ABSTRACT For a chronic disease, besides the treatment induction effect, it is also important to demonstrate the maintenance effect of long‐term treatment use. To fulfill these and other objectives for a clinical study, we often apply one of three designs: the active treatment lead‐in followed by randomized maintenance design, the randomized induction followed by re‐randomized withdrawal maintenance design and the treat‐through design (FDA 2022). Separately, a two‐stage sequential parallel comparison design (SPCD) is frequently used in therapeutic areas where placebo has a large effect. In this paper, we use a SPCD for a clinical trial with a binary endpoint for induction, maintenance, long‐term and other treatment effect assessments. This SPCD can actually be treated as a hybrid of the above three designs and has some additional advantages. For example, compared to the re‐randomized withdrawal maintenance design, the SPCD does not need a re‐randomization to simplify trial operation and it also provides controlled data for formal long‐term efficacy and safety analyses. To fully utilize all available data of the two stages for an overall treatment effect evaluation, a weighted combination test is considered with the incorporation of correlations of the components. Further, a multiple imputation approach is applied to handle missing not at random data. Simulations are conducted to evaluate the performances of the methods and a data example is employed to illustrate the applications of the methods.
Quan et al. (Thu,) studied this question.