The Effect of the Drug Life Cycle Price on Cost-Effectiveness: Case Studies Using Real-World Pricing Data.

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.

Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

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.

Cost-effectiveness and impact on infections and associated antimicrobial resistance of 20-valent pneumococcal conjugate vaccine in US children previously immunized with PCV13.

AIM: The US Food and Drug Administration approved the 20-valent pneumococcal conjugate vaccine (PCV20) to prevent pneumococcal disease. In the context of routine PCV20 vaccination, we evaluated the cost-effectiveness and public health and economic impact of a PCV20 catch-up program and estimated the number of antibiotic prescriptions and antibiotic-resistant infections averted. MATERIALS AND METHODS: A population-based, multi-cohort, decision-analytic Markov model was developed using parameters consistent with previous PCV20 cost-effectiveness analyses. In the intervention arm, children aged 14-59 months who previously completed PCV13 vaccination received a supplemental dose of PCV20. In the comparator arm, no catch-up PCV20 dose was given. The direct and indirect benefits of vaccination were captured over a 10-year time horizon. RESULTS: A PCV20 catch-up program would prevent 5,469 invasive pneumococcal disease cases, 50,286 hospitalized pneumonia cases, 218,240 outpatient pneumonia cases, 582,302 otitis media cases, and 1,800 deaths, representing a net gain of 30,014 life years and 55,583 quality-adjusted life years. Furthermore, 720,938 antibiotic prescriptions and 256,889 antibiotic-resistant infections would be averted. A catch-up program would result in cost savings of $800 million. These results were robust to sensitivity and scenario analyses. CONCLUSIONS: A PCV20 catch-up program could prevent pneumococcal infections, antibiotic prescriptions, and antimicrobial-resistant infections and would be cost-saving in the US.

Cost-effectiveness of 20-valent pneumococcal conjugate vaccine in US infants.

BACKGROUND: As of June 2023, two pneumococcal conjugate vaccines, 20- (PCV20) and 15- (PCV15) valent formulations, are recommended for US infants under a 3 + 1 schedule. This study evaluated the health and economic impact of vaccinating US infants with a new expanded valency PCV20 formulation. METHODS: A population-based, multi cohort, decision-analytic Markov model was developed to estimate the public health impact and cost-effectiveness of PCV20 from both societal and healthcare system perspectives over 10 years. Epidemiological data were based on published studies and unpublished Active Bacterial Core Surveillance System (ABCs) data. Vaccine effectiveness was based on PCV13 effectiveness and PCV7 efficacy studies. Indirect impact was based on observational studies. Costs and disutilities were based on published data. PCV20 was compared to both PCV13 and PCV15 in separate scenarios. RESULTS: Replacing PCV13 with PCV20 in infants has the potential to avert over 55,000 invasive pneumococcal disease (IPD) cases, 2.5 million pneumonia cases, 5.4 million otitis media (OM) cases, and 19,000 deaths across all ages over a 10-year time horizon, corresponding to net gains of 515,000 life years and 271,000 QALYs. Acquisition costs of PCV20 were offset by monetary savings from averted cases resulting in net savings of $20.6 billion. The same trend was observed when comparing PCV20 versus PCV15, with a net gain of 146,000 QALYs and $9.9 billion in net savings. A large proportion of the avoided costs and cases were attributable to indirect effects in unvaccinated adults and elderly. From a health-care perspective, PCV20 was also the dominant strategy compared to both PCV13 and PCV15. CONCLUSIONS: Infant vaccination with PCV20 is estimated to further reduce pneumococcal disease and associated healthcare system and societal costs compared to both PCV13 and PCV15.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine Among US Children with Underlying Medical Conditions.

