The "best balance" allocation led to optimal balance in cluster-controlled trials.

Objective: Balance of prognostic factors between treatment groups is desirable because it improves the accuracy, precision, and credibility of the results. In cluster-controlled trials, imbalance can easily occur by chance when the number of cluster is small. If all clusters are known at the start of the study, the "best balance" allocation method (BB) can be used to obtain optimal balance. This method will be compared with other allocation methods.

Study Design And Setting: We carried out a simulation study to compare the balance obtained with BB, minimization, unrestricted randomization, and matching for four to 20 clusters and one to five categorical prognostic factors at cluster level.

Results: BB resulted in a better balance than randomization in 13-100% of the situations, in 0-61% for minimization, and in 0-88% for matching. The superior performance of BB increased as the number of clusters and/or the number of factors increased.

Conclusion: BB results in a better balance of prognostic factors than randomization, minimization, stratification, and matching in most situations. Furthermore, BB cannot result in a worse balance of prognostic factors than the other methods.