Volume 39 · Number 7
JULY 2009

Why Does the Randomized Clinical Trial Methodology So Often Mislead Clinical Decision Making? Focus on Moderators and Mediators of Treatment

By Helena Chmura Kraemer, PhD; Robert D. Gibbons, PhD

To provide a foundation for our discussion on moderators and mediators of treatment efficacy and effectiveness, we begin with a detailed discussion of the strengths and weaknesses of randomized clinical trials (RCTs).

Helena Chmura Kraemer, PhD, is Professor of Biostatistics in Psychiatry (Emerita), Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. Robert D. Gibbons, PhD, is with the Center for Health Statistics,

University of Illinois at Chicago.

Address correspondence to: Helena Chmura Kraemer, PhD, Professor of Biostatistics in Psychiatry (Emerita), Department of Psychiatry and Behavioral Sciences, Stanford University, 1116 Forest Avenue, Palo Alto, CA 94301; or e-mail hckhome@pacbell.net.

Dr. Kraemer has disclosed no relevant financial relationships. Dr. Gibbons disclosed the following relevant financial relationships: National Institutes of Mental Health: research grant recipient (R56-MH078580 and R01-MH8012201).

doi: 10.3928/00485713-20090625-06

EDUCATIONAL OBJECTIVES

1. Review moderators and mediators of treatment efficacy and effectiveness.

2. Identify limitations of randomized clinical trials for generalizing to the population.

3. Identify moderators and mediators for treatment-related effects.