A behavioural Bayes approach to the determination of sample size for clinical trials considering efficacy and safety: imbalanced sample size in treatment groups.

The behavioural Bayes approach to sample size determination for clinical trials assumes that the number of subsequent patients switching to a new drug from the current drug depends on the strength of the evidence for efficacy and safety that was observed in the clinical trials. The optimal sample size is the one which maximises the expected net benefit of the trial. The approach has been developed in a series of papers by Pezeshk and the present authors (Gittins JC, Pezeshk H. A behavioral Bayes method for determining the size of a clinical trial. Drug Information Journal 2000; 34: 355-63; Gittins JC, Pezeshk H. How Large should a clinical trial be? The Statistician 2000; 49(2): 177-87; Gittins JC, Pezeshk H. A decision theoretic approach to sample size determination in clinical trials. Journal of Biopharmaceutical Statistics 2002; 12(4): 535-51; Gittins JC, Pezeshk H. A fully Bayesian approach to calculating sample sizes for clinical trials with binary responses. Drug Information Journal 2002; 36: 143-50; Kikuchi T, Pezeshk H, Gittins J. A Bayesian cost-benefit approach to the determination of sample size in clinical trials. Statistics in Medicine 2008; 27(1): 68-82; Kikuchi T, Gittins J. A behavioral Bayes method to determine the sample size of a clinical trial considering efficacy and safety. Statistics in Medicine 2009; 28(18): 2293-306; Kikuchi T, Gittins J. A Bayesian procedure for cost-benefit evaluation of a new drug in multi-national clinical trials. Statistics in Medicine 2009 (Submitted)). The purpose of this article is to provide a rationale for experimental designs which allocate more patients to the new treatment than to the control group. The model uses a logistic weight function, including an interaction term linking efficacy and safety, which determines the number of patients choosing the new drug, and hence the resulting benefit. A Monte Carlo simulation is employed for the calculation. Having a larger group of patients on the new drug in general makes it easier to recruit patients to the trial and may also be ethically desirable. Our results show that this can be done with very little if any reduction in expected net benefit.