DoH-Oct2013

Handbook of WMA Policies
World Medical Association ⏐ D-1964-01-2013
WMA 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
52nd
WMA General Assembly, Edinburgh, Scotland, October 2000
53rd
WMA General Assembly, Washington DC, USA, October 2002
(Note of Clarification added)
55th
WMA General Assembly, Tokyo, Japan, October 2004
(Note of Clarification added)
59th
WMA General Assembly, Seoul, Republic of Korea, October 2008
64th
WMA General Assembly, Fortaleza, Brazil, October 2013
PREAMBLE
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 para-
graphs should be applied with consideration of all other relevant paragraphs.
2. Consistent with the mandate of the WMA, the Declaration is addressed primarily to
physicians. The WMA encourages others who are involved in medical research in-
volving human subjects to adopt these principles.
GENERAL PRINCIPLES
3. 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.”
4. It is the duty of the physician to promote and safeguard the health, well-being and
rights of patients, including those who are involved in medical research. The physi-
cian’s knowledge and conscience are dedicated to the fulfilment of this duty.
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Handbook of WMA Policies
World Medical Association ⏐ D-1964-01-2013
5. Medical progress is based on research that ultimately must include studies involving
human subjects.
6. 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
proven interventions must be evaluated continually through research for their safety,
effectiveness, efficiency, accessibility and quality.
7. Medical research is subject to ethical standards that promote and ensure respect for all
human subjects and protect their health and rights.
8. While the primary purpose of medical research is to generate new knowledge, this
goal can never take precedence over the rights and interests of individual research
subjects.
9. It is the duty of physicians who are involved in medical research to protect the life,
health, dignity, integrity, right to self-determination, privacy, and confidentiality of
personal information of research subjects. The responsibility for the protection of
research subjects must always rest with the physician or other health care pro-
fessionals and never with the research subjects, even though they have given consent.
10. Physicians must 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.
11. Medical research should be conducted in a manner that minimises possible harm to
the environment.
12. Medical research involving human subjects must be conducted only by individuals
with the appropriate ethics and scientific education, training and qualifications. Re-
search on patients or healthy volunteers requires the supervision of a competent and
appropriately qualified physician or other health care professional.
13. Groups that are underrepresented in medical research should be provided appropriate
access to participation in research.
14. Physicians who combine medical research with medical care should involve their
patients in research only to the extent that this 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.
15. Appropriate compensation and treatment for subjects who are harmed as a result of
participating in research must be ensured.
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D-1964-01-2013 ⏐ Fortaleza
Medical Rsearch involving Human Subjects (Helsinki)
RISKS, BURDENS AND BENEFITS

16. In medical practice and in medical research, most interventions involve risks and
burdens.
Medical research involving human subjects may only be conducted if the importance
of the objective outweighs the risks and burdens to the research subjects.
17. All medical research involving human subjects must be preceded by careful assess-
ment of predictable risks and burdens to the individuals and groups involved in the
research in comparison with foreseeable benefits to them and to other individuals or
groups affected by the condition under investigation.
Measures to minimise the risks must be implemented. The risks must be continuously
monitored, assessed and documented by the researcher.
18. Physicians may not be involved in a research study involving human subjects unless
they are confident that the risks have been adequately assessed and can be satis-
factorily managed.
When the risks are found to outweigh the potential benefits or when there is con-
clusive proof of definitive outcomes, physicians must assess whether to continue,
modify or immediately stop the study.
VULNERABLE GROUPS AND INDIVIDUALS

19. Some groups and individuals are particularly vulnerable and may have an increased
likelihood of being wronged or of incurring additional harm.
All vulnerable groups and individuals should receive specifically considered protec-
tion.
20. Medical research with a vulnerable group is only justified if the research is responsive
to the health needs or priorities of this group and the research cannot be carried out in
a non-vulnerable group. In addition, this group should stand to benefit from the
knowledge, practices or interventions that result from the research.
SCIENTIFIC REQUIREMENTS AND RESEARCH PROTOCOLS
21. 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.
22. The design and performance of each research study involving human subjects must be
clearly described and justified in a research protocol.
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Handbook of WMA Policies
World Medical Association ⏐ D-1964-01-2013
The protocol should contain a statement of the ethical considerations involved and
should indicate how the principles in this Declaration have been addressed. The pro-
tocol should include information regarding funding, sponsors, institutional affilia-
tions, potential conflicts of interest, incentives for subjects and information regarding
provisions for treating and/or compensating subjects who are harmed as a conse-
quence of participation in the research study.
In clinical trials, the protocol must also describe appropriate arrangements for post-
trial provisions.
RESEARCH ETHICS COMMITTEES

