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Objective. Tumour necrosis factor (TNF) antagonists have been shown to improve the outcomes in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We assess the cost-effectiveness of two TNF antagonists and so-called ‘palliative care’ for the treatment of active PsA from the perspective of the UK National Health Service (NHS). Methods. Bayesian statistical methods were used to synthesize evidence from three Phase III trials, identified through a systematic review, and estimate the relative efficacy of etanercept, infliximab and palliative care. A probabilistic decision analytic model was then used to compare these treatments after the failure of at least two conventional disease-modifying anti-rheumatic drugs (DMARDs), following the British Society for Rheumatology (BSR) guidelines for use. The primary outcome measure, quality-adjusted life years (QALYs), was derived from utility values estimated as a function of disability measured by the Health Assessment Questionnaire (HAQ). The deterioration experienced in HAQ at treatment withdrawal (rebound) was incorporated using alternative scenarios to represent best- and worst-case assumptions. The model was extended beyond the trial duration to a 10-yr and lifetime horizon, using available evidence and expert opinion-based assumptions on disease progression. Resource utilization was based on literature, national databases and expert opinion. Prices were obtained from routine NHS sources and published literature. Results. At a 10-yr time horizon, the incremental cost-effectiveness ratio (ICER) for etanercept compared with palliative care was £26 361 per QALY gained for the best-case rebound scenario, which increased to £30 628 for the worst-case. The ICERs for infliximab compared with etanercept were £165 363 and £205 345 per QALY, respectively. These findings are mainly explained by the fact that infliximab has higher acquisition and administration costs without substantially superior effectiveness compared with etanercept. Results were sensitive to estimates of rebound assumptions at withdrawal and the time horizon. Conclusions. Only results for etanercept remained within the range of cost-effectiveness estimates considered to represent value for money in the NHS by the National Institute for Health and Clinical Excellence. Further research appears most valuable in relation to the short-term effectiveness, utility parameters and assumptions regarding the effect of rebound. [ABSTRACT FROM AUTHOR]

Introduction: Diffractive trifocal intraocular lenses (IOLs) provide good vision at distance, intermediate, and near, but can also cause positive dysphotopsias. This meta-analysis pooled published evidence on visual disturbances after bilateral implantation of the PanOptix (TFNTXX) IOL for patients undergoing cataract surgery., Method: A systematic literature search was conducted in PubMed and congress presentations from April 2021 to December 2022 to identify studies with patient-reported outcomes on the incidence of visual disturbances (starbursts, halos, glare) post bilateral implantation of PanOptix IOL during cataract surgery. Random-effects meta-analysis was performed to generate pooled proportions for patient-reported visual disturbances with a 95% confidence interval [CI]., Results: Eleven unique studies were included, spanning 580 patients with bilateral implantation of PanOptix IOL from 10 countries with 1 to 12 months follow-up. In summary, 33.6% of patients with bilateral PanOptix implantation experienced glare, 43.9% experienced halos, and 30.4% experienced starbursts. Among these patients, small percentages reported severe glare (2.9%), severe halos (5.4%), and severe starbursts (3.4%). Only 0.8%, 1.4%, and 2.6% of patients found glare, halos, and starbursts, respectively, to be very bothersome., Conclusion: Halos are the most frequently reported visual disturbances. However, the likelihood of experiencing severe and/or very bothersome visual disturbances (halos, glare, starbursts) is approximately 5% and 3%, respectively, after bilateral implantation of PanOptix IOL. These findings should inform clinical decision-making and treatment choices when selecting the most appropriate IOL implant for cataract surgery., Competing Interests: Declarations. Conflict of Interest: Dagny Zhu has received consulting fees and honorariums for participation in advisory boards from Alcon and Johnson & Johnson, as well as a speaker honorarium from Alcon. Alcon is a manufacturer of multiple IOLs. Mukesh Dhariwal is an employee of Alcon. ESiOR Oy received consulting fees from Alcon to conduct the study. ESiOR Oy is an expert company that carries out health economics and outcomes research HEOR, data science and evidence generation, real-world data and biobank studies, health technology assessment HTA, market access, and other services as well as provides certified secure processing environment SPESiOR® for several institutions and projects, including also the producers and marketers of IOLs. Erkki Soini is a partner of ESiOR Oy, and chairman of the board at Kuopio Health cooperative. Suyen Karki, Christian Asseburg, and Erkki Soini are employed by ESiOR Oy. Dagny Zhu, Mukesh Dhariwal, Erkki Soini, Suyen Karki and Christian Asseburg have no other conflicts of interest related to this work. Ethical Approval: This article is based on previously conducted studies and does not contain new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s).)

