European survey on acute coronary syndrome diagnosis and revascularisation treatment: Assessing differences in reported clinical practice with a focus on strategies for specific patient cases.

RATIONALE, AIMS, AND OBJECTIVES: While different imaging and treatment options are available in acute coronary syndrome (ACS) care, there is a lack of data regarding their use across Europe. We examined the diagnostic and treatment strategies in patients with known or suspected ACS as reported by physicians and identified variations in responses across European countries and geographical areas. METHOD: A web-based clinician survey focusing on ACS imaging and revascularization treatments was circulated through email distribution lists and websites of European professional societies in the field of cardiology. We collected information on respondents' clinical setting and specialty. Reported percentages of patients receiving imaging or treatment modalities and percentages of clinicians reporting to use modalities in a range of clinical scenarios were analyzed. Statistical comparisons were performed. RESULTS: In total, 69 responses were received (Sweden [n = 20], United Kingdom [n = 16], Northern/Western Europe [n = 17], Southern Europe [n = 9], and Central Europe [n = 7]). Considerable variations between geographical areas were seen in terms of reported diagnostic modalities and treatment strategies. For example, when presented with the scenario of a theoretical 45-year-old smoking female with a suspected ACS, 56% of UK clinicians reported to use coronary computed tomography angiography, compared to only 10% of Swedish clinicians (P = .002). Large variations were observed regarding the reported use of fractional flow reserve by physicians for non-culprit lesions during invasive management of myocardial infarction patients (44% in Sweden, 31% in the United Kingdom, and 30% in Northern/Western Europe vs non-use in Central and Southern Europe). CONCLUSIONS: In this survey, respondents reported different diagnostic and treatment strategies in ACS care. These variations seem to have geographic components. Larger studies or real world data are needed to verify these observations and investigate their causes. More research is needed to compare the quality and efficiency of ACS care across countries and explore pathways for improvement.

Adverse events associated with bone-conduction and middle-ear implants: a systematic review.

PURPOSE: To review types and frequencies of adverse events (AE) associated with bone-conduction hearing implants (BCHIs) and active middle-ear implants (aMEIs) as reported in the literature. METHODS: Cochrane, PubMed, and EMBASE libraries were searched for primary articles in English or German language that reported on adverse events following BCHI or aMEI implantation, included at least five patients and were published between 1996 and 2016. Study characteristics, demographics, and counts of adverse events were tabulated and analyzed within the R statistical programming environment. RESULTS: Following assessment of the reporting quality of adverse events, we present a brief guideline that potentially improves AE reporting in this field of research. For the full dataset, we summarize study-level adverse event frequencies in terms of ratio of events to ears (REE) by AE groups and by device. For a subset of studies, we also report cumulative incidence (risk) for minor- and major adverse-events by device and by device groups. CONCLUSIONS: Data analyzed in this review show that: (1) the reporting quality of adverse events associated with BCHI and aMEIs is often very low; (2) adverse events associated with BCHI and aMEIs are qualitatively different and not equally frequent among devices; (3) state-of-the-art implantable BCHIs and aMEIs are a safe treatment option for hearing loss.

Systematic reviews as a "lens of evidence": Determinants of cost-effectiveness of breast cancer screening.

Systematic reviews with economic components are important decision tools for stakeholders seeking to evaluate technologies, such as breast cancer screening (BCS) programs. This overview of systematic reviews explores the determinants of the cost-effectiveness of BCS and assesses the quality of secondary evidence. The search identified 30 systematic reviews that reported on the determinants of the cost-effectiveness of BCS, including the costs of breast cancer and BCS. While the quality of the reviews varied widely, only four out of 30 papers were considered to be of a high quality. We did not identify publication bias in the original evidence on the cost-effectiveness of mammography screening; however, we highlight a need for improved clarity in both reporting and data verification. The reviews consisted mainly of studies from high-income countries. Breast cancer costs varied widely among the studies. Factors leading to higher costs included: time (diagnosis and last months before death), later stage or metastases, recurrence of the disease, age below 64 years and type of follow-up (more intensive or more specialized). Overall, screening with mammography was considered cost-effective in the age range 50-69 years in Western European and Northern American countries but not for older or younger women. Its cost-effectiveness was questionable for low-income settings and Asia. Mammography screening was more cost-effective with biennial screening compared to annual screening and single reading using computer-aided detection vs double reading. No information on the cost-effectiveness of ultrasonography was found, and there is much uncertainty on the cost-effectiveness of CBE because of methodological limitations.

