Publikationen
Wilke T, Groth A, Fuchs A, Seitz L, Kienhöfer J, Lundershausen R, Maywald U. Real life treatment of diabetes mellitus type 2 patients: An analysis based on a large sample of 394,828 German patients. Diabetes Res Clin Pract. 2014;Epub ahead of print.
Wilke T, Groth A, Fuchs A, Seitz L, Kienhöfer J, Lundershausen R, Maywald U. Real life treatment of diabetes mellitus type 2 patients: An analysis based on a large sample of 394,828 German patients. Diabetes Res Clin Pract. 2014;Epub ahead of print.
Abstract
OBJECTIVES
The aim of this claims-based data analysis was to describe the care of German T2DM patients and to determine which subgroups could be differentiated in terms of the achieved T2DM-related treatment results, the underlying comorbidities, and the achieved comorbidity-related treatment results.
METHODS
We included all T2DM patients insured by a large sickness fund in 2010/2011. We defined 12 subgroups according to observed HbA1C, blood pressure and Charlson Comorbidity Index (CCI). For each subgroup, available sociodemographic and clinical information were reported. Different treatment variables were described. T2DM-related events leading to acute hospitalisations were reported.
RESULTS
We included 394,828 T2DM patients in our analysis; for 228,703 patients’ detailed data as basis for subgroup classification were available. For 4.5% of these patients, a HbA1C >9% was observed.
21,833 of the T2DM patients were affected by a T2DM-related event; the risk was 5.53% per patient year; 1.74% of the patients suffered from more than one event. Most frequent event types were hospitalisation with T2DM as primary diagnosis (2.39%), vascular interventions/stent implantations (1.92%), and ischaemic stroke (1.19%). There were significant differences between the observed subgroups in terms of T2DM-related event risk.
CONCLUSION
Overall, our data indicate that the typically treated T2DM patient has a number of comorbidities and thus treatment focused solely on T2DM is neither possible nor clinically meaningful. Particularly those patients who reached HbA1C goals, but had also achieved relevant additional treatment goals reached low yearly T2DM event rates whereas subgroups failing to achieve one or several treatment goals are facing much higher event risks
Müller S, Pfannkuche M, Breithardt G, Bauersachs R, Maywald U, Kohlmann T, Wilke T. The quality of oral anticoagulation in general practice in patients with atrial fibrillation. Eur J Intern Med. 2014;25(3):247-254.
Müller S, Pfannkuche M, Breithardt G, Bauersachs R, Maywald U, Kohlmann T, Wilke T. The quality of oral anticoagulation in general practice in patients with atrial fibrillation. Eur J Intern Med. 2014;25(3):247-254.
Abstract
BACKGROUND
The aims of this study were to evaluate the quality of oral anticoagulation (OAC) in AF patients in the practices of general practitioners (GPs) in Germany and to investigate possible causal factors which influence OAC quality.
METHODS
We conducted a multi-center, non-interventional, prospective observational cohort study among general practitioners (GPs) in Germany. To assess the quality of OAC on the basis of the prospectively documented international normalized ratio (INR) values, the time in therapeutic range (TTR) was calculated using the Rosendaal linear trend method. The causes of poor OAC quality were identified by a multivariate analysis model (logistical regression; poor OAC quality: TTR < 60%).
RESULTS AND CONCLUSIONS
For 525 OAC patients (66.8%; patients with at least 2 prospectively documented INR values) the average TTR (target range of 2.0–3.0) was 67.6%. About 34.7% of the patients had a TTR < 60%.
None of the variables representing characteristics of the medical practices were capable of explaining the occurrence of poor OAC quality. However, with regard to care provision-based variables, the existence of a brief discontinuation of medication was important. As the existence of adherence barriers increased, the probability of poor anticoagulation quality increased.
In conclusion, the provision of OAC in the German health care system is to be regarded as good, but far from ideal. Our causal analysis shows that patient-based factors should be addressed through the provision of improved training and that the rationale behind the interruption of OAC treatment should be critically examined.
