Economic Analysis of Renal Replacement Therapy Modality in Acute Kidney Injury Patients With Fluid Overload.

Acute kidney injury (AKI) and fluid overload (FO) are among the top reasons to initiate intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Prior research suggests CRRT provides more precise volume control, but whether CRRT is cost-effective remains unclear. We assessed the cost-effectiveness of CRRT for volume control compared with IHD from a U.S. healthcare payer perspective. DESIGN: Decision analytical model comparing health outcomes and healthcare costs of CRRT versus IHD initiation for AKI patients with FO. The model had an inpatient phase (over 90-d) followed by post-discharge phase (over lifetime). The 90-day phase had three health states: FO, fluid control, and death. After 90 days, surviving patients entered the lifetime phase with four health states: dialysis independent (DI), dialysis dependent (DD), renal transplantation, and death. Model parameters were informed by current literature. Sensitivity analyses were performed to evaluate results robustness to parametric uncertainty. SETTING: ICU. PATIENTS OR SUBJECTS: AKI patients with FO. INTERVENTIONS: IHD or CRRT. MEASUREMENTS AND MAIN RESULTS: The 90-day horizon revealed better outcomes for patients initiated on CRRT (survival: CRRT 59.2% vs IHD 57.5% and DD rate among survivors: CRRT 5.5% vs IHD 6.9%). Healthcare cost was 2.7% (+$2,836) higher for CRRT. Over lifetime, initial CRRT was associated with +0.313 life years (LYs) and +0.187 quality-adjusted life years (QALYs) compared with initial IHD. Even though important savings were observed for initial CRRT with a lower rate of DD among survivors (-$13,437), it did not fully offset the incremental cost of CRRT (+$1,956) and DI survival (+$12,830). The incremental cost-per-QALY gained with CRRT over IRRT was +$10,429/QALY. Results were robust to sensitivity analyses. CONCLUSIONS: Our analysis provides an economic rationale for CRRT as the initial modality of choice in AKI patients with FO who require renal replacement therapy. Our finding needs to be confirmed in future research.

Public health impact and return on investment of Belgium's pediatric immunization program.

Objective: We evaluated the public health impact and return on investment of Belgium's pediatric immunization program (PIP) from both healthcare-sector and societal perspectives. Methods: We developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0-10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre-vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit-cost ratio. Scenario analyses considered alternate assumptions for key model inputs. Results: Across all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium's PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs. Conclusion: Belgium's PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact.

Estimating the lifetime cost of vaccination in 23 European Countries: a modeling study.

BACKGROUND: All European countries have national immunization programs (NIPs) to protect gainst infectious diseases. We aimed to estimate the individual lifetime cost of vaccination in 23 European countries, assuming full compliance with NIP schedules. RESEARCH DESIGN AND METHODS: We used publicly available data to estimate the individual lifetime cost of vaccination with the vaccines that are currently recommended and funded in each country for healthy individuals and for individuals with underlying medical conditions. We included a scenario analysis for healthy individuals in which all currently recommended vaccines were universally funded, and compared the annual costs per person of vaccination to the annual per-capita costs of all-cause hospitalization and anti-infective medications. RESULTS: The individual lifetime cost of vaccination was €592-3,504 for healthy individuals (median: €1,663; 13-20 diseases), €744-9,081 for individuals with underlying conditions (median: €2,992; 13-21 diseases), and €1,225-4,832 (median: €2,565; 21-22 diseases) in the scenario analysis, with median values for vaccine acquisition of €1,203, €1,731, and €1,788, respectively. CONCLUSIONS: Our estimates show that the maximum potential cost of vaccination requires a relatively low level of investment assuming full compliance. These data could be useful for policymakers in future financial planning and evaluation of NIPs.

Early versus delayed initiation of renal replacement therapy in cardiac-surgery associated acute kidney injury: an economic perspective.

