NIH Collaboratory Trials

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.

April 15, 2024: TAICHIKNEE Randomizes First Cohort in Study to Improve Knee Osteoarthritis Pain

Posted on by Damon Seils

Logo for the TAICHIKNEE trialThe TAICHIKNEE study randomized its first cohort of participants this month, and the intervention group began tai chi classes this week. Congratulations to the TAICHIKNEE team for reaching this important milestone!

TAICHIKNEE will compare the effects of web-based tai chi interventions versus routine care for individuals experiencing knee pain due to osteoarthritis. The practice of tai chi integrates physical, psychosocial, and behavioral components and has exhibited clinically significant improvements in chronic knee osteoarthritis pain. The results of the study will inform widespread adoption of mind-body approaches for knee osteoarthritis across healthcare systems.

TAICHIKNEE is supported within the NIH Pragmatic Trials Collaboratory through a cooperative agreement from the National Center for Complementary and Integrative Medicine. Learn more about TAICHIKNEE.

April 14, 2025: In INSPIRE Trials, Automated Prompts Reduced Unnecessary Prescribing of Extended-Spectrum Antibiotics

Posted on by Damon Seils
Headshot of Dr. Shruti Gohil
Dr. Shruti Gohil

A program that used automated prompts to deliver patient-specific risk information to clinicians led to significant reductions in the use of extended-spectrum antibiotics for hospitalized patients, according to the INSPIRE trials.

The results of the trials were published online ahead of print in JAMA Internal Medicine and JAMA Surgery.

INSPIRE, an NIH Collaboratory Trial, consists 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.

Although fewer than 5% of such patients have an antibiotic-resistant infection, more than half receive extended-spectrum antibiotics. Tools to support judicious antibiotic prescribing are needed to curb the public health threat of antibiotic resistance. More than 2.8 million antimicrobial-resistant infections occur each year in the United States alone, and more than 35,000 people die as a result, according to the Centers for Disease Control and Prevention.

Conducted at 92 hospitals in the United States, INSPIRE compared routine care under hospital-based antibiotic stewardship programs with an enhanced program that added a predictive algorithm to reduce unnecessary prescribing of extended-spectrum antibiotics. The computerized provider order entry system at the intervention sites notified physicians when the antibiotic they selected was discordant with the estimated need for that antibiotic.

Logo for the INSPIRE Demonstration ProjectIn the skin and soft tissue infections trial, which included 60,725 patients, the automated prompts reduced the use of empiric extended-spectrum antibiotics targeting Pseudomonas and multidrug-resistant gram-negative bacteria by 28% without increasing intensive care unit admissions or hospital length of stay. Read the full report in JAMA Internal Medicine.

Likewise, in the abdominal infection trial, among 105,004 patients, the prompts led to a 35% relative reduction in empiric extended-spectrum antibiotic days of therapy without increasing intensive care unit transfers or length of stay. Read the full report in JAMA Surgery.

In an invited commentary accompanying the JAMA Surgery report, Joshua Brown of the University of Pittsburgh Medical Center wrote, “Now that Gohil and colleagues have shown efficacy of their intervention, the next big question is how well it will scale to be implemented broadly.”

“These trials represent a major step forward for the field of antibiotic stewardship,” wrote Shinya Hasegawa and Daniel Livorsi of University of Iowa Health Care in an editorial in JAMA Network Open. “By next exploring the why behind the bundle’s success, strategies to replicate INSPIRE can be developed and tailored to a variety of hospital settings.”

Headshot of Dr. Susan Huang
Dr. Susan Huang
Headshot of Dr. Richard Platt
Dr. Richard Platt

INSPIRE is supported within the NIH Pragmatic Trials Collaboratory by a grant from the National Institute of Allergy and Infectious Diseases. Shruti Gohil of the University of California, Irvine, is INSPIRE’s lead investigator. Susan Huang of UC Irvine and Richard Platt of the Harvard Pilgrim Health Care Institute are the co–principal investigators.

