Winhusen Theresa M, Lewis Daniel F, Somoza Eugene C, Horn Paul
Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA.
Addiction Sciences Division, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, College of Medicine, 3131 Harvey Avenue, Cincinnati, OH 45229, USA ; Veterans Affairs Medical Center (VISN 10), 3200 Vine Street, Cincinnati, OH 45220, USA.
ISRN Addict. 2014 Feb 5;2014:927290. doi: 10.1155/2014/927290. eCollection 2014.
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 (P = 0.49) or diastolic (P = 0.59) blood pressure. Contrariwise, the model based on the pharmacodynamics of reserpine found a significant effect for both systolic (P = 0.002) and diastolic (P = 0.004) 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.
背景。目前尚无美国食品药品监督管理局（FDA）批准的用于治疗可卡因依赖的药物，对于可卡因依赖药物治疗试验数据的统计分析方法也未达成共识。本文的目的是说明在确定用于检验药物疗效的统计模型时，理解药物药效学的重要性。方法。分析了利血平治疗可卡因依赖的双盲安慰剂对照试验的数据。由于利血平的降压特性已得到充分证实，因此利用血压数据来评估两种统计模型检测利血平降压效果的能力，一种模型未考虑利血平的药效学，另一种则考虑了。结果。未考虑利血平药效学的统计模型未发现收缩压（P = 0.49）或舒张压（P = 0.59）有显著的药物效应。相反，基于利血平药效学的模型发现收缩压（P = 0.002）和舒张压（P = 0.004）均有显著效应。结论。在确定统计模型时若不考虑研究药物的药效学，可能会得出错误结论。该试验已在ClinicalTrials.gov上注册，注册号为NCT00033033。
