Speaker: Steephanson Anthonymuthu

Title: Estimation of the mitigated fraction from ordinal data in the evaluation of vaccine efficacy 

Abstract:

Vaccine efficacy can be established through the estimation of several numerical measures found in the literature. A widespread and common measure of efficacy for vaccines, especially those designed to prevent a given disease, is the prevented fraction.  Unfortunately, the prevented fraction can be used only when the outcome is dichotomous. It is worth noting that some useful vaccines reduce the severity of the targeted disease rather than entirely prevent its occurrence. The concept of the mitigated fraction was introduced in veterinary medicine to quantify the reduction in the severity of disease occurring in vaccinated animals as compared to non-vaccinated animals. The USDA’s Center for Veterinary Biologics (CVB) recommends a form of the mitigated fraction proposed by Siev (2005) which can be easily calculated when the disease severity can be graded by some continuous measure or by some discrete assessment resulting in unambiguous ranks. Current CVB guidance suggests that the mitigated fraction be estimated non-parametrically via the use of the mean ridit (Bross, 1958) and Wilcoxon rank sum statistics.

A survey of recent literature indicates a growing interest in measures of effect size when the outcome variable is ordinal, especially when observations are clustered or measured longitudinally. Here, a parametric approach has been carried out using several statistical procedures under different experimental designs to estimate the mitigated fraction from an ordinal response. Preliminary work shows the parametric approach works well for a completely randomized design and may be extended to studies where more than two treatments are compared whereas the method of Siev (2005) can handle only two treatment levels (vaccinated and non-vaccinated). Furthermore, analysis results for datasets with a clustered ordinal response are explored under various statistical procedures. Extension of these procedures to multisite vaccine trials will also be discussed.