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Objectives: Cost-effectiveness analyses (CEAs) generally assume constant drug prices throughout the model time horizon, yet it is known that prices are not constant, often with price decreases near loss of exclusivity (LOE). This study explores the impact of using dynamic drug-specific prices on the incremental cost-effectiveness ratio (ICER) using selected reproduced case studies.Methods: Case studies were selected following explicit criteria to reflect a variety of drug characteristics. For each drug, a published CEA model was identified, replicated, and modified with dynamic real-world pricing data, to compare ICERs based on constant drug prices with estimates obtained when including drug life cycle pricing. The impact of dynamic real-world pricing—inclusive LOE—was analyzed using a single patient cohort and multiple cohorts over time.Results: Fluvastatin, alendronic acid + colecalciferol combination therapy, letrozole and clopidogrel were selected as case studies. Inclusion of real-world pricing data compared with applying constant prices reduced the ICER in a single-cohort setting up to 43%. In the multicohort analyses, further reductions of the ICERs were observed of up to 113%. The ICERs were sensitive to the period of drug usage relative to the models’ time horizons, the relative proportions of drug costs in the overall treatment costs, and timing of LOE compared with the cost year of the original analysis.Conclusions: Assuming dynamic drug prices may lead to more representative ICER estimates. Future CEAs for drugs could account for predicted and disaggregated life cycle price developments based on retrospective data.

Aim The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs). Methods and results A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32–5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21–4.74) in favour of tafamidis. Conclusion Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings. Clinical trials.gov identifier NCT01994889 (date of registration: 26 November 2013).

Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic delay and misdiagnosis in ATTR-CM. Methods The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed. Results Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34–57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic “red flags” were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences. Conclusion ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s40119-021-00219-5.

Introduction This study investigates the gender distribution in patients diagnosed with wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt). Methods A systematic review and meta-analysis of the male proportion in diagnosed ATTRwt patients were conducted. To avoid overlapping population, pooled estimates in the primary analysis were based on all unique studies. In secondary analyses, we considered predefined subsets of studies based on study sample size, recruitment years, geography, study design, age at diagnosis, and method of diagnosis. Additional meta-regression analyses were tested for potential determinants of gender distribution. Results Twenty-eight unique studies (2542 patients) were included in the meta-analysis. Male proportion in patients with ATTRwt was 86.9% (95% confidence interval 81.5–91.6%). Studies, including patients older than 80 years at diagnosis, had a 29.1% (p value

Introduction Widespread use of ten-valent (Synflorix™, GSK) or 13-valent (Prevenar 13™; Pfizer) conjugate vaccination programs has effectively reduced invasive pneumococcal disease (IPD) globally. However, IPD caused by serotypes not contained within the respective vaccines continues to increase, notably serotypes 3, 6A, and 19A in countries using lower-valent vaccines. Our objective was to estimate the clinical and economic benefit of replacing PCV10 with PCV13 in Colombia, Finland, and The Netherlands. Methods Country-specific databases, supplemented with published and unpublished data, informed the historical incidence of pneumococcal disease as well as direct and indirect medical costs. A decision-analytic forecasting model was applied, and both costs and outcomes were discounted. The observed invasive pneumococcal disease (IPD) trends from each country were used to forecast the future number of IPD cases given a PCV13 or PCV10 program. Results Over a 5-year time horizon, a switch to a PCV13 program was estimated to reduce overall IPD among 0–2 year olds by an incremental − 37.6% in Colombia, − 32.9% in Finland, and − 26% in The Netherlands, respectively, over PCV10. Adults > 65 years experienced a comparable incremental decrease in overall IPD in Colombia (− 32.2%), Finland (− 15%), and The Netherlands (− 3.7%). Serotypes 3, 6A, and 19A drove the incremental decrease in disease for PCV13 over PCV10 in both age groups. A PCV13 program was dominant in Colombia and Finland and cost-effective in The Netherlands at 1 × GDP per capita (€34,054/QALY). Conclusion In Colombia, Finland, and The Netherlands, countries with diverse epidemiologic and population distributions, switching from a PCV10 to PCV13 program would significantly reduce the burden of IPD in all three countries in as few as 5 years. Electronic supplementary material The online version of this article (10.1007/s40121-020-00287-5) contains supplementary material, which is available to authorized users.