The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

BACKGROUND: Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. METHODS: Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. RESULTS: The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. CONCLUSION: Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment required by governments and their development partners within all reasonable scenarios. Given the concentration of the NTDs among the poorest households, these investments represent good value for money in efforts to share the world's prosperity and reduce inequity.

Abiraterone Acetate for the Treatment of Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Evidence Review Group Perspective of an NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited Janssen, the company manufacturing abiraterone acetate (AA; tradename Zytiga®), to submit evidence for the clinical and cost effectiveness of AA in combination with prednisone/prednisolone (AAP) compared with watchful waiting (i.e. best supportive care [BSC]) for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG report, subsequent addenda, and the development of the NICE guidance for the use of this drug in England and Wales by the Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost effectiveness of AAP based on the CS. An important question in this appraisal was, according to the ERG, whether AAP followed by docetaxel is more effective than BSC followed by docetaxel. In the COU-AA-302 trial, 239 of 546 (43.8 %) AAP patients and 304 of 542 (56.1 %) BSC patients received docetaxel as subsequent therapy, following AA or placebo. The results for this specific group of patients were not presented in the CS; therefore, the ERG asked the company to provide these data in the clarification letter; however, these data were presented as commercial-in-confidence and cannot therefore be reported here. The ERG's critical assessment of the company's economic evaluation highlighted a number of concerns, including (a) not using the intention-to-treat (ITT) population; (b) inconsistencies in estimating prediction equations; (c) not fully incorporating the impact of adverse events; (d) incorrectly incorporating the new patient access scheme (PAS); and (e) the assumption that AA non-compliance leads to recoverable drug costs. Although some of these issues were adjusted in the ERG base case, the ERG could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. With the exception of the ERG's preference for using the ITT population, the AC agreed with the approach taken in the ERG base case. The original company and ERG base-case incremental cost-effectiveness ratios (ICERs) were £46,722 and £57,688 per QALY gained, respectively; these changed to £28,563 and £38,061 per QALY gained, respectively, in the revised base cases applying a new PAS. Regarding the end-of-life criteria, after 24 months approximately 63 % of patients in the control group of the COU-AA-302 trial were still alive, and the median survival was 30.1 months (95 % CI 27.3-34.1). Therefore, it is unlikely that life expectancy would be less than 24 months. The AC stated that the most plausible ICER is likely between £28,600 and £32,800 per QALY gained, and concluded that AAP at this stage in the treatment pathway did not meet the end-of-life criterion for short life expectancy. Moreover, in March 2016, the AC produced the final guidance, stating that AAP is recommended, within its marketing authorisation, as an option for treating mCRPC.

Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review.

BACKGROUND: Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). METHODOLOGY/PRINCIPAL FINDINGS: Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. CONCLUSIONS: It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes.

Upfront Genotyping of DPYD*2A to Individualize Fluoropyrimidine Therapy: A Safety and Cost Analysis.

