Mark Jit
Mark Jit
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Chair and Professor of the Department of Global and Environmental Health
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Professional overview
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Mark Jit is the inaugural chair and a professor in the Department of Global and Environmental Health. He was formerly head of the Department of Infectious Disease Epidemiology & Dynamics and co-director of the Global Health Economics Centre (GHECO) at the London School of Hygiene & Tropical Medicine (LSHTM). He holds honorary appointments at LSHTM as well as the University of Hong Kong (HKU) and the National University of Singapore (NUS).
Dr. Jit’s research focuses on epidemiological and economic modeling of vaccines to support evidence-based public health decision making. He has published papers covering a range of vaccine-preventable or potentially vaccine-preventable diseases including COVID-19, measles, HPV, pneumococcus, rotavirus, influenza, Group B Streptococcus, dengue, EV71 and RSV as well as methodological papers advancing the ways vaccines are evaluated. This work has influenced many of the major changes to immunization policy in countries around the world. Dr. Jit has served on a number of expert advisory committees in the UK as well as for international organizations such as the World Health Organization. He also organises or contributes to academic and professional courses on vaccine modeling, economics and decision science around the world.
Dr. Jit received his BSc and PhD in Mathematics from University College London, specializing in mathematical biology, and a Master of Public Health degree from King’s College London.
Visit Dr. Jit's Google Scholar's page to learn more about his research portfolio.
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Education
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BSc, Mathematics, University College LondonPhD, Mathematics, University College LondonMPH, Public Health, King's College London
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Honors and awards
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Clarivate Highly Cited Researcher (20222023)Fellow of the Academy of Medical Sciences (2023)Training Fund Award, Health Protection Agency (2007)Andrew Rosen Prize, University College London (1999)Institute of Mathematics and its Applications Award (1998)Departmental Research Studentship, University College London (1998)Student Union Commendation, University College London (1997)Fillon Prize, University College London (1996)Pathfinder Award, University College London (1995)
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Publications
Publications
A Randomized, Observer-Blinded Immunogenicity Trial of Cervarix® and Gardasil® Human Papillomavirus Vaccines in 12-15 Year Old Girls
AbstractDraper, E., Bissett, S. L., Howell-Jones, R., Waight, P., Soldan, K., Jit, M., Andrews, N., Miller, E., & Beddows, S. (n.d.).Publication year
2013Journal title
PloS oneVolume
8Issue
5AbstractBackground:The current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals.Methods and Findings:Serum and genital samples were collected from 12-15 year old girls following vaccination with either Cervarix® (n = 96) or Gardasil® (n = 102) HPV vaccine. Serum-neutralizing antibody responses against non-vaccine HPV types were broader and of higher magnitude in the Cervarix®, compared to the Gardasil®, vaccinated individuals. Levels of neutralizing and binding antibodies in genital secretions were closely associated with those found in the serum (r = 0.869), with Cervarix® having a median 2.5 (inter-quartile range, 1.7-3.5) fold higher geometric mean HPV-specific IgG ratio in serum and genital samples than Gardasil® (p = 0.0047). There was a strong positive association between cross-neutralizing antibody seropositivity and available HPV vaccine trial efficacy data against non-vaccine types.Conclusions:These data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines.Trial Registration:ClinicalTrials.gov NCT00956553.Acceptability and uptake of female adolescent HPV vaccination in Hong Kong: A survey of mothers and adolescents
AbstractChoi, H. C., Leung, G. M., Woo, P. P., Jit, M., & Wu, J. T. (n.d.).Publication year
2013Journal title
VaccineVolume
32Issue
1Page(s)
