Cost-effectiveness of the next generation of RSV intervention strategies
Bibliographic record
Abstract
ABSTRACT Background With a suite of promising new RSV prophylactics on the horizon, including long-acting monoclonal antibodies and new vaccines, it is likely that one or more of these will replace the current monoclonal Palivizumab programme. However, choosing the optimal intervention programme will require balancing the costs of the programmes with the health benefits accrued. Methods To compare the next generation of RSV prophylactics, we integrated a novel transmission model with an economic analysis. We estimated key epidemiological parameters by calibrating the model to seven years of historical epidemiological data using a Bayesian approach. We determined the cost-effective and affordable maximum purchase price for a comprehensive suite of intervention programmes. Findings Our transmission model suggests that maternal protection of infants is seasonal, with 2-14% of infants born with protection against RSV. Our 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, vaccinating the elderly is not likely to be affordable. Conversely, vaccinating infants at 2 months seasonally would be cost-effective and affordable if priced less than £80. Interpretations 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 seasonal RSV dynamics like England, seasonal programmes rather than year-round intervention programmes are always optimal. Funding Medical Research Council and National Institute for Health Research RESEARCH IN CONTEXT Evidence before this study A recent systematic review identified RSV prophylactic candidates currently in clinical trials, including a maternal vaccine (RSV F-nanoparticles vaccine), long-acting monoclonal antibodies aimed at neonates (MEDI8897), and an active adenovirus vector-based vaccine aimed at infants and/or the elderly (ChAd155-RSV). Given the significant observed health burden due to RSV in children, these products, which are mainly aimed at children, are likely to be effective at preventing RSV disease. However, uncertainties surrounding i) the dynamics of maternally-derived protection in neonates, ii) the impact of herd immunity, and iii) the purchasing cost of these prophylactics, means it is not clear if these products are cost-effective. Therefore, evaluating the purchasing price required for these prophylactics to remain cost-effective using a dynamic transmission model, in which the herd immunity is included and the dynamics of maternally-derived immunity is determined by calibrating the model to data, is a public health priority. Added-value of this study Our study finds that in a setting with seasonal RSV epidemiology, maternal protection conferred to newborns is also seasonal. In addition, our study estimates the maximum purchasing price per course for various potential RSV intervention programmes to be cost-effective in England, assuming a cost-effectiveness threshold of £20,000/QALY as recommended by the National Institute of Clinical Excellence (NICE). We find 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, and vaccinating the elderly is not likely to be affordable. Implications of all the available evidence The seasonal protection conferred to newborns is consistent with empirical immunological data from maternal cord blood and ecological evidence from hospital records. Further, extending a monoclonal antibody programme would be possible if there is a considerable drop in price and maternal vaccination remains the only realistic vaccination strategy in the UK. With further clinical trials planned for RSV F-nanoparticles vaccine to evaluate its efficacy, and with clinical trial completion dates set at the end of 2021 for the other two prophylactic candidates, the results of this study provide a comprehensive overview of the impact of potential RSV intervention programmes both in the present and in the coming years.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.027 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".