Speakers
Stephanie Morain, PhD, MPH
Associate Professor, Berman Institute of Bioethics & Department of Health Policy & Management
Johns Hopkins University
Nancy Kass, ScD
Phoebe Berman Professor of Bioethics & Public Health
Berman Institute of Bioethics & Department of Health Policy & Management
Johns Hopkins University
Ruth Faden, PhD, MPH
Philip Franklin Wagley Professor of Biomedical Ethics
Berman Institute of Bioethics & Department of Health Policy & Management
Johns Hopkins University
Keywords
Comparative Effectiveness Research; Research Ethics; Oversight; Fit for Purpose
Key Points
- There are 2 key problems with the ethical oversight of comparative effectiveness research (CER): insufficient evidence to guide key clinical decisions and challenges with ethical oversight for trials aimed at guiding those decisions.
- The vast majority of clinical decisions are still made in the absence of high-quality evidence. For example, fewer than 10% of current recommendations in cardiology are based on the highest quality evidence; expert opinion, on the other hand, guides over 40% of recommendations.
- There are challenges with ethical oversight in clinical trials, particularly when comparing existing therapies in widespread clinical use. The traditional approach to research ethics holds that research is conceptually different from care, undertaken for the sake of future patients. The oversight system, established in the 1970s, ensure that the risk/benefit ratio was acceptable; that people knew they were taking part in a study, and that it is not equivalent to care; and that people can voluntarily agree (or refuse) to take part.
- But the reality isn’t so tidy: A clinical trial really might be someone’s “best treatment option.” In the meantime, clinical care has wasted billions of dollars delivering care that was unproven, unnecessary, or in error. Ongoing learning in healthcare settings is essential but must have sound ethical oversight.
- Clinical research is not all the same; oversight must be matched (“fit”) to the specifics of the study. Sometimes it does, e.g. for studies of experimental, pre-market products, with high uncertainty. But one-size fits-all oversight can be problematic, e.g. for CER on approved products, and excessive oversight results in a greater-than-appropriate burdens for researchers and collaborating clinicians.
- The team at the Berman Institute proposed a new model to improve the “fit for purpose” of research ethics oversight that might be feasible within current regulatory structures. There were two key considerations: participation’s impact on welfare and on autonomy. Oversight bodies should consider how much additional risk and burden is introduced with participation and studies shouldn’t restrict a decision that would have been available and meaningful to patients.
- To achieve “fit for purpose” oversight, observational studies will require minimal oversight due to minimal increased risk compared to usual care, and no restriction of meaningful choice. Randomized trials will require case-by-case evaluation.
Discussion Themes
The origins of informed consent have their roots in paternalism, in which a physician makes all the judgement calls on behalf of a patient. Yet researchers and clinicians must make judgement calls about which of the many decision points involved in care are worth highlighting; to run through all of them risks losing an emphasis on those that have more serious implications.
The team noted that respect for autonomy (like other ethics commitments) is not absolute. It is bounded by other morally important duties, such as promoting welfare and seeking justice. In the clinical context, it’s also bounded by tradeoffs where patients have other interests.