research methods Archives - Page 4 of 7 - Rethinking Clinical Trials

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

Posted on June 22, 2020July 9, 2025 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.

June 17, 2020: Living Textbook Grand Rounds Series Continues With “Demystifying Biostatistical Concepts”

Posted on June 17, 2020March 30, 2023 by Damon Seils

Join us Friday, June 19, for “Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials,” the fourth session in our special 5-part Grand Rounds series focused on the Living Textbook. NIH Collaboratory investigators Drs. Liz Turner, Patrick Heagerty, and David Murray will discuss statistical design considerations, choosing the right design, and implications for the analysis. Topics covered will include:

RCTs, CRTs, and IRGTs: selecting the right trial design
Clustering and statistical power
Other analytical issues

See below for the full schedule of Living Textbook sessions and a special message from Dr. Kevin Weinfurt.

**Living Textbook Grand Rounds Series**
Date	Title	Speakers
January 31, 2020	Pragmatic Clinical Trials: How Do I Start?	Greg Simon, MD, MPH, Kaiser Permanente Washington Health Research Institute Lesley H. Curtis, PhD, Duke University
February 28, 2020	Preparing for the Unknown: Conducting Pragmatic Research in Real-World Contexts	Jerry Jarvik, MD, MPH, University of Washington Vince Mor, PhD, Brown University Leah Tuzzio, MPH, Kaiser Permanente Washington Health Research Institute
March 27, 2020	Tips for Putting Together a Successful PCT Grand Application	Wendy Weber, ND, PhD, MPH, National Center for Complementary and Integrative Health
June 19, 2020	Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials	Liz Turner, PhD, Duke University Patrick Heagerty, PhD, University of Washington David M. Murray, PhD, National Institutes of Health
July 17, 2020	Choosing What to Measure and Making It Happen: Your Keys to Pragmatic Trial Success	Rachel Richesson, PhD, MPH, Duke University Emily O’Brien, PhD, Duke University

June 5, 2020: PCORnet COVID-19 Common Data Model Design and Results (Thomas Carton, PhD, MS; Keith Marsolo, PhD; Jason Perry Block, MD, MPH)

Posted on June 9, 2020 by Gina Uhlenbrauck

Speakers

Thomas W. Carton, PhD, MS
Chief Data Officer
Louisiana Public Health Institute

Keith Marsolo, PhD
Associate Professor
Department of Population Health Sciences
Duke Clinical Research Institute
Duke University School of Medicine

Jason Perry Block, MD, MPH
Associate Professor of Population Medicine
Department of Population Medicine Harvard
Pilgrim Health Care Institute
Harvard Medical School

Topic

PCORnet COVID-19 Common Data Model Design and Results

Keywords

COVID-19; PCORnet; Common Data Model; CDM; Data query; Health disparities; Distributed data network

Key Points

For data to be useful in research, they have to be standardized across systems. The PCORnet Common Data Model standardizes data into a single language, enabling fast insights.
All the core data elements needed to support COVID-19 research and surveillance have a home in the PCORnet CDM. The goal for PCORnet is to characterize the cohort of COVID-19 patients and provide detailed information on demographics and pre-existing conditions.

Discussion Themes

Can PCORnet partners stand up a version of the CDM with more up-to-date information to allow for a faster characterization of the PCORnet COVID-19 population?

Is there a query to discover and address COVID-19 health disparities and social determinants of health?

Can PCORnet and NCATS’ National COVID Cohort Collaborative (N3C) work together?

Read more about PCORnet’s code lists and case definitions on GitHub.

Tags

#COVID19, #pctGR, @Collaboratory1

May 28, 2020: New Updates to Design and Analysis Plan Chapters in the Living Textbook

Posted on May 28, 2020May 28, 2020 by Damon Seils

The annual update of the Living Textbook has brought new content and organization to the Experimental Designs and Analysis Plan chapters. We invite you to explore these chapters and the external resources linked from the resources sidebar in each section.

The NIH Collaboratory Coordinating Center regularly refreshes content in the Living Textbook to improve the robust collection of resources it offers to the wider research community about how to plan and implement pragmatic clinical trials.

