Implications of Clinical Trial Design on Sample Size Requirements

The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, dou-ble-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide suf-ficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I er-ror. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two particularly rele-vant aspects of such a design often receive insufficient at-tention 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 unre-liability 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 over-come the problems of unreliability and multiplicity. Key words: multiplicity/reliability/sample size/statistical powe