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience infiltrative cardiomyopathy and heart failure symptoms requiring costly hospitalizations. The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) demonstrated the efficacy of tafamidis on the frequency of cardiovascular (CV)-related hospitalizations in patients with ATTR-CM.As length of stay can affect the total hospitalization burden, our study aimed to better understand the impact of tafamidis on the number of CV-related hospital days avoided in the management of ATTR-CM patients.Data from ATTR-ACT were used to calculate the total burden of CV-related hospitalization (days) by treatment arm in this post hoc analysis.In the total trial population, patients receiving tafamidis had significantly fewer CV-related hospitalizations per year (relative risk reduction [RRR] 0.68; 0.4750 vs. 0.7025, p0.0001) and a shorter mean length of stay per CV-related hospitalization event (8.6250 vs. 9.5625 days) than patients receiving placebo. Taken together, tafamidis prevented 2.62 CV-related hospitalization days per patient per year. A subgroup analysis showed that with earlier treatment initiation of tafamidis, the annual number of CV-related hospitalizations was significantly lowered by 52% compared with placebo (RRR 0.48; 0.3378 vs. 0.7091, p0.0001). With 1.14 fewer days per hospitalization, tafamidis reduced the annual number of CV-related hospitalization days by 3.96 days per New York Heart Association class I/II patient.In patients with ATTR-CM, tafamidis was associated with a lower rate of CV-related hospitalizations and shorter length of hospital stay. Timely diagnosis and treatment with tafamidis could further decrease the total number of CV-related hospitalization days per year.NCT01994889.

ObjectiveTransthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and fatal condition caused by deposition of transthyretin amyloid fibrils in the heart. This study aims to identify all patients diagnosed with ATTR-CM in Sweden, estimate the prevalence of ATTR-CM, describe patient characteristics and mortality, assess the importance of early symptoms (red flags) for identification of ATTR-CM, and compare with patients with heart failure (HF).MethodsThis retrospective study combined multiple national health registers covering all specialist visits and prescriptions for the entire population of Sweden. Between January 2008 and December 2018, patients with ATTR-CM were identified retrospectively based on a combination of diagnosis codes and compared with matched, all-cause non-ATTR HF patients.ResultsOverall, a total of 994 patients diagnosed with ATTR-CM were identified, with an average age at diagnosis of 73 years, and 30% of whom were female. The prevalence of diagnosed ATTR-CM cases in 2018 was 5.0 per 100 000. The median survival from diagnosis was 37.6 months (CI 33.8 to 43.8), with a lower median survival in women (27.9 months, CI 23.3 to 33.8) compared with men (43.5 months, CI 37.6 to 49.6). Patients with ATTR-CM demonstrated reduced survival compared with patients with HF (pConclusionsThis study provides the first nationwide estimates of ATTR-CM prevalence and risk factors. The results reinforce the severity of the disease and the importance of earlier diagnosis, especially for female patients, in order to allow effective treatment and prevention of disease progression.

