Development and validation of the IPF Coughing Severity Scale v2© (IPF CSS v2): a simple patient reported outcome measure (PROM) for assessing cough severity in IPF

While several PROMs are used to assess IPF cough severity, none have been developed and validated to the standard needed to support regulatory approval of new drugs. We set out to develop and validate a simple PROM that could be completed by patients with IPF cough to support drug approval. Following literature review and expert interviews, a one question 11-point numerical rating scale (NRS, recall=24hrs) was tested in an observational study in IPF patients, including cognitive debriefing. This led to the addition of 2 severity questions at different times of the day (Early Morning, Rest of the Day) resulting in the 3-item IPF CSS (v2). Psychometric properties were evaluated qualitatively (37 interviews) and quantitatively (N=80) in the ORV-PF-01 study (<ext-link>NCT05185089</ext-link>). Analyses were done on mean weekly scores with a focus on the Daily (last 24 hours) question. Within subject, mean scores are stable and between subject variance is low (CV%=17.8%). Floor and ceiling score effects are minimal. Test-retest reliability is good (ICC 0.81 in stable patients) and scores respond to change during treatment. Known groups validity and construct validity is shown through correlation with other cough assessments (global ratings of status/change, Leicester Cough Questionnaire). Distribution-based methods show a group mean difference of -0.7 points is clinically meaningful, and anchor-based methods show the meaningful within subject change is -1.1 points. Findings were similar for the other 2 questions. The IPF CSS v2 is a simple, valid NRS PROM for assessing cough severity in IPF; clinically relevant differences and changes are defined.