Revision process

Revising the 2002 CIOMS Ethical Guidelines for Biomedical Research Involving Human Subjects

J.J.M. van Delden

November 2016



During its annual meeting in 2009, the Executive Committee (EC) of CIOMS considered the desirability of a revision of the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects. The last revision of that document dated from 2002 and since then several developments had taken place, both in the field of biomedical research itself and in the field of research ethics. Among the latter developments was the revision of the Declaration of Helsinki in 2008, which at the moment was revised again. The Executive Committee therefore decided to first explore the desirability of such a revision.

In its 2010 meeting the report on the desirability, drafted by Professor J.J.M. van Delden, at that time member of the EC of CIOMS, was discussed. The CIOMS Ethical Guidelines for biomedical research are mostly viewed and presented as detailed rules of application of the principles listed in the various Guidelines including the Declaration of Helsinki. As such they are unique in offering a practical approach and working tool for all actors involved in biomedical research involving human subjects. Therefore, most experts consulted found the CIOMS Guidelines had an additional value. All experts consulted, for various reasons, were of the opinion that a revision of the 2002 CIOMS Guidelines for Biomedical Research Involving Human Subjects was indeed desirable. The EC therefore decided to start preparations for the revision process.

In one of the preparatory meetings with WHO the relation between CIOMS and WHO with respect to these guidelines was discussed. The 2002 version of these guidelines, on the second page, states that these guidelines are developed “in collaboration” with WHO. At that time no specific regulations applied that governed the possibility for including such a statement. At the present time however, WHO has clear guidelines that shape the process of drafting a guideline. Therefore a Memorandum of Understanding was signed between CIOMS and WHO in which the terms of the cooperation were defined.

Composition of the groups involved in the revision

The CIOMS Executive Committee in its 2011 meeting decided to set up a Working Group to revise the International Ethical Guidelines for Biomedical Research involving Human Subjects. The Working Group consisted of 10 members, one chair (president of CIOMS), four advisers (from WHO, UNESCO, COHRED and WMA) and one scientific secretary. The composition of the Working Group ensured that different cultural perspectives were present, members varied in experience and expertise, and a gender balance was achieved. One of the members represented the perspective of research participants.

The revision process

The above mentioned Working Group to revise the CIOMS Guidelines met three times each year from September 2012 until September 2015. At its first meeting the Group considered which Guidelines needed major and minor revisions. Guidelines that required major revision included the Guideline on risks and benefits (2002 Guideline 8), choice of control (2002 Guideline 11) and women (2002 Guideline 16). The Group also discussed which Guidelines could be merged (for example, 2002 Guidelines 4 and 6 both dealt with informed consent). Furthermore, the Group decided to merge the “Green Book” (the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects, 2002) with the “Blue Book” (the CIOMS International Ethical Guidelines for Epidemiological Studies 2009). The 2009 CIOMS Guidelines were produced to be used as a standalone rather complementary to 2002 CIOMS Guidelines. This obviously resulted in certain parts of the 2009 Guidelines being generally the same as the 2002 Guidelines. Revisions to the “green book” would therefore necessarily impact the “blue book”. In order to ensure the epidemiological dimension of the new merged and revised Guidelines, Rodolfo Saracci, a distinguished epidemiologist who was also a member of the Working Group, was assigned the duty of evaluating the revisions from an epidemiological perspective.

At the end of September 2015, the Working Group opened its draft Guidelines for public comments until 1 March 2016. The Working Group received comments from 57 individuals and institutions. In many cases these comments were prepared by several persons from one institution. The commentators represented all parts of the world. The Working Group received over 250 pages of comments, which all were carefully documented and weighed for appropriateness of being considered in the final text.

In June 2016 the Working Group met a final time. At the beginning of October 2016, the final draft was submitted to the Executive Committee of CIOMS for approval during the General Assembly in Geneva at the end of November 2016.

Evidence retrieval and deliberative process

In the revision process, literature reviews were used as sources for further ethical deliberation. Authoritative declarations, reports and guidance documents have had a prominent role in these discussions, such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the International Covenant on Civil and Political Rights of the United Nations (1966), the Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997), the UNAIDS/WHO Ethical Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of the World Medical Association (2013).

