A multistage analysis strategy for a clinical trial to assess successively more stringent criteria for a primary endpoint with a low event rate

摘要: This paper describes how a multistage analysis strategy for clinical trial can assess sequence of hypotheses that pertain to successively more stringent criteria excess risk exclusion or superiority primary endpoint with low event rate. The assessment correspond an adverse guideline sufficient efficacy as in the case vaccine trials. proposed is implemented through set interim analyses, and success one less at be basis regulatory submission, whereas continues accumulate information address stringent, but not futile, criteria. Simulations show satisfactory control type I error, power, potential analyses when true relative favorable than assumed planned sample size. Copyright © 2013 John Wiley & Sons, Ltd.