The present paper deals with the problem of designing randomized multiarm clinical trials for treatment comparisons in order to achieve a suitable trade-off among inferential precision and ethical concerns. Although the large majority of the literature is focused on the estimation of the treatment effects, in particular for the case of two treatments with binary outcomes, the present paper takes into account the inferential goal of maximizing the power of statistical tests to detect correct conclusions about the treatment effects for normally response trials. After discussing the allocation optimizing the power of the classical multivariate test of homogeneity, we suggest a multipurpose design methodology, based on constrained optimization, which maximizes the power of the test under a suitable ethical constraint reflecting the effectiveness of the treatments. The ensuing optimal allocation depends in general on the unknown model parameters but, contrary to the unconstrained optimal solution or to some targets proposed in the literature, it is a non-degenerate continuous function of the treatment contrasts, and therefore it can be approached by standard response-adaptive randomization procedures. The properties of this constrained optimal allocation are described both theoretically and through suitable examples, showing good performances both in terms of ethical gain and statistical efficiency, taking into account estimation precision as well.
A simple solution to the inadequacy of asymptotic likelihood-based inference for response-adaptive clinical trials
