents.
6.2.4. Description and explanation of the route of administration, dosage, dosage regimen and length of therapy.
6.2.5. A statement that the trial will be conducted in accordance with the Clinical Trial Protocol, Good Clinical
practice and applicable law.
6.2.6. Description of the respondent population.
6.2.7. References from the literature and data relevant to the test that confirm the rational basis for the test.
6.3. Aims and purpose of the test
A detailed description of the objectives and purpose of the test.
6.4. Test protocol
The scientific integrity of the test and the credibility of the information obtained in the test depend significantly
of the Protocol. The description of the test plan should include:
6.4.1. Detailed description of primary and secondary test objectives.
6.4.2. Description of test type / design (eg double-blind, comparative, placebo-controlled) i
schematic diagram of test plan, procedures and phases.
6.4.3. Description of measures taken to avoid bias, including:
a) randomization,
b) blindness.
6.4.4. Description of therapy, dose and dosage regimen of the test product. This includes a description of the dosage forms,
packaging and labeling of the product under test.
6.4.5. Expected duration of participation of respondents in the examination and description and duration of all examination periods, including
and monitoring period (if provided).
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6.4.6. Description of criteria for termination or termination of examination for individual respondents, parts of the examination
or the entire examination.
6.4.7. Procedures for keeping records of the tested product, including placebo and comparator.
6.4.8. Description of storing randomization codes and procedures for decrypting them.
6.4.9. A description of all data to be entered directly into the test list of respondents (ie without prior written or
electronic record) and data considered original.
6.5. Selection and exclusion of respondents
6.5.1. Criteria for inclusion of respondents.
6.5.2. Criteria for excluding respondents.
6.5.3. Criteria for withdrawal of subjects, that is, termination of test product therapy and procedures
specifying the following:
a) when and how the respondent withdraws from the test / therapy of the test product;
b) the type of data required and the time limit for their collection;
c) whether these respondents change and how;
d) monitoring of subjects who withdraw from testing / therapy with the product under test.
6.6. Respondent therapy
6.6.1. Planned therapy, including names of all products, doses and dosage regimens, route of administration and
therapeutic period, including the follow-up period of the subjects for each product and treatment group tested.
6.6.2. Permitted medication, that is, therapy (including emergency therapy) and one that is not
allowed before or during the examination.
6.6.3. Procedures for monitoring compliance with the test plan by the respondent.
6.7. Evaluation of efficiency
6.7.1. Determination of efficiency parameters.
6.7.2. Methods and timeframe for estimating, recording and analyzing efficiency parameters.
6.8. Security assessment
6.8.1. Determining security parameters.
6.8.2. Methods and time period for estimating, recording and analyzing security parameters.
6.8.3. Procedures for recording and reporting adverse events and associated diseases.
6.8.4. The manner and length of the follow-up period of the respondent after an adverse event.
6.9. Statistical data
6.9.1. A description of the statistical methods that will be applied, including the time for any planned
interanalysis.
6.9.2. Number of planned respondents. In multicenter trials, the planned number should be indicated
respondents for each testing center. Reason for choosing a specific sample size (number
subjects), including the impact on the significance of the trial and its clinical justification.
6.9.3. The degree of significance that will be used.
6.9.4. Criteria for completing the test.
6.9.5. Procedures for explaining gaps, unused or false information.
6.9.6. Procedures for reporting deviations from the original statistical plan (any
deviation from the original statistical plan should be described and explained in the Protocol and / or final
report).
6.9.7. Selection of respondents to be included in the analyzes (eg all randomized, received subjects
drug tested, eligible subjects, evaluable subjects).
6.10. Direct access to original data / documents The sponsor should ensure that it is in the Protocol or another
indicate in the written document that the researcher / institution will allow monitoring and departure, considered by the Ethical
board and inspection by the competent authorities, by allowing access to the original
data / documents.
6.11. Quality assurance and quality control
6.12. Ethical aspects of testing
Description of ethical considerations related to clinical trial.
6.13. Handling data and keeping records
6.14. Financing and insurance
The method of financing and insurance should be indicated only if they are not specified in a separate contract.