BACKGROUND: Timing for renal replacement therapy (RRT) initiation for cardiac-surgery associated acute kidney surgery (CSA-AKI) is subject to debate. Evidence suggests earlier initiation leads to shorter length of stay (LoS). We investigated differences in healthcare costs associated with timing of RRT initiation in CSA-AKI. METHODS: A cost-consequences model compared costs of Early (<24 h) vs. Delayed (>24 h) RRT initiation. Data were from the ELAIN trial in Germany, and the HiDenIC database, a US multi-hospital database. Resource utilization was determined by RRT duration, ICU, and hospital LoS. All resources were costed from a US healthcare perspective. Extensive sensitivity analyses (SA) were conducted, notably regarding the proportion of patients not initiated on RRT with the Delayed strategy. RESULTS: Early RRT initiation exhibited cost savings compared to Delayed RRT initiation. With ELAIN data, savings reached -$122,188 (ranging from -$157,707 to -$74,763 in the SA). Findings were confirmed with HiDenIC data; Early RRT initiation showed savings of -$77,303 (ranging from -$108,971 to -$47,012 in the SA). CONCLUSIONS: Our costing model indicates that Early RRT initiation for CSA-AKI may result in appreciable cost savings. Delaying RRT, in the setting of CSA-AKI, may lead to longer LoS and increased healthcare costs.

Addressing HCV Elimination Barriers in Italy: Healthcare Resource Utilization and Cost Impact Using 8 Weeks' Glecaprevir/Pibrentasvir Therapy.

INTRODUCTION: In Italy, hepatitis C virus (HCV) elimination is achievable; however, barriers remain to achieving the World Health Organization's elimination targets, and have become more pronounced with the spread of COVID-19. Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral therapy for HCV, approved for 8-week treatment in patients without cirrhosis, and with compensated cirrhosis (CC). Previously, 12 weeks of therapy was recommended for patients with CC. Shortened treatment may reduce the burden on healthcare resources, allowing more patients to be treated. This study presents the benefits that 8-week vs 12-week treatment with G/P may have in Italy. METHODS: A multicohort Markov model was used to assess the collective number of healthcare visits and time on treatment with 8-week vs 12-week G/P in the HCV-infected population of Italy from 2019 to 2030, using healthcare resource data from post-marketing observational studies of G/P. Increased treatment capacity and downstream clinical and economic benefits were also assessed assuming the reallocation of saved healthcare visits to treat more patients. RESULTS: Modeled outcomes showed that by 2030, 8-week treatment saved 27,006 years on therapy compared with 12-week treatment, with 21,065 fewer hepatologist visits. Reallocating these resources to treat more patients could increase capacity to treat 5064 (1.4%) more patients with 8 weeks of G/P, all with CC. This increased treatment capacity would further avoid 2257 cases of end-stage liver disease, 893 liver-related deaths, and provide net savings to the healthcare system of nearly €70 million. CONCLUSION: The modeled comparisons between 8- and 12-week treatment with G/P show that shorter treatment duration can lead to greater time and resource savings, both in terms of healthcare visits and downstream costs. These benefits have the potential to enable the treatment of more patients to overcome elimination barriers in Italy through programs aimed to engage and treat targeted HCV populations.

Economic Evaluation of Vaccines: Belgian Reflections on the Need for a Broader Perspective.

OBJECTIVES: The standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination. METHODS: In 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations. RESULTS: They concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs. CONCLUSIONS: Here, suggestions are made regarding how these shortcomings can be addressed in future economic evaluations of vaccines and how a more level playing field between vaccines and other health programs can be created.

Cost-Effectiveness of Gliclazide-Based Intensive Glucose Control vs. Standard Glucose Control in Type 2 Diabetes Mellitus. An Economic Analysis of the ADVANCE Trial in Vietnam.

