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Christine de la Loge,1 Fatoumata Fofana,2 Paul Williams,1 Sarah Rusch,3 Marita Stevens,4 Jane Scott5 1Patient-Centered Outcomes, Mapi (an ICON Plc. company), Lyon, France; 2Patient-Centered Outcomes, Mapi (an ICON Plc. company), Leiden, the Netherlands; 3Statistical Decisions and Sciences, Janssen Biostatistics Research & Development, Beerse, B-2340, Belgium; 4Global Clinical Development Infectious Diseases, Janssen Research & Development, Beerse, B-2340, Belgium; 5Janssen Global Services LLC, High Wycombe, UKCorrespondence: Christine de la Loge Tel +33 7 85 61 78 59Email cdelaloge@outlook.frPurpose: PRESORS ClinRO completed by clinicians and ObsRO completed by caregivers were developed to characterize the clinical course of respiratory syncytial virus (RSV) infection. This study describes preliminary analysis of PRESORS’ measurement properties using clinical trial data.Patients and Methods: PRESORS ClinRO and ObsRO data were collected in a 28-day randomized, double-blind, Phase 1b trial of JNJ-53718678 or placebo in infants and children ≤ 24 months of age treated for RSV infection in hospitals. PRESORS data were scored and key psychometric properties of scores were evaluated, including ability to discriminate between known groups and to detect change over time. Time to resolution of RSV signs was explored using two responder definitions.Results: Daily completion rates for PRESORS ClinRO and ObsRO were high for the 44 children in the study (median: 100% and 93%, respectively). Large floor effects were observed at baseline for signs of severe RSV infection that were either absent (cyanosis, fever, apnea) or rarely reported (reduced urination/dehydration, vomiting). Implausible ObsRO ratings suggested some caregivers could not accurately measure heart rate. Known-group validity was confirmed: children in poor health based on baseline ClinRO had mean baseline composite scores that were significantly worse for both ObsRO (p=0.001) and ClinRO (p< 0.001) compared to those with better overall health. ObsRO (p=0.009) and ClinRO (p< 0.001) composite scores were responsive to change in overall health status from baseline to Day 3. Mean scores for RSV sign dimensions decreased rapidly from baseline to Day 7 except for coughing and sleep ratings by caregivers. Time to recovery varied greatly depending on definitions used.Conclusion: PRESORS ClinRO and ObsRO can inform endpoints and enable monitoring the clinical course of RSV in pediatric trials. Improved alignment between ClinRO and ObsRO and revisions ensuring caregivers can assess all signs will be addressed in revised PRESORS.Keywords: psychometric validation, clinician-reported outcomes, observer-reported outcomes, pediatrics, respiratory syncytial virus

Abstract Background The QUALIOST® was designed for use with the SF-36 to measure established osteoporosis-specific quality of life (QoL). The reliability (internal consistency and test-retest) and validity of the questionnaire were established in a stand-alone psychometric validation study. The objective of this paper is to provide additional information on the instrument's responsiveness using clinical trial data, along with the reliability and validity of translated versions. Methods The Spinal Osteoporosis Therapeutic Intervention (SOTI) was an international clinical trial comparing strontium ranelate to placebo on the occurrence of new vertebral fracture in patients with postmenopausal osteoporosis. QoL was a secondary endpoint, assessed using the SF-36 and QUALIOST® at baseline and every six months, with the main analysis at 3-year follow-up. Questionnaire acceptability, analysis of the hypothesised structure, internal consistency reliability and responsiveness to clinical change over time were assessed at the 3-year follow up. Results 1592 patients from 11 countries completed at least one QoL questionnaire. The psychometric properties of the questionnaires were assessed on cross-sectional (N = 1486) and longitudinal (N = 1288) data. Item discriminant validity of the QUALIOST® was excellent, as was item convergent validity, with 100% of item-scale correlations being above the 0.40 level. Internal consistency reliability was also extremely good, with high Cronbach's alpha scores above the 0.70 benchmark. Responsiveness results were consistent for all QUALIOST® scores, indicating that greater decreases in QoL corresponded to greater numbers of fractures experienced. QUALIOST® scores also differed according to the type of fracture suffered. This was demonstrated by increased effect sizes for more severe vertebral fractures (clinical vertebral and painful vertebral). In comparing responsiveness, the QUALIOST® scores were generally more consistent than those of the SF-36. Most notably, the QUALIOST® was more responsive with regard to painful vertebral fractures than the SF-36. Conclusion The QUALIOST® is a reliable and valid tool for measuring QoL in postmenopausal osteoporotic women. Being available in several validated language versions, it is ready to be used in a variety of settings, including international clinical trials.