study design

June 30, 2020: Special Issue of JAGS Features NIA IMPACT Collaboratory’s Work on Embedded Pragmatic Trials and Dementia Care

Posted on by Karen Staman

Members of the National Institute on Aging (NIA) IMPACT Collaboratory (Imbedded Pragmatic Alzheimer’s Disease [AD] and AD-Related Dementias [AD/ADRD] Clinical Trials) recently contributed 10 articles to a special issue of the Journal of the American Geriatrics Society. The articles support the IMPACT Collaboratory’s mission to “build the nation’s capacity to conduct ePCTs within healthcare systems for people living with dementia and their caregivers.”

The NIA IMPACT Collaboratory was modeled after the NIH Collaboratory; it has Working Group Cores to help advance the mission and support pilot and NIH Collaboratory Trials. The Cores include Administration, Design and Statistics, Dissemination and Implementation, Health Care Systems, Health Equity, Patient/Caregiver Reported Outcomes, Pilot Studies, Regulation and Ethics, Stakeholder Engagement, Technical Data, and Training.

Each of the Cores contributed an article to the special issue to describe how they are working to improve the quality and effectiveness of ePCTs for people living with dementia and their care partners.

The full list of articles (below) also includes an introductory article by leadership of the NIA IMPACT Collaboratory, Drs. Susan Mitchell, Vincent Mor, Ellen McCarthy, and Jill Harrison.

  • Embedded Pragmatic Trials in Dementia Care: Realizing the Vision of the NIA IMPACT Collaboratory
  • Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers
  • Building a National Program for Pilot Studies of Embedded Pragmatic Clinical Trials in Dementia Care
  • Training the Workforce to Conduct Embedded Pragmatic Clinical Trials to Improve Care for People Living with Dementia and Their Caregivers
  • Dissemination and Implementation of Evidence-Based Dementia Care Using Embedded Pragmatic Trials
  • Ethical and Regulatory Issues for Embedded Pragmatic Trials Involving People Living with Dementia
  • Transforming Dementia Care Through Pragmatic Clinical Trials Embedded in Learning Healthcare Systems
  • Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art
  • Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia
  • Engaging Stakeholders in the Design and Conduct of Embedded Pragmatic Clinical Trials for Alzheimer’s Disease and Alzheimer’s Disease–Related Dementias
  • Statistical Considerations for Embedded Pragmatic Clinical Trials in People Living with Dementia

Drs. Mitchell and Mor are also co–principal investigators of the Pragmatic Trial of Video Education in Nursing Homes (PROVEN), an NIH Collaboratory Trial. See the Living Textbook for more on the NIH Collaboratory Core Working Groups and NIH Collaboratory Trials.

June 19, 2020: Living Textbook Grand Rounds Series: Part 4-Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials (Elizabeth Turner, PhD; Patrick Heagerty, PhD; David Murray, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Elizabeth Turner, PhD
Associate Professor
Department of Biostatistics & Bioinformatics
Duke Global Health Institute
Duke University  

Patrick Heagerty, PhD
Professor Department of Biostatistics
University of Washington  

David Murray, PhD
Associate Director for Prevention
Director, Office of Disease Prevention National Institutes of Health

Topic

Demystifying Biostatistical Concepts for Embedded Pragmatic Clinical Trials

Keywords

Embedded PCTs; Biostatistics; Trial design; Cluster-randomized trial (CRT); Stepped-wedge; Intraclass correlation coefficient; NIH Collaboratory Trial; Sample size; Individually randomized group treatment

Key Points

  • Focus on the research question, because that will drive the design, and the design will drive the analysis.
  • Select design features with analysis in mind, and collaborate early with a statistician. Weigh statistical choices against the challenges of implementation.
  • If possible, choose individual randomization. However, sometimes there is a strong rationale for choosing cluster/group randomization. Clustering must be accounted for in both design and analysis for CRTs and individually randomized group treatment (IRGT) trials.
  • The intraclass correlation coefficient (ICC) is a common measure of outcome clustering. Estimating the ICC is needed for study planning and power.
  • Increasing the number of clusters has more impact on power than increasing the number of patients per cluster.

Discussion Themes

With the move to virtual healthcare, the boundaries between clinic-based clusters have become more fluid. What approaches should trials use to describe contamination and estimate the impact of contamination on outcomes?

Read more about ICC in a Living Textbook resource and visit the Training Resources page for practical help on how to plan and conduct ePCTs.

Learn more in the Living Textbook about considerations for trial design and analysis for ePCTs.

Visit the NIH Collaboratory’s Biostatistics and Study Design Core webpage for more resources around design and analysis issues in ePCTs.

The NIH hosts a Research Methods Resources website with materials on this topic.

Tags

#pctGR, @Collaboratory1

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.

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

Posted on 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 12, 2020: A Cluster Randomized Pragmatic Trial of an Advance Care Planning Video Intervention in Long-Stay Nursing Home Residents: Main Findings from the PROVEN Trial (Susan Mitchell, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Susan L. Mitchell, MD, MPH
Senior Scientist
Hebrew SeniorLife
Hinda and Arthur Marcus Institute for Aging Research
Professor of Medicine
Harvard Medical School

Topic

A Cluster Randomized Pragmatic Trial of an Advance Care Planning Video Intervention in Long-Stay Nursing Home Residents: Main Findings from the PROVEN Trial

Keywords

Embedded pragmatic trial; PROVEN; Advance care planning; Nursing homes; Video intervention; Medicare; Care preferences; Decision support tool; Minimum data set; Intention to treat

Key Points

  • The PROVEN trial was the first large-scale embedded pragmatic trial conducted in nursing homes.
  • The advance care planning (ACP) video intervention in PROVEN was meant as an adjunct to first-person discussions with the clinical care provider.
  • The levels of care preferences described in the ACP videos were life prolongation, limited care, and comfort care.
  • PROVEN’s primary outcome was the number of transfers to the hospital from the nursing home.

