[Ip-health] JAMA: Revised CIOMS International Ethical Guidelines for Health-Related Research Involving Humans

Thiru Balasubramaniam thiru at keionline.org
Sun Dec 11 11:48:15 PST 2016


December 06, 2016
Revised CIOMS International Ethical Guidelines for Health-Related Research
Involving Humans
Johannes J. M. van Delden, MD, PhD1
; Rieke van der Graaf, PhD1
Author Affiliations Article Information
JAMA. Published online December 6, 2016. doi:10.1001/jama.2016.18977

The Council for International Organizations of Medical Sciences (CIOMS) was
established jointly by the World Health Organization (WHO) and the United
Nations Educational, Scientific and Cultural Organization (UNESCO) in 1949
as an international, nongovernmental, nonprofit organization and now
includes 45 international, national, and associate member organizations,
representing many of the biomedical disciplines, national academies of
sciences, and medical research councils. CIOMS recently released a new
version of its International Ethical Guidelines for Health-Related Research
Involving Humans.1
<http://jamanetwork.com/journals/jama/fullarticle/2592245#jvp160174r1> These
guidelines were developed in collaboration with WHO and based on
authoritative ethical guidance documents, such as the World Medical
Association’s Declaration of Helsinki2
<http://jamanetwork.com/journals/jama/fullarticle/2592245#jvp160174r2> and
UNESCO’s Universal Declaration on Bioethics and Human Rights.3
<http://jamanetwork.com/journals/jama/fullarticle/2592245#jvp160174r3> The
aim of the guidelines is to provide internationally vetted ethical
principles and detailed commentary on how these principles should be
applied, with particular attention to conducting research in low- and
middle-income countries (LMICs).
Reasons for Revisions

Several challenges and reasons prompted CIOMS to revise its ethical
guidelines. A first challenge was to provide clearer guidance for ensuring
that research addresses important questions for improving health using
sound research methods. The ethical acceptability of research fundamentally
depends on its social and scientific value,4
some of the research currently conducted is of questionable value.5

A second challenge was to further clarify what can be regarded as fair
benefits of research in low-resource settings. Although the CIOMS
guidelines have always addressed the interests of research participants and
those in LMICs in particular, the previous version of the CIOMS guidelines
(issued in 2002) was criticized for not providing sufficient guidance
focused on this issue. That version required that externally sponsored
research should be responsive to the health needs and priorities of the
host country and that any proven products, such as drugs, should be made
reasonably available to that population or community. However, the
requirement was difficult to apply in practice, in particular because of
its narrow focus on benefits that may, but not always will, result from a

A third challenge was to address the increased need to engage communities
from the planning to the implementation phase of research.

A fourth reason was a change in global perspectives about inclusion of
potentially vulnerable groups. In the 2002 version, certain groups, such as
children and incompetent individuals, were explicitly labeled as
vulnerable. However, a group approach to vulnerability may no longer be
appropriate because it may have led to the routine exclusion of certain
groups from research and hence has exacerbated knowledge gaps.6
a group approach could also lead to underprotection because it does not
address different ways in which people can be vulnerable, for example, an
illiterate woman in a low-resource setting participating in a study on
domestic violence.6

A fifth challenge was that the increase in the collection, storage, and use
of biological material and health-related data has changed the practice of
research from an activity mainly carried out in individual projects to an
activity that is organized around research infrastructures such as biobanks
and databanks. CIOMS recognized the need to provide guidance to
researchers, sponsors, members of research ethics committees, and other
stakeholders in dealing with these challenges and started a revision
process. The process of development and revision of these guidelines was
approved by the WHO Guidelines Review Committee and received extensive
input from the WHO Ethics Review Committee.
Significant Changes

As a general response to these developments in research involving humans,
the scope of the guidelines has been broadened from biomedical research to
health-related research because the term *biomedical research* would not
cover research with health-related data. In addition, the 2002
International Ethical Guidelines for Biomedical Research Involving Human
Subjects were merged with the CIOMS 2009 International Ethical Guidelines
for Epidemiological Studies, which included topics such as biobanking and
research with health-related data. The following major changes have been
made to the previous guidelines as a response to the specific challenges
that have emerged during the last decade.

