Publications by authors named "Joke Bilcke"

34 Publications

Strategies for typhoid conjugate vaccines in endemic nations - Authors' reply.

Lancet Infect Dis 2021 03;21(3):321-322

Center for Health Economic Research and Modelling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, 2610 Antwerp, Belgium. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(21)00018-9DOI Listing
March 2021

A Computationally Efficient Method for Probabilistic Parameter Threshold Analysis for Health Economic Evaluations.

Med Decis Making 2020 07 5;40(5):669-679. Epub 2020 Jul 5.

Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Antwerp, Belgium.

. Threshold analysis is used to determine the threshold value of an input parameter at which a health care strategy becomes cost-effective. Typically, it is performed in a deterministic manner, in which inputs are varied one at a time while the remaining inputs are each fixed at their mean value. This approach will result in incorrect threshold values if the cost-effectiveness model is nonlinear or if inputs are correlated. . To propose a probabilistic method for performing threshold analysis, which accounts for the joint uncertainty in all input parameters and makes no assumption about the linearity of the cost-effectiveness model. . Three methods are compared: 1) deterministic threshold analysis (DTA); 2) a 2-level Monte Carlo approach, which is considered the gold standard; and 3) a regression-based method using a generalized additive model (GAM), which identifies threshold values directly from a probabilistic sensitivity analysis sample. . We applied the 3 methods to estimate the minimum probability of hospitalization for typhoid fever at which 3 different vaccination strategies become cost-effective in Uganda. The threshold probability of hospitalization at which routine vaccination at 9 months with catchup campaign to 5 years becomes cost-effective is estimated to be 0.060 and 0.061 (95% confidence interval [CI], 0.058-0.064), respectively, for 2-level and GAM. According to DTA, routine vaccination at 9 months with catchup campaign to 5 years would never become cost-effective. The threshold probability at which routine vaccination at 9 months with catchup campaign to 15 years becomes cost-effective is estimated to be 0.092 (DTA), 0.074 (2-level), and 0.072 (95% CI, 0.069-0.075) (GAM). GAM is 430 times faster than the 2-level approach. . When the cost-effectiveness model is nonlinear, GAM provides similar threshold values to the 2-level Monte Carlo approach and is computationally more efficient. DTA provides incorrect results and should not be used.
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http://dx.doi.org/10.1177/0272989X20937253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401185PMC
July 2020

Economic costs analysis of uncomplicated malaria case management in the Peruvian Amazon.

Malar J 2020 Apr 21;19(1):161. Epub 2020 Apr 21.

Centre for Health Economics Research and Modelling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, 2000, Antwerp, Belgium.

Background: Case management is one of the principal strategies for malaria control. This study aimed to estimate the economic costs of uncomplicated malaria case management and explore the influence of health-seeking behaviours on those costs.

Methods: A knowledge, attitudes and practices (KAP) survey was applied to 680 households of fifteen communities in Mazan-Loreto in March 2017, then a socio-economic survey was conducted in September 2017 among 161 individuals with confirmed uncomplicated malaria in the past 3 months. Total costs per episode were estimated from both provider (Ministry of Health, MoH) and patient perspectives. Direct costs were estimated using a standard costing estimation procedure, while the indirect costs considered the loss of incomes among patients, substitute labourers and companions due to illness in terms of the monthly minimum wage. Sensitivity analysis evaluated the uncertainty of the average cost per episode.

Results: The KAP survey showed that most individuals (79.3%) that had malaria went to a health facility for a diagnosis and treatment, 2.7% received those services from community health workers, and 8% went to a drugstore or were self-treated at home. The average total cost per episode in the Mazan district was US$ 161. The cost from the provider's perspective was US$ 30.85 per episode while from the patient's perspective the estimated cost was US$ 131 per episode. The average costs per Plasmodium falciparum episode (US$ 180) were higher than those per Plasmodium vivax episode (US$ 156) due to longer time lost from work by patients with P. falciparum infections (22.2 days) than by patients with P. vivax infections (17.0 days). The delayed malaria diagnosis (after 48 h of the onset of symptoms) was associated with the time lost from work due to illness (adjusted mean ratio 1.8; 95% CI 1.3, 2.6). The average cost per malaria episode was most sensitive to the uncertainty around the lost productivity cost due to malaria.

Conclusions: Despite the provision of free malaria case management by MoH, there is delay in seeking care and the costs of uncomplicated malaria are mainly borne by the families. These costs are not well perceived by the society and the substantial financial impact of the disease can be frequently undervalued in public policy planning.
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http://dx.doi.org/10.1186/s12936-020-03233-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175533PMC
April 2020

Health and economic burden of respiratory syncytial virus (RSV) disease and the cost-effectiveness of potential interventions against RSV among children under 5 years in 72 Gavi-eligible countries.

BMC Med 2020 04 6;18(1):82. Epub 2020 Apr 6.

Centre for Health Economics Research & Modelling Infectious Diseases, Vaccine & Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Antwerp, Belgium.

Background: Respiratory syncytial virus (RSV) frequently causes acute lower respiratory infection in children under 5, representing a high burden in Gavi-eligible countries (mostly low-income and lower-middle-income). Since multiple RSV interventions, including vaccines and monoclonal antibody (mAb) candidates, are under development, we aim to evaluate the key drivers of the cost-effectiveness of maternal vaccination and infant mAb for 72 Gavi countries.

Methods: A static Multi-Country Model Application for RSV Cost-Effectiveness poLicy (MCMARCEL) was developed to follow RSV-related events monthly from birth until 5 years of age. MCMARCEL was parameterised using country- and age-specific demographic, epidemiological, and cost data. The interventions' level and duration of effectiveness were guided by the World Health Organization's preferred product characteristics and other literature. Maternal vaccination and mAb were assumed to require single-dose administration at prices assumed to align with other Gavi-subsidised technologies. The effectiveness and the prices of the interventions were simultaneously varied in extensive scenario analyses. Disability-adjusted life years (DALYs) were the primary health outcomes for cost-effectiveness, integrated with probabilistic sensitivity analyses and Expected Value of Partially Perfect Information analysis.