PURPOSE: Fluoropyrimidines are frequently prescribed anticancer drugs. A polymorphism in the fluoropyrimidine metabolizing enzyme dihydropyrimidine dehydrogenase (DPD; ie, DPYD*2A) is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity. This study determined the feasibility, safety, and cost of DPYD*2A genotype-guided dosing. PATIENTS AND METHODS: Patients intended to be treated with fluoropyrimidine-based chemotherapy were prospectively genotyped for DPYD*2A before start of therapy. Variant allele carriers received an initial dose reduction of ≥ 50% followed by dose titration based on tolerance. Toxicity was the primary end point and was compared with historical controls (ie, DPYD*2A variant allele carriers receiving standard dose described in literature) and with DPYD*2A wild-type patients treated with the standard dose in this study. Secondary end points included a model-based cost analysis, as well as pharmacokinetic and DPD enzyme activity analyses. RESULTS: A total of 2,038 patients were prospectively screened for DPYD*2A, of whom 22 (1.1%) were heterozygous polymorphic. DPYD*2A variant allele carriers were treated with a median dose-intensity of 48% (range, 17% to 91%). The risk of grade ≥ 3 toxicity was thereby significantly reduced from 73% (95% CI, 58% to 85%) in historical controls (n = 48) to 28% (95% CI, 10% to 53%) by genotype-guided dosing (P < .001); drug-induced death was reduced from 10% to 0%. Adequate treatment of genotype-guided dosing was further demonstrated by a similar incidence of grade ≥ 3 toxicity compared with wild-type patients receiving the standard dose (23%; P = .64) and by similar systemic fluorouracil (active drug) exposure. Furthermore, average total treatment cost per patient was lower for screening (€2,772 [$3,767]) than for nonscreening (€2,817 [$3,828]), outweighing screening costs. CONCLUSION: DPYD*2A is strongly associated with fluoropyrimidine-induced severe and life-threatening toxicity. DPYD*2A genotype-guided dosing results in adequate systemic drug exposure and significantly improves safety of fluoropyrimidine therapy for the individual patient. On a population level, upfront genotyping seemed cost saving.

Lenalidomide for the Treatment of Low- or Intermediate-1-Risk Myelodysplastic Syndromes Associated with Deletion 5q Cytogenetic Abnormality: An Evidence Review of the NICE Submission from Celgene.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of lenalidomide (Celgene) to submit evidence of the clinical and cost effectiveness of the drug for treating adults with myelodysplastic syndromes (MDS) associated with deletion 5q cytogenetic abnormality, as part of the Institute's single technology appraisal (STA) process. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company's submission, the ERG review, and the NICE's subsequent decisions. The ERG reviewed the evidence for clinical and cost effectiveness of the technology, as submitted by the manufacturer to the NICE. The ERG searched for relevant additional evidence and validated the manufacturer's decision analytic model to examine the robustness of the cost-effectiveness results. Clinical effectiveness was obtained from a three-arm, European, randomized, phase III trial among red blood cell (RBC) transfusion-dependent patients with low-/intermediate-1-risk del5q31 MDS. The primary endpoint was RBC independence for ≥26 weeks, and was reached by a higher proportion of patients in the lenalidomide 10 and 5 mg groups compared with placebo (56.1 and 42.6 vs 5.9 %, respectively; both p < 0.001). The option of dose adjustments after 16 weeks due to dose-limiting toxicities or lack of response made long-term effectiveness estimates unreliable, e.g. overall survival (OS). The de novo model of the manufacturer included a Markov state-transition cost-utility model implemented in Microsoft Excel. The base-case incremental cost-effectiveness ratio (ICER) of the manufacturer was £56,965. The ERG assessment indicated that the modeling structure represented the course of the disease; however, a few errors were identified and some of the input parameters were challenged. In response to the appraisal documentation, the company revised the economic model, which increased the ICER to £68,125 per quality-adjusted life-year. The NICE Appraisal Committee (AC) did not recommend lenalidomide as a cost-effective treatment. Subsequently, the manufacturer submitted a Patient Access Scheme (PAS) that provided lenalidomide free of charge for patients who remained on treatment after 26 cycles. This PAS improved the ICER to £25,300, although the AC considered the proportion of patients who received treatment beyond 26 cycles, and hence the ICER, to be uncertain. Nevertheless, the AC accepted a commitment from the manufacturer to publish, once available, data on the proportion of patients eligible for the PAS, and believed this provided reassurance that lenalidomide was a cost-effective treatment for low- or intermediate-1-risk MDS patients.