Aims: Risk assessment is essential in the prevention of cardiovascular disease. In patients with recent acute coronary syndrome (ACS) or coronary revascularization, risk prediction tools, like the European Society of Cardiology guideline recommended SMART-REACH risk score, are increasingly used to predict the risk of recurrent cardiovascular events enabling risk-based personalized prevention. However, little is known about the association between risk stratification and the social and healthcare costs at a population level. This study evaluated the associations between baseline SMART-REACH risk scores, long-term recurrent clinical events, cumulative costs, and post-index event LDL-C goal attainment in patients with recent ACS and/or revascularization., Methods and Results: This retrospective study used electronic health records and was conducted in the North Karelia region of Finland. The study cohort included all patients aged 45-85 admitted to a hospital for ACS or who underwent percutaneous coronary intervention or coronary artery bypass surgery between 1 January 2017 and 31 December 2021. Patients were divided into quintiles based on their baseline SMART-REACH risk scores to examine the associations between predicted 5-year scores and selected clinical and economic outcomes. In addition, simple age-based stratification was conducted as a sensitivity analysis. The observed 5-year cumulative incidence of recurrent events ranged from 20% in the lowest to 41% in the highest risk quintile, whereas the corresponding predicted risks ranged from 13% to 51%, and cumulative 5-year mean total costs per patient ranged from 15 827 to 46 182€, respectively. Both monitoring and attainment of low LDL-C values were suboptimal., Conclusion: The use of the SMART-REACH quintiles as a population-level risk stratification tool successfully stratified patients into subgroups with different cumulative numbers of recurrent events and cumulative total costs. However, more research is needed to define clinically and economically optimal threshold values for a population-level stratification., Competing Interests: Conflict of interest: M.O. and C.A. are employees of ESiOR Oy. At the time of writing, J.P. was an employee of ESiOR Oy. J.P. is no longer an employee of ESiOR Oy. J.M. is a founding partner and shareholder of ESiOR Oy. A.K. is an employee of Novartis. Other declare no competing interest to the current study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Structural uncertainty can affect model-based economic simulation estimates and study conclusions. Unfortunately, unlike parameter uncertainty, relatively little is known about its magnitude of impact on life-years (LYs) and quality-adjusted life-years (QALYs) in modeling of diabetes. We leveraged the Mount Hood Diabetes Challenge Network, a biennial conference attended by international diabetes modeling groups, to assess structural uncertainty in simulating QALYs in type 2 diabetes simulation models., Methods: Eleven type 2 diabetes simulation modeling groups participated in the 9th Mount Hood Diabetes Challenge. Modeling groups simulated 5 diabetes-related intervention profiles using predefined baseline characteristics and a standard utility value set for diabetes-related complications. LYs and QALYs were reported. Simulations were repeated using lower and upper limits of the 95% confidence intervals of utility inputs. Changes in LYs and QALYs from tested interventions were compared across models. Additional analyses were conducted postchallenge to investigate drivers of cross-model differences., Results: Substantial cross-model variability in incremental LYs and QALYs was observed, particularly for HbA1c and body mass index (BMI) intervention profiles. For a 0.5%-point permanent HbA1c reduction, LY gains ranged from 0.050 to 0.750. For a 1-unit permanent BMI reduction, incremental QALYs varied from a small decrease in QALYs (-0.024) to an increase of 0.203. Changes in utility values of health states had a much smaller impact (to the hundredth of a decimal place) on incremental QALYs. Microsimulation models were found to generate a mean of 3.41 more LYs than cohort simulation models ( P = 0.049)., Conclusions: Variations in utility values contribute to a lesser extent than uncertainty captured as structural uncertainty. These findings reinforce the importance of assessing structural uncertainty thoroughly because the choice of model (or models) can influence study results, which can serve as evidence for resource allocation decisions.HighlightsThe findings indicate substantial cross-model variability in QALY predictions for a standardized set of simulation scenarios and is considerably larger than within model variability to alternative health state utility values (e.g., lower and upper limits of the 95% confidence intervals of utility inputs).There is a need to understand and assess structural uncertainty, as the choice of model to inform resource allocation decisions can matter more than the choice of health state utility values.

Introduction: Intravenous infusion therapy is a common and challenging invasive treatment procedure in hospital wards. Administration mistakes can have serious, even life-threatening, consequences. The Monidor solution was developed to help nurses administer gravity-based infusions and monitor them remotely, to avoid complications and reduce workload. Its real-world effects and economic consequences were unknown., Methods: An exploratory survey was carried out to estimate the potential impact of the Monidor solution on events and nurse time use. At the end of their shift, nurses estimated effects in terms of routine room visits avoided, prevention of complications, and impact on nurse time requirements. Linear regression was applied to estimate predictors of time freed. A health economic model was developed to evaluate economic consequences and to calculate the net return on investment for a hypothetical hospital ward. A 1-month time horizon was used, and discounting was not applied., Results: A total of 216 responses were obtained from 6 Finnish hospitals, from a total of 15 wards, and 56.3% of nurses found that the Monidor solution freed nurse time, while < 3.5% experienced additional time requirements. Per nurse shift, the Monidor solution avoided on average 2.064 routine room visits, helped detect end of infusion 1.340 times, and led to 5.045 min of time freed. One routine visit avoided was associated with 2.453 min of time freed in the linear regression. In the conservative setting, the freed monthly capacity in the hypothetical ward amounted to €1270.90 per month (year 2021), yielding a return on investment of 2.63. Uncertainty of linear regression coefficient values was identified as a driver of uncertainty in sensitivity analysis, with return on investment ranging from 1.55 to 3.71., Conclusions: The study demonstrated that management and remote monitoring with the Monidor solution frees nurse time and reduces routine activities associated with gravity-based intravenous infusions. These findings could be confirmed in a comparative empirical study., (© 2022. The Author(s).)

Purpose: Direct oral anticoagulant (DOAC) use for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) has increased steadily in Finland. DOACs have been shown to be cost-effective in comparison to warfarin, but published evidence of relative cost-effectiveness between DOACs is still scarce and mostly based on indirect comparisons of clinical trial evidence. The aim of this study was to compare the cost-effectiveness of apixaban to dabigatran, rivaroxaban and warfarin in a Finnish setting using real-life evidence where available., Patients and Methods: A lifetime Markov simulation model used previously in a published Finnish assessment comparing apixaban and warfarin was modified and updated with the relative effectiveness and safety data available from the real-world NAXOS-study and representative Finnish input data for patient characteristics, event risks, mortality, resource use, costs, and quality of life. Apixaban's cost-effectiveness was assessed from health care payer perspective (using 3% per year discount rate) based on incremental cost-effectiveness ratio (ICER, cost per quality-adjusted life year [QALY] gained), probability of cost-effectiveness (at willingness-to-pay [WTP] of 35,000 euros/QALY), and net monetary benefit (NMB)., Results: Apixaban increased the average modelled quality-adjusted life-expectancy and reduced the average total health care costs of AF patients when compared to warfarin (+0.14 QALYs, -3691 euros), dabigatran (+0.11 QALYs, -404 euros), and rivaroxaban (+0.03 QALYs, -43 euros). The resulting NMB of apixaban versus warfarin, dabigatran and rivaroxaban was 8723, 4168, and 1129 euros, respectively. The respective probabilities of apixaban being cost-effective against each comparator were 100%, 92.7%, and 64.0%., Conclusion: In this modelling study, apixaban dominated other anticoagulants in the Finnish real-life setting., Competing Interests: TH and ES are partners and employees, and CA is an employee of ESiOR Oy, which was commissioned by Pfizer Oy to perform this study. ESiOR has carried out commissioned studies and health-economic analyses for several other pharmaceutical companies, food industry companies, device companies, research groups, health care organizations, and hospitals. ML is an employee of Aalto University. PE, SS and MK are employees of Pfizer Oy. This study was sponsored by Pfizer and Bristol Myers Squibb. Medical Writing support was provided by Taru Hallinen at ESiOR Oy and was funded by Pfizer and Bristol Myers Squibb. The authors report no other conflicts of interest in this work., (© 2021 Hallinen et al.)