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initial anticoagulation therapy in patients with venous thromboembolism and impaired renal function. J Public Health. 2014;22(2):89-99.
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initial anticoagulation therapy in patients with venous thromboembolism and impaired renal function. J Public Health. 2014;22(2):89-99.
Abstract
AIM
Patients undergoing initial therapeutic anticoagulation after a venous thromboembolic event (VTE) with severely impaired renal function (RI-VTE-patients) are at high risk of accumulating the anticoagulants resulting in an increased risk of bleeding events. Current guidelines/approved summary of product characteristics (SPC) recommend usage of specific anticoagulants only, monitoring of aXa-activity, and/or dose adjustment (in the case of enoxaparin) for initial therapeutic anticoagulation of RI-VTE patients. This study investigates the treatment of German RI-VTE-patients and evaluates whether guideline/SPC recommendations are implemented in the practice of real life care.
SUBJECTS AND METHODS
We conducted a chart review in five German acute hospitals. All VTE patients treated in these hospitals from 01/01/2007–31/12/2011 were included. Renal insufficiency (RI) was defined as CrCl < 30 ml/min. Treatment did not conform to the recommendations in guidelines/SPCs, if (1) a drug was used that is contraindicated according to the SPC or no initial anticoagulation treatment was implemented at all; (2) the recorded daily dose of enoxaparin was higher than the recommended weight-adjusted dose.
RESULTS
Of 5,263 VTE patients identified, 709 (13.5 %) cases could not be documented due to missing charts (601) or no documented creatinine serum levels (108). Of the remaining 4,554 patients (mean age ±SD 67.4 years ±15.7; 53.0 % female; weight 80.2 kg ±20.0; 54.5 % deep VT), 337 (7.4 %) had a mean estimated GFR < 30 ml/min. In 19 (5.6 %) of these cases, patients were treated with a drug not recommended for use, 21 (6.2 %) did not receive any initial anticoagulation treatment and 91 (27.0 %) received a higher than recommended dosage of enoxaparin. Additionally, for 22 patients (6.5 %) receiving enoxaparin, no weight information was recorded and it is therefore unlikely that the dosage was adjusted correctly.
CONCLUSION
VTE treatment in RI-VTE-patients differs remarkably from labelled recommendations; over-dosage of enoxaparin is common. It seems fair to assume that these patients face a higher risk of adverse reactions, in particular bleeding events.
Wilke T, Groth A, Müller S, Hastedt C, Fuchs A, Maywald U. Interruption/Bridging of VKA Treatment of Patients with Atrial Fibrillation: Analysis of Incidence and Clinical Outcomes Based on a German Claims Based Data Set. Value in Health. 2013;16(7):A517.
Wilke T, Groth A, Müller S, Hastedt C, Fuchs A, Maywald U. Interruption/Bridging of VKA Treatment of Patients with Atrial Fibrillation: Analysis of Incidence and Clinical Outcomes Based on a German Claims Based Data Set. Value in Health. 2013;16(7):A517.
Abstract
OBJECTIVES
For patients with atrial fibrillation (AF) undergoing a surgery, guidelines recommend the interruption of VKA-treatment combined with LMWH/UFH bridging. As a result, patients may be placed at higher risk for thromboembolic events during this time. This study investigates the incidence of such perioperative management situations and describes clinical event rates.
METHODS
Claims data from a large German statutory health insurance (period 01/01/2007-31/12/2011) was analysed. AF-patients who started VKA-treatment within this period and continued therapy until 31/12/2011 were included. VKA-interruption/bridging was assumed when the patient was admitted to a hospital due to an inpatient surgical procedure (case 1) or the patient experienced an outpatient surgery, combined with an outpatient prescription of a LMWH/UFH within 10 days after surgery (case 2). Clinical events of interest were cardiovascular (strokes, TIA, embolism, myocardial infarctions) and bleedings leading to inpatient hospitalization. Daily event rates during regular VKA usage days were compared to those 5 days before/30 days after surgery (“interruption/bridging days”).