6.15. Publication policy
The agreement to publish the test results should be stated only if they are not specified in a separate contract.
6.16. Extras
(Note: Given that the Protocol and clinical trial / study report are very close,
additional information can be found in the "ICH" Guidelines for the structure and content of clinical trial reports.)
7. RESEARCH BROCHURE
7.1. Introduction
The Researcher's Brochure is a collection of clinical and preclinical data on the product under study that is important
for testing it on humans. Its purpose is to provide researchers and other persons involved in
examination of information that facilitates understanding and facilitates adherence to the Clinical Protocol
tests, clarify many protocol items such as dosage, dosage regimen, route of administration, and control procedures
test security. The Researcher's Brochure also provides insights into the clinical processing of subjects throughout
clinical trial. Avoiding product promotion, information should be presented in a concise, simple,
an objective and balanced manner that enables the clinician or researcher to understand fully and independently
making an objective assessment of the propriety of the proposed examination based on the assessment of the relationship
risks and profits. For this reason, in general, the development of a Researcher Brochure should be medically involved
qualified person, but the content may only be approved by medical professionals in the field to which the data relate.
These Guidelines set out only a minimum of the information that should be contained in the Prospectus Booklet and propose it
appearance. The type and extent of information available is expected to depend on the stage of development of the product under study.
If the test product is already on the market and its pharmacological properties are generally known to doctors, it is not
an extensive Researcher Brochure required. If authorized by the competent authorities, appropriate replacement for the Brochure
may be basic information about the product under study and the text of the package leaflet provided that
include valid, comprehensive and detailed information on all aspects of the product under examination that may be relevant
researchers. If a new use of the tested product is authorized (eg new
indication), a Brochure specific to this new application should be prepared. The brochure should be reviewed at least once
annually, and if necessary audited in accordance with the sponsor's written procedures. More frequent controls can be
needed depending on the stage of development and new important information. However, new information can be so important
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that - adhering to Good Clinical Practice - before being included in the revised Brochure, it should be considered with
researchers, the Ethics Committee and / or competent authorities.
It is the sponsor's duty to make available to the researchers an updated Researcher's Brochure, a
the researchers are responsible for submitting the updated Brochure to the Ethics Committee. In case the examination sponsors
researcher, sponsor-researcher should determine if it is possible to obtain the Brochure from the manufacturer. If examined
the product is provided by the sponsor-researcher, then he is required to provide the necessary information to the participating personnel
examination. In cases where it is not practical to produce an official Brochure, the sponsor-researcher should
replacement of the introductory part of the Test Protocol, which contains a minimum of current information described in these guidelines.
7.2. General provisions
The booklet for the researcher should include:
7.2.1. Front page
The front page should include the name of the sponsor, the product tested (i.e., the research number,
chemical name, generic name - INN, registered name if applicable and legally possible) and date of issue
Brochures. The number of the Brochures valid until then, the date and number of the issue being replaced, are also indicated. Example for the cover
see Appendix 1 (see 7.4).
7.2.2. Privacy Statement
The sponsor may include a statement requesting the researcher to consider the Brochure a confidential document
which can only be made available to the research team, the Ethics Committee and the competent authorities.
7.3. Content of Researcher Brochure
The booklet should include the following chapters, documented by available literature data
(references):
7.3.1. Content
An example of the content is given in Appendix 2 (see 7.5).
7.3.2. Summary
A brief summary (preferably no longer than two pages) should be provided, listing the most important ones available
information on physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic,
metabolic traits and available clinical data relevant to a particular phase of clinical development
of the tested product.
7.3.3. Introduction
Briefly state the chemical name of the product under test (generic name - INN and protected name, if
all active ingredients, the pharmacological group to which it belongs and the expected indications for
prophylaxis, treatment and diagnosis. Finally, a general approach to assessment should be defined in the introduction
of the tested product.
7.3.4. Physico-chemical and pharmaceutical properties and formulation of the product
The substances that make up the test product (including chemical and / or structural) should be described
formulas) and a brief overview of the major physical, chemical and pharmaceutical properties.