Aim: Delayed diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) represents a missed opportunity for intervention. This study estimates the health benefits of timely diagnosis and treatment with tafamidis. Methods: A disease simulation model was developed to predict health outcomes under scenarios of timely and delayed diagnosis and treatment. Efficacy and quality of life (QoL) profiles were derived from the pivotal tafamidis trial and diagnostic delay durations from the literature. Results: Timely diagnosis and treatment were predicted to extend mean life expectancy by 5.46 and 7.76 years, relative to delayed diagnosis, for wild-type and hereditary ATTR-CM, respectively. Corresponding QALY gains were 4.50 and 6.22. Conclusion: Timely diagnosis and treatment with tafamidis are predicted to significantly improve survival and QoL for ATTR-CM patients.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Background: Currently literature on the impact of patent expiry on drug prices is lacking. Objective: To determine the impact of patent expiration and generic entry on drug prices in the Netherlands. Methods: Prescription and price data from 1999 up to and including December 2016 were collected from two national databases. The overall price ratio of drugs prices up to 48 months after patent expiration was compared to the price in the month before expiry. Sub-analyses were performed to provide insights in generic uptake, length of market exclusivity and price development for originators and generics separately. Results: In total 250 drugs faced patent expiration during the study period. Forty-eight months after patent expiration the median price ratio decreased to 0.59 (IQR = 0.23–0.86) compared to the month prior patent expiry. Major differences in price developments were observed depending on the level of revenue prior to patent expiration and the time of patent expiration with ratios ranging from 0.08 (IQR = 0.07–0.16) to 0.81 (IQR = 0.62–0.97). Prior to patent expiry, the price decreased by 2.3% annually while having market exclusivity for 11.3 years on average. Conclusion: This study showed that the median drug price after patent expiration decreased by 41% after 4 years. The results of this study can be used to provide more reliable estimates on drug prices over its lifecycle and can be implemented in economic evaluations to inform the cost-effectiveness and long-term budget impact of new drugs.

Carta al editor: Vondeling et al. Recientemente han publicado en Applied Health Economics and Health Policy (AHEHP) una revisión sistemática (SR) sobre el impacto de la caducidad de la patente en los precios de los medicamentos (original y genérico). La estrategia de búsqueda incluyó tres bases de datos: PubMed, EconLit y Google Scholar (GS). Al final del proceso de selección, el SR incluyó 16 publicaciones: Nueve para los EE. UU., Una para Canadá, los Países Bajos y España, respectivamente; y cuatro estudios para múltiples países de altos ingresos (HIC). A pesar de la amplitud de la estrategia de búsqueda y los rigurosos procedimientos aplicados a sus criterios de selección, los autores concluyeron que había una gran variabilidad en los métodos y resultados de los estudios primarios evaluados. Por lo tanto, es necesario llevar a cabo análisis específicos por país para comprender realmente el problema y mejorar los procesos de toma de decisiones a nivel de políticas de salud". To the Editor: Vondeling et al., recently have published in Applied Health Economics and Health Policy (AHEHP) a systematic review (SR) about the impact of patent expiry on drug prices (originator and generic). The search strategy included three databases: PubMed, EconLit and Google Scholar (GS). At the end of the selection process, the SR included 16 publications: Nine for the USA, one for Canada, the Netherlands, and Spain, respectively; and four studies for multiple high-income countries (HIC). Despite the wide breadth of the search strategy and the rigorous procedures applied for their selection criteria, the authors concluded that there was a very high variability in the methods and results of the primary studies evaluated. Thus, making it necessary to carry out separate country-specific analyses to really understand the problem and improve the decision-making processes at the health policy level

Background Historically, the prognosis of newly diagnosed patients with transthyretin amyloid cardiomyopathy (ATTR-CM) was poor with a median survival of only 2-6 years. The ATTR-ACT trial showed that tafamidis reduced all-cause mortality by 30.2% resulting in a hazard ratio (HR) of 0.70 [95% CI 0.51 to 0.96] compared to placebo by slowing disease progression. The aim of this study was to estimate the impact of tafamidis on mean survival and quality adjusted life years (QALY) using a disease simulation model. Methods A multi-state cohort Markov model was developed to simulate the disease course of ATTR-CM patients. In the model, patients were followed throughout a lifetime, and survival was stratified by prognostic NYHA I/II and NYHA III patient subgroups using individual patient-level data from both the ATTR-ACT and the long-term extension study to ATTR-ACT. Based on the patients’ distribution in the ATTRACT trial, the total patient cohort entering the model was comprised of 68% in NYHA class I/II and 32% in NYHA class III. Technical best practices were followed to extrapolate survival. Given that the proportional hazard assumption was violated, curves were fitted by treatment arm and by subgroup. The base case parametric distributions selected were Gompertz for NYHA class I/II and Weibull for NYHA class III, based on statistical tests of fit and clinical plausibility of the extrapolations. Utility values for the health states were derived from ATTR-ACT EQ-5D-3L using US tariffs. The outcomes were mean and incremental mean survival and QALYs. Univariate deterministic and multivariate probabilistic sensitivity analyses were conducted. Analyses were conducted for each NYHA class and weighted results presented. Results The overall predicted mean survival for the total population in the simulated patient cohort was 7.01 for tafamidis and 2.82 years for placebo, resulting in an incremental mean survival of 4.19 years [95% CI 1.32 to 5.55]. The corresponding QALYs were 5.64 and 2.09 respectively, resulting in 3.54 incremental QALYs [95% CI 1.20 to 4.72] in favor of tafamidis. The results were sensitive to parametric distributions selected for both placebo and tafamidis. Conclusions Based on the results of the disease simulation model, tafamidis is expected to increase the life expectancy and QALYs of ATTR-CM patients by 4.19 years and 3.54 QALYs, respectively. Longer term follow-up data from the ATTR-ACT extension study will further inform these findings when available.