RESULTS
41,170 patients were included (mean age 74.8 years; 50.8% male; average CHA2DS2-VASc score 5.2). 11,695 (28.4%) VKA-patients experienced a hospital admission due to a surgery (case 1). 464 patients (1.1%) experienced an outpatient surgery with outpatient LMWH prescription (case 2). Overall (both cases) potential interruption/bridging occurred 0.24 times per person-year. The daily cardiovascular/bleeding event risk during potential VKA-interruption/bridging was about 10fold/25fold higher than during a regular VKA-usage day (0.08%/0.21% vs. 0.0078%/0.0083%, vs. (p<0.0001)). About half of the bleedings were coded by treating physicians as due to anticoagulation therapy.
CONCLUSIONS
Periods in which VKA-interruption/bridging due to surgery was required frequently occur during the VKA-treatment of AF patients. The cardiovascular/bleeding event risk of VKA-patients is significantly higher during such periods compared to periods of regular VKA-treatment. Whether this is due to VKA-interruption/bridging or the surgical procedures themselves needs to be analysed in future.
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initiale therapeutische Antikoagulation nach einem venösen thromboembolischen Ereignis von Patienten mit schwerer Nierenfunktionseinschränkung. German Medical Science. 2013;Epub
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initiale therapeutische Antikoagulation nach einem venösen thromboembolischen Ereignis von Patienten mit schwerer Nierenfunktionseinschränkung. German Medical Science. 2013;Epub
Abstract
HINTERGRUND
Für Patienten mit schwerer Nierenfunktionseinschränkung, die nach einem venösen thromboembolischen Ereignis (VTE) therapeutisch antikoaguliert werden, besteht ein erhöhtes Risiko der Akkumulation der Antikoagulantien, die mit einem erhöhten Blutungsrisiko verbunden sein kann.
In den aktuellen Fachinformationen der zur Therapie zugelassenen Wirkstoffe sowie den aktuellen VTE-Therapie-Leitlinien wird diesem Aspekt besondere Aufmerksamkeit gewidmet. So sind einige Wirkstoffe in dieser Patientengruppe kontrainduziert, für einige Wirkstoffe wird eine erhöhte Kontrollintensität (anti-Xa) empfohlen und für den Wirkstoff Enoxaparin ist eine Dosisreduktion vorgesehen.
Ziel dieser Studie war es, die initiale therapeutische Antikoagulation von niereninsuffizienten VTE-Patienten in der Versorgungspraxis zu analysieren und herauszufinden, in welchem Umfang den Empfehlungen der Leitlinien bzw. Fachinformationen im klinischen Alltag gefolgt wird.
MATERIAL UND METHODEN
Im Rahmen dieser Studie wurden in 5 deutschen Krankenhäusern die Patientenakten der Jahre 2007–2011, die in einem Zusammenhang mit einem VTE-Ereignis standen, analysiert. Als schwere Niereninsuffizienz wurde eine geschätzte glomeruläre Filtrationsrate (eGFR) von kleiner 30 ml/min, gemessen anhand des Serum-Kreatinin-Spiegels, definiert. Als Abweichung von der aktuellen Fachinformation bzw. Leitlinie wurde definiert, wenn einer der folgenden Empfehlungen nicht gefolgt wurde:
- Kontraindiziert bzw. Anwendung nicht empfohlen (Certoparin, Nadroparin, Reviparin, Fondaparinux),
- Überwachung der anti-Xa-Aktivität (Tinzaparin, Dalteparin),
- Überwachung der anti-Xa-Aktivität und Dosisreduktion auf ½ der normalen gewichtsdaptierten Dosis (Enoxaparin),
- Präzise Kontrolle der Antikoagulationswerte durch Messung der „aktivierten partiellen Thromboplastinzeit (aPTT)“ (UFHs).