Learn more about INSPIRE.

April 7, 2025: Study Design Paper Published for IMPACt-LBP

Posted on by Damon Seils

Logo for the IMPACt-LBP Demonstration ProjectThe study design paper for IMPACt-LBP has been published online in BMJ Open. Congratulations to the study team on reaching this important milestone for all NIH Collaboratory Trials!

IMPACt-LBP is evaluating the effect of first-contact patient referral to physical therapists and doctors of chiropractic for low back pain. The study team is seeking to determine if initial contact with these “primary spine practitioners” will improve physical function and pain, decrease opioid prescriptions, improve patient satisfaction, and reduce the costs and use of health care services in patients with low back pain when compared with usual medical care.

The study is being led by Christine Goertz, Adam Goode, and Hrishikesh Chakraborty of Duke University and Jon Lurie of Dartmouth Hitchcock Medical Center and is supported by a grant award from the National Center for Complementary and Integrative Health.

Read the full study design paper.

March 20, 2025: iPATH Team Explores Integration of Artificial Intelligence Into Analysis of Qualitative Data

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

Researchers from iPATH, an NIH Collaboratory Trial, described key considerations for integrating artificial intelligence tools into analyses of qualitative data.

The report was posted this month on the AcademyHealth Blog.

The iPATH trial, led by principal investigator Sara Singer at Stanford University, will test the implementation of a practice transformation strategy for type 2 diabetes in federally qualified health centers in California, Massachusetts, Ohio, and Puerto Rico. In the first phase of the project, the study team is refining the strategy by conducting case studies with 12 health centers to identify organizational conditions and processes that promote or impede the effectiveness of diabetes care.

Interviews for the 12 case studies generated 170 hours of qualitative data plus related materials. The study team explored how rapidly evolving artificial intelligence tools, such as large language models, might enhance researchers’ handling of large qualitative datasets, including labor-intensive and time-consuming processes of transcription, coding, and analysis.

Read the full report.

iPATH is supported by a grant award from the National Institute on Minority Health and Health Disparities. Learn more about iPATH.

March 18, 2025: ABATE Infection Analysis Explores Cost-Effectiveness of Strategies to Prevent Hospital-Acquired Infections

Posted on by Damon Seils

Logo for the ABATE Infection Demonstration ProjectIn a cost-effectiveness analysis using data from the ABATE Infection trial, a strategy of chlorhexidine bathing and nasal decolonization targeted to hospitalized adults with medical devices in non–intensive care unit (ICU) settings was cost-effective in reducing hospital-acquired infections.

The study results were published this month in JAMA Network Open.

ABATE Infection, an NIH Collaboratory Trial, was a cluster randomized pragmatic trial of universal chlorhexidine bathing and nasal decolonization compared with usual care for more than 500,000 hospitalized patients. Previous research had shown the effectiveness of the intervention in ICUs. ABATE Infection studied the intervention in non-ICU settings, finding no significant effect overall but a significant reduction in infections among patients with medical devices.

The Agency for Healthcare Research and Quality later published a toolkit to help clinical teams reduce hospital-acquired infections based on the intervention materials used in the ABATE Infection trial.

For the cost-effectiveness analysis, researchers created a decision analysis model using a simulated cohort of patients based on the ABATE Infection study population. The targeted strategy for patients with medical devices was cost-effective in a wide range of scenarios from the perspectives of both hospitals and healthcare payers. Universal decolonization for all hospitalized adults in non-ICU settings was cost-effective in some scenarios.

Read the full report.

ABATE Infection was supported within the NIH Collaboratory by the National Institute of Allergy and Infectious Diseases. Learn more about ABATE Infection.

March 11, 2025: Study Design Paper Published for MOMs Chat & Care Study

Posted on by Damon Seils

MOMs Chat and Care Study logoThe study design paper for the MOMs Chat & Care Study has been published online ahead of print in Contemporary Clinical Trials. Congratulations to the study team on reaching this important milestone for all NIH Collaboratory Trials!

