On the detection of outlier clinics in medical and surgical trials: II. Theoretical considerations

In the conduct of multicenter clinical trials, comparisons among the clinical centers are often made with respect to such measures as incidence of diagnosis of various events, operative mortality, and patient adherence to the treatment regimen. Slippage and outlier tests for statistically identifying clinics that are outliers-that is, truly different from the rest of the clinics-with respect to such measures are described. Critical values obtained for these tests by computer simulation are given for various numbers of clinics, numbers of patients enrolled per clinic, and probabilities (p) of a patient incurring a given event under the null hypothesis of no differences among the clinics. Previously published critical values based on normally distributed response variables are applicable only for p close to 0.5. The slippage and outlier tests are compared with respect to statistical power. Alternative forms of the slippage test based on the angular transformation and on hypergeometric probabilities are considered.