Is the classical Wald test always suitable under response-adaptive randomization?

Abstract

The aim of this paper is to analyze the impact of response-adaptive randomization rules for normal response trials intended to test the superiority of one of two available treatments. Taking into account the classical Wald test, we show how response-adaptive methodology could induce a consistent loss of inferential precision. Then, we suggest a modified version of the Wald test which, by using the current allocation proportion to the treatments as a consistent estimator of the target, avoids some degenerate scenarios and so it should be preferable to the classical test. Furthermore, we show both analytically and via simulations how some target allocations may induce a locally decreasing power function. Thus, we derive the conditions on the target guaranteeing its monotonicity and we show how a correct choice of the initial sample size allows one to overcome this drawback regardless of the adopted target.