Western-led team delivers world-first ethics guidelines for cluster randomized trials

The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials provides researchers and research ethics committees with detailed guidance on the ethical design, conduct, and review of cluster randomized trials (CRTs). Published in the current edition of PLoS Medicine, this marks the first time dedicated ethical guidelines have been established for CRTs and it is expected that these recommendations will become part of research ethics policies and practice around the world.

The research was led by Charles Weijer of Western University's Schulich School of Medicine & Dentistry and Rotman Institute of Philosophy, and Jeremy Grimshaw and Monica Taljaard of the Ottawa Hospital Research Institute.

"Cluster randomized trials are a critical research method in medicine, but until now their ethical challenges were poorly understood," explains Weijer, Canada Research Chair in Bioethics. "The fact that CRTs randomize groups rather than individuals raises all kind of ethical questions."

These ethical questions include:

• Who are the research participants?
• From whom does one need to get informed consent?
• Is the permission of a gatekeeper required?

Weijer continues, "Researchers told us that the lack of an answer to these questions was a practical impediment to being able to do these important studies."

CRTs are an important new method in health research in which groups or 'clusters' of individuals are randomized, as opposed to just individuals. Although they are a new method in health research, CRTs have already had a major impact on the quality of health care delivery and on global health. For instance, a CRT conducted in 19 units caring for stroke patients in Australia that sought to optimize nursing care led to a 16 per cent reduction in severe disability and death following stroke (Lancet 2011). In another example, a CRT conducted in impoverished communities in eastern India brought together women's groups to address neonatal health and reduced neonatal mortality by 45 per cent and maternal depression by 57 per cent (Lancet 2010).

Principal investigators Grimshaw, Taljaard and Weijer led an interdisciplinary research team from six institutions in three countries in the project funded by the Canadian Institutes of Health Research to answer these ethical questions and develop international ethics guidelines.

"Members of the research team, which included clinical trialists, social scientists, and statisticians, became aware of the need for ethics guidelines from their extensive experience in designing, submitting for ethics review, and conducting cluster randomized trials," says Taljaard, a scientist and statistician who designs CRTs at the Ottawa Hospital Research Institute. "We teamed with Dr. Weijer's group in 2007 to embark on a five-year project to address this need. There was tremendous support for our project amongst trialists and research ethics chairs internationally."

The research team examined published CRTs, interviewed researchers, and surveyed both researchers and chairs of research ethics committees as part of its investigations. A series of background papers presented in-depth ethical analyses of specific issues in CRTs. The team's research was presented to a multidisciplinary expert panel in Ottawa in November 2011. A writing group, made up of seven members of the original research team, produced a draft of the consensus statement from this expert panel, which was then approved by the entire expert panel. This statement was released on November 20, 2012 in PLoS Medicine.

"We expect that these recommendations will go a long way towards alleviating many of the challenges that have been encountered in the conduct and review of cluster randomized trials," says Taljaard.

"The ethics guidelines are a win-win solution to an important problem," offers Weijer. "They simultaneously promote high ethical standards and facilitate CRTs that will improve healthcare and save lives. The success of the project as a whole demonstrates the value of collaborations between philosophers and scientists to address pressing problems in contemporary science."

The full Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, by Charles Weijer, Jeremy M. Grimshaw, Martin P. Eccles, Andrew D. McRae, Angela White, James C. Brehaut, Monica Taljaard and the Ottawa Ethics of Cluster Randomized Trials Consensus Group is available at PLoS Medicine: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001346