End Point Selection in ADPKD Clinical Trials.

Autosomal dominant polycystic kidney disease (ADPKD) is the leading hereditary cause of kidney failure. Challenges have arisen in developing consensus-based clinical trial end points endorsed by the wider ADPKD research community and regulators. Disease progression in ADPKD occurs slowly and is highly variable between patients. Clinical end points such as death or kidney failure occur infrequently and late in the condition. Thus, their use as outcomes in ADPKD trials requires prolonged follow-up and large sample sizes. Furthermore, because of the nature of ADPKD progression, surrogate outcomes such as change in glomerular filtration rate (GFR) or kidney volume, have varying validity in different populations of patients with ADPKD. Alternative trial approaches, such as enriching trial populations with patients at high risk of disease progression, have the potential to mitigate some of these challenges, although they limit the generalizability of results. The emergence of novel trial designs presents potential approaches to alleviate some of these issues. This paper explores some of the unique features of ADPKD from which difficulties in outcome selection arise, examines how modern trial designs can lessen some of these features, and provides an overview of commonly reported outcomes in ADPKD trials.