Analysis of factorial survival experiments.

Several new methodological issues that arise within two-way factorial designs for survival experiments are discussed within the framework of asymptotic theory for the proportional hazards model with two binary treatment covariates. These issues include: the proper formulation of null hypotheses and alternatives, the choice among log-rank and adjusted or stratified log-rank statistics, the asymptotic correlation between test statistics for the separate main effects, the asymptotic power (under the various possible methods of analysis) of tests to detect main effects and interactions, the comparison of power to detect main effects within a 2 x 2 factorial design with power in a three-group trial where no patients are randomized simultaneously to both treatments, and the problems of analysis arising when accrual or exposure to one of the treatments is terminated early for ethical reasons.

A comparison of reflected versus test-based confidence intervals for the median survival time, based on censored data.

The small-sample performance of some recently proposed nonparametric methods of constructing confidence intervals for the median survival time, based on randomly right-censored data, is compared with that of two new methods. Most of these methods are equivalent for large samples. All proposed intervals are either 'test-based' or 'reflected' intervals, in the sense defined in the paper. Coverage probabilities for the interval estimates were obtained by exact calculation for uncensored data, and by stimulation for three life distributions and four censoring patterns. In the range of situations studied, 'test-based' methods often have less than nominal coverage, while the coverage of the new 'reflected' confidence intervals is closer to nominal (although somewhat conservative), and these intervals are easy to compute.