NIH Collaboratory Trials

October 2, 2025: Study Design Paper Published for I CAN DO Surgical ACP

Posted on by Damon Seils

Logo for the I CAN DO Surgical ACP trialThe study design paper for I CAN DO Surgical ACP has been published online in BMJ Open. Congratulations to the study team on reaching this important milestone for all NIH Collaboratory Trials!

I CAN DO Surgical ACP, an NIH Collaboratory Trial, is testing a system-based approach to help older adults undergoing elective surgery engage in advance care planning. Another goal of the study is to understand digital engagement, language, and social drivers of health that drive engagement in the intervention.

The study is being led by Elizabeth Wick and Rebecca Sudore of the University of California, San Francisco, and Genevieve Melton-Meaux of the University of Minnesota and is supported by a grant award from the National Institute on Aging.

Read the full study design paper.

September 25, 2025: iPATH Researchers Identify Factors Linked to Cardiovascular Care Performance in Community Health Centers

Posted on by Damon Seils
Headshot of Dr. Sara Singer
Dr. Sara Singer, principal investigator for iPATH

Community health centers serving a higher percentage of unhoused patients and patients who are best served in a language other than English had lower rates of diabetes control, hypertension control, or both, according to an analysis from the iPATH research team. The findings can inform initiatives to improve care in community health centers.

The report was published online ahead of print in AJPM Focus.

iPATH, an NIH Collaboratory Trial led by principal investigator Sara Singer of Stanford University, is a stepped-wedge, cluster randomized, hybrid effectiveness-implementation trial of a practice transformation strategy for type 2 diabetes in federally qualified health centers in California, Massachusetts, Ohio, and Puerto Rico. The study will evaluate the impact of the practice transformation strategy and identify process elements that influence implementation effectiveness.

In the research team’s analysis of community health center characteristics, facilities serving a large percentage of unhoused patients had lower performance for both diabetes and hypertension control. Facilities serving a large percentage of patients best served in a non-English language had poorer performance for diabetes control.

“The association between having more unhoused patients and lower performance for diabetes and hypertension management points to housing inequality as a key source of disparity,” the authors wrote. Facilities serving more unhoused patients may benefit from additional support and evidence-based healthcare strategies.

The iPATH team also found that facilities serving more patients at high risk for cardiovascular events and receiving statin therapy had better performance for diabetes management. Statin treatment is an evidence-based standard of care for the prevention of cardiovascular events in patients with diabetes.

“Our finding for cardiovascular risk management suggests that [community health centers] capable of adhering to these evidence-based standard of care guidelines for cardiovascular disease may also be able to follow therapeutic protocols more generally, and to those supporting diabetes management in particular,” the authors wrote.

iPATH is supported within the NIH Pragmatic Trials Collaboratory by the National Institute on Minority Health and Health Disparities. Learn more about iPATH.

September 15, 2025: In BackInAction Pragmatic Trial, Acupuncture Improved Back Pain–Related Disability in Older Adults

Posted on by Damon Seils
Headshots of Dr. Lynn DeBar and Dr. Andrea Cook
Dr. Lynn DeBar and Dr. Andrea Cook, co–principal investigators for BackInAction

Older patients with chronic low back pain who receive acupuncture treatment have greater improvements in pain and disability compared with patients who receive usual care alone, according to the BackInAction trial.

The results of the study were published online in JAMA Network Open.

BackInAction, an NIH Collaboratory Trial, compared standard and enhanced courses of acupuncture with usual care alone in adults aged 65 years and older with chronic low back pain. Previous studies found acupuncture to be a safe and effective treatment for chronic low back pain in adults, and the American College of Physicians recommends the treatment as first-line therapy. However, few studies, and no large-scale randomized trials, have examined the safety and efficacy of acupuncture in older adults specifically.

“We worked hard to involve adults in multiple regions of the country so that participant demographics were consistent with the US census for older adults,” Lynn DeBar told the NIH. “And we worked with licensed acupuncturists in the community, who are most likely to deliver these services,” she said. DeBar is a senior investigator at the Kaiser Permanente Center for Health Research and a co–principal investigator for BackInAction.

The study team randomly assigned 800 patients to 1 of 3 groups: (1) a standard 12-week course of acupuncture plus usual medical care; (2) standard acupuncture enhanced with 4 to 6 maintenance sessions plus usual care; or (3) usual care alone. The study was conducted in 4 healthcare systems in the Pacific Northwest, Northern California, and New York, including a network of federally qualified health centers in an urban setting, 2 integrated health insurance and care delivery systems serving broad geographic regions, and a fee-for-service system serving a relatively urban and suburban population.

