Impact of the adjustment of stratification factors on time-to-event
analyses
- Madan Kundu,
- Shoubhik Mondal
Abstract
In a stratified clinical trial design with time to event end points,
stratification factors are often accounted for the log-rank test and the
Cox regression analyses. In this work, we have evaluated the impact of
inclusion of stratification factors on the power of the stratified
log-rank test and have compared the bias and standard error in HR
estimate between multivariate and stratified Cox regression analyses
through simulation. Results from our investigation suggests that both
failing to consider stratification factor in presence of their
prognostic effect and stratification with smaller number of events may
substantially reduce the power of the log-rank test. Further, the HR
estimate from the multivariate Cox analysis is more accurate and precise
compared to the stratified Cox analysis. Our findings point towards the
necessity of evaluating the impact of stratification factors on the time
to event analyses at the time of study design which is presently not a
norm.