Log-rank tests for censored clustered data under generalized randomized block design: Saddlepoint approximation

Abstract

ABSTRACT The weighted log-rank class is the common and widely used class of two-sample tests for clustered data. Clustered data with censored failure times often arise in tumorigenicity investigations and clinical trials. The randomized block design is a significant design that reduces both unintentional bias and selection bias. Accordingly, the p-values of the null permutation distribution of weighted log-rank class for clustered data are approximated using the double saddlepoint approximation technique. Comprehensive simulation studies are carried out to appraise the accuracy of the saddlepoint approximation. This approximation exhibits a significant improvement in precision over the asymptotic approximation. This precision motivates us to determine the approximated confidence intervals for the treatment impact.