Complex Innovative Design for NASH Clinical Trials

Abstract

The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing world-wide. The development of drug product for treating NASH is considered unmet medical need. Due to the increasing prevalence and the health burden, there is a high need to develop therapeutic strategies for patients with NASH. The primary objective of the treatment for NASH is to prevent liver-related morbidity and mortality, which generally takes a long time (e.g., more than 10-20 years) to develop. In practice, it is not feasible to conduct such clinical studies. Thus, regulatory agencies such as United States Food and Drug Administration (FDA) encourage to look at surrogate endpoints for review and approval. Seamless adaptive clinical trial designs in NASH provide an opportunity to shorten the overall path to registration for a new drug and offer continuity for patients enrolled in the study. In this article, Characteristics for applying various seamless adaptive designs to clinical trials in NASH are reviewed. Statistical, clinical, and strategic issues related to drug development of NASH are also discussed.