The influence of incomplete case ascertainment on measures of vaccine efficacy
YueWu a, Julie A. Marsh a,b , Emma S. McBryde c , Thomas L. Snelling a,d,e,f. The influence of incomplete case ascertainment on measures of vaccine efficacy. Vaccine, Volume 36, Issue 21, 17 May 2018, Pages 2946-2952, https://doi.org/10.1016/j.vaccine.2018.04.046
Abstract
Background
Motivated by the unexplained variation in the performance of some vaccines across different settings, we extend previous theoretical work to consider the potential impact of incomplete case ascertainment on measures of vaccine efficacy (VE), which is more likely in subclinical or clinically unimportant infections, such as rotavirus gastroenteritis.
Methods
By simulating the measurement of VE under outbreak conditions using a discrete time stochastic SIR model, we compare three commonly used measures, VERisk, VERate, and VEHazard, calculated respectively based on risk ratio, rate ratio and hazard ratio of disease. We investigate how these measures are influenced by factors such as biological activity, action mechanism of vaccine, proportion of cases ascertained, and underlying force of infection.
Results
Under plausibly low levels of ascertainment, the group with the most infections, and therefore the most missed cases, has the most falsely inflated denominator, producing similar rates in the control and intervention groups. As a result, VERate and VEHazard will underestimate the true VE compared to high case ascertainment scenarios. Furthermore, the extent of underestimation is greater for leaky vaccine models with lower biological protective effects and under conditions which are conducive to high transmission.
Conclusions
This study demonstrates that a biologically active vaccine may produce a low measured VE under a range of epidemiological, vaccine-related and logistical conditions. Low case ascertainment may partly explain the observed heterogeneity in the performance of rotavirus vaccine across different settings, and should be considered in the design and interpretation of future field trials.
a Wesfarmers Centre of Vaccines & Infectious Diseases, Telethon Kids Institute, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia
b School of Mathematics & Statistics, University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009, Australia
c Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia
d Princess Margaret Hospital for Children, Roberts Road, Subiaco, Western Australia 6008, Australia
e Menzies School of Health Research, Charles Darwin University, Casuarina, Northern Territory 0811, Australia
f School of Public Health, Curtin University, Kent Street, Bentley, Western Australia 6102, Australia