Pearl O’Rourke

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

Posted on by Sophia Ramirez

Dr. Pearl O'Rourke and Dr. Dave WendlerIn 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.

Podcast August 12, 2025: Disentangling Informing Participants From Obtaining Their Consent (Pearl O’Rourke, MD; David Wendler, MA, PhD)

Posted on by Sophia Ramirez

In this episode of the NIH Collaboratory podcast, Drs. Pearl O’Rourke and David Wendler discuss their recent publication, “Disentangling Informing Participants From Obtaining Their Consent.”

Read the transcript. For alerts about new episodes, subscribe for free on Spotify, Amazon Music, Apple Podcasts, or SoundCloud.

December 3, 2024: Sharing Results With Research Participants Raises Special Considerations in Pragmatic Trials

Posted on by Damon Seils

Cover image of the journal Clinical TrialsIn a new report from the NIH Pragmatic Trials Collaboratory, a team of bioethicists explores the ethical obligation to share aggregate results from pragmatic clinical trials with research participants. They conclude with recommendations for how to meet this obligation.

The article was published online ahead of print in Clinical Trials.

There is growing appreciation of the importance of sharing aggregate results of clinical trials with research participants. However, this practice has not been examined in the context of pragmatic clinical trials, which have special features that may complicate the ethics and logistics of sharing aggregate results.

The report’s authors summarize the ethical arguments for sharing aggregate results and describe the features of pragmatic trials that may raise logistical and other barriers to disclosure. They also discuss the important role healthcare system partners play in sharing results from pragmatic trials.

The authors offer the following recommendations:

  • Sharing aggregate results with research participants should be the default, and decisions not to share should be justified
  • Planning for sharing aggregate results should begin early in the planning of the trial
  • The healthcare care systems in which the trial is embedded should be key partners in decisions about what and how to share
  • Proactive sharing of results from a pragmatic trial that was conducted under a waiver or alteration of consent, including an explanation for why consent was not obtained in the study, can promote trust in the investigators and their healthcare system partners

Read the full report.

The article was coauthored by members of the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core, including Stephanie Morain, Abigail Brickler, Joseph Ali, Caleigh Propes, and Kayla Mehl of Johns Hopkins University; Pearl O’Rourke, formerly of Partners HealthCare; Kayte Spector-Bagdady of the University of Michigan; Benjamin Wilfond of the Seattle Children’s Hospital; Vasiliki Rahimzadeh of the Baylor College of Medicine; and David Wendler of the NIH Clinical Center.

August 19, 2024: Ethics Core and Biostatistics Core Guide Newest Trials Through Planning Phase

Posted on by Damon Seils

Leaders of 2 of the NIH Pragmatic Trials Collaboratory’s long-standing Core Working Groups recently shared updates from their work with the newest cohort of NIH Collaboratory Trials. We spoke with them during the NIH Collaboratory’s 2024 Annual Steering Committee Meeting in May.

Over the last year, the Ethics and Regulatory Core engaged in a formal onboarding process with the program’s 9 newest pragmatic trials, consulting with the investigators about their trial planning and implementation. Cochairs Stephanie Morain and Pearl O’Rourke summarized several of the ongoing and emerging challenges.

“One of the challenges we’re continuing to see is understanding what are the appropriate duties that institutions and investigators have in the context of a [pragmatic clinical trial],” said Morain. “One concrete area is in data and safety monitoring. What kinds of issues need to be monitored as adverse events? How do we think about them as being related to the trial vs relating to the background care?” she added.

Onboarding documentation from the Ethics and Regulatory Core’s consultations with the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

We also spoke with Liz Turner and Patrick Heagerty, cochairs of the Biostatistics and Study Design Core. They have spent the past year advising the NIH Collaboratory Trial investigators on key study design challenges.

“Many of these studies have individually randomized patients but then they’re studying implementation pathways when they implement through a specific person that puts them in groups—these are individually randomized group treatment trials,” said Heagerty. “Several of the studies didn’t see that, and so we helped them see it and we helped them work through how to adapt their analysis and modify their sample size work to ensure the trial was properly sized,” he explained.

In addition to consultations with the NIH Collaboratory Trials, the Biostatistics and Study Design Core continues to develop and innovate pragmatic trials methodology.

