%0 Journal Article
%T Pharmacodynamics Must Inform Statistics: An Example from a Cocaine Dependence Pharmacotherapy Trial
%A Theresa M. Winhusen
%A Daniel F. Lewis
%A Eugene C. Somoza
%A Paul Horn
%J ISRN Addiction
%D 2014
%R 10.1155/2014/927290
%X Background. There is no FDA-approved medication for cocaine dependence or consensus on the statistical approach for analyzing data from cocaine dependence pharmacotherapy trials. The goal of this paper is to illustrate the importance of understanding medication¡¯s pharmacodynamics when specifying the statistical model to test its efficacy. Method. Data from a double-blind placebo controlled trial of reserpine for cocaine dependence are analyzed. Since the antihypertensive properties of reserpine are well established, blood pressure data are utilized to evaluate the ability of two statistical models, one that does not take the pharmacodynamics of reserpine into account and one that does, to detect reserpine¡¯s antihypertensive effect. Results. The statistical model specified without regard to reserpine¡¯s pharmacodynamics failed to find a significant medication effect for either systolic ( ) or diastolic ( ) blood pressure. Contrariwise, the model based on the pharmacodynamics of reserpine found a significant effect for both systolic ( ) and diastolic ( ) blood pressure. Conclusions. If the pharmacodynamics of a study medication are not considered when specifying statistical models, then erroneous conclusions may be reached. This trial is registered with NCT00033033. 1. Introduction According to the Office of National Drug Control Policy, there are over 3 million long-term cocaine users in the USA [1]. Because psychosocial interventions for cocaine dependence are associated with high relapse rates [2, 3], substantial resources have been devoted to finding a pharmacological treatment. Despite these efforts, there is no FDA-approved pharmacological treatment for cocaine dependence. In view of this fact, it seems wise to carefully review the current designs of cocaine pharmacotherapy trials with the goal of identifying and correcting existing inefficiencies to maximize our ability to detect a medication effect if such were to exist in a future clinical trial. The gold standard for determining the efficacy of a medication is the double-blind randomized placebo controlled clinical trial with statistical analysis of the study data. While there is wide-spread agreement that ¡°double-blind¡± and ¡°randomized¡± are gold standards for study design there is less agreement on the statistical approach that should be utilized; other than that the statistical plan should be defined a priori. The trend over the past 15 years has been the use of increasingly sophisticated statistical analytic approaches, about which the study investigators, who have posed the hypotheses to be
%U http://www.hindawi.com/journals/isrn.addiction/2014/927290/