Background: Widely used risk equations for cardiovascular outcomes for individuals with type 2 diabetes mellitus (T2DM) have been incapable of predicting cardioprotective effects observed in recent cardiovascular outcomes trials (CVOTs) involving individuals with T2DM at high risk for or with established cardiovascular disease (CVD)., Objective: We developed cardiovascular and mortality risk equations using patient-level data from the CANVAS (CANagliflozin cardioVascular Assessment Study) Program to address this shortcoming., Methods: Data from 10,142 patients with T2DM at high risk for or with established CVD, randomized to canagliflozin + standard of care (SoC) or SoC alone and followed for a mean duration of 3.6 years in the CANVAS Program were used to derive parametric risk equations for myocardial infarction (MI), stroke, hospitalization for heart failure (HHF), and death. Accumulated knowledge from the widely used UKPDS-OM2 (United Kingdom Prospective Diabetes Study Outcomes Model 2) was leveraged, and any departures in parameterization were limited to those necessary to provide adequate goodness of fit. Candidate explanatory covariates were selected using only the placebo arm to minimize confounding effects. Internal validation was performed separately by study treatment arm., Results: UKPDS-OM2 predicted CANVAS Program outcomes poorly. Recalibrating UKPDS-OM2 intercepts improved calibration in some cases. Refitting the coefficients but otherwise preserving the UKPDS-OM2 structure improved the fit substantially, which was sufficient for stroke and death. For MI, reselecting UKPDS-OM2 covariates and functional form proved sufficient. For HHF, selection from a broad set of candidate covariates and inclusion of a canagliflozin indicator was required., Conclusion: These risk equations address some of the limitations of widely used risk equations, such as the UKPDS-OM2, for modeling cardioprotective treatments for individuals with T2DM and high cardiovascular risk, including derivation from overly healthy patients treated with agents that lack cardioprotection and have been described as reflecting a different therapeutic era. Future work is needed to examine external validity.

Introduction: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study showed that compared with placebo, canagliflozin 100 mg significantly reduced the risk of major cardiovascular events and adverse renal outcomes in patients with diabetic kidney disease (DKD). We developed a simulation model that can be used to estimate the long-term health and economic consequences of DKD treatment interventions for patients matching the CREDENCE study population., Methods: The CREDENCE Economic Model of DKD (CREDEM-DKD) was developed using patient-level data from CREDENCE (which recruited patients with estimated glomerular filtration rate 30 to < 90 mL/min/1.73 m 2 , urinary albumin to creatinine ratio > 300-5000 mg/g, and taking the maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor). Risk prediction equations were fit for start of maintenance dialysis, doubling of serum creatinine, hospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. A micro-simulation model was constructed using these risk equations combined with user-definable kidney transplant event risks. Internal validation was performed by loading the model to replicate the CREDENCE study and comparing predictions with trial Kaplan-Meier estimate curves. External validation was performed by loading the model to replicate a subgroup of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program with patient characteristics that would have qualified for inclusion in CREDENCE., Results: Risk prediction equations generally fit well and exhibited good concordance, especially for the placebo arm. In the canagliflozin arm, modest underprediction was observed for myocardial infarction, along with overprediction of dialysis, doubling of serum creatinine, and all-cause mortality. Discrimination was strong (0.85) for the renal outcomes, but weaker for the macrovascular outcomes and all-cause mortality (0.60-0.68). The model performed well in internal and external validation exercises., Conclusion: CREDEM-DKD is an important new tool in the evaluation of treatment interventions in the DKD population., Trial Registration: ClinicalTrials.gov identifier, NCT02065791.

