EASL-AASLD Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis

Drug development in primary biliary cholangitis (PBC) has led to the conditional approval of three second-line therapies, yet the transition to full regulatory approval remains challenging due to (1) the reliance on liver biochemistry and non-invasive measures of liver fibrosis as biomarkers of clinical outcomes, which are not accepted by regulatory authorities as validated efficacy endpoints; (2) the limited integration of real-world data and real-world evidence to complement clinical trials; and (3) the absence of harmonised and standardised use of patient-reported outcomes (PROs). To address these limitations, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) commissioned an international, multi-stakeholder consensus panel to conduct a modified Delphi process to review current evidence, identify unmet research needs, and create a framework aligned with regulatory expectations to guide ongoing and future research in PBC. A total of 62 panellists, including clinicians, methodologists, regulators, industry partners, and patient representatives, were divided into three working groups and participated in regular online meetings, one in-person conference, and two online Delphi voting rounds. Response rates across the two voting sessions were 88% and 60%, respectively. The Delphi process resulted in agreement on 16 statements and 42 recommendations across the three thematic domains. Collectively, these consensus recommendations provide a comprehensive and pragmatic framework to support and expand the existing regulatory pathway for the development and approval of new therapies in PBC.