August 11, 2025: New Living Textbook Chapter Explores Implementation in Pragmatic Clinical Trials

The NIH Pragmatic Trials Collaboratory Implementation Science Core, led by Devon Check and Hayden Bosworth, has developed a new chapter on implementation to assist study teams with the complex process of using and studying implementation strategies to help implement research findings into clinical care. The chapter includes sections on:

Case studies are used to illustrate how pragmatic clinical trials embedded in healthcare systems use implementation frameworks, including examples from RAMP, BEST-ICU, STOP CRC, TSOS, ABATE, STEP-2, and GRACE.

For more, see our collection of chapters on Dissemination and Implementation, which includes chapters on Dissemination to Different Stakeholders, Data Sharing and Embedded Research, and End-of-Trial Decision-Making.

June 23, 2025: How to Choose Patient-Reported Outcome Measures in Pragmatic Clinical Trials?

Living Textbook iconA new section of the Living Textbook of Pragmatic Clinical Trials describes considerations for choosing patient-reported outcome measures in pragmatic clinical trials.

“Where possible, investigators are encouraged to use measures with adequate support for validity that are in the public domain,” the authors wrote.

The authors provide a set of questions to guide investigators in choosing appropriate measures. For example, investigators may want to understand whether the patient-reported outcome is in electronic health records, is in the public domain, and is valid for the use case in question.

The considerations were developed by members of the NIH Pragmatic Trials Collaboratory’s Patient-Centered Outcomes Core in collaboration with the Health Care Systems Interactions Core, the Electronic Health Records Core, and colleagues at the NIH.

Grand Rounds March 28, 2025: A Cross-Sectional Study of GPT-4–Based Plain Language Translation of Clinical Notes to Improve Patient Comprehension of Disease Course and Management (Anivarya Kumar, BA; Matthew Engelhard, MD, PhD)

Speakers

Anivarya Kumar, BA
Fourth-Year Medical Student
Duke University School of Medicine

Matthew Engelhard, MD, PhD
Assistant Professor, Department of Biostatistics & Bioinformatics
Duke University School of Medicine

Keywords

Health Literacy; Large Language Models; Artificial Intelligence; Electronic Health Records

Key Points

  • Limited health literacy (HL) has tangible effects on morbidity and mortality: it’s associated with higher rates of hospital admissions and readmissions; medication nonadherence; healthcare costs; and all-cause mortality. 9 in 10 adults have limited HL, and rates are 2 – 3 times lower in marginalized populations.
  • 71% of patients report accessing their electronic health records (EHRs) to read documentation from their clinical visits, particularly the discharge summary notes (DSNs). But clinical notes have low levels of readability, hindering patients’ ability to engage in shared decision-making.
  • The research team looked at whether a Generative-Pre-trained-Transformer-4 (GPT-4)-based plain language translation of DSNs could improve patient comprehension of disease course and management.
  • 533 patients, recruited from a pool of EHR users, were randomly assigned 4 DSNs to assess. After reading the DSNs – 2 translated into more accessible language, 2 untranslated – patients answered questions assessing their objective comprehension, subjective comprehension, confidence, and time spent on each DSN.
  • Compared to the untranslated DSNs, objective understanding of the translated DSNs increased by 6.1%; subjective understanding increased 18%; confidence increased 45%; and average time spent with the DSNs decreased 51%.
  • The research team concluded that GPT translation of DSNs significantly improved patient comprehension of disease course and management and optimized time spent reading them. The effect was significantly greater in marginalized populations with historically low health literacy, reducing the gap in comprehension scores between patient populations.
  • Limitations included the use of standardized DSNs as opposed to real-world DSNs; the use of MyChart when enrolling patients, leading to a participant group with a higher baseline HL; and the modest number of Hispanic patients enrolled in the study.
  • Race is a significant and independent factor for HL. Preliminary data suggests that GPT translation can help close this gap. The research team identified this as an area for further study.

Discussion Themes

While discharge instructions alone can be great for providing patients with action items, they lack some of the context that DSNs can provide, lending the patient a more complete understanding of their condition.

The advantages of providing pre-generated materials, as opposed to pointing patients to an large language model (LLM) like Chat GPT for a more interactive explanation of their condition, include the potential for screening by a healthcare professional and less of a burden on the patient.

The study team ended up favoring “semantically-focused” translations over translations that focused solely on simplifying the language or avoiding jargon. When the LLM was asked to focus on semantics, it was more likely to define concepts and their implications.

Health literacy and reading level are not necessarily on par, and patient-centric or accessible language/LLMs are very important to consider. This may require further investigation, e.g. through qualitative interviews.

