Ethical issues in pragmatic randomized controlled trials: a review of the recent literature identifies gaps in ethical argumentation

Abstract

BackgroundPragmatic randomized controlled trials (RCTs) are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature.MethodsWe conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using content analysis.ResultsOur review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low.ConclusionThe current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question the need for informed consent. But the function of oversight should be understood broadly as protecting the liberty and welfare interest of participants and promoting public trust in research. This understanding, we suggest, will focus discussion on questions about appropriate ethical review for pragmatic RCTs.

The ethical challenges raised in the design and conduct of pragmatic trials: an interview study with key stakeholders

“…In the present study we interviewed a range of stakeholders to explore their perspectives on ethical issues raised by pragmatic RCTs. The substantive areas of discussion were highly consistent with topics in the clinical trials literature, including risk [32–34], consent [35, 36], the governance of research activities [24, 37, 38], the selection of study participants [39], the roles and responsibilities of different stakeholders [40–42], and the publication and reporting transparency of trials [43–46], but also indicated that the available literature on ethics in pragmatic RCTs is relatively narrow in its focus. Our findings suggest that not only do we need to discuss familiar topics (such as appropriate consent approaches and participant protections) in new ways, but also that there are new questions (such as the different roles and responsibilities of a broader range of stakeholders in pragmatic RCTs) that need to be addressed.…”

Physicians’ Recognition and Management of Kidney Disease: A Randomized Vignette Study Evaluating the Impact of the KDIGO 2012 CKD Classification System

“…However, a traditional randomized clinical trial is not feasible for the questions posed here and may be considered by some to be unethical. 20 , 39 , 40 Furthermore, physicians can change their behavior when directly observed or evaluated, whereas the vignette design creates a distance and is considered the most effective design for minimizing such effects. 20 …”

Lost in translation: the valley of death across preclinical and clinical divide – identification of problems and overcoming obstacles

“…These studies are often cannot be performed because funds required to conduct these studies exceed the resources available to the researchers. One approach to overcome this problem may be by designing more streamlined randomized trials [106,107] however, even for such trials, the cost may still be an issue. One approach to address this issue may be the participation of the pharmaceutical industry by contributing more funds towards these trials.…”