Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension

Authors

Jason Weatherald, Department of Medicine, Division of Pulmonary Medicine, University of Alberta, Edmonton, AB, Canada weathera@ualberta.ca.
Thomas R. Fleming, Department of Biostatistics, University of Washington, Seattle, WA, USA.
Martin R. Wilkins, National Heart and Lung Institute, Imperial College London, London, UK.
Thomas M. Cascino, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
Mitchell A. Psotka, Inova Schar Heart and Vascular, Falls Church, VA, USA.
Roham Zamanian, Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University School of Medicine, Palo Alto, CA, USA.
Werner Seeger, Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Institute for Lung Health (ILH), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Giessen, Germany.
Nazzareno Galiè, Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna and Dipartimento DIMEC, Università di Bologna, Bologna, Italy.
Mardi Gomberg-Maitland, Division of Cardiovascular Medicine, Department of Medicine, George Washington University, School of Medicine, Washington, DC, USA.

Document Type

Journal Article

Publication Date

8-29-2024

Journal

The European respiratory journal

DOI

10.1183/13993003.01205-2024

Abstract

Clinical trials in pulmonary arterial hypertension (PAH) have led to the approval of several effective treatments that improve symptoms, exercise capacity and clinical outcomes. In phase 3 clinical trials, primary end-points must reflect how a patient "feels, functions or survives". In a rare disease like PAH, with an ever-growing number of treatment options and numerous candidate therapies being studied, future clinical trials are now faced with challenges related to sample size requirements, efficiency and demonstration of incremental benefit on traditional end-points in patients receiving background therapy with multiple drugs. Novel clinical trial end-points, innovative trial designs and statistical approaches and new technologies may be potential solutions to tackle the challenges facing future PAH trials, but these must be acceptable to patients and regulatory bodies while preserving methodological rigour. In this World Symposium on Pulmonary Hypertension task force article, we address emerging trial end-points and designs, biomarkers and surrogate end-point validation, the concept of disease modification, challenges and opportunities to address diversity and representativeness, and the use of new technologies such as artificial intelligence in PAH clinical trials.

APA Citation

Weatherald, Jason; Fleming, Thomas R.; Wilkins, Martin R.; Cascino, Thomas M.; Psotka, Mitchell A.; Zamanian, Roham; Seeger, Werner; Galiè, Nazzareno; and Gomberg-Maitland, Mardi, "Clinical trial design, end-points, and emerging therapies in pulmonary arterial hypertension" (2024). GW Authored Works. Paper 5415.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5415

Department

Medicine