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Background: PRO measures of symptoms in clinical trials have historically utilized visual and numerical scales but verbal descriptors may make it easier for patients to clearly differentiate between response options. This study assessed content validity and meaningful change in five verbal response scales (VRSs) used to assess chronic rhinosinusitis with nasal polyp (CRSwNP) symptom severity., Methodology: This qualitative, semi-structured interview study recruited adults from the US, Germany, and China with confirmed moderate-to-severe CRSwNP. Interviews included a concept elicitation section, where participants were asked about their experience of living with CRSwNP including symptoms and health-related quality-of-life impacts, and a cognitive debriefing section, where participants were debriefed and participant understanding and real-life relevance of the CRSwNP symptom VRS content were assessed. Interview transcripts were qualitatively analyzed using thematic analysis methods., Results: Among the 24 participants interviewed, the most frequently reported CRSwNP symptoms were nasal obstruction, runny nose, mucus in the throat, loss of smell and facial pain/pressure. Participants demonstrated good understanding of the CRSwNP symptom VRS instructions, items, recall period, and response options. The five CRSwNP symptom VRS items were relevant to the majority of participants' experience of CRSwNP. At the item level, a one-category within-person improvement was the level most frequently reported by participants to be a meaningful change., Conclusion: The CRSwNP symptom VRSs assess relevant and bothersome symptoms experienced by patients with moderate-to-severe CRSwNP, supporting content validity of this measure. The findings of this study provided preliminary insights into meaningful change in the VRS. Further quantitative assessment of meaningful change is needed, and psychometric evaluation of the CRSwNP symptom VRSs will be required to evaluate their appropriateness for assessment of clinical trial endpoints in patients with CRSwNP., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted according to the principles outlined in the Declaration of Helsinki, and according to guidelines published by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Additionally, all data was handled in accordance with the European General Data Protection Regulation (GDPR), and data from China was handled in accordance with the PIPL and Data Security Law (DSL). Ethical approval was obtained from Salus Institutional Review Board (IRB), a centralized IRB that provides ethical oversight to research conducted globally for multi-country studies, prior to the collection or processing of participant data (Salus IRB: C218108 GK9381A). Each participant provided written and verbal consent via the informed consent form before their interview was conducted. Consent for publication: Not applicable. Competing interests: TK, NG, WA, RA-C and ARS are employed by GSK and hold financial equities in GSK; KF, RS, SW and AG are employees of Adelphi Values, a consulting company that received funds from GSK to conduct this study but did not receive payment for manuscript development., (© 2024. The Author(s).)

Background: This randomised, double-blind, placebo-controlled, parallel-group, 52-week Phase III study (MERIT; NCT04607005) assessed mepolizumab efficacy and safety in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS (ECRS) in Japan, Russia, and China, for which data are limited., Methodology: Eligible patients (enrolled at 60 centres) had blood eosinophil count >2%, endoscopic bilateral NP score ≥5, nasal obstruction visual analogue scale (VAS) score >5, ≥2 sinonasal symptoms, and either previous sinus surgery or systemic corticosteroid use/intolerance. Patients were randomised (1:1) to receive mepolizumab 100 mg subcutaneously or placebo every 4 weeks, plus standard of care. Co-primary endpoints: change from baseline in total endoscopic NP score (ENPS) (Week 52) and nasal obstruction VAS score (Weeks 49-52). Post hoc analyses conducted in a modified intent-to-treat (mITT) population excluded patients from two study sites, related to Good Clinical Practice violations by the Site Management Organisation overseeing these sites. These were considered the primary efficacy analyses., Results: In the mITT population, mepolizumab (n=80) versus placebo (n=83) significantly improved nasal obstruction VAS score from baseline to Week 49-52 and was associated with a trend of total ENPS improvements at Week 52. Mepolizumab/placebo on-treatment adverse events (AEs) occurred in 68/84 and 65/85 patients in the safety population (treatment-related AEs: 2/84 and 5/85, respectively), and on-treatment serious AEs in 0/84 and 4/85 patients, respectively (no fatalities reported)., Conclusions: Mepolizumab was effective and well-tolerated in patients with CRSwNP/ECRS from Japan, Russia, and China.