Hodgson, David; (2020) Mathematical modelling and cost-effectiveness of future RSV intervention strategies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

New Respiratory Syncytial Virus (RSV) prophylactics are likely to be licensed in the next few years. Such prophylactics, including long-acting monoclonal antibodies and new vaccines, will aim to either replace or supplement the current monoclonal Palivizumab programme. This thesis explores the implications of these changes to RSV health policy by developing and using a novel mathematical model for RSV transmission and evaluating the impact of potential intervention programmes. The model will be combined with an economic analysis and a cross-sectional survey of RSV burden in England and Wales. Specifically, this thesis is split into six chapters which outline different topics of RSV research which are used collectively to inform RSV policy decision making in England and Wales. Chapter 1 provides the background information, giving context for the chapters that follow, as well as the aims and objectives of the thesis. Chapter 2 outlines a study that determines the health burden due to RSV in England and Wales through a cross-sectional survey performed in the winter of 2016/17. Chapter 3 describes a review of existing transmission models outlining the key epidemiological features that characterise RSV transmission and determines gaps in the current literature. Chapter 4 then presents a novel mathematical model for RSV transmission, parametrised and calibrated to seven years of historical epidemiological data using a Bayesian approach. Impact projections of the model for different RSV intervention programmes are given in Chapter 5. Finally, Chapter 6 combines the impact projections with an economic model to showcase the cost-effectiveness and affordability for a suite of RSV intervention programmes. The results of the calibrated model suggest that maternal protection of infants is seasonal, with 2-14% of infants born with protection against RSV. Further, the economic analysis found that to cost-effectively and affordably replace the current monoclonal antibody Palivizumab programme with long-acting monoclonal antibodies, the purchase price per dose would have to be less than around £4,350 but dropping to £200 for vaccinated heightened risk infants or £90 for all infants. A seasonal maternal vaccine would have to be priced less than £85 to be cost-effective and affordable. While vaccinating pre-school and school-age children is likely not cost-effective relative to elderly vaccination programmes, an elderly vaccination programme is not likely to be affordable. Conversely, vaccinating infants seasonally at two months of age would be cost-effective and affordable if priced less than £80. In a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal, an assumption not previously incorporated in transmission models of RSV. For a country with periodic RSV dynamics like England, seasonal programmes rather than year-round intervention programmes are always optimal.

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