78-84AbstractBackground: Organized population-based HPV vaccination programs can be effective in reducing the burden of cervical cancer, especially in the absence of a comprehensive cervical screening program (e.g. Hong Kong). Assessment of vaccine acceptability is important when evaluating the feasibility and cost-effectiveness of such vaccination programs. Methods: To provide a more representative and updated assessment on the acceptability of female adolescent HPV vaccination in Hong Kong, we conducted surveys in 2008 among 1022 mothers with daughters aged ≤18 years through random digit-dialing telephone interviewing and 2167 schoolgirls aged 11-18 years using two-stage stratified cluster sampling. We conducted the maternal survey again in 2012 with an independent group of 1005 mothers. Results: In 2008, 2.4% (95% confidence interval [CI] = 1.8-3.2%) of the recruited schoolgirls reported having received HPV vaccination. In 2012, the mothers reported that 9.1% (7.0-11.6%) of their daughters who were in the same age range (11-18 years) as the schoolgirls had been vaccinated (p < 0.01). Regarding acceptability, 27.5% (24.8-30.4%) and 37.6% (34.5-40.8%) of the mothers were willing to have their daughters vaccinated at market price in 2008 and 2012 (p < 0.01), respectively. 27.1% (25.2-29.1%) of the schoolgirls were willing to receive HPV vaccination at market price in 2008. The willingness to pay for full-course vaccination among mothers had a median of US$128/HK$1000 (50% central range = US$64-192/HK$500-1500), i.e. substantially lower than the current market price. Conclusions: The gap between acceptability and actual uptake of HPV vaccination among adolescent girls suggested that coverage is likely to be low without an organized HPV vaccination program, although the difference might be partially attributed to the possibility that at the time of the interview female adolescents who were willing to be vaccinated had not yet taken action. Policymakers should devise tailored, targeted and efficient vaccination strategies to achieve universal coverage for an effectively organized HPV vaccination program.An integrated approach to evaluating alternative risk prediction strategies: A case study comparing alternative approaches for preventing invasive fungal disease
AbstractSadique, Z., Grieve, R., Harrison, D. A., Jit, M., Allen, E., & Rowan, K. M. (n.d.).Publication year
2013Journal title
Value in HealthVolume
16Issue
8Page(s)
1111-1122AbstractObjectives This article proposes an integrated approach to the development, validation, and evaluation of new risk prediction models illustrated with the Fungal Infection Risk Evaluation study, which developed risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD). Methods Our decision-analytical model compared alternative strategies for preventing IFD at up to three clinical decision time points (critical care admission, after 24 hours, and end of day 3), followed with antifungal prophylaxis for those judged "high" risk versus "no formal risk assessment." We developed prognostic models to predict the risk of IFD before critical care unit discharge, with data from 35,455 admissions to 70 UK adult, critical care units, and validated the models externally. The decision model was populated with positive predictive values and negative predictive values from the best-fitting risk models. We projected lifetime cost-effectiveness and expected value of partial perfect information for groups of parameters. Results The risk prediction models performed well in internal and external validation. Risk assessment and prophylaxis at the end of day 3 was the most cost-effective strategy at the 2% and 1% risk threshold. Risk assessment at each time point was the most cost-effective strategy at a 0.5% risk threshold. Expected values of partial perfect information were high for positive predictive values or negative predictive values (£11 million-£13 million) and quality-adjusted life-years (£11 million). Conclusions It is cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients. This integrated approach to developing and evaluating risk models is useful for informing clinical practice and future research investment.Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: A systematic review
AbstractFesenfeld, M., Hutubessy, R., & Jit, M. (n.d.).Publication year
2013Journal title
VaccineVolume
31Issue
37Page(s)
3786-3804AbstractThe World Health Organization recommends establishing that human papillomavirus vaccination is cost-effective before vaccine introduction. We searched Pubmed, Embase and the Cochrane Library to 1 April 2012 for economic evaluations of human papillomavirus vaccination in low and middle income countries. We found 25 articles, but almost all low income countries and many middle income countries lacked country-specific studies. Methods, assumptions and consequently results varied widely, even for studies conducted for the same country. Despite the heterogeneity, most studies conclude that vaccination is likely to be cost-effective and possibly even cost saving, particularly in settings without organized cervical screening programmes. However, study uncertainty could be reduced by clarity about vaccine prices and vaccine delivery costs. The review supports extending vaccination to low income settings where vaccine prices are competitive, donor funding is available, cervical cancer burden is high and screening options are limited.Cost-effectiveness of point-of-care C-reactive protein testing to inform antibiotic prescribing decisions
AbstractOppong, R., Jit, M., Smith, R. D., Butler, C. C., Melbye, H., Mölstad, S., & Coast, J. (n.d.).Publication year
2013Journal title
British Journal of General PracticeVolume
63Issue
612Page(s)
