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

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

Olivier Sitbon  1 , Sylvia Nikkho  2 , Raymond Benza  3 , Chunqin Cq Deng  4 , Harrison W Farber  5 , Mardi Gomberg-Maitland  6 , Paul Hassoun  7 , Christian Meier  2 , Joanna Pepke-Zaba  8 , Krishna Prasad  9 , Werner Seeger  10 , Paul A Corris  11
Affiliations

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

Olivier Sitbon et al. Pulm Circ. .

Erratum in

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.

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Conflict of interest statement

Conflict of interest: The author(s) declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Steps to a novel composite endpoint. Source: Modified after Armstrong and Westerhout, 2017.
Fig. 2.
Fig. 2.
Components of composite endpoint in AIR study. 6MWD: six-minute walking distance; NYHA: York Heart Association. Source: based on Olschewski et al., 2002.
Fig. 3.
Fig. 3.
Components of combined clinical endpoints in various studies. 1AIR study: Olschewski et al., 2002,29 2AMBITION study: Galie et al., 2015,19 3RESPITE study: Hoeper et al., 2017,31 4REPLACE study: Hoeper et al., 2017,32 and Simonneau et al., 2019,33 FC: functional class; 6MWD: six-minute walking distance.
Fig. 4.
Fig. 4.
Current risk scores based on different registries and numbers of variables and discrimination indices. 12015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension – Eur Heart J 2016.42 22015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2015.51 3Pulmonary arterial hypertension: baseline characteristics from the REVEAL registry.52 4The REVEAL Registry risk score calculator in patients newly diagnosed with pulmonary arterial hypertension.48 5Prognostic implications of serial risk score assessments in patients with pulmonary arterial hypertension.44 6A comprehensive risk stratification at early follow-up determines prognosis in pulmonary arterial hypertension.36 7Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.34 8Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model.35 9The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies.37 10Comparison of Three Risk Assessment Strategies as Predictors of One Year Survival in US Pulmonary Arterial Hypertension (PAH) Patient.49 ERS: European Respiratory Society; ESC: European Society of Cardiology; REVEAL: Registry to Evaluate Early and Long-Term PAH Disease Management.
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References

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