Economic analysis based on multinational studies: methods for adapting findings to national contexts

Background: Health economic parameters are increasingly considered as variables in health care decisions, but decision makers are interested in country-specific evaluations. However, a large number of studies are performed in foreign countries or in a multinational setting, which limits the transferability to a single nation’s context. Objective: The present analysis summarises several of the most common international methods for generating health economic analyses based on clinical studies from different settings. Methods: A narrative literature review was performed to identify potential reasons for limited transferability of health economic evaluation results from one country to another. Based on these results, we searched the methodological literature for analytic approaches to handle the restrictions. Additionally we describe the possibility of transferring foreign economic study results to the country of interest by matching trial data with routine data of national databases. Results: The main factors for limited transferability of health economic findings were found in country-specific differences in resource consumption and the resulting costs. These differences are affected by a number of influencing cofactors (demography, epidemiology and individual patient’s factors) and the overall health care system structures (e.g. payment systems, health provider incentives). However, despite the limitations country-specific health economic assessments could be realised using the pooled/ split analyses approach, some statistical approaches and modelling approaches. Conclusion: A variety of methods for identifying and adjusting country-specific differences in costs, effects and cost-effectiveness was established during the past decades. Multinational studies will continue to play a crucial role in the evaluation of cost-effectiveness at national levels. It seems likely that the growing interest in multinational studies will lead to continued developments in adaptation methods

Positive Behavior Support Systems in a Rural West Texas Middle School

Positive Behavior Support (PBS) programs are being implemented in schools in the United States to support faculty, staff, and students. The purpose of this study was to evaluate a PBS system at a rural west Texas middle school to discover what improvements are necessary for district-wide implementation and sustainability. The study drew on Bandura\u27s social learning theory, which posits that people learn from each other through observation, imitation, and modeling. PBS systems provide the framework for exhibiting specific behavior expectations so students and teachers can get the most from their educational experiences. A program evaluation was completed using discipline data from 2008-2012 from the middle school, observations at the middle school, and archival campus improvement plan results from the campus needs assessment from 2012. The research instrument used to assess the information was a pre-established PBS evaluation system called the School-Wide Evaluation Tool (SET) designed for programmatic assessment. The SET assessment tool guided the evaluation of information gathered from 100 students, 15 teachers, and an administrative team survey to highlight the strengths and weaknesses of the PBS program in the school and district, identify necessary changes to improve its effectiveness, and determine how to best implement the system district-wide. These findings were used to inform a white paper outlining how to implement a successful program and how to maintain the program over time. This evaluation provided specific steps to strengthen each component of a PBS program to ensure school-wide application and sustainability. A positive social change is experienced by students, teachers, and parents by the enhancement of a PBS system that improves student behavior in the school and district

Antithrombotic management and outcomes of patients with atrial fibrillation treated with NOACs early at the time of market introduction:Main results from the PREFER in AF Prolongation Registry

International audienceAbstract The management of patients with atrial fibrillation (AF) has rapidly changed with increasing use of non-vitamin K antagonist oral anticoagulants (NOACs) and changes in the use of rhythm control therapy. The prevention of thromboembolic events European Registry in Atrial Fibrillation Prolongation Registry (PREFER Prolongation) enrolled consecutive patients with AF on NOACs between 2014 and 2016 in a multicentre, prospective, observational study with one-year follow-up, focusing on the time of introduction of NOACs. Overall, 3783 patients were enrolled, with follow-up information available in 3223 (85%). Mean age was 72.2 ± 9.4 years, 40% were women, mean CHA 2 DS 2 VASc score was 3.4 ± 1.6, and 2587 (88.6%) had a CHA 2 DS 2 VASc score ≥ 2. Rivaroxaban was used in half of patients, and dabigatran and apixaban were used in about a quarter of patients each; edoxaban was not available for use in Europe at the time. Major cardiovascular event rate was low: serious events occurred in 74 patients (84 events, 2%), including 24 strokes (1%), 62 major bleeds (2%), of which 30 were life-threatening (1%) and 3 intracranial (0.1%), and 28 acute coronary syndromes (1%). Mortality was 2%. Antiarrhythmic drugs were used in about 50% of patients, catheter ablation in 5%. Adverse events were low in this contemporary European cohort of unselected AF patients treated with NOACs already at the time of their first introduction, despite high thromboembolic risk

