In this chapter, we review six case studies of basket and umbrella trials. This chapter is intended to complement the previous chapters on master protocols and basket and umbrella trials.

In this chapter, we discuss the key concepts, terminologies, and principles of master protocols. The term ‘master protocol’ is often misunderstood and misused. This term refers to a single overarching protocol document that is developed with the intention of evaluating multiple interventional hypotheses. ‘Master protocol’ itself does not refer to a specific type of clinical trial. There are three types of clinical trials that are conducted using the master protocol framework: platform trials, basket trials, and umbrella trials. While master protocols can naturally extend to adaptive trial designs, the use of adaptive trial designs is not a defining feature of master protocols nor of platform, basket, and umbrella trials. Master protocols implement common screening, trial systems, and standardised operating procedures across multiple trial institutions under one centralised governance model. In addition to statistical efficiencies, operational efficiencies can be gained by adopting the master protocol framework.

This chapter discusses characteristics of basket and umbrella trials and their key design considerations. Basket trials refer to clinical trials conducted to test one or more targeted therapies on multiple diseases that share common molecular alternations or other predictive risk factors. Umbrella trials refer to clinical trials that test two or more targeted therapies for a single disease that is stratified into multiple groups. In addition to sample size and randomisation considerations that are important to all clinical trials, specific design considerations that are important for basket and umbrella trials include: biological plausibility of targeted intervention(s), accuracy of biomarker assays, biospecimen collection procedures, and prevalence of targeted biomarker.