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A multistage analysis strategy for a clinical trial to assess successively more stringent criteria for a primary endpoint with a low event rate
Author(s) -
Li Siying,
Hussey Michael A.,
Schwartz Todd A.,
Koch Gary G.
Publication year - 2013
Publication title -
pharmaceutical statistics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.421
H-Index - 38
eISSN - 1539-1612
pISSN - 1539-1604
DOI - 10.1002/pst.1554
Subject(s) - interim , interim analysis , event (particle physics) , sample size determination , clinical endpoint , clinical trial , type i and type ii errors , guideline , computer science , statistics , risk analysis (engineering) , econometrics , medicine , mathematics , physics , archaeology , pathology , quantum mechanics , history
This paper describes how a multistage analysis strategy for a clinical trial can assess a sequence of hypotheses that pertain to successively more stringent criteria for excess risk exclusion or superiority for a primary endpoint with a low event rate. The criteria for assessment can correspond to excess risk of an adverse event or to a guideline for sufficient efficacy as in the case of vaccine trials. The proposed strategy is implemented through a set of interim analyses, and success for one or more of the less stringent criteria at an interim analysis can be the basis for a regulatory submission, whereas the clinical trial continues to accumulate information to address the more stringent, but not futile, criteria. Simulations show that the proposed strategy is satisfactory for control of type I error, sufficient power, and potential success at interim analyses when the true relative risk is more favorable than assumed for the planned sample size. Copyright © 2013 John Wiley & Sons, Ltd.