NIH Collaboratory Trials

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.

July 8, 2025: PRIM-ER Team Observes More Healthy Days at Home for Patients With Cancer Diagnosis

Posted on by Damon Seils
Headshot of Dr. Oluwaseun Adeyemi with screenshot of PRIM-ER article
Dr. Oluwaseun Adeyemi, lead author of the report

In an analysis of data on seriously ill older adults from emergency departments that participated in the PRIM-ER trial, poor prognosis was associated with fewer healthy days at home. However, a cancer diagnosis was associated with more healthy days at home.

The analysis was published online this month in BMC Geriatrics.

PRIM-ER, an NIH Collaboratory Trial, was a stepped-wedge, cluster randomized trial of a palliative care training program in emergency departments in the United States. The program consisted of training in palliative care, simulation-based communication workshops, clinical decision support tools, and audit and feedback.

In the new analysis of data for nearly 123,000 seriously ill older adults, worse prognosis was associated with a lower rate of healthy days at home for patients both with and without cancer. However, having a cancer diagnosis was associated with more healthy days at home. Demographic factors such as age and race/ethnicity were also associated with healthy days at home.

The authors of the report, led by Oluwaseun Adeyemi of New York University, under the guidance of principal investigators Corita Grudzen and Keith Goldfeld, believe this difference may be related to the “structured and comprehensive care pathways available to cancer patients, such as outpatient oncology services, home-based palliative care, and symptom management plans designed to minimize hospitalizations.”

“Our findings highlight the need for tailored care models, including enhanced outpatient services and home-based care to reduce hospitalizations and increase [healthy days at home] for patients with serious non-cancer illnesses,” the authors wrote.

Read the full article.

PRIM-ER was supported within the NIH Pragmatic Trials Collaboratory by a grant award from the National Institute on Aging. Learn more about PRIM-ER.

July 3, 2025: OPTIMUM Team Identifies Facilitators of Participant Retention and Engagement

Posted on by Damon Seils
Headshot of Dr. Natalia Morone, principal investigator for OPTIMUM
Dr. Natalia Morone, principal investigator for OPTIMUM

Trust in their clinicians, positive interactions with study staff, and opportunities for social connection can improve recruitment, retention, and engagement with research participants, according to focus groups of participants in the OPTIMUM trial. These factors can be especially important for first-time research participants and for groups that are historically underrepresented in clinical trials.

The article was published online in Global Advances in Integrative Medicine and Health.

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. Patients in the control group were also offered free mindfulness sessions after the end of the 12-month follow-up period.

Understanding of randomized controlled trials and general research processes emerged as another important theme in the focus groups. In particular, appreciating the value of the control group in a randomized controlled trial can support participants’ ongoing engagement.

“Consistent, positive study staff interactions were particularly important for control group participants who were not immediately receiving the intervention that initially interested them in the trial,” the authors wrote.

The OPTIMUM trial, which is embedded in safety net hospitals and federally qualified health centers, includes a large number of first-time participants in research and patients from racial and ethnic groups that tend to be underrepresented in research. Understanding the needs and perspectives of first-time research participants and those from underrepresented groups can improve recruitment and retention strategies and help ensure the representativeness of study populations.

Read the full report.

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.

July 1, 2025: As Their Studies Wrap Up, Researchers Share Lessons for Pragmatic Trials

Posted on by Damon Seils

Headshots of Drs. Christine Goertz, Andrea Cook, Shruti Gohil, and Stacy SterlingA key feature of the NIH Pragmatic Trials Collaboratory is its culture of learning and knowledge sharing among investigators who are planning and conducting pragmatic clinical trials. In a session at the program’s 2025 Annual Steering Committee Meeting, a panel of investigators discussed their recently completed NIH Collaboratory Trials and their thoughts about future directions for pragmatic research.

The panelists included Andrea Cook, co–principal investigator (PI) for BackInAction; Shruti Gohil, lead investigator for INSPIRE; and Stacy Sterling, co-PI for GGC4H. Christine Goertz, a co-PI for IMPACt-LBP, moderated the discussion.

Key Takeaways

What do investigators wish they had known before starting a pragmatic trial? Sterling highlighted a need for ongoing engagement with partnering healthcare systems’ senior leaders to ensure they understand the challenges of adopting and sustaining the study intervention. Cook stressed the importance of educating site personnel about what it means to participate in the trial, including the potential for randomization to a usual care arm.

“We also included nonphysician clinicians in the education about the intervention, because they are often doing the steps being targeted by the intervention,” Gohil added.

How can we apply these lessons in future pragmatic trials? “Doing an embedded pragmatic trial is sort of like having a child: You really need the guidance of people who have gone before you and have real-life experience,” Goertz said.

The panelists proposed the development of more standardized materials for the consent process and other trial elements. They also discussed the need for broader dissemination strategies and new ways to promote implementation tools from trials with successful interventions.

Gohil described her research team’s commitment to developing a dissemination toolkit so people will understand how to approach implementation. She noted that, as soon as the trial was completed but before publication, the research team presented the results to the participating sites.

Greg Simon, the PI for SPOT and a member of the NIH Collaboratory Coordinating Center’s leadership team, stressed the importance of including research partners in dissemination.

“Don’t write the discussion section [of your study results paper] until you’ve talked with your healthcare system partners; they might have something to teach us about what the results mean,” he said.

About the Trials

  • BackInAction, supported by the National Center for Complementary and Integrative Health (NCCIH), is comparing standard and advanced courses of acupuncture with usual care for older adults with chronic low back pain.
  • GGC4H, supported by NCCIH, is testing the feasibility and effectiveness of implementing within healthcare systems the Guiding Good Choices program for caregivers of early adolescents to prevent common behavioral problems, such as substance use.
  • IMPACt-LBP, supported by NCCIH, is evaluating the effect of first-contact patient referral to physical therapists and doctors of chiropractic for low back pain.
  • INSPIRE, supported by the National Institute of Allergy and Infectious Diseases, used personalized clinical decision support to improve judicious antibiotic prescribing for non–critically ill patients hospitalized with abdominal infections or skin and soft tissue infections.
  • SPOT, supported by the National Institute of Mental Health, compared care management and dialectical behavior therapy skills training to usual care for adults at risk of self-harm or suicidal behavior.

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

June 24, 2025: Study Design Paper Published for ARBOR-Telehealth

Posted on by Damon Seils

ARBOR-Telehealth logoThe study design paper for ARBOR-Telehealth has been published online in BMJ Open. Congratulations to the study team on reaching this important milestone for all NIH Collaboratory Trials!

The ARBOR-Telehealth study 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. A secondary aim of the study is to compare the effectiveness of the study’s risk-stratification approach.

The study is being led by Richard Skolasky and Kevin McLaughlin of Johns Hopkins University and is supported by a grant award from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Read the full study design paper.

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.