List of the topics recommended for the revision in the Declaration of Helsinki
Following the request of WMA to collect suggestions for the planned revision of the DoH, the IFAPP WG on Ethics recommends to the President of IFAPP and the BoOs to submit on behalf of IFAPP to the WMA the following suggestions by Dr. Gustavo Kesselring.
The Members of the WG of Ethics would highly appreciate if in the final submission to the WMA the work of the IFAPP WG on Ethics in compiling this document would be specifically acknowledged.
1. Connection between Declaration of Helsinki (DoH) and Declaration of Taipei (DoT)
The scope of DoH is “research”; and the scope of DoT is “health databases and biobanks”. But it remains unclear, whether data and/or biological material collected as a part of the research and used for secondary analysis, fall under the scope of DoT. IFAPP believes it should be in the scope of DoT, in case of intended data/material sharing and/or secondary use . This should be clarified in the “General Principles” of the DoH.
2. Ethical approval and consent for secondary use
If future secondary analyses of data/material collected in research is expected, it should be written in the research protocol and informed consent form, to be assessed by an ethics committee. Once approved, the candidate subject can then make a decision whether to accept or refuse this secondary use. This should be clarified by revisions of paragraphs 22 (protocol) and 26 (informed consent). This consent to future secondary use should be separated from the consent to participation in proposed research, and this consent could be valid on condition that the above connection between the DoH and DoT is clarified.
3. Incidental finding
The last sentence of the paragraph 26 of the DoH states that “All medical research subjects should be given the option of being informed about the general outcome and results of the study.”, but “incidental finding” is not mentioned. Meanwhile, paragraph 11 of the DoT states that returning results including incidental findings is one of the conditions of valid consent. The right of an individual of taking option of knowing/not knowing the results should be the same in both frameworks of the DoH and DoT, thus it should be clarified that the “results” in the DoH includes “incidental findings”.
4. Registration of “data sharing plan” and “result” in publicly available database
Study registration requirement was included in the paragraph 35 of the DoH in 2008 with no further revision in 2013. “Result registration” has come to be legal requirement in many countries but many cases of non-compliance have been reported. Responsible data sharing is believed by the ICMJE to be an “ethical obligation” and considered necessary in the WHO’s list of items but registration of data sharing plan has not been well facilitated. These registrations should be promoted by the paragraph 35. In addition, if the secondary use plan is registered in the same registry, an individual can track it.
5. Shared responsibility
Recently, especially related to the development of advanced medicinal products, non-medically qualified personnel became increasingly involved in the work of clinical drug development teams. Frequently their activities influence directly the well-being of the trial subjects. Therefore, IFAPP recommended recently that also non-medically qualified personnel should jointly share the ethical responsibility of such trials. We suggest including additionally one sentence into the paragraph 12 of the DoH: “All medically or non-medically qualified members of a research team having direct effect on the well-being of the trial subjects should share jointly the ethical responsibility for their welfare.”
6. Patient and public involvement plan
An increasing number of research projects in the world has come to have a “patient and public involvement (PPI) plan” in their medicines development project. Although there is no international consensus, there is one guideline (in Canada) recommending it to be described in a protocol before assessment by the concerned ethics committee. To avoid misuse of a PPI plan and as a physician’s responsibility to protect a patient involved in a research project even not as a study subject, it should be recommended in paragraph 22 that PPI (if any) should be described in the research protocol.
7. Diversity of membership and qualified expertise of Research Ethics Committee
It is considered international standard that membership of research ethics committees required to provide multiple perspectives, e.g., scientific and non-scientific; affiliated and not affiliated to the institution; all genders. As for non-scientific perspective, there are a variety of aspects to be considered, e.g., expertise of humanities; perspectives of lay persons such as study volunteer, citizen, or patient; religion; law, etc. Paragraph 23 mentions “qualification”, “transparency” and “independency” of Research Ethics Committee. It is recommended that “diversity” is added as one of the necessary characteristics. Sufficient education in topic and process of research is recommended for the qualification of the committee, and additional experts should be consulted when expertise is not within the core ethics committee competency.
8. Terminology of key concepts: human subjects, humans, participants, patients, etc.
There have been substantial discussions on the correct wording of “human subject”. It is recommended that WMA in cooperation with other organizations and patient representatives to agree upon a mutually acceptable nomenclature.
9. Terminology of key concepts: medical research
Previously DoH had changed the terminology from “clinical research” to “biomedical research” and then to “medical research”. CIOMS has changed from “biomedical” to “health-related” with inclusion of epidemiological research and expansion of the scope. Wording “medical” in DoH should be revisited. Some types of research may involve physicians but not strictly considered “medical”: for example, behavioral or educational research using MRI (for which physician takes responsibility for safety); social science research (to which physician contributes with medical knowledge). It is not clear whether these types of research are in the scope of DoH.
10. Vulnerable population
CIOMS 2016 took position that vulnerable people should be included in research unless there is justifiable reason to exclude. This reverse theory is because routine exclusion causes lack of evidence of these populations, but this theory should not be abused. Meanwhile, paragraph 20 of the DoH justifies research with vulnerable group only when 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. This theory may exclude participation of vulnerable patients who are willing to participate in research with expected direct benefit to this individual but not directly responsive to health needs or priority of this group. It is recommended that WMA should discuss these two opposite theories and clarify its position.
CIOMS 2016 took the standard of “minor increase above minimal risk” as the limit of acceptable risk of placebo control, when there is an established effective intervention. The standard in paragraph 33 of the DoH “no additional serious or irreversible harm” is almost the same as CIOMS 2002 and ICH E-10 in 2000. Considering the revised standard (or wording) in CIOMS, WMA should discuss these two different standards (or wordings) and clarify its position.
12. Post-trial access
Paragraph 34 recommends to make provision for appropriate post-trial intervention in advance of the trial. If the meaning of “an intervention identified as beneficial in the trial” is not limited to the tested drug/intervention, but any intervention identified as beneficial for each participant, it would be physician’s obligation to provide such intervention to each participant who needs it, after the completion of the trial. In addition, community involvement strategy to make the proven intervention available in the host community would be important. These two points should be clarified in this paragraph.