Adaptive design in clinical trials: benefits and risks

Abstract

Over the past several decades, adaptive design methods in clinical trials has become more popular as a way to increase the efficiency of the early and late phases of clinical development by means of reducing costs, resources and duration as well as increasing the likelihood of trial success and the chance for patients of being allocated to the treatment that’s more effective and safe. The following prospectively planned modifications can be implemented in an adaptive study: eligibility criteria, sample size and/or study duration, randomization procedure, treatment regimens, including the number of treatment groups, concomitant medication, patient evaluation schedule, endpoints, statistical methods. Opportunity to change some elements of the design based on interim results during the course of the study provides advantages over the traditional fixed design. Nevertheless, the implementation of adaptive designs is more complex, such trials require more thorough planning, and are often accompanied with various degrees of statistical, procedural, logistic and regulatory issues. The aim of this article is to provide the main definitions, to highlight the pros, cons of adaptive design at different phases of drug development from statistical and regulatory point of view for better understanding of the methodology.

Keywords

• адаптивные конструкции
• гибкие конструкции
• групповые последовательные методы
• повторная оценка размера выборки
• прекращение бесперспективности
• промежуточный анализ
• операционный уклон
• статистический уклон
• adaptive designs
• flexible designs
• group sequential methods
• sample size re-estimation
• futility stopping
• interim analyses
• operational bias
• statistical bias