Impact of model calibration on cost-effectiveness analysis of cervical cancer prevention

Markov chain models are commonly used to simulate the natural history of human papillomavirus infection and subsequent cervical lesions with the aim of predicting future benefits of health interventions. Developing and calibrating these models entails making a number of critical decisions that will influence the ability of the model to reflect real conditions and predict future situations. Accuracy of selected inputs and calibration procedures are two of the crucial aspects for model performance and understanding their influence is essential, especially when involves policy decisions. The aim of this work is to assess the health and economic impact on cervical cancer prevention strategies currently under discussion according to the most common methods of model calibration combined with different accuracy degree of initial inputs. Model results show large differences on the goodness of fit and cost-effectiveness outcomes depending on the calibration approach used, and these variations may affect health policy decisions. Our findings strengthen the importance of obtaining good calibrated probability matrices to get reliable health and cost outcomes, and are directly generalizable to any cost-effectiveness analysis based on Markov chain models

Moving towards an organized cervical cancer screening: costs and impact

Background: HPV screening has been shown to be more cost-effective than cytology screening under most scenarios. Furthermore, it should be offered only in organized programmes with good quality assurance mechanisms. This study analyses the comparative cost of the current policy of opportunistic cytology screening vs. a hypothetical organized programme based on primary HPV screening. Methods: Total cervical cancer expenditure was defined as the sum of three cost elements: (i) direct (medical and non-medical) costs, obtained from a calibrated Markov model of the natural history of HPV and cervical cancer; (ii) programmatic costs, estimated based on other organized screening programmes; and (iii) indirect costs, extrapolated from previously published data. Results: Organized HPV screening at 5-year intervals costs consistently less across all coverage levels than opportunistic cytology screening at 3-year intervals. The current annual direct medical cost to the public health system of the opportunistic cytology at 40% coverage is estimated at (sic)33.2 per woman screened aged 25-64. Under an organized programme of primary HPV screening at 70% coverage, the cost is estimated to be (sic)18.4 per woman screened aged 25-64. Conclusion: Our study concludes that the economic resources currently devoted to providing opportunistic cytology screening to 40% of the target population at 3-year intervals could be more effectively used to screen 70% of the target population at 5-year intervals by switching to an organized programme based on primary HPV screening. This finding is of relevance to other European countries or regions with similar screening policies and health infrastructures

Quantifying the under-reporting of uncorrelated longitudal data: the genital warts example

Abstract Background: Genital warts are a common and highly contagious sexually transmitted disease. They have a large economic burden and affect several aspects of quality of life. Incidence data underestimate the real occurrence of genital warts because this infection is often under-reported, mostly due to their specific characteristics such as the asymptomatic course. Methods: Genital warts cases for the analysis were obtained from the Catalan public health system database (SIDIAP) for the period 2009-2016. People under 15 and over 94 years old were excluded from the analysis as the incidence of genital warts in this population is negligible. This work introduces a time series model based on a mixture of two distributions, capable of detecting the presence of under-reporting in the data. In order to identify potential differences in the magnitude of the under-reporting issue depending on sex and age, these covariates were included in the model. Results: This work shows that only about 80% in average of genital warts incidence in Catalunya in the period 2009-2016 was registered, although the frequency of under-reporting has been decreasing over the study period. It can also be seen that this issue has a deeper impact on women over 30 years old. Conclusions: Although this study shows that the quality of the registered data has improved over the considered period of time, the Catalan public health system is underestimating genital warts real burden in almost 10,000 cases, around 23% of the registered cases. The total annual cost is underestimated in about 10 million Euros respect the 54 million Euros annually devoted to genital warts in Catalunya, representing 0.4% of the total budget

Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis

Background: Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Methods: Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. Findings: From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39-55 million) received the full course of vaccine, representing a total population coverage of 1.4% (95% CI 1.1-1.6), and 59 million women (48-71 million) had received at least one dose, representing a total population coverage of 1.7% (1.4-2.1). In more developed regions, 33.6% (95% CI 25.9-41.7) of females aged 10-20 years received the full course of vaccine, compared with only 2.7% (1.8-3.6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13.3 million vs 32.2 million). Interpretation Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention

Comprehensive Control of Human Papillomavirus Infections and Related Diseases

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread optimally universal implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. (C) 2013 Elsevier Ltd. All rights reserved

Modelos de coste-efectividad en la prevención del cáncer de cuello de útero en países en desarrollo

INTRODUCCIÓN: Introducir la vacunación del Virus del Papiloma Humano (VPH) en un programa nacional de inmunización no es trivial y depende de múltiples factores tales como la carga de la enfermedad, la eficacia de la vacuna, el coste-efectividad o su viabilidad. Los análisis económicos son un componente común del proceso de decisión en los países industrializados. Sin embargo, aunque cada vez se utilizan más este tipo de análisis en los países menos desarrollados, la alta incidencia de cáncer de cuello de útero (CCU) es la que ha llevado a considerar la introducción de la vacuna del VPH. OBJETIVO: Evaluar el impacto sanitario y económico de la vacunación contra los VPHs 16 y 18 en niñas preadolescentes y ayudar a la toma de decisiones en países en desarrollo METODOLOGÍA: Se han llevado a cabo una serie de análisis utilizando dos modelos analíticos en función de los datos disponibles: modelo de microsimulación y modelo simple de cohortes. CONCLUSIÓN: La vacunación contra los VPHs 16 y 18 se considera una estrategia efectiva para reducir tanto la carga en salud como económica producida por el CCU, pero el coste-efectividad depende en gran medida de algunas asunciones sobre las vacunas como la eficacia o la duración de la protección y sobretodo del coste, además de la capacidad de cada país para administrar la vacuna a niñas antes de las edades con mayor riesgo de infección.BACKGROUND: Introducing Human Papillomavirus (HPV) vaccination in a national immunization programme is not straightforward and depends on multiple factors, including disease burden, vaccine effectiveness, cost-effectiveness and affordability of the vaccination program. The economic analyses are a common component of the decision process in industrialized countries. However, although cost-effectiveness analyses are increasingly used in less developed countries, the burden of cervical cancer has clearly led the consideration of the HPV vaccine introduction. OBJECTIVE: To assess the health and economic impact of the HPV 16 and 18 vaccination of pre-adolescents girls and to assist decision makers in less developed countries. METHODOLOGY: A series of analyses have been conducted using two models depending on the data available: micro-simulation model and simple cohort model. CONCLUSION: HPV 16 and 18 vaccination would be considered an effective strategy to reduce the health and economic burden of cervical cancer, but the cost-effectiveness depends on some vaccine assumptions such as the efficacy and the duration of protection and mostly on cost, in addition to the ability of the countries to reach girls before the ages at the highest risk of infection