Background The aim of this study was to estimate the total economic and health related burden of breast cancer in the Netherlands. Methods Data on incidence, prevalence, mortality and survival were extracted from the Dutch National Cancer Registry and were used to calculate the economic and health related burden of breast cancer for overall, DCIS (stage 0), early- (stage I), locally advanced- (stage II-III) and metastatic- (stage IV) breast cancer by age groups and by year (if applicable). Results The overall incidence of breast cancer increased from 103.4 up to 153.2 per 100,000 women between 1990 and 2014. The increase was driven by DCIS and early breast cancer as the incidence of locally advanced and metastatic breast cancer remained stable. Between 1990 and 2014, ten-year overall survival rates increased from 87% to 93% for early breast cancer, 41% to 62% for locally advanced- and from 6% to 9% for metastatic disease. Annually, breast cancer in the Netherlands is responsible for approximately 3100 deaths, 26,000 life years lost, 65,000 Disability Adjusted Life Years (DALYs) and an economic burden of €1.27 billion. Conclusions This study provides a comprehensive assessment of the burden of breast cancer and subsequent trends over time in the Netherlands. Electronic supplementary material The online version of this article (10.1186/s12885-018-4158-3) contains supplementary material, which is available to authorized users.

The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands. Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65–74 years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted. The ICER for base-case was €8650 per QALY (95% CI 5750–17 100). Vaccination of high-risk individuals aged 65–74 years was cost-saving and extension to medium-risk individuals aged 65–74 years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ≥18 years yielded an ICER of €3100. PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries., Vaccinating the elderly with 13-valent pneumococcal conjugate vaccine is highly cost-effective http://ow.ly/NVeui

Background Streptococcus pneumoniae causes significant morbidity and mortality among adults, especially among the elderly and those with underlying medical conditions. To reduce the disease burden the Health Council of the Netherlands recently recommended that people aged 60 and over should be offered vaccination against pneumococcal infections with the vaccine 23 valent polysaccharide vaccine (PPV23). This study aimed to evaluate the cost-effectiveness vaccinating people aged 60 with PPV23 compared with sequential vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) followed by vaccination with PPV23. Methods A previously published microsimulation model was used to compare the cost-effectiveness of PPV23 vaccination vs. sequential PCV13-PPV23 vaccination by age and risk group. PPV23 effectiveness was based on published literature, PCV13 effectiveness was based on CAPiTA; all other model parameters were based on published data. Outcomes and costs were evaluated assuming use of PPV23 alone, and alternatively, use of PCV13 → PPV23 among all adults aged 60 years and those at with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) aged 60 years. Results Vaccinating individuals aged 60 years with PCV13 followed by vaccination with PPV23 would prevent 215 cases of IPD, 360 cases of hospitalized pneumonia, and 2,200 cases of outpatient pneumonia cases per vaccinated cohort compared with vaccination with PPV23 alone. At list price (€68.56 for PCV13 and €19.99 for PPV23) the ICER of vaccinating all adults of 60 years of age resulted in an ICER of €5,000/QALY. Adding a single dose of PCV13 for those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) was shown to be cost saving compared with vaccination with PPV23 alone. Sensitivity analysis showed that a proportional decrease in list price decreased the ICER disproportionally in favor of adding a single dose of PCV13. Conclusion Expanding the recommendation of only PPV23 to PCV13→PPV23 among Dutch adults aged 60 years and older is a cost-effective use of healthcare resources. In particular adding a single dose of PCV13 for those with moderate or high risk of pneumococcal disease was shown to be cost-saving. Disclosures M. Rozenbaum, Pfizer: Employee and Shareholder, Salary.

