ethics

October 27, 2025: Study Snapshot and Updated Ethics Documentation Available for APA-SM Study

Posted on by Damon Seils
APA-SM Investigators
Dr. Jennifer Kawi, Dr. Jane Bolin, and Dr. Hulin Wu, principal investigators for APA-SM

A new study snapshot and updated ethics and regulatory documentation are now available for the APA-SM study. A year into the project, the research team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core.

New resources for APA-SM include:

APA-SM is testing a 4-week auricular point acupressure intervention for self-management of chronic pain in rural communities in South Carolina and Texas. The study will also include implementation outcomes, a cost-effectiveness analysis, and an evaluation of predictive factors for treatment response.

APA-SM is supported within the NIH Pragmatic Trials Collaboratory by the National Center for Complementary and Integrative Health, with additional oversight from the National Institute of Neurological Disorders and Stroke. Learn more about APA-SM.

October 16, 2025: New Article Surveys Landscape of Empirical Ethics Research Related to Pragmatic Clinical Trials

Posted on by Damon Seils
Headshots of Dr. Kayla Mehl, Dr. Stephanie Morain, and Dr. Jeremy Sugarman
Left to right: Kayla R. Mehl, Stephanie R. Morain, and Jeremy Sugarman

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.”

Read the full article.

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.

August 25, 2025: NIH Collaboratory Researchers Consider Posttrial Responsibilities

Posted on by Damon Seils

At the NIH Pragmatic Trials Collaboratory’s 2025 Annual Steering Committee Meeting, researchers discussed the obligations pragmatic trials researchers have to research participants, partnering healthcare systems, and each other after a trial is complete.

Panelists for the session included moderators Pearl O’Rourke and Jeremy Sugarman, cochairs of the NIH Collaboratory’s Ethics and Regulatory Core; Stephanie Morain, also from the Ethics and Regulatory Core; Hayden Bosworth from the Implementation Science Core; and Angelo Volandes, co–principal investigator for the ACP PEACE trial. They were joined by Andrea Cook from the BackInAction trial, Shruti Gohil from the INSPIRE trial, and Mike Ho from the Nudge trial and the Chat 4 Heart Health trial.

Morain introduced the ethical foundations for posttrial responsibilities, noting that the Declaration of Helsinki requires that “post-trial provisions must be arranged by sponsors and researchers to be provided…for all participants who still need an intervention identified as beneficial and reasonably safe in the trial.” The Declaration also states that “researchers have a duty to make publicly available the results of their research on human participants.”

Read more: Morain et al, “Post-Trial Responsibilities in Pragmatic Clinical Trials: Fulfilling the Promise of Research to Drive Real-World Change”

Bosworth encouraged attendees to think about sustainability as an integral part of the research process for pragmatic trials. “I may need to continue this intervention in some way, but that means I have to prepare for that even before I have the results,” he said.

Read more: Green et al, “Factors Affecting Post-trial Sustainment or De-implementation of Study Interventions: A Narrative Review”

Cook, Gohil, and Ho gave examples of how their research teams prepared for posttrial follow-up and implementation. In both BackInAction and INSPIRE, the investigators planned to provide cost-effectiveness information to the partnering healthcare systems to help them make the business case for sustaining the interventions. In Nudge, the investigators were working with partnering healthcare systems to understand how modifications to the intervention could improve adherence to future implementations.

Volandes shared his experience in the ACP PEACE trial, which tested a video decision aid for older patients with advanced cancer, by highlighting focus groups in which the study team asked trial participants what they felt the researchers owed to them after the study.

“They said, we love your tools but some don’t reflect who we are,” Volandes said. “So we went back and updated our tools to reflect the community served by the system, and to mention in the tool that this tool is a product of research conducted by patients in the community.

Volandes showed the modified video decision aid, which featured images and content to highlight that studies conducted in the healthcare system showed that participating patients found the tool to be helpful.

This summer, we are sharing highlights from the 2025 Annual Steering Committee Meeting. Access the complete collection of meeting materials.

June 12, 2025: Living Textbook Chapter Covers Consent, Disclosure, and Nondisclosure for Pragmatic Trials

Posted on by Karen Staman

A new chapter of the Living Textbook of Pragmatic Clinical Trials describes regulatory requirements for informed consent, waivers and alterations of consent, mechanisms for notification, and research participants’ perspectives on a variety of approaches to consent and notification—all with a focus on special considerations for pragmatic clinical trials.

