%0 Journal Article
%T Vaccine-Preventable Disease Incidence Based on Clinically, Radiologically and Etiologically Confirmed Outcomes: Systematic Literature Review and Re-analysis of Pneumococcal Conjugate Vaccine Efficacy Trials.
%A Bollaerts K
%A Fletcher MA
%A Suaya JA
%A Hanquet G
%A Baay M
%A Gessner BD
%J Clin Infect Dis
%V 0
%N 0
%D Jul 2021 27
%M 34313721
%F 20.999
%R 10.1093/cid/ciab649
%X <B>BACKGROUND: </B>Vaccine regulatory decision-making is based on vaccine efficacy against etiologically confirmed outcomes; however, these outcomes may underestimate the preventable disease burden. To quantify this underestimation, we compared vaccine-preventable disease incidence (VPDI) of clinically defined outcomes to radiologically/etiologically confirmed outcomes.<BR><B>METHODS: </B>We performed a systematic review of efficacy trials for several vaccines (1997-2019) and report results for pneumococcal conjugate vaccines [CRD42019145268]. Data were extracted for outcomes within a clinical syndrome, organized from most sensitive to most specific. VPDI was determined for each outcome, and VPDI ratios were calculated, with a clinically defined outcome (numerator) and a radiologically/etiologically confirmed outcome (denominator).<BR><B>RESULTS: </B>Among 9 studies, we calculated 27 VPDI ratios; 24 had a value >1. Among children, VPDI ratios for clinically defined versus vaccine serotype otitis media were 0.6 [95%CI not calculable], 2.1 [95%CI: 1.5;3.0], and 3.7 [95%CI: 1.0;10.2]; the VPDI ratios comparing clinically defined to radiologically confirmed pneumonia ranged from not calculable to 2.7 [95%CI: 1.2;10.4]; the VPDI ratio comparing clinically suspected invasive pneumococcal disease (IPD) to laboratory confirmed IPD was 3.8 [95%CI not calculable]. Among adults, the ratio comparing clinically defined to radiologically confirmed pneumonia was 1.9 [95%CI: -6.0;9.1] and to vaccine serotype confirmed pneumonia was 2.9 [95%CI: 0.5;7.8].<BR><B>CONCLUSIONS: </B>While there is substantial uncertainty around individual point estimates, there is a consistent trend in VPDI ratios, most commonly showing under-ascertainment of 1.5- to 4-fold, indicating that use of clinically defined outcomes is likely to provide a more accurate estimate of a pneumococcal conjugate vaccine's public health value.