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 59th WMA
General Assembly, Seoul, October 2008

A. INTRODUCTION
1. The World Medical Association (WMA) has developed the Declaration of Helsinki
as a statement of ethical principles for medical research involving human
subjects, including research on identifiable human material and data. The
Declaration is intended to be read as a whole and each of its constituent
paragraphs should not be applied without consideration of all other relevant
paragraphs.

2. Although the Declaration is addressed primarily to physicians, the WMA

encourages other participants in medical research involving human subjects to
adopt these principles.

3. It is the duty of the physician to promote and safeguard the health of patients,
including those who are involved in medical research. The physician's
knowledge and conscience are dedicated to the fulfillment of this duty.

4. The Declaration of Geneva of the WMA 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 in
the patient's best interest when providing medical care.”

5. Medical progress is based on research that ultimately must include studies

involving human subjects. Populations that are underrepresented in medical
research should be provided appropriate access to participation in research.
 6. In medical research involving human subjects, the well-being of the individual
research subject must take precedence over all other interests.

7. The primary purpose of medical research involving human subjects is to

understand the causes, development and effects of diseases and improve
preventive, diagnostic and therapeutic interventions (methods, procedures and
treatments). Even the best current interventions must be evaluated continually
through research for their safety, effectiveness, efficiency, accessibility and
quality.

8. In medical practice and in medical research, most interventions involve risks

and burdens.

DoH/Oct2008
9. Medical research is subject to ethical standards that promote respect for all
human subjects and protect their health and rights. Some research populations
are particularly vulnerable and need special protection. These include those
who cannot give or refuse consent for themselves and those who may be
vulnerable to coercion or undue influence.

10. Physicians should consider the ethical, legal and regulatory norms and
standards for research involving human subjects in their own countries as well
as applicable international norms and standards. No national or international
ethical, legal or regulatory requirement should reduce or eliminate any of the
protections for research subjects set forth in this Declaration.

B. PRINCIPLES FOR ALL MEDICAL RESEARCH

11. It is the duty of physicians who participate in medical research to protect the
life, health, dignity, integrity, right to self-determination, privacy, and
confidentiality of personal information of research subjects.

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12. 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 adequate laboratory and,
as appropriate, animal experimentation. The welfare of animals used for
research must be respected.

13. Appropriate caution must be exercised in the conduct of medical research that
may harm the environment.

14. The design and performance of each research study involving human subjects
must be clearly described in a research protocol. The protocol should contain a
statement of the ethical considerations involved and should indicate how the
principles in this Declaration have been addressed. The protocol should include
information regarding funding, sponsors, institutional affiliations, other
potential conflicts of interest, incentives for subjects and provisions for
treating and/or compensating subjects who are harmed as a consequence of
participation in the research study. The protocol should describe arrangements
for post-study access by study subjects to interventions identified as beneficial
in the study or access to other appropriate care or benefits.

15. The research protocol must be submitted for consideration, comment,

guidance and approval to a research ethics committee before the study begins.
This committee must be independent of the researcher, the sponsor and any
other undue influence. It must take into consideration the laws and regulations
of the country or countries in which the research is to be performed as well as
applicable international norms and standards but these must not be allowed to
reduce or eliminate any of the protections for research subjects set forth in
this Declaration. The committee must have the right to monitor ongoing
studies. The researcher must provide monitoring information to the committee,

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 especially information about any serious adverse events. No change to the
protocol may be made without consideration and approval by the committee.
16. Medical research involving human subjects must be conducted only by
individuals with the appropriate scientific training and qualifications. Research
on patients or healthy volunteers requires the supervision of a competent and
appropriately qualified physician or other health care professional. The
responsibility for the protection of research subjects must always rest with the
physician or other health care professional and never the research subjects,
even though they have given consent.

17. Medical research involving a disadvantaged or vulnerable population or

community is only justified if the research is responsive to the health needs
and priorities of this population or community and if there is a reasonable
likelihood that this population or community stands to benefit from the results
of the research.

18. Every medical research study involving human subjects must be preceded by
careful assessment of predictable risks and burdens to the individuals and
communities involved in the research in comparison with foreseeable benefits
to them and to other individuals or communities affected by the condition
under investigation.

19. Every clinical trial must be registered in a publicly accessible database before
recruitment of the first subject.

20. Physicians may not participate in a research study involving human subjects
unless they are confident that the risks involved have been adequately assessed
and can be satisfactorily managed. Physicians must immediately stop a study
when the risks are found to outweigh the potential benefits or when there is
conclusive proof of positive and beneficial results.

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21. Medical research involving human subjects may only be conducted if the
importance of the objective outweighs the inherent risks and burdens to the
research subjects.

