Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England.

BACKGROUND: Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7) since 2006 and PCV13 since 2010), as well as a 23-valent pneumococcal polysaccharide (PPV23) vaccination programme targeting clinical risk-groups and those ≥65 years. METHOD: A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results. RESULTS: The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP), and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs) and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust. CONCLUSIONS: Vaccinating immunocompetent individuals aged ≥65 years with PCV13 is efficacious. However the absolute incidence of vaccine-type disease will likely become very low due to wider benefits of the childhood PCV13 vaccination programme, such that a specific PCV13 vaccination programme targeting the immunocompetent elderly would not be cost-effective

Huge impact of assumptions on indirect effects on the cost-effectiveness of routine infant vaccination with 7-valent conjugate vaccine (Prevnar (R))

Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar (R)) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups of 5 years of age and older with updated assumptions regarding epidemiologic data and health care unit costs. Without net-indirect benefits for non-vaccine protected groups included the cost-effectiveness ratio is estimated at (sic)72,360 per QALY. In order to obtain cost-effectiveness ratios below the threshold of (sic)50,000 per QALY - which is in the middle of the range that is often referred to in the Netherlands - the net-indirect protective effect should at least be 16% of which has been observed in the USA after the introduction of PCV-7. (C) 2010 Elsevier Ltd. All rights reserved

Changing socio-economic and ethnic disparities in influenza/A/H1N1 infection early in the 2009 UK epidemic:a descriptive analysis

BACKGROUND: Higher incidence of and risk of hospitalisation and death from Influenza A(H1N1)pdm09 during the 2009 pandemic was reported in ethnic minority groups in many high-income settings including in the United Kingdom (UK). Many of these studies rely on geographical and temporal aggregation of cases and can be difficult to interpret due to the spatial and temporal factors in outbreak spread. Further, it can be challenging to distinguish between disparities in health outcomes caused by variation in transmission risk or disease severity. METHODS: We used anonymised laboratory confirmed and suspected case data, classified by ethnicity and deprivation status, to evaluate how disparities in risk between socio-economic and ethnic groups vary over the early stages of the 2009 Influenza A(H1N1)pdm09 epidemic in Birmingham and London, two key cities in the emergence of the UK epidemic. We evaluated the relative risk of infection in key ethnic minority groups and by national and city level deprivation rank. RESULTS: We calculated higher incidence in more deprived areas and in people of South Asian ethnicity in both Birmingham and London, although the magnitude of these disparities reduced with time. The clearest disparities existed in school-aged children in Birmingham, where the most deprived fifth of the population was 2.8 times more likely to be infected than the most affluent fifth of the population. CONCLUSIONS: Our analysis shows that although disparities in reported cases were present in the early phase of the Influenza A(H1N1)pdm09 outbreak in both Birmingham and London, they vary substantially depending on the period over which they are measured. Further, the development of disparities suggest that clustering of social groups play a key part as the outbreak appears to move from one ethnic and socio-demographic group to another. Finally, high incidence and large disparities between children indicate that they may hold an important role in driving inequalities

Clustering of contacts relevant to the spread of infectious disease.

OBJECTIVE: Infectious disease spread depends on contact rates between infectious and susceptible individuals. Transmission models are commonly informed using empirically collected contact data, but the relevance of different contact types to transmission is still not well understood. Some studies select contacts based on a single characteristic such as proximity (physical/non-physical), location, duration or frequency. This study aimed to explore whether clusters of contacts similar to each other across multiple characteristics could better explain disease transmission. METHODS: Individual contact data from the POLYMOD survey in Poland, Great Britain, Belgium, Finland and Italy were grouped into clusters by the k medoids clustering algorithm with a Manhattan distance metric to stratify contacts using all four characteristics. Contact clusters were then used to fit a transmission model to sero-epidemiological data for varicella-zoster virus (VZV) in each country. RESULTS AND DISCUSSION: Across the five countries, 9-15 clusters were found to optimise both quality of clustering (measured using average silhouette width) and quality of fit (measured using several information criteria). Of these, 2-3 clusters were most relevant to VZV transmission, characterised by (i) 1-2 clusters of age-assortative contacts in schools, (ii) a cluster of less age-assortative contacts in non-school settings. Quality of fit was similar to using contacts stratified by a single characteristic, providing validation that single stratifications are appropriate. However, using clustering to stratify contacts using multiple characteristics provided insight into the structures underlying infection transmission, particularly the role of age-assortative contacts, involving school age children, for VZV transmission between households

Quantifying the public's view on social value judgments in vaccine decision-making:A discrete choice experiment

Vaccination programs generate direct protection, herd protection and, occasionally, side effects, distributed over different age groups. This study elicits the general public's view on how to balance these outcomes in funding decisions for vaccines. We performed an optimal design discrete choice experiment with partial profiles in a representative sample (N = 1499) of the population in the United Kingdom in November 2016. Using a panel mixed logit model, we quantified, for four different types of infectious disease, the importance of a person's age during disease, how disease was prevented-via direct vaccine protection or herd protection-and whether the vaccine induced side effects. Our study shows clear patterns in how the public values vaccination programs. These diverge from the assumptions made in public health and cost-effectiveness models that inform decision-making. We found that side effects and infections in newborns and children were of primary importance to the perceived value of a vaccination program. Averting side effects was, in any age group, weighted three times as important as preventing an identical natural infection in a child whereas the latter was weighted six times as important as preventing the same infection in elderly aged 65-75 years. These findings were independent of the length or severity of the disease, and were robust across respondents' backgrounds. We summarize these patterns in a set of preference weights that can be incorporated into future models. Although the normative significance of these weights remains a matter open for debate, our study can, hopefully, contribute to the evaluation of vaccination programs beyond cost-effectiveness

