This paper evaluates the loss of power of the simple and stratified logrank tests due to heterogeneity of patients in clinical trials and proposes a flexible and efficient method of estimating treatment effects adjusting for prognostic factors. The results of the paper are based on the analyses of survival data from a large clinical trial which includes more than 6000 cancer patients. Major findings from the simulation study on power are: (i) for a heterogeneous sample, such as advanced cancer patients, a simple logrank test can yield misleading results and should not be used; (ii) the stratified logrank test may suffer some power loss when many prognostic factors need to be considered and the number of patients within stratum is small. To address the problems due to heterogeneity, the Cox regression method with a special hazard model is recommended. We illustrate the method using data from a gastric cancer clinical trial.
1997 by John Wiley & Sons, Ltd.
* Increase in survival rate in the treated group when controls survive 50 per cent; 10 per cent corresponds to log "!0โข305 and 13โข8 per cent to log "!0โข305( 2The simulation with ns"1 represents the case of homogeneous sample. Ranges of log-hazards in (a) and (b) are 4 and 0, respectively. The ranges are equally divided into each stratum