Results: The RSV-associated disease burden among children in these 72 countries is estimated at an average of 20.8 million cases, 1.8 million hospital admissions, 40 thousand deaths, 1.2 million discounted DALYs, and US$611 million discounted direct costs. Strategy 'mAb' is more effective due to its assumed longer duration of protection versus maternal vaccination, but it was also assumed to be more expensive. Given all parameterised uncertainty, the optimal strategy of choice tends to change for increasing willingness to pay (WTP) values per DALY averted from the current situation to maternal vaccination (at WTP > US$1000) to mAB (at WTP > US$3500). The age-specific proportions of cases that are hospitalised and/or die cause most of the uncertainty in the choice of optimal strategy. Results are broadly similar across countries.

Conclusions: Both the maternal and mAb strategies need to be competitively priced to be judged as relatively cost-effective. Information on the level and duration of protection is crucial, but also more and better disease burden evidence-especially on RSV-attributable hospitalisation and death rates-is needed to support policy choices when novel RSV products become available.
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http://dx.doi.org/10.1186/s12916-020-01537-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132892PMC
April 2020

Cost-effectiveness of routine and campaign use of typhoid Vi-conjugate vaccine in Gavi-eligible countries: a modelling study.

Lancet Infect Dis 2019 07 23;19(7):728-739. Epub 2019 May 23.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA. Electronic address:

Background: Typhoid fever is a major cause of morbidity and mortality in low-income and middle-income countries. In 2017, WHO recommended the programmatic use of typhoid Vi-conjugate vaccine (TCV) in endemic settings, and Gavi, The Vaccine Alliance, has pledged support for vaccine introduction in these countries. Country-level health economic evaluations are now needed to inform decision-making.

Methods: In this modelling study, we compared four strategies: no vaccination, routine immunisation at 9 months, and routine immunisation at 9 months with catch-up campaigns to either age 5 years or 15 years. For each of the 54 countries eligible for Gavi support, output from an age-structured transmission-dynamic model was combined with country-specific treatment and vaccine-related costs, treatment outcomes, and disability weights to estimate the reduction in typhoid burden, identify the strategy that maximised average net benefit (ie, the optimal strategy) across a range of country-specific willingness-to-pay (WTP) values, estimate and investigate the uncertainties surrounding our findings, and identify the epidemiological conditions under which vaccination is optimal.

Findings: The optimal strategy was either no vaccination or TCV immunisation including a catch-up campaign. Routine vaccination with a catch-up campaign to 15 years of age was optimal in 38 countries, assuming a WTP value of at least US$200 per disability-adjusted life-year (DALY) averted, or assuming a WTP value of at least 25% of each country's gross domestic product (GDP) per capita per DALY averted, at a vaccine price of $1·50 per dose (but excluding Gavi's contribution according to each country's transition phase). This vaccination strategy was also optimal in 48 countries assuming a WTP of at least $500 per DALY averted, in 51 with assumed WTP values of at least $1000, in 47 countries assuming a WTP value of at least 50% of GDP per capita per DALY averted, and in 49 assuming a minimum of 100%. Vaccination was likely to be cost-effective in countries with 300 or more typhoid cases per 100 000 person-years. Uncertainty about the probability of hospital admission (and typhoid incidence and mortality) had the greatest influence on the optimal strategy.

Interpretation: Countries should establish their own WTP threshold and consider routine TCV introduction, including a catch-up campaign when vaccination is optimal on the basis of this threshold. Obtaining improved estimates of the probability of hospital admission would be valuable whenever the optimal strategy is uncertain.

Funding: Bill & Melinda Gates Foundation, Research Foundation-Flanders, and the Belgian-American Education Foundation.
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http://dx.doi.org/10.1016/S1473-3099(18)30804-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595249PMC
July 2019

Sponsorship Bias in Base-Case Values and Uncertainty Bounds of Health Economic Evaluations? A Systematic Review of Herpes Zoster Vaccination.

Med Decis Making 2018 08 25;38(6):730-745. Epub 2018 May 25.

Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Antwerp, Belgium.

Background: New health technologies are more likely adopted when they have lower incremental cost-effectiveness ratios (ICERs) and/or when their ICER is presented with more certainty. Industry-funded (IF) health economic evaluations use often more favorable base-case values, leading to more favorable conclusions.

Purpose: To study whether IF health economic evaluations of varicella-zoster virus vaccination in the elderly use more favorable base-case values and account for less uncertainty than non-industry-funded (NIF) evaluations.

Methods:

Data Source: PubMed. Data extracted: funding source; incremental cost per quality-adjusted life year (QALY) gained; vaccine price; study quality score; base-case values, uncertainty ranges, and data sources for influential parameters: duration of vaccine protection, utility loss due to herpes zoster (HZ) disease, percentage of HZ patients developing postherpetic neuralgia (PHN), and duration of PHN.

Data Synthesis: qualitative comparisons; Fisher exact test for differences in study quality score and 1-sided Mann-Whitney U tests for differences in base-case values and uncertainty ranges.

Results: Despite using the same data sources, IF studies ( n = 10) assume a longer duration of vaccine protection ( U = 56, P = 0.03), have a higher percentage of HZ patients developing PHN ( U = 22/33, P = 0.02/0.03 for ages 60-64/65-69), and tend to use higher HZ utility loss than NIF studies ( n = 11) for their baseline. IF studies show lower ICERs given similar or even higher vaccine prices than NIF studies, consider less uncertainty around the duration of vaccine protection ( U = 8, P < 0.001), and tend to use less uncertainty around the duration of PHN. Yet their quality has been rated equally well, using current standard quality rating tools.

Conclusion: Researchers and decision makers should be aware of potential sponsorship bias in health economic evaluations, especially in the way source data are used to specify base-case values and uncertainty ranges.
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http://dx.doi.org/10.1177/0272989X18776636DOI Listing
August 2018

Case Fatality Rate of Enteric Fever in Endemic Countries: A Systematic Review and Meta-analysis.

Clin Infect Dis 2018 08;67(4):628-638

Vaccine & Infectious Disease Institute, University of Antwerp, Wilrijk.

