A new article from the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core offers a comprehensive scoping review of published empirical ethics research related to pragmatic clinical trials. These trials, which are designed to assess evidence-based interventions in real-world settings, present a variety of unique ethical and regulatory challenges.
The article was published online ahead of print in Learning Health Systems.
The review analyzed 82 published studies of ethics issues that have been explored in the context of pragmatic clinical trials. The authors, led by Kayla Mehl at Johns Hopkins University, identified 22 distinct ethical themes, with the 5 most prevalent being consent and disclosure, risk assessment, trust and transparency, operational burdens and implementation barriers, and the role of engagement.
- Consent and disclosure: Traditional written informed consent is often impractical in pragmatic trials, prompting the exploration of alternative approaches such as opt-out or general notification.
- Risk assessment: Pragmatic trials present challenges in risk assessment, particularly regarding how “minimal risk” is defined and communicated, which complicates regulatory determinations and participant protections.
- Trust and transparency: Trust-building practices, such as results sharing and transparent data use disclosures, are essential for fostering participant confidence.
- Burdens, barriers, and costs: Institutions, investigators, and research teams face a variety of operational and logistical burdens in pragmatic trials, especially when integrating interventions into routine care and navigating ethics concerns around data governance and data sharing.
- Engagement: Engagement practices in pragmatic trials have been limited and inconsistent, highlighting “a persistent gap between the ideal of inclusive, sustained collaboration and the realities of constrained resources, power dynamics, and unclear stakeholder roles.”
The authors point out that most empirical ethics research related to pragmatic trials has been concentrated in the United States and other Western countries and is heavily reliant on surveys and hypothetical scenarios. This limits the generalizability and real-world applicability of current findings. The authors advocate for future research that is geographically inclusive and that employs innovative methodologies, including nested empirical studies within ongoing pragmatic trials, to provide richer, context-sensitive insights.
Mehl completed a postdoctoral fellowship in the ethics and regulatory aspects of pragmatic clinical trials at the Berman Institute for Bioethics at Johns Hopkins University. Coauthor Stephanie Morain is a core faculty member at the Berman Institute and an associate professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health. Coauthor Jeremy Sugarman is the Harvey M. Meyerhoff Professor of Bioethics and Medicine, professor of medicine, and professor of health policy and management at Johns Hopkins and the deputy director for medicine of the Berman Institute.
Morain and Sugarman are cochairs of the NIH Collaboratory’s Ethics and Regulatory Core.
When research and clinical care are deliberately integrated in an embedded pragmatic clinical trial, the nature and extent of investigators’ obligations to patient-subjects are blurred, as is the clinician’s duty to participate is such research. To address these questions, the American Journal of Bioethics (AJOB) recently published commentaries on 2 target articles in a special issue on pragmatic clinical trials. Both of the target articles for the special issue are from the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core.
Respect for persons is a central obligation for the ethical conduct of research with human subjects. Traditionally, clinical trials have primarily relied on informed consent practices to fulfill this ethical obligation.
Based on your experience working with the NIH Collaboratory Trials, what are some of the common challenges of the Core?
In this Friday’s PCT Grand Rounds, Dr. Jeremy Sugarman, Dr. Stephanie Morain, and Juli Bollinger of Johns Hopkins University and Dr. Kevin Weinfurt of Duke University will present