Statistical Methods for Standard Membrane-Feeding Assays to Measure Transmission Blocking or Reducing Activity in Malaria

<p>Transmission blocking vaccines for malaria are not designed to directly protect vaccinated people from malaria disease, but to reduce the probability of infecting other people by interfering with the growth of the malaria parasite in mosquitoes. Standard membrane-feeding assays compare the growth of parasites in mosquitoes from a test sample (using antibodies from a vaccinated person) compared to a control sample. There is debate about whether to estimate the transmission reducing activity (TRA) which compares the mean number of parasites between test and control samples, or transmission blocking activity (TBA) which compares the proportion of infected mosquitoes. TBA appears biologically more important since each mosquito with any parasites is potentially infective; however, TBA is less reproducible and may be an overly strict criterion for screening vaccine candidates. Through a statistical model, we show that the TBA estimand depends on μ_<i>c</i>, the mean number of parasites in the control mosquitoes, a parameter not easily experimentally controlled. We develop a standardized TBA estimator based on the model and a given target value for μ_<i>c</i> which has better mean squared error than alternative methods. We discuss types of statistical inference needed for using these assays for vaccine development. Supplementary materials for this article are available online.</p

Restricted Likelihood Ratio Tests for Functional Effects in the Functional Linear Model

<div><p>The goal of our article is to provide a transparent, robust, and computationally feasible statistical approach for testing in the context of scalar-on-function linear regression models. Assuming linearity between response and predictors, we are interested in testing for the necessity of functional effects. Our methods are motivated by and applied to a large longitudinal study involving diffusion tensor imaging of intracranial white matter tracts in a susceptible cohort. In the context of this study, we conduct hypothesis tests that are motivated by anatomical knowledge and support recent findings regarding the relationship between cognitive impairment and white matter demyelination. R code and data are in the examples of refund::rlrt.pfr(). Supplementary materials for this article are available online.</p></div