WORLD MEDICAL 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, September 1989
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000
Note of Clarification on Paragraph 29 added by the WMA General Assembly,
Washington 2002
A. INTRODUCTION
1. The World Medical Association has developed the Declaration
of Helsinki as a statement of ethical principles 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 ethical standards that
promote respect for all human beings and protect their health and rights. Some
research populations are 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 requirement should be allowed to reduce or eliminate any of
the protections for human subjects set forth in this Declaration.
B. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH
10. It is the duty of the physician in medical research to
protect the life, health, privacy, and dignity of the human subject.
11. Medical research involving human subjects must conform to
generally 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.
12. Appropriate caution must be exercised in the conduct of
research which may affect the environment, and the welfare of animals used for
research must be respected.
13. 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.
14. 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.
15. Medical research involving human 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.
16. Every medical research project involving human subjects
should be preceded by careful assessment of predictable risks 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.
17. Physicians should abstain from engaging in research
projects involving human subjects unless they are confident that the risks
involved have been adequately assessed and can be satisfactorily managed.
Physicians should cease any investigation if the risks are found to outweigh the
potential benefits or if there is conclusive proof of positive and beneficial
results.
18. 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.
19. 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 results of the research.
20. The subjects must be volunteers and informed participants
in the research project.
21. The right of research subjects to safeguard their
integrity must always be respected. Every precaution should be taken to respect
the privacy of the subject, the confidentiality of the 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.
22. In any research on 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.
23. 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.
24. For a research subject who is legally incompetent,
physically or mentally 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.
25. 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.
26. 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 characteristic of the research population. The specific reasons 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 the
individual or a legally authorized surrogate.
27. Both authors and publishers have ethical obligations. 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 publicly 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 principles laid down in this Declaration should not be accepted for
publication.
C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH
MEDICAL CARE
28. 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 protect the patients who are
research subjects.
29. 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. See footnote
30. 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.
31. 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.
32. 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 made 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.
Footnote: Note of clarification on paragraph 29 of the WMA Declaration of
Helsinki
The WMA hereby reaffirms its position that extreme care must be taken in making
use of a placebo-controlled trial and that in general this methodology should
only be used in the absence of existing proven therapy. However, a
placebo-controlled trial may be ethically acceptable, even if proven therapy is
available, under the following circumstances:
- Where for compelling and scientifically sound methodological reasons its use
is necessary to determine the efficacy or safety of a prophylactic, diagnostic
or therapeutic method; or
- Where a prophylactic, diagnostic or therapeutic method is being investigated
for a minor condition and the patients who receive placebo will not be subject
to any additional risk of serious or irreversible harm.
All other provisions of the Declaration of Helsinki must be adhered to,
especially the need for appropriate ethical and scientific review.
The Declaration of Helsinki (Document 17.C) is an official policy document of
the World Medical Association, the global representative body for physicians. It
was first adopted in 1964 (Helsinki, Finland) and revised in 1975 (Tokyo,
Japan), 1983 (Venice, Italy), 1989 (Hong Kong), 1996 (Somerset-West, South
Africa) and 2000 (Edinburgh, Scotland). Note of clarification on Paragraph 29
added by the WMA General Assembly, Washington 2002.