e465-e471AbstractBackground Point-of-care C-reactive protein (POCCRP) is a biomarker of inflammation that offers clinicians a rapid POC test to guide antibiotic prescribing decisions for acute cough and lower respiratory tract infections (LRTI). However, evidence that POCCRP is cost-effective is limited, particularly outside experimental settings. Aim To assess the cost-effectiveness of POCCRP as a diagnostic tool for acute cough and LRTI from the perspective of the health service. Design and setting Observational study of the presentation, management, and outcomes of patients with acute cough and LRTI in primary care settings in Norway and Sweden. Method Using hierarchical regression, data were analysed in terms of the effect on antibiotic use, cost, and patient outcomes (symptom severity after 7 and 14 days, time to recovery, and EQ-5D), while controlling for patient characteristics (self-reported symptom severity, comorbidities, and health-related quality of life) at first attendance. Results POCCRP testing is associated with non-significant positive reductions in antibiotic prescribing (P = 0.078) and increased cost (P = 0.092). Despite the uncertainty, POCCRP testing is also associated with a cost per quality-adjusted life year (QALY) gain of €9391. At a willingness-to-pay threshold of €30 000 per QALY gained, there is a 70% probability of CRP being cost-effective. Conclusion POCCRP testing is likely to provide a cost-effective diagnostic intervention both in terms of reducing antibiotic prescribing and in terms of QALYs gained.Development and validation of a risk model for identification of non-neutropenic, critically-ill, adult patients at high risk of invasive Candida infection
AbstractHarrison, D., Muskett, H., Harvey, S., Grieve, R., Shahin, J., Patel, K., Sadique, Z., Allen, E., Dybowski, R., Jit, M., Edgeworth, J., Kibbler, C., Barnes, R., Soni, N., & Rowan, K. (n.d.).Publication year
2013Journal title
Health Technology AssessmentVolume
17Issue
3Page(s)
1-30AbstractBackground There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. Objectives To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. Design Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. Setting Ninety-six UK adult general critical care units. Participants Consecutive admissions to participating critical care units. Interventions None. Main outcome measures Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. Results Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. Data collection: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs. Conclusions The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis. Funding Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.Economic analyses to support decisions about HPV vaccination in low- and middle-income countries: A consensus report and guide for analysts
AbstractJit, M., Levin, C., Brisson, M., Levin, A., Resch, S., Berkhof, J., Kim, J., & Hutubessy, R. (n.d.). In BMC Medicine (1–).Publication year
2013Volume
11Issue
1AbstractLow- and middle-income countries need to consider economic issues such as cost-effectiveness, affordability and sustainability before introducing a program for human papillomavirus (HPV) vaccination. However, many such countries lack the technical capacity and data to conduct their own analyses. Analysts informing policy decisions should address the following questions: 1) Is an economic analysis needed? 2) Should analyses address costs, epidemiological outcomes, or both? 3) If costs are considered, what sort of analysis is needed? 4) If outcomes are considered, what sort of model should be used? 5) How complex should the analysis be? 6) How should uncertainty be captured? 7) How should model results be communicated? Selecting the appropriate analysis is essential to ensure that all the important features of the decision problem are correctly represented, but that the analyses are not more complex than necessary. This report describes the consensus of an expert group convened by the World Health Organization, prioritizing key issues to be addressed when considering economic analyses to support HPV vaccine introduction in these countries.Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza vaccines in low and middle income countries: A systematic review and meta-analysis
AbstractBreteler, J. K., Tam, J. S., Jit, M., Ket, J. C., & De Boer, M. R. (n.d.).Publication year
2013Journal title
VaccineVolume
31Issue
45Page(s)