Logo for the BackInAction trial

At 6 months and 12 months after treatment, patients in both the standard and enhanced acupuncture groups experienced significantly greater reductions in pain and pain-related disability than patients in the usual care group. The improvements did not differ significantly between the standard and enhanced courses of acupuncture.

Read the full article.

“Older adults often are dealing with other medical problems in addition to back pain,” said co–principal investigator Andrea Cook, senior biostatistics investigator at the Kaiser Permanente Washington Health Research Institute. “Acupuncture offers a less invasive option that has a better safety profile than a lot of the common treatments for back pain in older adults,” she said.

BackInAction is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative by a grant from the National Center for Complementary and Integrative Health. Learn more about BackInAction.

September 10, 2025: Initial Outcomes of OPTIMUM, in This Week’s Rethinking Clinical Trials Grand Rounds

Posted on by Damon Seils

Headshots of Drs. Natalia Morone, Carol Greco, and Kim FaurotIn this Friday’s Rethinking Clinical Trials Grand Rounds, Natalia Morone, Carol Greco, and Kim Faurot will present “Initial Outcomes of the Optimizing Pain Treatment in Medical Settings Using Mindfulness (OPTIMUM) Pragmatic Trial.”

The Grand Rounds session will be held on Friday, September 12, 2025, at 1:00 pm eastern.

OPTIMUM, an NIH Collaboratory Trial, is studying the addition of mindfulness-based stress reduction to usual care for patients with chronic low back pain, compared with usual care alone, with the goal of improving pain outcomes and reducing opioid prescriptions. Learn more about OPTIMUM.

Morone, the principal investigator for OPTIMUM, is an associate professor of medicine at Boston University and a clinical general internist at Boston Medical Center. Greco is an associate professor of psychiatry and psychical therapy at the University of Pittsburgh. Faurot is an assistant professor of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

Join the online meeting.

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.

August 19, 2025: INSPIRE Sees Sustained Reductions in Use of Extended-Spectrum Antibiotics

Posted on by Damon Seils

Logo for the INSPIRE Demonstration ProjectA new analysis from the INSPIRE research team found that automated prompts to improve judicious use of antibiotics for hospitalized patients led to sustained reductions in the use of extended-spectrum antibiotics.

The findings were reported in a research letter in JAMA.

INSPIRE, an NIH Collaboratory Trial, consisted of 2 cluster randomized trials that used personalized clinical decision support to improve judicious antibiotic prescribing for non–critically ill hospitalized patients with abdominal or skin and soft tissue infections during the first 3 days of hospitalization. The research program also included 2 other trials, which evaluated the same intervention for hospitalized patients with pneumonia and urinary tract infection.

In the new analysis, 65% to 84% of the reductions achieved in the use of extended-spectrum antibiotics in the first 3 days of hospitalization persisted through the remainder of the hospital stay.

“These findings suggest that investing in stewardship for initial antibiotic selection, rather than primarily focusing on de-escalating antibiotics once started, would reduce unnecessary extended-spectrum antibiotics for millions of patients in US hospitals annually,” the authors wrote.

INSPIRE was supported within the NIH Pragmatic Trials Collaboratory by a grant from the National Institute of Allergy and Infectious Diseases. The primary results were reported this year in JAMA Internal Medicine and JAMA Surgery.

Learn more about INSPIRE.

August 18, 2025: After Early Termination, HiLo Team Shares Insights From Pragmatic Trial Implementation

Posted on by Damon Seils
Headshot of Dr. Hrishikesh Chakraborty
Dr. Hrishikesh Chakraborty, principal investigator for HiLo

Does a higher or lower target for phosphate control offer the best balance of benefits and risks in patients receiving maintenance hemodialysis? This important question remains unanswered, after the HiLo research team reported on the challenges that led to early termination of their innovative pragmatic clinical trial.

The article was published online ahead of print in the Journal of the American Society of Nephrology.

HiLo, an NIH Collaboratory Trial, compared the effects of higher vs lower serum phosphate targets on all-cause mortality and all-cause hospitalization in patients undergoing maintenance hemodialysis. Evidence from randomized clinical trials to inform the optimal phosphate target is lacking.

Patients in the low phosphate target group received the standard clinical approaches to phosphate management. For patients in the high phosphate target group, clinicians and dietitians withdrew phosphate binders and relaxed dietary restrictions if the phosphate level remained below target.

