Informed consent Archives - Rethinking Clinical Trials

August 14, 2025: New Podcast Episode Addresses Keeping Participants Informed in Trials With Waivers of Consent

Posted on August 14, 2025August 14, 2025 by Sophia Ramirez

Dr. Pearl O'Rourke and Dr. Dave Wendler In a new episode of the Rethinking Clinical Trials Podcast, Pearl O’Rourke and Dave Wendler discuss their recent publication, “Disentangling Informing Participants From Obtaining Their Consent.”

Listen and subscribe to the podcast on Spotify, Amazon Music, Apple Podcasts, or SoundCloud.

O’Rourke and Wendler noted that IRBs will often assume nothing needs to be communicated to participants in trials that have a waiver of informed consent. But research and research oversight is poorly understood by the public, an issue compounded by a lack of transparency.

“For any research going forward, it would be information out. Even if you think about just a general notification: ‘We do research at this institution, your information may be used.’ That’s what we do. Why aren’t we telling people that?” O’Rourke said.

In the article, O’Rourke and Wendler outlined 6 goals that the research community can advance by informing participants. These include respect for persons, participant understanding of the research, and trust and trustworthiness.

O’Rourke, now retired, was the director of human research affairs at Partners HealthCare Systems in Boston and an associate professor of pediatrics at Harvard. She currently serves as cochair of the NIH Collaboratory’s Ethics and Regulatory Core. Wendler is the head of the Section on Research Ethics at the NIH Clinical Center.

Grand Rounds June 28, 2024: Using ChatGPT to Facilitate Truly Informed Medical Consent (Fatima N. Mirza, MD, MPH)

Posted on June 30, 2024February 24, 2026 by Sophia Ramirez

Speaker

Fatima N. Mirza, MD, MPH
Chief Resident
Department of Dermatology
Warren Alpert Medical School of Brown University

Keywords

Artificial Intelligence; ChatGPT; Informed Consent

Key Points

Artificial Intelligence (AI), when implemented thoughtfully in clinical settings, can lead to meaningful results for patients.

Medicine has long fallen short of the ideal of informed consent, in part due to the limited readability of informed consent forms; as of 2020, 54% of Americans were estimated to read below the sixth-grade reading level. This has implications for patient understanding and quality of care.

Using ChatGPT-4, the research team took LifeSpan Healthcare System’s (LHS) surgical consent form from a 12.6 Flesch-Kincaid reading level to a 6.7. After hospital leadership reviewed the revised form and the research team had addressed concerns around biases, approvals, and future needs, the revised form was deployed across LHS.

This real-world implementation demonstrated the potential for AI to make meaningful improvements to patient care and communication. As a proof-of-concept, it sparked the interest of other health systems.

To investigate the clinical implications of consent form readability, the research team analyzed 798 federally funded clinical trials providing accessible informed consent forms. A 16% increase in the dropout rate was associated with each additional Flesch-Kincaid grade-level increase in the language.

The observed association between consent form complexity and participant dropout rate could be attributed to misaligned expectations; erosion of trust; participant surprise and dissatisfaction; and reduced engagement. This highlights the importance of clear, accessible communication throughout the entire trial process, not just enrollment.

Improved readability of consent forms is crucial for the design and implementation of clinical trials, potentially leading to more inclusive, efficient, and impactful clinical research.

Discussion Themes

Medical malpractice attorneys were part of the cohort that reviewed the simplified consent forms. They shared that when these cases go to court, a jury will often review the informed consent document. In these cases, it can more protective to have documentation that people can understand.

There is the potential for tailored chatbots that could personalize the consent process for patients, but expert oversight would be crucial. AI models can “hallucinate,” saying something incorrect with absolute certainty. Dr. Mirza indicated that the field isn’t ready for those bespoke consents; centralized documents, as least for the time being, are the way to go.

AI is going to be integrated into our healthcare system. It’s important for clinicians, researchers, and people who really care about patients, as well as the patients themselves, to have a seat at the table discussing these early models.

July 3, 2019: New Article Describes the Public’s Beliefs Regarding Responsibility to Participate in Research

Posted on July 3, 2019July 9, 2025 by Karen Staman

Findings from a new article suggest that the majority of patients do not feel a personal responsibility to participate in clinical research. In the article, Kevin Weinfurt, Li Lin, and Jeremy Sugarman report the results of a national survey of nearly 3000 people regarding their attitudes towards research responsibilities as well as their trust in doctors, healthcare systems, and medical research. Ethical frameworks for learning health systems have suggested that patients have a responsibility to contribute to learning activities, including research. The findings from this survey suggest that most patients in the U.S. do not currently endorse such a responsibility.

“These data provide a useful snapshot of the public’s views toward the obligation to participate in research. It is unclear how, if at all, these views will shift with increased efforts to create mature learning health systems. And if such views do not shift, it is uncertain what that would mean for the success of learning health systems.” —Kevin Weinfurt, PhD

Read the full article: Public Views Regarding the Responsibility of Patients, Clinicians, and Institutions to Participate in Research in the U.S.

For more on alternate approaches to consent, see the Living Textbook Chapter on Consent, Disclosure, and Non-Disclosure

FDA Issues Draft Guidance on Use of Electronic Informed Consent (eIC)

Posted on March 10, 2015September 8, 2017 by Gina Uhlenbrauck

On March 9, 2015, the U.S. Food and Drug Administration (FDA) issued draft guidance on the Use of Electronic Informed Consent in Clinical Investigations (document opens as a PDF). In a question-and-answer format, the guidance provides recommendations for investigators, sponsors, and institutional review boards (IRBs) on the use of electronic media and processes to obtain informed consent for FDA-regulated clinical investigations of medical products, including human drug and biological products, and medical devices, and combinations thereof.

Electronic informed consent, or eIC, refers to the use of electronic systems and processes to convey information related to the study and to obtain and document informed consent. Electronic media formats may include text, graphics, audio, video, podcasts, and interactive websites, biological recognition devices, and card readers. Use of electronic systems may allow for rapid notification to study participants of any amendments pertaining to the informed consent, promote timely entry of eIC data into the study database, and allow for timely collection of the informed consent data from remote locations.

The guidance provides answers to these questions:

How should the information in the eIC be presented to the subject?
How and where may the eIC process be conducted?
How and when should questions from subjects be answered?
What steps may be taken to facilitate the subject’s understanding of the information being presented?
What steps may be taken to ensure that new or additional information is conveyed to the subject during the course of the clinical investigation?
Does FDA allow the use of electronic signatures to document eIC?
What special considerations should be given to the use of eIC for pediatric studies?
Should subjects receive a copy of their eIC and have easy access to the material and information presented to them in their eIC?
What steps can be taken to help ensure confidentiality of the information once eIC is obtained?
Can HIPAA authorizations for research, which are frequently combined with informed consent documents, be obtained electronically?
What are the IRB’s responsibilities in the eIC process?
What eIC documentation does FDA require for submission with applications?
What steps can be taken to ensure the system archives the documents appropriately?
What materials or documents will FDA require during an inspection?

The comment period ends May 7, 2015. Users can submit electronic comments using the docket number HHS-OPHS-2015-0002 at the Federal eRulemaking Portal: http://www.regulations.gov.

Report from NIH Collaboratory Workshop Examines Ethical and Regulatory Challenges for Pragmatic Cluster Randomized Trials

Posted on March 4, 2015July 9, 2025 by Gina Uhlenbrauck

A new article by researchers from the NIH Collaboratory, published online this week in the journal Clinical Trials, explores some of the challenges facing physicians, scientists, and patient groups who are working to develop innovative methods for performing clinical trials. In the article, authors Monique Anderson, MD, Robert Califf, MD, and Jeremy Sugarman, MD, MPH, MA, describe and summarize discussions from a Collaboratory workshop on ethical and regulatory issues relating to pragmatic cluster-randomized trials.

