WMA Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Participants

Adopted by the 18^th WMA General Assembly, Helsinki, Finland, June 1964
and amended by the:
29^th WMA General Assembly, Tokyo, Japan, October 1975
35^th WMA General Assembly, Venice, Italy, October 1983
41^st WMA General Assembly, Hong Kong, September 1989
48^th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
52^nd WMA General Assembly, Edinburgh, Scotland, October 2000
53^rd WMA General Assembly, Washington DC, USA, October 2002 (Note of Clarification added)
55^th WMA General Assembly, Tokyo, Japan, October 2004 (Note of Clarification added)
59^th WMA General Assembly, Seoul, Republic of Korea, October 2008
64^th WMA General Assembly, Fortaleza, Brazil, October 2013
and by the 75^th WMA General Assembly, Helsinki, Finland, October 2024

PREAMBLE

1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles for medical research involving human participants, including research using identifiable human material or data.

The Declaration is intended to be read as a whole, and each of its constituent paragraphs should be applied with consideration of all other relevant paragraphs.

2. While the Declaration is adopted by physicians, the WMA holds that these principles should be upheld by all individuals, teams, and organizations involved in medical research, as these principles are fundamental to respect for and protection of all research participants, including both patients and healthy volunteers.

GENERAL PRINCIPLES

3. The WMA Declaration of Geneva binds the physician with the words, “The health and well-being of my patient will be my first consideration,” and the WMA International Code of Medical Ethics declares “The physician must commit to the primacy of patient health and well-being and must offer care in the patient’s best interest.”

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 physician’s knowledge and conscience are dedicated to the fulfilment of this duty.

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

Even well-proven interventions should be evaluated continually through research for their safety, effectiveness, efficiency, accessibility, and quality.

6. Medical research involving human participants is subject to ethical standards that promote and ensure respect for all participants and protect their health and rights.

Since medical research takes place in the context of various structural inequities, researchers should carefully consider how the benefits, risks, and burdens are distributed.

Meaningful engagement with potential and enrolled participants and their communities should occur before, during, and following medical research. Researchers should enable potential and enrolled participants and their communities to share their priorities and values; to participate in research design, implementation, and other relevant activities; and to engage in understanding and disseminating results.

7. The primary purpose of medical research involving human participants is to generate knowledge to understand the causes, development and effects of diseases; improve preventive, diagnostic and therapeutic interventions; and ultimately to advance individual and public health.

These purposes can never take precedence over the rights and interests of individual research participants.

8. While new knowledge and interventions may be urgently needed during public health emergencies, it remains essential to uphold the ethical principles in this Declaration during such emergencies.

9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, autonomy, privacy, and confidentiality of personal information of research participants. The responsibility for the protection of research participants must always rest with physicians or other researchers and never with the research participants, even though they have given consent.

10. Physicians and other researchers must consider the ethical, legal and regulatory norms and standards for research involving human participants in the country or countries in which the research originated and where it is to be performed, 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 participants set forth in this Declaration.

11. Medical research should be designed and conducted in a manner that avoids or minimizes harm to the environment and strives for environmental sustainability.

12. Medical research involving human participants must be conducted only by individuals with the appropriate ethics and scientific education, training and qualifications. Such research requires the supervision of a competent and appropriately qualified physician or other researcher.

Scientific integrity is essential in the conduct of medical research involving human participants. Involved individuals, teams, and organizations must never engage in research misconduct.

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 will not adversely affect the health of the patients who serve as research participants.

15. Appropriate compensation and treatment for participants who are harmed as a result of participating in research must be ensured.

Risks, Burdens, and Benefits

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

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

17. All medical research involving human participants must be preceded by careful assessment 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 minimize the risks and burdens must be implemented. The risks and burdens must be continuously monitored, assessed, and documented by the researcher.

18. Physicians and other researchers may not engage in research involving human participants unless they are confident that the risks and burdens have been adequately assessed and can be satisfactorily managed.