For a variety of reasons, the  application of ethical principles and regulations regarding informed consent can be complex for pragmatic clinical trials. For example, pragmatic trials often use novel study designs, including cluster randomization, in which the unit of randomization may be a clinic, hospital, or healthcare system rather than the individual. Some pragmatic trials also use stepped-wedge designs, in which the study intervention is introduced to sites at different times.

The new chapter has 5 sections:

  • Section 1 discusses reasons why the application of ethical principles and regulations regarding informed consent can be complex for pragmatic trials.
  • Section 2 describes the regulatory requirements for informed consent.
  • Section 3 focuses on waivers and alterations of the informed consent process.
  • Section 4 provides examples of mechanisms for notifying participants about the trial when consent is not required.
  • Section 5 presents findings on research partners’ preferences regarding various approaches to research and consent.

The chapter was developed by members of the NIH Pragmatic Trials Collaboratory’s Ethics and Regulatory Core.

April 22, 2025: New Report Highlights Value of Informing Participants About Research Conducted Under a Waiver of Consent

Posted on by Karen Staman

Even in minimal-risk studies that do not use the standard consent process, there may be value in informing participants about the research. Such notifications should be considered the default for clinical trials conducted under a waiver of informed consent, argue the authors of a new report from the NIH Pragmatic Trials Collaboratory.

The open-access article was published online ahead of print this week in Learning Health Systems.

Pragmatic clinical trials conducted in the context of routine healthcare often meet the regulatory criteria for a waiver or alteration of the standard informed consent process. In such cases, researchers and reviewers might assume there is no reason to communicate information about the study to participants. However, providing information to participants, even in minimal-risk research conducted with a waiver of consent, can promote important ethical values.

Experts from the NIH Collaboratory’s Ethics and Regulatory Core teamed up with investigators from several of the NIH Collaboratory Trials to describe methods of informing participants in minimal-risk research.

The investigators used a variety of notification approaches in their studies, including letters and email campaigns, posters in waiting rooms and other common areas, conversations with clinicians, and presentations at staff meetings. The amount of information provided to participants ranged from a general statement that research was being conducted at the institution to detailed information about the study in question.

“When a study is approved with a waiver of research consent, investigators and review committees should consider on a case-by-case basis what information, if any, to disclose to participants, and how it will be disclosed,” the authors wrote. The costs, benefits, and feasibility of these approaches vary from study to study.

Communicating information to participants can promote several important goals:

  • The ethical principle of respect for persons
  • Participants’ understanding of the study and of research in general
  • Participants’ understanding of their contributions to the research
  • Participants’ ability to voice and discuss any concerns about the study
  • Participant engagement in research
  • Trust in research and researchers

“Providing information to the participants should thus be the default for trials conducted under a waiver of research consent,” the authors wrote.

Read the full report.

April 21, 2025: Ethics Consultation Documentation Now Available for LungSMART and STEP-2 Trials

Posted on by Damon Seils
Headshots of LungSMART investigators David Wetter, Guilherme Del Fiol, and Ken Kawamoto
Left to right: LungSMART investigators Drs. David Wetter, Guilherme Del Fiol, and Ken Kawamoto

Ethics and regulatory onboarding documentation for 2 of the NIH Pragmatic Trials Collaboratory’s newest studies is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the LungSMART trial and the STEP-2 trial.

The consultations took place by video conference and included representation from the study teams, members of the NIH Collaboratory’s Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

LungSMART will test telehealth interventions designed to address logistical barriers and hesitancy around completing lung cancer screening among patients receiving care in community health centers in Utah.

Headshots of Drs. Rachel Winer, Amanda Petrik, and Jasmin Tiro
Left to right: STEP-2 investigators Drs. Rachel Winer, Amanda Petrik, and Jasmin Tiro

The STEP-2 trial will evaluate the comparative effectiveness and cost-effectiveness of in-clinic vs mailed distribution of human papillomavirus (HPV) self-sampling kits to improve cervical cancer screening rates among patients receiving care in community health centers in Oregon and Washington.

LungSMART and STEP-2 are the first NIH Collaboratory Trials to be supported by grant awards from the National Cancer Institute.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

March 10, 2025: Developing Monitoring Plans Warrants Special Attention in Pragmatic Clinical Trials

Posted on by Karen Staman

Cover of Contemporary Clinical TrialsIn an article published online ahead of print, leaders from the NIH Pragmatic Trials Collaboratory share lessons learned about the importance of independent oversight by a safety office or data and safety monitoring board in pragmatic clinical trials, even for trials deemed to have minimal risk.

