Publikationen

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

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

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

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

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

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.

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

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.

Wilke T, Ahrendt P, Schwartz D, Linder R, Ahrens S, Verheyen F. Incidence and prevalence of type 2 diabetes mellitus in Germany: an analysis based on 5.43 million patients. Dtsch Med Wochenschr. 2013;138(3):69-75.

Abstract

BACKGROUND AND OBJECTIVE

Based on claims-data of 5.43 million members of a large German statutory health insurance fund in 2008 (Techniker Krankenkasse), the aim of this contribution is to update and more precisely quantify age- and gender-specific prevalence and incidence of type 2 diabetes mellitus (T2DM) in a German setting.

METHODS

A patient was classified as T2DM prevalent if he or she had received at least two outpatient diagnoses of T2DM in two different quarters of the year and/or had received at least one T2DM diagnosis during inpatient treatment between 01/01/2006 and 12/31/2008. A patient was considered to have had new onset T2DM in 2008 under one of three conditions: 1. no diagnosis of T2DM in 2006 and 2007, 2. no presripction of oral antidiabetics in 2006 and 2007, 3. either one inpatient or two outpatient diagnoses of T2DM conducted in two different quarters of 2008 or one outpatient T2DM diagnosis in 2006/07 when the second diagnosis was made in 2008.

RESULTS

A total of 254,524 patients had T2DM. Compared to the total membership of the medical insurance fund, the prevalence of T2DM was 4.69 %. The average age was 64.8 years, and 66.37 % were male. The incidence of T2DM in our sample was 2.814 cases per 1,000 person-years in men and 1.690 cases in 1,000 person-years in women. Based on our sample and on official population data, 4,704,585 patients (5.75 %) in Germany would be T2DM prevalent in 2009. The number of incident T2DM cases would amount to 215,746 patients (0.264 %).

CONCLUSIONS

T2DM is one of the most common chronic diseases in Germany. The expected demographic changes in Germany will increase the burden on the German health system caused by T2DM.

Wilke T, Groth A, Müller S, Verheyen F, Linder R, Pfannkuche M, Maywald U,  Bauersachs R, Breithardt G. Prevalence and Incidence of Atrial Fibrillation: An Analysis Based on 8.3 Million Patients. Value in Health. 2012;15(4):A115–A116.

Abstract

OBJECTIVES

The aims of this contribution are to update and more precisely quantify the age and gender-specific prevalence and incidence of atrial fibrillation (AF) in an European setting (Germany).

METHODS

To fulfill the aims of the study, it was decided to make a population-based analysis of the claims data collected by a statutory health insurance fund, and concerning its 8.298 million members. A patient was classified as AF prevalent if he/she 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 January 1, 2007 and December 31, 2008. A patient was considered to have had new onset AF in 2008 under one of three conditions; firstly, he/she had not received a diagnosis of AF in 2007; secondly, had not received oral anticoagulant medication in 2007; and thirdly, had received either one inpatient AF diagnosis in 2008, or two such outpatient diagnosis made in different quarters of that year. AF prevalence is reported in %, AF incidence is reported as cases per 1000 person-years.

RESULTS

In our sample, a total of 176,891 patients had AF. By reference to the total membership of the two medical insurance funds, the prevalence of AF was 2.132% (men: 2.369 %; women: 1.895%). 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 4358 cases per 1000 person-years in men and 3.868 cases in 1000 person-years in women. AF prevalence/incidence clearly depends on age and gender.

CONCLUSIONS