Read the full article.

HiLo began as a cluster randomized trial with randomization at the dialysis facility level. Nearly 2 years into the trial, an imbalance in baseline serum phosphate between the study groups raised concern about biased recruitment. The study team transitioned to patient-level randomization before eventually stopping the trial early due to insufficient enrollment and inadequate phosphate separation between groups. As a result, the study team was unable to detect a difference in the primary outcome or to make inferences about secondary outcomes.

Logo for the HiLo Demonstration ProjectAlthough HiLo was stopped early, the trial’s design had several pragmatic features that point the way for future trials. The trial used no onsite research staff, instead engaging sites’ clinical staff to deliver the intervention as part of routine care. The study team monitored monthly laboratory data remotely and provided real-time feedback to the sites. All laboratory and outcome data were collected in the context of clinical care.

Disruptions from the COVID-19 pandemic, complications related to the trial’s original cluster randomized design, and other challenges also offer lessons for future studies.

HiLo was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases.

Learn more about HiLo.

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

Posted on by Karen Staman

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.

July 22, 2024: Key Decisions for Integrating Digital Tools Into EHR Systems for Pragmatic Trials

Posted on by Karen Staman

At the NIH Pragmatic Trials Collaboratory’s 2025 Annual Steering Committee Meeting, a team of experts shared key decisions about whether or not to integrate digital tools into the electronic health record (EHR). The panel, moderated by Steve George of the NIH Collaboratory Coordinating Center, explained that the decision hinges on 4 critical factors: complexity, institutional governance, requirements for integration, and involvement of personnel.

Complexity

Complexity depends on the number of participating systems, the type of healthcare systems (such as private clinics, federally qualified health centers, and academic medical centers), and the number of EHR vendors involved. Complexity is also driven by the level of integration required: sending a result or message is fairly easy, while embedding a decision support application within a screen is more difficult.

For more, see the Living Textbook chapter on Intervention Delivery and Complexity.

Institutional Governance

Institutional governance varies by health system. There may be single or multiple review committees, long wait times for implementation and deployment, or multiple levels of approval needed (including corporate and C-suite), all of which can impact possible EHR integration and timelines.

Requirements for Integration

Panelists suggested that investigators weigh whether the trial or intervention requires EHR integration for meaningful results or if integration would just be nice to have. If EHR integration is required, are there pieces that could be removed or deferred if implementation timelines are delayed?

Involvement of Personnel

Finally, the panelists suggested that researchers should be prepared to account for the human factors that affect intervention uptake, fidelity, and sustainability.

Key Questions

  • If the intervention requires someone to push a button or click on something, does that role or person exist at each institution?
  • Has there been buy-in from sites to assess whether the intervention is compatible with clinical workflows to ensure fidelity?
  • What types of updates or modifications are necessary over time? Will sites need to do additional work after the initial implementation? If so, are there plans for handling site IT staff turnover?

The panelists included Keith Marsolo, chair of the EHR Core, Mike Ho, co–principal investigator (PI) for Nudge, Andrea Cheville, PI for NOHARM, and Michele Balas, co-PI for BEST-ICU.

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

July 16, 2025: OPTIMUM Team Explores Complexities of Virtual Intervention Delivery

Posted on by Damon Seils

OPTIMUM logoFeatures of the external environment during online medical group visits and interacting with the technology itself emerged as key themes in interviews with patients participating in the OPTIMUM trial.

The findings were published online in Global Advances in Integrative Medicine and Health.

OPTIMUM, an NIH Collaboratory Trial led by Natalia Morone of Boston University and Boston Medical Center, is studying the addition of mindfulness-based stress reduction to usual care for patients with chronic low back pain, compared with usual care alone, with the goal of improving pain outcomes and reducing opioid prescriptions.

Patients’ experiences varied significantly during the online group medical visits and were influenced by social determinants of health. Exploring these differences in a racially and ethnically diverse group of participants enabled the researchers to begin developing a framework for comparing disparate experiences with virtual vs in-person mindfulness-based stress reduction interventions.

“On closer look, there are multiple variables at play that differentially affect how participants interact with the virtual setting,” the authors wrote. Jessica Barnhill of the University of North Carolina at Chapel Hill was the lead author of the report.

Read the full article.

OPTIMUM is supported within the NIH Pragmatic Trials Collaboratory through the NIH HEAL Initiative by a grant award administered by the National Center for Complementary and Integrative Health. Learn more about OPTIMUM.