Stepped-wedge trial

November 29, 2023: Special Biostatistics Series Continues With Guidelines for Stepped-Wedge Trials

Posted on by Damon Seils

In this Friday’s PCT Grand Rounds, Jim Hughes of the University of Washington will continue our special series, Advances in the Design and Analysis of Pragmatic Clinical Trials, with his presentation, “Guidelines for Design and Analysis of Stepped-Wedge Trials.” The session will be held on Friday, December 1, at 1:00 pm eastern.

Hughes is a professor emeritus of biostatistics at the University of Washington. This session’s moderator, Patrick Heagerty, is a professor of biostatistics at the University of Washington and a cochair of the NIH Pragmatic Trials Collaboratory’s Biostatistics and Study Design Core.

Join the online meeting.

This special Grand Rounds series will include additional moderated webinar discussions that bring together biostatisticians, clinical trials methodologists, and investigators to discuss challenges and share lessons learned in the design, implementation, and analysis of pragmatic trials. Download the series flyer and see the full schedule below.

All sessions are free and open to the public; no registration is required.

December 7, 2022: Ethics and Regulatory Grand Rounds Series Explores Stepped-Wedge Designs This Friday

Posted on by Damon Seils

Headshots of Monica Taljaard and David MagnusThis Friday’s PCT Grand Rounds will feature the next installment of our special series, Ethical & Regulatory Dimensions of Pragmatic Clinical Trials. Monica Taljaard and David Magnus will present “The Stepped Wedge Cluster Randomized Trial: Friend or Foe?”

The Grand Rounds session will be held on Friday, December 9, 2022, at 1:00 pm eastern.

Taljaard is a senior scientist in the Clinical Epidemiology Program at the Ottawa Hospital Research Institute and a professor of epidemiology and community medicine at the University of Ottawa. Magnus is the director of the Stanford Center for Biomedical Ethics and the Thomas A. Raffin Professor of Medicine and Biomedical Ethics and associate dean for research at the Stanford University School of Medicine.

Join the online meeting.

This special Grand Rounds series features moderated webinar discussions with panels of experts. The sessions focus on a range of topics, including the ethics of data sharing; ethical and regulatory considerations in the design and conduct of pragmatic trials; pragmatic research involving patients with dementia; and the use of waivers and alterations of consent.

Read the full program.

September 22, 2020: New Article Highlights Ethical and Regulatory Challenges of Conducting PCTs

Posted on by Gina Uhlenbrauck

Cover of Ethics & Human ResearchA recent article in Ethics & Human Research describes the experience and management of regulatory noncompliance during the conduct of a large, multisite embedded pragmatic clinical trial (ePCT). The Trauma Survivors Outcomes and Support (TSOS), an NIH Collaboratory Trial, was a stepped-wedge, cluster-randomized clinical trial of a collaborative care intervention for injured patients with symptoms of posttraumatic stress disorder in 25 level 1 trauma centers in the United States. The article, Ethical and Regulatory Concerns in Pragmatic Clinical Trial Monitoring and Oversight, was coauthored by members of the TSOS study team, the Collaboratory’s Ethics and Regulatory Core, and colleagues.

The authors describe how the study encountered variabilities in participant tracking across sites, which led to a study-wide internal audit and corrective action. The study team implemented a revision of the participant tracking system and retrained site staff in new procedures. Based on the lessons learned, the authors offer recommendations for future PCTs and relevant stakeholders, including institutional review boards, data safety and monitoring boards, institutions, and trial sponsors.

Among the recommendations:

  • Use a single IRB of record to streamline regulatory processes and reduce variability among research sites.
  • Standardize research procedures but allow for real-world flexibility; this could include real-time, workflow-integrated study logging that captures and documents provider turnover and regulatory training compliance.
  • Implement thorough, specific, and practical training in procedures, especially around participant enrollment and tracking.
  • Ensure that research procedures, monitoring and oversight plans, and training are study specific to account for unique issues, contexts, and needs.

Thoughtful planning, communication, and development and dissemination of standardized procedures remain hallmarks of successful research operations both to advance biomedical research and to ensure appropriate safeguards for its participants. –Roberts et al.

September 16, 2020: Results of TSOS Trial to Be Announced in NIH Collaboratory Grand Rounds

Posted on by Damon Seils

Photo of Dr. Doug Zatzick

The principal investigator of the Trauma Survivors Outcomes and Support (TSOS) pragmatic clinical trial, an NIH Collaboratory Trial, will announce the study’s primary results in the next session of PCT Grand Rounds on September 18.

Dr. Doug Zatzick of the University of Washington will present “The Trauma Survivors Outcomes and Support (TSOS) Pragmatic Clinical Trial: Effectiveness and Implementation Process Assessment Results.” The Grand Rounds session will be held on Friday, September 18, at 1:00 pm eastern. Join the online meeting.

TSOS was a stepped-wedge, cluster randomized clinical trial of a collaborative care intervention for injured patients with symptoms of posttraumatic stress disorder in 25 level 1 trauma centers in the United States.

TSOS is supported within the NIH Collaboratory by a cooperative agreement from the National Institute of Mental Health.

