How is the "most bothersome symptom" construct measured across health conditions? A systematic review of patient-reported outcome measures.

OBJECTIVE: Patient-reported outcome measures (PROMs) capture patients' experiences and perspectives of symptoms. One approach involves measuring the "most bothersome symptom," an outcome recommended in some regulatory guidance and core outcome sets. This systematic review aimed to identify and characterize PROMs to measure the "most bothersome symptom," describe available measurement properties, and examine terminology used to describe "bother." METHODS: This review was registered in PROSPERO (CRD42022210384). A systematic search of EMBASE, MEDLINE, PsycINFO, and PROQOLID was conducted. Reviewers independently screened and extracted data on PROMs that directly measured the "most bothersome symptom" or indirectly assessed symptom bothersomeness. PROMs using related terminology (e.g. troublesome, distressing) were included. PROMs directly measuring the "most bothersome symptom" were evaluated using COSMIN and modified GRADE criteria. RESULTS: In total, 270 articles describing 171 PROMs were included. Most PROMs (n = 135) indirectly captured bothersomeness through symptom scoring. Terminology inconsistencies were common; among 130 PROMs measuring "bother," authors also used "distress" (10%), "severity" (8%), and "burden" (6%). Fourteen PROMs directly measured the "most bothersome symptom," with only three demonstrating adequate content validity. CONCLUSIONS: Limited high-quality evidence supporting the measurement properties of PROMs designed to directly assess this construct, particularly content validity, restricts interpretability. More rigorous PROM development is required.