cluster randomized trials

January 8, 2026: Study Design Paper Published for BEST-ICU

Posted on by Damon Seils
Headshots of Dr. Michele Balas and Dr. Eduard Vasilevskis
Dr. Michele Balas and Dr. Eduard Vasilevskis, principal investigators for BEST-ICU

The study design paper for BEST-ICU has been published online in Trials. Congratulations to the study team on reaching this important milestone for all NIH Collaboratory Trials!

The BEST-ICU trial is evaluating 2 strategies grounded in behavioral economics theory and implementation science to increase adoption of the ABCDEF bundle in the intensive care unit and improve care for critically ill adults across a variety of healthcare systems. The ABCDEF bundle is a multicomponent, evidence-based intervention to improve team-based care.

The study is being led by Eduard Vasilevskis of the University of Wisconsin and Michele Balas of the University of Nebraska and is supported by a grant award from the National, Heart, Lung, and Blood Institute.

Read the full study design paper.

June 25, 2025: The BETTER CARE-HF Pragmatic Trial, in This Week’s Rethinking Clinical Trials Grand Rounds

Posted on by Damon Seils
Headshot of Dr. Amrita Mukhopadhyay
Dr. Amrita Mukhopadhyay

In this Friday’s Rethinking Clinical Trials Grand Rounds, Amrita Mukhopadhyay of the NYU Grossman School of Medicine will present “The BETTER CARE-HF Study: A Pragmatic Cluster Randomized Trial to Improve Heart Failure Care.”

The live webinar will be held on Friday, June 27, 2025, at 1:00 pm eastern.

Mukhopadhyay is the Eugene Braunwald, MD, Assistant Professor of Cardiology at the NYU Grossman School of Medicine.

Join the online meeting.

June 3, 2025: GGC4H Team Sees Good Intervention Fidelity With Virtual Delivery, but Faces Engagement Challenge

Posted on by Damon Seils
Headshots of Dr. Margaret Kuklinski and Dr. Stacy Sterling
Dr. Margaret Kuklinski and Dr. Stacy Sterling, co–principal investigators for GGC4H

In an evaluation conducted alongside the GGC4H trial, researchers assessed the intervention fidelity of a version of the Guiding Good Choices parenting program that was adapted for online delivery. They found that virtual delivery of the intervention was feasible but that retention of participants was a challenge.

The report was published in the Journal of Community Psychology.

GGC4H, an NIH Collaboratory Trial, is a pragmatic, cluster randomized clinical trial testing the feasibility and effectiveness of implementing within healthcare systems the Guiding Good Choices program for caregivers of adolescents aged 11 to 13 years to prevent common behavioral problems, such as substance use. The trial is the first large-scale implementation of the virtual adaptation of the Guiding Good Choices program, and of the program in pediatric primary care settings.

The researchers used attendance records, interventionist surveys and focus groups, and observer reports to examine attendance, dosage, adherence, quality of intervention delivery, and participant engagement in the program. They reported high marks for all of these outcomes but found that attendance was lower than expected.

Read the full report.

GGC4H is supported within the NIH Collaboratory by a grant award from the National Center for Complementary and Integrative Health. Learn more about GGC4H.

May 13, 2025: Video Decision Aid and Clinician Communication Training Boost Advance Care Planning in Oncology Clinics

Posted on by Damon Seils
Headshots of Dr. James Tulsky and Dr. Angelo Volandes
Dr. James Tulsky and Dr. Angelo Volandes, principal investigators for ACP PEACE

A video decision aid for older patients with advanced cancer, coupled with communication skills training for clinicians, led to higher rates of documented advance care planning in oncology clinics, according to the ACP PEACE study.

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

Many older adults with advanced cancer do not discuss treatment preferences or goals of care with their clinicians. Lack of communication about patients’ preferences can lead to patients receiving care that does not match their values.

ACP PEACE, an NIH Collaboratory Trial, was a stepped-wedge, cluster randomized trial testing the delivery of a video decision aid to patients together with goals-of-care communication skills training to oncology clinicians in 3 healthcare systems. The study included 13,800 patients at 29 clinics. Each clinic was randomly assigned to either the intervention or usual care at the beginning of the study. Due to the stepped-wedge design of the trial, all clinics were exposed to the intervention by the end of the study.

Logo for the ACP PEACE Demonstration Project

The intervention included an evidence-based, patient-facing video decision aid available in 25 languages. It also included a communication training program to improve clinicians’ skills in delivering serious news, responding to emotion, and eliciting patients’ goals. The primary outcome was documentation of advance care planning in the electronic health record, which could include documentation of a goals-of-care conversation, palliative care, hospice, or limitation of life-sustaining treatments.

The proportion of patients with documentation of advance care planning was greater with the ACP PEACE intervention than with usual care. The difference was attributable to a greater proportion of patients in the intervention phase having a goals-of-care conversation. There were no significant differences between the intervention and usual care for the documentation of palliative care, hospice, or limitation of life-sustaining treatments.

Read the full article.

“By focusing concurrently on both clinicians and patients—giving clinicians the skills to have these difficult conversations and preparing patients to engage with them—we were able to increase the number of documented goals-of-care conversations,” said James Tulsky, the Poorvu Jaffe Chair in Supportive Oncology at the Dana-Farber Cancer Institute and a co–principal investigator for ACP PEACE.