Impact of model calibration on cost-effectiveness analysis of cervical cancer prevention

Markov chain models are commonly used to simulate the natural history of human papillomavirus infection and subsequent cervical lesions with the aim of predicting future benefits of health interventions. Developing and calibrating these models entails making a number of critical decisions that will influence the ability of the model to reflect real conditions and predict future situations. Accuracy of selected inputs and calibration procedures are two of the crucial aspects for model performance and understanding their influence is essential, especially when involves policy decisions. The aim of this work is to assess the health and economic impact on cervical cancer prevention strategies currently under discussion according to the most common methods of model calibration combined with different accuracy degree of initial inputs. Model results show large differences on the goodness of fit and cost-effectiveness outcomes depending on the calibration approach used, and these variations may affect health policy decisions. Our findings strengthen the importance of obtaining good calibrated probability matrices to get reliable health and cost outcomes, and are directly generalizable to any cost-effectiveness analysis based on Markov chain models

Global estimates of human papillomavirus vaccination coverage by region and income level: a pooled analysis

Background: Since 2006, many countries have implemented publicly funded human papillomavirus (HPV) immunisation programmes. However, global estimates of the extent and impact of vaccine coverage are still unavailable. We aimed to quantify worldwide cumulative coverage of publicly funded HPV immunisation programmes up to 2014, and the potential impact on future cervical cancer cases and deaths. Methods: Between Nov 1 and Dec 22, 2014, we systematically reviewed PubMed, Scopus, and official websites to identify HPV immunisation programmes worldwide, and retrieved age-specific HPV vaccination coverage rates up to October, 2014. To estimate the coverage and number of vaccinated women, retrieved coverage rates were converted into birth-cohort-specific rates, with an imputation algorithm to impute missing data, and applied to global population estimates and cervical cancer projections by country and income level. Findings: From June, 2006, to October, 2014, 64 countries nationally, four countries subnationally, and 12 overseas territories had implemented HPV immunisation programmes. An estimated 118 million women had been targeted through these programmes, but only 1% were from low-income or lower-middle-income countries. 47 million women (95% CI 39-55 million) received the full course of vaccine, representing a total population coverage of 1.4% (95% CI 1.1-1.6), and 59 million women (48-71 million) had received at least one dose, representing a total population coverage of 1.7% (1.4-2.1). In more developed regions, 33.6% (95% CI 25.9-41.7) of females aged 10-20 years received the full course of vaccine, compared with only 2.7% (1.8-3.6) of females in less developed regions. The impact of the vaccine will be higher in upper-middle-income countries (178 192 averted cases by age 75 years) than in high-income countries (165 033 averted cases), despite the lower number of vaccinated women (13.3 million vs 32.2 million). Interpretation Many women from high-income and upper-middle-income countries have been vaccinated against HPV. However, populations with the highest incidence and mortality of disease remain largely unprotected. Rapid roll-out of the vaccine in low-income and middle-income countries might be the only feasible way to narrow present inequalities in cervical cancer burden and prevention

Cost-effectiveness of strategies to increase screening coverage for cervical cancer in Spain: the CRIVERVA study

Background: The aim of the study is to carry out a cost-effectiveness analysis of three different interventions to promote the uptake of screening for cervical cancer in general practice in the county of Valles Occidental, Barcelona, Spain. Methods: Women aged from 30 to 70 years (n = 15,965) were asked to attend a general practice to be screened. They were randomly allocated to one of four groups: no intervention group (NIG); one group where women received an invitation letter to participate in the screening (IG1); one group where women received an invitation letter and informative leaflet (IG2); and one group where women received an invitation letter, an informative leaflet and a phone call reminder (IG3). Clinical effectiveness was measured as the percentage increase in screening coverage. A cost-effectiveness analysis was performed from the perspective of the public health system with a time horizon of three to five years - the duration of the randomised controlled clinical trial. In addition, a deterministic sensitivity analysis was performed. Results are presented according to different age groups. Results: The incremental cost-effectiveness ratio (ICER) for the most cost-effective intervention, IG1, compared with opportunistic screening was (sic)2.78 per 1% increase in the screening coverage. The age interval with the worst results in terms of efficiency was women aged < 40 years. Conclusions: In a population like Catalonia, with around 2 million women aged 30 to 70 years and assuming that 40% of these women were not attending general practice to be screened for cervical cancer, the implementation of an intervention to increase screening coverage which consists of sending a letter would cost on average less than (sic)490 for every 1000 women

Comprehensive Control of Human Papillomavirus Infections and Related Diseases

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread optimally universal implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. (C) 2013 Elsevier Ltd. All rights reserved