When the risks and burdens are found to outweigh the potential benefits or when there is conclusive proof of definitive outcomes, physicians and other researchers must assess whether to continue, modify or immediately stop the research.

Individual, Group, and Community Vulnerability

19. Some individuals, groups, and communities are in a situation of more vulnerability as research participants due to factors that may be fixed or contextual and dynamic, and thus are at greater risk of being wronged or incurring harm. When such individuals, groups, and communities have distinctive health needs, their exclusion from medical research can potentially perpetuate or exacerbate their disparities. Therefore, the harms of exclusion must be considered and weighed against the harms of inclusion. In order to be fairly and responsibly included in research, they should receive specifically considered support and protections.

20. Medical research with individuals, groups, or communities in situations of particular vulnerability is only justified if it is responsive to their health needs and priorities and the individual, group, or community stands to benefit from the resulting knowledge, practices, or interventions. Researchers should only include those in situations of particular vulnerability when the research cannot be carried out in a less vulnerable group or community, or when excluding them would perpetuate or exacerbate their disparities.

Scientific Requirements and Research Protocols

21. Medical research involving human participants must have a scientifically sound and rigorous design and execution that are likely to produce reliable, valid, and valuable knowledge and avoid research waste. The research 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 all medical research involving human participants must be clearly described and justified 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 aims, methods, anticipated benefits and potential risks and burdens, qualifications of the researcher, sources of funding, any potential conflicts of interest, provisions to protect privacy and confidentiality, incentives for participants, provisions for treating and/or compensating participants who are harmed as a consequence of participation, and any other relevant aspects of the research.

In clinical trials, the protocol must also describe any post-trial provisions.

Research Ethics Committees

23. The protocol must be submitted for consideration, comment, guidance, and approval to the concerned research ethics committee before the research This committee must be transparent in its functioning and must have the independence and authority to resist undue influence from the researcher, the sponsor, or others. The committee must have sufficient resources to fulfill its duties, and its members and staff must collectively have adequate education, training, qualifications, and diversity to effectively evaluate each type of research it reviews.

The committee must have sufficient familiarity with local circumstances and context, and include at least one member of the general public.  It must take into consideration the ethical, legal, and regulatory norms and standards 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 participants set forth in this Declaration.

When collaborative research is performed internationally, the research protocol must be approved by research ethics committees in both the sponsoring and host countries.

The committee must have the right to monitor, recommend changes to, withdraw approval for, and suspend ongoing research.  Where monitoring is required, the researcher must provide information to the committee and/or competent data and safety monitoring entity, especially about any serious adverse events. No amendment to the protocol may be made without consideration and approval by the committee. After the end of the research, the researchers must submit a final report to the committee containing a summary of the findings and conclusions.

Privacy and Confidentiality

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

Free and Informed Consent

25. Free and informed consent is an essential component of respect for individual autonomy. Participation by individuals capable of giving informed consent in medical research must be voluntary. Although it may be appropriate to consult family members or community representatives, individuals capable of giving informed consent may not be enrolled in research unless they freely agree.

26. In medical research involving human participants capable of giving informed consent, each potential participant must be adequately informed in plain language of the aims, methods, anticipated benefits and potential risks and burdens, qualifications of the researcher, sources of funding, any potential conflicts of interest, provisions to protect privacy and confidentiality, incentives for participants, provisions for treating and/or compensating participants who are harmed as a consequence of participation, and any other relevant aspects of the research.

The potential participant must be informed of the right to refuse to participate in the research or to withdraw consent to participate at any time without reprisal. Special attention should be given to the specific information and communication needs of individual potential participants as well as to the methods used to deliver the information.

After ensuring that the potential participant has understood the information, the physician or another qualified individual must then seek the potential participant’s freely given informed consent, formally documented on paper or electronically.  If the consent cannot be expressed on paper or electronically, the non-written consent must be formally witnessed and documented.