In order to be able to take appropriate precautionary measures during testing, the formulations,
including excipients and justify their use where clinically relevant. Also, it should be stated
instructions for storing and handling certain pharmaceutical forms.
Any structural similarity to other known preparations should be indicated.
7.3.5. Preclinical trials
Results of all major preclinical studies in pharmacology, toxicology, pharmacokinetics and
metabolism
the test product should be summarized. The summary should include methodology, results and
consideration of the importance of the results for the tested beneficial or potential adverse effects in humans.
- species of experimental animals;
- number and half of animals in each group;
- unit dose (eg mg / kg);
- dose interval;
- method of administration;
- length of application;
- system allocation information;
- the length of the follow-up period after therapy;
- the results, including the following aspects:
- the nature and frequency of pharmacological and toxicological reactions;
- severity and intensity of pharmacological and toxicological reactions;
- the time of their beginning;
- Reversibility of reactions;
- duration of reactions;
- dose-response.
For the sake of clarity, it is preferable that the data be presented in tabular form.
In the sections below, the most important results of the preclinical trials, including those observed, should be considered
effects at administered doses, relevance to human administration, and other aspects to be studied
people. If possible, the results of administering effective and non-toxic doses for the same species should be compared
animals (e.g. consider therapeutic index). The importance of all data in the planning of dosing should be considered
in humans. Whenever possible, the dosage should be based on blood / tissue levels, not mg / kg.
(1) Preclinical pharmacology
A summary of the pharmacological aspects of the product under study and significant metabolic studies should be provided
to animals, where it exists. Such summary should include tests where possible
therapeutic effect of the drug (eg mode of action, receptor binding and specificity) and its
safety (eg special studies of pharmacological effects other than therapeutic).
(2) Pharmacokinetics and metabolism of the test product in animals
The pharmacokinetics, biotransformation and distribution of the test product in all animals should be summarized
who have undergone preclinical research. Resorption should be considered when considering the results
and the local and systemic bioavailability of the test product and its metabolites as well as their own
correlation with pharmacological and toxicological findings from animal species experiments.
(3) Toxicology
The summary should describe the toxic effects from significant studies carried out on different animal species, namely
that it contains the following:
- single dose;
- repeated dose;
- carcinogenicity;
- special tests (eg irritation and sensitization);
- reproductive toxicology;
- genotoxicity (mutagenicity).
7.3.6. Acting in humans
The known effects of the test product in humans, including data, should be specified
about his
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pharmacokinetics, metabolism, pharmacodynamics, dose / effect ratio, safety, efficacy and other
pharmacological actions. Wherever possible, a summary of all completed clinical trials should be provided.
Also, information regarding the use of the test product outside the clinical should be provided
tests, such as post-marketing experience.
(1) Pharmacokinetics and metabolism of the test product in humans
If available, they should be included in the summary of the pharmacokinetics of the test product
the following:
pharmacokinetics (including metabolism and resorption, binding to plasma proteins, distribution
and elimination);
- bioavailability of the test product (absolute and relative, if possible) for different doses
forms;
- Population subgroups (eg by sex, age and impaired organ function);
- interactions (eg drug interactions and the impact of food);
- other pharmacokinetic data (eg clinical trial results
for different population groups).
(2) Safety and efficiency
A summary of the data on safety, pharmacodynamics, efficacy (i
metabolism, if necessary), as well as information on the dose dependence of the effect obtained from earlier studies
tests in humans (healthy volunteers and / or patients). The significance of this data should be considered. Where it is
completed multiple clinical trials, review summaries of safety findings and
efficacy by indication or subgroup can give a clear view of the data. Together
a tabular summary of adverse reactions to the product under study (for all indications tested) can be very significant.
Significant differences in adverse reactions to the indications and subgroups of subjects should be considered.
The booklet for the researcher should describe the possible risks and side effects of the drug on the basis
previous experience with the product tested and related drugs. Warnings and specials should also be mentioned
measures as an integral part of the application of the test product.
