In this chapter, we review six case studies of adaptive clinical trials. This chapter is intended to complement the previous chapters. We have organised the case studies by their main adaptive design feature. Each case study describes the background of individual trial and summarises key design details and overall results. Our presentation and discussion do not necessarily represent the official view of the trial investigators. Our discussion is intended to improve the reader’s general literacy and comprehension of published results of adaptive clinical trials.

This chapter discusses the common types of adaptive trial designs and their motivations and challenges. The common types covered in this chapter include: sequential designs, sample size re-assessment, adaptive randomisation, minimisation, response adaptive randomisation, enrichment design, and seamless design. Sequential designs that use interim analyses to allow for early stopping are the most common type of adaptive trial design. Sequential designs are often used with other types of adaptive trial designs. Other common types of adaptive trial designs include sample size re-assessment that uses blinded or unblinded data for re-estimation of sample size during the trial; response adaptive randomisation that preferentially increases allocation ratio in favour of treatment arm based on interim trial data; adaptive enrichment design that allows for modification of patient eligibility criteria; and seamless design that combines two phases of clinical trial research into one trial. Adaptive trial designs offer more flexibility in comparison to conventional fixed trial designs, but this comes with complexities that usually require more thorough and thoughtful planning in the design stage. Trade-offs for different design options should be carefully considered.