Introduction: ADVANCE was a large, multinational clinical study conducted over 5 years in type 2 diabetes mellitus (T2DM). In all, 11,140 patients were randomly assigned to receive gliclazide-based intensive glucose control (IGC) or standard glucose control (SGC). IGC was shown to significantly reduce the incidence of major macrovascular and microvascular events (composite endpoint) or major microvascular events compared with SGC, primarily by enhancing renal protection. We assessed the cost-effectiveness of IGC vs. SGC, based on the ADVANCE results, from a Vietnamese healthcare payer perspective. Materials and Methods: A partitioned survival times model across five health states (no complications, myocardial infarction, stroke, end-stage renal disease [ESRD], and diabetes-related eye-disease) was designed. Time-to-event curves were informed by the cumulative incidence of events and corresponding hazard ratios from the ADVANCE study. Health outcomes were expressed in terms of ESRD avoided and quality-adjusted life years (QALYs). Costs (in US $) comprised treatment costs and health state costs. Utility weights and costs were documented from literature reporting Vietnamese estimates. For sensitivity analyses, all parameters were individually varied within their 95% confidence interval bounds (when available) or within a ±30% range. Results: Over a 5-year horizon, IGC avoided 6.5 additional ESRD events per 1,000 patients treated compared with SGC (IGC, 3.5 events vs. SGC, 10.0 events) and provided 0.016 additional QALYs (IGC, 3.570 QALYs vs. SGC, 3.555 QALYs). Total costs were similar for the two strategies (IGC, $3,786 vs. SGC, $3,757). Although the total drug costs were markedly higher for IGC compared with SGC ($1,703 vs. $873), this was largely offset by the savings from better renal protection with IGC (IGC, $577 vs. SGC, $1,508). The incremental cost-effectiveness ratio (ICER) of IGC vs. SGC was $1,878/QALY gained, far below the threshold recommended by the World Health Organization (i.e., 1-3 × gross domestic product per inhabitant ≈$7,500 in Vietnam). The ICER of IGC vs. SGC per ESRD event avoided was $4,559/event. The findings were robust to sensitivity analysis. Conclusion: In Vietnam, gliclazide-based IGC was shown to be cost-effective compared with SGC from a healthcare payer perspective, as defined in the ADVANCE study.

Economic impact of contagious caprine pleuropneumonia and cost-benefit analysis of the vaccination programmes based on a one-year continuous monitoring of flocks in the arid and semi-arid lands of Kenya.

In Kenya and East Africa, contagious caprine pleuropneumonia (CCPP) is one of the most prevalent infectious diseases affecting small ruminants in pastoral areas with adverse consequences on livelihoods. This is so despite the implementation of bi-annual vaccination campaigns. Unfortunately, the impact of the disease and the cost-effectiveness of its prevention and control in a pastoral context have been difficult to assess due to a lack of reliable data. The dynamic of flock population, high illiteracy and limited outreach are the main challenges for proper data collection. Nevertheless, such analysis is important to justify the implementation of national vaccination campaign for livestock disease control and to contribute to pastoral households' economy support programme. A continuous flock monitoring was performed for a year in Turkana County to collect data on flock dynamics and the different causes of mortalities. A stochastic model was developed to evaluate the annual economic losses due to CCPP in a standard flock of 100 heads and evaluate the cost-benefit ratio of the vaccination programmes based on different scenarios of 95%, 50% and 20% vaccination effectiveness. The annual economic losses due to CCPP for a standard flock of 100 heads were estimated at Euros 1,712.66 in average. The benefits-costs ratio of the vaccination supports the current bi-annual vaccination campaigns, even with a vaccine effectiveness limited to 20% (average benefits-costs ratio of 5.715 with SD of 3.914). This justifies the campaigns as part of a food security or livelihood support programme. However, from an overall health perspective and for long-term effects on livestock asset protection and disease control, a higher vaccination effectiveness is required.

The health economics burden of sarcopenia: a systematic review.

Despite of better knowledge about sarcopenia, an optimal understanding of its consequences from a public health perspective remains a challenge. Specifically, the economic burden of the illness is unclear. As a support for the public health policy makers and other health actors, our objective was to perform a systematic review of the literature comparing healthcare costs between sarcopenic and non-sarcopenic patients (under the registration number CRD42018099291). A search for relevant articles was conducted on the Medline and Scopus databases. Rigorous eligibility criteria were established (e.g., subjects with sarcopenia, both men and women, mean age of the sarcopenic population) and applied by two investigators to identify suitable studies. The first screening phase, performed by 2 independent reviewers, covered 455 references. Fourteen relevant studies were included in the final analysis. Overall, we noted an important heterogeneity between studies in the way of assessing sarcopenia (i.e. operational definitions, tools and cut-offs used). There were also large variations between studies in their cost analysis settings (i.e., discrepancies in time horizon, types and sources of economic data). Most of the studies focused on hospitalization costs following surgery for a specific disease such as cancer. Finally, 11 out of the 14 studies reported higher healthcare costs for sarcopenic patients. However, most of the included studies have important methodological bias (e.g. potential confusion factors rarely taken into account), and low to moderate quality scores. More standardized research, taking into account all the limitations of the published studies, should be conducted to assess the true impact of sarcopenia on healthcare consumption.

