by Elisa A. Hurley, PhD, Education Director

Last Wednesday, August 28, 2013, the Department of Health and Human Service (DHHS) held a public meeting in Washington, DC on “matters related to protection of human subjects and research considering standard of care interventions.” It was an unprecedented event on a historic day—the 50th anniversary of the March on Washington—and I was lucky enough to attend the event as a representative for PRIM&R. Over the course of two posts, I want to share some of my reflections from this remarkable day.

Those of you who have been following events for the past five months know that this meeting was scheduled following the heated public debate that erupted in response to the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT), which we’ve been covering on Ampersand. The debate around SUPPORT has illuminated deep disagreements within the research and ethics communities about how risk should be assessed and disclosed to subjects (or their surrogates) in randomized studies on interventions that are used in standard care, but about whose relative effectiveness there is widespread disagreement (often called “comparative effectiveness research”). The lack of consensus within the field about this growing area of research prompted DHHS to announce, in late June, that it would hold a meeting to “seek public input and comment on how certain provisions of the [DHHS] requirements related to the protection of human subjects should be applied to research studying one or more interventions which are used as standard of care treatment in the non-research context.”

The day-long meeting was held at DHHS’s headquarters, a stone’s throw from the United States Capitol. Two hundred and twenty individuals were registered for the meeting. Twenty-seven presenters, including me, were on the agenda. Each one of us was allowed seven minutes to present our comments in response to DHHS’s request, and five minutes to answer questions from the DHHS panel, which included Jerry Menikoff, director of OHRP; Kathy Hudson, deputy director of science, outreach, and policy at NIH; and Robert Temple, deputy director for clinical science at the Center for Drug Evaluation and Research at the FDA. Presenters included parents of children enrolled in SUPPORT, bioethicists, representatives of public advocacy organizations, SUPPORT investigators, neonatologists, and other researchers, and represented the entire spectrum of views on both SUPPORT and the broader issues regarding research on standard of care.

That said, one of the many remarkable aspects of the day was how much common ground there was, even among those who seemed, at the height of the controversy, to be at the starkest of odds with each other. While some, including representatives of Public Citizen and the Alliance for Human Research Protection, continue to argue that SUPPORT was an unethical study to conduct, the majority of presenters agreed that SUPPORT, and studies like it, are worth doing and, more generally, that we collectively should be committed to addressing the alarming fact that much of what is done as a matter of routine clinical care is not supported by good evidence.

There was also surprisingly widespread—though not unanimous—agreement around the idea that respect for persons demands a comprehensive informed consent process, a view that cut across very different conceptions of the level of risk involved in research on standard of care interventions. For one thing, most presenters seemed to agree that the informed consent documents used in SUPPORT were woefully inadequate, precisely because they did not mention what was known at the time of the study about the risks to premature infants of receiving the oxygen levels under study. More generally, many suggested that what is included in consent forms and processes should serve the goal of transparency about precisely what is being asked of subjects and their surrogates, and what it might mean for them—whether or not those elements are “novel” to the research context or not—rather than follow the letter of the law, i.e., regulations that explicitly require only the disclosure of the nature, risks, and benefits of research procedures. Some of the strongest presentations on this topic were those by Peter Vasilenko, from Alion Science and Technology; Lois Shepherd, from the University of Virginia School of Law; and David Forster, from WIRB.

I was particularly pleased to see this consensus emerge, because it is very much in line with PRIM&R’s own recommendations. In our comments, we proposed a framework to guide institutional review boards (IRBs) when they are asked to review research on standard of care. According to our framework, IRBs have a responsibility to make sure that individuals being asked to enroll in studies examining standard of care interventions are adequately informed about all of the following:

• The nature, potential benefits, harms, and burdens of the interventions being compared
• The fact that they’re being asked to participate in research
• That they have a choice, with regards to the specific interventions being studied, between remaining in a therapeutic, doctor-patient relationship, and entering an investigator-subject relationship, in which the physician will not routinely be making personalized clinical decisions about the use of the interventions under study
• That the research may impose particular burdens and potential harms beyond those involved in receiving the interventions solely as ordinary care, and what those specific burdens and risks are

An even more surprising theme regarding informed consent also emerged on Wednesday, namely, that consent may be wholly inadequate in the context of clinical care, given that, in many cases, there is a lack of certainty about which intervention physicians might choose from a set of generally accepted alternatives, and that when there are multiple standards, their profiles of risks and benefits may differ in ways that are of import to patients. It would be hard not to emerge from the day thinking that physicians ought to be talking about alternatives with their patients much more regularly than they currently do—though what sort of policy implications such a conclusion has was, of course, outside the scope of this group’s purview.

While there was a surprising amount of convergence across the perspectives shared last week, there were also, of course, areas of disagreement. I will highlight some areas of contention that arose at the meeting in a second blog post, tomorrow.