Grand Rounds January 10, 2025: FM-TIPS Community Engagement Methods for Recruitment (Dana Dailey PT, PhD; Heather Schacht Reisinger, PhD)

Speakers

Dana Dailey PT, PhD
Assistant Research Scientist
Physical Therapy and Rehabilitation Science
University of Iowa
Associate Professor, Physical Therapy Department
St. Ambrose University

Heather Schacht Reisinger, PhD
Director, Implementation Science Center
Associate Director for Engagement, Integration, and Implementation
Institute for Clinical and Translational Science
Professor, Division of General Internal Medicine at the University of Iowa

Keywords

Community-Engaged Research; Recruitment

Key Points

  • The Fibromyalgia TENS in Physical Therapy (FM-TIPS) study sought to test the feasibility and effectiveness of adding Transcutaneous Electrical Nerve Stimulation (TENS) to standard physical therapy (PT) care in a real-world PT setting. Their primary outcome was the change in movement pain, from baseline to 50 days.
  • By February 2022, the team had activated 25 active PT clinics across seven Midwestern states. In February 2023, the team received a diversity supplement for community engagement and brought on a Community Engagement Coordinator.
  • After developing a community engagement process and implementing six community engagement strategies, inquiries about the study increased significantly, screening rates held steady, and enrollment rates increased. These effects were more pronounced in targeted clinics.
  • Engagement with the clinics, clinicians, and community had a significant impact on the pragmatic trial. Dr. Dailey noted that clinicians felt more supported and seen as a part of both the clinic and the community. Conversations with participants were also fruitful, helping the researchers understand how participants were feeling when they weren’t in therapy.
  • Clinical research in community physical therapy clinics is not common, and there was a steep learning curve for many of the physical therapists involved. Community support helped them navigate screening and enrollment.
  • The study team developed individualized clinic plans through inquiry of clinicians and clinics. This feedback helped them identify organizations to collaborate with, local events, etc.
  • Process building, including implementation and complete documentation of outcome measures, was important to site evaluation. As a result of these activities, the research team was able to carry lessons over into low-enrolling clinics, adapt, and make productive changes.

Discussion Themes

When researchers think about pragmatic trials involving clinics, Dr. Reisinger noted, it becomes difficult to delineate the concepts of “community members” and “participants.” For example, it’s important to also think about clinicians also as community members who are living and working in those spaces, and who have a deep knowledge of and commitment to their community. All of that knowledge will be important to decision-making.

Intensive and responsive community engagement was made possible for this pragmatic trial by the diversity supplement, which enabled the team to hire two full-time community engagement coordinators. At the rate they were going before they implemented community engagement, the study team would not have hit their enrollment target; in the end, they exceeded it.

Researcher teams should always be adaptive and flexible when doing community engagement, even when it comes to documentation.

May 2024 Annual Steering Committee Meeting

May 9-10, 2024 | Bethesda, MD

Main Purpose

Day 1: Hear from the newest NIH Collaboratory Trials; share challenges and lessons learned to promote successful trial conduct; discuss the evolution and current state of the NIH Collaboratory ecosystem; identify gaps and areas of opportunity for expanding the ecosystem of embedded pragmatic clinical trials (ePCTs).
Day 2: Have rich discussions on overcoming challenges in ePCTs, fostering patient engagement, and creating reusable infrastructure; share insights from seasoned NIH Collaboratory Trials on posttrial activities and moving to the next ePCT.

Fireside chat 3

Agenda and Slides

Day 1: Thursday, May 9, 2024

Welcome and Opening Remarks

Wendy Weber, ND, PhD, MPH; Lesley Curtis, PhD

Highlights of the NIH Pragmatic Trials Collaboratory

Feature major accomplishments of the program; review specific requirements for the new trials; offer guidance and answer questions

Wendy Weber, ND, PhD, MPH

Ethical and Regulatory Challenges/Lessons Learned

Hear from the NIH Collaboratory Trials about ethical and regulatory challenges encountered; Discuss strategies for navigating ethical and regulatory complexities of ePCTs

Moderator: Stephanie Morain, PhD

Panel:

  • Michele Balas, PhD, RN, CCRN-K, FCCM, FAAN
  • Diana Burgess, PhD
  • Richard Skolasky, ScD, MA

Study Design Challenges/Lessons Learned

Learn about study design issues faced by the NIH Collaboratory Trials; Share statistical and methodological considerations important for the planning phase and beyond

Moderator: Patrick Heagerty, PhD

Panel:

  • Sheana Bull, PhD, MPH

  • Stephanie Fitzpatrick, PhD
  • Chenchen Wang, MD, MSc

Data Access and Management Challenges/Lessons Learned

Hear from the NIH Collaboratory Trials about challenges with data access, planning for data management, and data sharing; Review methods for addressing issues related to data security, privacy, and approval for data use

Moderator: Rachel Richesson, PhD, MPH, MS, FACMI

Panel:

  • Richard Skolasky, ScD, MA

  • Ed Vasilevskis, MD, MPH

Lessons and Challenges Engaging Rural Populations

Share progress on ePCTs for the prevention and management of chronic pain in rural populations, describing challenges and lessons learned; Begin communication that may lead to joint publications on methods and strategies, and/or future collaborations

Moderators: Karen Kehl, PhD, RN, FPCN

Panel:

  • Julie Fritz, PhD, PT

  • Richard Skolasky, ScD, MA

  • Sebastian Tong, MD, MPH
  • Katie Hadlandsmyth, PhD

Welcome and Introduction of Fireside Chat

Welcome participants, introduce the Fireside Chat, and kick off the afternoon session for all NIH Collaboratory Trials

Helene Langevin, MD, PhD; Richard Hodes, MD; David Shurtleff, PhD

Fireside Chat: Pragmatic Research and National Health Priorities

Hear thoughts on how pragmatic research can help address the nation’s top health priorities; Discuss how to maximize evidence generation from ePCTs and achieve the greatest benefits for the U.S. population

Moderator: Wendy Weber, ND, PhD, MPH

Guests:

  • Monica Bertagnolli, MD
  • Robert Califf, MD

State of the NIH Pragmatic Trials Collaboratory Ecosystem

Share an overview of the characteristics of trials in the NIH Collaboratory, such as populations, partner types (e.g., hospitals, primary care, community clinics, FQHCs); Discuss the evolution of the program and identify gaps and areas of opportunity

Kevin Weinfurt, PhD

Addressing Barriers to ePCTs Involving Approved Drugs

Describe barriers to conducting ePCTs involving approved drugs, including trials with repurposed drugs and A vs B trials; Explore potential ways to overcome these barriers, including how the NIH Collaboratory might contribute

Moderator: Adrian Hernandez, MD, MHS

Panel:

  • Pearl O'Rourke, MD
  • Kevin Bugin, PhD
  • Leonard Sacks, MD
  • Tracy Wang, MD, MHS, MSc

Promoting Patient Engagement in ePCTs

Review the Coordinating Center’s efforts to support patient engagement; Hear from NIH Collaboratory Trials on challenges and methods for engaging patients in ePCTs

Moderator: Steven George, PT, PhD

Panel:

  • Natalia Morone, MD, MS
  • Chenchen Wang, MD, MSc

Fostering Development of Up-and-Coming ePCT Investigators

Hear flash talks from NIH Collaboratory fellows

Moderator: Emily O'Brien, PhD

Presenters:

  • Lindsay Ballangee, DPT
  • Kaitlyn McLeod, MD

Closing Remarks

Wendy Weber, ND, PhD, MPH; Lesley Curtis, PhD

Day 2: Friday, May 10, 2024

Opening Remarks

Wendy Weber, ND, PhD, MPH; Lesley Curtis, PhD

BackInAction Results

Hear preliminary main outcomes

*No slides for this presentation

Lynn DeBar, PhD

Clinician and Health System Engagement Challenges/Lessons Learned

Hear about challenges engaging clinicians and health systems; Discuss ways to strengthen these relationships to support ePCTs; Share how trials are planning for retraining of clinical staff when there is turnover

*No slides for this panel

Moderator: Greg Simon, MD, MPH

Panel:

  • Andrea Cheville, MD
  • Christine Goertz, DC, PhD
  • James Tulsky, MD

Data Extraction and Quality Challenges/Lessons Learned

Learn about issues encountered with EHR integration, data extraction, and data quality; Share ways to mitigate data-related challenges, such as cleaning as you go and strong investigator–analytic team collaborations

Moderator: Keith Marsolo, PhD

Panel:

  • Dana Dailey, PT, PhD
  • Shruti Gohil, MD, MPH
  • Corita Grudzen, MD, MSHS

Expanding the ePCT Ecosystem to Better Serve Minoritized Communities

Discuss the increasing burden on minoritized communities and health systems serving them; Review the makeup of NIH Collaboratory Trial sites (academic medical centers, community hospitals, etc.) and explore how to expand the types

Moderator: Cherise Harrington, PhD, MPH

Panel:

  • Eliseo J. Pérez-Stable, MD
  • Stephanie Fitzpatrick, PhD
  • Sebastian Tong, MD, MPH