5168-5177AbstractPurpose: Influenza vaccines have been recommended for populations at risk for severe infection in low and middle income countries (LMICs) although knowledge of the evidence-base for their effectiveness and efficacy is limited in these countries. The aim of this systematic review is to provide an overview of the evidence-base for the effectiveness and efficacy of influenza vaccines in LMICs and to explore critical knowledge gaps. Methods: PubMed, EMBASE, and Cochrane were searched for seasonal and pandemic A (H1N1) 2009 influenza vaccine effectiveness and efficacy studies performed in LMICs. Eligible studies included RCTs and observational studies, published in English, French, Spanish or Portuguese between 1960 and 2011, which assessed laboratory-confirmed influenza and/or influenza-related outcomes in any population. Risk of bias was assessed by two reviewers independently. Random effects pooled estimates were obtained when sufficient data were available. Results: A total of 6465 articles were screened. Forty-one studies were included on seasonal influenza vaccine effectiveness and efficacy and one study on pandemic vaccine effectiveness. In middle income countries (MICs), efficacy of seasonal influenza vaccines was shown against laboratory-confirmed influenza in children (pooled efficacy 72% (95%CI: 65-77) and 81% (95%CI: 69-89), for one and two years follow-up respectively) and in the elderly (pooled efficacy 43% (95%CI: 25-56) and 58% (95%CI: 23-78), for live attenuated and inactivated vaccine respectively). Inactivated influenza vaccines were also found to be effective against cardiovascular outcomes in patients with coronary syndromes. Conclusions: Seasonal influenza vaccines can provide protection in children, the elderly and patients with coronary syndromes in MICs, and seem to be equally effective as compared to high income countries. Data for other high risk groups and from low income countries were limited or prone to bias, and are needed to further facilitate evidence-based decision making regarding influenza vaccination in LMICs.Influenza vaccines in low and middle income countries: A systematic review of economic evaluations
AbstractOtt, J. J., Breteler, J. K., Tam, J. S., Hutubessy, R. C., Jit, M., & De Boer, M. R. (n.d.).Publication year
2013Journal title
Human Vaccines and ImmunotherapeuticsVolume
9Issue
7Page(s)
1500-1511AbstractObjectives: Economic evaluations on influenza vaccination from low resource settings are scarce and have not been evaluated using a systematic approach. Our objective was to conduct a systematic review on the value for money of influenza vaccination in low- and middle-income countries. Methods: PubMed and EMBASE were searched for economic evaluations published in any language between 1960 and 2011. Main outcome measures were costs per influenza outcome averted, costs per quality-adjusted life years gained or disability-adjusted life years averted, costs per benefit in monetary units or cost-benefit ratios. Results: Nine economic evaluations on seasonal influenza vaccine met the inclusion criteria. These were model- or randomized-controlled-trial (RCT)-based economic evaluations from middle-income countries. Influenza vaccination provided value for money for elderly, infants, adults and children with high-risk conditions. Vaccination was cost-effective and costsaving for chronic obstructive pulmonary disease patients and in elderly above 65 y from model-based evaluations, but conclusions from RCTs on elderly varied. Conclusion: Economic evaluations from middle income regions differed in population studied, outcomes and definitions used. Most findings are in line with evidence from high-income countries highlighting that influenza vaccine is likely to provide value for money. However, serious methodological limitations do not allow drawing conclusions on cost-effectiveness of influenza vaccination in middle income countries. Evidence on cost-effectiveness from low-income countries is lacking altogether, and more information is needed from full economic evaluations that are conducted in a standardized manner.Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies
AbstractJit, M., Newall, A. T., & Beutels, P. (n.d.).Publication year
2013Journal title
Human Vaccines and ImmunotherapeuticsVolume
9Issue
4Page(s)
834-840AbstractMany countries have considered or are considering modifying their seasonal influenza immunization policies. Estimating the impact of such changes requires understanding the existing clinical and economic burden of influenza, as well as the potential impact of different vaccination options. Previous studies suggest that vaccinating clinical risk groups, health care workers, children and the elderly may be cost-effective. However, challenges in such estimation include: (1) potential cases are not usually virologically tested; (2) cases have nonspecific symptoms and are rarely reported to surveillance systems; (3) endpoints for influenza proxies (such as influenzalike illness) need to be matched to case definitions for treatment costs, (4) disease burden estimates vary from year to year with strain transmissibility, virulence and prior immunity, (5) methods to estimate productivity losses due to influenza vary, (6) vaccine efficacy estimates from trials differ due to variation in subtype prevalence, vaccine match and case ascertainment, and (7) indirect (herd) protection from vaccination depends on settingspecific variables that are difficult to directly measure. Given the importance of knowing the impact of changes to influenza policy, such complexities need careful treatment using tools such as population-based trial designs, meta-analyses, timeseries analyses and transmission dynamic models.Modelling the transmission of healthcare associated infections: A systematic review