Health Economic Analyses and Decision-Making in Healthcare

Ziel der vorliegenden Habilitationsschrift ist es, am Beispiel ausgewählter Arbeiten die Anwendung von gesundheitsökonomischen Analysen im Rahmen von Entscheidungsprozessen im Gesundheitswesen darzustellen, sowie die aktuellen Umsetzungs- und Entwicklungsmöglichkeiten im deutschen Gesundheitswesen aufzuzeigen. Gesundheitsökonomische Modelle dienen dem Verständnis der Kostenstruktur ausgewählter Erkrankungen und helfen, die kurz- und langfristigen Effekte und Kosten einer Technologie abzubilden. Modellierungen kommen insbesondere in Situationen mit nicht ausreichender Datenlage zum Einsatz und liegen überwiegend als Entscheidungsbaumverfahren bzw. Markov- Modelle vor. Sie unterstützen die Synthese von Kurz- und Langzeitergebnissen, helfen den Transfer von Studien in Alltagsbedingungen zu modellieren oder werden im Rahmen der Evaluation eingesetzt. Mit Hilfe der Versorgungsforschung können reale setting-bezogenen Daten in die entscheidungsunterstützende Modellierung integriert werden. Die Analyse detaillierter Kostenstrukturen wurde am Beispiel der überaktiven Blase (OAB) aufgezeigt. Auf Basis epidemiologischer Studien belaufen sich die direkten OAB-bezogenen Kosten auf € 3,98 Mio., wovon die gesetzliche Krankenversicherung € 1,76 Mio. tragen muss. € 1,8 Mio. entstehen im Rahmen der Leistungen der Pflegeversicherung und € 0,41 Mio. werden von den Patienten selbst getragen. Der größte Kostenblock der OAB sind die Aufwendungen für pflegerische Maßnahmen. Krankheitskosten- Analysen helfen Kostenstrukturen aufzudecken und erste Hinweise für Größenordnungen von gesundheitlichen Problemen zu geben. In der zweiten vorgestellten Arbeit wurden die langfristigen Konsequenzen einer einjährigen Gabe von Clopidogrel bei Patienten mit akutem Koronarsyndrom ohne ST- Streckenhebung betrachtet. Mit Gesamt-Kosten in der Clopidogrel Gruppe von € 8.953 pro Patient und in der ASS-Gruppe von € 8.548, konnte auf Basis der Zulassungsstudien ein Kosten-Nutzen-Verhältnis von € 3.113 pro gewonnenen Lebensjahr ermittelt werden. Das Kosten-Nutzen-Verhältnis aus Sicht der Krankenversicherung liegt international im mittleren Bereich. Alle Analysen basierten auf einer Markov-Modellierung, die den langfristigen Verlauf der Erkrankung beschreibt. Die dritte Publikation berichtet über den Kostenvergleich eines flexiblen Asthmatherapieregimes gegenüber einer starren Dosierung bei der Anwendung fixer Budesonid/Formoterol-Kombinations- Inhalatoren. Asthmabezogene Gesamtkosten (€ 277 vs. € 340), direkte Kosten (€ 221 vs. € 292) und Kosten durch Studienmedikation (€ 162 vs. € 234) waren für das flexible Regime niedriger als bei konventioneller Behandlung. Die Kostenstruktur wurde im Versorgungsalltag erhoben, was aus Sicht der Krankenversicherungen als Bewertungsansatz bedeutsam ist. Die Kosten der Versorgung von Patienten mit Knieknorpelläsionen in den ersten fünf Jahren nach Operation werden in der vierten Publikation dargestellt. Die direkten Kosten betrugen in Jahr eins bis fünf € 782, € 398, € 420, € 272 und € 361. Die Höhe der Folgetherapiekosten, sowie die trotz umfangreicher Behandlungen nachhaltig reduzierte Lebensqualität der Patienten machen deutlich, dass ein großes Potential zu Verbesserung des Nutzens sowie des Kosten-Nutzen- Verhältnisses in der Patientenversorgung besteht. Ökonomische Evaluationen können auch auf Basis vorhandener Primärdaten erstellt wer-den, was in der vierten Arbeit am Beispiel der BASS Studie gezeigt wurde. Durchschnittliche direkte Schlaganfall-Kosten pro Patient mit Vorhofflimmern waren höher als die Kosten von Patienten ohne Vorhofflimmern (€ 11.799 vs. € 8.817). Auch nach Adjustierung blieb die signifikante Differenz in Bezug auf die akuten Hospitalisierungskosten bestehen. Die medizinische Versorgung von Schlaganfall-Patienten mit Vorhofflimmern erfordert einen höheren Ressourcenverbrauch. In der letzten Arbeit wurde die Einführung einer Technologie am Beispiel der Sirolimus-freisetzenden Stents (SES) mit Hilfe eines sequentiellen Kontrolldesigns untersucht. Die SES-Patienten verursachten im Vergleich zu unbeschichteten Stents (BMS) über 18 Monate aufgrund der höheren Stentpreise höhere Gesamtkosten (SES € 13.950 versus BMS € 12.273). Die Ergebnisse der allgemeinen und krankheitsspezifischen Lebensqualität zeig- ten nach Implantation eines SES verbesserte Werte. Die Ergebnisse der Studie können als Grundlage für Entscheidungen bezüglich der Leistungsplanung und -erstattung dienen. Gesundheitsökonomische Evaluationen sollten sektor- und budgetübergreifend durchgeführt werden. Um eine Vergleichbarkeit von Publikationen zu erreichen, ist bei der Erhebung der Kostendaten ein standardisierter Ansatz zu fordern. Kosten-Nutzen-Bewertungen können zum Einführungszeitpunkt eines neuen Verfahrens noch nicht über Nutzen- und Kosteneffekte im Versorgungsalltag verfügen. Daher wäre eine zunächst befristete bzw. probatorische Erstattungszusage aus ökonomischer Sicht sinnvoll. Parallel zur Einführung der Kosten-Nutzen-Bewertung sollte eine gesellschaftliche Wertediskussion im Sinne einer Priorisierung von Leistungen öffentlich und transparent geführt werden, da der wissenschaftliche Nutzenbeleg und die Kosten-Nutzen-Bewertung allein nicht zu einer Entscheidungsfindung ausreichen.The objective of this cumulative summary for a postdoctoral qualification as lecturer is to outline the use of health economic analyses in decision-making processes, exemplified by six previously published articles of the author. Furthermore, current implementation and development opportunities concerning health economic