Minimization in crossover trials with non-prognostic strata: theory and practical application.

To obtain meaningful results in any clinical trial, patients need to be allocated to treatments in such a way that valid analysis can be carried out. Balancing treatment groups before analysis is carried out is more desirable than trying to compensate for incomparability at a later date. Therefore, the development of allocation procedures to produce comparable groups in which prognostic factors are equally represented is important. Minimization, a deterministic allocation method, aims to ensure balance on such factors, particularly in small trials when traditional randomization methods are likely to fail. However, views on the use of conventional analysis following minimization are divided. The use of minimization in two randomised crossover trials is described where, in addition to the comparisons between randomised treatments, it was desired to have balance between groups based on differential trial procedures. Theoretical concerns about the use of minimization are not applicable in this setting, and therefore minimization is shown to be a useful technique for obtaining balance.