Impact on total population health and societal cost, and the implication on the actual cost-effectiveness of including tumour necrosis factor-α antagonists in management of ankylosing spondylitis: a dynamic population modelling study.

BACKGROUND: Sequential treatment of ankylosing spondylitis (AS) that includes tumour necrosis factor-α antagonists (anti-TNF agents) has been applied in most of the Western countries. Existing cost-effectiveness (CE) models almost exclusively presented the incremental CE of anti-TNF agents using a closed cohort while budget impact studies are mainly lacking. Notwithstanding, information on impact on total population health and societal budget as well as on actual incremental CE for a given decision time span are important for decision makers. This study aimed at quantifying, for different decision time spans starting from January 1, 2014 in the Dutch society, (1) impact of sequential drug treatment strategies without and with inclusion of anti-TNF agents (Strategies 1 and 2, respectively) on total population health and societal cost, and (2) the actual incremental CE of Strategy 2 compared to Strategy 1. METHODS: Dynamic population modelling was used to capture total population health and cost, and the actual incremental CE. Distinguishing the prevalent AS population on January 1, 2014 and the incident AS cohorts in the subsequent 20 years, the model tracked individually an actual number of AS patients until death or end of the simulation time. During the simulation, data on patient characteristics, history of drug use, costs and health at discrete time points were generated. In Strategy 1, five nonsteroidal anti-inflammatory drugs (NSAIDs) were available but anti-TNF agents withdrawn. In Strategy 2, five NSAIDs and two anti-TNF agents continued to be available. RESULTS: The predicted size of the prevalent AS population in the Dutch society varied within the range of 67,145-69,957 with 44-46 % of the patients receiving anti-TNF agents over the period 2014-2034. The use of anti-TNF agents resulted in an increase in the annual drug costs (168.54-205.28 million Euros), but at the same time caused a decrease in the annual productivity costs (12.58-31.21 million Euros) and in annual costs of healthcare categories other than drugs (7.23-11.90 million Euros). Incremental cost (Euros) per QALY gained in Strategy 2 compared to Strategy 1 corresponding to decision time spans of 5, 10, 15 and 20 years improved slightly from 75,379 to 67,268, 63,938 and 61,129, respectively. At willingness-to-pay thresholds of 118,656, 112,067, 110,188 and 110,512 Euros, it was 99 % certain that Strategy 2 was cost-effective for decision time spans of 5, 10, 15 and 20, respectively. CONCLUSIONS: Using the dynamic population approach, the present model can project real-time data to inform a healthcare system decision that affects all actual number of AS patients eligible for anti-TNF agents within different decision time spans. The predicted total population costs of different categories in the present study can help plan the organization of the healthcare resources based on the national budget for the disease.

Cost-effectiveness of adding rituximab to fludarabine and cyclophosphamide for treatment of chronic lymphocytic leukemia in Ukraine.

The aim of this study was to assess the cost-effectiveness, from a health care perspective, of adding rituximab to fludarabine and cyclophosphamide scheme (FCR versus FC) for treatment-naïve and refractory/relapsed Ukrainian patients with chronic lymphocytic leukemia. A decision-analytic Markov cohort model with three health states and 1-month cycle time was developed and run within a life time horizon. Data from two multinational, prospective, open-label Phase 3 studies were used to assess patients' survival. While utilities were generalized from UK data, local resource utilization and disease-associated treatment, hospitalization, and side effect costs were applied. The alternative scenario was performed to assess the impact of lower life expectancy of the general population in Ukraine on the incremental cost-effectiveness ratio (ICER) for treatment-naïve patients. One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the robustness of the results. The ICER (in US dollars) of treating chronic lymphocytic leukemia patients with FCR versus FC is US$8,704 per quality-adjusted life year gained for treatment-naïve patients and US$11,056 for refractory/relapsed patients. When survival data were modified to the lower life expectancy of the general population in Ukraine, the ICER for treatment-naïve patients was higher than US$13,000. This value is higher than three times the current gross domestic product per capita in Ukraine. Sensitivity analyses have shown a high impact of rituximab costs and a moderate impact of differences in utilities on the ICER. Furthermore, probabilistic sensitivity analyses have shown that for refractory/relapsed patients the probability of FCR being cost-effective is higher than for treatment-naïve patients and is close to one if the threshold is higher than US$15,000. State coverage of rituximab treatment may be considered a cost-effective treatment for the Ukrainian population under conditions of economic stability, cost-effectiveness threshold growth, or rituximab price negotiations.

