Application of boundary calculation methodologies to group sequential testing in general parametric models

For clinical trials with interim analyses, there have been methodologies and software to calculate boundaries for comparing binomial, normal, and survival data from two treatment groups. Jennison & Turnbull (1991) extended Pocock (1977) and O'Brien-Fleming (1979) boundaries to t-tests, x²-tests and F-tests for comparing normal data from several treatment groups. This paper demonstrates that the above boundaries can be applied to a wide variety of test statistics based on general parametric settings. We show that asymptotically the x² boundaries as well as the corresponding nominal significance levels calculated by Jennison & Turnbull can be applied to interim analyses based on the score test, the Wald test, and the likelihood ratio test for general parametric models. Based on the results of this paper, currently available software in group sequential testing can be used to calculate the nominal significance levels (or boundaries) for group sequential testing based on logistic regression, ANOVA, and other parametric methods.

Duke Scholars

Author Hussein Rashid Al-Khalidi Biostatistics & Bioinformatics, Division of Biostatistics