evaluations in the German healthcare setting will be highlighted. Health economic models provide an understanding of cost structures of diseases, as well as short and long-term impact of interventions on costs and outcomes. Modelling is applied particularly in complex situations with restricted or not yet available evidence from studies, with decision trees and Markov models being the predominant technologies utilised. These economic models support the synthesis of short and long-term results, simulating the transfer of study results into real life settings which can then be applied to compare treatment strategies. Data from health services research can further strengthen decision-supporting modelling by addressing setting-related issues. The burden of disease study of overactive bladder (OAB) provides an example for the analysis of detailed cost structures. Based on German epidemiological data, OAB-related costs accrue to € 3,98 mill. with € 1,76 mill. to be borne by the statutory health insurance (SHI). € 1,8 mill. arise due to nursing care services whereas € 0,41 mill. are out of pocket payments of patients. The major cost component is costs related to nursing care. Cost of disease analyses help understand cost structures and provide a initial indication of the magnitude of healthcare resource spending in selected health issues. The second publication presents long-term consequences of a one-year administration of Clopidogrel in addition to aspirin (ASA) compared to ASA monotherapy in patients with acute coronary syndrome without ST-segment elevation. Patients receiving Clopidogrel plus ASA or ASA alone accrued cumulative costs of € 8,953 and € 8,548 per patient respectively. Based on the clinical approval study, a cost-efficacy ratio of € 3,113 per life-year saved was calculated. In an international context the cost-efficacy ratio from a sickfund perspective ranks a medium-range position. Analyses were based on a Markov model, which allowed depiction of the long-term course of disease, related costs and potential treatment impact. The third study highlights the contribution of real healthcare data to modelling by a cost comparison of an adjustable maintenance treatment of asthma with budesonide/formoterol in a single inhaler versus fixed treatment over 12 weeks. Both asthma-related total costs (€ 277 vs. € 340), direct costs (€ 221 vs. € 292), as well as costs due to study medication (€ 162 vs. € 234) were lower for the adjustable regime compared to fixed treatment. The fact that costs were based on a real-life setting was of particular importance from a third party payer perspective. The cost of care of patients with cartilage lesions of the knee after a first surgical intervention are described in the fourth publication selected. From the first to the fifth post-operative year, the respective annual direct costs totalled € 782, € 398, € 420, € 272 and € 361. These substantial follow-up costs of patients occurred despite intensive treatment efforts and demonstrate the broad potential to improve patient outcomes and related cost-efficacy ratios when delivering care for patients with knee cartilage lesions. Primary study data might also serve as a sound basis for economic evaluations, as illustrated in the fifth study using data from the German Berlin Acute Stroke Study (BASS). Average direct stroke- related costs per patient with atrial fibrillation were higher compared to those in patients without atrial fibrillation (€ 11,799 vs. € 8,817). After adjusting for confounders, necessary due to the real-life nature of the study, the difference between acute hospitalisation costs remained significant. Delivering healthcare to stroke patients with atrial fibrillation induces higher resource consumption and costs. With the last selected study, the author exemplifies the economic evaluation of a newly launched medical technology using the example of sirolimus-eluting stents (SES) in patients with coronary disease. The total costs of SES implantation were compared to bare metal stents (BMS) applying a sequential control design. In comparison to patients with BMS, SES patients incurred higher total costs (SES € 13,950 versus BMS € 12,273) during the follow-up period of 18 months, primarily due to the higher SES price. After implantation of SES, both generic and disease- specific quality of life data showed better outcomes compared to BMS. With the incorporation of real-life evidence into new health technology appraisals by German decision-making bodies, these study results could serve as a basis for resource planning and reimbursement allocation. Health economic evaluations should incorporate all relevant sectors and budgets along the course of the disease. With regard to obtaining unit costs, crucial in guaranteeing comparability of results and publications, a standardised official costing data set has yet to be established for Germany. Additionally, cost-benefit assessments of medical technologies at market launch can not yet incorporate real-life data with regard to long-term costs and clinical outcomes. Hence, from an economic perspective, a conditional and restricted reimbursement approval would be recommendable until these data become available. In parallel to introducing cost-benefit assessments a transparent and public discussion on societal values for priorisation of healthcare services should be conducted, as these are essential elements of the complex allocation decisions in healthcare. As such, scientific clinical evidence and cost-benefit assessment are vital but are not the only criteria sufficient for decision-making in healthcare