The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.

Despite childhood vaccination programs, pertussis remains endemic. To reduce the burden of pertussis, various extended pertussis vaccination strategies have been suggested. The aim of this article is to evaluate dynamic models used to assess the cost-effectiveness of vaccination. In total, 16 studies using a dynamic model were included, of which four also studied the cost-effectiveness of extended pertussis vaccination strategies. Generally, adolescent vaccination was found to be cost effective, but not highly effective in protecting infants too young to be vaccinated. The models also predicted that owing to age shifts, reduced pertussis disease in adolescents and young adults comes with an increase in later stages of life. This underpins the use of dynamic transmission models for interventions directed against pertussis. In future, dynamic transmission models for pertussis should be used widely to further enhance understanding of pertussis epidemiology and of extended pertussis vaccination programs that are currently considered in various countries.

Introduction: Respiratory syncytial virus (RSV) infection is one of the major causes of respiratory illness in infants, infecting virtually every child before the age of 2 years. Currently, several Phase 1 trials with RSV vaccines in infants are ongoing or have been completed. As yet, no efficacy estimates are available for these vaccine candidates. Nevertheless, cost-effectiveness estimates might be informative to enable preliminary positioning of an RSV vaccine.Methods: A decision analysis model was developed in which a Dutch birth cohort was followed for 12 months. A number of potential vaccination strategies were reviewed such as vaccination at specific ages, a two- or three-dosing scheme and seasonal vaccination versus year-round vaccination. The impact of the assumptions made was explored in various sensitivity analyses, including probabilistic analysis. Outcome measures included the number of GP visits, hospitalizations and deaths, costs, quality-adjusted life years and incremental cost-effectiveness ratios (ICERs).Results: Currently, without vaccination, an annual number of 28,738 of RSV-related GP visits, 1623 hospitalizations, and 4.5 deaths are estimated in children in the age of 0-1 year. The total annual cost to society of RSV in the non-vaccination scenario is (sic)7.7 million (95%CI: 1.7-16.7) and the annual disease burden is estimated at 597 QALYs (95%CI: 133-1319). In case all infants would be offered a potentially safe and effective 3-dose RSV vaccination scheme at the age of 0, 1 and 3 months, the total annual net costs were estimated to increase to (sic)21.2 million, but 544 hospitalizations and 1.5 deaths would be averted. The ICER was estimated at (sic)34,142 (95%CI: (sic) 21,652-(sic) 87,766) per QALY gained. A reduced dose schedule, seasonal vaccination, and consideration of out-of-pocket expenses all resulted in more favorable ICER values, whereas a reduced vaccine efficacy or a delay in the timing of vaccination resulted in less favorable ICERs.Discussion: Our model used recently updated estimates on the burden of RSV disease in children and it included plausible utilities. However, due to the absence of clinical trial data, a number of crucial assumptions had to be made related to the characteristics of potential RSV vaccine. The outcomes of our modeling exercise show that vaccination of infants against RSV might be cost-effective. However, clinical trial data are warranted. (C) 2012 Elsevier Ltd. All rights reserved.