(3) Experiences after placing the test product on the market The Brochure should indicate the countries where it is
interrogated
the product has been granted marketing authorization. A summary of all relevant information obtained from
markets (e.g., formulations, dosage, routes of administration, adverse reactions). The Brochure should, too
indicate the countries in which the product tested has not been approved, or is
withdrawn from the market, ie his registration was revoked.
7.3.7. Data Summary and Researcher's Guide
This chapter should include a comprehensive review of preclinical and clinical data and provide a summary
different aspects of the tested product based on data from different sources. This is given to the researcher
the most relevant presentation of the data available and an evaluation of their significance for future clinical
testing.
When available, published reports of related products should be considered. The researcher can
help predict adverse reactions to the product being tested or other problems in the clinical trial.
The aim of this chapter is to provide the researcher with a clear insight into the possible risks and side effects, u
specific tests,
observations and precautions that may be required during the clinical trial. Insights need to be made
be based on available physical, chemical, pharmaceutical, pharmacological, toxicological and
clinical data on the product tested. The researcher should also be given guidelines for identifiable and
overdose treatment and adverse reactions based on previous experience in humans and
pharmacology of the product under study.
7.4. APPENDIX 1:
Example for cover page of Researcher Brochure:
Sponsor:
Product:
Number of tests:
Product name (s): Chemical name, (approved) generic name, protected name (if desired by sponsor):
Brochure Issue Number:
Brochure release date:
Previous brochure number:
Date of issue of previous version of brochure:
7.5. APPENDIX 2:
Example content for Researcher Brochure:
Confidentiality Statement (optional) Signature Scheme (optional) Contents
Abstract Introduction
Physico-chemical and pharmaceutical properties and formulation of the product:
Preclinical trials Preclinical pharmacology
Pharmacokinetics and metabolism of the test product in animals
Toxicology Action in humans
Pharmacokinetics and metabolism of test product in
people
Safety and efficiency
Experiences after placing the test product on the market Summary data and guide for the researcher
References: 1) Publications
2) reports
References, if any, should be agreed at the end of each chapter.
Attachments (if any).
8. BASIC DOCUMENTS FOR CONDUCTING A CLINICAL TEST
8.1. Introduction
Basic documents are those documents which, individually or together, enable the assessment of the conduct of the examination
and the quality of clinical trial data. These documents serve as proof that
researcher, sponsor and monitor adhere to the standards of good clinical practice and all applicable legal regulations.
In addition, basic documents play an important role. Completion of basic documents in a timely manner
with the researcher / institution and the sponsor can significantly contribute to the successful conduct of the test from
by researchers, sponsors, and monitors.
In addition, these documents are the most frequent subject of audits by independent evaluators and the inspection of appropriate ones
of the competent authorities as part of the procedure to confirm the validity of the tests and the quality of the collected
data.
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Below are lists of basic documents. They are divided into three groups according to the test phase in which
are created:
1) before the test begins,
8.2.7. DATED AND DOCUMENTED APPROVAL / POSITIVE OPINION OF ETHICAL
Document that X X examination considered
Ethics Committee and gave its approval / positive
2) during testing,
3) after completion or termination of testing.
The purpose of each document and the place where it should be stored is indicated; with researchers / institutions, sponsors or code
both sides. At the beginning of the test, a master test archive should be established with both the researcher / institution and the code
sponsors.
Closing the research site or completing the clinical trial is only possible when the monitor
review all documentation with both the researcher / institution and the sponsor and confirm that all necessary
keeps the documentation in appropriate places.
All documents referred to in this Regulation shall be subject to inspection by the sponsor or the inspection of appropriate ones
competent authorities.
8.2. Before starting a clinical trial
COMMITTEES ON THE FOLLOWING: Opinion. Identify
version, number and date of each document
- protocol and amendments
- test sheets
- informed consent
- other written notices intended for the respondents
- Respondent engagement ad (if scheduled)
- Respondent's fees (if any):
- other approved documents
At this stage of test planning, the following documents must be prepared, which must be formed beforehand
the official start of the examination.