23. The research protocol must be submitted for consideration, comment, guidance and
approval to the concerned research ethics committee before the study begins. This
committee must be transparent in its functioning, must be independent of the
researcher, the sponsor and any other undue influence and must be duly qualified. 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, especially information about any
serious adverse events. No amendment to the protocol may be made without con-
sideration and approval by the committee. After the end of the study, the researchers
must submit a final report to the committee containing a summary of the study’s find-
ings and conclusions.
PRIVACY AND CONFIDENTIALITY

24. Every precaution must be taken to protect the privacy of research subjects and the
confidentiality of their personal information.
INFORMED CONSENT

25. Participation by individuals capable of giving informed consent as subjects in medical
research must be voluntary. Although it may be appropriate to consult family mem-
bers or community leaders, no individual capable of giving informed consent may be
enrolled in a research study unless he or she freely agrees.
26. In medical research involving human subjects capable of giving informed consent,
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, post-study provisions 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 with-
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D-1964-01-2013 ⏐ Fortaleza
Medical Rsearch involving Human Subjects (Helsinki)
draw 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.
All medical research subjects should be given the option of being informed about the
general outcome and results of the study.
27. When seeking informed consent for participation in a research study the physician
must 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 must be sought by an appropriately qualified individual who is completely
independent of this relationship.
28. For a potential research subject who is incapable of giving informed consent, the
physician must seek informed consent from the legally authorised 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 group represented
by the potential subject, the research cannot instead be performed with persons
capable of providing informed consent, and the research entails only minimal risk and
minimal burden.
29. When a potential research subject who is deemed incapable of giving informed con-
sent 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 authorised representa-
tive. The potential subject’s dissent should be respected.
30. Research involving subjects who are physically or mentally incapable of giving con-
sent, 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 group. In such circumstances the physician must seek informed consent
from the legally authorised 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
research must be obtained as soon as possible from the subject or a legally authorised
representative.
31. The physician must fully inform the patient which aspects of their 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 adversely affect the patient-physician
relationship.
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Handbook of WMA Policies
World Medical Association ⏐ D-1964-01-2013
32. For medical research using identifiable human material or data, such as research on
material or data contained in biobanks or similar repositories, physicians must seek
informed consent for its collection, storage and/or reuse. There may be exceptional
situations where consent would be impossible or impracticable to obtain for such
research. In such situations the research may be done only after consideration and
approval of a research ethics committee.
USE OF PLACEBO

33. The benefits, risks, burdens and effectiveness of a new intervention must be tested
against those of the best proven intervention(s), except in the following circums-
tances:
Where no proven intervention exists, the use of placebo, or no intervention, is accept-
able; or
Where for compelling and scientifically sound methodological reasons the use of any
intervention less effective than the best proven one, the use of placebo, or no inter-
vention is necessary to determine the efficacy or safety of an intervention
and the patients who receive any intervention less effective than the best proven one,
placebo, or no intervention will not be subject to additional risks of serious or
irreversible harm as a result of not receiving the best proven intervention.
Extreme care must be taken to avoid abuse of this option.
POST-TRIAL PROVISIONS

34. In advance of a clinical trial, sponsors, researchers and host country governments
should make provisions for post-trial access for all participants who still need an
intervention identified as beneficial in the trial. This information must also be dis-
closed to participants during the informed consent process.
RESEARCH REGISTRATION AND PUBLICATION AND DISSEMINATION OF RESULTS
35. Every research study involving human subjects must be registered in a publicly
accessible database before recruitment of the first subject.
36. Researchers, authors, sponsors, editors and publishers all have ethical obligations with
regard to the publication and dissemination of the results of research. Researchers
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. All parties
should adhere to accepted guidelines for ethical reporting. Negative and inconclusive
as well as positive results must be published or otherwise made publicly available.
Sources of funding, institutional affiliations and conflicts of interest must be declared
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D-1964-01-2013 ⏐ Fortaleza
Medical Rsearch involving Human Subjects (Helsinki)
in the publication. Reports of research not in accordance with the principles of this
Declaration should not be accepted for publication.
UNPROVEN INTERVENTIONS IN CLINICAL PRACTICE
37. In the treatment of an individual patient, where proven interventions do not exist or
other known interventions have been ineffective, the physician, after seeking expert
advice, with informed consent from the patient or a legally authorised representative,
may use an unproven intervention if in the physician’s judgement it offers hope of
saving life, re-establishing health or alleviating suffering. This intervention should
subsequently be made the object of research, designed to evaluate its safety and effi-
cacy. In all cases, new information must be recorded and, where appropriate, made
publicly available.
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