COST-EFFECTIVENESS OF TREATMENTS FOR MILD-TO-MODERATE OBSTRUCTIVE SLEEP APNEA IN FRANCE.

OBJECTIVES: Untreated obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with excessive daytime sleepiness, increased risk of cardiovascular (CV) disease, and road traffic accidents (RTAs), which impact survival and health-related quality of life. This study, funded by the French National Authority for Health (HAS), aimed to assess the cost-effectiveness of different treatments (i.e., continuous positive airway pressure [CPAP], dental devices, lifestyle advice, and no treatment) in patients with mild-to-moderate OSAHS in France. METHODS: A Markov model was developed to simulate the progression of two cohorts, stratified by CV risk, over a lifetime horizon. Daytime sleepiness and RTAs were taken into account for all patients while CV events were only considered for patients with high CV risk. RESULTS: For patients with low CV risk, incremental cost-effectiveness ratio (ICER) of dental devices versus no treatment varied between 32,976 EUR (moderate OSAHS) and 45,579 EUR (mild OSAHS) per quality-adjusted life-year (QALY), and CPAP versus dental devices, above 256,000 EUR/QALY. For patients with high CV risk, CPAP was associated with a gain of 0.62 QALY compared with no treatment, resulting in an ICER of 10,128 EUR/QALY. CONCLUSION: The analysis suggests that it is efficient to treat all OSAHS patients with high CV risk with CPAP and that dental devices are more efficient than CPAP for mild-to-moderate OSAHS with low CV risk. However, out-of-pocket costs are currently much higher for dental devices than for CPAP (i.e., 3,326 EUR versus 2,430 EUR) as orthodontic treatment is mainly non-refundable in France.

Long-term clinical impact of introducing a human papillomavirus 16/18 AS04 adjuvant cervical cancer vaccine in Spain.

BACKGROUND: Human papillomavirus (HPV) epidemiology and screening practices vary considerably between countries and specific analyses are required to estimate the impact of HPV vaccination. This study aimed to predict the clinical benefits of introducing a bivalent HPV16/18 vaccine in Spain, where the cervical cancer (CC) incidence is 10.3 per 100 000. METHODS: A Markov model based upon the natural history of HPV and CC was developed to simulate transitions between health states, in the presence of specific screening programmes. Published data were used to reflect the Spanish situation in terms of epidemiological characteristics, screening and treatment practices. Calibration consisted of varying disease progression rates within established ranges until model predictions matched observed epidemiological data. The clinical impact of vaccinating a cohort of 12-year-old girls against HPV was assessed over their lifetime using the calibrated model. RESULTS: Vaccination of all 12-year-old girls would result in a reduction of 75% (from 0.32% to 0.08%) in the prevalence of high-grade precancerous lesions due to oncogenic HPV, and a 79% reduction in both CC cases (from 1745 to 365) and CC deaths (from 417 to 86). Assuming a vaccine coverage of 80%, the number of CC cases and deaths would decrease by 63%. Vaccination could also substantially reduce the number of screening tests and treatments required for cervical dysplasia. CONCLUSION: Our model was successfully adapted to the Spanish epidemiological environment, screening and treatment practices and predicted a substantial long-term benefit of HPV vaccination despite a low HPV prevalence in Spain.

A new paradigm evaluating cost per cure of HCV infection in the UK.

BACKGROUND: New interferon (IFN)-free treatments for hepatitis C are more effective, safer but more expensive than current IFN-based therapies. Comparative data of these, versus current first generation protease inhibitors (PI) with regard to costs and treatment outcomes are needed. We investigated the real-world effectiveness, safety and cost per cure of 1st generation PI-based therapies in the UK. METHODS: Medical records review of patients within the HCV Research UK database. Patients had received treatment with telaprevir or boceprevir and pegylated interferon and ribavirin (PR). Data on treatment outcome, healthcare utilisation and adverse events (AEs) requiring intervention were collected and analysed overall and by subgroups. Costs of visits, tests, therapies, adverse events and hospitalisations were estimated at the patient level. Total cost per cure was calculated as total median cost divided by SVR rate. RESULTS: 154 patients from 35 centres were analysed. Overall median total cost per cure was £44,852 (subgroup range,: £35,492 to £107,288). Total treatment costs were accounted for by PI: 68.3 %, PR: 26.3 %, AE management: 5.4 %. Overall SVR was 62.3 % (range 25 % to 86.2 %). 36 % of patients experienced treatment-related AEs requiring intervention, 10 % required treatment-related hospitalisation. CONCLUSIONS: This is the first UK multicentre study of outcomes and costs of PI-based HCV treatments in clinical practice. There was substantial variation in total cost per cure among patient subgroups and high rates of treatment-related discontinuations, AEs and hospitalisations. Real world safety, effectiveness and total cost per cure for the new IFN free combinations should be compared against this baseline.