Enteric fever is a febrile illness, occurring mostly in Asia and Africa, which can present as a severe and possibly fatal disease. Currently, a case fatality rate (CFR) of 1% is assumed when evaluating the global burden of enteric fever. Until now, no meta-analysis has been conducted to summarize mortality from enteric fever. Therefore, we conducted a systematic review and meta-analysis to aggregate all available evidence. We estimated an overall CFR of 2.49% (95% confidence interval, 1.65%-3.75%; n = 44), and a CFR in hospitalized patients of 4.45% (2.85%-6.88%; n = 21 of 44). There was considerably heterogeneity in estimates of the CFR from individual studies. Neither age nor antimicrobial resistance were significant prognostic factors, but limited data were available for these analyses. The combined estimate of the CFR for enteric fever is higher than previously estimated, and the evaluation of prognostic factors, including antimicrobial resistance, urgently requires more data.
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http://dx.doi.org/10.1093/cid/ciy190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070077PMC
August 2018

Economic evaluation of pneumococcal vaccines for adults aged over 50 years in Belgium.

Hum Vaccin Immunother 2018 05 22;14(5):1218-1229. Epub 2018 Feb 22.

a Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp , Antwerp , Belgium.

Streptococcus pneumoniae causes a high disease burden including pneumonia, meningitis and septicemia. Both a polysaccharide vaccine targeting 23 serotypes (PPV23) and a 13-valent conjugate vaccine (PCV13) are indicated for persons aged over 50 years. We developed and parameterized a static multi-cohort model to estimate the incremental cost-effectiveness and budget-impact of these vaccines at different uptake levels. Using three different vaccine efficacy scenarios regarding non-invasive pneumococcal pneumonia and extensive uni- and multivariate sensitivity analyses, we found a strong preference for PPV23 over PCV13 in all age groups at willingness to pay levels below €300 000 per quality adjusted life year (QALY). PPV23 vaccination would cost on average about €83 000, €60 000 and €52 000 per QALY gained in 50-64, 65-74 and 75-84 year olds, whereas for PCV13 this is about €171 000, €201 000 and €338 000, respectively. Strategies combining PPV23 and PCV13 vaccines were most effective but generally less cost-effective. When assuming a combination of increased duration of PCV13 protection, increased disease burden preventable by PCV13 and a 75% reduction of the PCV13 price, PCV13 could become more attractive in <75 year olds, but would remain less attractive than PPV23 from age 75 years onwards. These observations are independent of the assumption that PPV23 has 0% efficacy against non-invasive pneumococcal pneumonia. Pneumococcal vaccination would be most cost-effective in Belgium, when achieving high uptake with PPV23 in 75-84 year olds, as well as by negotiating a lower market-conform PPV23 price to improve uptake and cost-effectiveness.
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http://dx.doi.org/10.1080/21645515.2018.1428507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989887PMC
May 2018

Lessons from a decade of individual-based models for infectious disease transmission: a systematic review (2006-2015).

BMC Infect Dis 2017 09 11;17(1):612. Epub 2017 Sep 11.

Centre for Health Economics Research & Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium.

Background: Individual-based models (IBMs) are useful to simulate events subject to stochasticity and/or heterogeneity, and have become well established to model the potential (re)emergence of pathogens (e.g., pandemic influenza, bioterrorism). Individual heterogeneity at the host and pathogen level is increasingly documented to influence transmission of endemic diseases and it is well understood that the final stages of elimination strategies for vaccine-preventable childhood diseases (e.g., polio, measles) are subject to stochasticity. Even so it appears IBMs for both these phenomena are not well established. We review a decade of IBM publications aiming to obtain insights in their advantages, pitfalls and rationale for use and to make recommendations facilitating knowledge transfer within and across disciplines.

Methods: We systematically identified publications in Web of Science and PubMed from 2006-2015 based on title/abstract/keywords screening (and full-text if necessary) to retrieve topics, modeling purposes and general specifications. We extracted detailed modeling features from papers on established vaccine-preventable childhood diseases based on full-text screening.

Results: We identified 698 papers, which applied an IBM for infectious disease transmission, and listed these in a reference database, describing their general characteristics. The diversity of disease-topics and overall publication frequency have increased over time (38 to 115 annual publications from 2006 to 2015). The inclusion of intervention strategies (8 to 52) and economic consequences (1 to 20) are increasing, to the detriment of purely theoretical explorations. Unfortunately, terminology used to describe IBMs is inconsistent and ambiguous. We retrieved 24 studies on a vaccine-preventable childhood disease (covering 7 different diseases), with publication frequency increasing from the first such study published in 2008. IBMs have been useful to explore heterogeneous between- and within-host interactions, but combined applications are still sparse. The amount of missing information on model characteristics and study design is remarkable.

Conclusions: IBMs are suited to combine heterogeneous within- and between-host interactions, which offers many opportunities, especially to analyze targeted interventions for endemic infections. We advocate the exchange of (open-source) platforms and stress the need for consistent "branding". Using (existing) conventions and reporting protocols would stimulate cross-fertilization between research groups and fields, and ultimately policy making in decades to come.
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http://dx.doi.org/10.1186/s12879-017-2699-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594572PMC
September 2017

Cost-effectiveness analysis of typhoid conjugate vaccines in five endemic low- and middle-income settings.

Vaccine 2017 06 17;35(27):3506-3514. Epub 2017 May 17.

Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06520-8034, USA. Electronic address:

Background: Typhoid fever remains endemic in low- and middle-income countries. Programmatic use of existing vaccines is limited, but upcoming typhoid conjugate vaccines (TCVs) could warrant wider use. We evaluated the cost-effectiveness of five TCV delivery strategies in three urban areas (Delhi and Kolkata, India and Nairobi, Kenya) and two rural settings (Lwak, Kenya and Dong Thap, Vietnam) with varying incidence.