The MOMs Chat and Care Study is testing the effectiveness of an integrated care model approach at 2 levels of intensity designed to facilitate timely, appropriate care for Black birthing people to reduce their risk for severe maternal morbidity. Patients in both study arms will receive close clinical and behavioral health monitoring and navigation to timely care and services.

The study is being led by Stephanie Fitzpatrick at the Feinstein Institutes for Medical Research and is supported by an R01 grant award from the National Institute of Nursing Research.

Read the full study design paper.

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.

March 6, 2025: Enrollment Begins for Several of the Newest NIH Collaboratory Trials

Posted on by Damon Seils

In recent months, 5 of the newest NIH Collaboratory Trials have begun to enroll research participants. Congratulations to the study teams from ARBOR-Telehealth, BEST-ICU, Chat 4 Heart Health, I CAN DO Surgical ACP, and the MOMs Chat & Care Study for reaching this important project milestone!

 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 study is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

BEST-ICU is evaluating 2 strategies grounded in behavioral economics theory and implementation science to increase ABCDEF bundle adoption in the intensive care unit and improve care for critically ill adults across a variety of healthcare systems, particularly those serving populations with known health disparities. The ABCDEF bundle is a multicomponent, evidence-based intervention to improve team-based care. The trial is supported by the National, Heart, Lung, and Blood Institute (NHLBI).

Chat 4 Heart Health is testing the comparative effectiveness of 3 text messaging delivery strategies that have been shown to improve individuals’ self-management health behaviors, including physical activity and medication adherence. The study will provide evidence regarding the best population-based strategy for universal delivery to engage patients in self-management to improve the American Heart Association’s “Life’s Essential 8” measures for improving and maintaining cardiovascular health. The project is supported by NHLBI.

I CAN DO Surgical ACP 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 trial is supported by the National Institute on Aging.

The MOMs Chat and Care Study is testing the effectiveness of an integrated care model approach at 2 levels of intensity designed to facilitate timely, appropriate care for Black birthing people to reduce their risk for severe maternal morbidity. Patients in both study arms will receive close clinical and behavioral health monitoring and navigation to timely care and services. The study is supported by the National Institute of Nursing Research.

 

March 4, 2025: PRIM-ER Team Develops Innovative Statistical Techniques for Stepped-Wedge Trials

Posted on by Damon Seils

Cover image of Statistics in MedicineResearchers with PRIM-ER, an NIH Collaboratory Trial, published 2 innovative statistical techniques for evaluating intervention effects in stepped-wedge, cluster randomized trials. The new models, which use Bayesian methods, outperformed traditional analytic methods and other Bayesian approaches in simulations and real-world applications.

The article was published online in Statistics in Medicine.

In cluster randomized trials with stepped-wedge designs, the clusters are randomized into several groups, and all groups start the trial in the control condition. Groups of clusters cross over to the intervention condition on a staggered timeline, and all groups receive the intervention before the end of the trial.

Stepped-wedge designs can be advantageous when simultaneous rollout of the intervention to all clusters is infeasible, or when withholding the intervention from any cluster would be unethical, or when there is a risk of contamination between intervention subjects and control subjects. However, stepped-wedge designs can also introduce confounding by time, as the intervention is rolled out to clusters in waves. Temporal trends during the study can influence the study’s outcomes.

(Learn more about stepped-wedge designs in the Living Textbook.)

The PRIM-ER researchers tested 2 new Bayesian hierarchical penalized spline models to improve the estimation of intervention effects in stepped-wedge trials. The first model focuses on immediate intervention effects and accounts for large numbers of clusters and time periods. The second model extends the first by accounting for time-varying intervention effects. The researchers applied both models to data from PRIM-ER.

Read the full report.

PRIM-ER tested a multidisciplinary primary palliative care intervention in a diverse mix of emergency departments in the United States to improve the delivery of goal-directed emergency care of older adults. The study was supported by the National Institute on Aging. Learn more about PRIM-ER.