ERGEBNISSE
Insgesamt konnten 5.263 VTE-Patienten identifiziert werden. Von diesen konnten 709 (13,5%) Patienten nicht für die Studie berücksichtigt werden, da die relevanten Akten entweder nicht vorhanden waren (601) oder in diesen kein Serum-Kreatinin-Wert dokumentiert war (108). Von den verbleibenden 4.554 Patienten (MWAlter ±SD 67,4 Jahre ±15,7; 53,0% weiblich; Körpergewicht 80,2 kg ±20,0; 54,5% tiefe VT), hatten 337 (7,4%) eine durchschnittliche eGFR<30 ml/min; zusätzlich hatten 1.630 Patienten (35,8%) eine eGFR<60 ml/min. In 19 (5,6%) Fällen wurden die Patienten mit einem Wirkstoff behandelt, welcher für diese kontraindiziert ist, 21 (6,2%) erhielten kein initiales therapeutisches Antikoagulanz und 91 (27,0%) Patienten wurde Enoxaparin in einer Dosis verabreicht, die höher als die jeweilig empfohlene Tagesdosis war. Zusätzlich erhielten 22 Patienten (6,5%) Enoxaparin, ohne dass in der Akte ein Körpergewicht dokumentiert war.
SCHLUSSFOLGERUNG
Die initiale therapeutische Antikoagulation von VTE-Patienten mit schwerer Nierenfunktionseinschränkung weicht im klinischen Alltag in ca. 50% der Fälle von den Empfehlungen der Fachinformationen/Leitlinien ab. Es ist zu vermuten, dass diese Patienten einem erhöhten Risiko für Komplikationen, insbesondere Blutungsereignissen, ausgesetzt sind.
Charokopou M, Heeg B, Schoeman O, Müller S, Tempest M.J, Schlagmuller S.C, Wilke T. A Comparison of Coverage and Reimbursement Decisions in Germany (AMNOG) and Scotland (SMC). Value in Health. 2013;16(7):A475–A476.
Charokopou M, Heeg B, Schoeman O, Müller S, Tempest M.J, Schlagmuller S.C, Wilke T. A Comparison of Coverage and Reimbursement Decisions in Germany (AMNOG) and Scotland (SMC). Value in Health. 2013;16(7):A475–A476.
Abstract
OBJECTIVES
In Scotland, drug reimbursement is predominantly based on cost-effectiveness in contrast to the corresponding German AMNOG process. The study compares the reimbursement and pricing process in Germany (AMNOG), as reformed in 2011, and Scotland (SMC) based on reimbursement assessments.
METHODS
All AMNOG and SMC appraisal decisions made in 2011-2012 were identified. Matching AMNOG-SMC cases were found and compared in terms of final appraisal decision and rationale.
RESULTS
For 2011-2012, forty-one AMNOG cases over 60 subgroups and 193 SMC cases were identified; twenty five matching cases were compared as these were assessed by both organizations. Regarding these 25 cases, AMNOG deemed ten cases demonstrated no additional benefit, in two cases the additional benefit was unquantifiable, slight benefit was acknowledged in seven cases and in six there were significant benefits. Based on the benefit assessment the negotiated price rebates ranged from 4.7% to 70.7% based on manufacturer set price. No restrictions to subgroups were opposed to any reimbursement decision. The SMC reimbursed 18 products (72%), of which four were restricted to a certain population due to cost-effectiveness. SMC rejected 7 cases (28%) based on weak economic evidence. Both organizations reached the same assessment regarding clinical benefit in only 13 cases (52%).
CONCLUSIONS
AMNOG implements a more rigorous process with respect to clinical evidence assessment compared to SMC. All AMNOG decisions are positive; however final prices may resemble generic prices for products that demonstrate low additional benefit (“Festbetragsgruppen”). In comparison, a negative decision by SMC warrants re-submission and re-assessment of the set price for successful drug reimbursement. Orphan drugs are assessed as normal products in Scotland and may be rejected on the grounds of economic evidence, while in Germany the additional benefit is presumed and price negotiation starts automatically. Furthermore, the SMC assessment process starts later than the AMNOG process.
Heeg B, Schoeman O, Müller S, Wilke T. The Impact of AMNOG on Drug Reimbursement in Germany.Value in Health. 2013;16(7):A459.
Heeg B, Schoeman O, Müller S, Wilke T. The Impact of AMNOG on Drug Reimbursement in Germany.Value in Health. 2013;16(7):A459.