Methods And Findings: We evaluated routine infant vaccination with and without catch-up campaigns among older individuals. We used a dynamic model of typhoid transmission to simulate cases, hospitalizations, deaths, disability-adjusted life-years (DALY) lost, treatment and intervention costs. We estimated cost-effectiveness (in terms of cost in international dollars (I$) per DALY averted) from the healthcare payer perspective, and assessed how it was influenced by uncertain model parameters. Compared to no vaccination, routine infant vaccination at I$1/dose was cost-saving in Delhi and Dong Thap, "very cost-effective" in Kolkata and Nairobi, and "cost-effective" in Lwak according to World Health Organization thresholds. However, routine vaccination was not the optimal strategy compared to strategies that included a catch-up campaign, which yielded the highest probability of being cost-saving in Delhi and Dong Thap and were most likely to provide a return on investment above a willingness-to-pay threshold of I$1440 in Kolkata, I$2300 in Nairobi, and I$5360 in Lwak. Vaccine price impacted the optimal strategy, and the number of doses required and rate of hospitalization were the primary sources of uncertainty.

Conclusion: Routine vaccination with TCV would be cost-effective in most settings, and additional one-time catch-up campaigns would also be economically justified.
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http://dx.doi.org/10.1016/j.vaccine.2017.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462484PMC
June 2017

Quality-of-life: a many-splendored thing? Belgian population norms and 34 potential determinants explored by beta regression.

Qual Life Res 2017 08 27;26(8):2011-2023. Epub 2017 Mar 27.

Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp - CDE R2.07, 2610, Wilrijk, Belgium.

Purpose: To identify determinants of health-related quality-of-life in the Belgian population and to provide age-specific population norms of health-related quality-of-life.

Methods: Between September 2010 and February 2011, a representative sample of 1774 persons (age 0-99) was surveyed using the standard Euroqol questionnaire (EQ-5D-3L) with a Visual Analogue Scale (VAS). Significant determinants were identified using multivariate beta (VAS) and one-inflated beta (EQ-5D) regression, the latter modelling the probability to be in perfect health separately from the average EQ-5D score if not in perfect health.

Results: Health-related quality-of-life depends largely on age and experience with severe disease. The probability to be in perfect health is highest for children. For 0-2 years children who are not in perfect health, proxies report EQ-5D and VAS scores as low as that of the elderly. Also smoking behaviour, educational attainment, pet ownership, working or having worked in health care, and potentially household size and 60+ living on their own (yes/no) are associated with health-related quality-of-life, whereas no association was found with gender, living in a single-parent home, educational attainment of mothers, alcohol consumption of 60+, having (grand-) children and the frequency of seeing them. The same determinants are significant for VAS and the probability to be in perfect health, but not for the average EQ-5D score if not in perfect health.

Conclusions: The population norms provided can be used directly as input in health economic evaluations. Estimating health-related quality-of-life in children and developing statistical tools capturing the particular features of health-related quality-of-life measures are important areas for future research.
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http://dx.doi.org/10.1007/s11136-017-1556-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509833PMC
August 2017

Sustained low rotavirus activity and hospitalisation rates in the post-vaccination era in Belgium, 2007 to 2014.

Euro Surveill 2016 Jul;21(27)

Service of Epidemiology of Infectious Diseases, Department of Public Health and Surveillance, Scientific Institute of Public Health, Brussels, Belgium.

In 2006, Belgium was the first country in the European Union to recommend rotavirus vaccination in the routine infant vaccination schedule and rapidly achieved high vaccine uptake (86-89% in 2007). We used regional and national data sources up to 7 years post-vaccination to study the impact of vaccination on laboratory-confirmed rotavirus cases and rotavirus-related hospitalisations and deaths. We showed that (i) from 2007 until 2013, vaccination coverage remained at 79-88% for a complete course, (ii) in children 0-2 years, rotavirus cases decreased by 79% (95% confidence intervals (CI): 68--89%) in 2008-2014 compared to the pre-vaccination period (1999--2006) and by 50% (95% CI: 14-82%) in the age group ≥ 10 years, (iii) hospitalisations for rotavirus gastroenteritis decreased by 87% (95% CI: 84-90%) in 2008--2012 compared to the pre-vaccination period (2002--2006), (iv) median age of rotavirus cases increased from 12 months to 17 months and (v) the rotavirus seasonal peak was reduced and delayed in all post-vaccination years. The substantial decline in rotavirus gastroenteritis requiring hospitalisations and in rotavirus activity following introduction of rotavirus vaccination is sustained over time and more pronounced in the target age group, but with evidence of herd immunity.
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http://dx.doi.org/10.2807/1560-7917.ES.2016.21.27.30273DOI Listing
July 2016

The cost-effectiveness of pneumococcal vaccination in healthy adults over 50: An exploration of influential factors for Belgium.

Vaccine 2016 Apr 14;34(18):2106-12. Epub 2016 Mar 14.

Centre for Health Economic Research and Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; School of Public Health and Community Medicine, University of New South Wales, Australia.

Background: A recent trial demonstrated the 13 valent conjugate pneumococcal vaccine (PCV13) to be effective against invasive and non-invasive pneumococcal disease in healthy adults. PCV13 might therefore be considered as an alternative to the 23 valent polysaccharide vaccine (PPV23).

Aim: To explore the cost-effectiveness of vaccinating healthy adults over 50, with either PCV13 or PPV23 alone, or with a combined strategy using both PCV13 and PPV23.

Methods: A static multi-cohort model was developed simulating the consequences of pneumococcal vaccination in adults over 50 from a health care payer's perspective, for different scenarios of duration of vaccine protection and serotype evolution.

Results: At currently expected prices, PCV13 vaccination of healthy adults over 50 is unlikely to be cost-effective either compared with no vaccination or in combination with PPV23 versus PPV23 only.

Conclusion: Further research is needed on vaccine efficacy of the combination strategy and of risk groups, as well as the duration of vaccine protection. Serotype evolutions under the influence of the childhood PCV program should be closely monitored.
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http://dx.doi.org/10.1016/j.vaccine.2016.03.003DOI Listing
April 2016

Environmental triggers of acute myocardial infarction: results of a nationwide multiple-factorial population study.

Acta Cardiol 2015 Dec;70(6):693-701

Objective: The objective of this study was to study the independent environmental triggers of ST-elevation myocardial infarction (STEMI) in a multifactorial environmental population model.