8.2.8. COMPOSITION OF THE ETHICAL COMMITTEE
Document that board composition is in accordance with Good Clinical Practice
X X (if necessary)
The name of the document
Purpose
Researcher / Institution
Sponsor
8.2.9. LICENSE / APPLICATION Document that the COMPETENT AUTHORITY (where the permit / application was obtained
X
(if
X
(if
8.2.1. BROCHURE FOR RESEARCHERS
Document that X have been submitted to the researcher
relevant scientific information on the product tested
X is required)
8.2.10. BIOGRAPHIES AND / OR
from the competent authority prior to the commencement of the examination, and in accordance with applicable legal regulations
needed)
X
needed)
X
8.2.2. SIGNED
Document that X
X OTHER DOCUMENTS WHICH qualifications and suitability
TEST PROTOCOL WITH AMENDMENTS AND TEST LIST EXAMPLE
8.2.3. INFORMATION TO THE RESPONDENTS
- INFORMED
CONNECTION (including all relevant translations)
- OTHER WRITTEN NOTES
researcher and sponsor agreed on protocols / amendments and test list
Document X
informed consent
Document that X respondent will receive
appropriate written
TESTIMONY OF RESEARCH / SUB-RESEARCH QUALIFICATIONS
8.2.11. NORMAL VALUES / RANGE
X VALUES FOR MEDICAL / LABORATO RIJEKA / TECHNICAL
X PROTOCOL PROCEDURES / TESTS
8.2.12.
researcher to conduct the test
Document normal X X values ​​/ ranges
test values
Document X X
notifications based on
MEDICAL / LABORATO suitability
(if
- ADVERTISEMENT TO INCLUDE
RESPONDENT (if advertising is planned)
8.2.4. FINANCIAL ASPECTS OF TESTING
8.2.5. INSURANCE STATEMENT (where applicable)
8.2.6. SIGNED CONTRACTS BETWEEN TEST PARTNERS, eg:
- researcher / institution and sponsor
- the researcher / institution and the contracting research organization
- sponsors and contract research organizations
- Researchers / Institution and Competent Authorities (where applicable)
which can be independently decided to participate in the examination
Document that respondent involvement is appropriate and without coercion
Document the financial agreement between the researcher / institution and the sponsor
Document that the respondent will be compensated for any injuries resulting from his / her participation in the examination
Document those contracts
X
X X
X X
X X
X (if X is required)
X
X X
RIJEKA / TECHNICAL PROCEDURES / TESTS
- certificates or
- accreditation or
- established quality control and / or external control
- other forms of validation (where appropriate)
8.2.13. SAMPLE OF THE LABEL TO BE TESTED ON THE TESTED PRODUCT
8.2.14. INSTRUCTIONS FOR MANAGING TEST PRODUCTS AND TEST MATERIALS (if not included in the Protocol or
Researcher brochure)
8.2.15. RECORDS OF TRANSPORT OF THE TESTED PRODUCT AND TEST MATERIALS
departments / laboratories to perform the predicted tests and confirm the reliability of the findings
Document compliance with applicable labeling regulations and the appropriateness of respondent instructions
Document the instruction required to properly store, package, distribute, pull and remove the subject
products and test materials
Document the date of shipment, batch number and method of transport of the test product and test material. Lets
monitoring the product series, checking transport conditions and recording inputs and outputs
needed)
X
X X
X X
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8.2.16. CERTIFICATE OF ANALYSIS OF THE TESTED PRODUCT
2/8/17 DECCRIPTION PROCEDURES
Document the identity, purity and strength of the product under investigation Document the identification method
X
X X (po
need and
8.3.5. BIOGRAPHIES OF NEW RESEARCHERS / SUB-RESEARCHERS
8.3.6. NORMAL SUPPLEMENTS
(see 8.2.10.) X X
Document that X X normal values ​​and
BLIND TESTING of the tested product in
emergency, without
on the other hand-
VALUES / VALUES FOR
their ranges are revised during testing
8.2.18. MAIN RANDOMIZATION LIST
blindness detection for other subjects Document the randomization method
stu)
X (if necessary,
MEDICAL / LABORATO (see 8.2.11.) RIJEKA / TECHNICAL PROCEDURES / TESTS
PROVIDED FOR BY THE PROTOCOL
2/8/19 MONITOR REPORT BEFORE STARTING TEST
8.2.20. REPORT
Document that the test site is appropriate (may be combined with 8.2.20.) Document that they are
place)
X
X X
8.3.7. MEDICAL / LABORATES OF ORIGINAL / TECHNICAL PROCEDURES / TESTS
- certificates or
- accreditation or
Document the suitability of tests for the duration of the test (see 8.2.12.)