INTRODUCTION: A 20-valent pneumococcal conjugate vaccine (PCV20) was recently recommended for use among US children. We evaluated the cost-effectiveness of PCV20 among children aged 6 years with chronic medical conditions (CMC+) and children aged 6 years with immunocompromising conditions (IC) versus one and two doses of 23-valent pneumococcal polysaccharide vaccine (PPSV23), respectively. METHODS: A probabilistic model was employed to depict 10-year risk of clinical outcomes and economic costs of pneumococcal disease, reduction in life years from premature death, and expected impact of vaccination among one cohort of children with CMC+ and IC aged 6 years. Vaccine uptake was assumed to be 20% for both PCV20 and PPSV23. Cost per quality-adjusted life year (QALY) gained was evaluated from the US societal and healthcare system perspectives; deterministic and probabilistic sensitivity analyses (DSA/PSA) were also conducted. RESULTS: Among the 226,817 children with CMC+ aged 6 years in the US, use of PCV20 (in lieu of PPSV23) was projected to reduce the number cases of pneumococcal disease by 5203 cases, medical costs by US$8.7 million, and nonmedical costs by US$6.2 million. PCV20 was the dominant strategy versus PPSV23 from both the healthcare and societal perspectives. In the PSA, 99.9% of the 1000 simulations yielded a finding of dominance for PCV20. Findings in analyses of children with IC aged 6 years in the USA were comparable (i.e., PCV20 was the dominant vaccination strategy). Scenario analyses showed that increasing PCV20 uptake to 100% could potentially prevent > 22,000 additional cases of pneumococcal disease and further reduce medical and nonmedical costs by US$70.0 million among children with CMC+ and IC. CONCLUSIONS: Use of PCV20 among young children with CMC+ and IC in the USA would reduce the clinical burden of pneumococcal disease and yield overall cost savings from both the US healthcare system and societal perspectives. Higher PCV20 uptake could further reduce the number of pneumococcal disease cases in this population.

An update of "Cost-effectiveness of rotavirus vaccination in the Netherlands: the results of a Consensus Rotavirus Vaccine model".

BACKGROUND: To update a cost-effectiveness analysis of rotavirus vaccination in the Netherlands previously published in 2011. METHODS: The rotavirus burden of disease and the indirect protection of older children and young adults (herd protection) were updated. RESULTS: When updated data was used, routine infant rotavirus vaccination in the Netherlands would potentially become an even more cost-effective strategy than previously estimated with the incremental cost per QALY at only €3,000-4,000. Break-even total vaccination costs were indicated at €92-122, depending on the applied threshold. CONCLUSIONS: We concluded that the results on potentially favourable cost-effectiveness in the previous study remained valid, however, the new data suggested that previous results might represent an underestimation of the economic attractiveness of rotavirus vaccination.

Reanalysis of the Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children < 5 Age: A Societal Perspective.

INTRODUCTION: Studies that estimate the economic burden of pediatric pneumococcal disease often only report direct medical costs and omit indirect non-medical costs. Given these indirect costs are not included in most calculations, the full economic burden attributable to pneumococcal conjugate vaccine (PCV) serotypes is often underestimated. This study seeks to quantify the full broader economic burden of pediatric pneumococcal disease associated with PCV serotypes. METHODS: We conducted a reanalysis of a previous study where non-medical costs associated with caregiving for a child with pneumococcal disease are considered. The annual indirect non-medical economic burden attributed to PCV serotypes was subsequently calculated for 13 countries. We included five countries with 10-valent (PCV10) national immunization programs (NIPs) (Austria, Finland, The Netherlands, New Zealand, and Sweden) and eight countries with 13-valent (PCV13) NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, and the UK). Input parameters were derived from published literature. Indirect costs were inflated to 2021 values in US dollars (USD). RESULTS: The total annual indirect economic burden associated with pediatric pneumococcal diseases attributable to PCV10, PCV13, the 15-valent (PCV15), and the 20-valent (PCV20) serotypes were $46.51 million, $158.95 million, $223.00 million, and $413.97 million, respectively. The five countries with PCV10 NIPs bear a greater societal burden associated with PCV13 serotypes, whereas the residual societal burden in the eight countries with PCV13 NIPs was primarily attributable to non-PCV13 serotypes. CONCLUSION: The inclusion of non-medical costs nearly tripled the total economic burden compared with only including direct medical costs estimated from a previous study. The results from this reanalysis can help inform decision-makers on the broader economic societal burden associated with PCV serotypes and the need for higher-valent PCVs.

