Approaches to the design of clinical trials for primary sclerosing cholangitis*** Design of clinical trials for primary sclerosing cholangitis

Mohamad H Imam, Keith D Lindor, Jayant A Talwalkar

Clinical trial design is one of the most important aspects of advancing therapeutic interventions in the management of chronic liver diseases. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of uncertain etiology and pathogenesis. The natural history of PSC is often assessed through a variety of clinical and histological end points. However, none of the therapeutic options examined in clinical trials for PSC to date has demonstrated benefit in halting or slowing disease progression. Furthermore, the emerging recognition of several subtypes in PSC, coupled with limitations in histological and cholangiographic staging, makes subject stratification and trial design challenging. This article will review approaches that have been used for designing clinical trials for assessing potential therapies for PSC as well as provide recommendations on future clinical trials design and explore the potential use of novel surrogate end points that may improve patient selection and treatment efficacy assessment.