Methods And Results: Daily counts of all STEMI patients who underwent urgent percutaneous coronary intervention over the period 2006-2009 in Belgium were associated with average daily meteorological data and influenza-like illness incidence data. The following meteorological measures were investigated: particulate matter less than 10 μM (PM10) and less than 2.5 μM (PM(2.5)), ozone, black smoke, temperature and relative humidity. During the study period a total of 15,964 STEMI patients (mean age 63, 75% male) were admitted with a daily average admission rate of 11 ± 4 patients. A multivariate Poisson regression analysis showed that only the temperature was significantly correlated with STEMI, with an 8% increase in the risk of STEMI for each 10°C decrease in temperature (adjusted incidence risk ratio (IRR) 0.92, 95% CI 0.89-0.96). The effects of temperature were consistent among several subpopulations but the strongest effect was seen in diabetic patients (IRR 0.85, 95% CI 0.78 -0.95). There was a trend for an incremental risk of STEMI for each 10 μg/m³ PM(2.5) increase and during influenza epidemics with IRR of 1.02 (95% CI 1.00-1.04) and 1.07 (95% CI 0.98-1.16), respectively.

Conclusion: In a global environmental model, low temperature is the most important environmental trigger for STEMI, whereas air pollution and influenza epidemics only seem to have a modest effect.
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http://dx.doi.org/10.2143/AC.70.6.3120182DOI Listing
December 2015

Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

Sci Rep 2015 Dec 21;5:18585. Epub 2015 Dec 21.

KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.

Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes.
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http://dx.doi.org/10.1038/srep18585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685644PMC
December 2015

Methods for Health Economic Evaluation of Vaccines and Immunization Decision Frameworks: A Consensus Framework from a European Vaccine Economics Community.

Pharmacoeconomics 2016 Mar;34(3):227-44

Department for Infectious Disease Epidemiology, Immunisation Unit, Robert Koch Institute (RKI), Seestr. 10, 13353, Berlin, Germany.

Background: Incremental cost-effectiveness and cost-utility analyses [health economic evaluations (HEEs)] of vaccines are routinely considered in decision making on immunization in various industrialized countries. While guidelines advocating more standardization of such HEEs (mainly for curative drugs) exist, several immunization-specific aspects (e.g. indirect effects or discounting approach) are still a subject of debate within the scientific community.

Objective: The objective of this study was to develop a consensus framework for HEEs of vaccines to support the development of national guidelines in Europe.

Methods: A systematic literature review was conducted to identify prevailing issues related to HEEs of vaccines. Furthermore, European experts in the field of health economics and immunization decision making were nominated and asked to select relevant aspects for discussion. Based on this, a workshop was held with these experts. Aspects on 'mathematical modelling', 'health economics' and 'decision making' were debated in group-work sessions (GWS) to formulate recommendations and/or--if applicable--to state 'pros' and 'contras'.

Results: A total of 13 different aspects were identified for modelling and HEE: model selection, time horizon of models, natural disease history, measures of vaccine-induced protection, duration of vaccine-induced protection, indirect effects apart from herd protection, target population, model calibration and validation, handling uncertainty, discounting, health-related quality of life, cost components, and perspectives. For decision making, there were four aspects regarding the purpose and the integration of HEEs of vaccines in decision making as well as the variation of parameters within uncertainty analyses and the reporting of results from HEEs. For each aspect, background information and an expert consensus were formulated.

Conclusions: There was consensus that when HEEs are used to prioritize healthcare funding, this should be done in a consistent way across all interventions, including vaccines. However, proper evaluation of vaccines implies using tools that are not commonly used for therapeutic drugs. Due to the complexity of and uncertainties around vaccination, transparency in the documentation of HEEs and during subsequent decision making is essential.
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http://dx.doi.org/10.1007/s40273-015-0335-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766233PMC
March 2016

Quantifying Parameter and Structural Uncertainty of Dynamic Disease Transmission Models Using MCMC: An Application to Rotavirus Vaccination in England and Wales.

Med Decis Making 2015 07 26;35(5):633-47. Epub 2015 Jan 26.

Department of Infectious Diseases Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK (JB, HJ, WJE, MJ)

Background: Two vaccines (Rotarix and RotaTeq) are highly effective at preventing severe rotavirus disease. Rotavirus vaccination has been introduced in the United Kingdom and other countries partly based on modeling and cost-effectiveness results. However, most of these models fail to account for the uncertainty about several vaccine characteristics and the mechanism of vaccine action.

Methods: A deterministic dynamic transmission model of rotavirus vaccination in the United Kingdom was developed. This improves on previous models by 1) allowing for 2 different mechanisms of action for Rotarix and RotaTeq, 2) using clinical trial data to understand these mechanisms, and 3) accounting for uncertainty by using Markov Chain Monte Carlo.

Results: In the long run, Rotarix and RotaTeq are predicted to reduce the overall rotavirus incidence by 50% (39%-63%) and 44% (30%-62%), respectively but with an increase in incidence in primary school children and adults up to 25 y of age. The vaccines are estimated to give more protection than 1 or 2 natural infections. The duration of protection is highly uncertain but has only impact on the predicted reduction in rotavirus burden for values lower than 10 y. The 2 vaccine mechanism structures fit equally well with the clinical trial data. Long-term postvaccination dynamics cannot be predicted reliably with the data available.

Conclusion: Accounting for the joint uncertainty of several vaccine characteristics resulted in more insight into which of these are crucial for determining the impact of rotavirus vaccination. Data for up to at least 10 y postvaccination and covering older children and adults are crucial to address remaining questions on the impact of widespread rotavirus vaccination.
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http://dx.doi.org/10.1177/0272989X14566013DOI Listing
July 2015

Cost-effectiveness of seasonal influenza vaccination in pregnant women, health care workers and persons with underlying illnesses in Belgium.

Vaccine 2014 Oct 18;32(46):6075-83. Epub 2014 Sep 18.

Centre for Health Economics Research and Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium; School of Public Health and Community Medicine, The University of New South Wales, Sydney, Australia.

