Robust allocation schemes for clinical trials with prognostic factors

We present schemes for the allocation of subjects to treatment groups, in the presence of prognostic factors. The allocations are robust against incorrectly specified regression responses, and against possible heteroscedasticity. Assignment probabilities which minimize the asymptotic variance are obtained. Under certain conditions these are shown to be minimax (with respect to asymptotic mean squared error) as well. We propose a method of sequentially modifying the associated assignment rule, so as to address both variance and bias in finite samples. The resulting scheme is assessed in a simulation study. We find that, relative to common competitors, the robust allocation schemes can result in significant decreases in the mean squared error when the fitted models are biased, at a minimal cost in efficiency when in fact the fitted models are correct.