The mathematics of falling vaccine efficacy with rising disease incidence.

News article 8 Jun 2016

Researchers at LSTM have provided a mathematical explanation for the general trend of lower vaccine efficacy in settings where the disease incidence is higher.

Led by first author Dr Gabriela Gomes, a reader in Biomathematics at LSTM, they set out to address the issue of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world. In a paper published in the journal Vaccine today, the team acknowledged that disease risks vary between individuals participating in a trial and reformulated efficacy calculations accordingly. This approach enabled them to estimate vaccine protection in a manner that is consistent across epidemiological settings and is expected to increase predictive value in models of intervention impact.

To illustrate the procedure they looked at published data with three vaccines that have undergone randomised controlled trials throughout the globe. These were the BCG to protect against pulmonary tuberculosis, RotaTeq against rotavirus gastroenteritis and RTS,S against malaria. While consistent with these data, they also indicate that the framework is applicable more generally to vaccines and other interventions against, not only infectious diseases, but non-communicable disorders provided that the relevant information is available.

Dr Gomes said: “Unexplained discrepancies in the estimated efficacy of vaccines clearly call into question the suitability of analytic methods whose validity relies on implicit homogeneity assumptions. It is surprising that current analyses do not account for individual variation given that trialists themselves recognise the importance of individual variation in the design of randomised controlled trials. We are simply proposing the incorporation of frailty distributions in the analysis of multicentre clinical trials.” The team now call for further research into the establishment of a new suite of methods. She continued: “We hope to have laid the basis for future work on this important topic, where methodological development can be as elaborate as the detail in available data allows.”