title: Sample size calculations for noninferiority trials with Poisson distributed count data.
abstract: Clinical trials with Poisson distributed count data as the primary outcome are common in various medical areas such as relapse counts in multiple sclerosis trials or the number of attacks in trials for the treatment of migraine. In this article, we present approximate sample size formulae for testing noninferiority using asymptotic tests which are based on restricted or unrestricted maximum likelihood estimators of the Poisson rates. The Poisson outcomes are allowed to be observed for unequal follow-up schemes, and both the situations that the noninferiority margin is expressed in terms of the difference and the ratio are considered. The exact type I error rates and powers of these tests are evaluated and the accuracy of the approximate sample size formulae is examined. The test statistic using the restricted maximum likelihood estimators (for the difference test problem) and the test statistic that is based on the logarithmic transformation and employs the maximum likelihood estimators (for the ratio test problem) show favorable type I error control and can be recommended for practical application. The approximate sample size formulae show high accuracy even for small sample sizes and provide power values identical or close to the aspired ones. The methods are illustrated by a clinical trial example from anesthesia.
authors: Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany.
authors: Kathrin
authors: K
authors: Stucke
authors: Meinhard
authors: M
authors: Kieser
mesh_terms: D000758:Anesthesia; D001699:Biometry / Q000379:methods*; D002986:Clinical Trials as Topic / Q000379:methods*; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D016013:Likelihood Functions; D010614:Pharynx; D016012:Poisson Distribution; D015742:Propofol / Q000494:pharmacology; D018401:Sample Size
chemical_list: D008012:Lidocaine; D015742:Propofol