Risk groups with increased vulnerability for influenza complications such as pregnant women, persons with underlying illnesses as well as persons who come into contact with them, such as health care workers, are currently given priority (along with other classic target groups) to receive seasonal influenza vaccination in Belgium. We aimed to evaluate this policy from a health care payer perspective by cost-effectiveness analysis in the three specific target groups above, while accounting for effects beyond the target group. Increasing the coverage of influenza vaccination is likely to be cost-effective for pregnant women (median €6589 per quality-adjusted life-year (QALY) gained [€4073-€10,249]) and health care workers (median €24,096/QALY gained [€16,442-€36,342]), if this can be achieved without incurring additional administration costs. Assuming an additional physician's consult is charged to administer each additional vaccine dose, the cost-effectiveness of vaccinating pregnant women depends strongly on the extent of its impact on the neonate's health. For health care workers, the assumed number of preventable secondary infections has a strong influence on the cost-effectiveness. Vaccinating people with underlying illnesses is likely highly cost-effective above 50 years of age and borderline cost-effective for younger persons, depending on relative life expectancy and vaccine efficacy in this risk group compared to the general population. The case-fatality ratios of the target group, of the secondary affected groups and vaccine efficacy are key sources of uncertainty.
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http://dx.doi.org/10.1016/j.vaccine.2014.08.085DOI Listing
October 2014

Herpes zoster is associated with herpes simplex and other infections in under 60 year-olds.

J Infect 2015 Feb 9;70(2):171-7. Epub 2014 Sep 9.

Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium; School of Public Health and Community Medicine, The University of New South Wales, Level 3, Samuels Building Gate 11, Botany Street, 2052 Sydney, Australia. Electronic address:

Objectives: We assessed the association between herpes zoster (HZ) and herpes simplex (HS) occurrence whilst controlling for risk factors of HZ.

Methods: Using a Belgian general practitioner network, a retrospective cohort study with 3736 HZ patients and 14,076 age-gender-practice matched controls was performed, covering over 1.5 million patient-years. Multiple logistic regression was used with HZ as outcome and several diagnoses (malignancy, depression, diabetes mellitus, auto-immune diseases, asthma, multiple sclerosis, HIV, fractures), medications (systemic corticosteroids, biologicals, vaccination), HS and other infections as variables.

Results: HS was significantly associated with HZ for all analysed time intervals (up to five years) post HZ (OR of 3.51 [2.09 5.88] 95%CI one year post HZ) and to a lesser extent for time ranges pre HZ. Registration of other infections was significantly associated with HZ in all time intervals pre and post HZ (OR up to 1.37). Malignancy up to five years pre HZ, depression up to one year pre or post HZ, fractures up to two years pre HZ, asthma, auto-immune diseases, and immunosuppressive medication one year pre or post HZ were also associated with HZ.

Conclusions: HZ and HS occurrences are significantly associated and potentially share a common susceptibility beyond the known risk factors.
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http://dx.doi.org/10.1016/j.jinf.2014.08.016DOI Listing
February 2015

Influenza-like-illness and clinically diagnosed flu: disease burden, costs and quality of life for patients seeking ambulatory care or no professional care at all.

PLoS One 2014 17;9(7):e102634. Epub 2014 Jul 17.

Centre for Health Economics Research & Modelling Infectious Diseases (CHERMID), Vaccine & Infectious Disease Institute (VAXINFECTIO) WHO collaborating Centre, Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp, Belgium; School of Public Health and Community Medicine, Sydney, Australia.

This is one of the first studies to (1) describe the out-of-hospital burden of influenza-like-illness (ILI) and clinically diagnosed flu, also for patients not seeking professional medical care, (2) assess influential background characteristics, and (3) formally compare the burden of ILI in patients with and without a clinical diagnosis of flu. A general population sample with recent ILI experience was recruited during the 2011-2012 influenza season in Belgium. Half of the 2250 respondents sought professional medical care, reported more symptoms (especially more often fever), a longer duration of illness, more use of medication (especially antibiotics) and a higher direct medical cost than patients not seeking medical care. The disease and economic burden were similar for ambulatory ILI patients, irrespective of whether they received a clinical diagnosis of flu. On average, they experienced 5-6 symptoms over a 6-day period; required 1.6 physician visits and 86-91% took medication. An average episode amounted to €51-€53 in direct medical costs, 4 days of absence from work or school and the loss of 0.005 quality-adjusted life-years. Underlying illness led to greater costs and lower quality-of-life. The costs of ILI patients with clinically diagnosed flu tended to increase, while those of ILI patients without clinically diagnosed flu tended to decrease with age. Recently vaccinated persons experienced lower costs and a higher quality-of-life, but this was only the case for patients not seeking professional medical care. This information can be used directly to evaluate the implementation of cost-effective prevention and control measures for influenza. In particular to inform the evaluation of more widespread seasonal influenza vaccination, including in children, which is currently considered by many countries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102634PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102549PMC
December 2015

Cost-effectiveness of socioeconomic support as part of HIV care for the poor in an urban community-based antiretroviral program in Uganda.

J Acquir Immune Defic Syndr 2014 Oct;67(2):e76-83

*Executive Directors Office, Reach Out Mbuya HIV/AIDS Initiative, Kampala, Uganda; †Center for Health Economics Research & Modeling Infectious Diseases (CHERMID, Vaccine & Infectious Disease Institute [Vaxinfectio]), University of Antwerp, Antwerp, Belgium; and ‡Institute of Tropical Medicine Antwerp, Antwerp, Belgium.

Background: Socioeconomic support reduced nonretention in a community-based antiretroviral therapy (ART) program in Uganda. However, resource implications of expanding socioeconomic support are large, and cost-effectiveness analysis can inform budget priorities. We compared the incremental benefits and costs of providing education, food, or both forms of support (dual support) with existing ART services from a health care provider's perspective.

Methods: Costs and outcome data were collected from a cohort of 2371 adult patients with HIV receiving education, food, or dual support from Reach Out Mbuya between 2004 and 2010. The primary outcome was averted loss to follow-up. The number of follow-up days was calculated for each patient along with accrued service and fixed program costs for the alternative forms of socioeconomic support in USD by standard costing methods. The socioeconomic support types were compared incrementally over the study period.

Results: After 7 years, 762 (33%) of the patients were loss to follow-up with 42% of them receiving food. In the presence of providing ART, education support was less costly and more effective than the alternatives. The average unit cost for education, food, and dual support were $237, $538, and $776, respectively. The average total annual costs were $88,643 for education, $538,005 for food, and $103,045 for dual support.

