Abstract

Sequential testing can be used to meet the specific needs of a clinical trial, all while adhering to the study’s ethical, financial, and administrative considerations. When the assumption of proportional hazards or exponentially distributed lifetimes is not satisfied, the researcher can rely on the Proportional Time assumption for sample size calculation. The proportional time method has the advantage that previous study results can be used to bolster the current study design and provide an easier interpretation of the treatment benefit by reporting results as an improvement in longevity versus the more traditional interpretation of reduction in risk. This ease in interpretation of treatment benefit helps in raising interest in study participation. This novel method can be applied through a SAS macro and can be utilized for all distributions that belong to the generalized gamma family. The macro incorporates features specific to time-to-event data such as loss to follow-up, administrative censoring, differing accrual times and patterns, binding or non-binding futility rules with or without skips, and flexible alpha and beta spending functions. The macro includes validation for any parameters defined by the user, as well as suggestions for correcting erroneous input. This paper demonstrates two practical applications of the SAS macro with varying design inputs.

Keywords

efficacy, error spending, futility, proportional time, sample size, SAS software