A comparative public health and budget impact analysis of pneumococcal vaccines: The French case.

In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years. A previously published population-based Markov model was adapted to the French situation. At-risk adults received either PPV23 (pneumococcal polysaccharide vaccine; for the immunocompetent) or PCV13 (for the immunosuppressed). The strategy was compared to PCV13 alone. Uncertainty was addressed using extreme scenario analyses. Between 2014 and 2018, vaccination with PPV23/PCV13 led to a higher reduction in terms of IPD and non-bacteremic pneumococcal pneumonia cases avoided in most scenarios analyzed when compared to PCV13 alone. For budget impact, none of the scenarios was in favor of PCV13. Under conservative coverage assumptions, the total incremental budget impact ranged from € 39.8 million to € 69.3 million if PCV13 were to replace PPV23 in the immunocompetent. With the epidemiological changes of pneumococcal diseases and the broader serotype coverage of PPV23, the current program remains an optimal strategy from public health perspective. Given the additional budget required for the use of PCV13 alone and its uncertain public health benefits, vaccination with PPV23 remains the preferred strategy.

Cost-effectiveness of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

OBJECTIVE: The introduction of routine childhood vaccination with pneumococcal conjugate vaccines (PCVs) has led to a decrease in the overall incidence of pneumococcal disease in all ages and a change in the serotype distribution of the remaining disease. This study assessed the cost-effectiveness of vaccinating ≥65 years and at risk adults with either the 23-valent pneumococcal polysaccharide vaccine (PPV23) or the 13-valent conjugate vaccine (PCV13) in the UK, accounting for epidemiological changes. METHODS: A population-based Markov model was used to track one UK-based cohort of individuals assuming PPV23, PCV13 or no vaccination until death. RESULTS: The ICER was estimated at £8413 when PPV23 was compared to no vaccination. PPV23 dominated PCV13. CONCLUSION: This model suggests that vaccinating with PPV23 is cost-effective when compared to both PCV13 and no vaccination. As PPV23 covers 80-90% in the UK of all serotypes causing invasive pneumococcal diseases, it remains cost-effective despite recent reductions in invasive pneumococcal diseases incidence in adults.

A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

OBJECTIVE: Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. METHODS: The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. RESULTS: Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). CONCLUSION: PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.

Herpes zoster as a risk factor for stroke and TIA: a retrospective cohort study in the UK.

OBJECTIVES: Stroke and TIA are recognized complications of acute herpes zoster (HZ). In this study, we evaluated HZ as a risk factor for cerebrovascular disease (stroke and TIA) and myocardial infarction (MI) in a UK population cohort. METHODS: A retrospective cohort of 106,601 HZ cases and 213,202 controls matched for age, sex, and general practice was identified from the THIN (The Health Improvement Network) general practice database. Cox proportional hazard models were used to examine the risks of stroke, TIA, and MI in cases and controls, adjusted for vascular risk factors, including body mass index >30 kg/m(2), smoking, cholesterol >6.2 mmol/L, hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent arterial claudication, carotid stenosis, and valvular heart disease, up to 24 years (median 6.3 years) after HZ occurrence. RESULTS: Risk factors for vascular disease were significantly increased in cases of HZ compared with controls. Adjusted hazard ratios (AHRs) for TIA and MI but not stroke were increased in all patients with HZ (AHR [95% confidence interval]: 1.15 [1.09-1.21] and 1.10 [1.05-1.16], respectively). However, stroke, TIA, and MI were increased in cases whose HZ occurred when they were younger than 40 years (AHR [95% confidence interval]: 1.74 [1.13-2.66], 2.42 [1.34-4.36], 1.49 [1.04-2.15], respectively). Subjects younger than 40 years were significantly less likely to be asked about vascular risk factors than were older patients (p < 0.001). CONCLUSION: HZ is an independent risk factor for vascular disease in the UK population, particularly for stroke, TIA, and MI in subjects affected before the age of 40 years. In older subjects, better ascertainment of vascular risk factors and earlier intervention may explain the reduction in risk of stroke after the occurrence of HZ.