Low Levels of RSV Testing Among Adults Hospitalized for Lower Respiratory Tract Infection in the United States.

INTRODUCTION: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI)-related hospitalizations in older adults. Without RSV-specific treatment for adults, testing is uncommon, leading to potential underestimation of RSV incidence in real-world data studies. This study aimed to quantify the frequency of RSV testing during LRTI-related hospitalizations of older adults to inform interpretation of incidence estimates. METHODS: Administrative and billing data for hospitalizations of adults aged ≥ 65 years with a primary or secondary diagnosis of LRTI during the 2016-2019 RSV seasons (October-April) were extracted from the US all-payer Premier Healthcare Database (PHD). Billing codes identified RSV tests administered during eligible hospitalizations. The proportion of LRTI-related hospitalizations with a billed RSV test was calculated for each hospital in PHD, and summarized descriptively by hospital bed size, teaching status, and population served. RESULTS: Most of the 937 study hospitals performed RSV testing infrequently during LRTI hospitalization; median percentage of LRTI hospitalizations with RSV testing was 4.3%, and 78.4% of hospitals performed RSV testing in less than 25% of LRTI-related hospitalizations. RSV testing varied extensively by hospital type. Median percentage tested was significantly higher for hospitals with ≥ 200 beds (9.1%) versus < 200 beds (1.6%), for teaching (11.0%) versus non-teaching (2.5%) hospitals, and in urban (7.4%) versus rural (0.7%) settings. The median percentage of RSV testing increased over time, from 0.8% to 6.3% between the 2016/17 and 2018/19 seasons. CONCLUSION: A small proportion of older adults hospitalized with LRTI are tested for RSV in US hospitals. Large variability occurs across hospital types. Consequently, retrospective database analyses likely result in a substantial underestimation of the true RSV-related hospitalization incidence. RSV incidence studies using real-world data need to assess for RSV testing frequency and adjust their results for under ascertainment associated with limited testing.

Incidence of Respiratory Syncytial Virus Infection in Older Adults: Limitations of Current Data.

INTRODUCTION: Respiratory syncytial virus (RSV) is an important cause of severe respiratory illness in older adults and adults with respiratory or cardiovascular comorbidities. Published estimates of its incidence and prevalence in adult groups vary widely. This article reviews the potential limitations affecting RSV epidemiology studies and suggests points to consider when evaluating or designing them. METHODS: Studies reporting the incidence or prevalence of RSV infection in adults in high-income Western countries from 2000 onwards were identified via a rapid literature review. Author-reported limitations were recorded, together with presence of other potential limitations. Data were synthesized narratively, with a focus on factors affecting incidence estimates for symptomatic infection in older adults. RESULTS: A total of 71 studies met the inclusion criteria, most in populations with medically attended acute respiratory illness (ARI). Only a minority used case definitions and sampling periods tailored specifically to RSV; many used influenza-based or other criteria that are likely to result in RSV cases being missed. The great majority relied solely on polymerase chain reaction (PCR) testing of upper respiratory tract samples, which is likely to miss RSV cases compared with dual site sampling and/or addition of serology. Other common limitations were studying a single season, which has potential for bias due to seasonal variability; failure to stratify results by age, which underestimates the burden of severe disease in older adults; limited generalizability beyond a limited study setting; and absence of measures of uncertainty in the reporting of results. CONCLUSIONS: A significant proportion of studies are likely to underestimate the incidence of RSV infection in older adults, although the effect size is unclear and there is also potential for overestimation. Well-designed studies, together with increased testing for RSV in patients with ARI in clinical practice, are required to accurately capture both the burden of RSV and the potential public health impact of vaccines.

On discounting of health gains from human papillomavirus vaccination: effects of different approaches.

OBJECTIVES: Discounting has long been a matter of controversy in the field of health economic evaluations. How to weigh future health effects has resulted in ongoing discussions. These discussions are imminently relevant for health care interventions with current costs but future benefits. Different approaches to discount health effects have been proposed. In this study, we estimated the impact of different approaches for discounting health benefits of human papillomavirus (HPV) vaccination. METHODS: An HPV model was used to estimate the impact of different discounting approaches on the present value of health effects. For the constant discount approaches, we varied the discount rate for health effects ranging from 0% to 4%. Next, the impact of relevant alternative discounting approaches was estimated, including hyperbolic, proportional, stepwise, and time-shifted discounting. RESULTS: The present value of health effects gained through HPV vaccination varied strongly when varying discount rates and approaches. The application of the current Dutch guidelines resulted in a present value of health effects that was eight or two times higher than that produced when using the proportional discounting approach or when using the internationally more common 4% discount rate for health effects, respectively. Obviously, such differences translate into large variations in corresponding incremental cost-effectiveness ratios. CONCLUSION: The exact discount rate and approach chosen in an economic evaluation importantly impact the projected value of health benefits of HPV vaccination. Investigating alternative discounting approaches in health-economic analysis is important, especially for vaccination programs yielding health effects far into the future. Our study underlines the relevance of ongoing discussions on how and at what rates to discount.

Until which age should women be vaccinated against HPV infection? Recommendation based on cost-effectiveness analyses.

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.

Annual Cardiovascular-Related Hospitalization Days Avoided with Tafamidis in Patients with Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: 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. PURPOSE: 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. METHODS: Data from ATTR-ACT were used to calculate the total burden of CV-related hospitalization (days) by treatment arm in this post hoc analysis. RESULTS: 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, p < 0.0001) 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, p < 0.0001). 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. CONCLUSIONS: 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. GOV IDENTIFIER: NCT01994889.

Assessing the value of orphan drugs using conventional cost-effectiveness analysis: Is it fit for purpose?

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.

Health impact of tafamidis in transthyretin amyloid cardiomyopathy patients: an analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and the open-label long-term extension studies.

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).

Prevalence, characteristics, and mortality of patients with transthyretin amyloid cardiomyopathy in the Nordic countries.

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.

Healthcare resource use of patients with transthyretin amyloid cardiomyopathy.

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.

Comparative review of three cost-effectiveness models for rotavirus vaccines in national immunization programs; a generic approach applied to various regions in the world.

BACKGROUND: This study aims to critically review available cost-effectiveness models for rotavirus vaccination, compare their designs using a standardized approach and compare similarities and differences in cost-effectiveness outcomes using a uniform set of input parameters. METHODS: We identified various models used to estimate the cost-effectiveness of rotavirus vaccination. From these, results using a standardized dataset for four regions in the world could be obtained for three specific applications. RESULTS: Despite differences in the approaches and individual constituting elements including costs, QALYs Quality Adjusted Life Years and deaths, cost-effectiveness results of the models were quite similar. Differences between the models on the individual components of cost-effectiveness could be related to some specific features of the respective models. Sensitivity analysis revealed that cost-effectiveness of rotavirus vaccination is highly sensitive to vaccine prices, rotavirus-associated mortality and discount rates, in particular that for QALYs. CONCLUSIONS: The comparative approach followed here is helpful in understanding the various models selected and will thus benefit (low-income) countries in designing their own cost-effectiveness analyses using new or adapted existing models. Potential users of the models in low and middle income countries need to consider results from existing studies and reviews. There will be a need for contextualization including the use of country specific data inputs. However, given that the underlying biological and epidemiological mechanisms do not change between countries, users are likely to be able to adapt existing model designs rather than developing completely new approaches. Also, the communication established between the individual researchers involved in the three models is helpful in the further development of these individual models. Therefore, we recommend that this kind of comparative study be extended to other areas of vaccination and even other infectious disease interventions.

Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model.

BACKGROUND: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios. METHODS: Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies. RESULTS: It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K € - 50K € per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was € 57.76 -€ 77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis. CONCLUSIONS: Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life.

Estimating the health benefits of timely diagnosis and treatment of transthyretin amyloid cardiomyopathy.

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.