AbstractVan Kleef, E., Robotham, J. V., Jit, M., Deeny, S. R., & Edmunds, W. J. (n.d.).Publication year
2013Journal title
BMC Infectious DiseasesVolume
13Issue
1AbstractBackground: Dynamic transmission models are increasingly being used to improve our understanding of the epidemiology of healthcare-associated infections (HCAI). However, there has been no recent comprehensive review of this emerging field. This paper summarises how mathematical models have informed the field of HCAI and how methods have developed over time.Methods: MEDLINE, EMBASE, Scopus, CINAHL plus and Global Health databases were systematically searched for dynamic mathematical models of HCAI transmission and/or the dynamics of antimicrobial resistance in healthcare settings.Results: In total, 96 papers met the eligibility criteria. The main research themes considered were evaluation of infection control effectiveness (64%), variability in transmission routes (7%), the impact of movement patterns between healthcare institutes (5%), the development of antimicrobial resistance (3%), and strain competitiveness or co-colonisation with different strains (3%). Methicillin-resistant Staphylococcus aureus was the most commonly modelled HCAI (34%), followed by vancomycin resistant enterococci (16%). Other common HCAIs, e.g. Clostridum difficile, were rarely investigated (3%). Very few models have been published on HCAI from low or middle-income countries.The first HCAI model has looked at antimicrobial resistance in hospital settings using compartmental deterministic approaches. Stochastic models (which include the role of chance in the transmission process) are becoming increasingly common. Model calibration (inference of unknown parameters by fitting models to data) and sensitivity analysis are comparatively uncommon, occurring in 35% and 36% of studies respectively, but their application is increasing. Only 5% of models compared their predictions to external data.Conclusions: Transmission models have been used to understand complex systems and to predict the impact of control policies. Methods have generally improved, with an increased use of stochastic models, and more advanced methods for formal model fitting and sensitivity analyses. Insights gained from these models could be broadened to a wider range of pathogens and settings. Improvements in the availability of data and statistical methods could enhance the predictive ability of models.Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England
AbstractMesher, D., Soldan, K., Howell-Jones, R., Panwar, K., Manyenga, P., Jit, M., Beddows, S., & Gill, O. N. (n.d.).Publication year
2013Journal title
VaccineVolume
32Issue
1Page(s)
26-32AbstractBackground: Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised. Methods: Residual vulva-vaginal swab (VVS) specimens from young women aged 16-24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010-2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008. Results: A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16-18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16-18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16-18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation. Conclusions: These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types.Trends in parameterization, economics and host behaviour in influenza pandemic modelling: A review and reporting protocol
AbstractCarrasco, L. R., Jit, M., Chen, M. I., Lee, V. J., Milne, G. J., & Cook, A. R. (n.d.).Publication year
2013Journal title
Emerging Themes in EpidemiologyVolume
10Issue
1AbstractBackground: The volume of influenza pandemic modelling studies has increased dramatically in the last decade. Many models incorporate now sophisticated parameterization and validation techniques, economic analyses and the behaviour of individuals. Methods. We reviewed trends in these aspects in models for influenza pandemic preparedness that aimed to generate policy insights for epidemic management and were published from 2000 to September 2011, i.e. before and after the 2009 pandemic. Results: We find that many influenza pandemics models rely on parameters from previous modelling studies, models are rarely validated using observed data and are seldom applied to low-income countries. Mechanisms for international data sharing would be necessary to facilitate a wider adoption of model validation. The variety of modelling decisions makes it difficult to compare and evaluate models systematically. Conclusions: We propose a model Characteristics, Construction, Parameterization and Validation aspects protocol (CCPV protocol) to contribute to the systematisation of the reporting of models with an emphasis on the incorporation of economic aspects and host behaviour. Model reporting, as already exists in many other fields of modelling, would increase confidence in model results, and transparency in their assessment and comparison.Use of measles supplemental immunization activities (SIAs) as a delivery platform for other maternal and child health interventions: Opportunities and challenges
