The ABCs of RCTs

More and more, clinicians have a growing number of possible treatments available to choose from, but lack evidence to guide those decisions. This situation prompted the development of the Sequential, Multiple Assignment, Randomized Trial (SMART), in which sequential steps are adapted to a patient’s individual response, subjects are randomized to feasible options at key decision points in which equipoise is achieved, and evolving characteristics—beyond just baseline characteristics—are collected between and at decision points.

To illustrate this model, Dr. Schanberg discussed a trial that would seek to treat patients with juvenile idiopathic arthritis who have had inadequate response to a tumor necrosis factor (TNF) alpha inhibitor. At decision point #1 (i.e., at initial TNF-alpha failure), the participant can either be treated with a different TNF-alpha inhibitor or receive medication with a different mechanism of action. At decision point #2 (i.e., after 3–6 months of the initial treatment), responders could be continued on treatment and non-responders could be switched to a new non-TNF-alpha biologic.

The SMART design for a clinical trial is meant to mimic what which would occur in real-life and create a plan for how patients within a trial will be treated depending on their course and response—or lack of response—to a treatment within a trial.

Dr. Schanberg noted several potential benefits to SMART design of clinical trials, including the ability to target a range of scientific questions, the ability to use smaller sample sizes of participants and still yield important outcomes data, and yield scientific insights that are highly relevant to clinical practice.

In Sum

The session was full of wisdom for those willing to modify classic models of RCT design. With more talks like these, the RCT space is likely to continue to evolve—and improve—in the coming years.

Dr. Jason Liebowitz

Jason Liebowitz, MD, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

Reference

1. Allen KD, Woolson S, Hoenig HM, et al. Stepped exercise program for patients with knee osteoarthritis: A randomized controlled trial. Ann Intern Med. 2021 Mar;174(3):298–307.