Design of field trials for the evaluation of transmissible vaccines in animal populations.

Vaccines which can transmit from vaccinated to unvaccinated animals may be especially useful for increasing immunity in hard to reach populations or in populations where achieving high coverage is logistically infeasible. However, gauging the public health utility for future use of such transmissible vaccines and assessing their risk-benefit tradeoff, given their potential for unintended evolution, hinges on accurate estimates of their indirect protective effect. Here, we establish the conditions under which a two-stage randomized field trial can characterize the protective effects of a transmissible vaccine relative to a traditional vaccine. We contrast the sample sizes required to adequately power these trials when the vaccine is weakly and strongly transmissible. We also identify how required sample sizes change based on the characteristics of host ecology such as the overdispersion of the contact structure of the population, as well as the efficacy of the vaccine and timing of vaccination. Our results indicate the range of scenarios where two-stage randomized field trial designs are feasible and appropriate to capture the protective effects of transmissible vaccines. Our estimates identify the protective benefit of using transmissible vaccines compared to traditional vaccines, and thus can be used to weigh against evolutionary risks.