Cost Effectiveness of Human Papillomavirus Vaccination for Men Who have Sex with Men; Reviewing the Available Evidence

BACKGROUND: Men who have sex with men require special attention for human papillomavirus vaccination given elevated infection risks and the development of, in particular, anal cancer. OBJECTIVE: Our purpose was to review the cost effectiveness of human papillomavirus vaccination for both currently vaccine-eligible and non-eligible individuals, particularly the men-who-have-sex-with-men population, and synthesize the available evidence. METHODS: We systematically searched for published articles in two main databases (PubMed and EMBASE). Screening and data extraction were performed by two independent reviewers. The risk of bias was assessed using a validated instrument (Bias in Economic Evaluation, ECOBIAS). Methodological aspects, study results, and sensitivity analyses were extracted and synthesized to generate a consistent overview of the cost effectiveness of human papillomavirus vaccination in the men-who-have-sex-with-men population. RESULTS: From 770 identified articles, four met the inclusion criteria. Across the studies, human papillomavirus vaccination showed incremental cost-effectiveness ratios ranging from dominant to US$96,146 and US$14,000 to US$18,200 for tertiary prevention and primary prevention, respectively. The incremental cost-effectiveness ratio seemed most sensitive to vaccine efficacy, vaccine costs, and the incidence of anal cancer in the selected target populations. CONCLUSION: This review presents the human papillomavirus vaccine, both as a primary and adjuvant (tertiary) vaccination, as a potentially cost-effective strategy for preventing mainly-but not limited to only-anal cancer in men-who-have-sex-with-men populations

Additional file 3: of Investigating the pertussis resurgence in England and Wales, and options for future control

Graphical User Interface programme to present pertussis simulation model results

Burden of paediatric respiratory syncytial virus disease and potential effect of different immunisation strategies: a modelling and cost-effectiveness analysis for England.

BACKGROUND: Vaccines and prophylactic antibodies against respiratory syncytial virus (RSV) are in development and likely to be available in the next 5-10 years. The most efficient way to use these products when they become available is an important consideration for public health decision makers. METHODS: We performed a multivariate regression analysis to estimate the burden of RSV in children younger than 5 years in England (UK), a representative high-income temperate country, and used these results to assess the potential effect of different RSV immunisation strategies (targeting vaccination for infants, or pregnant women, or prophylactic antibodies for neonates). We did a cost-effectiveness analysis for these strategies, implemented either separately or concurrently, and assessed the effect of restricting vaccination to certain months of the year. FINDINGS: We estimated that RSV is responsible for 12 primary care consultations (95% CI 11·9-12·1) and 0·9 admissions to hospital annually per 100 children younger than 5 years (95% CI 0·89-0·90), with the major burden occurring in infants younger than 6 months. The most cost-effective strategy was to selectively immunise all children born before the start of the RSV season (maximum price of £220 [95% uncertainty interval (UI) 208-232] per vaccine, for an incremental cost-effectiveness ratio of £20 000 per quality-adjusted life-year). The maximum price per fully protected person that should be paid for the infant, newborn, and maternal strategies without seasonal restrictions was £192 (95% UI 168-219), £81 (76-86), and £54 (51-57), respectively. INTERPRETATION: Nearly double the number of primary care consultations, and nearly five times the number of admissions to hospital occurred with RSV compared with influenza. RSV vaccine and antibody strategies are likely to be cost-effective if they can be priced below around £200 per fully protected person. A seasonal vaccination strategy is likely to provide the most direct benefits. Herd effects might render a year-round infant vaccination strategy more appealing, although it is currently unclear whether such a programme would induce herd effects. FUNDING: UK National Institute for Health Research

Impact and cost-effectiveness of different vaccination strategies to reduce the burden of pneumococcal disease among elderly in the Netherlands

BACKGROUND: Streptococcus pneumoniae causes morbidity and mortality among all ages in The Netherlands. To reduce this burden, infants in The Netherlands receive the 10-valent pneumococcal conjugated vaccine (PCV10), but older persons are not targeted. We assessed the impact and cost-effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) or 13-valent PCV (PCV13) among all those aged 60, 65 or 70 and/or in combination with replacing PCV10 with PCV13 in the infant vaccination programme.METHODS: A static cost-effectiveness model was parameterized including projected trends for invasive pneumococcal disease (IPD) and hospitalised community acquired pneumonia (CAP). The different strategies were evaluated using vaccine list prices and a 10-year time horizon. Incremental cost-effectiveness ratios (ICER) were calculated with the current strategy (infant vaccination program with PCV10) as reference.RESULTS: Compared to the reference, the largest impact on pneumococcal disease burden was projected with a combined use of PCV13 among infants and PPV23 at 60, 65 and 70 years, preventing 1,635 cases of IPD and 914 cases of CAP. The most cost-effective strategy was vaccinating with PPV23 at 70 years only with similar low ICERs at age 60 and 65. The impact of the use of PCV13 among infants depends strongly on the projected herd-immunity effect on serotype 19A. Vaccinating elderly with either PCV13 or PPV23 was dominated by PPV23 in all investigated scenarios, mainly due to the lower price of PPV23.CONCLUSION: Under the current assumptions, the best value for money is the use of PPV23 for elderly, with a single dose or at five year increment between age 60 to age 70.</p