Monitoring Severity of Respiratory Syncytial Virus (RSV) in Infants and Young Children Using the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS): Results of Initial Quantitative Validation

Abstract

Purpose 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.

Clinical course and complications of RSV versus non-RSV bronchiolitis in hospitalised children

“…On the contrary, we found (in both univariate and multivariate models) higher odds of cough and (in the univariate model only) vomiting; the latter may play a role (unlike cough, which does not seem to be a significant discriminator in the case of LRTI). Previous work has described more frequent vomiting in children with RSV disease (24) , a probable association with RSV A infection has been raised (our study did not distinguish between RSV A and RSV B infection) (25) , and a suggestion has been made to include vomiting in the disease severity scoring system, especially vomiting unrelated to cough episodes (26) . Contrary to Ramagopal et al (10) , we did not assess the frequency of wheezing because the Polish definition of bronchiolitis already includes wheezing as one of the main features of AB (7) .…”

Exploration of Caregiver Interrater Agreement and Test-Retest Reliability on the Infant Cleft Observer Outcomes (iCOO)

“…The high test-retest reliability has been document in ObsROs for infants and children for other conditions such as cystic fibrosis 23 and validity for similar ObsROs has also been documented in other conditions such as respiratory syncytial virus. [24][25][26] Additional research is needed to determine if each caregiver's ratings are providing different information or if one caregiver's assessment is more accurate than the other's.…”

Measuring respiratory syncytial virus infection severity in hospitalized children using the Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS)

“…The ClinRO includes 12 items reflecting signs of RSV infection that had been identified in earlier development steps: activity level , sleep , feeding , dehydration , apnea , retractions , tachypnea , breathing problems , cyanosis , cough , nasal secretions , and wheezing (Table S1). 8 For each item, possible responses reflect potential diagnoses or other key elements. For example, the clinician can indicate for the item retractions whether any subcostal, intercostal, or tracheosternal retractions were observed in the relevant time window.…”

“…The Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS) is under development to assess the severity of RSV infection in children based on the presence and severity of signs and symptoms of RSV disease as reported by clinicians (the PRESORS Clinician‐Reported Outcome questionnaire [ClinRO]) and the child's caregiver (the PRESORS Observer‐Reported Outcome questionnaire [ObsRO]) 8 . The ClinRO and ObsRO measures were developed in parallel based on ethnographic and qualitative interview studies with clinicians and caregivers of children with RSV and consultations with pediatric clinical experts 8–11 . Other tools in development include the Respiratory Syncytial Virus Network (ReSViNET) Scale, 12,13 the Global Respiratory Severity Score (GRSS), 14 and the Gilead RSV Caregiver Diary (GRCD) 7 …”

“…8 The ClinRO and ObsRO measures were developed in parallel based on ethnographic and qualitative interview studies with clinicians and caregivers of children with RSV and consultations with pediatric clinical experts. [8][9][10][11] Other tools in development include the Respiratory Syncytial Virus Network (ReSViNET) Scale, 12,13 the Global Respiratory Severity Score (GRSS), 14 and the Gilead RSV Caregiver Diary (GRCD). 7 For clinician ratings, an RSV severity rating scale needs to be reliable such that different clinicians provide the same rating for the same child.…”