Advantages in Management and Remote Monitoring of Intravenous Therapy: Exploratory Survey and Economic Evaluation of Gravity-Based Infusions in Finland.

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.

In hospitals, patients often receive fluids intravenously. These fluids enter the blood circulation directly, and their incorrect administration (too much or too little, too slow or too fast) can have serious and potentially life-threatening consequences. The Monidor solution aims to improve administration of intravenous fluids. It consists of two components: a mobile app for remote monitoring and a meter for bedside management. This study aimed to estimate the impact of the Monidor solution on administration of intravenous fluids and to assess how the Monidor solution would affect costs. Among the factors considered were the price of the devices, nurse time freed, and prevention of complications with the intravenous therapies. The data were collected via questionnaires from nurses from 15 wards in 6 Finnish hospitals. According to the responses and a health economic model designed for this study, the Monidor solution freed capacity with a value of €1270.90 per month. When considering the local cost of the Monidor solution, the return on investment was positive. In summary, the Monidor solution is cost-effective; routine room visits by nurses were avoided, problems with infusions were detected earlier, and nurse time was freed. These findings could be confirmed in a larger study.

Exploring Structural Uncertainty and Impact of Health State Utility Values on Lifetime Outcomes in Diabetes Economic Simulation Models: Findings from the Ninth Mount Hood Diabetes Quality-of-Life Challenge.

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.

Cost-Effectiveness of Apixaban versus Other Direct Oral Anticoagulants and Warfarin in the Prevention of Thromboembolic Complications Among Finnish Patients with Non-Valvular Atrial Fibrillation.

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.

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

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.

Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data.

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 m2, 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.

Challenges and Opportunities Associated with Incorporating New Evidence of Drug-Mediated Cardioprotection in the Economic Modeling of Type 2 Diabetes: A Literature Review.

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).

Computer Modeling of Diabetes and Its Transparency: A Report on the Eighth Mount Hood Challenge.

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 (R2). 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.

Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland.

PURPOSE: To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. METHODS: A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. RESULTS: In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. CONCLUSION: The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients. FUNDING: UCB Pharma.

Multivariate Prediction Equations for HbA1c Lowering, Weight Change, and Hypoglycemic Events Associated with Insulin Rescue Medication in Type 2 Diabetes Mellitus: Informing Economic Modeling.

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 A1c lowering and weight change were estimated separately for insulin-naive and insulin-experienced patients. Goodness of fit (R2) 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 A1c 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.

Validation of the Economic and Health Outcomes Model of Type 2 Diabetes Mellitus (ECHO-T2DM).

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.

Warfarin treatment among Finnish patients with atrial fibrillation: retrospective registry study based on primary healthcare data.

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%.

Validation of economic and health outcomes simulation model of type 2 diabetes mellitus (ECHO-T2DM).

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.

Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany.

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.

Cost-effectiveness of oral triptans for acute migraine: mixed treatment comparison.

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.

Hospitalisation Utilisation and Costs in Schizophrenia Patients in Finland before and after Initiation of Risperidone Long-Acting Injection.

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.

Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

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.

The cost-effectiveness of different chemotherapy strategies for patients with poor prognosis advanced colorectal cancer (MRC FOCUS).

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.

Cost effectiveness of golimumab for the treatment of active psoriatic arthritis.

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.

Cost-effectiveness of targeted therapy with cetuximab in patients with K-ras wild-type colorectal cancer presenting with initially unresectable metastases limited to the liver in a German setting.

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.

[Indirect comparison and network meta-analyses--new tools for the assessment of evidence on the relative efficacy of drugs]. / Epäsuora vertailu ja verkostometa-analyysit --uudet työkalut lääkkeiden suhteellisen tehon ja vaikuttavuuden arviointiin.

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.