Vaccination budget in Europe: an update.

Immunization has been shown to be the most effective disease prevention measure of all time, apart from water purification. However, vaccination programs remain highly vulnerable to budget cuts as their benefits may not be immediately and fully identifiable. Therefore, monitoring of healthcare expenditures allocated to prevention and vaccination is critical. This letter updates our previous observation of expenditure for prevention and vaccination programs in eight European countries by adding data from 2014, where available. Prevention and vaccines still entail a relatively low level of investment in European countries. Less than 0.5% of GDP is allocated to disease prevention programs and vaccine expenditure fall below 0.5% of healthcare spending in many of the countries. An adequate level of resources needs to be allocated to ensure efficient and sustainable vaccination programs.

Optimising the introduction of multiple childhood vaccines in Japan: A model proposing the introduction sequence achieving the highest health gains.

BACKGROUND: Many countries struggle with the prioritisation of introducing new vaccines because of budget limitations and lack of focus on public health goals. A model has been developed that defines how specific health goals can be optimised through immunisation within vaccination budget constraints. METHODS: Japan, as a country example, could introduce 4 new pediatric vaccines targeting influenza, rotavirus, pneumococcal disease and mumps with known burden of disease, vaccine efficacies and maximum achievable coverages. Operating under budget constraints, the Portfolio-model for the Management of Vaccines (PMV) identifies the optimal vaccine ranking and combination for achieving the maximum QALY gain over a period of 10 calendar years in children <5 years old. This vaccine strategy, of interest and helpful for a healthcare decision maker, is compared with an unranked vaccine selection process. RESULTS: Results indicate that the maximum QALY gain with a fixed annual vaccination budget of 500 billion Japanese Yen over a 10-year period is 72,288 QALYs using the optimal sequence of vaccine introduction (mumps [1st], followed by influenza [2nd], rotavirus [3rd], and pneumococcal [4th]). With exactly the same budget but without vaccine ranking, the total QALY gain can be 20% lower. CONCLUSION: The PMV model could be a helpful tool for decision makers in those environments with limited budget where vaccines have to be selected for trying to optimise specific health goals.

Public health impact of comprehensive hepatitis C screening and treatment in the French baby-boomer population.

OBJECTIVE: To estimate the public health impact of comprehensive hepatitis C virus (HCV) screening and access to all-oral, interferon (IFN)-free direct-acting antivirals (DAAs) in the French baby-boomer population (1945-1965 birth cohorts). METHODS: A sequential, multi-cohort, health-state transition model was developed to assess the impact of different hepatitis C screening and treatment strategies on clinical and economic outcomes in the 1945-1965 birth cohorts. Patients newly-diagnosed with chronic HCV were projected each year from 2016 to 2036 under three screening scenarios (70% [low], 75% [intermediate], and 80% [high] HCV awareness in 2036). Healthcare costs and clinical outcomes (number of liver-related deaths, quality-adjusted life-years [QALYs], life-years [LYs] spent in sustained virologic response [SVR] or with decompensated cirrhosis, hepatocellular carcinoma, or liver transplant) were compared among five treatment strategies (no antiviral therapy; IFN + ribavirin + protease inhibitor for fibrosis stages F2-F4, IFN-based DAAs for stages F2-F4, IFN-free DAAs for stages F2-F4, and IFN-free DAAs for stages F0-F4). RESULTS: Diagnosis of HCV genotype 1 was projected for 4,953, 6,600, and 8,368 individuals in the low, intermediate, and high screening scenarios, respectively. In the intermediate scenario, IFN-free DAAs for stages F0-F4 had a favorable cost-effectiveness profile vs IFN-based or IFN-free treatment strategies for F2-F4 and offered the greatest return on investment (0.899 LYs gained in SVR and 0.933 QALYs per €10,000 invested). CONCLUSION: Comprehensive HCV screening and access to all-oral, IFN-free DAAs is a cost-effective strategy that could help diminish the upcoming burden of HCV in the French baby-boomer population.