Learn more about the Core Working Groups.

July 23, 2024: Article From Ethics and Regulatory Core Highlights Key Challenges for Pragmatic Trials

Posted on by Damon Seils

Headshots of Caleigh Propes, Stephanie Morain, and Pearl O'RourkeIn an invited commentary published this month in Circulation: Cardiovascular Quality and Outcomes, authors from the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core describe the recurring and emerging ethical issues in pragmatic clinical trials.

Coauthors Caleigh Propes, Stephanie Morain, and Pearl O’Rourke discuss 3 key challenges facing pragmatic trials researchers:

  • waivers and alterations of informed consent and their implications for transparency
  • managing and responding to “collateral findings” in pragmatic trials
  • representativeness of study populations, and the risk of reinforcing existing inequalities in healthcare delivery systems

Read the full article.

Each of the 3 challenges has taken on increasing importance for the NIH Collaboratory’s Ethics and Regulatory Core. For example, the group completed a 2-year multimethod investigation of collateral findings in pragmatic trials, identifying the core themes and proposing directions for future research.

Propes is a doctoral student in bioethics and health policy, and Morain is an associate professor of health policy and management and a core faculty member of the Berman Institute of Bioethics—both at Johns Hopkins University. O’Rourke is a retired bioethicist who served as the director of human research affairs at Partners HealthCare Systems in Boston and as an associate professor of pediatrics at Harvard Medical School.

Learn more about the Ethics and Regulatory Core.

July 11, 2024: PCORI Leader Discusses Challenges of Conducting Pragmatic A vs B Clinical Trials of Approved Drugs

Posted on by Damon Seils

In an interview during the NIH Pragmatic Trials Collaboratory’s 2024 Annual Steering Committee Meeting, Tracy Wang of the Patient-Centered Outcomes Research Institute (PCORI) discussed challenges of conducting A vs B pragmatic clinical trials of approved drugs in routine clinical practice. Wang joined Adrian Hernandez, co–principal investigator of the NIH Collaboratory Coordinating Center, and Pearl O’Rourke, cochair of the program’s Ethics and Regulatory Core.

“There are a couple of key challenges, the first of which is, who’s going to pay for the drug, especially if the [drugs being compared] have differential drug costs,” Wang said. “The other aspect is, how do we preserve the rigor of that comparison, [such as] the need for blinding, which is not as pragmatic in routine practice,” she said.

Most pragmatic trials, including the NIH Collaboratory Trials and those conducted through the National Patient-Centered Clinical Research Network (PCORnet), compare standard care with proposed improvements to standard care, or “A vs A-plus trials.” Trials that compare 2 alternative treatments that are in current use, or A vs B trials, are rare.

The problem of A vs B pragmatic trials was the subject of an NIH Collaboratory workshop, as well as an article from the Coordinating Center in the New England Journal of Medicine.

Wang, a cardiologist and clinical researcher, is PCORI’s chief officer for comparative clinical effectiveness research. Hernandez is a professor of medicine and the vice dean and executive director of the Duke Clinical Research Institute in the Duke University School of Medicine. Prior to her retirement, O’Rourke was the director of human research affairs at Partners HealthCare Systems in Boston and an associate professor of pediatrics at Harvard Medical School.

Access the complete meeting materials from the 2024 Annual Steering Committee Meeting.

February 8, 2023: Goals of Informing and Consenting, This Friday in the Ethics and Regulatory Grand Rounds Series

Posted on by Damon Seils

Headshots of Pearl O'Rourke, Dave Wendler, Miguel Vazquez, and Michael HoThis Friday’s PCT Grand Rounds will feature the next installment of our special series, Ethical & Regulatory Dimensions of Pragmatic Clinical Trials. Pearl O’Rourke, Dave Wendler, Miguel Vazquez, and Michael Ho will present “Informing and Consenting: What Are the Goals?”

The Grand Rounds session will be held on Friday, February 10, 2023, at 1:00 pm eastern.

