Methodological Issues in Clinical Trials of Drug and Behavior Therapies


  • Kenneth A. Holroyd PhD,

  • Scott W. Powers PhD, ABPP,

  • Frank Andrasik PhD

  • From the Department of Psychology, Ohio University, Athens, OH (Dr. Holroyd); Division of Psychology, Cincinnati Children's Hospital, Cincinnati, OH (Dr. Powers); and Institute for Human and Machine Cognition, University of West Florida, Pensacola, FL (Dr. Andrasik).

Address all correspondence to Dr. Kenneth A. Holroyd, Psychology Department, Ohio University, Athens, OH 45701-2979.


Trials that compare drug and behavior therapies or evaluate combination therapy raise special methodological issues. This article reviews these methodological issues and, where possible, offers guidelines for addressing them. Sources of bias in the selection and recruitment of participants and in the measurement of treatment outcomes are discussed. In addition, methodological problems presented by the differing structures of behavior and drug therapy, by confounding variables, such as allegiance effects, differential expectations and preferences for drug or behavior therapy, and differential adherence with drug or behavior therapy also are reviewed. Issues in the selection of appropriate control groups are also discussed.