Conclusions: Compared with food or dual support, investing in education of the children of ART patients is less costly and more effective in improving patient retention. Reach Out Mbuya should embrace this paradigm shift and channel its resources more efficiently and effectively by focusing on education support.
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http://dx.doi.org/10.1097/QAI.0000000000000280DOI Listing
October 2014

Influence of frequent infectious exposures on general and varicella-zoster virus-specific immune responses in pediatricians.

Clin Vaccine Immunol 2014 Mar 15;21(3):417-26. Epub 2014 Jan 15.

Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.

Reexposure to viruses is assumed to strengthen humoral and cellular immunity via the secondary immune response. We studied the effects of frequent exposure to viral infectious challenges on immunity. Furthermore, we assessed whether repetitive exposures to varicella-zoster virus (VZV) elicited persistently high immune responses. Blood samples from 11 pediatricians and matched controls were assessed at 3 time points and 1 time point, respectively. Besides the assessment of general immunity by means of measuring T-cell subset percentages, antibody titers and gamma interferon (IFN-γ)/interleukin 2 (IL-2)-producing T-cell percentages against adenovirus type 5 (AdV-5), cytomegalovirus (CMV), tetanus toxin (TT), and VZV were determined. Pediatricians had lower levels of circulating CD4(+)-naive T cells and showed boosting of CD8(+) effector memory T cells. Although no effect on humoral immunity was seen, repetitive exposures to VZV induced persistently higher percentages of IFN-γ-positive T cells against all VZV antigens tested (VZV glycoprotein E [gE], VZV intermediate-early protein 62 [IE62], and VZV IE63) than in controls. T cells directed against latency-associated VZV IE63 benefitted the most from natural exogenous boosting. Although no differences in cellular or humoral immunity were found between the pediatricians and controls for AdV-5 or TT, we did find larger immune responses against CMV antigens in pediatricians. Despite the high infectious burden, we detected a robust and diverse immune system in pediatricians. Repetitive exposures to VZV have been shown to induce a stable increased level of VZV-specific cellular but not humoral immunity. Based on our observations, VZV IE63 can be considered a candidate for a zoster vaccine.
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http://dx.doi.org/10.1128/CVI.00818-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3957663PMC
March 2014

Childhood varicella-zoster virus vaccination in Belgium: cost-effective only in the long run or without exogenous boosting?

Hum Vaccin Immunother 2013 Apr 15;9(4):812-22. Epub 2013 Jan 15.

Center for Health Economic Research and Modeling Infectious Diseases (CHERMID); Vaccine and Infectious Disease Institute (Vaxinfectio); University of Antwerp; Wilrijk, Belgium.

Aim: To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y.

Methods: An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys.

Results And Conclusions: If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.
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http://dx.doi.org/10.4161/hv.23334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903901PMC
April 2013

Cost-effectiveness of vaccination against herpes zoster in adults aged over 60 years in Belgium.

Vaccine 2012 Jan 24;30(3):675-84. Epub 2011 Nov 24.

Center for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Aim: To assess the cost-effectiveness of vaccinating all or subgroups of adults aged 60 to 85 years against herpes zoster.

Methods: A deterministic compartmental static model was developed (in freeware R), in which cohorts can acquire herpes zoster according to their age in years. Surveys and database analyses were conducted to obtain as much as possible Belgian age-specific estimates for input parameters. Direct costs and Quality-Adjusted Life-Year (QALY) losses were estimated as a function of standardised Severity Of Illness (SOI) scores (i.e. as a function of the duration and severity of herpes zoster disease).

Results: Uncertainty about the average SOI score for a person with herpes zoster, the duration of protection from the vaccine, and the population that can benefit from the vaccine, exerts a major impact on the results: under assumptions least in favour of vaccination, vaccination is not cost-effective (i.e. incremental cost per QALY gained >€48,000 for all ages considered) at the expected vaccine price of €90 per dose. At the same price, but under assumptions most in favour of vaccination, vaccination is found to be cost-effective (i.e. incremental cost per QALY gained <€5500 for all ages considered). Vaccination of age cohort 60 seems more cost-effective than vaccination of any older age cohort in Belgium.

Discussion: If the vaccine price per dose drops to €45, HZ vaccination of adults aged 60-64 years is likely to be cost-effective in Belgium, even under assumptions least in favour of vaccination. Unlike previous studies, our analysis acknowledged major methodological and model uncertainties simultaneously and presented outcomes for 26 different target ages at which vaccination can be considered (ages 60-85).
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http://dx.doi.org/10.1016/j.vaccine.2011.10.036DOI Listing
January 2012

The cost-effectiveness of varicella and combined varicella and herpes zoster vaccination programmes in the United Kingdom.

Vaccine 2012 Feb 23;30(6):1225-34. Epub 2011 Nov 23.

Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, LondonNW9 5EQ, UK.

Background: Despite the existence of varicella vaccine, many developed countries have not introduced it into their national schedules, partly because of concerns about whether herpes zoster (HZ, shingles) will increase due to a lack of exogenous boosting. The magnitude of any increase in zoster that might occur is dependent on rates at which adults and children mix - something that has only recently been quantified - and could be reduced by simultaneously vaccinating older individuals against shingles. This study is the first to assess the cost-effectiveness of combined varicella and zoster vaccination options and compare this to alternative programmes.

Methods And Findings: The cost-effectiveness of various options for the use of varicella-zoster virus (VZV) containing vaccines was explored using a transmission dynamic model. Underlying contact rates are estimated from a contemporary survey of social mixing patterns, and uncertainty in these derived from bootstrapping the original sample. The model was calibrated to UK data on varicella and zoster incidence. Other parameters were taken from the literature. UK guidance on perspective and discount rates were followed. The results of the incremental cost-effectiveness analysis suggest that a combined policy is cost-effective. However, the cost-effectiveness of this policy (and indeed the childhood two-dose policy) is influenced by projected benefits that accrue many decades (80-100 years or more) after the start of vaccination. If the programme is evaluated over shorter time frames, then it would be unlikely to be deemed cost-effective, and may result in declines in population health, due to a projected rise in the incidence of HZ. The findings are also sensitive to a number of parameters that are inaccurately quantified, such as the risk of HZ in varicella vaccine responders.