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

Introduction. Cervical cancer is caused by infection with human papillomavirus (HPV). Several countries have implemented vaccination programs against HPV for teenage girls before sexual debut. However, recent clinical trials have demonstrated that vaccination of older women is highly effective as well. Accordingly, it has been suggested that these older women should also be offered vaccination. Here, the cost-effectiveness of HPV vaccination for older women was assessed.Methods. A Markov model was used to estimate age-specific health benefits and cost savings of HPV vaccination for women 12-50 years of age, in the Netherlands. Sensitivity analyses were performed to test the robustness of the outcomes. State-of-the-art health-economic methods were used, and international health-economic guidelines were followed.Results. HPV vaccination is highly cost-effective for girls aged 12-16 years. Remarkably, cost-effectiveness only slowly declines with increasing age of the vaccinees up to 25 years. Indeed, substantial health benefits can be obtained by vaccinating women in this age group at acceptable costs. Beyond this age, cost-effectiveness of HPV-vaccination rapidly declines.Conclusions. Not only HPV vaccination of girls before sexual debut is a highly effective and cost-effective strategy for prevention of cervical cancer, but also vaccination of women until the age of 25 years is generally cost-effective.

Healthcare decisions on vaccination programs mainly rely on the direct burden of illness and related costs of the disease. Next to the expected direct beneficial effect of pediatric immunization programs against Streptococcus pneumoniae, worldwide implementation of these programs has also been driven by the indirect beneficial impact as observed among various nontargeted age groups in Northern America. In this article, we provide a descriptive overview of the post-marketing surveillance and show that there are large differences in the observed disease epidemiology after implementation of pediatric pneumococcal immunization programs across countries. Possible factors responsible for these differences may include vaccine-serotype coverage, implemented vaccination schedules, antibiotic resistance rates and pneumococcal disease incidence prior to vaccination. A potential limitation can be found in the installation or enhancement of existing surveillance systems as well as other potential confounding bias, which may have influenced observed disease rates in the included observational studies. We conclude that the health and economic impact should be addressed in light of the country specific pneumoccocal disease epidemiology to support decisions on immunization programs.

Background There is currently no data on the age- and risk-group-specific cost-effectiveness of the 13 valent pneumococcal vaccine (PCV13) compared with the 23 valent polysaccharide vaccine (PPV23). The aim of this study was to evaluate the cost-effectiveness of vaccinating these specific groups against pneumococcal disease. Methods A previously published and independently validated (by The Dutch National Health-Care Institute) age-and risk-group-specific Markov-type model was used to compare the cost-effectiveness of PCV13 vaccination vs. PPV23 vaccination of all adults at increased risk of pneumococcal disease (i.e., adults with underlying disease and those ≥50 years). Efficacy estimates for PCV13 were extrapolated from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Efficacy estimates for PPV23 were based on systematic literature reviews and other published data. Results At list price (€68.56 for PCV13 and €19.99 for PPV23), vaccination of all adults at increased risk of pneumococcal disease resulted in an ICER of €20,186/QALY, while vaccinating those with chronic medical conditions (moderate risk) and immunocompromising conditions (high risk) resulted in an ICER of

Background: Community-acquired pneumonia and invasive pneumococcal disease are common among older people (ie, those aged >= 65 years). A new 13-valent pneumococcal conjugate vaccine (PCV-13) is under study in the Netherlands.Objective: The aim of this work was to model the cost-effectiveness of PCV-13 vaccination among those aged >= 65 years in the Netherlands, both in the total population and in those at increased risk for pneumonia, for various levels of efficacy (30%-90%) assumed.Methods: Our previously published cost-effectiveness model was updated to include age-specific epidemiologic data and health-care utilization and costs for a hypothetical cohort of adults aged >= 65 years in the Netherlands. This cohort was followed twice-once as unvaccinated and once as vaccinated-over a time period of 5 years, with differences between both analyses reported. Outcome measures included costs, life-years gained (LYGs), quality-adjusted life-years, and incremental cost-effectiveness ratios (ICERs). All analyses were performed from a societal perspective.Results: In the model, the ICER for vaccination remained below (sic)80,000/LYG, except when the vaccine was assumed to protect only against bacteremic pneumonia, with a relatively low effectiveness (40%) in combination with a high vaccine price ((sic)65), and indirect effects of serotype replacement would largely offset the direct effect of vaccination. For various assumptions, introduction of widespread PCV-13 vaccination (assuming a 60% efficacy against invasive and noninvasive disease because of vaccine serotypes, and a cost of (sic)50 per vaccinated person) was associated with the ICERs varying from cost-saving to (sic)50,676/LYG.Conclusions: In this model analysis of a hypothetical cohort in the Netherlands, vaccination with PCV-13 might be considered cost-effective, both for the total population and for the high-risk population aged >= 65 years, from a societal perspective, over a 5-year time horizon. The main limitation of this study was uncertainty regarding how great a proportion of pneumonia could be attributed to pneumococcal disease. (Clin Ther. 2010;32:1517-1532) (C) 2010 Excerpta Medica Inc.

