The Grand Rounds session will be held on Friday, September 22, 2023, at 1:00 pm eastern.
Coker is the chief of general pediatrics and a professor of pediatrics at the University of Washington School of Medicine and Seattle Children’s Hospital. She is the former and founding research director for the Health Equity Research Program at Seattle Children Hospital’s Center for Diversity and Health Equity, and she currently serves as the codirector of the University of Washington’s NIH-funded Child Health Equity Research Fellowship.
The Grand Rounds session will be held on Friday, September 8, 2023, at 1:00 pm eastern.
Prekker is an associate professor of emergency medicine and pulmonary and critical care medicine at the University of Minnesota. Casey is an assistant professor of pulmonary and critical care at Vanderbilt University and the director of the coordinating center for the Pragmatic Critical Care Research Group.
The NIH Pragmatic Trials Collaboratory is launching a special Grand Rounds series to share advances in the design and analysis of pragmatic clinical trials.
Join us on the first Friday of each month, October through January, to hear the latest best practices and explore emerging questions with experts from the program’s Biostatistics and Study Design Core.
Over the past decade, the Core has worked with investigators to fine-tune study designs, develop rigorous analysis plans, and offer guidance to the broader community of researchers who are planning pragmatic trials. With this new Grand Rounds series, the Core is bringing together biostatisticians, clinical trials methodologists, and investigators to discuss challenges and share lessons learned in the design, implementation, and analysis of pragmatic trials.
The webinar series, Advances in the Design and Analysis of Pragmatic Clinical Trials, will kick off on Friday, October 6, at 1:00 pm ET with a presentation on design and analysis considerations for implementation trials by David Murray, NIH associate director for disease prevention and director of the NIH Office of Disease Prevention.
The series will include 3 additional moderated webinar discussions. These sessions will focus on a range of topics, including complex clustering, best practices in the design and analysis of stepped-wedge trials, and handling missing data in cluster randomized trials.
Clinical trials face challenges that were amplified during the COVID-19 public health emergency, including avoiding shortcomings of prior data, equipoise, heterogeneity of treatment effect, making trials happen quickly, the complexity of studying a single intervention in isolation, and the sustainability and efficiency of trial conduct.
REMAP-CAP is an adaptive platform trial simultaneously evaluation multiple treatments in domains using a master protocol. In adaptive trials, trial design features are modified during the trial to maximize statistical efficiency or achieve better patient outcomes. Examples include response-adaptive randomization, sample size reassessment, multi-arm designs, group sequential stopping, and others.
Most diseases have multiple component therapies, and several questions must be evaluated for each component, including whether there is heterogeneity of treatment effect. Clinical trials generally assume homogenous treatment effects; in reality there are heterogeneous treatment effects.
In therapeutic anticoagulation domain of REMAP-CAP, Bayesian techniques allowed for greater statistical efficiency in arriving at conclusions about effectiveness. A post hoc analysis evaluated strategies for further studying heterogeneity of treatment effect.
REMAP-CAP offered operational and statistical efficiencies, addressing challenges associated with the COVID-19 pandemic. The trial shortened the divide between clinical care and research and demonstrated a capacity for “parabiosis” with other trials in a multiple-platform trial. Adaptive designs increasingly empowered the trial to hunt for heterogeneity of treatment effect.
Discussion Themes
– When an adaptive design enables researchers to control for variations in usual baseline care for complex conditions, there are benefits for statistical efficiency and power and possibly an ability to isolate heterogeneity of treatment effect.
– There were advantages and disadvantages to the multi-platform approach. The approach definitely generated evidence more quickly. Prospective harmonization with other platform trials also brought operational efficiencies, including accelerated recruitment and enrollment.
– In applying this approach to studies of chronic conditions, different monitoring guidelines may be needed to evaluate more modest treatment effect. For example, futility criteria could be lowered. Two-stage designs could also be helpful, such as first evaluating safety outcomes before scaling up to a phase 3 study, or evaluating surrogate outcomes in a phase 2 component and then graduating the treatments that appear more likely have a greater benefit in phase 3, or other ways of mitigating the need for a large sample size.
– An adaptive platform can place additional burdens on the DSMB. REMAP-CAP has a single DSMB overseeing all domains, with its membership having both clinical expertise and experience adaptive trials, and the committee needing to review both primary outcome data and secondary endpoints and other information.
The Grand Rounds session will be held on Friday, August 11, 2023, at 1:00 pm eastern.
The REMAP-CAP trial (Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia) has a novel adaptive trial design to evaluate several treatment options simultaneously and efficiently. The design is able to adapt in the event of pandemics, and it increases the likelihood that patients will receive the treatment that is most likely to be effective for them.
REMAP-CAP was previously in the Rethinking Clinical Trials Grand Rounds spotlight on May 15, 2020, and April 2, 2021.
Lawler is a cardiologist and clinician-scientist at the McGill University Health Centre in Montreal and the Peter Munk Cardiac Centre at University Health Network in Toronto.
The Grand Rounds session will be held on Friday, July 28, 2023, at 1:00 pm eastern.
Bergstrom is a professor of biology at the University of Washington. He writes frequently on the spread of misinformation. In 2020, Bergstrom coauthored a book, Calling Bullshit: The Art of Skepticism in a Data-Driven World, to offer readers “tools to dismantle misinformation and think clearly in a world of fake news and bad data.”
The Grand Rounds session will be held on Friday, July 21, 2023, at 1:00 pm eastern.
IMPACt-LBP, an NIH Pragmatic Trials Collaboratory Trials, is a cluster randomized trial of a multidisciplinary collaborative team approach for low back pain vs usual care. The study will determine whether receiving first-line care from “primary spine practitioners” improves physical function, decreases pain and opioid prescriptions, improves patient satisfaction, and decreases costs and utilization of healthcare services.
Dr. Goertz is a professor in musculoskeletal research and the vice chair for implementation of spine health innovations in the Department of Orthopaedic Surgery, and Dr. Goode is an associate professor of orthopaedic surgery—both at Duke University.
In this Friday’s PCT Grand Rounds, Tumaini Rucker Coker of the University of Washington and Seattle Children’s Hospital will present “Community Health Workers in Early Childhood Well-Child Care.”
In this Friday’s PCT Grand Rounds, Pasquale Rummo of the NYU Grossman School of Medicine will present 
In this Friday’s PCT Grand Rounds, Matthew Prekker of the University of Minnesota and Jonathan Casey of Vanderbilt University will present 
The NIH Pragmatic Trials Collaboratory is launching a 
In this Friday’s PCT Grand Rounds, Gabriela Schmajuk of the University of California, San Francisco, will present 