Conclusions: Policy makers should be aware of the potential negative benefits in the first 30-50 years after introduction of a childhood varicella vaccine. This can only be partly mitigated by the introduction of a herpes zoster vaccine. They have to decide how they value the potential benefits beyond this time to consider childhood vaccination cost effective.
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http://dx.doi.org/10.1016/j.vaccine.2011.11.026DOI Listing
February 2012

Estimating the age-specific duration of herpes zoster vaccine protection: a matter of model choice?

Vaccine 2012 Apr 1;30(17):2795-800. Epub 2011 Oct 1.

Center for Health Economic Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Universiteitsplein 1, Wilrijk, Belgium.

Introduction: The estimation of herpes zoster (HZ) vaccine efficacy by time since vaccination and age at vaccination is crucial to assess the effectiveness and cost-effectiveness of HZ vaccination. Published estimates for the duration of protection from the vaccine diverge substantially, although based on data from the same trial for a follow-up period of 5 years. Different models were used to obtain these estimates, but it is unclear which of these models is most appropriate (if any). Only one study estimated vaccine efficacy by age at vaccination and time since vaccination combined. Recently, data became available from the same trial for a follow-up period of 7 years.

Aim And Methods: We aim to elaborate on estimating HZ vaccine efficacy (1) by estimating it as a function of time since vaccination and age at vaccination, (2) by comparing the fits of a range of models, and (3) by fitting these models on data for a follow-up period of 5 and 7 years.

Results: Although the models' fit to data are very comparable, they differ substantially in how they estimate vaccine efficacy to change as a function of time since vaccination and age at vaccination.

Discussion: An accurate estimation of HZ vaccine efficacy by time since vaccination and age at vaccination is hampered by the lack of insight in the biological processes underlying HZ vaccine protection, and by the fact that such data are currently not available in sufficient detail. Uncertainty about the choice of model to estimate this important parameter should be acknowledged in cost-effectiveness analyses.
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http://dx.doi.org/10.1016/j.vaccine.2011.09.079DOI Listing
April 2012

Accounting for methodological, structural, and parameter uncertainty in decision-analytic models: a practical guide.

Med Decis Making 2011 Jul-Aug;31(4):675-92. Epub 2011 Jun 8.

Modelling and Economics Unit, Health Protection Agency, London, United Kingdom (MJ)

Unlabelled: Accounting for uncertainty is now a standard part of decision-analytic modeling and is recommended by many health technology agencies and published guidelines. However, the scope of such analyses is often limited, even though techniques have been developed for presenting the effects of methodological, structural, and parameter uncertainty on model results. To help bring these techniques into mainstream use, the authors present a step-by-step guide that offers an integrated approach to account for different kinds of uncertainty in the same model, along with a checklist for assessing the way in which uncertainty has been incorporated. The guide also addresses special situations such as when a source of uncertainty is difficult to parameterize, resources are limited for an ideal exploration of uncertainty, or evidence to inform the model is not available or not reliable.

Methods: for identifying the sources of uncertainty that influence results most are also described. Besides guiding analysts, the guide and checklist may be useful to decision makers who need to assess how well uncertainty has been accounted for in a decision-analytic model before using the results to make a decision.
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http://dx.doi.org/10.1177/0272989X11409240DOI Listing
November 2011

An update to "The cost-effectiveness of rotavirus vaccination: comparative analyses for five European countries and transferability in Europe".

Vaccine 2010 Nov 21;28(47):7457-9. Epub 2010 Sep 21.

A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to remain valid. Vaccination remains cost-effective in Finland only when using plausible tender prices.
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http://dx.doi.org/10.1016/j.vaccine.2010.08.060DOI Listing
November 2010

Rotavirus disease and vaccination: impact on genotype diversity.

Future Microbiol 2009 Dec;4(10):1303-16

Laboratory of Clinical and Epidemiological Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.

Temporal and spatial fluctuations in the genotype distribution of human rotaviruses are continuously observed in surveillance studies. New genotypes, such as G9 and G12, have emerged and spread worldwide in a very short time span. In addition, reassortment events have the potential to contribute substantially to genetic diversity among human and animal rotaviruses. With the recent introduction of the two rotavirus vaccines, RotaTeq and Rotarix, in many countries, it appears that the total number of hospitalizations due to rotavirus infections is being reduced, at least in developed countries that implemented a universal immunization program. However, continued surveillance is warranted, especially regarding the long-term effects of the vaccines. No data analyses are available to clarify whether rotavirus vaccine introduction would allow other rotavirus P and G genotypes, which are not covered by the current vaccines, to emerge into the human population and fill the apparent gap. This kind of data analysis is essential, but its interpretation is hampered by natural and cyclical genotype fluctuations.
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http://dx.doi.org/10.2217/fmb.09.96DOI Listing
December 2009

The cost-effectiveness of rotavirus vaccination: Comparative analyses for five European countries and transferability in Europe.

Vaccine 2009 Oct 26;27(44):6121-8. Epub 2009 Aug 26.

Health Economics Unit, University of Birmingham, United Kingdom.

Cost-effectiveness analyses are usually not directly comparable between countries because of differences in analytical and modelling assumptions. We investigated the cost-effectiveness of rotavirus vaccination in five European Union countries (Belgium, England and Wales, Finland, France and the Netherlands) using a single model, burden of disease estimates supplied by national public health agencies and a subset of common assumptions. Under base case assumptions (vaccination with Rotarix, 3% discount rate, health care provider perspective, no herd immunity and quality of life of one caregiver affected by a rotavirus episode) and a cost-effectiveness threshold of euro30,000, vaccination is likely to be cost effective in Finland only. However, single changes to assumptions may make it cost effective in Belgium and the Netherlands. The estimated threshold price per dose for Rotarix (excluding administration costs) to be cost effective was euro41 in Belgium, euro28 in England and Wales, euro51 in Finland, euro36 in France and euro46 in the Netherlands.
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http://dx.doi.org/10.1016/j.vaccine.2009.08.030DOI Listing
October 2009