Optimal Ethical Balance for Phase III Trials Planning

The need of an ethical evaluation is mandatory for every clinical trial, Ethics Committees have been built for that. The distinction between individual and collective ethics has been introduced in a seminal work by Lellouch and Schwartz in 1971, where individual ethics regard concerns related to the patients enrolled in the trial, and collective ethics those of the patients not enrolled who would benefit of a positive trial result. In this paper, a metrization of individual and collective ethics is proposed in order to evaluate their balance in a confirmatory clinical trial. The ethical balance evaluation, among these two aspects of ethics, can be performed before trial starting in order to address sample size determination. The metrization is based, among other parameters, on the drug effect size, on the quality of life of patients under therapy or placebo, and of that induced by adverse reactions. Some numerical examples show that the optimal ethical balance can be provided by sample sizes far from those computed by adopting the usual paradigm based on the prefixed power of 80-90%