February 13, 2020

This roundtable will be videocast on March 11, 2020.

See draft agenda

See participant list


DRAFT Backgrounder

  • Current State: Most clinical trials funded by NIAMS use traditional randomized clinical trial (RCT) designs, which measure the difference in average outcome between participants assigned to one intervention or another. However, it would be more clinically useful to understand who, within the relevant population, would likely benefit more from (or be harmed by) either intervention. This can be addressed to some extent in an RCT by stratification, but at a significant increase in costs and requiring pre-specification. Other strategies may also provide practical means to uncover “whom to treat, when, with what?”
  • Objectives: The roundtable will gather input as to how clinical studies can be designed to identify groups of individuals that are more likely to benefit from a given intervention in order to better inform clinical care. At the end of the roundtable, attendees should be able to answer the following questions:
    • In general terms, how do results from clinical studies impact treatment decisions in the clinic?
    • When should RCTs intended to test the efficacy of an intervention be designed to estimate the benefits and harms of interventions in subsets of the participants?
    • When should other study approaches to subset analysis, including the incorporation of such methods into longitudinal observational studies, be used to understand the benefits and harms of interventions in subsets of participants?
    • How can these principles be applied to clinical research relevant to the NIAMS mission?Hand of doctor examining hand of patient
  • Desired Outputs
    • Ideas about clinical study designs that could inform NIAMS Funding Opportunity Announcements
    • A white paper summarizing ideas from the roundtable to emphasize NIAMS interest in this area
  • Intended Audience
    • NIAMS staff
      • To inform the review of clinical study applications
      • To inform discussions with investigators about their research studies
    • Research community
      • To help investigators explore options in the design of clinical studies
      • To communicate NIAMS support for these approaches
  • Questions to be Addressed
    • Background: Update on research on clinical decision-making
      • What is the literature on how information from clinical studies can impact decisions by patients and providers in the clinic?
      • Can alternative study designs be sufficiently rigorous to be included in practice guidelines?
    • Study Design Perspective: What are the advantages and disadvantages of different clinical study designs in terms of informing the clinical care and outcomes for individual patients?
      • Study designs could include
        • RCTs with strata or Bayesian analysis for assessing likelihood of response
        • Master protocols
        • Regression discontinuity methods
        • N of 1 / sequential studies
        • Observational studies designed and analyzed using advanced causal inference approaches
        • Others?
      • Considerations could include
        • Statistical requirements (e.g., how to power?)
        • Cost/benefit of creating platforms or infrastructure
        • Building studies embedded into electronic health records
  • Clinical Research Perspective: What clinical questions in NIAMS mission areas could be best addressed by different study designs? Are any types of intervention (e.g., surgical, biopsychosocial) more likely to be appropriate for certain study designs?

DRAFT Agenda

8:00-8:20 Welcome and Introductions (Bob Carter)
8:20-8:30 Goals (Tor Tosteson and Jeff Katz)
8:30-9:00 What matters in the clinic
            8:30-8:45 Patient perspective (Jennifer Horonjeff)
            8:45-9:00 Physician perspective and guidelines (Art Kavanaugh)
9:00-11:10 Innovative methods for subset analysis in randomized clinical trials (Tor Tosteson, moderator)
            9:00-9:20 Stratification and exploratory subset analysis (George Howard)
            9:20-9:40 Adaptive master protocols for subsets of patients with one disease (Lisa LaVange)
            9:40-9:55 Break
            9:55-10:15 Adaptive enrichment (Michael Rosenblum)
            10:15-10:35 Sequential, Multiple Assignment, Randomized Trials (SMART) (Kelley Kidwell)
            10:35-10:55 Desirability of outcome ranking (DOOR) (Scott Evans)
            10:55-11:10 Discussion
11:10-12:30 Subset analyses in cohort studies (Jeff Katz, moderator)
            11:10-11:30 Causal inference in follow-up of RCT cohorts: key concepts and methods (Eleanor Murray)
            11:30-11:50 Causal inference in longitudinal cohort studies: key concepts and methods (Patrick Heagerty)
            11:50-12:10 Machine learning in causal inference (David Benkeser)
            12:10-12:30 Examples of use of cohorts (Dennis Black)
12:30-1:10 Lunch
1:10-1:30 FDA snapshots: what a patient can expect based on a clinical trial (Mark Rothmann)
1:30-2:20 Creating a sustainable ecosystem for clinical studies (Tor Tosteson, discussant and moderator)
2:20-3:45 Application of methods for subset analysis in clinical research in NIAMS mission areas (Jeff Katz, discussant and moderator)
3:45-4:00 Closing thoughts (Tor Tosteson and Jeff Katz)

Confirmed participants

  • David Benkeser, PhD, MPH, Emory University
  • Dennis Black, PhD, University of California, San Francisco
  • Leigh Callahan, PhD, University of North Carolina
  • Scott Evans, PhD, George Washington University
  • Joel Gelfand, MD, University of Pennsylvania
  • Stuart Goodman, MD, Stanford University
  • Patrick Heagerty, PhD, University of Washington
  • Jennifer Horonjeff, PhD, Savvy Cooperative
  • George Howard, PhD, University of Alabama
  • Jeffrey Katz, MD, Brigham and Women's Hospital (co-chair)
  • Arthur Kavanaugh, MD, University of California, San Diego
  • Kelley Kidwell, PhD, University of Michigan
  • Wendy Kohrt, PhD, University of Colorado
  • Lisa LaVange, PhD, University of North Carolina
  • Timothy McAlindon, MD, MPH, Tufts Medical Center
  • Joan Merrill, MD, Oklahoma Medical Research Foundation
  • Eleanor (Ellie) Murray, PhD, Boston University
  • Nikolay Nikolov, MD, U.S. Food and Drug Administration
  • Michael Rosenblum, PhD, The Johns Hopkins University
  • Mark Rothmann, PhD, U.S. Food and Drug Administration
  • Ken Saag, MD, MSc, University of Alabama
  • Tor Tosteson, ScD, The Dartmouth Institute (co-chair)
  • Victoria Werth, MD, University of Pennsylvania