Cost-effectiveness analysis of pharmaceutical treatment options in the first-line management of major depressive disorder in Belgium.

OBJECTIVE: The objective of this study was to assess the cost effectiveness of commonly used antidepressants as first-line treatment of major depressive disorder (MDD) in Belgium. METHODS: The model structure was based on a decision tree developed by the Swedish TLV (Tandvårds- och läkemedelsförmånsverket) and adapted to the Belgium healthcare setting, using primary local data on the patterns of treatment and following KCE [Federal Knowledge Center (Federaal Kenniscentrum voor de Gezondheidszorg)] recommendations. Comparators were escitalopram, citalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, and mirtazapine. In the model, patients not achieving remission or relapsing after remission on the assessed treatment moved to a second therapeutic step (titration, switch, add-on, or transfer to a specialist). In case of failure in the second step or following a suicide attempt, patients were assumed to be referred to secondary care. The time horizon was 1 year and the analysis was conducted from the National Institute for Health and Disability Insurance (NIHDI; national health insurance) and societal perspectives. Remission rates were obtained from the TLV network meta-analysis and risk of relapse, efficacy following therapeutic change, risk of suicide attempts and related death, utilities, costs (2012), and resources were derived from the published literature and expert opinion. The effect of uncertainty in model parameters was estimated through scenario analyses and a probabilistic sensitivity analysis (PSA). RESULTS: In the base-case analysis, escitalopram was identified as the optimal strategy: it dominated all other treatments except venlafaxine from the NIHDI perspective, against which it was cost effective with an incremental cost-effectiveness ratio of 6,352 per quality-adjusted life-year (QALY). Escitalopram also dominated all other treatments from the societal perspective. At a threshold of 30,000 per QALY and from the NIHDI perspective, the PSA showed that the probability of escitalopram being identified as the optimal strategy ranged from 61 % (vs. venlafaxine) to 100 % (vs. fluoxetine). CONCLUSION: Escitalopram was associated with the highest probability of being the optimal treatment from the NIHDI and societal perspectives. This analysis, based on new Belgian clinical practice data and following KCE requirements, provides additional information that may be used to guide the choice of treatments in the management of MDD in Belgium.

Vaccination against herpes zoster and postherpetic neuralgia in France: a cost-effectiveness analysis.

This study assesses the cost-effectiveness of vaccination against herpes zoster (HZ) and postherpetic neuralgia in France, using a published Markov model. The cost-effectiveness of vaccinating individuals aged from 65 years or between 70 and 79 years was evaluated over their lifetime, from a third-party payer perspective. French-specific data were combined with results from clinical studies and international quality-of-life-based (EuroQol five-dimension questionnaire) utilities from the literature. HZ vaccination was highly cost effective in both populations. Incremental cost-effective ratios were estimated between €9513 and 12,304 per quality-adjusted life year gained, corresponding to €2240-2651 per HZ case avoided and €3539-4395 per postherpetic neuralgia case avoided. In addition to epidemiological and clinical evidence, economic evidence also supports the implementation of HZ vaccination in France.

A critical review of cost-effectiveness analyses of vaccinating males against human papillomavirus.

A critical review of cost-effectiveness analyses of HPV vaccination in males was conducted and nine studies were identified in different countries. Due to the heterogeneity among these studies in terms of modeling approach, vaccination strategies, health outcomes considered, assumptions and parameters, limited conclusions can be drawn with regard to the absolute cost-effectiveness. Nevertheless, key drivers were identified. More favorable cost-effectiveness appeared when all HPV-related diseases outcomes were considered, a suboptimal vaccine coverage among girls and/or lower vaccine prices were assumed. There was a general lack of transparency to fully describe the details of the methodological approach of modeling and calibration. Further research should be conducted to generate robust evidence-based data sets (HPV-related diseases epidemiology, costs and quality of life). The best modeling practice for HPV vaccination and how to better capture the true economic value of vaccination beyond cost-effectiveness in a broader policy context need to be investigated.