Sections of the Experimental Designs and Randomization Schemes chapter include:

Statistical Design Considerations
Cluster Randomized Trials
Randomization Methods
Choosing Between Cluster and Individual Randomization
Alternative Cluster Randomized Designs
Concealment and Blinding
Designing to Avoid Identification Bias
Additional Resources

Sections of the Analysis Plan chapter include:

Intraclass Correlation
Unequal Cluster Sizes
Accounting for Residual Confounding in the Analysis
Missing Data and Intention-to-Treat Analyses
EHR Data Extraction
Unanticipated Changes
Case Study: STOP CRC Trial

May 19, 2020: New Updates to What is a Pragmatic Clinical Trial Chapter in the Living Textbook

Posted on May 19, 2020January 17, 2024 by Gina Uhlenbrauck

The NIH Collaboratory regularly refreshes content in the Living Textbook in order to offer a robust collection of resources to the wider research community about how to plan and implement a pragmatic clinical trial. We invite you to explore recent additions to the introductory chapter What Is a Pragmatic Clinical Trial?

Highlights include information on the broader embedded PCT (ePCT) ecosystem, an updated table describing the 19 NIH Collaboratory Trials, a new illustration of the PRECIS-2 continuum, webinars on how to start a PCT, and more.

“The Living Textbook reflects a collection of expert consensus regarding special considerations, standard approaches, and best practices in the design, conduct, and reporting of PCTs.” – Dr. Kevin Weinfurt, Editor-in-Chief of the Living Textbook

Sections in What is a Pragmatic Clinical Trial include:

May 15, 2020: Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial (Derek Angus, MD, MPH)

Posted on May 15, 2020July 9, 2025 by Gina Uhlenbrauck

Speaker

Derek C. Angus, MD, MPH, FRCP
Distinguished Professor and Mitchell P. Fink Endowed Chair
Department of Critical Care Medicine
University of Pittsburgh and UPMC Health System

Topic

Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial

Keywords

Adaptive study design; REMAP-CAP; Community-acquired pneumonia; Embedded research; Learning health system; Pandemic; Response-adaptive randomization; Global adaptive platform; COVID-19

Key Points

The Randomised, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) aims to determine and continuously update the optimal set of treatments for community-acquired pneumonia.
An important aspect of adaptive trial designs is that already accrued data are used to increase the likelihood that patients within the trial are randomized to treatments that are beneficial.
With the onset of the COVID-19 pandemic, the REMAP study made use of an adaptive sub-platform called REMAP-COVID, which is studying multiple questions around COVID treatment simultaneously.

Discussion Themes

The COVID-19 pandemic requires us to do two things at once: learn and do. An integrated approach finds the optimal balance to treat patients as well as possible and learn as fast as possible.

Adaptive randomization is potentially more comfortable for physicians, where patients are preferentially assigned to the best therapy over time.

Read more about REMAP-CAP and Dr. Angus’ research in Optimizing the Trade-off Between Learning and Doing in a Pandemic (JAMA, March 2020).

Tags

#pctGR, @Collaboratory1, @remap_cap

May 8, 2020: Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions (Patrick Heagerty, PhD, Jacqueline Corrigan-Curay, JD, MD, Joshua C. Denny, MD, MS)

Posted on May 8, 2020 by Gina Uhlenbrauck

Speakers

Guest Moderator:
Patrick J. Heagerty, PhD
Professor, Department of Biostatistics, University of Washington

Panel:
Jacqueline Corrigan-Curay, JD, MD
Director of CDER’s Office of Medical Policy (OMP)
U.S. Food and Drug Administration (FDA)

Joshua C. Denny, MD, MS, FACMI
Chief Executive Officer, All of Us Research Program, NIH

Topic

Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Real World Evidence: Contemporary Experience and Future Directions

Keywords

Electronic health records; Real-world evidence; RWE; Real-world data; RWD; FDA; All of Us; Phenotypes; Regulatory; Fit-for-use data; Digital heath

Key Points

To create quality clinical/research records, we must design for multiuse by integrating standards-based tools in the EHR to bring together health care and research.
Quality real-world evidence cannot be built without quality real-world data. With greater efficiencies in data capture, randomization with real-world data provides a pathway for reliable—and persuasive—real-world evidence.

Discussion Themes

Patient-generated health data is part of FDA’s MyStudies Application, designed to facilitate the input of real-world data directly by patients, which can be linked to electronic health data supporting traditional clinical trials, pragmatic trials, observational studies, and registries.

In assessing data quality we can ask, How does a data element travel from clinical care to a research data set?

The NIH’s All of Us program is building a diverse database that can inform thousands of studies on a variety of health conditions.

The All of Us study is tracking COVID-19 in its patients. Sites have identified their COVID-19 participants and relevant labs. Consent is obtained for future sharing of data.

