Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems

Cluster randomized trials (CRTs) randomly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals. Recent emphasis on quality improvement, comparative effectiveness, and learning health systems has prompted expanded use of pragmatic CRTs in routine healthcare settings, which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address. The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic CRTs but challenges remain, including some arising from the current U.S. research and healthcare regulations. In order to examine the ethical, regulatory, and practical questions facing pragmatic CRTs in healthcare settings, the National Institutes of Health (NIH) Health Care Systems Research Collaboratory convened a workshop in Bethesda, Maryland in July of 2013. Attendees included experts in clinical trials, patient advocacy, research ethics, and research regulations from academia, industry, the NIH, and other federal agencies. Workshop participants identified substantial barriers to implementing these types of CRTs, including issues related to research design, gatekeepers and governance in health systems, consent, institutional review boards, data monitoring, privacy, and special populations. We describe these barriers and suggest means for understanding and overcoming them to facilitate pragmatic CRTs in healthcare settings.