MRC DiMeN Doctoral Training Partnership: Improving methods to determine vaccine impact in low and middle income countries at University of Liverpool on FindAPhD.com

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Dr Daniel Hungerford, Prof N French, Dr Pete Dodd, Dr Anja (DJ) Terlouw No more applications being accepted Competition Funded PhD Project (Students Worldwide)

Liverpool United Kingdom Data Science Epidemiology Mathematical Modelling Statistics

About the Project

Background

Measuring vaccine impact, both the direct and indirect effects of vaccines on population health, is essential for new vaccines. Attributing improvements in health to vaccine effects in a context with rapidly changing public health and social-welfare interventions often is problematic, and is limited by available data. Most current approaches to vaccine impact measurement rely on using pre-vaccine data to predict an expected burden of disease based on past-trends and compare to what is observed, but improved understanding of confounding and indirect effects is essential to improve the accuracy of these estimates. The key question is how to better quantify full vaccine population impacts from observational data, differentiating vaccine-attributable effects from those of other concurrent public health interventions?

Objectives

Through a scoping review, describe the designs and analytical methods of vaccine impact evaluations (VIE) in resource limited settings.

Compare the performance of existing impact assessment methods using VIEs of malaria RTS,S as a gold-standard, and extend to pneumococcal conjugate and rotavirus vaccine introduction in Malawi and consider logical method modification.

Through simulation-based approach applied to the methods investigated in objective 2, identify improved methods and the most important confounding factors and indirect benefits to include in future evaluations.

Experimental Approach. Using the cluster randomised impact evaluation of malaria RTS,S vaccine and an upcoming evaluation of Typhoid vaccine in Malawi, we will use VIEs on under 5-child mortality from this study as a gold-standard to 1) compare different observational method performance and how they deviate from the gold-standard 2) investigate the role and relative importance of confounders through simulation studies 3) reanalyse data from published pneumococcal and rotavirus vaccine evaluations to investigate how impact estimates alter.

Novelty

Incorporating cutting-edge infectious disease modelling and simulation approaches into VIEs in low and middle income countries (LMIC) to determine more robust and complete effectiveness measures.

Utilising the unusual opportunity of an ongoing cluster-randomised controlled VIEs of RTS,S in Malawi to benchmark and test new methodology.

Use this approach to answer key questions on optimising real-life delivery of the RTS,S and Typhoid vaccines in terms of scheduling, dosing, and impact on target/high-risk groups.

Training

This project offers excellent candidate skill development:

Interdisciplinary and quantitative skills: this project involves advanced statistical modelling and simulation techniques and data analytics and epidemiology. Their application to answer a key question in Global Health on improving the accuracy of vaccine introduction evaluations covers, vaccine effect and safety and the related disciplines of pharmacovigilance, disease burden and epidemiology.
Translational skills: are incorporated through the application to vaccine impact in routine health systems in LMICs which will capture health systems research, involve health economics skills, and policy-maker interaction.

Links

Centre for Global Vaccine Research @CGVR_liverpool

https://www.liverpool.ac.uk/infection-veterinary-and-ecological-sciences/research/groups/vaccines/

Dan Hungerford @danhungi https://www.liverpool.ac.uk/infection-veterinary-and-ecological-sciences/staff/dan-hungerford/

Neil French

https://www.liverpool.ac.uk/infection-veterinary-and-ecological-sciences/staff/n-french/

Pete Dodd @petedodd24

https://www.sheffield.ac.uk/scharr/people/staff/pete-dodd

Anja Terlouw

https://www.lstmed.ac.uk/about/people/dr-anja-dj-terlouw

Benefits of being in the DiMeN DTP:

This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.

We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.

Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards

Further information on the programme and how to apply can be found on our website:

http://www.dimen.org.uk/how-to-apply/application-overview

Funding Notes

Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover UK tuition fees, stipend and project costs as standard. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will be awarded to exceptional candidates only, due to the competitive nature of this scheme. Please read additional guidance here: http://www.dimen.org.uk/how-to-apply/eligibility-funding
Studentships commence: 1st October 2022
Good luck!

References

[1] King C, Bar-Zeev N, Phiri T, Beard J, Mvula H, Crampin A, et al. Population impact and effectiveness of sequential 13-valent pneumococcal conjugate and monovalent rotavirus vaccine introduction on infant mortality: prospective birth cohort studies from Malawi. BMJ Glob Health 2020;5. https://doi.org/10.1136/bmjgh-2020-002669.
[2] Hungerford D, Vivancos R, Read JM, Bonnett LJ, Bar-Zeev N, Iturriza-Gómara M, et al. Mitigating bias in observational vaccine effectiveness studies using simulated comparator populations: Application to rotavirus vaccination in the UK. Vaccine 2018;36:6674–82. https://doi.org/10.1016/j.vaccine.2018.09.051.
[3] Hungerford D, Vivancos R, Read JM, Iturriza-Gόmara M, French N, Cunliffe NA. Rotavirus vaccine impact and socioeconomic deprivation: an interrupted time-series analysis of gastrointestinal disease outcomes across primary and secondary care in the UK. BMC Med 2018;16:10. https://doi.org/10.1186/s12916-017-0989-z.
[4] Bar-Zeev N, Swarthout TD, Everett DB, Alaerts M, Msefula J, Brown C, et al. Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006–18: prospective observational time-series and case-control studies. Lancet Glob Health 2021;9:e989–98. https://doi.org/10.1016/S2214-109X(21)00165-0.
[5] Bennett A, Pollock L, Bar-Zeev N, Lewnard JA, Jere KC, Lopman B, et al. Community transmission of rotavirus infection in a vaccinated population in Blantyre, Malawi: a prospective household cohort study. Lancet Infect Dis 2021;21:731–40. https://doi.org/10.1016/S1473-3099(20)30597-1.
[6] Ndeketa L, Mategula D, Terlouw DJ, Bar-Zeev N, Sauboin CJ, Biernaux S. Cost-effectiveness and public health impact of RTS,S/AS01E malaria vaccine in Malawi, using a Markov static model 2021. https://doi.org/10.12688/wellcomeopenres.16224.2.
[7] Halloran M Elizabeth, Hudgens Michael G. Estimating population effects of vaccination using large, routinely collected data. Stat Med 2017;37:294–301. https://doi.org/10.1002/sim.7392.
[8] Lopez Bernal JA, Andrews N, Amirthalingam G. The Use of Quasi-experimental Designs for Vaccine Evaluation. Clin Infect Dis 2019;68:1769–76. https://doi.org/10.1093/cid/ciy906.

Where will I study?

University of Liverpool

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