Discussion Themes

Widely adoptable, effective interventions to improve ACP in nursing homes remain elusive.

Of the challenges of conducting PCTs embedded in nursing homes, it is important not to overlook the real-world priorities of stakeholders. A high level of endorsement, from C-suite to frontline care providers, is needed before attempting such a trial.

While a priority for nursing home administrators is the number of residents who transfer to the hospital, an essential question for patients and palliative care experts is whether patients receive care that matches their goals and preferences. This is hard to ascertain in a pragmatic way.

Read more about the PROVEN trial, and learn about a new research initiative built on the success of the NIH Collaboratory: the National Institute on Aging’s IMPACT Collaboratory, which is directly funding pilots of embedded PCTs across diverse healthcare settings to improve the care of patients with dementia and their caregivers.

Tags

#pctGR, @Collaboratory1

June 4, 2020: New Chapter in the Living Textbook Describes the Uses and How-tos of Patient-Reported Outcomes

Posted on by Karen Staman

A new chapter in the Living Textbook describes how patient-reported outcomes (PROs) are used in different settings and how to choose and integrate PRO measures into an embedded pragmatic clinical trial.

The chapter also characterizes PRO use within the PRISM program (Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing) of the NIH HEAL Initiative (Helping End Addiction Long-term Initiative). NIH Collaboratory Trials supported through the PRISM program include:

AcuOA: Pragmatic Trial of Acupuncture for Chronic Low Back Pain in Older Adults
FM TIPS: Fibromyalgia TENS in Physical Therapy Study
NOHARM: Non-pharmacological Options in Postoperative Hospital-Based and Rehabilitation Pain Management
OPTIMUM: Group-based mindfulness for patients with chronic low back pain in the primary care setting

The main topics of the chapter are:

The authors also include Core Outcome Sets for chronic pain, low back pain, musculoskeletal pain, and cancer.

May 29, 2020: Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Experiences from the Collaboratory PCTs (Wendy Weber, ND, PhD, MPH; Jerry Jarvik, MD, MPH; Lynn DeBar, PhD, MPH; Doug Zatzick, MD; Vince Mor, PhD)

Posted on by Gina Uhlenbrauck

Speakers

Guest Moderator
Wendy Weber, ND, PhD, MPH
Branch Chief, Clinical Research in Complementary and Integrative Health
Division of Extramural Research
National Center for Complementary and Integrative Health, NIH

Panel
Jeffrey (Jerry) G. Jarvik, MD, MPH
LIRE NIH Collaboratory Trials
Professor of Radiology, Neurological Surgery and Health Services
Adjunct Professor of Pharmacy and Orthopedics & Sports Medicine
Co-Director, Comparative Effectiveness, Cost and Outcomes Research Center
Director, UW CLEAR Center for Musculoskeletal Disorders
University of Washington School of Medicine

Lynn DeBar, PhD, MPH
PPACT NIH Collaboratory Trials
Senior Scientist
Kaiser Permanente Washington Health Research Institute

Doug Zatzick, MD
TSOS NIH Collaboratory Trial
Professor, Department of Psychiatry and Behavioral Sciences
University of Washington School of Medicine

Vince Mor, PhD
PROVEN NIH Collaboratory Trial
Florence Pirce Grant University Professor and Professor of Health Services, Policy and Practice
Brown University School of Public Health

Topic

Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials: Experiences from the Collaboratory PCTs

Keywords

EHRs; PCTs; Embedded PCTs; NIH Collaboratory; NIH Collaboratory Trial; PROVEN; LIRE; PPACT; TSOS; Patient-reported outcomes; PROs; Data collection

Key Points

  • Lessons and experiences from the NIH Collaboratory Trials include:
    • Pilot the intervention at the partnering health systems and work closely with site programmers who know the systems best.
    • Monitor the trial’s implementation at regular intervals to detect breakage.
    • Keep both the intervention and the outcomes as simple as possible.
    • Choose endpoints that matter to patients and providers and that are captured reliably as part of routine clinical care.
  • Enabling rapid outcome ascertainment in large pragmatic trials can be a game changer.
  • The Emergency Department Information Exchange (EDIE) in Washington state is an innovative technology platform that can help with the collection of population-level administrative data for acute care follow-up and ongoing care plans.
  • It might be better to uncouple some types of patient-reported outcome (PRO) data collection from the routine clinical care visit.

Discussion Themes

A common theme throughout all the NIH Collaboratory Trial PCTs is how dynamic and ever-changing health care delivery settings are. The reality is that the trial as planned is often not the trial as piloted or conducted.

What type of education is most effective about how to use a PRO to inform care plans and decision-making?

There is nothing like a crisis (eg, the coronavirus pandemic) for people to do things that were before thought impossible. Now, the concept of a “visit” is changing, and there will likely be more uncoupling.

Read more about all 19 of the NIH Collaboratory Trials.

Tags

#pctGR, @Collaboratory1

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

Posted on 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 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:

  1. Why Are We Talking About Pragmatic Trials?
  2. The Embedded Pragmatic Clinical Trial Ecosystem
  3. Differentiating Between RCTs, PCTs, and Quality Improvement Activities
  4. Pragmatic Elements: An Introduction to PRECIS-2
  5. Key Considerations for PCTs
  6. Additional Resources

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

Posted on 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