O’Rourke is the director of human research affairs at Partners HealthCare Systems in Boston and an associate professor of pediatrics at Harvard. She serves as cochair of the NIH Collaboratory’s Ethics and Regulatory Core. Wendler is the head of the Section on Research Ethics in the NIH Clinical Center and a member of the Ethics and Regulatory Core. Vazquez is a professor of internal medicine at UT Southwestern Medical Center and the principal investigator of the ICD-Pieces NIH Collaboratory Trial. Ho is a professor medicine at the University of Colorado and the principal investigator of the Nudge NIH Collaboratory Trial.

Join the online meeting.

This special Grand Rounds series features moderated webinar discussions with panels of experts. The sessions focus on a range of topics, including the ethics of data sharing; ethical and regulatory considerations in the design and conduct of pragmatic trials; pragmatic research involving patients with dementia; and the use of waivers and alterations of consent.

Read the full program.

June 23, 2022: Ethics and Regulatory Core Aims for Better Design and Improved Implementation

Posted on by Damon Seils

In an interview at the NIH Pragmatic Trials Collaboratory's annual Steering Committee meeting and 10th anniversary celebration, we asked Drs. Jeremy Sugarman and Pearl O'Rourke to discuss the role of the Ethics and Regulatory Core in helping the NIH Collaboratory Trial teams plan and implement their pragmatic trials, and the contributions the Core has made to the literature on ethics and regulatory challenges in pragmatic clinical research.

Headshot of Dr. Jeremy SugarmanBased on your experience working with the NIH Collaboratory Trials, what are some of the common challenges of the Core?

A common challenge the NIH Collaboratory Trial investigators face is determining their study’s level of risk, specifically whether the research is determined to be “minimal risk.” This issue is important, because it influences the permissibility of using alternatives to conventional written informed consent, such as waiving consent or waiving the requirement to document consent.

A recent focus of the Ethics and Regulatory Core is the challenge some studies face with “collateral findings.” These are findings, whether discovered intentionally or unintentionally, that don’t address the trial’s research questions, but may have implications for the health of patients in the trial. For example, when collecting data from electronic health records, researchers might detect the possible use of contraindicated medications in some patients. We recently completed a multimethod investigation of the ethical and regulatory implications of collateral findings in pragmatic clinical trials.

The Core has also offered advice and guidance on several other issues, including innovative study designs such as cluster randomization and stepped-wedge designs, data and privacy issues, collaborating and communicating with healthcare system representatives and clinicians, and challenges related to conducting research at multiple sites.

Headshot of Dr. Pearl O'Rourke

What strategies have NIH Collaboratory Trials used to overcome these barriers?

The Ethics and Regulatory Core hosts an initial consultation with each NIH Collaboratory Trial in the planning phase, and then a follow-up consultation when the project transitions to the implementation phase. We also invite the study teams to consult with us to help address any ethical challenges they’re facing. Sometimes these consultations result in changes in study design, partnerships with the Core to nest empirical ethics studies within the NIH Collaboratory Trials, and other approaches.

How are the NIH Collaboratory Trials’ experiences with the Core helping the field of pragmatic research?

The Core’s work with the NIH Collaboratory Trials has created a body of knowledge and guidance that we have made available to help those engaged in pragmatic research. In addition to a series of published articles in the peer-reviewed literature, we have included some related content in the Living Textbook of Pragmatic Clinical Trials.

Can you describe the impact the Core has had on pragmatic trials over the past decade?

The Core’s consultations during the development stage of these trials has improved investigators’ understanding, appreciation, and planning for the relevant ethical and regulatory issues. The result has hopefully been better research design and improved implementation. Likewise, routine conference calls with active studies have provided opportunities for investigators to hear about the challenges encountered and the solutions developed by other study teams. Sharing these experiences has been invaluable.

The Core is available for ad hoc consultation regarding the ethical and regulatory issues facing any of the projects. Such issue-specific consultations hopefully help study teams develop appropriate solutions.

Finally, Core members have generated a substantial amount of empirical and conceptual scholarship related to the ethical and regulatory issues encountered in the NIH Collaboratory. This work is helping to expand understanding of pragmatic clinical research for the broader research community.

What do you think the Core can contribute over the next decade?

The Core’s ongoing consultations during all phases of the NIH Collaboratory Trials will promote improvements to research protocols and offer real-time check-ins for unanticipated challenges. Our regular conference calls, contributions to the Living Textbook, and scholarly publications will continue to provide an important resource for investigators as well as IRBs.