Varicella is one of the most common infectious diseases in childhood, caused by the varicella zoster virus. Although vaccines are available, there are only a few countries with an early-childhood vaccination program. Most countries mainly focus on vaccination of high-risk groups, such as susceptible healthcare workers. One of the main concerns with a routine early-childhood vaccination program is a potential (temporal) increase of the incidence of herpes zoster among elderly adults. In this review, we focus on the cost-effectiveness of varicella vaccination and on the methodology used in the health-economic studies. In particular, we focus on the perspective adopted, type of model used, the modeled effect on herpes zoster, the vaccine efficacy and price, and on the value of time lost by infection. The vast majority of studies show vaccination of high-risk groups - including susceptible adolescents - to be cost saving. Routine early-childhood vaccination programs are always cost saving if indirect costs of production losses are included, or cost effective, as long as the potential negative effects on zoster are not taken into account. We note that most studies included in the review used old vaccine prices and a single dose of the varicella vaccine, whereas multiple doses are now becoming the standard. Despite that, those aspects limit the timeliness of our review and we believe that the current work does provide useful insights in the cost-effectiveness of varicella vaccination.

Background: Community-acquired pneumonia (CAP) is one of the most common acute infections associated with a substantial clinical and economic burden. There have been few studies assessing incidence rate, duration of hospitalization, and costs of hospitalized CAP by age and care-setting.Methods: A retrospective study was conducted using a nationwide Dutch database containing healthcare claims data of 16.7 million inhabitants. Patients with at least one claim with a discharge diagnosis of CAP between January 2008 and December 2011 were selected. The main outcome measures considered were the incidence rate, duration of hospitalization, and the direct costs of hospitalized CAP stratified by age and care-setting.Results: In total, 195,372 CAP cases were included in the analysis resulting in an average incidence of 295 per 100,000 population per year. Sixty-three percent (123,357) of the included patients were hospitalized for 1 or more nights, of which 5.9% (n=7241) spent at least one night in the Intensive Care Unit (ICU). Overall, these 123,357 patients spent 824,985 days in the hospital of which 48,324 were spent on the ICU. The mean duration of hospitalization of ICU patients and general ward patients was 15.2 days and 6.2 days, respectively. The total costs related to all 195,372 CAP episodes during these 4 years were (sic)711 million, with the majority (76%) occurring among those aged 50 years and older. Median (and mean) costs were dependent on age and type of care with costs ranging from (sic)344 ((sic)482) per episode for 0-9 year olds treated in the outpatient hospital setting up to (sic)10,284 ((sic)16,374) per episode for 50-64 year olds admitted to the ICU.Conclusion: There is a large variation in terms of incidence, disease burden and costs across different age groups and the treatment setting. Effective interventions, targeted at older adults, to prevent pneumonia could reduce the (financial) burden due to pneumonia. (C) 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BackgroundStroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.ObjectiveTo estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands.MethodsPreviously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER).ResultsTreatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust.ConclusionsIn patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.

Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar (R)) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups of 5 years of age and older with updated assumptions regarding epidemiologic data and health care unit costs. Without net-indirect benefits for non-vaccine protected groups included the cost-effectiveness ratio is estimated at (sic)72,360 per QALY. In order to obtain cost-effectiveness ratios below the threshold of (sic)50,000 per QALY - which is in the middle of the range that is often referred to in the Netherlands - the net-indirect protective effect should at least be 16% of which has been observed in the USA after the introduction of PCV-7. (C) 2010 Elsevier Ltd. All rights reserved.