“If we are going to achieve shared decision-making, we need to bring everyone onto the same page,” Tulsky said.

Angelo Volandes, the Anna Gundlach Huber Professor in Medicine at the Geisel School of Medicine at Dartmouth and a co–principal investigator for ACP PEACE, highlighted the logistical challenge of conducting a large pragmatic clinical trial across 3 major healthcare systems during the COVID-19 pandemic.

“What made it work was a shared commitment—from frontline clinicians to healthcare system leaders—to ensure that older adults with advanced cancer had the opportunity to reflect on their values and have those conversations documented,” Volandes said.

“This trial wasn’t just about changing documentation rates, it was about changing the culture of communication, at scale,” he added.

ACP PEACE is supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute on Aging.

Learn more about ACP PEACE.

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 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 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.

October 15, 2024: Case Study Describes a Reassessment of Sample Size in an Ongoing Cluster Randomized Trial

Posted on by Damon Seils

FM-TIPS logoA new case study from the NIH Pragmatic Trials Collaboratory highlights an interim reassessment of sample size during an ongoing cluster randomized trial. The case study was published this week in the Living Textbook of Pragmatic Clinical Trials.

Researchers in cluster randomized trials must account for potential correlation between clusters in the design and analysis of their trial by estimating the intraclass correlation when calculating the target sample size. Often they use preliminary data from the planned enrollment sites to estimate the correlation. However, when preliminary data are unavailable at the time of study design, they may use interim data collected during the trial itself to reassess the trial’s sample size.

The contributors of the case study focus on FM-TIPS, an NIH Collaboratory Trial, to describe an approach to conducting an interim reassessment of sample size in an ongoing trial. Read the full case study.

FM-TIPS is examining whether the addition of transcutaneous electrical nerve stimulation to routine physical therapy improves movement-evoked pain compared with physical therapy alone among patients with fibromyalgia. The trial is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases through the NIH HEAL Initiative. Learn more about FM-TIPS.

The contributors of the case study include members of the FM-TIPS study team and leaders of the NIH Collaboratory’s Biostatistics and Study Design Core. David-Erick Lafontant is a statistician, Bridget Zimmerman is a clinical professor of biostatistics, and Emine Bayman is an associate professor of biostatistics—all at the University of Iowa. Megan McCabe is an assistant professor of biostatistics at the University of Alabama at Birmingham. Patrick Heagerty is a professor of biostatistics at the University of Washington. Liz Turner is an associate professor of biostatistics and bioinformatics at Duke University.

April 4, 2024: ICD-Pieces Trial Sees No Reduction in Hospitalization for Patients With Chronic Kidney Disease

Posted on by Damon Seils
Dr. Miguel Vazquez, principal investigator for ICD-Pieces

A primary care intervention for patients with coexisting chronic kidney disease, type 2 diabetes, and hypertension did not reduce the hospitalization rate for these patients when compared to usual care, according to the ICD-Pieces study.

The results of the study were published this week in the New England Journal of Medicine.

ICD-Pieces, an NIH Collaboratory Trial, was a cluster randomized, pragmatic clinical trial testing an intervention that used an electronic health record–based algorithm and practice facilitators in 141 primary care practices. The study team randomly assigned more than 11,000 adults to receive either the intervention or usual care. The large, diverse study population—of whom 20% were Black and almost 20% were Hispanic or Latino—was representative of the population with chronic kidney disease, type 2 diabetes, and hypertension in the United States.

In the intervention group, the study team used an algorithm to identify patients in the electronic health record in real time. Practice facilitators then worked with the participating primary care providers and patients to meet blood pressure targets, promote use of appropriate medications, achieve goals for blood glucose control, and engage in other guideline-directed care. The intervention period lasted 12 months, and the primary outcome was hospitalization for any reason.

At the end of the study, the hospitalization rates were similar between the intervention group and the usual care group. Rates of key secondary outcomes, such as emergency department visits and cardiovascular events, were also similar between the groups.

Read the full article.

“Although we did not observe a difference in the primary outcome, we believe the study is an important step in advancing our understanding of how to conduct pragmatic trials embedded in healthcare systems,” said Dr. Miguel Vazquez, the principal investigator for ICD-Pieces and a professor of internal medicine at UT Southwestern Medical Center in Dallas.

The study team identified and enrolled a large number of patients, including a large proportion of patients who are members of racial and ethnic groups that are usually underrepresented in clinical trials, Vazquez explained. Moreover, the intervention was delivered across 4 large healthcare systems using a variety of electronic health record systems, there was fidelity in intervention delivery, and there was robust capture of outcomes in a diverse population with multiple chronic conditions.

Vazquez also emphasized the value of conducting the ICD-Pieces study as an NIH Collaboratory Trial.

“The opportunity to work within the NIH Pragmatic Trials Collaboratory was essential for the successful completion of our trial,” Vazquez said. “Access to the expertise from the Coordinating Center and ongoing interactions with investigators from other projects provided critical knowledge to conduct our study embedded in large health systems,” he added.

ICD-Pieces is 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 ICD-Pieces.