Objectives: The cardiovascular outcomes challenge examined the predictive accuracy of 10 diabetes models in estimating hard outcomes in 2 recent cardiovascular outcomes trials (CVOTs) and whether recalibration can be used to improve replication., Methods: Participating groups were asked to reproduce the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program. Calibration was performed and additional analyses assessed model ability to replicate absolute event rates, hazard ratios (HRs), and the generalizability of calibration across CVOTs within a drug class., Results: Ten groups submitted results. Models underestimated treatment effects (ie, HRs) using uncalibrated models for both trials. Calibration to the placebo arm of EMPA-REG OUTCOME greatly improved the prediction of event rates in the placebo, but less so in the active comparator arm. Calibrating to both arms of EMPA-REG OUTCOME individually enabled replication of the observed outcomes. Using EMPA-REG OUTCOME-calibrated models to predict CANVAS Program outcomes was an improvement over uncalibrated models but failed to capture treatment effects adequately. Applying canagliflozin HRs directly provided the best fit., Conclusions: The Ninth Mount Hood Diabetes Challenge demonstrated that commonly used risk equations were generally unable to capture recent CVOT treatment effects but that calibration of the risk equations can improve predictive accuracy. Although calibration serves as a practical approach to improve predictive accuracy for CVOT outcomes, it does not extrapolate generally to other settings, time horizons, and comparators. New methods and/or new risk equations for capturing these CV benefits are needed., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular disease is a leading cause of mortality in people with type 2 diabetes mellitus (T2DM). Beginning in 2015, long-term cardiovascular outcomes trials (CVOTs) have reported cardioprotective benefits for two classes of diabetes drugs. In addition to improving the lives of patients, these health benefits affect relative value (i.e., cost-effectiveness) of these agents compared with each other and especially compared with other agents. While long-term CVOT data on hard outcomes are a great asset, economic modeling of the value of this cardioprotection faces many new empirical challenges. The aim of this study was to identify different approaches used to incorporate drug-mediated cardioprotection into T2DM economic models, to identify pros and cons of these approaches, and to highlight additional considerations., Methods: A review of T2DM modeling applications (manuscript or conference abstracts) that included direct cardioprotective effects was conducted from January 2015 to September 2018. Model applications were classified on the basis of the mechanism used to model cardioprotection [i.e., directly via hazard ratios (HRs) for cardiovascular outcomes or indirectly via biomarker mediation]. Details were extracted and the studies were evaluated., Results: Five full-length articles and 16 conference abstracts (of which 11 posters were found) qualified for study inclusion. While the approaches used were diverse, the five full-length publications and all but two of the abstracts modeled cardioprotection used direct HRs from the relevant CVOT. The remaining two posters modeled cardioprotection using CVOT HRs in combination with treatment effects mediated through known risk factors., Conclusion: The classification of empirical methods in cardioprotection was intended to facilitate a better understanding of the pros and cons of different methodologies. A substantial diversity was observed, though most used trial HRs directly. Given the differences observed, we believe that diabetes modelers and other stakeholders can benefit from a formal discussion and evolving consensus., Funding: Janssen Global Services, LLC (Raritan, NJ, USA).

Aims: Network meta-analyses (NMAs) are valuable ways to generate comparative effectiveness data for therapies available to treat type 2 diabetes mellitus (T2DM). This review assesses NMAs that evaluate sodium glucose co-transporter 2 (SGLT2) inhibitors for treatment of T2DM and discusses potential issues in conducting and interpreting NMAs., Methods: A systematic literature search was conducted on September 13, 2018 using the search terms "network meta-analysis," "SGLT2," variations of these terms, and individual SGLT2 inhibitor names. Extracted data included NMA objectives, methods, target populations, treatments, study endpoints, length of follow-up, and funding. Differences between NMAs were investigated., Results: Thirty-five full-length publications met criteria for inclusion. In most NMAs, the target population was defined by therapeutic regimen (e.g., combination with metformin). Follow-up intervals permitted in NMAs varied considerably (range, 4-208 weeks). Twenty-nine NMAs included dapagliflozin, 28 evaluated canagliflozin, and 27 evaluated empagliflozin. Nine NMAs used frequentist methods; 16 used Bayesian methods. Six NMAs were funded by pharmaceutical manufacturers. Heterogeneity across NMAs was seen in scope, time frame, and other aspects of analytic design., Conclusions: Although this review indicates that methodological guidelines for reporting NMAs were generally followed, it also emphasizes the need for T2DM-specific guidance requiring clear reporting of NMA scope and objectives to aid appropriate interpretation and use of NMA results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The Eighth Mount Hood Challenge (held in St. Gallen, Switzerland, in September 2016) evaluated the transparency of model input documentation from two published health economics studies and developed guidelines for improving transparency in the reporting of input data underlying model-based economic analyses in diabetes., Methods: Participating modeling groups were asked to reproduce the results of two published studies using the input data described in those articles. Gaps in input data were filled with assumptions reported by the modeling groups. Goodness of fit between the results reported in the target studies and the groups' replicated outputs was evaluated using the slope of linear regression line and the coefficient of determination (R 2 ). After a general discussion of the results, a diabetes-specific checklist for the transparency of model input was developed., Results: Seven groups participated in the transparency challenge. The reporting of key model input parameters in the two studies, including the baseline characteristics of simulated patients, treatment effect and treatment intensification threshold assumptions, treatment effect evolution, prediction of complications and costs data, was inadequately transparent (and often missing altogether). Not surprisingly, goodness of fit was better for the study that reported its input data with more transparency. To improve the transparency in diabetes modeling, the Diabetes Modeling Input Checklist listing the minimal input data required for reproducibility in most diabetes modeling applications was developed., Conclusions: Transparency of diabetes model inputs is important to the reproducibility and credibility of simulation results. In the Eighth Mount Hood Challenge, the Diabetes Modeling Input Checklist was developed with the goal of improving the transparency of input data reporting and reproducibility of diabetes simulation model results., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: The Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM) was developed to address study questions pertaining to the cost-effectiveness of treatment alternatives in the care of patients with type 2 diabetes mellitus (T2DM). Naturally, the usefulness of a model is determined by the accuracy of its predictions. A previous version of ECHO-T2DM was validated against actual trial outcomes and the model predictions were generally accurate. However, there have been recent upgrades to the model, which modify model predictions and necessitate an update of the validation exercises., Objectives: The objectives of this study were to extend the methods available for evaluating model validity, to conduct a formal model validation of ECHO-T2DM (version 2.3.0) in accordance with the principles espoused by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Society for Medical Decision Making (SMDM), and secondarily to evaluate the relative accuracy of four sets of macrovascular risk equations included in ECHO-T2DM., Methods: We followed the ISPOR/SMDM guidelines on model validation, evaluating face validity, verification, cross-validation, and external validation. Model verification involved 297 'stress tests', in which specific model inputs were modified systematically to ascertain correct model implementation. Cross-validation consisted of a comparison between ECHO-T2DM predictions and those of the seminal National Institutes of Health model. In external validation, study characteristics were entered into ECHO-T2DM to replicate the clinical results of 12 studies (including 17 patient populations), and model predictions were compared to observed values using established statistical techniques as well as measures of average prediction error, separately for the four sets of macrovascular risk equations supported in ECHO-T2DM. Sub-group analyses were conducted for dependent vs. independent outcomes and for microvascular vs. macrovascular vs. mortality endpoints., Results: All stress tests were passed. ECHO-T2DM replicated the National Institutes of Health cost-effectiveness application with numerically similar results. In external validation of ECHO-T2DM, model predictions agreed well with observed clinical outcomes. For all sets of macrovascular risk equations, the results were close to the intercept and slope coefficients corresponding to a perfect match, resulting in high R 2 and failure to reject concordance using an F test. The results were similar for sub-groups of dependent and independent validation, with some degree of under-prediction of macrovascular events., Conclusion: ECHO-T2DM continues to match health outcomes in clinical trials in T2DM, with prediction accuracy similar to other leading models of T2DM.

