Selection of patient-reported outcome measures in pulmonary arterial hypertension clinical trials: a systematic review, meta-analysis and health-related quality of life framework

Introduction

Health-related quality of life (HRQoL) in pulmonary arterial hypertension (PAH) is valued as an outcome measure by patients, clinicians and regulators. The selection of patient-reported outcome measures (PROMs) for measurement of HRQoL in PAH clinical trials lacks systematic evaluation of their suitability, accuracy and reliability.

Methods

We report a systematic review (PROSPERO ID: CRD42024484021) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of PROMs selected in PAH clinical trials. PROM measurement properties were then evaluated according to the 10-step COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and graded by recommendation for use. Finally, HRQoL was modelled into a conceptual framework using patient interviews and surveys.

Results

Screening of 896 records identified 90 randomised controlled trials. 43 trials selected PROMs, of which 20 were sufficiently validated to detect meaningful change. Of these, eight trials were adequately powered, using either EuroQol-five dimensions-five levels (EQ-5D-5L), Short-Form-36 (SF-36) or the Living with Pulmonary Hypertension Questionnaire (LPHQ). The COSMIN evaluation recommended EmPHasis-10 and the LPHQ for use (grade A); whereas, SF-36 and EQ-5D-5L require further study (grade B). A conceptual framework of HRQoL was developed from literature comprising 8045 patients. This framework can be used to visualise the different HRQoL concepts measured by different PROMs.

Conclusion

To improve patient-centred research, greater consistency in PROM selection is required. Three of 90 randomised controlled trials have selected COSMIN-recommended PROMs. Whilst the PROMs evaluated require development across the 10 areas of psychometric property measurement, EmPHasis-10 and the LPHQ can be recommended for use. The ratified conceptual framework can further support PROM selection by identifying the HRQoL concepts they are likely to capture.