Designing group dose-response studies in the presence of transmission

Math Biosci. 2018 Oct:304:62-78. doi: 10.1016/j.mbs.2018.07.007. Epub 2018 Jul 25.

Abstract

Dose-response studies are used throughout pharmacology, toxicology and in clinical research to determine safe, effective, or hazardous doses of a substance. When involving animals, the subjects are often housed in groups; this is in fact mandatory in many countries for social animals, on ethical grounds. An issue that may consequently arise is that of unregulated between-subject dosing (transmission), where a subject may transmit the substance to another subject. Transmission will obviously impact the assessment of the dose-response relationship, and will lead to biases if not properly modelled. Here we present a method for determining the optimal design - pertaining to the size of groups, the doses, and the killing times - for such group dose-response experiments, in a Bayesian framework. Our results are of importance to minimising the number of animals required in order to accurately determine dose-response relationships. Furthermore, we additionally consider scenarios in which the estimation of the amount of transmission is also of interest. A particular motivating example is that of Campylobacter jejuni in chickens. Code is provided so that practitioners may determine the optimal design for their own studies.

Keywords: Bayesian optimal experimental design; Dose-response experiments; Epidemic model.; Markov chains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Campylobacter Infections / transmission*
  • Campylobacter jejuni*
  • Chickens
  • Markov Chains
  • Models, Biological*
  • Research Design*