How much money is spent on vaccines across Western European countries?

Prevention programs, particularly vaccinations, remain highly vulnerable to budget cuts because their benefits may not be immediately identifiable. Seven Western European countries were selected (Germany, England, France, Italy, Spain, Sweden and Portugal) constituting a good mix of vaccine procurement modalities, with the objective to document the proportion of healthcare spending devoted to vaccines and its evolution. A data search was performed using the OECD online databases and official national sources from 2008 (2006 for England). No country spent more than 0.5% of its healthcare budget on vaccines. The proportion ranged from 0.25% in Spain (2012) and France (2013) to 0.47% in Germany (2014). Whereas healthcare spending increased in all countries but Spain (with increases ranging from +2.6% per year in France between 2008 and 2013 to +8.1% per year in England between 2006/07 and 2009/10), vaccine spending diminished markedly in Germany (-6.2% per year from 2008 to 2014), Spain (-6.7% per year from 2008 to 2012) and France (-4.2% per year from 2008 to 2013). Only Sweden (+5.9% per year from 2011 to 2013) and England (+18.9% per year from 2006/07 to 2009/10) increased their spending on vaccines. Vaccination involves relatively low levels of healthcare investment in Western Europe relative to the far-reaching public health benefits that it provides. We found a net trend toward a decrease in such spending in recent years, with the exception of Sweden and England. Vaccination budgets should be preserved or even increased to sustain a life-course approach to immunization with sufficient coverage rates.

The cost of vaccination throughout life: A western European overview.

Despite the interest of policy makers, the actual investment in vaccination is poorly documented. Our study assessed the costs of vaccination throughout life for a fully immunized Western European citizen. National vaccination calendars for England, France, Germany, Italy, Portugal, Spain and Sweden were retrieved. We differentiated men from women and healthy individuals from those suffering from underlying conditions who require specific additional vaccinations. Vaccine costs and administration fees were retrieved from official national source and calculated from the national healthcare perspective. Vaccinating an individual against up to 17 diseases throughout his entire life and in full compliance with national vaccination calendars cost between €328 and €2,352 (vaccines costs only) and between €443 and €3,395 (administration costs included), the lowest range corresponds to a healthy man in Sweden and the highest to a woman with underlying conditions in England. Vaccination costs varied among countries due to heterogeneous national vaccination calendars and organization. In all countries, adults (18-64 y) and elderly (≥65 y) accounted for the lowest vaccines costs compared with infants (0-24 m) and children/adolescents (2-17 y). In comparison, other mass secondary preventive therapies may be at least 3 times more costly. Vaccination requires a relatively low level of investment per individual. Our estimates should be considered to be the maximum potential costs due to our 100% compliance assumption. Increasing coverage rates would bring additional public health benefits for a relatively low incremental cost. A life-course approach of vaccination should also be encouraged because some missed opportunities remain in senior vaccinations.

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO).

PURPOSE: This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. METHODS: This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. RESULTS: The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. DISCUSSION: Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. CONCLUSIONS: Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.

Public health impact and cost-effectiveness of dairy products supplemented with vitamin D in prevention of osteoporotic fractures.

BACKGROUND: Dietary sources of calcium and vitamin D are recommended as a first-line strategy in prevention of osteoporosis-related fractures but their public health and economic impact has never been studied. METHODS: We designed a population-based model to forecast the potential health outcomes and medical effectiveness of the daily administration of dairy supplements containing 800 IU of vitamin D and 1 g of calcium in cohorts of subjects, from both genders, aged 50, 60, 70 and 80 years. Annual costs of dairy products were tested at €150, €250 and €350. RESULTS: In total, the daily intake of vitamin-D rich dairy products reduces by 30,376 and 16,105 events the number of osteoporotic fractures in women and men respectively and permits to gain 6605 and 6144 life-years, in women and men respectively. This intervention is cost-effective from 70 years on in the general population and from 60 years on in patients at increased risk of osteoporotic fractures. CONCLUSION: The recommendation to use dairy products as the preferred source of calcium and vitamin D in aging males and females is supported by public health and health economic analyses.

Economics of dialysis dependence following renal replacement therapy for critically ill acute kidney injury patients.