AbstractJohri, M., Sharma, J. K., Jit, M., & Verguet, S. (n.d.).Publication year
2013Journal title
VaccineVolume
31Issue
9Page(s)
1259-1263AbstractMeasles supplementary immunization activities (SIAs) offer children in countries with weaker immunization delivery systems like India a second opportunity for measles vaccination. They could also provide a platform to deliver additional interventions, but the feasibility and acceptability of including add-ons is uncertain. We surveyed Indian programme officers involved in the current (2010-2012) measles SIAs concerning opportunities and challenges of using SIAs as a delivery platform for other maternal and child health interventions. Respondents felt that an expanded SIA strategy including add-ons could be of great value in improving access and efficiency. They viewed management challenges, logistics, and safety as the most important potential barriers. They proposed that additional interventions be selected using several criteria, of which importance of the health problem, safety, and contribution to health equity figured most prominently. For children, they recommended inclusion of basic interventions to address nutritional deficiencies, diarrhoea and parasites over vaccines. For mothers, micronutrient interventions were highest ranked.Cross-protective efficacy of two human papillomavirus vaccines: A systematic review and meta-analysis
AbstractMalagón, T., Drolet, M., Boily, M. C., Franco, E. L., Jit, M., Brisson, J., & Brisson, M. (n.d.).Publication year
2012Journal title
The Lancet Infectious DiseasesVolume
12Issue
10Page(s)
781-789AbstractBackground: The extent of cross-protection is a key element in the choice of human papillomavirus (HPV) vaccine to use in vaccination programmes. We compared the cross-protective efficacy of the bivalent vaccine (HPV 16 and 18; Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and quadrivalent vaccine (HPV 6, 11, 16, and 18; Gardasil, Merck, Whitehouse Station, NJ, USA) against non-vaccine type HPVs. Methods: We searched Medline and Embase databases, conference abstracts, and manufacturers' websites for randomised clinical trials assessing the efficacy of bivalent and quadrivalent vaccines against persistent infections (lasting ≥6 months) and cervical intraepithelial neoplasia (CIN) associated with the non-vaccine type HPVs (types 31, 33, 45, 52, and 58). We included studies of participants who were HPV DNA negative before vaccination for all HPV types assessed. We assessed heterogeneity in vaccine efficacy estimates between trials with I2 and χ2 statistics. Findings: We identified two clinical trials (Females United to Unilaterally Reduce Endo/Ectocervical Disease [FUTURE] I and II) of the quadrivalent vaccine and three (Papilloma Trial Against Cancer In Young Adults [PATRICIA], HPV007, and HPV-023) of the bivalent vaccine. Analysis of the most comparable populations (pooled FUTURE I/II data vs PATRICIA) suggested that cross-protective vaccine efficacy estimates against infections and lesions associated with HPV 31, 33, and 45 were usually higher for the bivalent vaccine than the quadrivalent vaccine. Vaccine efficacy in the bivalent trial was higher than it was in the quadrivalent trial against persistent infections with HPV 31 (77·1% [95% CI 67·2 to 84·4] for bivalent vaccine vs 46·2% [15·3 to 66·4] for quadrivalent vaccine; p=0·003) and HPV 45 (79·0% [61·3 to 89·4] vs 7·8% [-67·0 to 49·3]; p=0·0003), and against CIN grade 2 or worse associated with HPV 33 (82·3% [53·4 to 94·7] vs 24·0% [-71·2 to 67·2]; p=0·02) and HPV 45 (100% [41·7 to 100] vs -51·9% [-1717·8 to 82·6]; p=0·04). We noted substantial heterogeneity between vaccine efficacy in bivalent trials against persistent infections with HPV 31 (I2=69%, p=0·04) and HPV 45 (I2=70%, p=0·04), with apparent reductions in cross-protective efficacy with increased follow-up. Interpretation: The bivalent vaccine seems more efficacious against non-vaccine HPV types 31, 33, and 45 than the quadrivalent vaccine, but the differences were not all significant and might be attributable to differences in trial design. Efficacy against persistent infections with types 31 and 45 seemed to decrease in bivalent trials with increased follow-up, suggesting a waning of cross-protection; more data are needed to establish duration of cross-protection. Funding: Public Health Agency of Canada.Economic evaluations of childhood influenza vaccination: A critical review
AbstractNewall, A. T., Jit, M., & Beutels, P. (n.d.).Publication year
2012Journal title
PharmacoEconomicsVolume
30Issue
8Page(s)