First, the 2016 CIOMS guidelines include an increased emphasis on the
scientific and social value of research: the prospect of generating the
knowledge and the means necessary to protect and promote health (guideline
1). Many stakeholders in health-related research rely on the results of
research for activities and decisions that affect individual and public
health, welfare, and the use of limited resources. Therefore, researchers
and sponsors must ensure that research addresses important and unsolved
questions to improve health and increase the reliability of scientific
information, promote efficient translation, and reduce research waste, even
when the research investigation poses few or only minor risks to study

Second, the importance of social value is part of a larger effort to
clarify considerations of fairness in research conducted in low-resource
settings. The guidelines now recognize that low-resource settings are not
limited to low-income countries but can exist within middle- and
high-income countries (guideline 2). In addition, CIOMS now lists the
obligation to make available the interventions proven effective in research
as part of a broader obligation to care for participants’ health needs
(guideline 6). This broader obligation also requires, for example, that
before a study begins, researchers and sponsors make plans for
transitioning participants who continue to need treatment after their
participation in research to appropriate health services.

Third, a new guideline on community engagement is included (guideline 7).
Proactive and sustained engagement with the communities from which
individuals will be invited to participate shows respect for them and for
the traditions and norms that they share. Community engagement is also
valuable for the translation of research into outcomes that are both
clinically relevant and meaningful for patients and communities.

Fourth, the new guidelines no longer label entire classes of individuals as
vulnerable. Moreover, CIOMS more clearly emphasizes that unless a good
scientific reason justifies their exclusion, children and persons who are
incapable of giving informed consent must be included in research
investigations, provided that appropriate safeguards are in place.
Moreover, the revised guidelines require researchers and research ethics
committees to evaluate the specific context-dependent characteristics that
may place study participants at increased risk of being harmed or wronged.

Just as the definition of vulnerability is context dependent, so is the
delineation of special protections. Researchers and research ethics
committees can devise special protections for groups considered to be
vulnerable, including allowing for no more than minimal risks for research
procedures that offer no potential individual benefits for participants, or
requiring that the research be carried out only when it targets conditions
that affect these groups. Researchers and research ethics committees should
enable the participation of vulnerable individuals by protecting their
rights and interests through special safeguards and protections.

Special protections are warranted in research involving pregnant and
breastfeeding women to ensure that their rights and interests are
protected. The 2002 guideline on research with pregnant women underwent
major revisions to strengthen the specific protection mechanisms (guideline
19), such as the conditions under which risks in research with pregnant
women are acceptable. In addition, the guidelines require that research
that has the potential to harm the fetus should be conducted only in
settings where women can be guaranteed access to a safe, timely, and legal
abortion in the event that participation in the research makes the
pregnancy unwanted.

Fifth, the traditional method of informed consent for specific research
projects is proving inappropriate for the increasing number of studies that
use biological material and health-related data. Concepts of broad informed
consent and informed opt-out procedures have therefore been adopted in the
new CIOMS guidelines for research in this area (guidelines 11 and 12).
Broad informed consent in essence is consent for governance. Adequate
governance systems substitute for the loss of an individual’s control over
her or his data and biological material. These governance systems should
specify—among other items—to which legal entity the material is entrusted,
how authorization from the donor is obtained, and what procedure determines
whether unsolicited findings should be disclosed. Proper governance systems
are also important because complete anonymization is becoming increasingly
difficult owing to increases in cross-matching large data sets.

Progress toward a world in which everyone can enjoy optimal health and
health care is crucially dependent on all kinds of research, including
research involving humans. This research needs to be conducted according to
guidelines such as the ethical principles set forth in the CIOMS
guidelines. As research practice changes, new challenges emerge and
guidelines need to be adapted. The changes in the new CIOMS guidelines
reflect an international effort to provide well-reasoned answers to these
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Article Information

*Corresponding Author:* Johannes J. M. van Delden, MD, PhD, Julius Center,
Department of Medical Humanities, University Medical Center Utrecht, PO Box
85500, 3508 GA Utrecht, the Netherlands (j.j.m.vandelden at umcutrecht.nl).

*Published Online:* December 6, 2016. doi:10.1001/jama.2016.18977

*Conflict of Interest Disclosures:* All authors have completed and
submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest
and none were reported.

*Additional Contributions:* Members of the Working Group on the revision of
the 2002 CIOMS guidelines include Anant Bhan, MBBS, MHSc, Eugenijus
Gefenas, MD, PhD, Dirceu Greco, MD, PhD, David H.-U. Haerry, Bocar Kouyaté,
Alex John London, PhD, Ruth Macklin, PhD, Annette Rid, MD, Rodolfo Saracci,
MD, Abha Saxena, MD, and Aissatou Touré, PhD. Observers and advisors of the
Working Group include Ingrid Callies, Joan Dzenowagis, Hans-Joerg Ehni,
Dafna Feinholz, Sev Fluss, Melba Gomes, Carel Ijsselmuiden, Ronnie Johnson,
Lembit Rägo, Gunilla Sjölin-Forsberg, Sheryl VanderPoel, and Urban Wiesing.
More than 57 institutions and organizations provided comments and helped to
shape the final version of the guidelines.
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