Background: Type 2 diabetes mellitus (T2DM) is chronic and progressive and the cost-effectiveness of new treatment interventions must be established over long time horizons. Given the limited durability of drugs, assumptions regarding downstream rescue medication can drive results. Especially for insulin, for which treatment effects and adverse events are known to depend on patient characteristics, this can be problematic for health economic evaluation involving modeling., Objectives: To estimate parsimonious multivariate equations of treatment effects and hypoglycemic event risks for use in parameterizing insulin rescue therapy in model-based cost-effectiveness analysis., Methods: Clinical evidence for insulin use in T2DM was identified in PubMed and from published reviews and meta-analyses. Study and patient characteristics and treatment effects and adverse event rates were extracted and the data used to estimate parsimonious treatment effect and hypoglycemic event risk equations using multivariate regression analysis., Results: Data from 91 studies featuring 171 usable study arms were identified, mostly for premix and basal insulin types. Multivariate prediction equations for glycated hemoglobin A 1c lowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R 2 ) for both outcomes were generally good, ranging from 0.44 to 0.84. Multivariate prediction equations for symptomatic, nocturnal, and severe hypoglycemic events were also estimated, though considerable heterogeneity in definitions limits their usefulness., Conclusions: Parsimonious and robust multivariate prediction equations were estimated for glycated hemoglobin A 1c and weight change, separately for insulin-naive and insulin-experienced patients. Using these in economic simulation modeling in T2DM can improve realism and flexibility in modeling insulin rescue medication., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To assess the frequency of warfarin use, the achieved international normalised ratio (INR) balance among warfarin users and the primary healthcare outpatient costs of patients with atrial fibrillation (AF)., Design: Retrospective, non-interventional registry study., Setting: Primary healthcare., Participants: All patients with AF (n=2746) treated in one Finnish health centre between October 2010 and March 2012., Methods: Data on healthcare resource use, warfarin use, individually defined target INR range and INR test results were collected from the primary healthcare database for patients with AF diagnosis. The analysed dataset consisted of a 1-year follow-up. Warfarin treatment balance was estimated with the proportion of time spent in the therapeutic INR range (TTR). The cost of used healthcare resources was valued separately with national and service provider unit costs to estimate the total outpatient treatment costs. The factors potentially impacting the treatment costs were assessed with a generalised linear regression model., Results: Approximately 50% of the patients with AF with CHADS-VASc ≥1 used warfarin. The average TTR was 65.2% but increased to 74.5% among patients using warfarin continuously (ie, without gaps exceeding 56 days between successive INR tests) during follow-up. One-third of the patients had a TTR of below 60%. The average outpatient costs in the patient cohort were €314.44 with the national unit costs and €560.26 with the service provider unit costs. The costs among warfarin users were, on average, €524.11 or €939.54 higher compared with the costs among non-users, depending on the used unit costs. A higher TTR was associated with lower outpatient costs., Conclusions: The patients in the study centre using warfarin were, on average, well controlled on warfarin, yet one-third of patients had a TTR of below 60%.

Objective: This study constructed the Economic and Health Outcomes Model for type 2 diabetes mellitus (ECHO-T2DM), a long-term stochastic microsimulation model, to predict the costs and health outcomes in patients with T2DM. Naturally, the usefulness of the model depends upon its predictive accuracy. The objective of this work is to present results of a formal validation exercise of ECHO-T2DM., Methods: The validity of ECHO-T2DM was assessed using criteria recommended by the International Society for Pharmacoeconomics and Outcomes Research/Society for Medical Decision Making (ISPOR/SMDM). Specifically, the results of a number of clinical trials were predicted and compared with observed study end-points using a scatterplot and regression approach. An F-test of the best-fitting regression was added to assess whether it differs statistically from the identity (45°) line defining perfect predictions. In addition to testing the full model using all of the validation study data, tests were also performed of microvascular, macrovascular, and survival outcomes separately. The validation tests were also performed separately by type of data (used vs not used to construct the model, economic simulations, and treatment effects)., Results: The intercept and slope coefficients of the best-fitting regression line between the predicted outcomes and corresponding trial end-points in the main analysis were -0.0011 and 1.067, respectively, and the R(2) was 0.95. A formal F-test of no difference between the fitted line and the identity line could not be rejected (p = 0.16). The high R(2) confirms that the data points are closely (and linearly) associated with the fitted regression line. Additional analyses identified that disagreement was highest for macrovascular end-points, for which the intercept and slope coefficients were 0.0095 and 1.225, respectively. The R(2) was 0.95 and the estimated intercept and slope coefficients were 0.017 and 1.048, respectively, for mortality, and the F-test was narrowly rejected (p = 0.04). The sub-set of microvascular end-points showed some tendency to over-predict (the slope coefficient was 1.095), although concordance between predictions and observed values could not be rejected (p = 0.16)., Limitations: Important study limitations include: (1) data availability limited one to tests based on end-of-study outcomes rather than time-varying outcomes during the studies analyzed; (2) complex inclusion and exclusion criteria in two studies were difficult to replicate; (3) some of the studies were older and reflect outdated treatment patterns; and (4) the authors were unable to identify published data on resource use and costs of T2DM suitable for testing the validity of the economic calculations., Conclusions: Using conventional methods, ECHO-T2DM simulated the treatment, progression, and patient outcomes observed in important clinical trials with an accuracy consistent with other well-accepted models. Macrovascular outcomes were over-predicted, which is common in health-economic models of diabetes (and may be related to a general over-prediction of event rates in the United Kingdom Prospective Diabetes Study [UKPDS] Outcomes Model). Work is underway in ECHO-T2DM to incorporate new risk equations to improve model prediction.

