Randomization in clinical trials: stratification or minimization

Objectives. Operative clinical trials are often small and open-label. Randomization is therefore very important. Stratification and minimization are two randomization options in such trials. The first aim of this study was to compare stratification and minimization in terms of predictability and balance in order to help investigators choose the most appropriate allocation method. Our second aim was to evaluate the influence of various parameters on the performance of these techniques. Materials and Methods. Software was created which generated patients according to chosen trial parameters (e.g., number of important prognostic factors, number of operators or centers, etc.) and which [HF1]computed predictability and balance indicators for several stratification and minimization methods over a given number of simulations. Block size and proportion of random allocations could be chosen. A reference trial was chosen (50 patients, 1 prognostic factor, 2 operators) and 8 other trials derived from this reference trial were modeled. Predictability and balance indicators were calculated from 10,000 simulations per trial. Results. Minimization performed better with complex trials (e.g., smaller sample size, increasing number of prognostic factors and operators); stratification imbalance increased when the number of strata increased. An inverse correlation between imbalance and predictability was observed. Conclusions. A compromise between predictability and imbalance still has to be found by the investigator but our software (HERMES) gives concrete reasons for choosing between stratification and minimization; it can be downloaded free of charge. Clinical relevance. This software will help investigators choose the appropriate randomization method in future two-arm trials.