Risk in comparative effectiveness research: Reflections from DHHS public meeting

by Elisa A. Hurley, PhD, Education Director

As I shared in yesterday’s blog post, I had the privilege of attending the Department of Health and Human Service (DHHS) public meeting in Washington, DC, on “matters related to protection of human subjects and research considering standard of care interventions,” which was convened to address some of the issues raised by the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT).

Yesterday I mentioned the surprising areas of convergence among the 27 presenters who took their turn at the podium. Today I will focus on some of the areas of disagreement. One issue that continues to provoke widespread disagreement is how to conceptualize and assess the risks of comparative effectiveness research. David Magnus, from the Stanford School of Medicine, for instance, argued that when there is no evidence of an increase in risk for individuals enrolled in a study versus those not enrolled, the research is appropriately classified as minimal risk, regardless of what risks are associated with each arm of the study.

On the other hand, George Annas, from Boston University School of Public Health, claimed that randomization always harms the subject by depriving her of the doctor-patient fiduciary relationship in which her physician is obligated to act in her best interest, and so, presumably, enrollment in a randomized study of any standard of care interventions could never be classified as minimal risk.

Steven Joffe, from the Perelman School of Medicine, made a characteristically articulate and concise case that the definition of minimal risk in the regulations is woefully unclear, perhaps contributing to much of the confusion about how to assess comparative effectiveness research, and proposed guidance clarifying that assessments of minimal risk should be made based only on risks that result from research, and not therapies that the subject would receive if not involved in the research.

John Lantos, from Children’s Mercy, and Nancy Kass, from the Bloomberg School of Public Health, provided the most eloquent, persuasive, and provocative challenges to the assumption that participating in research is always riskier than receiving conventional treatment, or that receiving individualized care is always better than receiving care through research. Both went so far as to suggest that we should, through informed consent forms, be more transparent about the fact that receiving unvalidated therapies may be riskier than participating in randomized research.

Of course, many other fascinating questions and issues came up on Wednesday, and I encourage anyone who wasn’t at the meeting or watching it via live stream to watch the archives to get the full flavor of the richness and collegiality of the discussion, the graciousness and astoundingly thorough preparation of the panelists, and the mutual respect this community has for one another, regardless of where we all stand on the issues. It remains to be seen what the policy outcome of this special meeting will be, but there is no doubt in my mind that this was public policy deliberation at its very best, and it was a privilege to be part of it.