Cost-effectiveness of vaccinating adults with the 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany.

The introduction of routine infant vaccination against pneumococcal disease has resulted in a decreased overall invasive pneumococcal disease incidence in adults but also a change in invasive pneumococcal disease serotypes. This study aimed to assess the cost-effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) in Germany in this context. A population-based Markov model was developed. A cohort of adults currently eligible for vaccination was followed until death. Adult vaccination with PPV23 was associated with an incremental cost-effectiveness ratio of €17,065/quality-adjusted life years gained from the third-party payer's perspective. Univariate sensitivity analyses showed that the incremental cost-effectiveness ratio was below €50,000/quality-adjusted life years gained in most test scenarios. The model suggests that adult PPV23 vaccination is cost effective in Germany, due to its broad serotype coverage. This is despite epidemiological changes in Streptococcus pneumoniae serotypes caused by wider use of pneumococcal conjugate vaccines during childhood.

A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany.

To assess the comparative public health and budget impact over 5 years of several pneumococcal vaccination strategies (23-valent pneumococcal polysaccharide vaccine [PPV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]) in Germany, within the context of changing invasive pneumococcal disease (IPD) incidence over time. A multi-cohort, population-based Markov model was developed. Uncertainty around vaccine effectiveness, costs and IPD incidence change was handled through scenario analyses. Between 2012 and 2016, the introduction of PCV13 in adults, compared with the use of PPV23, would be associated with a net estimated budget increase of €59.7 million (+6.7%) to €151.6 million (+13.7%). Impact on IPD incidence ranged from -113 cases (-0.8%) to +298 cases (+2.8%). Introducing PCV13 in adults is expected to significantly affect healthcare budgets. Adult vaccination with PPV23 remains the optimal vaccination strategy from public health and budget perspectives.

Epidemiological burden of postmenopausal osteoporosis in the UK from 2010 to 2021: estimations from a disease model.

UNLABELLED: This article describes the adaptation of a model estimating the burden of postmenopausal osteoporosis (PMO) to the UK. PURPOSE: The purpose of this study was to estimate the present and future epidemiology of PMO in the UK. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures and death. Fracture by site was tracked for each health state. Transition probabilities reflected fracture site-specific risk of death and subsequent fractures. RESULTS: Assuming that the rate of incident fractures by age is constant over time, the model estimated the total number of PMO fractures at 224,219 in 2010, including 51,927 hip and 30,994 clinical vertebral fractures. These estimates were predicted to increase by 17.2%, 16.6% and 17.9%, respectively, by 2020. The number of postmenopausal women living with osteoporosis was predicted to increase from 1.8 million in 2010 to 2.1 million in 2020 (+16.5%). A sensitivity analysis demonstrated that the estimated number of fractures is most sensitive to the assumption made on the trends in the rate of incidence. CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to the UK. Due to demographic changes, the burden of osteoporosis is expected to increase by almost a fifth by 2020. Due to the lack of country-specific data, these results rely on several assumptions regarding the incidence of non-hip fractures, trends in BMD and rate of incidence over time.

Bayesian modelling of healthcare resource use in multinational randomized clinical trials.

BACKGROUND: Most cost-effectiveness analyses conducted alongside multinational randomized clinical trials (RCT) are carried out applying the unit costs from the country of interest to trial-wide resource use items with the objective of estimating total healthcare costs by treatment group. However, this approach could confound 'price effects' with 'country effects'. An alternative approach is to use multilevel modelling techniques to analyse healthcare resource use (HCRU) from the trial, and obtain country-specific total costs by applying country-specific unit costs to corresponding shrinkage estimates of differential HCRU. METHODS: To illustrate the feasibility of this approach, we analysed data from twin multinational RCTs, which enrolled approximately 2000 individuals into three treatment arms for the management of patients with chronic respiratory disease. The models were implemented using Bayesian multilevel models, to reflect the hierarchical structure of the data while controlling for co-variates at the patient and country level. RESULTS: This analysis showed that directly modelling the level of HCRU is a promising approach to facilitate cost-effectiveness analyses conducted alongside multinational RCTs, offering several advantages compared with the modelling of direct costs. CONCLUSIONS: It is argued that modelling the level of HCRU within the Bayesian framework avoids confounding the price effects with the country effects and facilitates the estimation of costs for several countries represented in the trial.