Real world effectiveness and cost consequences of grass pollen SCIT compared with SLIT and symptomatic treatment

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Purpose</jats:title> <jats:p>Real-world evidence (RWE) with regard to allergen-specific immunotherapy (AIT) adherence is increasingly available. Economic modelling has already shown AIT to be cost-effective in the treatment of allergic rhinitis compared with symptomatic treatment. However, analyzing sublingual (SLIT) and subcutaneous (SCIT) immunotherapeutic approaches based on RWE adherence data are not available for Germany. This analysis outlines the cost-effectiveness of SCIT compared with SLIT as well as a symptomatic treatment modality on the basis of recent RWE adherence data.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>A Markov model, with predefined disease stages and a time period of 9 years, was adapted for this analysis. A 6-grass subcutaneous allergoid SCIT preparation and a 5-grass pollen SLIT tablet was employed as AIT administrations. Quality-adjusted life years (QALYs) were calculated based on symptom scores and used as the effectiveness variable. Total costs and cost effectiveness of SCIT, SLIT and symptomatic treatment (ST) were calculated. Model uncertainties were estimated by means of additional sensitivity analyses. Applied discount rate was 3%.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Both SCIT and SLIT preparations proved superior compared to symptomatic treatment with regard to effectiveness. Although more expensive, AIT also proved to be cost-effective. A direct comparison of SCIT (Allergovit®) and SLIT (Oralair®) showed lower total costs for SCIT treatment over the study period of 9 years (SCIT 1779 € versus SLIT 2438 €) and improved effectiveness (SCIT 7.17 QALYs versus SLIT 7.11 QALYs).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>AIT represents a cost-effective treatment option for patients with allergic rhinitis compared with symptomatic treatment. SCIT appeared to be dominant and cost-effective, due in particular to higher patient adherence and lower drug costs.</jats:p> </jats:sec&gt

Cost-effectiveness of adjunctive eptifibatide in patients undergoing coronary stenting in Germany

To determine the cost-effectiveness of adding eptifibatide to the standard treatment for selected high-risk patients undergoing coronary stenting in Germany. Furthermore, to investigate the impact of several extrapolation methods on the results. A Markov model was developed to reflect the clinical events in this specific patient population, including target vessel revascularization, myocardial infarction, and death. To extrapolate clinical data beyond 1 year, a linear, an exponential, and a Weibull survival curves were estimated. Patient characteristics and transition probabilities were derived from a high-risk subgroup of the ESPRIT trial; patient-level utility data came from a published Dutch study. Costs were calculated from a hospital and from a third-party payer perspective. For both perspectives, the additional treatment with eptifibatide is the considered dominant alternative. The incremental net benefit of its use exceeds a,not sign10,000 for both perspectives. Results proved stable in probabilistic sensitivity analysis as well as under the different extrapolation scenarios. Eptifibatide is likely to be dominant strategy with 77.7 and 96.7% of the simulations leading to QALYs gained and generating cost savings from both the hospital and the third-party payer perspective. Eptifibatide offsets its additional treatment costs by avoiding costly repeat procedures and leads to positive QALY gains by preventing cardiovascular events lending themselves to transient or permanent lower quality of life. The method used to extrapolate the short-term risks did not impact on results, mainly due to similar clinical risk profiles between the two treatment groups in the long term