Establishing portable measures of vaccine efficacy

Many multicentre randomized controlled trials describe a tendency for lower vaccine efficacy in settings where the disease incidence is higher. A mathematical basis for such trends will be examined and consistent measures of efficacy will be derived. New tools will be developed to enable more accurate and portable measures of vaccine efficacy to be inferred.

Where does this project lie in the translational pathway

This project is most directly concerned with analysing vaccine trials (T2), although the resulting measures of vaccine efficacy will be relevant for making decisions on vaccine licensure and predictions of population health impact (T4).

Methodological aspects of the PhD project?

The project involves the construction of population models, with special care being devoted to the representation of individual variation both within and between study sites. It also involves systematic literature review and model-based inference for model selection and parameter estimation.

Expected outputs of the PhD project

The described trend for vaccine efficacy is observed in many vaccines and the proposed models are generally applicable. There is, therefore, potential for a substantial number of publications. We expect new hypotheses to emerge for each vaccine examined in this project, leading to new study protocols which will be presented to partners at GSK Vaccines and Butantan Institute. Finally, it is well recognised in theory that individual variation (e.g. “frailty distributions”) enables selection and invalidates analyses based on population averages. Therefore, we expect project results to impact future vaccination policies.

What external training opportunities will be available for the student (ex. SMEs, industry, health agencies)?

The primary supervisor has active links with GSK Vaccines, in Belgium, and Butantan Institute, in Brazil, and can facilitate the setting up of internships related to this project.

Required skills/experience/aptitudes

BSc level Mathematics and Statistics.

Key publications that relate to this proposed project

1.

Gomes MGM, Gordon SB, Lalloo DG (2016) Clinical trials: the mathematics of falling vaccine efficacy with rising disease incidence. Vaccine 34: 3007-3009.

2.

Gomes MGM, Barreto ML, Glaziou P, Medley GF, Rodrigues LC, Wallinga J, Squire SB (2016) End TB strategy: the need to reduce risk inequalities. BMC Infect Dis 16: 132.

3.

Gomes MGM, Lipsitch M, Wargo AR, Kurath G, Rebelo C, Medley GF, Coutinho A (2014) A missing dimension in measures of vaccination impacts. PLOS Pathog 10(3): e1003849.

4.

Palmer TM, Thompson JR, Tobin MD, Sheehan NA, Burton PR (2008) Adjusting for bias and unmeasured confounding in Mendelian randomization studies with binary responses. Int J Epidemiol 37(5): 1161-1168.

5.

Gomes MGM, White LJ, Medley GF (2004) Infection, reinfection, and vaccination under suboptimal immune protection: Epidemiological perspectives. J Theor Biol228: 539-549.

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