Year : 2023 | Volume
: 14 | Issue : 1 | Page : 1--2
Declaration of Helsinki: Can it still serve as a North star for ethics in regulatory trials?
Designation: President, Indian Society for Clinical Research, India
Dr. Sanish Davis
C/o, Pfizer Limited, The Capital, 1802, 18th Floor, Plot No. C- 70, 'G' Block, Bandra Kurla Complex, Bandra (E), Mumbai - 400 051, Maharashtra
|How to cite this article:|
Davis S. Declaration of Helsinki: Can it still serve as a North star for ethics in regulatory trials?.Perspect Clin Res 2023;14:1-2
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Davis S. Declaration of Helsinki: Can it still serve as a North star for ethics in regulatory trials?. Perspect Clin Res [serial online] 2023 [cited 2023 Feb 1 ];14:1-2
Available from: http://www.picronline.org/text.asp?2023/14/1/1/367303
One of the central missions of the World Medical Association (WMA) in its role as the global organization of physicians is to ensure the highest possible standard of ethical clinical practice and medical research. The WMA's Declaration of Helsinki (DoH) was first adopted in 1964. In its close to 60-year lifetime, the Declaration has been revised seven times and has risen to a position of prominence as a guiding statement of ethical principles for doctors involved in medical research.
Consistent with the mandate of the WMA, the DoH is addressed primarily to physicians. While geared toward the medical profession, WMA encourages the adoption of DoH as a practical tool for nonphysician researchers as well. In India, study protocols and informed consent forms regularly state that investigator responsibilities in a clinical trial are governed by the principles of DoH and the International Conference of Harmonization (ICH) Good clinical practices (GCP) guidelines. Hence, every stakeholder who is part of the clinical trial enterprise is very much bounden by the principles enshrined in DoH.
As per WMA, the 2013 version is the only official one; all previous versions have been replaced and should not be used or cited except for historical purposes. The DoH will undergo another revision starting in 2022. On the eve of the revision, there is always a discussion on the current relevance of DoH in the setting of Pharmaceutical Industry led clinical trial activity. In this Editorial, I would like to explore the stance of the different regulatory agencies and guideline-generating societies in the domain of medical research ethics. The United States (US) Food and Drug Administration (FDA) ceased compliance with the DoH (2000 revision and all subsequent revisions) for the conduct of clinical trials outside its borders. It is interesting to note in the introduction section of previous versions of the DoH, specific mention that “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.” The DoH version after Seoul (2008) has deleted this statement and this could probably be an indirect follow-on effect of some of the major regulatory agencies of the world, e.g., the USFDA following a different direction. The USFDA instead ruled that compliance with the GCP section of ICH is sufficient. However, the ICH-GCP guidelines do not address certain ethical requirements stipulated in the DoH, such as the use of placebos versus standard therapy, posttrial access to treatment, and other benefits for participants; public disclosure of trial design; publication of trial results; and the disclosure of conflicts of interest.
In the case of New Drugs and Clinical Trial (NDCT) Rules (2019) which govern regulatory clinical trials in India, there is No mention of DoH in any of the sections with regard to the responsibilities of investigators (e.g., the third schedule on the conduct of clinical trials). There is only a brief mention in the section [”structure, content, and format for clinical trial report” in Table 1] on how an Ethics committee should document that the study was conducted in an ethical manner as per the principles of DoH. The Indian GCP Guidelines (2001) which is cross-referenced by NDCT Rules, and is the legal guidance in India, has several sections where it mentions DoH and also gives the same in the Appendix of the guideline. It is to be noted that the Indian GCP Guidelines are now more than two decades old and there are several areas where it is not consistent with what is followed for both clinical trials and academic studies (NDCT Rules and ICMR Guidelines, respectively) and a revision is imminent. The ICMR National Ethical Guidelines for Biomedical and Health Research involving Human Participants (2017) in the sections on investigator responsibilities in a clinical trial primarily references DoH.
As DoH principles are gradually becoming no longer the central tenant of the regulations governing clinical trials most importantly in the section With reference to responsibilities of investigators, there is a question that is raised on the relevance of DoH principles in the context of Multiregional Clinical Trials. Given that, globally 33% of trials are funded by the pharmaceutical industry and more than 19% of Phase 3 trial sites are in countries with emerging economies (low-and middle-income), it would be intuitive to think that physician researchers and clinical trial investigators in these countries need to be aware and conduct trials as per the DoH principles. There is no training on DoH or its principles either as part of the investigator meeting/site initiation visits or as part of GCP training to the investigators. Formal training on DoH principles is also not part of the medical training curriculum for postgraduates in India or for those physician researchers who are formally inducted into clinical research.
There are several other guidelines, e.g., The Council for the International Organizations of Medical Sciences (CIOMS) guidelines on research ethics, Belmont Report, Nuffield Guidelines, etc. Which refer to the DoH in their respective texts. Given that the WMA has waded into contemporary areas (e.g., placebo usage, posttrial access, etc.) in the recent revisions of the DoH, shows ample demonstration that the declaration is a living document that is willing to consider current issues in medical research. While the DoH has been around for now close to six decades, it may be quite possible that the influence of DoH principles becomes “diluted” by the proliferation of international guidelines, codes of practice, and other ethical dictums such as those developed by CIOMS, by the ICH, and others. It is important to note that each of these derived guidelines/regulations is much lengthier and attempts to cover questions of what to do in particular practical situations. The DoH, on the other hand, seeks to articulate a basic set of principles, to function as a code of ethics, is still <2000 words, continues to adapt to the changing world of biomedical research, and will remain the one that will be the ethics North star in medical research.
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