IntroductionHealth-related quality of life (HRQoL) in pulmonary arterial hypertension (PAH) is valued as an outcome measure by patients, clinicians and regulators. Despite the incorporation of HRQoL in trials of PAH therapies, there is limited data on their suitability, accuracy and reliability.MethodWe report a systematic review following PRISMA guidelines (PROSPERO ID: CRD42024484021). Selection of PROMs included those powered to detect a minimal clinically important difference (MCID). Measurement properties were evaluated according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) and graded by recommendation for use. An a priori framework was then used to develop a ratified conceptual model from patient interviews and surveys to map the content of PROMs to HRQoL.ResultsScreening of 896 records was performed after removal of duplicates. Of 43 trials with a HRQoL endpoint, 20 selected an instrument with a MCID. Of these, only 8 trials were adequately powered. Three different PROMs (EuroQoL-5D-5L, Short Form-36, Living with Pulmonary Hypertension Questionnaire (LPHQ)) were used. For COSMIN measurement property evaluation, 389 records were screened and 21 were included; EmPHasis-10 was also evaluated due to its inclusion in forthcoming trials. Using COSMIN criteria EmPHasis-10 and LPHQ can be recommended (Grade A) for use in clinical trials in PAH. However, SF-36 and EQ-5D-5L (Grade B) require further study. Conceptual mapping from 8045 patients showed disease-specific instruments uniquely capture self-identity and autonomy.ConclusionTo improve evaluation of HRQoL outcomes, future PAH therapy trials require appropriate PROM selection, with adequate power, and consideration of conceptual mapping.Graphical abstracthealth-related quality of life outcomes in pulmonary arterial hypertension trialsCOSMIN 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 year, RCT randomised controlled trial, SF-36 36-item Short Form survey. Created with BioRender.comPlain language summaryIndividuals 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.
