Authors: Jesse D Kirkpatrick PhD, Mahesh Krishna, Sarah Curup Callif, Mary Vyas, Rachel Gomel, Matthew McMurtry MD, Willie J. McKinney PhD, Christopher L. Bowlus MD, Daniel Pratt MD, Joshua Korzenik MD, Ricky Safer, Joanne Hatchett, Stephen Rossi PharmD, Ruth-Anne Pai PhD.

Journal: Hepatology. 78(S1):S1-S2154, October 2023. 

Abstract:

Background: Primary sclerosing cholangitis (PSC) is a rare, progressive immune-mediated liver disease with no Food Drug and Administration (FDA) approved treatments available. Drug development is limited due to poor understanding of the pathophysiology of PSC, with no surrogate endpoints or validated patient-reported outcomes. PSC Partners Seeking a Cure aimed to generate an organizational research plan with patient and researcher input to better understand and address these gaps.

Methods: Our interdisciplinary team of PSC Partners representatives and clinical researchers led a two-year process to develop a strategic research plan (SRP) with 4 stages: 1) Organization of an externally-led patient-focused drug development (EL-PFDD) meeting with the FDA. 2) A series of focus groups to discuss symptoms, patient-reported outcomes, research, natural history, and drug development. 3) Review of the scientific literature and interviews with 9 PSC researchers to capture gaps in understanding of PSC. The first three steps informed the development of the draft research agenda. 4) Discussion of the draft research agenda within focus groups at the PSC Partners Annual Conference in 2022. Participants provided research recommendations which were analyzed by our interdisciplinary team and scored using a standardized rubric. Both qualitative and quantitative data guided generation of the SRP.

Results: These efforts incorporated the voices of more than 500 unique PSC patients and caregivers. More than 100 patients and caregivers participated in 15 focus groups and contributed 65 community recommendations across 6 diverse topics for future research directions. PSC researchers contributed 59 recommendations for future research directions, 22 of which (37%) aligned with the 65 community recommendations. Assessment of multi-stakeholder recommendations formed 4 pillars of focus for PSC Partners and the structure of the SRP: 1) Improve understanding of the mechanisms contributing to the development and progression of PSC, 2) Further understanding of the gut-liver connection in PSC, 3) Develop safe and effective treatments to slow progression and reduce symptom burden for those with PSC, and 4) Provide support and education through patient engagement and knowledge translation.

Conclusion: This initial round of prioritization resulted in PSC Partners' efforts to develop surrogate endpoints and patient-reported outcome measures for clinical trials. Future support and new partnerships will further work across the 4 pillars as PSC Partners plays an active role in research and drug development to find a cure for PSC.