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix(®) or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

Background: Golimumab is a novel TNF-α inhibitor licensed to treat patients with active PsA. Although its clinical efficacy has been proven in clinical trials, its cost effectiveness is yet to be established., Objectives: To estimate the cost effectiveness of golimumab among patients with active PsA from the UK NHS perspective., Methods: A decision analytic model was used to simulate progression of a hypothetical cohort of active PsA patients on golimumab and other TNF-α inhibitors as well as palliative care. The clinical evidence was derived from clinical trials of TNF-α inhibitors and compared using mixed treatment models. The primary outcome measure was quality-adjusted life years (QALYs) estimated based on change in Health Assessment Questionnaire (HAQ) and Psoriasis Area Severity Index (PASI) from baseline. The annual acquisition cost of golimumab was assumed to be identical to annual cost of other subcutaneous TNF-α inhibitors. The resource use costs and outcomes were discounted at 3.5% over a period of 40 years. The uncertainty surrounding important variables was further explored using probabilistic sensitivity analyses (PSA)., Results: TNF-α inhibitors were significantly superior to palliative care but comparable to each other on Psoriatic Arthritis Response Criteria (PsARC), HAQ and PASI response. The incremental cost effectiveness ratio (ICERs) for golimumab compared to palliative care was £16,811 for PsA patients and £16,245 for a subgroup of PsA patients with significant psoriasis. At an acceptability threshold of £30,000 per QALY, the probability of golimumab being cost effective is 89%., Conclusion: Once monthly, golimumab is a cost-effective treatment alternative for patients with active PsA. With its patient-focussed attributes, golimumab is likely to offer additional choice in PsA treatment.

Background: The cost-effectiveness of triptans in the treatment of migraine has not been assessed since generic sumatriptan entered the Finnish market in 2008., Methods: Using systematic review and mixed treatment comparison, the effectiveness of triptans was estimated with regard to 2-hour response, 2-hour pain-free, recurrence, and any adverse event, using published clinical data. Direct and indirect costs (2010 EUR, societal perspective) and quality-adjusted life-years (QALYs) were evaluated over one acute migraine attack using a decision-tree model., Results: The meta-analysis combined data from fifty-six publications. The highest probability of achieving the primary outcome, "sustained pain-free, no adverse event" (SNAE), was estimated for eletriptan 40 mg (20.9 percent). Sumatriptan 100 mg was the treatment with lowest estimated costs (€20.86), and the incremental cost-effectiveness ratio of eletriptan 40 mg compared with sumatriptan 100 mg was €43.65 per SNAE gained (€19,659 per QALY gained)., Conclusion: Depending on the decision-maker's willingness-to-pay threshold, either sumatriptan 100 mg or eletriptan 40 mg is likely to be cost-effective.

Objectives: To assess the value for money of alternative chemotherapy strategies for managing advanced colorectal cancer using irinotecan or oxaliplatin, either in sequence or in combination with fluorouracil., Methods: A cost-effectiveness model was developed using data from the U.K. fluorouracil, oxaliplatin, and CPT11 (irinotecan)--use and sequencing (FOCUS) trial. The analysis adopted the perspective of the U.K. National Health Service. Input parameters were derived using a system of risk equations (for probabilities), count data regression models (for resource use), and generalized linear models (for utilities). Parameter estimates were obtained using Markov chain Monte Carlo methods, propagating the simulation values through the state-transition model to characterize appropriately the joint distributions of expected cost, survival and quality-adjusted life years for each treatment strategy. An acceptability frontier was used to represent the probability that the optimal option is cost-effective at different values of the cost-effectiveness threshold., Results: The base-case analysis used drug unit costs provided by a typical English hospital. First-line doublet therapy combination therapy fluorouracil (5FU) plus irinotecan was the most cost-effective strategy at standard thresholds, with an incremental cost-effectiveness ratio (ICER) of £14,877 (pound sterling) compared with first-line 5FU until treatment failure followed by single agent irinotecan. Other strategies were all subject to extended dominance. A sensitivity analysis using published drug (list) prices found the most cost-effective strategy would be first-line fluorouracil until failure followed by 5FU plus irinotecan (ICER: £19,753)., Conclusions: The combination of 5FU and irinotecan (whether used first or second line) appears to be more cost-effective than the single agent sequential therapies used in the FOCUS trial, or 5FU plus oxaliplatin., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression., Design: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine). The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year., Data Sources: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources., Results: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine., Conclusion: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

Objectives. Quantify changes in hospital resource use in Finland following initiation of risperidone long-acting injection (RLAI). Materials and Methods. A retrospective multi-center chart review (naturalistic setting) was used to compare annual hospital bed-days and hospital episodes for 177 schizophrenia patients (mean age 47.1 years, 52% female, 72% hospitalized) before and after initiation of RLAI (between January 2004 and June 2005) using the within-patient "mirror-image" study design. The base case analytical approach allocated hospital episodes overlapping the start date entirely to the preinitiation period. In order to investigate the impact of inpatient care ongoing at baseline, the change in bed-days was also estimated using an alternative analytical approached related to economic modelling. Results. In the conventional analysis, the mean annual hospitalisation costs declined by €11,900 and the number of bed-days was reduced by 40%, corresponding to 0.19 fewer hospital episodes per year. The reductions in bed-days per patient-year were similar for patients switched to RLAI as inpatients and as outpatients. In the modelling-based analysis, an 8% reduction in bed-days per year was observed. Conclusion. Despite uncertainty in the choice of analytic approach for allocating inpatient episodes that overlapping this initiation, consistent reductions in resource use are associated with the initiation of RLAI in Finland.

