Say I’m planning a randomized trial (time-to-event outcome) with 4 sites and want to balance randomization for each site. Am I then committed to stratifying by site in analysis? Or including site as a fixed effect in regression models?
My understanding is: stratified randomization -> stratified analysis
and block-randomization for balance —> consider factors as fixed effects
Balance is obviously good, and stratification may be necessary if baseline hazards have a very different shape. But as you stratify by more and more factors, moving toward matched-pairs randomization, the large number of strata seems to decimate study power.
I’m available with the literature pointing out drawbacks of matched case-control studies (Pepe et al, Clin Chemistry 2012). Are there any manuscripts or texts that lay out these issues for trial design and analysis?