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

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

doi:10.1177/2045894020962960

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.

Highlights

Pulmonary arterial hypertension (PAH) is a serious chronic disease resulting in reduced life expectancy despite available medications.[1,2,3,4]
2 | Novel composite endpoints and risk scores Sitbon et al PAH patients suffer from dyspnoea, hypoxemia, heart failure and muscle weakness, which lead to limited physical activity
It is important to improve this level of physical activity in patients suffering from pulmonary hypertension (PH), as it has a direct impact on overall health, well-being and quality of life.[5]

Summary

Introduction

Pulmonary arterial hypertension (PAH) is a serious chronic disease resulting in reduced life expectancy despite available medications.[1,2,3,4] There is an urgent need to develop new drug therapies into routine clinical practice, requiring the development of novel study designs, including new endpoints. These endpoints will need to be meaningful to patients, physicians and regulators, as well as practical entities, in order to enable such trials to become feasible. It is important to improve this level of physical activity in patients suffering from PH, as it has a direct impact on overall health, well-being and quality of life.[5]

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Discussion

Conclusion