informed consent Archives - Rethinking Clinical Trials

October 9, 2025: New Living Textbook Chapter Explores Decentralized Elements of Pragmatic Clinical Trials

Posted on October 9, 2025October 7, 2025 by Karen Staman

The NIH Pragmatic Trials Collaboratory this week published a new chapter of its Living Textbook of Pragmatic Clinical Trials. The chapter, Decentralized Pragmatic Clinical Trials, covers activities of a pragmatic trial that can occur remotely—at a location separate from an investigator’s location—such as participant engagement, recruitment, consent, study interventions and procedures, collection of patient-reported outcomes, and follow-up.

The chapter describes special considerations for decentralized trials, such as community health considerations and the vigilance needed to assure data quality, particularly as it relates to adherence with the study intervention, outcome ascertainment, and event monitoring.

The new chapter includes the following sections:

Most of NIH Collaboratory Trials have decentralized elements, as described in detail in Section 2.

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

Posted on June 12, 2025June 10, 2025 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 April 22, 2025 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.

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

Posted on January 14, 2025 by Damon Seils

Headshots of Dr. Jennifer Kawi, Dr. Jane Bolin, and Dr. Hulin Wu Ethics 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.

Learn more about APA-SM.
View the ethics and regulatory documentation for APA-SM.

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 December 3, 2024 by Damon Seils

Cover image of the journal Clinical Trials In 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.

June 14, 2023: IMPACt-LBP and INSPIRE Have Updated Study Snapshots, Ethics and Regulatory Documentation

Posted on June 14, 2023July 9, 2025 by Damon Seils

Updated study snapshots and ethics and regulatory documentation are now available for the IMPACt-LBP and INSPIRE trials, both NIH Pragmatic Trials Collaboratory Trials.

Logo for the IMPACt-LBP NIH Collaboratory Trial IMPACt-LBP transitioned from the planning phase to the implementation phase in August. As part of the transition, the study team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core. The study is a cluster randomized trial evaluating the effect of first-contact patient referral to physical therapists and doctors of chiropractic for the treatment of low back pain. IMPACt-LBP is supported within the NIH Collaboratory under an award from the National Center for Complementary and Integrative Health.

Read the updated ethics and regulatory documentation, including information about the study team’s approach to informed consent and collection of patient-reported outcome data.

Also available is an updated study snapshot for IMPACt-LBP.

Logo for the INSPIRE NIH Collaboratory Trial INSPIRE joined the NIH Collaboratory at the beginning of its implementation phase. The study team held its initial consultation with the Ethics Regulatory Core to review their approach to consent, data privacy, and the applicability of recent FDA guidance regarding clinical decision support software functions. INSPIRE consists of 2 cluster randomized trials that are using personalized clinical decision support to improve judicious antibiotic prescribing for non–critically ill patients hospitalized with abdominal infections or skin and soft tissue infections. The project is supported within the NIH Collaboratory under an award from the National Institute of Allergy and Infectious Diseases.

Read the INSPIRE ethics and regulatory documentation.

See also the study snapshot for INSPIRE.

Grand Rounds Ethics and Regulatory Series February 10, 2023: Informing and Consenting: What Are the Goals? (P. Pearl O’Rourke, MD; David S. Wendler, PhD, MA; Miguel Vazquez, MD; P. Michael Ho, MD, PhD)

Posted on February 16, 2023 by Elizabeth Mccamic

Speakers

Pearl O’Rourke, MD (retired)
Harvard Medical School

David S. Wendler, PhD, MA
Senior Researcher
Head, Section on Research Ethics
Department of Bioethics
NIH Clinical Center

Miguel Vazquez, MD
Professor of Internal Medicine
UT Southwestern Medical Center

Michael Ho, MD, PhD
Professor of Medicine
University of Colorado School of Medicine

Keywords

Ethics and Regulatory, Consent, Waiver of Consent, Notification

Key Points

Using informed consent addresses two of the Belmont Principles, respect for persons by informing and autonomy by allowing choice. The regulations recognize that consent is not always possible and allow for alteration, where some of the required elements of informed consent can be altered or not included, and waiver of consent, where no consent is required.

It is not uncommon to see waivers of consent in pragmatic clinical trials because many trials meet minimal risk criteria and involve numerous institutions and thousands of subjects. There are also concerns that obtaining consent could alter the “real-world” medical care being studied, may introduce an alteration of routine care, may introduce bias or make research impossible to conduct.

Informed consent is not the only way to inform. Think about methods of notification, from detailed study-specific information to a general statement that research is being conducted. There are consequences of notification, such as logistics and cost. If you are notifying, when do you offer an opt-out option and what do you do when potential subjects have questions or do not want to be in the research?

ICD-Pieces studied patients with chronic kidney disease (CKD), diabetes and hypertension. The intervention was to facilitate delivery of guideline-based care. The study had a waiver of informed consent. The study used a patient-information sheet to inform patients about the research, how patient data would be handled, and an option to opt-out of including their data in the study.

The Nudge Study is a pragmatic clinical trial seeking to improve medication adherence to patients’ already-prescribed cardiovascular medications through a series of theory-based text or voice messages that served as “nudges.” The study mailed patients an opt-out packet that included an introductory letter from the site PI, a FAQ sheet and opt-out form. If they did not opt-out within a month, we would monitor their prescription refills and send a nudge if one went unfilled for more than 7 days.

Participants always know some things and agree to some extent. When not getting full regulatory consent, the relevant questions are: What should they know? What should they agree (not object) to?

Discussion Themes

– How did the various types of notifications in the ICD-Pieces study impact opt-outs? The patient population and geography across sites was very different. The opt-outs were also very different. It was up to individuals how to deliver or make information about the study available than other sites in the study. It would be difficult for us to say a poster or letter is better.

– Whichever type of notification was used, did you tell people they could opt-out and explain how they could opt-out and give them assurance that opting-out would not impact care? For ICD-Pieces, there was a bullet that stated clearly that patients could opt-out and a phone number to opt-out. There was also a statement that said they would receive the best care from their provider. For NUDGE, there was the initial letter where patients could opt-out by sending a postcard and they could also opt-out in response to the text messages. Opt-outs were different across health systems.

March 31, 2022: GRACE Trial Has New Study Snapshot, Updated Ethics and Regulatory Documentation

Posted on March 31, 2022July 9, 2025 by Damon Seils

GRACE Trial logo A downloadable study snapshot and updated ethics and regulatory documentation are now available for the GRACE trial, an NIH Pragmatic Trials Collaboratory Trial.

GRACE transitioned from the planning phase to the implementation phase in September. As part of the transition, the study team reviewed and updated the minutes of their initial consultation with the Ethics and Regulatory Core. The study is a hybrid effectiveness–implementation trial of guided relaxation and acupuncture for pain associated with chronic sickle cell disease in 3 large healthcare systems.

Read the updated ethics and regulatory documentation, including information about the study team’s approach to inclusion and exclusion criteria, informed consent, and collection of patient-reported outcome data.

Also available is a new study snapshot for GRACE. This downloadable handout summarizes the study’s aims, lessons from the planning phase, and links to other resources from this innovative pragmatic clinical trial.

GRACE is supported by the NIH through the NIH Heal Initiative under an award from the National Center for Complementary and Integrative Health. Learn more about the GRACE trial.