Applied Clinical Trials
Europe is issuing a significant update to its ethical guidelines governing health-related research involving humans.
It’s not just science that is leaping ahead and taking clinical trials into new territory. The world is changing around science, and one of the consequences is that there are changes, too, in the ethical context for medicine. What was until recently considered ethically sound is now no longer so adequate-and that is why, in February, the Council for International Organizations of Medical Sciences (CIOMS) is publishing its final version of its revision of one of the texts underlying all modern trial protocols, its 2002 International Ethical Guidelines for Health-related Research Involving Humans.
This 120-page document will have to become the new bible for everyone working in clinical trials, observational research, biobanking, and epidemiological studies. Its chapters cover virtually every aspect of trial design and conduct, from informed consent to compensation for research participants, and from ethics committees to cluster randomized trials. Almost all guidelines are newly drafted, and major revisions have been introduced to guidance on risks and benefits, choice of control, and women. Its scope has been expanded from “biomedical research” to cover all health-related research, and it has been merged with CIOMS’ 2009 International Ethical Guidelines for Epidemiological Studies.
Protecting the general good
Most notably, the document brings a new emphasis to what can best be described as the general good, in line with the development of more socially aware public discourse on health over the last two decades. There are now extensive guidelines on scientific and social value and respect for rights, on equitable distribution of benefits, on community engagement, on public accountability, and on conflicts of interest. CIOMS decided on an update because of developments since 2002, both in the field of biomedical research itself and in research ethics-including, notably, the revision of the Declaration of Helsinki in 2008.
So a new provision, right up at the front of the guidelines, is that “the ethical justification for undertaking health-related research involving humans is its scientific and social value.” To be ethically permissible, health-related research with humans, including research with samples of human tissue or data, must have social value, CIOMS insists. It explicitly outlaws “seeding trials” if their purpose is to influence participating clinicians to prescribe a new medication rather than to produce knowledge about the merits of these interventions. Similarly, even a well-designed, late-phase clinical trial could lack social value if the endpoints measured are not sufficiently related to clinical decision making.
Responsive to community needs
Keeping research relevant also gets new attention in these guidelines. “Before instituting a plan to undertake research in a population or community in low-resource settings, the sponsor, researchers, and relevant public health authority must ensure that the research is responsive to the health needs or priorities of the communities or populations where the research will be conducted,” says CIOMS. And benefits must be shared: "Sponsors, researchers, governmental authorities, and research ethics committees and other stakeholders must ensure that the benefits and burdens of research are equitably distributed,” the guidelines demand. So trial participants must be selected "for scientific reasons and not because they are easy to recruit given their compromised social or economic position or their ease of manipulability."
The rise of patient power is also reflected in the new guidelines. "Researchers, sponsors, health authorities and relevant institutions should engage potential participants and communities in a meaningful participatory process that involves them in an early and sustained manner in the design, development, implementation, informed consent process and monitoring of research, and in the dissemination of its results," according to CIOMS. This is a matter of showing respect for communities and for their traditions and norms, but it is also "valuable for the contribution it can make to the successful conduct of socially valuable research."
This injunction is not merely a form of words. The guidelines lay down what it means in practice. The research protocol should include a description of the plan for continued community engagement, and identify the resources allocated for this, with a list of what has been and will be done, and by whom, to ensure that the community is clearly defined and can be engaged to ensure that the research is relevant and accepted.
Women, and particularly pregnant and lactating women, benefit from additional attention in the new guidelines. Because they have distinctive physiologies and health needs, research designed to obtain knowledge relevant to their health needs must be promoted, says CIOMS, adding that research in pregnant women must be initiated only after careful consideration of the best available relevant data. In any research interventions or procedures that have no potential individual benefits for pregnant and breastfeeding women, the risks must be minimized, and the purpose of the research must be to obtain knowledge relevant to their particular health needs or those of their fetuses or infants.
Specimens and data
The rise in privacy concerns over recent years also informs new guidelines on biological materials and related data. In addition to provisions on governance for collection and storage of everything from tissue specimens to health records, CIOMS requires that when specimens are collected for research, either specific informed consent for a particular use or broad informed consent for unspecified future use must be obtained from the person from whom the material was originally obtained.
The guidelines demonstrate, however, a pragmatic approach to use of any residual tissue. Where this is stored for future research, a specific or broad informed consent may be used, or may be substituted by an informed opt-out procedure. And when researchers seek to use stored materials collected for past research or clinical purposes without having obtained informed consent for their future use for research, a research ethics committee may waive the requirement of individual informed consent if the research would not be feasible or practicable to carry out without the waiver and has important social value.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium