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Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden. Methods and results: Transthyretin amyloid cardiomyopathy patients were identified during 2008–2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non-ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR-CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR-CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR-CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR-CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort. Conclusions: This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR-CM, two-fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is the cardiac manifestation of transthyretin amyloidosis (ATTR). The aim of this study was to estimate healthcare resource use for ATTR-CM patients compared with heart failure (HF) patients, in Denmark, Finland, Norway, and Sweden. Methods and results: Data from nationwide healthcare registers in the four countries were used. ATTR-CM patients were defined as individuals diagnosed with amyloidosis and cardiomyopathy or HF between 2008 and 2018. Patients in the ATTR-CM cohort were matched to patients with HF but without ATTR-CM diagnosis. Resource use included number of visits to specialty outpatient and inpatient hospital care. A total of 1831 ATTR-CM and 1831 HF patients were included in the analysis. The mean number of hospital-based healthcare contacts increased in both the ATTR-CM and HF cohort during 3 years pre-diagnosis and was consistently higher for the ATTR-CM cohort compared with the HF cohort, with 6.1 [CI: 5.9–6.3] vs. 3.2 [CI: 3.1–3.3] outpatient visits and 1.03 [CI: 0.96–1.1] vs. 0.7 [CI: 0.7–0.8] hospitalizations. In the first year following diagnosis, patients with ATTR-CM continued to visit outpatient care (10.2 [CI: 10.1, 10.4] vs. 5.7 [CI: 5.6, 5.9]) and were admitted to hospital more frequently (3.3 [CI: 3.2, 3.4] vs. 2.5 [CI: 2.5, 2.6]) than HF patients. Conclusions: Transthyretin amyloid cardiomyopathy imposes a high burden on healthcare systems with twice as many outpatient specialist visits and 50% more hospitalizations in the year after diagnosis compared with HF patients without ATTR-CM. Studies to investigate if earlier diagnosis and treatment of ATTR-CM may lower resource use are warranted.

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).

Conventional cost-effectiveness analysis—i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework—originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward.

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.

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.

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.

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

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

OBJECTIVES: Community-acquired pneumococcal pneumonia is an important cause of hospitalization and death among adults, but figures on the prevalence of Streptococcus pneumoniae largely vary. We aimed to identify the prevalence of Streptococcus pneumoniae by systematically reviewing all available etiological studies of adult patients with community-acquired pneumonia (CAP) over the period January 1990- November 2011 across European countries. METHODS: Two reviewers conducted a systematic literature search using PubMed of English-language articles on the prevalence of adult CAP caused by S. Pneumoniae and manually reviewed the article bibliographies. A mixed-effects meta-regression model was developed and populated with 24,236 patients obtained from 79 articles that met in- and exclusion criteria. The meta-regression was adjusted for country and region characteristics as well as other possible independent covariates. RESULTS: The findings from the mixed-effects meta-regression model indicate that the observed prevalence of S. pneumoniae in CAP significantly differs between European regions even after adjusting for various covariates including patient characteristics, diagnostic tests, antibiotic resistance and health-care setting. Performing a diagnostic PCR assay increased the probability of detecting S. pneumoniae substantially, compared to all other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in cases treated in the ICU as compared to those treated in the hospital or in the community. CONCLUSIONS: This study provides estimates of the prevalence of S. Pneumoniae in CAP, independent of study design, or other risk factors, which could be used for predictions of the health and economic impact of adult pneumococcal vaccination.

Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine.Design Economic evaluation using a cohort model from the perspective of healthcare providers.Setting England.Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes.Main outcome measures Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios.Results Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions-that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme-the incremental cost effectiveness ratio was estimated to be more than 30 pound 000 ((sic)37 216; $48 210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates.Conclusion Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.

The aim of the current study is to estimate the epidemiological and economical consequences of several extended pertussis booster vaccination strategies and to explore the impact of parameters surrounded by large uncertainty on the cost-effectiveness. We developed an age structured transmission dynamic model to evaluate the impact of programs targeting (i) adolescents or adults using a single booster dose, (ii) a combination of adolescent and adult vaccination, and (iii) an every 10 years booster dose. The base case analysis, that is a single adolescent booster administered at the age of 12 years, resulted in a reduction of pertussis infections. However, due to an increase in the number of symptomatic infections in adults, the benefits in terms of QALYs gained and costs saved in children were partly offset. Despite these negative indirect effects in the adult population, administering an additional booster dose could still be considered cost effective with an ICER of €4200 per QALY gained. Combining an adolescent booster dose at the age of 10 (most cost-effective age for a single adolescent booster dose) with an adult (18-30 years) booster dose always resulted in favorable ICERs (

Introduction: Rotavirus is the most common cause of severe diarrhoea worldwide. Vietnam is situated in the region of high rotavirus infection incidence and eligible for financial support to introduce rotavirus vaccines into the Expanded Program of Immunization (EPI) from the GAVI. This study was designed to assess the cost-effectiveness of rotavirus immunization in Vietnam, explicitly the use of Rotateq (R) and to assess the affordability of implementing universal rotavirus immunization based on GAVI-subsidized vaccine price in the context of Vietnamese healthcare system for the next 5 years.Methodology: An age-structured cohort model was developed for the 2009 birth cohort in Vietnam. Two strategies were compared: one being the current situation without vaccination, and the other being mass universal rotavirus vaccination. The time horizon of the model was 5 years with time cycles of 1 month for children less than 1 year of age and annual analysis thereafter. Outcomes included mild, moderate, severe cases and death. Multiple outcomes per rotavirus infection are possible in the model. Monte Carlo simulations were used to examine the acceptability and affordability of the rotavirus vaccination. All costs were expressed in 2009 US$.Results: Rotavirus vaccination would not completely protect young children against rotavirus infection due to partial nature of vaccine immunity, however, would effectively reduce severe cases of rotavirus by roughly 55% during the first 5 years of life. Under GAVI-subsidized vaccine price (US$ 0.3/dose), the vaccine cost would amount to US$ 5.5 million per annum for 3-dose of the Rotateq (R) vaccine. In the base-case, the incremental cost per quality-adjusted-life-year (QALY) was US$ 665 from the health system perspective, much lower than per-capita GDP of similar to US$ 1150 in 2009. Affordability results showed that at the GAVI-subsidized vaccine price, rotavirus vaccination could be affordable for Vietnamese health system.Conclusion: Rotavirus vaccination in Vietnam would be a cost-effective health intervention. Vaccination only becomes affordable if the country receives GAVI's financial support due to the current high market vaccine price. Given the high mortality rate of under-five-year children, the results showed that rotavirus immunization is the "best hope" for prevention of rotavirus-related diarrhoeal disease in Vietnam. In the next five years, Vietnam is definitely in debt to financial support from international organizations in implementing rotavirus immunization. It is recommended that new rotavirus vaccine candidates be developed at cheaper price to speed up the introduction of rotavirus immunization in the developing world in general. (C) 2011 Elsevier Ltd. All rights reserved.

Diarrhea is a leading cause of mortality for children under 5 years of age, and rotavirus is identified as the main cause of severe diarrhea worldwide. Since 2006, two rotavirus vaccines, Rotarix and Rotateq, have been available in the market. These vaccines have proved to have high efficacy in developed countries. Clinical trials are being undertaken in Asia and Africa, and early clinical results found that the vaccine significantly reduces severe diarrhea episodes due to rotavirus (48.3% for Asia and 30.2% for Africa). The WHO recommended that rotavirus immunization be included in all national immunization programs. Based on WHO's recommendations, the Global Alliance for Vaccines and Immunization decided to provide financial support for rotavirus immunization in the developing world. In this article, we attempted to ascertain the cost-effectiveness of universal rotavirus immunization in developing countries. After an extensive literature search, we identified and evaluated 15 cost-effectiveness studies conducted in the developing world. The results from these studies showed that rotavirus immunization is a cost-effective strategy and one of the best interventions to prevent rotavirus-related diarrheal disease. However, rotavirus vaccines are expensive and the vaccine price appears to be the most challenging and crucial factor for decision-makers regarding whether to introduce this vaccine into developing countries' immunization schedules. All the studies concluded that rotavirus immunization is cost effective but may not be affordable for the developing world at present. Developing countries will definitely rely on financial support from international organizations to introduce rotavirus vaccination. It is recommended that more research on cost-effective rotavirus immunization with updated data be conducted and new rotavirus vaccine candidates be developed at a cheaper price to speed up the introduction of rotavirus immunization to the developing world.

The fields of pharmacogenetics and pharmacogenomics have become important practical tools to progress goals in medical and pharmaceutical research and development. As more screening tests are being developed, with some already used in clinical practice, consideration of cost-effectiveness implications is important. A systematic review was performed on the content of and adherence to pharmacoeconomic guidelines of recent pharmacoeconomic analyses performed in the field of pharmacogenetics and pharmacogenomics. Economic analyses of screening strategies for genetic variations, which were evidence-based and assumed to be associated with drug efficacy or safety, were included in the review. The 20 papers included cover a variety of healthcare issues, including screening tests on several cytochrome P450 (CYP) enzyme genes, thiopurine S-methyltransferase (TMPT) and angiotensin-converting enzyme (ACE) insertion deletion (ACE I/D) polymorphisms. Most economic analyses reported that genetic screening was cost effective and often even clearly dominated existing non-screening strategies. However, we found a lack of standardization regarding aspects such as the perspective of the analysis, factors included in the sensitivity analysis and the applied discount rates. In particular, an important limitation of several studies related to the failure to provide a sufficient evidence-based rationale for an association between genotype and phenotype. Future economic analyses should be conducted utilizing correct methods, with adherence to guidelines and including extensive sensitivity analyses. Most importantly, genetic screening strategies should be based on good evidence-based rationales. For these goals, we provide a list of recommendations for good pharmacoeconomic practice deemed useful in the fields of pharmacogenetics and pharmacogenomics, regardless of country and origin of the economic analysis. © 2008 Adis Data Information BV. All rights reserved.

Item does not contain fulltext This paper provides an estimation of the lifetime health-care cost of HIV-infected children and an update of the cost-effectiveness of universal HIV-screening of pregnant women in Amsterdam (The Netherlands). During 2003-2005, we collected data concerning the prevalence of newly diagnosed HIV-infected pregnant women in Amsterdam. Also, data on resource utilization and HAART regimen for HIV-infected children was gathered from a national registry. Using Kaplan-Meier survival analysis, we estimated the life-expectancy of a vertically HIV-infected child at 19 years, with the corresponding lifetime health-care costs of 179,974 Euros. HIV-screening of pregnant women could prevent 2.4 HIV transmissions annually in Amsterdam, based on an estimated prevalence of nine yet undiagnosed HIV-positive pregnant women per 10,000 pregnancies. We show that universal HIV screening during pregnancy generates significant net cost savings and health benefits in most situations. Universal antenatal HIV screening is justified in Amsterdam from a health-economic point of view.

Objective: Clinical experimental stem cell therapy after myocardial infarction appears feasible, but its use has preceded the understanding of the working mechanism. The ischemic recipient cardiac environment is determinative for the attraction and subsequent fate of stem cells. Here, we studied expression levels of genes that are anticipated to be essential for adequate stem cell-based cardiac repair at various time-points during the 1 month period following myocardial infarction (MI).Methods: Gene expression in the hearts of mice that underwent MI by permanent or transient (30 min) ligation of the coronary artery was monitored using quantitative RT-PCR analysis of mRNA isolated from whole heart sections as well as from specific, laser micro-dissected, regions of sections. Protein expression was performed by immunohistochemical stainings and Western blot analysis.Results: Many inflammatory genes were highly expressed for at least 1 week after MI. The expression of pro-angiogenic genes such as bFGF, VEGF-A and VEGF-R2 changed only marginally post-MI. Markers used to test stem cell gene expression remained unchanged post-MI with the exception of G-CSF and GM-CSF, which are genes that are also known to enhance the inflammatory response. Analysis of micro-dissected regions revealed that SDF-1, SCF (both stem cell attractants) and VEGF-R2 (involved in angiogenesis) gene expression was slightly decreased especially in the infarcted region.Conclusion: Genes that are generally considered to participate in stem cell-related processes and angiogenesis were not upregulated after MI, whereas the inflammatory gene expression dominated. Modulation of this imbalance might be of value for stem cell-mediated therapy. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Objectives: Stroke prevention is the main goal in treating patients with atrial fibrillation (AF). Treatment with anticoagulants, such as vitamin-K antagonists (VKAs; e.g. warfarin and cumarines), was demonstrated to be an effective strategy. However, even though VKAs are the current standard therapy recommended by different guidelines, the significant risk of bleeding and the requirement for a regular monitoring are limiting its use. Apixaban is a novel oral anticoagulant (NOAC) associated with significantly lower hazard rates for stroke/systemic embolism major hemorrhage and discontinuations, compared to VKAs. This study evaluated the cost-effectiveness (CE) of apixaban compared to VKAs in the base-case analysis and alternatively to other NOACs for stroke prevention in non-valvular AF patients in The Netherlands. Methods: A global Markov model developed by United BioSource Corporation was modified to reflect the use of oral anticoagulants in The Netherlands. The model used efficacy data from a published indirect treatment comparison of NOACs and cost data from Dutch costing studies as inputs. Following health states were included in the model: non-valvular AF, primary and recurrent ischemic and hemorrhagic stroke, systemic embolism, myocardial infarction intracranial hemorrhage, other major and non-major bleedings, treatment discontinuations and death. Main outcomes were quality adjusted life years (QALY) and costs. Univariate and probabilistic sensitivity analyses (PSA) were conducted on the incremental cost-effectiveness ratio (ICER). Results: In the base-case analysis apixaban treatment compared to VKAs has an ICER well below an informal minimal willingness-to-pay threshold of € 20,000/QALY for The Netherlands (i.e. around € 7,000/QALY). PSA showed that the results of the base-case analysis were quite robust. Potentials exist for apixaban to be dominant over the other NOACs, rivaroxaban and dabigatran depending on hazard ratios, risks for complications and local price levels. patients in The Netherlands. Conclusions: In patients with AF, we found apixaban to be a cost-effective option in The Netherlands, compared to VKAs.

INTRODUCTION: Hepatitis C virus (HCV) infection can lead to severe liver disease. Pregnant women are already routinely screened for several infectious diseases, but not yet for HCV infection. Here we examine whether adding HCV screening to routine screening is cost-effective.METHODS: To estimate the cost-effectiveness of implementing HCV screening of all pregnant women and HCV screening of first-generation non-Western pregnant women as compared to no screening, we developed a Markov model. For the parameters of the model, we used prevalence data from pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and from literature sources. In addition, we estimated the effect of possible treatment improvement in the future.RESULTS: The incremental costs per woman screened was €41 and 0.0008 life-years were gained. The incremental cost-effectiveness ratio (ICER) was €52,473 which is above the cost-effectiveness threshold of €50,000. For screening first-generation non-Western migrants, the ICER was €47,113. Best-case analysis for both scenarios showed ICERs of respectively €19,505 and €17,533. We estimated that if costs per treatment were to decline to €3,750 (a reduction in price of €31,000), screening all pregnant women would be cost-effective.CONCLUSIONS: Currently, adding HCV screening to the already existing screening program for pregnant women is not cost-effective for women in general. However, adding HCV screening for first-generation non-Western women shows a modest cost-effective outcome. Yet, best case analysis shows potentials for an ICER below €20,000 per life-year gained. Treatment options will improve further in the coming years, enhancing cost-effectiveness even more.