SEER-NTA

Statistical Methodology for Basket and Platform Trials 

in Non-oncology Therapeutic Areas

Plain English Summary of Research

Master protocols represent an innovative class of trial designs that investigate multiple drugs and/or disease (sub)populations in multiple substudies under one overarching protocol. Such designs are patient-centric, enhance trial efficiency, and aim to bring best-suited treatments to patients faster at reduced costs. One major type of master protocols is called basket trials where a new treatment can be simultaneously evaluated in various patient (sub)populations/across multiple indications, thereby providing substantial statistical efficiency (e.g., by utilising approaches to borrow information across substudies) and operational advantages (e.g., enhanced screening efficiencies, operational streamlining).

So far, methodology development and the implementation of basket trials have predominantly been in oncology, where the “standard” approach is to utilise a single-arm design per substudy. This means existing methodology for basket trial does not support selection of the “optimal” doses and thus hinders its application in non-oncology therapeutic areas where typically multiple active doses are compared against a control. There has been a growing interest in expanding basket trials to therapeutic areas beyond oncology, but the methodological gap greatly limits the wider uptake of such efficient designs in non-oncology therapeutic areas.

In this project, we aim to fill this gap, exploit advantage of basket trials in non-oncology settings, and develop innovative and efficient statistical methodology for next-generation basket trials. The new series of advanced designs will support simultaneous estimation of best-suited dose(s) in multiple disease (sub)types/patient (sub)populations. This project will start off by extending existing randomised controlled basket designs (Zheng and Wason, 2022; Ouma et al., 2022; Zheng et al., 2023) to include more doses alongside a control per substudy and allow for borrowing of information in accordance with the degree of similarity between the dose-response curves across substudies. Innovative methods will further be proposed to enable additional efficiency gains by 

1) incorporating mid-course modifications, e.g., adaptive allocation of patients to more effective doses or early termination of substudies less likely to benefit from the treatment;

2) eventually transforming basket trials to become platform trials. This would allow addition of substudies midway through the investigation.