Estimating Vaccine Efficacy from Household Data Using Surrogate Outcome and a Validation Sample

Abstract

Household data are frequently used in estimating vaccine efficacy because it provides information about every individual's exposure to vaccinated and unvaccinated infected household members. This information is essential for reliable estimation of vaccine efficacy for infectiousness (V E(subscript I) ), in addition to estimating vaccine efficacy for susceptibility (V E(subscript S)). However, accurate infection outcome data is not always available on each person due to high cost or lack of feasible methods to collect this information. Lack of reliable data on true infection status may result in biased or inefficient estimates of vaccine efficacy. In this paper, a semiparametric method that uses surrogate outcome data and a validation sample is introduced for estimation of V E(subscript S) and V E(subscript I) from a sample of households. The surrogate outcome data is usually based on illness symptoms. We report the results of simulations conducted to examine the performance of the estimates, compare the proposed semiparametric method with maximum likelihood methods that either use the validation data only or use the surrogate data only and address study design issues. The new method shows improved precision as compared to a method based on the validation sample only and smaller bias as compared to a method using surrogate outcome data only. In addition, the use of household data is shown to greatly improve the attenuation in the estimate of V E(subscript S) due to misclassification of the outcome, as compared to the use of a random sample of unrelated individuals.