Human papillomavirus vaccine introduction in low-income and middle-income countries: guidance on the use of cost-effectiveness models

BACKGROUND: The World Health Organization (WHO) recommends that the cost effectiveness of introducing human papillomavirus (HPV) vaccination is considered before such a strategy is implemented. However, developing countries often lack the technical capacity to perform and interpret results of economic appraisals of vaccines. To provide information about the feasibility of using such models in a developing country setting, we evaluated models of HPV vaccination in terms of their capacity, requirements, limitations and comparability. METHODS: A literature review identified six HPV vaccination models suitable for low-income and middle-income country use and representative of the literature in terms of provenance and model structure. Each model was adapted by its developers using standardised data sets representative of two hypothetical developing countries (a low-income country with no screening and a middle-income country with limited screening). Model predictions before and after vaccination of adolescent girls were compared in terms of HPV prevalence and cervical cancer incidence, as was the incremental cost-effectiveness ratio of vaccination under different scenarios. RESULTS: None of the models perfectly reproduced the standardised data set provided to the model developers. However, they agreed that large decreases in type 16/18 HPV prevalence and cervical cancer incidence are likely to occur following vaccination. Apart from the Thai model (in which vaccine and non-vaccine HPV types were combined), vaccine-type HPV prevalence dropped by 75% to 100%, and vaccine-type cervical cancer incidence dropped by 80% to 100% across the models (averaging over age groups). The most influential factors affecting cost effectiveness were the discount rate, duration of vaccine protection, vaccine price and HPV prevalence. Demographic change, access to treatment and data resolution were found to be key issues to consider for models in developing countries. CONCLUSIONS: The results indicated the usefulness of considering results from several models and sets of modelling assumptions in decision making. Modelling groups were prepared to share their models and expertise to work with stakeholders in developing countries. Please see related article: http://www.biomedcentral.com/1741-7007/9/55

Systematic Review of Economic Evaluations of Preparedness Strategies and Interventions against Influenza Pandemics

BACKGROUND: Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted. METHODS: The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers. RESULTS: 44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries. CONCLUSION: The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies

Seasonal Influenza Vaccination for Children in Thailand: A Cost-Effectiveness Analysis

10.1371/journal.pmed.1001829PLoS Medicine125e100182

Seasonal influenza vaccination for children in Thailand: a cost-effectiveness analysis.

BACKGROUND: Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly. METHODS AND FINDINGS: We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups. CONCLUSIONS: Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries

Mortality attributable to seasonal influenza A and B infections in Thailand, 2005-2009 : a longitudinal study

Influenza epidemiology differs substantially in tropical and temperate zones, but estimates of seasonal influenza mortality in developing countries in the tropics are lacking. We aimed to quantify mortality due to seasonal influenza in Thailand, a tropical middle-income country. Time series of polymerase chain reaction-confirmed influenza infections between 2005 and 2009 were constructed from a sentinel surveillance network. These were combined with influenza-like illness data to derive measures of influenza activity and relationships to mortality by using a Bayesian regression framework. We estimated 6.1 (95% credible interval: 0.5, 12.4) annual deaths per 100,000 population attributable to influenza A and B, predominantly in those aged ≥60 years, with the largest contribution from influenza A(H1N1) in 3 out of 4 years. For A(H3N2), the relationship between influenza activity and mortality varied over time. Influenza was associated with increases in deaths classified as resulting from respiratory disease (posterior probability of positive association, 99.8%), cancer (98.6%), renal disease (98.0%), and liver disease (99.2%). No association with circulatory disease mortality was found. Seasonal influenza infections are associated with substantial mortality in Thailand, but evidence for the strong relationship between influenza activity and circulatory disease mortality reported in temperate countries is lacking

Systematic review of model-based cervical screening evaluations.

BACKGROUND: Optimising population-based cervical screening policies is becoming more complex due to the expanding range of screening technologies available and the interplay with vaccine-induced changes in epidemiology. Mathematical models are increasingly being applied to assess the impact of cervical cancer screening strategies. METHODS: We systematically reviewed MEDLINE®, Embase, Web of Science®, EconLit, Health Economic Evaluation Database, and The Cochrane Library databases in order to identify the mathematical models of human papillomavirus (HPV) infection and cervical cancer progression used to assess the effectiveness and/or cost-effectiveness of cervical cancer screening strategies. Key model features and conclusions relevant to decision-making were extracted. RESULTS: We found 153 articles meeting our eligibility criteria published up to May 2013. Most studies (72/153) evaluated the introduction of a new screening technology, with particular focus on the comparison of HPV DNA testing and cytology (n = 58). Twenty-eight in forty of these analyses supported HPV DNA primary screening implementation. A few studies analysed more recent technologies - rapid HPV DNA testing (n = 3), HPV DNA self-sampling (n = 4), and genotyping (n = 1) - and were also supportive of their introduction. However, no study was found on emerging molecular markers and their potential utility in future screening programmes. Most evaluations (113/153) were based on models simulating aggregate groups of women at risk of cervical cancer over time without accounting for HPV infection transmission. Calibration to country-specific outcome data is becoming more common, but has not yet become standard practice. CONCLUSIONS: Models of cervical screening are increasingly used, and allow extrapolation of trial data to project the population-level health and economic impact of different screening policy. However, post-vaccination analyses have rarely incorporated transmission dynamics. Model calibration to country-specific data is increasingly common in recent studies