Evaluation of Efficacy Endpoints for a Phase IIb Study of a Respiratory Syncytial Virus Vaccine in Older Adults Using Patient-Reported Outcomes With Laboratory Confirmation.

There are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation. In a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged ≥60 years who had any respiratory symptom lasting ≥24 hours recorded symptoms in a FLU-PRO-based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSV-associated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation. The FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring ≥2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self- and site-collected swabs were highly correlated. Self-swabbing detected 9 additional cases that would have been missed by site swabbing only. These results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.

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