Background: Trastuzumab is a standard treatment of HER2-positive early breast cancer in many countries, and it is usually given as a one year adjuvant treatment. However, its cost-effectiveness has not been assessed in Finland. The Finland Herceptin (FinHer) trial has compared a shorter 9-week treatment protocol against no trastuzumab with promising results. The aim of this study was to assess the potential cost-effectiveness of the 9-week treatment based on the recently published five-year follow-up results of the FinHer trial., Methods: An evaluation model of breast cancer treatment was constructed using fitted survival estimates and a long-term Markov model. The cost-effectiveness of 9-week adjuvant treatment was assessed in a Finnish setting, compared to treatment without trastuzumab. The analysis was performed from a societal perspective, and a 3% discount rate was applied for future costs and outcomes. Value of information analysis was performed to estimate the potential value of further research., Results: According to the probabilistic analysis, the incremental cost-effectiveness ratio was €12 000 per quality adjusted life year (QALY), and €9300 per life year gained (LYG), when comparing adjuvant trastuzumab therapy to standard treatment without trastuzumab. The modelled incremental outcomes for trastuzumab treatment were 0.66 QALY and 0.85 LYG for a lifetime perspective. Value of information analysis showed that additional research on treatment effects would be most valuable for reducing uncertainty in the adoption decision., Conclusions: Adjuvant 9-week trastuzumab is likely to be a cost-effective treatment in the Finnish setting. Results from an ongoing trial comparing adjuvant 9-week treatment with the 12-month treatment will play a key role in addressing the uncertainty related to the treatment effect and potential cost-effectiveness of these two treatment protocols.

Background: In patients with metastases limited to the liver (liver-limited disease [LLD]), effective therapies such as monoclonal antibodies combined with chemotherapy may facilitate metastasis resection and improve long-term survival., Objective: This study assessed the cost-effectiveness of bevacizumab and cetuximab in the treatment of patients with colorectal cancer presenting with initially unresectable liver metastases of the Kirsten rat sarcoma viral oncogene homolog (K-ras) wild type, from the perspective of German statutory health insurance., Methods: The health-economic modeling approach presented here made indirect comparisons between available data on bevacizumab and cetuximab treatment outcomes using evidence synthesis techniques, extrapolating from the follow-up duration of identified clinical trials to a longer time horizon of up to 10 years and inferring costs and health outcomes based on modeled patient pathways. Expert opinion and Delphi panel methods were used for some assumptions, when evidence was missing. Probabilistic sensitivity analyses and different scenario analyses were applied to test for uncertainty around input parameters and assumptions., Results: For the metastatic colorectal cancer LLD population with K-ras wild-type genotype, mean overall survival estimates were 37.7 months for first-line treatment with cetuximab plus FOLFIRI (irinotecan, leucovorin, fluorouracil) and 30.4 months for bevacizumab plus FOLFOX (oxaliplatin, leucovorin, fluorouracil). Corresponding discounted survival estimates were 2.88 life-years with cetuximab plus FOLFIRI versus 2.38 life-years with bevacizumab plus FOLFOX, an average gain of 0.50 discounted life-years. The incremental cost-effectiveness ratio of cetuximab plus FOLFIRI versus bevacizumab plus FOLFOX was €15,020 (year 2010 €) per life-year gained in the base case (with a 95% CI from the probabilistic sensitivity analysis of €3806-€24,660). Results were robust in different scenario analyses as well as in the probabilistic sensitivity analysis., Conclusions: First-line treatment with cetuximab plus FOLFIRI offers a cost-effective treatment option versus bevacizumab plus FOLFOX for the metastatic colorectal cancer LLD population with K-ras wild-type genotype in Germany. K-ras testing should be performed on all presenting cases of metastatic colorectal cancer to ensure access to this treatment option., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Meta-analysis allows the quantitative combination of results of multiple studies that address similar research questions. Traditional meta-analysis of studies involving a direct comparison of two treatment alternatives can be applied to estimate the overall relative efficacy of these two treatment alternatives. All treatment options relevant to practical treatment decisions are, however, not always compared directly against each other in clinical studies, but indirect comparison via a common comparator may be possible. To use all relevant evidence from both direct and indirect comparisons of treatment options, advanced methods of meta-analysis have been developed. These so-called network meta-analyses extend the traditional meta-analysis to cases where a network of studies enables different pair-wise direct and indirect comparisons between multiple treatment alternatives, thereby forming a network of relevant evidence.

