What Is a Clinically Meaningful Effect?

Leslie Citrome, MD, MPH


August 27, 2013

Defining a Clinically Meaningful Effect for the Design and Interpretation of Randomized Controlled Trials

Keefe RS, Kraemer HC, Epstein RS, et al
Innov Clin Neurosci. 2013;10(Suppl A):4S-19S

Clinically Meaningful Effects

This review article summarized the proceedings of a meeting on how to define clinically meaningful effects when testing medications in randomized controlled trials. Defining a clinically meaningful effect can be difficult; the effect size may be modest, particularly over the short term, because of a strong response to placebo. Keefe and colleagues reveal that payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. They introduce the concept of moderators in success rate differences that may help better delineate clinically meaningful effects.


This review, available as an open-access publication, is a good starting point to better understand how limited the information from randomized controlled trials can be. Registration trials that bring new agents to market have as their main goal the demonstration of statistical superiority of the proposed new agent over placebo. This is not the same goal that clinicians (or patients) have when using a new product. The end-users of a product want an intervention that has clinically relevant superiority over a readily available alternative in terms of efficacy and/or tolerability. This review goes into some detail about different measures of effect size, and although some of the concepts and math may be more complex than typically found in a clinical review article, the summaries of the different perspectives on the term "clinically meaningful effect" are valuable. The unique concerns of patients, payers, healthcare economists, investors, and the US Food and Drug Administration are well articulated in this article. Additional discussion on comparative effectiveness research and a sophisticated discussion on clinical decision-making make this paper quite suitable as a teaching resource.



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