Risks (and Benefits) in Comparative Effectiveness Research Trials

NEJM: 8/21/13

Comparative effectiveness research (CER) aims to provide high-quality evidence to help patients and clinicians make informed clinical decisions and to assist health systems in improving the quality and cost-effectiveness of clinical care.1 Recently, the Department of Health and Human Services indicated that the regulatory framework for protecting human subjects is inadequate to evaluate the multifaceted risks of CER randomized, controlled trials (RCTs).2 As the federal Common Rule states, risks to subjects must be “reasonable in relation to anticipated benefit.” Institutional review boards (IRBs) are directed to “consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research).” Furthermore, unless the requirement for informed consent is waived by the IRB, subjects must be informed of “any reasonably foreseeable risks or discomforts” associated with participation. The enmeshment of research and standard clinical care makes evaluation of the risks posed by a CER RCT complex. In order to provide ethically appropriate oversight and informed consent, investigators should consider, manage, and communicate with potential participants about at least nine different types of potential risk — some unique to CER RCTs, some common to all RCTs. Read more