Qualitative exploration of women's experiences of vasomotor symptoms to support the content validity of patient-reported outcomes.

Background: Frequency and severity of vasomotor symptoms (VMS; hot flashes) associated with menopause significantly impact women's health-related quality of life (HRQoL). Treatment benefit in VMS clinical trials is assessed using patient-reported outcome (PRO) measures, which must demonstrate evidence of content validity. This research aimed to establish a conceptual model in VMS and evaluate content validity of the Hot Flash Daily Diary (HFDD), PROMIS Sleep Disturbance Short Form 8b (PROMIS SD SF 8b), and Menopause-Specific Quality of Life (MENQOL) questionnaire for use in VMS clinical trials.

Methods: Targeted searches were conducted to identify qualitative literature documenting women's VMS experiences. Qualitative concept elicitation (CE) and cognitive interviews (CI) were then conducted with 20 US participants experiencing VMS (n = 10 postmenopause; n = 10 AET-treated). Literature and CE findings were used to develop a conceptual model and confirm conceptual coverage of PRO measures selected for assessing efficacy in VMS clinical trials. CIs assessed the content validity of PRO measures.

Results: Findings from the literature and CE interviews informed a conceptual model depicting women's experiences of VMS. Thirty-three symptom concepts were identified with key symptoms including sweating, cold sweats/chills and tiredness/fatigue. Impacts of VMS on HRQoL were categorized into seven domains: sleep, emotional wellbeing, activities of daily living, social wellbeing, work/education, cognitive and physical functioning. The concepts assessed by the HFDD (VMS severity and frequency), PROMIS SD SF 8b (sleep disturbance) and MENQOL (menopause-related quality of life) aligned with those endorsed by women as relevant to their VMS experience. Instructions, recall periods and response options of the measures were understood. A reduction of one moderate or one severe hot flash in 24-hours (assessed by the HFDD) was considered a meaningful improvement by participants. Similar observations were made across study samples.

Conclusions: Findings provide detailed insights into women's experience of VMS, supporting the development of a conceptual model and assessment of conceptual coverage of selected PRO measures. Content validity of the HFDD, PROMIS SD SF 8b, and MENQOL for use in VMS clinical trials was supported. CI results suggest that a reduction of one moderate or one severe hot flash in 24-hours is meaningful to women with VMS.