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.
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.
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
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
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.
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.
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
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).
The Healthcare Worker Exposure Response & Outcomes (HERO) Registry invites both clinical and nonclinical healthcare workers to share their life experiences in order to understand the perspectives and problems faced by those on the COVID-19 pandemic frontlines. HERO Registry participants could have the opportunity to participate in future research studies to improve the understanding of COVID-19 and beyond, generating evidence to help healthcare workers stay safe and healthy.
The HERO Registry is open to all healthcare workers, including nurses, therapists, physicians, emergency responders, food service workers, environmental service workers, interpreters, transporters — anyone who works in a setting where people receive health care.
In case you missed the May 1 keynote address by Robert M. Califf, MD, MACC, you can now listen to the recorded webinar and Q&A. Dr. Califf, head of strategy and policy for Verily Life Sciences and Google Health, kicked off the Collaboratory’s Grand Rounds workshop series, Advances at the Intersection of Digital Health, Electronic Health Records, and Pragmatic Clinical Trials.
His presentation outlined several opportunities to drive change and rebuild clinical research in the aftermath of COVID-19, including:
Evaluate what has and has not worked in the changes that have been 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
Do everything possible to fix the “purposefulness issue”:
Create methods for deciding the most important questions
Reward behavior that gets important questions answered quickly
Develop inclusive networks driven by people with the health problems of interest; increase incentives for clinicians and investigators that lead to reliable and faster evidence generation (balance financial focus with purpose); and automate mapping of EHR data beyond individual systems
“The effective use of digital information such as electronic health records, telehealth, applications, and patient-reported outcomes should free up effort to fix the human components that are holding us back.” – Dr. Robert Califf
Recording June 30, Available July 7, 2020: Podcast: Summary Expert Panel Discussion (Patrick J. Heagerty, PhD; Keith Marsolo, PhD; Wendy Weber, ND, PhD, MPH; Moderator: Lesley H. Curtis, PhD)
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?
The annual update of the Living Textbook has brought new content and organization to the 
