A Scoping Literature Review of Digital Measures and Patient-Reported Outcomes for Refractory/Unexplained Chronic Cough: Assessment of Clinical Trials and Real-World Clinical Practice.

PURPOSE: Refractory/unexplained chronic cough (RCC/UCC) is a disease associated with substantial clinical and humanistic burden. A variety of endpoints have been used in RCC/UCC research to measure cough outcomes and impact on patients' quality of life (QoL), including clinical measures of cough using digital devices, or digital measures, and patient-reported outcomes (PROs). The aim of this review was to determine which endpoints are currently used in studies of RCC/UCC, and to explore the recent evolution of new digital measures used across research and clinical settings. METHODS: We conducted a scoping literature review (January 1, 2019-October 31, 2024), assessing studies of adults diagnosed with chronic cough (refractory/unexplained or newly diagnosed). Clinical trials and observational/real-world studies were included that evaluated objective and PRO measures of cough frequency, severity, symptoms, other cough characterization, and QoL. RESULTS: Overall, 70 studies (29 manuscripts, 35 clinicaltrials.gov entries, 6 posters/abstracts) were included: 36 clinical trials (Phase 2, 3, or 4), 34 observational/real-world studies. Objective cough frequency was the primary endpoint in 24/36 clinical trials. In contrast, objective cough frequency was reported in 10/34 observational/real-world studies. Observational/real-world studies had a greater variety of endpoints for cough outcomes and PROs compared with clinical trials. CONCLUSIONS: Clinical trials and observational/real-world studies of chronic cough and RCC use a wide range of outcome measures, including objective measures of cough frequency using digital devices (digital endpoints) and subjective PROs. New approaches to digital endpoints and PROs are being developed as the study and treatment of cough evolves.