Clinical Researcher—April 2024 (Volume 38, Issue 2)
RESOURCES & REVIEWS
Lindsay McNair, MD, MPH, MSB
[A review of Challenging Cases in Clinical Research Ethics. 2024. Wilfond BS, Johnson L-M, Duenas DM, Taylor HA (editors). CRC Press (Boca Raton, Fla.)]
Challenging Cases in Clinical Research Ethics may not be a book you take to the beach for a light read, but if you have a role, or an interest, in how we analyze the complex ethical challenges that are an integral part of conducting clinical research, it may be a good book for you. This is a reference book, a teaching tool, and, in some ways, a historical record.
While healthcare institutions have long had ethics committees or even trained clinical ethicists to provide consultation to staff and families during difficult situations in clinical care settings, the specialized practice of clinical research ethics consultation is much more recent. As described in the foreward of the book, the development of this kind of resource was spurred by the National Institutes of Health’s (NIH’s) Clinical and Translational Science Awards (CTSA) program, a funding mechanism which supports a network of almost 60 medical institutions across the United States to facilitate collaboration that expedites the design and dissemination of new medical advances. Since a requirement of the funding program is that the institutions must have ethical support services, the CTSA-funded institutions created ethics consultation services that focused on the research ethics issues likely to arise from the CTSA-funded work.
In 2014, the leaders of the clinical research consultation services across the organizations formed a group to share information and best practices, called the Clinical Research Ethics Consultation Collaborative (CRECC). The CRECC continues to be an active group, and membership is open to anyone who is in a role related to clinical research ethics practice, including representatives not just from the CTSA-funded institutions, but also from biopharmaceutical companies and independent contributors.
This book arose from the work of the CRECC. The cases discussed in the book are real situations at research institutions across the U.S. for which the persons involved sought advice from their local consultation services, and the consultants brought the case to CRECC for discussion. The editors make a point of saying that by the time of the finished case discussion, each case involved 30 to 50 consultants, and they recognize almost 170 contributors to the book, including most of the best-known and most well-respected research bioethicists.
Each year, the American Journal of Bioethics has published up to four of these case presentations, along with two to four commentaries on the case from different ethicists to provide a variety of approaches, perspectives, and opinions. These cases and the accompanying commentaries comprise this book.
The editors have organized the book around the ethical principles for research ethics that were described in a seminar paper by Emanuel, Wendler, and Grady in 2000,{1} resulting in five main sections focused on collaborative partnerships, respect for participants, fair participant selection, favorable risk-benefit ratio, and informed consent. Because they also recognize that there were many possible ways to organize the material and that someone looking for discussion of a specific topic may want to be able to search in more detail, the book includes three separate appendices; one that lists cases by primary and secondary ethical principles involved, one that lists cases by topic keywords (e.g., pediatrics, Phase I trials, social media), and one that lists cases by values relevant to the discussion (social value, equity, and trustworthiness), as well as a standard index which lists topics, people, policies, and keywords and the pages on which the terms appear or are discussed.
In each section, an editor presents a brief description of the unifying theme of that section, and then short summaries of each of the five to eight cases under that theme. The section then delves into each case in more detail with an introduction that includes any necessary background context (disease details, standard of care framing, existing policy), a case description (often just a page or two), references, and then one to four commentaries.
The commentaries, each by different authors, approach different considerations or aspects of the case, together providing a variety of opinions and a well-rounded discussion. For example, there is a case focused on a request from a study team to unblind a participant’s treatment assignment after an adverse event (to help determine relationship to study drug and whether other participants were also at risk, or whether the event was a symptom of the underlying condition). The commentaries are presented by two ethicists from a sponsor company discussing the ethical issues of unblinding and the impact on study data; an ethicist from the NIH discussing considerations of a data monitoring committee in making decisions that will impact studies; and an ethicist involved in health monitoring programs for chronic illness who discusses issues of community trust and communication. The editors and commentators are careful to focus on the relevant ethical issues and conflicts, and not on operational or regulatory requirements, although they do address those considerations.
Although the cases all stem from situations that developed at research institutions, almost all of the content is relevant to other audiences in the clinical research ecosystem, including situations encountered in biopharmaceutical-sponsored studies that industry leaders have to think about. For example, there are cases that discuss ethical implications of advertising for research participants on social media, whether compensation for participation can (or should) be withheld from a participant who was intentionally deceptive to get enrolled in the study, how extensive the “alternative options” presented in a consent form should be, and whether a patient with advanced cancer must exhaust all possible treatment options before being allowed to enroll in a Phase I study of a new immunotherapy.
There are a number of ways that teachers, trainers, and leaders could use the content of this book both for education, and as the basis for case-based discussions. Overall, I would recommend this book as a resource for anyone in a training or leadership role, both for personal education and as a useful tool for developing training content that will likely prompt thoughtful discussion.
Reference
- Emanuel EJ, Wendler D, Grady C. 2000. What makes clinical research ethical? JAMA 283(20):2701–11. doi:10.1001/jama.283.20.2701. PMID:10819955.
Lindsay McNair, MD, MPH, MSB, is a physician, research ethicist, and Founder and Principal Consultant of Equipoise Consulting LLC, which provides consulting for projects related to the scientific and ethical conduct of research studies and drug development programs. She joined the Clinical Research Ethics Collaboration Collective, from which the authors of the reviewed book drew their case discussions, in 2023, when the book was already in the process of publication.