BACKGROUND: The obective of this study was to perform a cost-effectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from $200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). RESULTS: Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental cost-effectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. CONCLUSIONS: Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivors.

Comparing cost-effectiveness results for a vaccine across different countries worldwide: what can we learn?

INTRODUCTION: Cost-effectiveness analysis (CEA) using country-specific thresholds tied to gross domestic product (GDP) might not be appropriate in countries with low healthcare investment and a high disease burden as a consequence. METHODS: Using data from previously published CEA of rotavirus vaccination across nine countries worldwide, we calculated the cost neutral price (Pn) for the new intervention that reflects the price resulting in no net increase in health care costs compared with the current situation, and the maximum price (Pm) obtained with an incremental cost-effectiveness ratio (ICER) at the threshold value of 1×GDP/capita. RESULTS: In countries with low GDP/capita, the paradoxical finding for rotavirus vaccination is that the Pm is much higher than in countries with a high GDP/capita. On the other hand, the Pn for the low GDP/capita countries is much lower than for high GDP/capita countries because of the low investment in health care. CONCLUSION: In countries with low healthcare investment and a high disease burden, the difference between the Pn and Pm for rotavirus vaccine which is the price range within which the ICER is below the World Health Organization (WHO) threshold value, is large. One reason could be that the WHO threshold value may not properly account for the local opportunity cost of health care expenditures. Therefore, either alternative threshold values should be selected or alternative economic assessment tools should be considered, such as budget optimisation or return on investment, if we want to communicate about real economic value of new vaccines in those countries.

Health economic value of an innovation: delimiting the scope and framework of future market entry agreements.

BACKGROUND AND OBJECTIVES: The objective of our paper is to offer a new, payer-friendly taxonomy of market entry agreements (MEAs) that aims to twin contracts with their methodological designs in an effort to clarify the distinction between contracts that are based on performance and those that are based on demonstrated effect. METHODS: Our analysis proceeds in two stages: First, we delimit the scope and framework of pay for performance (P4P) and pay for demonstrated effect (P4E) agreements. Second, we distinguish the methodological designs supporting the implementation of each of these contracts. RESULTS: We elucidate why P4P contracts prevent the payer from funding the true effectiveness of an innovation by expanding on their limitations. These include: 1) the normative nature of comparisons, 2) the impossibility of true effect imputability for each individual, and 3) the use of intermediary outcome measures. We then explore three main criticisms that payers must take into account when reasoning in terms of performance rather than in terms of the product effectiveness. CONCLUSION: The potential effect that performance-based reimbursements may have on dissociating the components of the cost-effectiveness ratio constitutes an obstacle to a true health economic reasoning.

Potential clinical and economic impact of nonadherence with osteoporosis medications.

This study aims to estimate the potential clinical and economic implications of therapeutic adherence to bisphosphonate therapy. A validated Markov microsimulation model was used to estimate the impact of varying adherence to bisphosphonate therapy on outcomes (the number of fractures and the quality-adjusted life-years [QALYs]), health-care costs, and the cost-effectiveness of therapy compared with no treatment. Adherence was divided into persistence and compliance, and multiple scenarios were considered for both concepts. Analyses were performed for women aged 65 years with a bone mineral density T-score of -2.5. Health outcomes and the cost-effectiveness of therapy improved significantly with increasing compliance and/or persistence. In the case of real-world persistence and with a medical possession ratio (MPR; i.e., the number of doses taken divided by the number of doses prescribed) of 100%, the QALY gain and the number of fractures prevented represented only 48 and 42% of the values estimated assuming full persistence, respectively. These proportions fell to 27 and 23% with an MPR value of 80%. The costs per QALY gained, for branded bisphosphonates (and generic alendronate), were estimated at 19,069 euros (4,871 euros), 32,278 euros (11,985 euros), and 64,052 euros (30,181 euros) for MPR values of 100, 80, and 60%, respectively, assuming real-world persistence. These values were 16,997 euros (2,215 euros), 24,401 euros (6,179 eruos), and 51,750 euros (20,569 euros), respectively, assuming full persistence. In conclusion, poor compliance and failure to persist with osteoporosis medications results not only in deteriorating health outcomes, but also in a decreased cost-effectiveness of drug therapy. Adherence therefore remains an important challenge for health-care professionals treating osteoporosis.