Regression to the Mean: Implications for Clinical Trials of Psychotropic Agents in Dementia

Authors: Jeffrey L. Cummings; Rochelle E. Tractenberg; Anthony Gamst; Linda Teri; Donna Masterman; Leon J. Thal

Source: Current Alzheimer Research, Volume 1, Number 4, November 2004 , pp. 323-328(6)

Publisher: Bentham Science Publishers

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Abstract:

Effective drug development depends on understanding and optimizing results from controlled clinical trials. A recent double-blind, randomized, controlled trial of the treatment of agitation in patients with Alzheimer's disease (AD) found no difference among the four arms of the study: haloperidol, trazodone, behavioral therapy, placebo. The current analysis was undertaken to further investigate the issues bearing on this outcome and to identify better means of detecting psychotropic effects in trials involving patients with AD.

This was post hoc analysis of a clinical trial data set. Patients in the placebo group were divided into responders (25% reduction in symptoms), worseners (25% worsening in baseline agitation scores), and those without a change in symptoms.

Analysis of the trial outcomes demonstrated that the reduction observed in the placebo group was of the same magnitude as predicted by regression to the mean. Patients exhibiting greater improvement had more severe baseline behavioral disturbances. The relatively modest severity of agitation and the low medication doses achieved in the study may have further contributed to the failure to distinguish among treatment groups.

Research design adjustments such as collection of both screening and baseline measures to determine eligibility may limit the effects of regression to the mean on trial outcomes and reduce this challenge to clinical trials.

Keywords: randomized controlled trials; alzheimers disease; psychotropic agents; placebo; pharmacotherapy; haloperidol; behavior rating scale

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567205043332027

Affiliations: 1: Reed Neurological Research Center, UCLA School of Medicine, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.

Publication date: 2004-11-01

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Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

Regression to the Mean: Implications for Clinical Trials of Psychotropic Agents in Dementia

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