Declaration of Helsinki 2004

1
June 1964 17.C/04
Original: English
THE WORLD MEDICAL ASSOCIATION, INC
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
Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004
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.
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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
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 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.
3. 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.
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 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.
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7. 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.
8. 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.
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 results 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 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.
13. 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.
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 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.
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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 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.
18. 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
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 protect the
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.1
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 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.
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1
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.
2
Note of clarification on paragraph 30 of the WMA Declaration of Helsinki
The WMA hereby reaffirms its position that it is necessary during the study planning process to
identify post-trial access by study participants to prophylactic, diagnostic and therapeutic procedures
identified as beneficial in the study or access to other appropriate care. Post-trial access arrangements
or other care must be described in the study protocol so the ethical review committee may consider
such arrangements during its review.
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