Complex Innovative Trial Designs: Current State and Future Prospects

To foster access to high-quality, affordable, and appropriate health technologies and interventions, and to effectively address public health emergencies, there is a growing demand to develop new interventions to treat acute and chronic diseases with unmet medical needs. However, over the years, traditional randomized clinical trials (RCTs) have increasingly become unable to meet the challenges of evaluating new therapies for patients with unmet medical needs in a timely manner and are known to be associated with increasingly high costs. Accordingly, much attention is paid to the so-called complex innovative designs (CIDs), with a view to accelerating drug development. One component of CIDs is master protocol trial design, which involves multiple sub-studies, evaluating one or more investigational drugs, in one or more disease subtypes, with one or more objectives, all within the same overall trial structure. Master protocol trials that are well designed and executed can accelerate drug development by maximizing the amount of information obtained from the research effort. These trials can be updated to incorporate new scientific information, as medical science advances. Master protocols also reduce administrative costs and time associated with starting up new trial sites for each investigational drug. They can also increase data quality and efficiency through shared and reusable infrastructure. The session aims to address emerging topics in the design and analysis of master protocol trials and CIDs in general, with emphasis on innovative methods and software, including the use of artificial intelligence, machine learning, and digital technology to streamline the data collection and reporting infrastructure, accelerate patient recruitment, increase diversity and identify the appropriate drugs and biologic targets for trials. Consistent with the 2025 JSM's theme, "Statistics, Data Science, and AI Enriching Society", in this session, world-renowned leaders and scientists from government, academia and the pharmaceutical industry are invited to present and discuss the state-of-the-science approaches to inform decision and drive innovation for master protocol trials. We believe that statisticians, biostatisticians and applied researchers from government, academia and industry, who are interested in cutting-edge statistical methods and software for complex innovative clinical trials, will be attracted by and benefit from in this unique invited session. Specifically, the first speaker Dr. Lei Nie will present guidelines improving the design and conduct of complex innovative clinical trials from the regulatory perspective. The second speaker Dr. Ting Ye will present an innovative estimand framework and robust inference methods for estimating treatment effects in platform trials. The third speaker Dr. Bo Huang will discuss innovative methods borrowing information from non-concurrent control to enhance the design and inference of platform trials. The fourth speaker Dr. Cindy Lu will discuss current practice for master protocol trials and innovative Bayesian methods borrowing real-world data enhancing the design and analysis of basket trials.