Challenges specific to pragmatic trials include:

  • complexity, quality, and timing of a real-world data pipeline, especially in trials with many heterogeneous sites
  • embedding of interventions in clinical workflows, so investigators have less control over treatments or interventions
  • potential for incidental and collateral findings

“We recommend regular, rigorous data quality checks, ongoing monitoring of adherence to interventions, and including someone who is knowledgeable about pragmatic clinical trials and novel research designs in the development of Data and Safety Monitoring Plans and Data and Safety Monitoring Boards,” the authors wrote.

By attempting to reflect real-world conditions, pragmatic trials are conducted in settings that cannot be closely controlled. Therefore, close monitoring is critical for a successful study that produces meaningful results, whether it be by independent monitors or data and safety monitoring boards.

The authors drew on experiences from 7 of the NIH Collaboratory Trials and the expertise of the Coordinating Center, the Ethics and Regulatory Core, the Biostatistics and Study Design Core, and the Health Care Systems Interactions Core.

The article was published in Contemporary Clinical Trials.

February 24, 2025: Study Snapshots and Updated Ethics Documentation Available for 3 NIH HEAL Initiative–Supported Trials in Rural Populations

Posted on by Damon Seils

New study snapshots and updated ethics and regulatory documentation are now available for the AIM-CP, ARBOR-Telehealth, and RAMP trials. The 3 NIH Collaboratory Trials, all supported through the NIH HEAL Initiative℠, or Helping to End Addiction Long-Term Initiative℠, reflect a special emphasis on developing strategies for the management of chronic pain in rural and remote populations. The trials have transitioned from the UG3 planning phase to the UH3 implementation phase.

“There are many known disparities between urban and rural populations,” said Karen Kehl, a program director at the National Institute of Nursing Research (NINR), in an interview at the NIH Pragmatic Trials Collaboratory’s 2024 Annual Steering Committee Meeting. “And when we talk about chronic pain, we know that there’s a higher incidence and a higher severity of pain in rural populations, and yet they don’t have access to many of the effective solutions that we have,” Kehl added.

AIM-CP

 AIM-CP is testing the implementation of a care management program to address disparate access to nonpharmacological treatments for chronic pain in rural populations. The principal investigators are Sebastian Tong and Kushang Patel of the University of Washington. The study is supported by NINR.

 

ARBOR-Telehealth

 ARBOR-Telehealth is evaluating the use of a telehealth physical therapy strategy for patients who present to primary care clinics with low back pain in rural communities. The principal investigators are Richard Skolasky and Kevin McLaughlin of Johns Hopkins University. The study is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

 

RAMP

 RAMP is evaluating the use of a 12-week mind-body skills training program for rural veterans with pain within the VA’s Whole Health initiative, including a one-on-one session with a Whole Health coach followed by 11 weekly group sessions to include prerecorded expert-led education videos, mind-body skills training and practice, and group discussions. The principal investigators are Diana Burgess and Roni Evans of the University of Minnesota and Katherine Hadlandsmyth of the University of Iowa. The study is supported by NINR.

 

January 14, 2025: Ethics Consultation Documents Now Available for APA-SM Trial

Posted on by Damon Seils

Headshots of Dr. Jennifer Kawi, Dr. Jane Bolin, and Dr. Hulin WuEthics and regulatory onboarding documentation for one of the NIH Pragmatic Trials Collaboratory’s newest trials is now available. The documents include meeting minutes and supplementary materials summarizing recent discussions of ethics and regulatory issues associated with the APA-SM trial.

The consultations took place by video conference and included representation from the study team, members of the NIH Collaboratory’s Ethics and Regulatory Core, NIH staff, and NIH Collaboratory Coordinating Center personnel.

APA-SM will test a 4-week auricular point acupressure intervention for self-management of chronic pain in rural communities in South Carolina and Texas. The study will also include implementation outcomes, a cost-effectiveness analysis, and an evaluation of predictive factors for treatment response.

APA-SM is supported through the NIH HEAL Initiative with administrative oversight by the National Center for Complementary and Integrative Health and the National Institute of Neurological Disorders and Stroke.

Ethics and regulatory documentation for all of the NIH Collaboratory Trials is available on our Data and Resource Sharing page.

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.