Saturday, September 1, 2007

Bias in group sequential designs - site effect and Cochran-Mantel-Hanszel odds ratio

It is well known that estimating treatment effects from a group sequential design results in a bias. When you use the Cochran-Mantel-Haenszel statistic to estimate an odds ratio, the number of patients within each site affects the bias in the estimate of the odds ratio. I've presented the results of a simulation study, where I created a hypothetical trial and then resampled from this trial 1000 times. I calculated the approximate bias in the log odds ratio (i.e. log of the CMH odds ratio estimate) and plotted that versus the estimated log odds ratio. The line is cubic smoothing spline, made by the statement symbol i=sm75ps in SAS. The actual values are underprinted in light gray circles just to get some idea of the variability.