Seamless multiarm multistage (MAMS) designs with treatment selection and interim change of outcome: An update to nstage

Multiarm multistage (MAMS) selection designs, as an extension of the standard MAMS designs, offer additional eaciencies that accelerate the evaluation of medical interventions in clinical trials. Standard MAMS designs use stagewise hypothesis testing to compare multiple experimental treatments against a common control at interim analyses, enabling early stopping for overwhelming eacacy or lack-of- beneRt. MAMS selection designs further incorporate predeRned rules to choose the best performing treatments. Incorporating intermediate outcomes, introduced to signiRcantly shorten the timing of interim analyses, naturally Rts into the seamless trial design framework, which allows for outcome changes at early stages of trial. Our existing nstage suite of commands calculates target sample sizes for MAMS designs with binary outcomes such as death or disease progression. The program also projects timelines for trial planning and computes overall operating characteristics (overall pairwise/familywise type I error rates, power, and expected sample sizes). We have enhanced the program to support interim outcome changing and the interim rules for treatment selection, lack of beneRt, and overwhelming eacacy. The updated nstage command is now more Xexible, enabling changes to trial outcomes at interim stages, making it well suited for seamless phase II/III trial designs. It also supports treatment selection based on either phase II (intermediate) or phase III (primary clinical) outcomes. We will describe the new MAMS design and the associated Stata command using a miscarriage MAMS platform trial in maternal health.