How Much Risk is Too Much? Revisiting the Ethics of Control Arms  - The Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard

Topic: How Much Risk is Too Much? Revisiting the Ethics of Control Arms

Abstract: Rigorous evaluation of investigational therapies often requires the presence of a control group that will not receive the therapy under evaluation. In active-controlled studies, people in the control arm receive a currently available treatment, but in some cases, they receive a placebo from which they are not likely to benefit. Furthermore, clinical research for certain conditions, such as rare neurological or genetic disorders, places increasing demands on all participants, including those in the control arm, for invasive and burdensome procedures. For example, in studies where a drug is delivered intrathecally to participants in an active arm over multiple cycles, participants in the control arm may also be asked to undergo serial lumbar puncture and placebo injections directly into the spinal canal, to maintain the blind or provide a baseline for safety and/or biomarker assessments. 

How much risk and burden is too much to ask individuals in these studies to accept— particularly those in control arms who will receive a placebo or otherwise fail to benefit? How should we think about the difference, if any, between active and placebo control arms on this issue? If intrusive elements of designs are truly indispensable to the research, should the IRB and research ethics community be willing to adjust their tolerance for risk? Are there practical mitigation strategies that can help? Do studies that include vulnerable populations, such as children and those unable to consent for themselves, demand heightened concern or a different analysis? Who decides what level of risk is acceptable? And what role, if any, should the perspectives of patient communities play in helping to set those limits? The December BC will aim to address these and related topics. 

---

This meeting is open to sponsors of the Bioethics Collaborative. For more information about the Bioethics Collaborative and how to become a sponsor, click here.