The advantages and disadvantages of adaptive designs for clinical trials

Abstract

Flexible designs for clinical trials permit mid-trial design modifications, which are based on interim information from inside or outside the trial while meeting (regulatory) requirements for the control of the type I error rate. The basic principle is to combine stage standardized test statistics such as p-values or z-scores in a pre-specified way. The flexibility covers changes of sample sizes, treatment allocation ratios and the number of interim analyses, as well as the selection of treatments, doses and end points. The price to be paid is that non-standard test statistics must be used after an adaptation.