Respiratory syncytial virus (RSV) infects almost all children by the age of 2 years causing significant respiratory symptoms. However, no suitable clinical outcome assessment for RSV-related symptoms exists. An observer-reported outcome (ObsRO) measure was developed in alignment with US FDA guidance to address this need.
A prospective observational study of the draft ObsRO was conducted in 6 US pediatric offices in the 2014-15 RSV season. Subjects were < 24 month, full-term, previously healthy infants with respiratory symptoms of ≤ 5 days duration. RSV was confirmed via rapid antigen detection. Caregivers were asked to complete the 19-item web- or paper-based ObsRo twice daily for 14 days. Data were collected at the initial visit, subsequent visits, and end-of-study interview. Test-retest reliability (kappas), construct validity (correlations and factor analysis), discriminating ability (analyses of variance), and responsiveness (effect sizes) were evaluated.
A total of 103 subjects were enrolled, ranging in age from 0 to 23 months (mean = 7.4 months, SD = 5.3). Subjects were typically male (58%) and white (73.8%), while caregivers were female (93.1%) and white (77.7%), with an average age of 31.4 years (SD = 5.5). Most of the 19 ObsRO items demonstrated very good test‑retest reliability and analyses showed they could be grouped into Respiratory and Behavioral domains. Hypothesized correlations with other measures provided support for validity; for example, “daytime shallow breathing” correlated with the Clinician’s Global Impression of Severity (0.34; p < 0.01) and with the Parent’s Global Impression of Severity (0.46; p < 0.01). Hypothesis tests were generally in the predicted direction and many were statistically significant, substantiating the discriminating ability of the RSV ObsRO. Effect sizes were quite large, with a maximum change of 2.16 in mean score over 14 days seen in daytime cough severity, indicating the items were responsive (Figure 1).
C. Demuro, Gilead: Consultant , Consulting fee
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