Selection of patient-reported outcome measures in pulmonary arterial hypertension clinical trials: a systematic review, meta-analysis and health-related quality of life framework
Authors: Varian Frances , Burney Rebecca , Pearson Charlotte , Goh Ze Ming , Newman Joseph , Rawlings Gregg , Zafar Hamza , Kiely David G , Thompson AA Roger , Condliffe Robin , Toshner Mark , McCormack Ciara , Armstrong Iain , Peasgood Tessa , Carlton Jill , Rothman Alex 
Published: August 2024

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 PROMs for measurement of HRQoL in PAH clinical trials lacks systematic evaluation of their suitability, accuracy and reliability.

Method

We report a systematic review (PROSPERO ID: CRD42024484021) following PRISMA guidelines of PROMs selected in PAH clinical trials. PROM measurement properties were then evaluated according to the ten-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 RCTs. 43 trials selected PROMs of which 20 were sufficiently validated to detect meaningful change. Of these, 8 trials were adequately powered, using either EQ-5D-5L, SF-36 or the Living with Pulmonary Hypertension Questionnaire (LPHQ). COSMIN evaluation recommended EmPHasis-10 and LPHQ for use (Grade A), however, SF-36 and EQ-5D-5L require further study (Grade B). A conceptual framework of HRQoL was developed from literature comprising 8,045 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. 3 of 90 RCTs have selected COSMIN-recommended PROMs. Whilst the PROMs evaluated require development across the ten areas of psychometric property measurement, EmPHasis-10 and 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.

Graphical abstract: selection of patient-reported outcome measures in pulmonary arterial hypertension clinical trials

COSMIN COnsensus-based standards for the Selection of health-Measurement INstruments, EQ-5D-5L EuroQol-5D-5L; HRQoL health-related quality of life; LPHQ Living with Pulmonary Hypertension Questionnaire, MCID minimal clinically important difference; PAH pulmonary arterial hypertension; PROM patient reported outcome measure, QALY quality-adjusted life years, RCT randomised controlled trial, SF-36 36-item Short Form survey.https://BioRender.com/u80X854

Plain language summary

Individuals living with pulmonary hypertension want to know which treatments improve their quality of life related to their health. We use questionnaires to capture the experiences of people living with pulmonary hypertension. Examples of this used in clinical practice are EmPHasis-10. We reviewed all the clinical trials in pulmonary hypertension to see which questionnaires were used to measure health-related quality of life. Some questionnaires may be better at capturing the experience of living with pulmonary hypertension than others. We found 20 clinical trials used a questionnaire that could detect a change in health-related quality of life in pulmonary hypertension. However, only 8 trials were designed to detect a significant treatment impact. We then evaluated these questionnaires against current best practice guidelines to ensure they are fit for purpose. EmPHasis-10 and the Living with Pulmonary Hypertension Questionnaire are preferred from the four evaluated in this study. The final part of this study was to look at what quality of life means for those living with pulmonary hypertension. Data from 8045 patients across the world was used to draft a health-related quality of life framework. We then finalised this design with professionals and patients. This framework can be used in the future to help understand how the well a questionnaire captures things important to those with lived experience of pulmonary hypertension. This will help us to better understand treatments that improve quality of life for people living with pulmonary hypertension.