Costs of Hospital Stay in Specialized Diabetic Foot Department in Russia.

BACKGROUND: Diabetic foot ulcer (DFU) is considered to be one of the most common and costly diabetic complications. The approach unanimously recommended for patients with DFU is treatment by a multidisciplinary foot care team, which in Russia mainly is limited to few federal and regional hospitals. Currently, financing schemes for medical institutions are changing, thus raising the issue of setting adequate tariffs. OBJECTIVE: To identify the cost of treatment in the specialized diabetic foot department and determinants of variation in cost among individual patients with DFU in the Russian setting from the perspective of a health care organization. METHODS: We collected data on treatment cost per admission to the Diabetic Foot Department of the Endocrinology Scientific Center and information on patients' characteristics derived from medical records. Data on costs were analyzed, and descriptive statistics are reported. A standard multiple regression analysis was performed to identify the main drivers of treatment cost for patients with DFU. RESULTS: The mean treatment cost was €3051. The mean cost of treatment for patients with DFU was significantly higher than that for diabetic patients without this complication. The most relevant predictors of the costs of treatment for patients with DFU were surgery provided and length of stay in hospital. CONCLUSIONS: The cost for treatment of DFU by a multidisciplinary team in the federal medical institution was substantially higher than basic medical insurance tariff for this disease. Because revascularization procedures appeared to be the main cost driver, our results stress the need for careful implementation of this type of treatment for patients with DFU.

The effect of presenting information about invasive follow-up testing on individuals' noninvasive colorectal cancer screening participation decision: results from a discrete choice experiment.

OBJECTIVES: Many national colorectal cancer screening campaigns have a similar structure. First, individuals are invited to take a noninvasive screening test, and, second, in the case of a positive screening test result, they are advised to undergo a more invasive follow-up test. The objective of this study was to investigate how much individuals' participation decision in noninvasive screening is affected by the presence or absence of detailed information about invasive follow-up testing and how this effect varies over screening tests. METHODS: We used a labeled discrete choice experiment of three noninvasive colorectal cancer screening types with two versions that did or did not present respondents with detailed information about the possible invasive follow-up test (i.e., colonoscopy) and its procedure. We used data from 631 Dutch respondents aged 55 to 75 years. Each respondent received only one of the two versions (N = 310 for the invasive follow-up test information specification version, and N = 321 for the no-information specification version). RESULTS: Mixed logit model results show that detailed information about the invasive follow-up test negatively affects screening participation decisions. This effect can be explained mainly by a decrease in choice shares for the most preferred screening test (a combined stool and blood sample test). Choice share simulations based on the discrete choice experiment indicated that presenting invasive follow-up test information decreases screening participation by 4.79%. CONCLUSIONS: Detailed information about the invasive follow-up test has a negative effect on individuals' screening participation decisions in noninvasive colorectal cancer screening campaigns. This result poses new challenges for policymakers who aim not only to increase uptake but also to provide full disclosure to potential screening participants.

Preferences for potential innovations in non-invasive colorectal cancer screening: A labeled discrete choice experiment for a Dutch screening campaign.