647-660AbstractThe potential benefits of influenza vaccination programmes targeted at children have gained increasing attention in recent years.We conducted a literature search of economic evaluations of influenza vaccination in those aged ≤18 years. The search revealed 20 relevant articles, which were reviewed. The studies differed widely in terms of the costs and benefits that were included. The conclusions were generally favourable for vaccination, but often applied a wider perspective (i.e. including productivity losses) than the reference case for economic evaluations used in many countries. Several evaluations estimated outcomes from a single-year epidemiological study, which may limit their validity given the year-to-year variation in influenza transmissibility, virulence, vaccine match and prior immunity. Only one study used a dynamic transmission model able to fully incorporate the indirect herd protection to the wider community.The use of dynamic models offers great scope to capture the population-wide implications of seasonal vaccination efforts, particularly those targeted at children. AdisEnzymes provide demographers with food for thought
Jit, M., & Gerland, P. (n.d.).Publication year
2012Journal title
eLifeVolume
2012Issue
1Health and economic impact of the seasonal influenza vaccination programme in England
AbstractBaguelin, M., Jit, M., Miller, E., & Edmunds, W. J. (n.d.).Publication year
2012Journal title
VaccineVolume
30Issue
23Page(s)
3459-3462AbstractBackground: The seasonal influenza vaccination programme in England targets individuals over 65. years old and in clinical risk groups. Methods: A model of influenza transmission and disease was fitted to weekly primary care consultations due to influenza in a typical pre-pandemic season (2006/2007). Different scenarios were constructed about influenza severity and how well vaccines match circulating strains to assess the impact and cost-effectiveness of the current vaccination programme. Results: A well-matched vaccine may reduce the incidence of laboratory-confirmed influenza illness from 8.2% (95% range 4.3-13%) to 5.9% (95% range 2.9-9.7%), with 56-73% of this due to indirect protection. The programme is likely to be cost-effective unless both low severity and poor matching is assumed. Conclusion: The current seasonal influenza vaccination programme appears to substantially reduce disease burden and provides good value for money.Mathematical modelling long-term effects of replacing prevnar7 with prevnar13 on invasive pneumococcal diseases in england and wales
AbstractChoi, Y. H., Jit, M., Flasche, S., Gay, N., & Miller, E. (n.d.).Publication year
2012Journal title
PloS oneVolume
7Issue
7AbstractIntroduction: England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. Methods: A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Results: Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000-62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Conclusion: Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.Potential overestimation of HPV vaccine impact due to unmasking of non-vaccine types: Quantification using a multi-type mathematical model
AbstractChoi, Y. H., Chapman, R., Gay, N., & Jit, M. (n.d.).Publication year
2012Journal title
VaccineVolume
30Issue
23Page(s)
3383-3388AbstractIntroduction: Estimates of human papillomavirus (HPV) vaccine impact in clinical trials and modelling studies rely on DNA tests of cytology or biopsy specimens to determine the HPV type responsible for a cervical lesion. DNA of several oncogenic HPV types may be detectable in a specimen. However, only one type may be responsible for a particular cervical lesion. Misattribution of the causal HPV type for a particular abnormality may give rise to an apparent increase in disease due to non-vaccine HPV types following vaccination (" unmasking" ). Methods: To investigate the existence and magnitude of unmasking, we analysed data from residual cytology and biopsy specimens in English women aged 20-64 years old using a stochastic type-specific individual-based model of HPV infection, progression and disease. The model parameters were calibrated to data on the prevalence of HPV DNA and cytological lesion of different grades, and used to assign causal HPV types to cervical lesions. The difference between the prevalence of all disease due to non-vaccine HPV types, and disease due to non-vaccine HPV types in the absence of vaccine HPV types, was then estimated. Results: There could be an apparent maximum increase of 3-10% in long-term cervical cancer incidence due to non-vaccine HPV types following vaccination. Conclusion: Unmasking may be an important phenomenon in HPV post-vaccination epidemiology, in the same way that has been observed following pneumococcal conjugate vaccination.Systematic review of studies evaluating the broader economic impact of vaccination in low and middle income countries
AbstractDeogaonkar, R., Hutubessy, R., Van Der Putten, I., Evers, S., & Jit, M. (n.d.).Publication year
2012Journal title
BMC public healthVolume
12Issue
