title: Implications of clinical trial design on sample size requirements.
abstract: The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly relevant aspects of such a design often receive insufficient attention in an RCT. Multiple outcomes inflate type I error, and an unreliable assessment process introduces bias and reduces statistical power. Here we describe how both unreliability and multiple outcomes can increase the study costs and duration and reduce the feasibility of the study. The objective of this article is to consider strategies that overcome the problems of unreliability and multiplicity.
authors.affiliation: Weill Medical College of Cornell University, New York, NY 10065, USA. acleon@med.cornell.edu
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Leon
mesh_terms: D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D035061:Control Groups; D004311:Double-Blind Method; D032984:Ethics, Research; D006801:Humans; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D017063:Outcome Assessment, Health Care / Q000191:economics / Q000706:statistics & numerical data; D010865:Pilot Projects; D011594:Psychometrics; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000592:standards* / Q000706:statistics & numerical data; D011930:Reaction Time / Q000502:physiology; D015203:Reproducibility of Results; D012107:Research Design / Q000592:standards*; D018401:Sample Size; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology; D013223:Statistics as Topic / Q000592:standards; D016896:Treatment Outcome