BACKGROUND: The introduction of innovative non-invasive screening tests (e.g. tests based on stool and blood samples or both) may be a solution to increase colorectal cancer (CRC) screening uptake. However, preferences for these non-invasive screening tests have not been investigated in great detail yet. The purpose of this article therefore is to elicit individuals' preferences for different non-invasive screening tests in a Dutch screening campaign context. MATERIAL AND METHODS: We investigate preferences by means of a labeled discrete choice experiment. Data of 815 individuals, aged 55-75 years, are used in the analysis. RESULTS: Multinomial logit model analysis showed that the combi-test is generally preferred over the blood-test and the (currently available) stool-test. Furthermore, besides the large effect of screening test type, there are significant differences in preference depending on participants' socio-demographic background. Finally, the analysis showed a significant positive effect on screening test choice for the attributes sensitivity, risk reduction, and level of evidence and a non-significant effect for the attribute unnecessary follow-up test. CONCLUSION: Introducing new non-invasive screening tests that are based on a combination of stool and blood samples (or blood sample only) has the potential to increase CRC screening participation compared to the current standard stool-based test.

Cost-effectiveness of primary prevention of paediatric asthma: a decision-analytic model.

BACKGROUND: Many children stand to benefit from being asthma-free for life with primary (i.e., prenatally started) prevention addressing one environmental exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF) approach. We assessed the cost-effectiveness of primary prevention programmes for Dutch children in a decision-analytic framework. METHODS: A decision-analytic tree model analysing healthcare costs and asthma cases prevented was developed to compare usual care (UC) with two UF and three MF programmes on the primary prevention of asthma amongst children. Programmes were evaluated through incremental cost-effectiveness ratios and net monetary benefits. Decision and parameter uncertainty were subjected to value-of-information analyses. RESULTS: The current UC and one of three MF programmes dominated the other alternatives. The MF programme was more costly but also more effective than UC at an incremental cost-effectiveness ratio of 8,209.20/additional asthma case prevented. The value of perfect information to reduce uncertainty was 291.6M at its lowest. Most of the uncertainty in the cost-effectiveness threshold was attributable to the probability and cost estimates for low-risk children. CONCLUSION: This study supports the feasibility of a structured programme that simultaneously addresses exposure to house dust mites, pet dander, environmental tobacco, and breast-feeding as a cost-effective alternative to UC in the primary prevention of asthma amongst children.

The long term effectiveness and cost-effectiveness of initiating treatment for ocular hypertension.

PURPOSE: To investigate the long-term health and economic consequences of direct treatment initiation in ocular hypertension patients. METHODS: A cost-effectiveness analysis with a societal perspective and a lifelong horizon was performed. The primary outcomes were the incremental quality-adjusted life years (QALYs) and costs of direct pressure-lowering treatment for ocular hypertension, compared to a strategy where treatment is postponed until conversion to glaucoma has been observed. We used a decision analytic model based on individual patient simulation to forecast disease progression and treatment decisions in both strategies in a representative heterogeneous patient population and in 18 patient subgroups stratified by initial intraocular pressure and additional risk factors for conversion. RESULTS: The incremental discounted health gain of direct treatment was 0.27 QALYs, whereas the incremental discounted costs were -€ 649 during an average lifetime of 26 years. In the simulations of patient subgroups, the model outcomes moved towards higher health gains and lower incremental costs with increasing risk of conversion in the patient population. The incremental cost-effectiveness ratio of direct treatment ranged from € 15,425 per QALY gained in the lowest-risk subgroup to dominance in the highest-risk subgroup. Probabilistic sensitivity analysis indicated that uncertainty surrounding the model input parameters did not affect the conclusions. CONCLUSION: Direct, early, pressure-lowering treatment is a dominant cost-effective treatment strategy over a strategy to start the same treatment approach later, after glaucoma has occurred for patients with ocular hypertension. Its implementation and consequences should be discussed with ophthalmologists and individual patients.