Textbooks, existing ethical frameworks for human subjects research and reports on human subjects research were also valuable sources of information. The Working Group reviewed papers in major ethics journals such as the American Journal of Bioethics; Bioethics; Developing World Bioethics; the Journal of Law Medicine and Ethics, the Journal of Bioethical Inquiry; Medicine, Health Care and Philosophy; Cambridge Quarterly of Healthcare Ethics; the Journal of Medicine and Philosophy; the Journal of Medical Ethics; the Hastings Center Report; BMC Medical Ethics and the Journal of Empirical Research on Human Research Ethics, as well as articles in leading medical or scientific journals, such as the New England Journal of Medicine, The Lancet, Science and BMJ.

Literature reviews were used in three ways. First, we searched main ethical guidelines on human subjects research and textbooks on research ethics to identify new topics or viewpoints in existing debates. For instance, many guidelines have included statements on biobanking which was one of the reasons to merge the CIOMS Guidelines for epidemiological research with those for biomedical research.

We performed searches in Embase and Medline on review papers and papers with strong positions on certain topics. For example, component analysis and the net risk test are two recent approaches to making risk-benefit assessments. There is no agreement among bioethicists which of these approaches is preferable. The Working Group read relevant papers on these approaches and developed a middle ground. A similar process was adopted for vulnerability. A consensus emerged in recent publications that vulnerability can no longer be applied to entire groups. As a result the Working Group eliminated the group approach, Instead, the Guidelines focus on characteristics that lead to considering certain groups as vulnerable and on the specific protections that are needed in those situations.

Third, literature reviews were performed to address relatively new topics, such as opt-out procedures in biobanking or informing research participants results of (un)solicited findings. The Working Group reviewed relevant papers on these topics and took a position accordingly. It is important to emphasize that the literature was used as a starting point for further discussion. Ultimately, the validity of the ethical positions in these Guidelines hinges on the strength of the arguments, not on the frequency of an ethical standpoint in the literature.

All decisions by the Working Group were reasoned decisions. Members discussed all proposals for revision of particular texts during the meetings. Members deliberated until they had reached a well-argued consensus. If no such consensus was reached, the previous text in the 2002 Guidelines remained in place.

Scope of the 2016 version

The Working Group decided to broaden the scope of the 2002 Guidelines from “biomedical research” to “health-related research”. The Working Group considered biomedical research too narrow since that term would not cover research with health-related data, for example. At the same time, the Working Group acknowledged that this new scope also had limits. For example, new developments such as the idea of the Learning Healthcare System that tries to integrate forms of research and care were beyond the scope of the draft of the Working Group. The Working Group also acknowledged that there is no clear distinction between the ethics of social science research, behavioural studies, public health surveillance and the ethics of other research activities. The current scope is confined to more classic activities that fall under health-related research with humans, such as observational research, clinical trials, biobanking and epidemiological studies.

Proactive international consultation

In June 2014, the Working Group organized a symposium during the 12th World Congress of the International Association of Bioethics (IAB) in Mexico City. Key issues were presented and opened for discussion in this process. The focus of the session was on aspects of CIOMS Guidelines when used in low- and middle-income settings, social value, and research including vulnerable persons. A good number of 80—90 of the congress participants attended the symposium and a lively discussion took place in which many helpful remarks were made. This session served as one element of the international consultation process for the proposed revision of the CIOMS Guidelines. In November 2014, the draft revision was discussed at the Forum of Ethical Review Committees in the Asian & Western Pacific Region (FERCAP) in Manilla in a plenary session with more than 800 attendees. The revision was also discussed at the Advancing Research Ethics Training in Southern Africa (ARESA) Seminar on 17—18 September 2015 in Cape Town and at CENTRES (Clinical Ethics Network & Research Ethics Support), in Singapore in November 2015.

Specific feedback was sought from the member organizations of CIOMS, from others through the Regional Offices of WHO, from the WHO network of Collaborating Centres for Bioethics and from a workshop with Ethical Review Committees at WHO and from members of National Ethics Committees participating in the Global Summit of National Ethics Committees.