Abstract
OBJECTIVES
There are three main governmental stakeholders in the German AMNOG process: The IQWiG assesses the AMNOG drug manufacturer’s submission and provides advice on any additional benefit to the GBA who makes the final decision. Following confirmation of additional benefit, manufacturers start price negotiations with the GKV-Spitzenverband (association of German sickness funds). The aim of this research is to assess the AMNOG-decisions so far.
METHODS
All AMNOG decisions up to December 2012 were analyzed in terms of additional benefit decision, reason for additional benefit decision, reimbursed price versus manufacturer set price, and consistency in IQWiG-recommendation and GBA-decision.
RESULTS
In total AMNOG decisions of 41 drugs (60 subgroups) were identified. IQWiG recommendations were as follows: 22 cases demonstrated no additional benefit, 2 unquantifiable benefit, 3 slight benefit, 7 significant benefit, and 7 additional benefit due to orphan-drug status. In 6 cases, the GBA upgraded IQWIG’s recommendations. In 3 cases it downgraded it. The following reasons were identified for GBA “additional benefit decisions” (multiple reasons apply for some decisions): No or non-quantifiable additional benefit (18 cases); no reliable clinical data (14 cases; 3 cases no submission), wrong comparator (5 cases); additional benefit in any form (23 cases): mortality advantages (7 cases), orphan drug status (7 cases), morbidity advantages (8 cases), and QoL advantages (3 cases). The negotiated price rebates varied from 4.7% to 70.7% based on manufacturer set price; the rebates show limited correlation to the degree of additional benefit so far.
CONCLUSIONS
Key factors for positive AMNOG decisions are conducting superiority trials on mortality or at least morbidity/QoL against active comparators. If benefits are based on soft end-points, it is crucial to demonstrate these on high quality, preferably German data. Indirect comparisons seem to be challenged as proof of additional benefits.
Wilke T, Groth A, Müller S, Reese D, Linder R, Ahrens S, Verheyen F. How to use pharmacy claims data to measure patient nonadherence? The example of oral diabetics in therapy of type 2 diabetes mellitus. Eur J Health Econ. 2013;14(3):551-568.
Wilke T, Groth A, Müller S, Reese D, Linder R, Ahrens S, Verheyen F. How to use pharmacy claims data to measure patient nonadherence? The example of oral diabetics in therapy of type 2 diabetes mellitus. Eur J Health Econ. 2013;14(3):551-568.
Abstract
INTRODUCTION
The purpose of this study was to describe the methodological framework underlying nonadherence (NA) measurement based on pharmacy claims data, its quantitative impact on the results of NA studies, and to identify those methodological categories most likely to explain diabetes-related clinical outcomes. We use the example of oral antidiabetics in the treatment of diabetes mellitus type 2; 113,108 patients derived from a German statutory health insurance fund were analyzed.
METHODS
We identified 12 methodological categories as pervasive features in pharmacy claims data based NA analyses. The influence of the different methodological categories and their parameters on analysis results was tested using sensitivity analysis. To validate alternative methodological framework options, we performed multivariate logistical regression estimates using diabetes-related hospitalization/clinical events as a combined dichotomized dependent variable.
RESULTS
The choice of parameters within the identified 12 methodological categories available has exceptional impact on the results of pharmacy data based claims NA analyses. When the full range of theoretically possible cases is considered in our sample, it can be seen that the resulting NA range is between 15.7% and 97.0%. The definition of the required daily dose, the decision to use either a prescription-/interval-based approach, and the classes of medication analyzed exert a notable influence on the study results. In our analysis, 69.4% of the 216 different study design options analyzed significantly explain the likelihood of diabetes-related clinical events.
CONCLUSION
We recommend strongly that methodological transparency is awarded a much more important role in the conduct of NA analyses made on the basis of pharmacy claims data.
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initial anticoagulation therapy in patients with venous thromboembolism and impaired renal function. Value in Health. 2013;16(7):A538.
Böttger B, Wehling M, Bauersachs RM, Amann S, Wilke T. Initial anticoagulation therapy in patients with venous thromboembolism and impaired renal function. Value in Health. 2013;16(7):A538.