Building and Sustaining Reusable Infrastructure for ePCTs

Describe reusable infrastructure being used to promote ePCTs outside the NIH Collaboratory; Explore different models for sustaining infrastructure for ePCTs

Moderator: Christine Goertz, DC, PhD

Panel:

  • Lynn DeBar, PhD
  • Julie Fritz, PhD, PT
  • Greg Simon, MD, MPH

Exploring the Generative Investment of an ePCT for Catalyzing Research

Discuss elements of research platforms in NIH Collaboratory Trials most at risk of dissipating and needing to be rebuilt for future research; Describe which elements could be reused (e.g., relationships, teams, interventions, EHR/IT systems)

Moderator: Greg Simon, MD, MPH

Panel:

  • Susan Huang, MD, MPH
  • Natalia Morone, MD, MS
  • Jon Tilburt, MD

Planning Effectively for Posttrial Activities

Discuss preparing for dissemination and sustainment or de-implementation before results are known; describe considerations for when and how to share results with partners and the public; Learn ways to share trial tools more widely, and explore Dissemination and Implementation R01s

Moderator: Hayden Bosworth, PhD

Panel:

  • Shruti Gohil, MD, MPH
  • Corita Grudzen, MD, MSHS
  • Stacy Sterling, DrPH, MSW

How to Transition to the Next Research Opportunity

Share insights from NIH Collaboratory Trials that informed subsequent pragmatic trials; Learn which aspects investigators preserved in subsequent trials, and which aspects they discontinued or added

Moderator: Rich Platt, MD, MSc

Panel:

  • Lynn DeBar, PhD
  • Mike Ho, MD, PhD
  • Angelo Volandes, MD, MPH

Closing Remarks

Wendy Weber, ND, PhD, MPH; Lesley Curtis, PhD

NIH-Hosted Workshop: Going From Zero to 100: Generating Evidence Through Pragmatic Research to Address Pressing Healthcare Issues (July 2024)

This 2-day workshop held during July 2024 explores the preparatory actions researchers can take in the planning and application phase (Phase Zero) to ensure pragmatic clinical trials yield actionable evidence for various settings.

 

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Case Study

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Podcast Blog: Reflections on the NIH Collaboratory: Highlights from the Past and Hopes for the Future

A podcast discussion with Drs. Adrian Hernandez and Kevin Weinfurt

NIH Collaboratory investigators and podcast moderators Drs. Adrian Hernandez and Kevin Weinfurt took time on the latest podcast to discuss the important work done by the NIH Collaboratory this year and what’s next.

Dr. Weinfurt spoke about his excitement to begin seeing results from NIH Collaboratory Trials in the coming years, and how those results will be received by various stakeholders. Specifically, he referenced groundbreaking results presented at a recent Grand Rounds by Dr. Greg Simon on the Suicide Prevention Outcomes Trial (SPOT), a project looking at the use of machine learning to predict patient behaviors and outcomes. Dr. Simon recently spoke on the podcast about the implications of using computer algorithms not only to prevent suicides, but also in broader healthcare settings to predict a variety of patient outcomes.

Dr. Hernandez noted that the NIH Collaboratory Trials to date have been truly pragmatic trials, and could offer valuable insights to inform the next wave of projects in the coming year. Dr. Weinfurt agreed that investigators could learn from these original NIH Collaboratory Trials, as well as reference The Living Textbook, to develop more mature research questions in the future. In particular, he said he looks forward to moving in the direction of “A versus B testing” in future trials.

Both Drs. Hernandez and Weinfurt said they expect that the Revised Common Rule will present a challenge for the upcoming year, as the research community explores how to run trials within the new regulations. Dr. Hernandez noted that there has often been an emphasis on the front half of the trials, and less clarity around the back half, when the data is collected and analyzed.  Refocusing on this later portion of trials, he said, will be crucial in order to ensure data is disseminated properly and ultimately used to create real change for patients.

In terms of expectations for the future, Dr. Hernandez said he hopes that there will be more data streams available, as companies like Amazon begin to move into the health data space. Both he and Dr. Weinfurt shared a hope that health systems will ultimately be able to pull data from a number of sources, from electronic health records (EHRs) to wearable devices, creating richer data sets to examine outcomes. In addition, Dr. Weinfurt proposed that moving forward, the NIH Collaboratory should include more educational opportunities for the research community on pragmatic trials, in order to teach investigators not only how to run these trials but also what to do with the results.

The NIH Collaboratory looks forward to presenting regular educational opportunities, in the form of weekly Grand Rounds presentations and monthly podcasts.

Read the full podcast transcript here.