Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension

Olivier Sitbon; Sylvia Nikkho; Raymond Benza; Chunqin Cq Deng; Harrison W Farber; Mardi Gomberg-Maitland; Paul Hassoun; Christian Meier; Joanna Pepke-Zaba; Krishna Prasad; Werner Seeger; Paul A Corris

doi:10.1177/2045894020962960

Novel composite clinical endpoints and risk scores used in clinical trials in pulmonary arterial hypertension

Pulm Circ. 2020 Nov 18;10(4):2045894020962960. doi: 10.1177/2045894020962960. eCollection 2020 Oct-Dec.

Authors

Affiliations

¹ Assistance Publique-Hôpitaux de Paris, Service de Pneumologie, Hôpital Bicêtre, Université Paris-Sud, Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique, Le Kremlin-Bicêtre, France.
² Bayer AG, Clinical Development, Berlin, Germany.
³ The Ohio State University, Columbus, OH, USA.
⁴ United Therapeutics Corporation, Raleigh-Durham, NC, USA.
⁵ Tufts Medical Center, Boston, MA, USA.
⁶ George Washington University of Medicine and Health Sciences, Washington, DC, USA.
⁷ Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
⁹ Medicines and Healthcare Products Regulatory Agency (MHRA), London, UK.
¹⁰ University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.
¹¹ Clinical and Translational Research Institute Newcastle University, Newcastle upon Tyne, UK.

Abstract

This manuscript on endpoints incorporates the broad experience of members of Pulmonary Vascular Research Institute's Innovative Drug Development Initiative as an open debate platform for academia, the pharmaceutical industry and regulatory experts surrounding the future design of clinical trials in pulmonary hypertension. It reviews our current understanding of endpoints used in phase 2 and 3 trials for pulmonary hypertension and discusses in detail the value of newer approaches. These include the roles of composite endpoints and how these can be developed and validated. The newer concept of risk analysis is also discussed, including how such risk scores might be utilised as endpoints in clinical trials.

Keywords: drug development; pulmonary arterial hypertension; risk factors; risk stratification and biomarkers.