1AbstractBackground: Most health economic evaluations of childhood vaccination only capture the health and short-term economic benefits. Measuring broader, long-term effects of vaccination on productivity and externalities could provide a more complete picture of the value of vaccines. Method. MEDLINE, EconLit and NHS-EED databases were searched for articles published between January 1990 and July 2011, which captured broader economic benefits of vaccines in low and middle income countries. Studies were included if they captured at least one of the following categories on broader economic impact: outcome-related productivity gains, behaviour-related productivity gains, ecological externalities, equity gains, financial sustainability gains or macroeconomic benefits. Results: Twenty-six relevant studies were found, including observational studies, economic models and contingent valuation studies. Of the identified broader impacts, outcome-related productivity gains and ecological externalities were most commonly accounted for. No studies captured behaviour-related productivity gains or macroeconomic effects. There was some evidence to show that vaccinated children 8-14 years of age benefit from increased cognitive ability. Productivity loss due to morbidity and mortality was generally measured using the human capital approach. When included, herd immunity effects were functions of coverage rates or based on reduction in disease outcomes. External effects of vaccines were observed in terms of equitable health outcomes and contribution towards synergistic and financially sustainable healthcare programs. Conclusion: Despite substantial variation in the methods of measurement and outcomes used, the inclusion of broader economic impact was found to improve the attractiveness of vaccination. Further research is needed on how different tools and techniques can be used in combination to capture the broader impact of vaccination in a way that is consistent with other health economic evaluations. In addition, more country level evidence is needed from low and middle income countries to justify future investments in vaccines and immunization programs. Finally, the proposed broader economic impact framework may contribute towards better communication of the economic arguments surrounding vaccine uptake, leading to investments in immunization by stakeholders outside of the traditional health care sector such as ministries of finance and national treasuries.The cost-effectiveness of a 13-valent pneumococcal conjugate vaccination for infants in England
AbstractVan Hoek, A. J., Choi, Y. H., Trotter, C., Miller, E., & Jit, M. (n.d.).Publication year
2012Journal title
VaccineVolume
30Issue
50Page(s)
7205-7213AbstractBackground: In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time. Aim: To investigate the cost effectiveness of the introduction of PCV-13. Method: Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether. Results: Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30. years, vaccine price of £49.60 a dose. +. £7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%. Conclusion: To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease.7-valent pneumococcal conjugate vaccination in england and wales: Is it still beneficial despite high levels of serotype replacement?
AbstractChoi, Y. H., Jit, M., Gay, N., Andrews, N., Waight, P. A., Melegaro, A., George, R., & Miller, E. (n.d.).Publication year
2011Journal title
PloS oneVolume
6Issue
10AbstractBackground: The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen in the US. Methods and Findings: A previous model of pneumococcal vaccination was re-parameterised using data on vaccine coverage and IPD from England and Wales between 2006 and 2009. Disease incidence was adjusted for the increasing trend in reported IPD cases prior to vaccination. Using this data we estimated that individuals carrying PCV7 serotypes have much higher protection (96%;95% CI 72%-100%) against acquisition of NVT carriage than the 15% previously estimated from US data, which leads to greater replacement. However, even with this level of replacement, the annual number of IPD cases may be 560 (95% CI, -100 to 1230) lower ten years after vaccine introduction compared to what it may have been without vaccination. A particularly marked fall of 39% in children under 15 years by 2015/6 is predicted. Conclusion: Our model suggests that PCV7 vaccination could result in a decrease in overall invasive pneumococcal disease, particularly in children, even in an environment of rapid replacement with non-PCV7 serotypes within 5 years of vaccine introduction at high coverage.Accounting for methodological, structural, and parameter uncertainty in decision-analytic models: A practical guide
AbstractBilcke, J., Beutels, P., Brisson, M., & Jit, M. (n.d.).Publication year
2011Journal title
Medical Decision MakingVolume
31Issue
4Page(s)
675-692AbstractAccounting 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.Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world
AbstractPostma, M. J., Jit, M., Rozenbaum, M. H., Standaert, B., Tu, H. A., & Hutubessy, R. C. (n.d.).Publication year
2011Journal title
BMC MedicineVolume
9AbstractBackground: This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters.Methods: We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications.Results: Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs.Conclusions: The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.