Pragmatic Cluster-Randomized Trials

Many of the clinical trials that evaluate the safety and effectiveness of new therapies do so by assigning individual volunteers to receive either an experimental treatment or a comparator, such as an existing alternative treatment, or a placebo. However, this process can be complex, expensive, and slow to yield results. Further, because these studies often take place in specialized research settings and involve patients who have been carefully screened, there are concerns that the results gathered from such trials may not be fully applicable to “real-world” patient populations.

For these reasons, some researchers, patients, and patient advocacy groups are interested in exploring different methods for conducting clinical trials, including designs known as pragmatic cluster-randomized trials, or CRTs. In a pragmatic CRT, groups of individuals (such as a clinic, hospital, or even an entire health system) are randomly assigned to receive one of two or more interventions being compared, with a focus on answering questions about therapies in the setting of actual clinical practice—the “pragmatic” part of “pragmatic CRT.”

Pragmatic CRTs have the potential to answer important questions quickly and less expensively, especially in an era in which patient data can be accessed directly from electronic health records. Just as importantly, that knowledge can then be fed back to support a “learning healthcare system” that is constantly improving in its approach to patient care. However, while cluster-randomized trials are not themselves new, their widespread use in patient-care settings raises a number of potential challenges.

For example: in a typical individually randomized clinical trial, patients are enrolled in a study only after first providing written informed consent. However, in a CRT, the entire hospital may be assigned to provide a given therapy. In such a situation, how should informed consent be handled? How should patients be notified that research is taking place, and that they may be part of it? Will they be able to “opt out” of the research? What will happen to the data collected during their treatment? And what do federal regulations governing clinical trials have to say about this? These are just a few of the questions raised by the use of pragmatic CRTs in patient-care settings.

The NIH Collaboratory Workshop on Pragmatic Cluster-Randomized Trials

The NIH Collaboratory Workshop of Pragmatic CRTs, held in Bethesda, Maryland in July of 2103, convened a panel of experts in clinical trials, research ethics, and regulatory issues to outline the challenges associated with conducting pragmatic CRTs and to explore ways for better understanding and overcoming them. Over the course of the intensive 1-day workshop, conference participants identified key areas for focused attention. These included issues relating to informed consent, patient privacy, oversight of research activities, insuring the integrity of data gathered during pragmatic CRTs, and special protections for vulnerable patient populations. The article by Anderson and colleagues provides a distillation of discussions that took place at the workshop, as well as noting possible directions for further work.

In the coming months and years, the NIH Collaboratory and its partners, including the National Patient-Centered Clinical Research Network (PCORnet), plan to build on this workshop experience. Together, they hope to explore these issues in greater detail and propose practical steps for moving forward with innovative clinical research methods, while at the same time maintaining robust protections for patients’ rights and well-being.

Jonathan McCall, MS, and Karen Staman, MS, contributed to this post.

Read the full text of the article here:

Anderson ML, Califf RM, Sugarman J. Ethical and regulatory issues of pragmatic cluster randomized trials in contemporary health systems. Clin Trials 2015 [e-Pub ahead of press].
doi:10.1177/1740774515571140

For further reading:

Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: Increasing the value of clinical research decision making in clinical and health policy. JAMA 2003;290(12):1624-32. PMID:14506122; doi:10.1001/jama.290.12.1624.

The Ottawa Hospital Research Institute Ethical Issues in Cluster Randomized Trials Wiki.

Special Report: Ethical Oversight of Learning Health Systems. Hastings Center Report 2013;43(s1):S2–S44, Si–Sii.

Sugarman J, Califf RM. Ethics and regulatory complexities for pragmatic clinical trials. JAMA 2014;311(23):2381-2. PMID: 24810723; doi: 10.1001/jama.2014.4164.