Tags

#pctGR, @Collaboratory1

May 4, 2020: TSOS Study Team Draws Lessons From Early COVID-19 Experiences in Washington State

Posted on May 4, 2020January 17, 2024 by Damon Seils

Clinicians and researchers at Seattle’s Harborview Medical Center documented their experiences in the early weeks of the COVID-19 outbreak in King County, Washington. Their report offers lessons from clinical and research personnel, patients, and peer interventionists during the evolving pandemic response in an early US COVID-19 epicenter.

The article, published online in Psychiatry, presents a case series of experiences of frontline clinical and research teams in incorporating COVID-19 prevention strategies in the context of an ongoing comparative effectiveness trial of multidisciplinary, peer-integrated care coordination for patients with severe injury. The report also describes key themes from qualitative data collected during daily team meetings for the Trauma Survivors Outcomes and Support (TSOS) study, a pragmatic clinical trial also underway at Harborview. TSOS, an NIH Collaboratory Trial, is a stepped-wedge, cluster randomized pragmatic trial testing the delivery of screening and intervention strategies for patients with posttraumatic stress disorder and comorbid conditions at 24 level I trauma centers in the United States.

The case series offers evidence that primary and secondary prevention strategies can be integrated into ongoing clinical and research interventions during pandemic response. Procedures can also be developed to support team members who are adapting to rapidly changing individual, organizational, and societal demands.

This work was supported in part by the Patient-Centered Outcomes Research Institute (PCORI). TSOS is supported within the NIH Collaboratory by a cooperative agreement from the National Institute of Mental Health and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director.

For more news and resources related to the COVID-19 public health emergency, see the COVID-19 Resources page.

May 1, 2020: Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Keynote-Can the COVID-19 Crisis Lead to Reformation of the Evidence Generation Ecosystem? (Robert Califf, MD, MACC)

Posted on May 1, 2020May 8, 2020 by Gina Uhlenbrauck

Speaker

Robert Califf, MD, MACC
Head of Strategy and Policy
Verily Life Sciences and Google Health

Topic

Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Keynote-Can the COVID-19 Crisis Lead to Reformation of the Evidence Generation Ecosystem?

Keywords

Electronic health records; Digital health; Mobile health; Coronavirus; COVID-19; Ecosystem; Clinical trials; Evidence generation

Key Points

The HERO Registry and RECOVERY Trial are good examples of a rapid clinical research response to the urgent COVID-19 health crisis.
Among the essential steps to move the evidence generation system in the right direction:
- Evaluate what has and has not worked in the changes made in response to the crisis
- Allocate a significant part of recovery funding to transition issues in evidence generation, especially at the interface of medicine and public health
- Increase purposefulness by creating methods for deciding the most important questions and rewarding behavior that gets those questions answered quickly

Discussion Themes

The COVID-19 pandemic has shone a spotlight on disparities in our current healthcare delivery system. How can we avoid leaving the most vulnerable of society behind?

Telemedicine can be a framework for the integration of research and clinical care. But the digital element must be integrated with the human element. The routine and effective use of digital information should free up effort to fix the human components that are holding us back.

We’ve been trying to modernize clinical trial design for decades (factorial/sequential/adaptive designs for example). While some positive movement in the past month has been made, the research enterprise remains largely conservative when it comes to design modernization. How do we make more rapid progress?

Tags

#pctGR, #COVID19, @Collaboratory1, @Califf001

April 7, 2020: Support for the PRISM Embedded PCTs From the Health Care Systems Interactions Core

Posted on April 7, 2020April 8, 2020 by Gina Uhlenbrauck

In a recent video interview, Dr. Eric Larson, chair of the Collaboratory’s Health Care Systems Interactions Core, and Leah Tuzzio, research associate, describe ways the Core is supporting the PRISM Demonstration Projects. A priority for conducting embedded PCTs (ePCTs) is establishing strong, sustainable relationships between the study team and health system leadership, clinicians, and staff.

For researchers who are evaluating pain management interventions, the Core advises remaining flexible when integrating the intervention and being mindful of documenting any adaptations made throughout the trial. Other best practices include understanding the context of the health setting, anticipating road blocks, and incorporating the intervention with minimal burden to clinicians and staff.

“Pain is a complicated area. It’s not a specific disease, it’s a state, and it’s a state that everybody experiences.”

For additional suggestions from the Core, read the new chapter in the Living Textbook on how to monitor intervention fidelity and adaptations. Learn more about the Health Care Systems Interactions Core and view interviews with the PRISM Demonstration Projects: