Performance of respiratory patient reported outcome instruments in systemic sclerosis associated interstitial lung...

Interstitial lung disease (ILD) affects up to half of individuals with systemic sclerosis (SSc), within which it is a major cause of disease-related morbidity and a leading cause of mortality. Forced vital capacity (FVC) has been endorsed as a primary outcome measure for randomised controlled trials (RCT) assessing the efficacy of novel treatments for SSc-ILD. The FVC is considered a suitable surrogate biomarker, although does not directly capture information on how patients 'feel' and 'function', which regulators consider essential for marketing authorisation. Only patient-reported outcome (PRO) instruments can provide this insight. This review aims to systematically examine the inclusion, validity and performance of respiratory-specific PRO instruments used in SSc-ILD RCTs, using the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) framework and regulatory guidance. Our search identified 10 respiratory-specific PRO instruments used in SSc-ILD RCTs. Of these, 4 are single-item instruments and 2 were developed with any ILD patient input. Seventeen studies assessing the measurement properties of respiratory-specific PRO instruments within an SSc-ILD population were identified, with varying methodologies. The findings of this review highlight the lack of consensus for the use of respiratory-specific PRO instrument use in SSc-ILD RCTs. Identified instruments have unproven content validity within this population and limited evidence for other measurement properties, primarily derived from post hoc analyses of RCT data or cross-sectional studies. Future work should prioritise assessing the content validity and measurement properties of existing ILD specific instruments according to COSMIN guidance.