All medical research participants should be given the option of being informed about the general outcome and results of the research.

27. When seeking informed consent for participation in research the physician or other researcher must be particularly cautious if the potential participant is in a dependent relationship with them or may consent under duress. In such situations, the informed consent must be sought by an appropriately qualified individual who is independent of this relationship.

28. In medical research involving human participants incapable of giving free and informed consent, the physician or other qualified individual must seek informed consent from the legally authorized representative, considering preferences and values expressed by the potential participant.

Those persons incapable of giving free and informed consent are in situations of particular vulnerability and are entitled to the corresponding safeguards. In addition to receiving the protections for the particularly vulnerable, those incapable of giving consent must only be included if the research is likely to either personally benefit them or if it entails only minimal risk and minimal burden.

29. When a potential research participant who is incapable of giving free and informed consent is able to give assent to decisions about participation in research, the physician or other qualified individual must seek that assent in addition to the consent of the legally authorized representative, considering any preferences and values expressed by the potential participant. The potential participant’s dissent should be respected.

30. Research involving participants 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 group. In such circumstances the physician or other qualified individual must seek informed consent from the legally authorized representative. If no such representative is available and if the research cannot be delayed, the research may proceed without informed consent provided that the specific reasons for involving participants with a condition that renders them unable to give informed consent have been stated in the research protocol and the research has been approved by a research ethics committee.

Free and informed consent to remain in the research must be obtained as soon as possible from a legally authorized representative or, if they regain capacity to give consent, from the participant.

31. The physician or other researcher must fully inform potential participants which aspects of their care are related to the research. The refusal of a patient to participate in research or the patient’s decision to withdraw from research must never adversely affect the patient-physician relationship or provision of the standard of care.

32. Physicians or other qualified individuals must obtain free and informed consent from research participants for the collection, processing, storage, and foreseeable secondary use of biological material and identifiable or re-identifiable data. Any collection and storage of data or biological material from research participants for multiple and indefinite uses should be consistent with requirements set forth in the WMA Declaration of Taipei, including the rights of individuals and the principles of governance. A research ethics committee must approve the establishment and monitor ongoing use of such databases and biobanks.

Where consent is impossible or impracticable to obtain, secondary research on stored data or biological material 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 circumstances:

• If no proven intervention exists, the use of placebo, or no intervention, is acceptable; or
• If for compelling and scientifically sound methodological reasons the use of any intervention other than the best proven one(s), the use of placebo, or no intervention is necessary to determine the efficacy or safety of an intervention; and the participants who receive any intervention other than the best proven one(s), 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, post-trial provisions must be arranged by sponsors and researchers to be provided by themselves, healthcare systems, or governments for all participants who still need an intervention identified as beneficial and reasonably safe in the trial. Exceptions to this requirement must be approved by a research ethics committee. Specific information about post-trial provisions must be disclosed to participants as part of informed consent.

Research Registration, Publication, and Dissemination of Results

35. Medical research involving human participants must be registered in a publicly accessible database before recruitment of the first participant.

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 participants and are accountable for the timeliness, 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 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. When an unproven intervention is utilized in an attempt to restore health or alleviate suffering for an individual patient because approved options are inadequate or ineffective and enrollment in a clinical trial is not possible, it should subsequently be made the object of research designed to evaluate safety and efficacy. Physicians participating in such interventions must first seek expert advice, weigh possible risks, burdens, and benefits, and obtain informed consent. They must also record and share data when appropriate and avoid compromising clinical trials. These interventions must never be undertaken to circumvent the protections for research participants set forth in this Declaration.

Disclaimer: ©2024 World Medical Association. All Rights Reserved. All intellectual property rights in the Declaration of Helsinki are vested in the World Medical Association. The WMA has granted JAMA exclusive rights to publish the English-language version of the Declaration through December 31, 2024.