Adrift in the gray zone: IRB perspectives on research in the learning health system

Abstract

Background Human subjects protection in healthcare contexts rests on the premise that a principled boundary distinguishes clinical research and clinical practice. However, growing use of evidence-based clinical practices by health systems makes it increasingly difficult to disentangle research from a wide range of clinical activities that are sometimes called “research on medical practice” (ROMP), including quality improvement activities and comparative effectiveness research. The recent growth of ROMP activities has created an ethical and regulatory gray zone with significant implications for the oversight of human subjects research. Methods We conducted six semi-structured, open-ended focus group discussions with IRB members to understand their experiences and perspectives on ethical oversight of ROMP, including randomization of patients to standard treatments. Results Our study revealed that IRB members are unclear or divided on the central questions at stake in the current policy debate over ethical oversight of ROMP: IRB members struggle to make a clear distinction between clinical research and medical practice improvement, lack consensus on when ROMP requires IRB review and oversight, and are uncertain about what constitutes incremental risk when patients are randomized to different treatments, any of which may be offered in usual care. They characterized the central challenge as a balancing act, between, on the one hand, making information fully transparent to patients and providing adequate oversight, and on the other hand, avoiding a chilling effect on the research process or harming the physician-patient relationship. Conclusions Evidence-based guidance that supports IRB members in providing adequate and effective oversight of ROMP without impeding the research process or harming the physician-patient relationship is necessary to realize the full benefits of the learning health system.

Stakeholder perspectives regarding alternate approaches to informed consent for comparative effectiveness research

“…These findings are consistent with those of Kraft et al, who found that, while patients generally had similar consent preferences for both observational and randomized studies, IRB professionals distinguished between different study designs when expressing preferences regarding approaches for disclosure/consent . One explanation for this difference, suggested by prior qualitative work, is that IRB professionals may view observational research as less risky than randomized trials . Qualitative comments from our participants support this hypothesis.…”

“…16 One explanation for this difference, suggested by prior qualitative work, is that IRB professionals may view observational research as less risky than randomized trials. 24 Qualitative comments from our participants support this hypothesis. Our qualitative data also suggest greater sophistication concerning research methodologies among diverse stakeholders than among patients or the general public, as well as potentially greater appreciation of other ways that randomization affects decisions about the course of treatment and patient valuesdistinctions which may have influenced their preferences regarding disclosure/consent approaches.…”

Informed consent within a learning health system: A scoping review

“…Indeed, different learning activities might imply different clinical benefits and risks for the participant and operate under different modalities . For example, Lee et al note that retrospective research, contrarily to prospective randomization of approved medical practices, “does not invol[ve] deviating from the care that patients would normally receive.”…”

A comparison of institutional review board professionals’ and patients’ views on consent for research on medical practices

“…10-11 In the absence of clear guidelines, IRB professionals have expressed uncertainty about where ROMP should fit within the existing regulatory scheme. 12 …”