Sequential treatment allocation procedures in clinical trials‐with particular attention to the analysis of results for the biased coin design

We discuss the advantages and problems of using sequential allocation procedures for assigning treatments in a clinical trial. We use Monte Carlo methods to study the exact distribution of the fourfold chi-squared statistic for the case of no stratifying variables except sequence of entry. We display situations in which the distribution is well-approximated by the chi-squared distribution or by Efron's adjusted chi-squared and situations where these approximations fail. We provide suggestions for recognition and handling of situations in which both approaches fail.