P-21. Comparison of Three RSV Vaccine Lower Respiratory Tract Disease Primary Endpoint Definitions for Adult Vaccine Open Access

Despite their public health importance, a consensus definition for lower respiratory tract disease (LRTD), or illness (LRTI) is lacking. Clinical trials of three respiratory syncytial virus (RSV) vaccines for older adults used different LRTI/LRTD definitions for vaccine efficacy (VE). We hypothesize differences between definitions could bias product comparisons.

We reviewed case definitions for LRTI/LRTD in RSV vaccine clinical trials conducted in older adults.

Two of three published RSV vaccine clinical trials from Pfizer and Moderna used two outcomes (LRTI/LRTD with ≥2 signs/symptoms or ≥3 signs/symptoms) to measure VE, while the third trial from GlaxoSmithKline (GSK) used one (combining ≥2 and ≥3 signs/symptoms) (Table 1). The Pfizer trial included 5 signs/symptoms as components of LRTI; three of these (tachypnea, wheezing, shortness of breath) suggest lower airway involvement and two (cough and self-reported sputum production) could also result from upper airway infection. At interim analysis, 29 of 45 cases had only 2 symptoms (64.4%). Of these 29, 25 had only cough and sputum production (86.2%). The GSK trial, by contrast, required all LRTD cases to include at least one sign, all of which indicated lower airway involvement (Table 2). The Moderna trial included 10 signs/symptoms, including the potential for subjects to have only cough and sputum production. Even within signs/symptoms, definitions differed (e.g., tachypnea cutoff ranged from 20 to 25 breaths per minute; Table 2). When using comparable definitions, full season 1 VEs for Pfizer and GSK products were similar while the point estimate for the Pfizer product was higher during season 2 (Table 3).