GUIDELINES FOR GOOD PRACTICE IN THE CONDUCT OF CLINICAL TRIALS IN HUMAN PARTICIPANTS IN SOUTH AFRICA

APPENDIX A

ICH Guideline for Good Clinical Practice

  1. Clinical trials should be conducted in accordance with the ethical principles that have their origin in Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).

  2. Before a trial is initiated, foreseeable risk and inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued if the anticipated benefits justify the risk.

  3. The rights, safety and well being of the trial subjects are the most important considerations and should prevail over interest of science and society.

  4. The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trials.

  5. Clinical trials should be scientifically sound, and described in a clear, detailed protocol.

  6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB) / independent ethics committee (IEC) approval/ favourable opinion.

  7. The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of the qualified physician or, when appropriate, of a qualified dentist.

  8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).

  9. Freely given informed consent should be obtained from every subject prior to clinical trial participant.

  10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.

  11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).

  12. Investigational product should be manufactured, handled, and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.

  13. Systems with procedures that assure the quality of every aspect of the trial should be implemented.

WORLD ASSOCIATION DECLARATION OF HELSINKI
Ethical Principles
For
Medical Research Involving Human Subjects

Adopted by the 18th WMA General Assembly
Helsinki, Finland, June 1964
and amended by the
29th WMA General Assembly, Tokyo, Japan, October 1975
35th WMA General Assembly, Venice, Italy, October 1983
41st WMA General Assembly, Hong Kong, September1989
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
and the
52nd WMA General Assembly, Edinburgh, Scotland, October 2000

  1. INTRODUCTION
  1. The World Medical Association has developed the Declaration of Helsinki as a statement of ethical principle to provide guidance to physicians and other participants in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material or identifiable data.
  2. It is the duty of the physician to promote and safeguard the health of the people. The physician’s knowledge and conscience are dedicated to the fulfillment of this duty.
  3. The Declaration of Geneva of the World Medical Association binds the physician with the words, "The health of my patient will be my first consideration," and the International Code of Medical Ethics declares that, " A physician shall act only in the patient’s interest when providing medical care which might have the effect of weakening the physical and mental condition of the patient."
  4. Medical progress is based on research which ultimately must rest in part on experimentation involving human subjects.
  5. In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society.
  6. The primary purpose of medical research involving human subjects is to improve prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic methods must continuously be challenged through research for their effectiveness, efficiency, accessibility and quality.
  7. In current medical practice and in medical research, most prophylactic, diagnostic and therapeutic procedures involve risks and burdens.
  8. Medical research is subject to ethics standards that promote respect for all human beings and protect their health and rights. Some research population is vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research and for those for whom the research is combined with care.
  9. Research investigators should be aware of the ethical, legal and regulatory requirements for research on human subjects in their own countries as well as applicable international requirements. No national ethical, legal or regulatory requirements should be allowed to reduce or eliminate any of the protections for human subjects set forth in this Declaration.
  1. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH
  1. It is the duty of the physician in medical research to protect the life, health, privacy, and dignity of the human subject.
  2. Medical research involving human subject must conform to general accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.
  3. Appropriate caution must be exercised in the conduct of research which may affect the environment, and the welfare of animal used for research must be respected.
  4. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol. This protocol should be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee, which must be independent of the investigator, the sponsor or any other kind of undue influence. This independent committee should be in conformity with the laws and regulations of the country in which the research experiment is performed. The committee has the right to monitor ongoing trials. The researcher has the obligation to provide monitoring information to the committee, especially any serious adverse events. The researcher should also submit to the committee, for review, information regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and incentives for subjects.
  5. The research protocol should always contain a statement of the ethical considerations involved and should indicate that there is compliance with the principles enunciated in this Declaration.
  6. Medical human research involving subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent.
  7. Every medical research project involving human subject should be preceded by careful assessment of predictable risk and burdens in comparison with foreseeable benefits to the subject or to others. This does not preclude the participation of healthy volunteers in medical research. The design of all studies should be publicly available.
  8. Physicians should abstain from engaging in research project involving human subjects unless they are confident that the risk involved have been adequately assessed and can be satisfactorily managed. Physicians should cease any investigations if the risks are found to outweigh the potential benefits or if there is conclusive proof of positive and beneficial results.
  9. Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and burdens to the subject. This is especially important when the human subjects are healthy volunteers.
  10. Medical research is only justified if there is a reasonable likelihood that the populations in which the research is carried out stand to benefit from the result of the research.
  11. The subjects must be volunteers and informed participants in the research project.
  12. The right of research subjects to safeguard their integrity must be always be respected. Every precaution should be taken to respect the privacy of the subject, the confidentiality of every patient’s information and to minimize the impact of the study on the subject’s physical and mental integrity and on the personality of the subject.
  13. In research of human beings, each potential subject must be adequately informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study and the discomfort it may entail. The subject should be informed of the right to abstain from participation in the study or to withdraw consent to participate at any time without reprisal. After ensuring that the subject has understood the information, the physician should then obtain the subject’s freely-given informed consent, preferably in writing. If the consent cannot be obtained in writing, the non-written consent must be formally documented and witnessed.
  14. When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship with the physician or may consent under duress. In that case the informed consent should be obtained by a well-informed physician who is not engaged in the investigation and who is completely independent of this relationship.
  15. For a research subject who is legally incompetent, physically or mental incapable of giving consent or is a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law. These groups should not be included in research unless the research is necessary to promote the health of the population represented and this research cannot instead be performed on legally competent persons.
  16. When a subject deemed legally incompetent, such as a minor child, is able to give assent to decisions about participation in research, the investigator must obtain that assent in addition to the consent of the legally authorized representative.
  17. Research on individuals from whom it is not possible to obtain consent, including proxy or advance consent, should be done only if the physical/mental condition that prevents obtaining informed consent is a necessary characteristics of the research population. The specific reason for involving research subjects with a condition that renders them unable to give informed consent should be stated in the experimental protocol for consideration and approval of the review committee. The protocol should state that consent to remain in the research should be obtained as soon as possible from individual or a legally authorized surrogate.
  18. Both authors and publishers have ethical obligation. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicity available. Sources of funding, institutional affiliations and any possible conflicts of interest should be declared in the publication. Reports of experimentation not in accordance with the principle laid down in this Declaration should no be acceptable for publication.
  1. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL CARE
  1. The physician may combine medical research with medical care, only to the extent that the research is justified by its potential prophylactic, diagnostic or therapeutic value. When medical research is combined with medical care, additional standards apply to patients who are research subjects.
  2. The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.
  3. At the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study
  4. The physician should fully inform the patient which aspects of the care are related to the research. The refusal of a patient to participate in a study must never interfere with the patient-physician relationship.
  5. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. Where possible, these measures should be the object of research, designed to evaluate their safety and efficacy. In all cases, new information should be recorded and, where appropriate, published. The other relevant guidelines of this Declaration should be followed.

Contents

Appendix B --->