X (if X is required)
MONITORS AT THE BEGINNING of the test procedure
- established quality control
TESTING
discussed with the researcher and his associates (may be consolidated with 8.2.19.)
and / or external control or
- other validations (where necessary)
8.3.8. DOCUMENTATION ON (See 8.2.15) X X TRANSPORT
8.3. During the examination
In addition to the documents listed above, the following table shows the documents that should be created during the course
clinical trial as evidence that all new data are documented and presented.
TEST PRODUCT AND TEST MATERIAL
8.3.9. NEW SERIES ANALYSIS CERTIFICATES
(see 8.2.16.) X
The name of the document
8.3.1. AMENDMENTS TO THE RESEARCH BROCHURE
Purpose
Document that the researcher is informed in a timely manner of the latest data as soon as it is available
Researcher / Institution X
Sponsor
X
TESTED
PRODUCTS
8.3.10. MONITOR VISIT REPORTS
8.3.11. OTHER COMMUNICATIONS SA
Document visits and X findings of the monitor at the center
conducting tests
Document contracts and X X important discussions related to
8.3.2. ALL CHANGES I
Document changes X
X CENTER OF ADMINISTRATION administration, violation
ADDITIONS:
- Protocols and amendments
- test sheets
- informed consent
- other written notices intended for the respondents
- Ads to include respondents (if planned
of the said documents in the examination
TESTING
- letters / letters
- meeting notes
- telephone conversation notes
3/8/12 SIGNED
the provisions of the Protocol,
conducting tests, reporting adverse events
Document that X
advertising)
8.3.3. DATED AND DOCUMENTED APPROVAL / POSITIVE OPINION OF ETHICAL
Document X changes and / or additions
reviewed and discussed by the Ethics Committee
INFORMED CONSTITUENTS respondent gave his
X consent in accordance with
Good clinical practice and the Protocol before his
COMMITTEES ON THE FOLLOWING: Adopted positively
opinion. Identify the number, version and date of each document
- Protocol modifications and additions
- changes:
- informed consent
- other written notices intended for the respondents
- Respondent engagement ads (if scheduled)
- other approved documents
- test monitoring reports (where applicable)
8.3.4. LICENSE / APPLICATION Document
X (if X
3/8/13 ORIGINAL DOCUMENTS
3/8/14 COMPLETED, SIGNED AND DATED TEST SHEETS
engaging in testing. In addition document the permission for direct access to the data (see 8.2.3.)
Document the existence of the interviewee and prove the integrity of the collected test data, including the original
documents related to examination, treatment and medical history
Document that the researcher or an authorized member of the research team has verified the information in the test list
X
X (copy)
X
(original)
THE COMPETENT AUTHORITY, WHERE REQUIRED, TO:
- amendments to the protocols and other documents
compliance with applicable legislation
needed)
3/8/15 DOCUMENTATION Document everything
ON THE TEST LIST AMENDMENTS, respectively
corrections to the test list after entering the initial data, as well as being signed and dated
X (copy) X (original)
Issue 19 - Page 68 S L U Ž B E N I G L A S N I K B i H
Monday, March 12, 2012
3/8/16 NOTICE OF SERIOUS ADVERSE EVENTS AND
Document X
notification of the researcher to the sponsor of serious
X 8.4. After completion or termination of testing
Upon completion or termination of the test, all documentation referred to in sections 8.2. and 8.3. should be guarded,
as well as
ASSOCIATED REPORTS TO ADVERSE EVENTS i
WHICH THE RESEARCH SUPPLIES TO THE SPONSOR
3/8/17 NOTICE
related reports in accordance with 4.11.