The impact of structural uncertainty on cost-effectiveness models for adjuvant endocrine breast cancer treatments: the need for disease-specific model standardization and improved guidance.

INTRODUCTION: Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics. METHODS: The analysis consisted of four steps: (1) review of the literature for identification of eligible CEAs; (2) definition and implementation of a base model structure, which included the core structural components for all identified CEAs; (3) definition and implementation of changes or additions in the base model structure or parameterization; and (4) quantification of the impact of changes in model structure or parameterizations on the analysis outcome metrics life-years gained (LYG), incremental costs (IC) and the incremental cost-effectiveness ratio (ICER). RESULTS: Eleven CEA analyses comparing anastrazole and tamoxifen as ABC treatment were identified. The base model consisted of the following health states: (1) on treatment; (2) off treatment; (3) local recurrence; (4) metastatic disease; (5) death due to breast cancer; and (6) death due to other causes. The base model estimates of anastrazole versus tamoxifen for the LYG, IC and ICER were 0.263 years, €3,647 and €13,868/LYG, respectively. In the published models that were evaluated, differences in model structure included the addition of different recurrence health states, and associated transition rates were identified. Differences in parameterization were related to the incidences of recurrence, local recurrence to metastatic disease, and metastatic disease to death. The separate impact of these model components on the LYG ranged from 0.207 to 0.356 years, while incremental costs ranged from €3,490 to €3,714 and ICERs ranged from €9,804/LYG to €17,966/LYG. When we re-analyzed the published CEAs in our framework by including their respective model properties, the LYG ranged from 0.207 to 0.383 years, IC ranged from €3,556 to €3,731 and ICERs ranged from €9,683/LYG to €17,570/LYG. CONCLUSION: Differences in model structure and parameterization lead to substantial differences in analysis outcome metrics. This analysis supports the need for more guidance regarding structural uncertainty and the use of standardized disease-specific models for health economic analyses of adjuvant endocrine breast cancer therapies. The developed approach in the current analysis could potentially serve as a template for further evaluations of structural uncertainty and development of disease-specific models.

A review of economic evaluations of behavior change interventions: setting an agenda for research methods and practice.

BACKGROUND: The objective of this study was to review methodological quality of economic evaluations of lifestyle behavior change interventions (LBCIs) and to examine how they address methodological challenges for public health economic evaluation identified in the literature. METHODS: Pubmed and the NHS economic evaluation database were searched for published studies in six key areas for behavior change: smoking, physical activity, dietary behavior, (illegal) drug use, alcohol use and sexual behavior. From included studies (n = 142), we extracted data on general study characteristics, characteristics of the LBCIs, methodological quality and handling of methodological challenges. RESULTS: Economic evaluation evidence for LBCIs showed a number of weaknesses: methods, study design and characteristics of evaluated interventions were not well reported; methodological quality showed several shortcomings and progress with addressing methodological challenges remained limited. CONCLUSIONS: Based on the findings of this review we propose an agenda for improving future evidence to support decision-making. Recommendations for practice include improving reporting of essential study details and increasing adherence with good practice standards. Recommendations for research methods focus on mapping out complex causal pathways for modeling, developing measures to capture broader domains of wellbeing and community outcomes, testing methods for considering equity, identifying relevant non-health sector costs and advancing methods for evidence synthesis.

The cloudy crystal ball of cost-effectiveness studies.

Despite the use of identical clinical trial data (Anastrazole, Tamoxifen, Alone or in Combination for the adjuvant treatment of postmenopausal women with localised hormone receptor-positive breast cancer data), not dependent on differences between countries, the outcome of 11 published cost-effectiveness analyses varied more than 20-fold. The observed wide variation in predicted life-years gained (a parameter derived from clinical trial data) demonstrates that authors used substantially different methods for handling the same data. We therefore consider it to be of utmost importance to strive for standardization of and better guidance for disease-specific modeling in economic evaluations.