22. Participation by competent individuals as subjects in medical research must be

voluntary. Although it may be appropriate to consult family members or
community leaders, no competent individual may be enrolled in a research
study unless he or she freely agrees.

23. Every precaution must be taken to protect the privacy of research subjects and
the confidentiality of their personal information and to minimize the impact of
the study on their physical, mental and social integrity.

24. In medical research involving competent human subjects, 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, and any other relevant aspects of the study. The potential subject
must be informed of the right to refuse to participate in the study or to
withdraw consent to participate at any time without reprisal. Special attention
should be given to the specific information needs of individual potential
subjects as well as to the methods used to deliver the information. After
ensuring that the potential subject has understood the information, the
physician or another appropriately qualified individual must then seek the
potential subject’s freely-given informed consent, preferably in writing. If the
consent cannot be expressed in writing, the non-written consent must be
formally documented and witnessed.

25. For medical research using identifiable human material or data, physicians
must normally seek consent for the collection, analysis, storage and/or reuse.
There may be situations where consent would be impossible or impractical to
obtain for such research or would pose a threat to the validity of the research.

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 In such situations the research may be done only after consideration and
approval of a research ethics committee.

26. When seeking informed consent for participation in a research study the
physician should be particularly cautious if the potential subject is in a
dependent relationship with the physician or may consent under duress. In such
situations the informed consent should be sought by an appropriately qualified
individual who is completely independent of this relationship.

27. For a potential research subject who is incompetent, the physician must seek
informed consent from the legally authorized representative. These individuals
must not be included in a research study that has no likelihood of benefit for
them unless it is intended to promote the health of the population represented
by the potential subject, the research cannot instead be performed with
competent persons, and the research entails only minimal risk and minimal
burden.

28. When a potential research subject who is deemed incompetent is able to give
assent to decisions about participation in research, the physician must seek
that assent in addition to the consent of the legally authorized representative.
The potential subject’s dissent should be respected.

29. Research involving subjects who are physically or mentally incapable of giving
consent, for example, unconscious patients, may be done only if the physical or
mental condition that prevents giving informed consent is a necessary
characteristic of the research population. In such circumstances the physician
should seek informed consent from the legally authorized representative. If no
such representative is available and if the research cannot be delayed, the
study may proceed without informed consent provided that the specific reasons
for involving subjects with a condition that renders them unable to give
informed consent have been stated in the research protocol and the study has
been approved by a research ethics committee. Consent to remain in the

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 research should be obtained as soon as possible from the subject or a legally
authorized representative.

30. Authors, editors and publishers all have ethical obligations with regard to the
publication of the results of research. Authors have a duty to make publicly
available the results of their research on human subjects and are accountable
for the completeness and accuracy of their reports. They should adhere to
accepted guidelines for ethical reporting. Negative and inconclusive as well as
positive results should be published or otherwise made publicly available.
Sources of funding, institutional affiliations and conflicts of interest should be
declared in the publication. Reports of research not in accordance with the
principles of this Declaration should not be accepted for publication.

C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH MEDICAL

CARE:

31. The physician may combine medical research with medical care only to the
extent that the research is justified by its potential preventive, diagnostic or
therapeutic value and if the physician has good reason to believe that
participation in the research study will not adversely affect the health of the
patients who serve as research subjects.

32. The benefits, risks, burdens and effectiveness of a new intervention must be
tested against those of the best current proven intervention, except in the
following circumstances:

 The use of placebo, or no treatment, is acceptable in studies where no

current proven intervention exists; or

 Where for compelling and scientifically sound methodological reasons

the use of placebo is necessary to determine the efficacy or safety of an
intervention and the patients who receive placebo or no treatment will

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 not be subject to any risk of serious or irreversible harm. Extreme care
must be taken to avoid abuse of this option.

33. At the conclusion of the study, patients entered into the study are entitled to
be informed about the outcome of the study and to share any benefits that
result from it, for example, access to interventions identified as beneficial in
the study or to other appropriate care or benefits.

34. The physician must fully inform the patient which aspects of the care are
related to the research. The refusal of a patient to participate in a study or
the patient’s decision to withdraw from the study must never interfere with
the patient-physician relationship.

35. In the treatment of a patient, where proven interventions do not exist or

have been ineffective, the physician, after seeking expert advice, with
informed consent from the patient or a legally authorized representative, may
use an unproven intervention if in the physician's judgment it offers hope of
saving life, re-establishing health or alleviating suffering. Where possible, this
intervention should be made the object of research, designed to evaluate its
safety and efficacy. In all cases, new information should be recorded and,
where appropriate, made publicly available.