September 8, 2020: LIRE Trial Finds No Change in Healthcare Utilization, Small Drop in Opioid Prescriptions

Posted on by Damon Seils
Photo of Jeffrey Jarvik
Dr. Jerry Jarvik, principal investigator of LIRE

Inserting benchmark prevalence information about common imaging findings into spine image reports did not reduce spine-related healthcare utilization but did slightly reduce subsequent opioid prescriptions. These were the main findings of the Lumbar Imaging With Reporting of Epidemiology (LIRE) trial, an NIH Collaboratory Trial.

The report was published this month in JAMA Network Open.

Spine imaging often has incidental findings that can lead to unnecessary tests and treatments. Prior observational research suggested that placing information about the prevalence of common findings in spine imaging reports may help reassure physicians and patients about such findings and reduce subsequent, unnecessary healthcare interventions.

LIRE was a stepped-wedge, cluster randomized trial of an intervention that placed age- and modality-appropriate epidemiological benchmark information about common imaging findings in lumbar spine imaging reports. The intervention did not reduce spine-related healthcare utilization overall.

In prespecified secondary analyses, the intervention slightly reduced subsequent opioid prescriptions, and patients for whom computed tomography was the imaging modality had lower spine-related healthcare utilization.

LIRE was supported within the NIH Collaboratory by a cooperative agreement from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Read more about the LIRE trial.

June 22, 2020: NIH Offers Methods Webinar on Stepped-Wedge Cluster Randomized Trials

Posted on by Damon Seils

The NIH Office of Disease Prevention will continue its Methods: Mind the Gap webinar series on July 14 with “Overview of Statistical Models for the Design and Analysis of Stepped Wedge Cluster Randomized Trials.” Dr. Fan Li of Yale University, a longtime participant in the NIH Collaboratory’s Biostatistics and Study Design Core Working Group, will lead the webinar.

The Methods: Mind the Gap series explores research design, measurement, intervention, data analysis, and other methods of interest in prevention science. The July 14 session will address the stepped-wedge cluster randomized design, which has received increasing attention in pragmatic clinical trials (PCTs) and implementation science research. Since the design’s introduction, a variety of mixed-effects model extensions have been proposed for the design and analysis of PCTs. Dr. Li will provide a general model representation and discuss model extensions as alternative ways to characterize secular trends, intervention effects, and sources of heterogeneity. He will also review key model ingredients and clarify their implications for the design and analysis of stepped-wedge cluster randomized trials.

Register in advance to join the online presentation. Registration is required.

Methods: Mind the Gap Webinar July 14: Overview of Statistical Models for the Design and Analysis of Stepped Wedge Cluster Randomized Trials

Speaker: 

Fan Li, PhD
Yale University School of Public Health

Description:

The stepped-wedge cluster randomized design has received increasing attention in pragmatic clinical trials (PCTs) and implementation science research. Since the design’s introduction, a variety of mixed-effects model extensions have been proposed for the design and analysis of PCTs. In this talk, Dr. Fan Li of Yale University will provide a general model representation and regard various model extensions as alternative ways to characterize secular trends, intervention effects, and sources of heterogeneity. He will also review key model ingredients and clarify their implications for the design and analysis of stepped-wedge trials.

Registration required: 

https://www.prevention.nih.gov/education-training/methods-mind-gap/overview-statistical-models-design-and-analysis-stepped-wedge-cluster-randomized-trials

April 19, 2019: Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims (Doug Zatzick, MD)

Posted on by Gina Uhlenbrauck

Speaker

Doug Zatzick, MD
Professor of Psychiatry
Harborview Medical Center
University of Washington School of Medicine

Topic

Trauma Survivors Outcomes & Support (TSOS) Pragmatic Trial: Revisiting Effectiveness & Implementation Aims

Keywords

Trauma outcomes; NIH Collaboratory Trial; Hybrid study design; Implementation science; Pragmatic clinical trial; Cluster randomization; Stepped-wedge design; Posttraumatic stress disorder; PRECIS-2; Mental health intervention

Key Points

  • The TSOS NIH Collaboratory Trial is a cluster-randomized, stepped-wedge trial conducted at 25 U.S. trauma centers. The intervention involves an electronic health record PTSD screen and a baseline PTSD and comorbidity assessment. TSOS is turned on at each site across 4 “waves.”
  • During the course of this hybrid effectiveness-implementation trial, two domains on PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) were scored as more pragmatic and one domain as more explanatory than at the outset of the study.
  • The study team developed a methodology for assessing TSOS implementation aims. Called RAPICE (Rapid Assessment Procedure Informed Clinical Ethnography), the method yielded findings around recurrent intervention and research staff turnover across sites; observations that some patients do not engage in the intervention; and ways to inform a priori secondary hypotheses that suggest per-protocol modifications to the original intention-to-treat analyses.
  • TSOS will present results at the 2020 summit of the American College of Surgeons with the potential to integrate findings into the College’s regulatory and verification processes.

Discussion Themes

Regarding the need to collect outcome data, there may be an important distinction between two aspects of “pragmatic.” That is, while collecting outcome data makes a trial more expensive (one aspect of pragmatic), it doesn’t necessarily affect relevance or generalizability (another, more important, aspect of pragmatic).

Might there be studies which, by design, are not aiming to be on the outer [more pragmatic] spokes of the PRECIS-2 wheel?

Read more about the TSOS NIH Collaboratory Trial.

Tags

#pctGR, @Collaboratory1, @PRECIS_2