Abstract
Objectives
Patients undergoing initial therapeutic anticoagulation after a venous thromboembolic event (VTE) with severely impaired renal function (RI-VTE-patients) are at high risk of accumulating the anticoagulants resulting in an increased risk of bleeding events. Current guidelines/approved summary of product characteristics (SPC) recommend usage of specific anticoagulants only, monitoring of aXa-activity, and/or dose adjustment (in the case of enoxaparin) for initial therapeutic anticoagulation of RI-VTE patients. This study investigates the treatment of German RI-VTE-patients and evaluates whether guideline/SPC recommendations are implemented in the practice of real life care.
METHODS
We conducted a chart review in five German acute hospitals. All VTE patients treated in these hospitals from 01/01/2007–31/12/2011 were included. Renal insufficiency (RI) was defined as CrCl < 30 ml/min. Treatment did not conform to the recommendations in guidelines/SPCs, if (1) a drug was used that is contraindicated according to the SPC or no initial anticoagulation treatment was implemented at all; (2) the recorded daily dose of enoxaparin was higher than the recommended weight-adjusted dose.
RESULTS
Of 5,263 VTE patients identified, 709 (13.5 %) cases could not be documented due to missing charts (601) or no documented creatinine serum levels (108). Of the remaining 4,554 patients (mean age ±SD 67.4 years ±15.7; 53.0 % female; weight 80.2 kg ±20.0; 54.5 % deep VT), 337 (7.4 %) had a mean estimated GFR < 30 ml/min. In 19 (5.6 %) of these cases, patients were treated with a drug not recommended for use, 21 (6.2 %) did not receive any initial anticoagulation treatment and 91 (27.0 %) received a higher than recommended dosage of enoxaparin. Additionally, for 22 patients (6.5 %) receiving enoxaparin, no weight information was recorded and it is therefore unlikely that the dosage was adjusted correctly.
CONCLUSION
VTE treatment in RI-VTE-patients differs remarkably from labelled recommendations; over-dosage of enoxaparin is common. It seems fair to assume that these patients face a higher risk of adverse reactions, in particular bleeding events.
Wilke T, Groth A, Müller S, Pfannkuche M, Verheyen F, Linder R, Maywald U, Bauersachs R, Breithardt G. Incidence and prevalence of atrial fibrillation: An analysis based on 8.3 million patients. Europace. 2013;15(4):486-93.
Wilke T, Groth A, Müller S, Pfannkuche M, Verheyen F, Linder R, Maywald U, Bauersachs R, Breithardt G. Incidence and prevalence of atrial fibrillation: An analysis based on 8.3 million patients. Europace. 2013;15(4):486-93.
Abstract
AIMS
Based on an analysis of claims-based data of 8.298 million members of two German statutory health insurance funds, the aim of this contribution is to quantify age-/gender-specific prevalence/incidence of atrial fibrillation (AF) in a German setting.
METHODS AND RESULTS
Patients were classified as AF prevalent, if they had received at least two outpatient diagnoses of AF (ICD10-Code I48.1-) in two different quarters of the year and/or had received at least one main AF diagnosis during inpatient treatment between 1 January 2007 and 12 December 2008. They were considered to have had new onset AF in 2008 under the following conditions; first, there was no AF diagnosis in 2007; secondly, patients had not received oral anticoagulant medication in 2007; and thirdly, patients had received either one inpatient/two outpatient diagnoses of AF in 2008. In our sample, a total of 176 891 patients had AF. AF prevalence was 2.132%. The average age of these AF patients was 73.1 years, and 55.5% (98 190 patients) were male. The incidence of AF in our sample was 4.358 cases/1000 person-years in men and 3.868 cases/1000 person-years in women.
CONCLUSION
A comparison of the distribution of AF prevalence/incidence in our population with that in already published studies showed that our figures were higher, especially in the age groups above 70 years. Our data show that in a large industrial nation such as Germany care provision structures are going to be challenged by a requirement to treat more AF patients in the future.