Document
X (if X
the following documents:
Document Title Purpose Researcher / Institution
Sponsor
SPONSOR / RESEARCH notification
needed)
8.4.1. RECORD
Document that X X
ABOUT THE unexpected unexpected unwanted
sponsors / researchers to the competent authorities,
INPUTS AND OUTPUTS OF TESTED
used the test product in accordance with
REACTIONS AND OTHERS
that is, the Ethics Committee
PRODUCTS IN THE CENTER By protocol and final
INFORMATION ON THE SAFETY OF THE MEDICINE SUBMITTED TO AUTHORITIES
3/8/18 NOTICE
of unexpected serious adverse reactions and other safety data in accordance with 5.17. and 4.11.1. i
other safety related information in accordance with 5.16.2.
Document X
TESTING
X
records of inputs and outputs of the test product: how much was delivered to the test site, how much
distributed to respondents, how much returned from respondents, how much returned to the sponsor
SPONSORS RESEARCH for safety information
8.4.2. DOCUMENTATION Document the destruction
X (if X
ABOUT SAFETY
3/8/19 PERIODIC OR ANNUAL REPORTS TO THE ETHICAL COMMITTEE AND AUTHORITIES
3/8/20 RECORD OF SELECTION OF EXAMINERS
8.3.21. RESPONDENT IDENTIFICATION LIST
8.3.22. RECORD
provided by the sponsor to the researcher in accordance with 5.16.2.
Periodic or annual reports to the Ethics Committee in accordance with 4.10. and competent authorities in accordance with 5.17.3.
Document the identity of the subjects selected for screening before the examination begins
Document that the researcher / institution keeps a confidential list of the names of all respondents with the assigned number under which they are
involved in the examination and to enable the researcher / institution to determine the identity of each respondent
Document chronologically
X X (if necessary)
X X (if necessary)
X
X
ON THE DESTRUCTION OF THE TESTED PRODUCT
8.4.3. LIST WITH RESPONDENTS IDENTIFICATION CODES
8.4.4. AUDIT CERTIFICATE (where available)
8.4.5. FINAL MONITOR REPORT ON EXAMINATION COMPLETION
8.4.6. THERAPY GROUPS AND DECISION DOCUMENTATION
unused test products at the test center or sponsored by Enable identification
all respondents who participated in the examination for the purpose of monitoring them. The list should be kept confidential at
the agreed time period
Document that the odit was performed
Document that all testing activities have been completed and that copies of basic documents are kept in appropriate
scriptures
Returns to the sponsor to document any decryption procedures
destroyed at the site of the test) X
X X
X
RESPONDENTS INCLUDED respondents' entry into
8.4.7. FINAL
Document the completion of X
IN TESTING
8.3.23. RECORDING OF INPUTS AND OUTPUTS OF THE TESTED PRODUCT IN THE TEST CENTER
8.3.24. LIST WITH SIGNATURES
examination according to their assigned number
Document the use of the X test product
in accordance with the Protocol
Document the signatures and X initials of all persons
authorized to enter
RESEARCH REPORT TO THE ETHICAL COMMITTEE AND / OR
X TO COMPETENT AUTHORITIES
8.4.8. CLINICAL TESTING FINAL REPORT
X
9. PUBLISHING
testing
Document test results and interpretation
X (if X is required)
8.3.25. RECORD OF THE SAVED
data and / or updates to the test lists
Document location X
storage and identification
These Guidelines shall enter into force on the day of their adoption and shall be published in the Official Gazette of BiH.
X The Chairman
BIOLOGICAL
keeping biological
No. 10-07.2-1174-1 / 12
Of the Expert Council
EXAMINER MATERIAL material in case yes
the analyzes should be repeated
February 27, 2012
Cf. mr. ph. Ivan Prlic, s. r.