Background: Despite its proven efficacy, infliximab is often considered to be an expensive treatment for patients with psoriatic arthritis., Objectives: To estimate the cost-effectiveness of infliximab among patients with active and progressive psoriatic arthritis., Methods: A decision analytic model was constructed to simulate disease progression in hypothetical cohorts of patients with psoriatic arthritis receiving infliximab maintenance treatment. The primary response measure was change in Health Assessment Questionnaire score from a baseline estimated from mixed treatment models drawn from published clinical trials. Palliative care, comprising nonbiologic disease-modifying antirheumatic drugs, was used as a comparator. The primary outcome was quality-adjusted life years. The dose of infliximab was estimated for a range of 60 to 80 kg per patient body weight. The costs and outcomes were discounted at 3.5% for a period of 40 years. Uncertainty around the results was explored with probabilistic sensitivity analysis., Results: The mixed treatment comparison showed a significant reduction in Health Assessment Questionnaire score across all patients. The tumor necrosis factor α inhibitors were significantly superior to palliative care but comparable with one another. The incremental cost-effectiveness ratios for etanercept, adalimumab, and infliximab relative to palliative care were £17,327; £19,246; and £16,942 to £23,022, respectively, across all patients with psoriatic arthritis and £16,613; £18,170; and £15,788 to £21,736, respectively, in the subgroup with significant psoriasis., Conclusion: Infliximab represents a cost-effective treatment option well within the National Institute for Health and Clinical Excellence threshold relative to palliative care. In light of equivalent outcomes with other tumor necrosis factor α inhibitors, its position in the treatment pathway is likely to be governed by treatment costs., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Predators can have profound impacts on the dynamics of their prey that depend on how predator consumption is affected by prey density (the predator's functional response). Consumption by a generalist predator is expected to depend on the densities of all its major prey species (its multispecies functional response, or MSFR), but most studies of generalists have focussed on their functional response to only one prey species., Methodology and Principal Findings: Using Bayesian methods, we fit an MSFR to field data from an avian predator (the hen harrier Circus cyaneus) feeding on three different prey species. We use a simple graphical approach to show that ignoring the effects of alternative prey can give a misleading impression of the predator's effect on the prey of interest. For example, in our system, a "predator pit" for one prey species only occurs when the availability of other prey species is low., Conclusions and Significance: The Bayesian approach is effective in fitting the MSFR model to field data. It allows flexibility in modelling over-dispersion, incorporates additional biological information into the parameter priors, and generates estimates of uncertainty in the model's predictions. These features of robustness and data efficiency make our approach ideal for the study of long-lived predators, for which data may be sparse and management/conservation priorities pressing.

Objective: To estimate the cost-effectiveness of primary angioplasty compared with thrombolysis for acute ST elevation myocardial infarction. Design Cost analysis of UK observational database, incorporated into decision analytical model., Methods: Patients receiving treatment within a comprehensive angioplasty service were compared with control patients receiving thrombolysis-based care. The treatment costs and delays to treatment of thrombolysis and angioplasty were estimated. These estimates were then incorporated into an existing model of cost-effectiveness that synthesises evidence from 22 randomised trials to estimate health outcomes measured by quality-adjusted life years (QALYs). Main outcome measures Costs from a health service perspective and outcomes measured as quality adjusted., Results: The mean cost of the initial treatment was 3509 pounds for thrombolysis at control sites, 5176 pounds for angioplasty in usual working hours at National Infarct Angioplasty Project sites and an additional 245 pounds if undertaken out of hours. Angioplasty-based care had an incremental cost of 4520 pounds per QALY gained and 0.9 probability of being cost-effective at a threshold of 20,000 pounds per QALY gained. This probability was >0.95 if patients were directly admitted to the cardiac catheter laboratory, 0.75 if admitted via the emergency department or coronary care unit and 0.38 if transferred to the angioplasty centre from another hospital., Conclusions: Overall, primary angioplasty-based care is highly likely to be cost-effective at an assumed threshold of 20,000 pounds per QALY gained. It is more likely to be cost-effective if patients are admitted directly to the cardiac catheter laboratory rather than via other hospital departments, or if transferred from another hospital.

Background: Atopic dermatitis (AD) affects health and quality of life and it has great impact on both health-care costs and costs to the society., Objectives: The objective of this study was to develop a model to analyse the cost-effectiveness of a barrier-strengthening moisturizing cream as maintenance therapy compared with no treatment after initial treatment with betamethasone valerate in adult patients with AD in Sweden. A further aim was to apply a similar health-economic analysis for Denmark, Norway and Finland., Methods: A Markov simulation model was developed including data from three sources: (i) efficacy data from a randomized controlled trial including patients with moderate AD treated with either a moisturizing cream or no treatment, (ii) resource utilization and quality of life data, and (iii) unit prices from official price lists. A societal perspective was used and the analysis was performed according to treatment practice in Sweden. The model simulation was also applied for Denmark, Norway and Finland with inclusion of country-specific unit costs. Sensitivity analyses were performed to test the robustness of the results., Results: The results from the present analyses of treatment for patients with moderate AD indicate that maintenance treatment with a moisturizing cream during eczema-free periods could be cost-effective in a societal perspective. Similar results were obtained for Sweden, Denmark, Norway and Finland., Conclusions: According to the analysis, treatment with a moisturizing cream was found to be a cost-effective option compared with no treatment in eczema-free periods in adult patients with AD in the four Nordic countries.

Background: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered., Objective: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships., Methods: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (CrI)) as a function of the additional time delay associated with angioplasty., Results: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean (SE) angioplasty-related time delay (over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis (OR = 0.68 (95% CrI 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 (95% CrI 0.20 to 0.51); for non-fatal stroke OR = 0.24 (95% CrI 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation., Conclusions: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1-month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays.

Objective: To assess the cost effectiveness of primary angioplasty, compared with medical management with thrombolytic drugs, to achieve reperfusion after acute myocardial infarction (AMI) from the perspective of the UK NHS., Design: Bayesian evidence synthesis and decision analytic model., Methods: A systematic review was conducted and Bayesian statistical methods used to synthesise evidence from 22 randomised control trials. Resource utilisation was based on UK registry data, published literature and national databases, with unit costs taken from routine NHS sources and published literature., Main Outcome Measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs)., Results: For the base case, the incremental cost-effectiveness ratio of primary angioplasty was 9241 pounds sterling for each additional QALY, with a probability of being cost effective of 0.90 for a cost-effectiveness threshold of 20,000 pounds sterling. Results were sensitive to variations in the additional time required to initiate treatment with primary angioplasty., Conclusions: Primary angioplasty is cost effective for the treatment of AMI on the basis of threshold cost-effectiveness values used in the NHS and subject to a delay of up to about 80 minutes. These findings are mainly explained by the superior mortality benefit and the prevention of non-fatal outcomes associated with primary angioplasty for delays of up to this length.