Ethics and Regulatory

Ethics and Regulatory

Co-Chairs: Judith Carrithers, Jeremy Sugarman

NIH Representative: David Wendler

Other Members: Benjamin Wilfond

Co-PI Representative: Kevin Weinfurt

PRISM Collaborators: Joe Ali, John Lantos, David Magnus, Stephanie Morain, Pearl O’Rourke, Kayte Spector-Bagdady,

Working Group Members: Andy Avins, Jenn Boggs, Sheana Bull, Diane Christiansen, Gregory Clarke, Leslie Crofford, Laura Dember, Dixie Ecklund, Janel Fedler, Susan Gaylord, Corita Grudzen, Margaret Kuklinski, Julie Lima, Natalia Morone, Tina Neill-Hudson, Michael Paasche-Orlow, Mehul Patel, Michelle Roberts, Marguerite Robinson, Stacy Sterling, Venky Sudaram, Jon Tilburt, Miguel Vazquez, Doug Zatzick

Project Manager: Tammy Reece


Products and Publications | Presentations

The advent of pragmatic clinical trials that leverage electronic health records and use research methods such as cluster randomization promises to answer critical research questions with increased sample sizes at lower costs, and could greatly increase production of the evidence needed to improve healthcare. This research, which relies on data collected as part of routine clinical care and may evaluate similar treatments in comparative effectiveness studies, poses a unique set of regulatory and ethical challenges. The Ethics and Regulatory Core identifies areas of regulatory and ethical uncertainty and works with the Demonstration Projects to navigate regulatory and ethical complexities associated with pragmatic clinical trials conducted within healthcare systems.

The Core is developing policies and practices to provide a framework for the conduct of pragmatic clinical trials in an ethical manner and in compliance with federal and state regulations. Its activities supporting this work include the following:

Demonstration Project Ethics/Regulatory Discussions: Minutes and Supplementary Materials

The Core facilitated a series of discussions on ethical and regulatory issues relevant to the Demonstration Projects. These discussions, which took place as teleconferences, included representation from study principal investigators and study teams, members of the Collaboratory's Ethics and Regulatory Core, NIH staff, and Collaboratory Coordinating Center personnel, with additional input provided by representatives from the Office for Human Research Protections.

Areas of Focus

The Core convened groups of stakeholders to produce academic articles on a set of 11 ethical and regulatory issues related to the conduct of pragmatic clinical trials. The papers review the issues, and where possible, identify best practices and provide guidance for future pragmatic clinical trials. The following topics are addressed:


Kevin Weinfurt, PhD, Duke Clinical Research Institute, and Jeremy Sugarman, MD, MPH, MA, Johns Hopkins Berman Institute of Bioethics, discuss a study comparing alternative approaches to notification and authorization of participants in pragmatic trials evaluating common medical practices.


11/20/2017: Reflections on the First 5 Years of the Ethics and Regulatory Core

9/12/2014: Drs. Rob Califf and Jeremy Sugarman Discuss Regulatory and Ethical Issues around NIH Collaboratory Projects

10/23/2012: Dr. Jeremy Sugarman Discusses Ethical Issues and the Collaboratory

Additional Resources

Mentz RJ, et al. Circulation 2016

Country-Specific Regulatory Information for Clinical Trials


2/3/2017: Grand Rounds Presentation: A Tentative Introduction to the Revised Common Rule for the Protection of Human Subjects (Audio; Slides)

12/16/2016: Grand Rounds Presentation: Comparison of Different Approaches for Notification and Authorization in Pragmatic Clinical Research Evaluating Commonly Used Medical Practices (Video; Slides)

10/16/2015: Grand Rounds Presentation: Data Monitoring Committees for Pragmatic Clinical Trials (Video; Slides)

Grand Rounds Special Series: Ethics and Regulatory Issues in Pragmatic Clinical Trials

9/25/2015: Grand Rounds Presentation: Ethical and Regulatory Issues in Pragmatic Clinical Trials: Introducing a Special Series in Clinical Trials (Slides)

2/13/2015: Grand Rounds Presentation: Data and Safety Monitoring in Pragmatic Trials (Video; Slides)

8/20/2014: Overview of Ethics and Regulatory Issues Presentation at Steering Committee Meeting

8/19/2014: Regulatory/Ethics Core Presentation at Steering Committee Meeting

7/18/2014: Grand Rounds Presentation: The Ethics and Regulatory Landscape: Is a Massive Public Campaign Needed?(Video; Slides)

4/25/2014: Grand Rounds Presentation: CTTI Advancing the Use of Central IRBs Project: Academic Institution and Government Sponsor Perspectives (Video; Slides)

10/25/2013: Grand Rounds Presentation: Synchronizing Operations, Ethics, and Regulatory Oversight, or Reducing Death and Disability Caused by Knowledge Deficits (Ignorance) (Video; Slides)

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Core Working Groups: Ethics and Regulatory. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials. Bethesda, MD: NIH Health Care Systems Research Collaboratory. Available at: Updated March 30, 2020.