Adaptive designs learn from accumulating trial data in real time and apply this knowledge to optimize subsequent study execution. A set of design rules define a priori which modifications may be incorporated into the trial design. Judicious use of adaptive designs may increase the information value per resource unit invested by avoiding allocation of patients to non-efficacious/unsafe therapies and allowing stopping decisions to be made at the earliest possible time point. Ultimately this may accelerate the development of promising therapies.

Adaptive design is regarded as an efficient method for clinical trials in order to increase the success rate of a new drug in development, and recently has been actively discussed among regulatory agencies, industry and academia. Since adaptive design involves interim analyses and is more complex than traditional fixed design, some points such as possibility of introducing statistical and operational bias should be considered when planning and implementing such trials. In this article, we share our perspectives in the consideration of adaptive design clinical trials based on our experiences discussing adaptive design in clinical trial consultation meetings in Japan.

Individuals from academia, the pharmaceutical industry, and the US Food and Drug Administration used a workshop format to discuss important methodological issues in the design of trials of pharmacological agents for improving negative symptoms in schizophrenia. The issues addressed included the need for a coprimary functional measure for registration trials; the characteristics of individuals who should enter negative symptom trials; the optimal duration for a proof-of-concept or registration trial; the optimal design of a study of a broad-spectrum agent that treats both positive and negative symptoms or a co-medication that is added to an antipsychotic; the relative strengths and weaknesses of available instruments for measuring negative symptoms; the definition of clinically meaningful improvement for these trials; and whether drugs can be approved for a subdomain of negative symptoms.

In this paper, the authors describe developments in adaptive design methodology and discuss implementation strategies and operational challenges in early-phase adaptive clinical trials. The BATTLE trial—the first completed biomarker-based Bayesian adaptive randomized study in lung cancer—is presented as a case study to illustrate main ideas and share learnings.