Can Routine Data be used to Determine the Target Population of Patients with Type 2 Diabetes in Early Benefit Assessments in Germany?

OBJECTIVES: Since 2011, early benefit assessment of all new drugs launched in Germany is mandatory. The exact determination of the appropriate target population (i. e. patients eligible for a drug) plays an important role for subsequent price negotiations. In type 2 diabetes, the size of the target population varies considerably between company dossiers submitted for assessment. Our aim was to explore whether routine data from all persons insured in German statutory health insurance (SHI) funds can be used to derive information on the size of the target population with type 2 diabetes. METHODS: We explored how the data available at the German Institute of Medical Documentation and Information (DIMDI) can be used to obtain the information required. A data-based concept was chosen and the selection criteria were developed in a multidisciplinary project group. Before finalizing the database query, the criteria were evaluated in a test database and the database query was then repeatedly modified. RESULTS: At the time of the design of our analysis in 2017, the most recent data available at DIMDI were for 2013. The algorithm we developed for identifying patients with type 2 diabetes and classifying them according to their medication, based primarily on the combination of ICD and ATC codes, enabled us to determine the size of target populations for different indications in diabetes mellitus type 2. CONCLUSION: Our methodological approach seems to be suitable to determine target populations in type 2 diabetes.

The efficiency-frontier approach for health economic evaluation versus cost-effectiveness thresholds and internal reference pricing: combining the best of both worlds?

INTRODUCTION: The efficiency-frontier approach (EFA) to health economic evaluation aims to benchmark the relative efficiency of new drugs with the incremental cost-effectiveness ratios (ICERs) of non-dominated comparators. By explicitly considering any differences in health outcomes and costs, it enhances the internal reference pricing (IRP) policy that was officially endorsed by Germany as the first country worldwide in 1989. However, the EFA has been repeatedly criticized since its official endorsement in 2009. Areas covered: This perspective aims to stimulate the debate by discussing whether the main objections to the EFA are technically valid, irrespective of national contextual factors in Germany with reservations towards using cost-per-quality-adjusted life year (QALY) thresholds. Moreover, we comparatively assessed whether the objections are truly unique to the EFA or apply equally to IRP and cost-effectiveness thresholds. Expert commentary: The plethora of objections to the EFA (n = 20) has obscured that many objections are neither technically valid nor unique to the EFA. Compared with cost-effectiveness thresholds, only two objections apply uniquely to the EFA and concern intended key properties: (1) no external thresholds are needed and (2) the EFA is sensitive to price changes of comparators. Combining these policies and developing them further are under-utilized research areas.

[Checklist for the Development and Assessment of Cost-of-Illness Studies]. / Checkliste zur Erstellung und Bewertung von Krankheitskostenstudien.

BACKGROUND: Cost-of-illness (CoI) studies are important instruments for estimating the socioeconomic burden of specified diseases. CoI studies provide important information about the cost structure of a disease, the resulting research need, approaches to improve aspects of care and, monetary consequences from different perspectives. This information can be useful for healthcare research and health policy. Due to heterogeneity of available Cost-of-Illness studies, the working group 'Health Economics' of the German Network for Healthcare Research (DNVF) in accordance with the German Society for Health Economics (DGGÖ) developed an instrument for the planning, conduct and assessment of CoI studies. METHODS: The checklist was developed based on a systematic literature search of published national and international checklists as well as guidelines and recommendations for development and assessment of CoI studies and health economic evaluations. Structure and subject matter of the generic checklist was designed, approved and, finally, examined in a pretest by the working group. RESULTS: Based on the results of the literature search (n=2 454), 58 articles were used for the identification of relevant criteria for the checklist. With respect to the results of the pretest, 6 dimensions were included in the checklist: (i) general aspects, (ii) identification of resources, (iii) description and quantification of resource consumption, (iv) valuation of resources (v) analysis and presentation of results and (vi) discussion and conclusion. In total, the 6 dimensions were operationalized through 37 items. CONCLUSION: This checklist is an initial approach to improve transparency and understanding of CoI studies in terms of the extent, structure and development of the socioeconomic burden of diseases. The checklist supports the comparability of different studies and facilitates study conception.

No suitable precise or optimized epidemiologic search filters were available for bibliographic databases.

OBJECTIVES: To determine a suitable approach to a systematic search for epidemiologic publications in bibliographic databases. For this purpose, suitable sensitive, precise, and optimized filters were to be selected for MEDLINE searches. In addition, the relevance of bibliographic databases was determined. STUDY DESIGN AND SETTING: Epidemiologic systematic reviews (SRs) retrieved in a systematic search and company dossiers were screened to identify epidemiologic publications (primary studies and SRs) published since 2007. These publications were used to generate a test and validation set. Furthermore, each SR's search strategy was reviewed, and epidemiologic filters were extracted. The search syntaxes were validated using the relative recall method. RESULTS: The test set comprises 729 relevant epidemiologic publications, of which 566 were MEDLINE-indexed. About 27 epidemiologic filters were extracted. One suitable sensitive filter was identified (Larney et al. 2013: 95.94% sensitivity). Precision was presumably underestimated so that no precise or optimized filters can be recommended. About 77.64% of the publications were found in MEDLINE. CONCLUSION: There is currently no suitable approach to conducting efficient systematic searches for epidemiologic publications in bibliographic databases. The filter by Larney et al. (2013) can be used for sensitive MEDLINE searches. No robust conclusions can be drawn on precise or optimized filters. Additional search approaches should be considered.

Cost-effectiveness and cost-utility of a structured collaborative disease management in the Interdisciplinary Network for Heart Failure (INH) study.

BACKGROUND: Non-pharmacological treatment programmes are being developed, in which specialised nurses take care of heart failure (HF) patients. Such disease management programmes might increase survival and quality of life in HF patients, but evidence on their cost-effectiveness remains limited. METHODS AND RESULTS: A prospective economic evaluation piggy-backed onto the randomised controlled Interdisciplinary Network for Heart Failure (INH) Study weighted costs of the intervention HeartNetCare -HF™ (HNC) regarding effectiveness, mortality and quality-adjusted life years (QALYs). To consider uncertainty sensitivity analyses were performed. Compared to usual care (UC), HNC revealed 8,284 per death avoided within the 6 month study follow-up period. The cost-utility analysis showed additional costs of 49,335 per QALY. CONCLUSION: Although HNC did not reduce short-term re-admission rates of HF patients hospitalised for cardiac decompensation within the first 180 days after discharge, HNC might reduce mortality and increase quality of life in these patients at reasonable costs. Therefore, long-term HNC-effects deserve further evaluation.

Decision making in Germany: is health economic evaluation as a supporting tool a sleeping beauty?

For many years, the legal situation within the statutory health insurance (SHI) system in Germany has allowed for health economic evaluations. There are various reasons why health economic evaluations have played virtually no role in decision making until now: to begin with, a method for the evaluation of the relation between benefits and costs which needed to be in accordance with the legal requirements had to be developed, the outcome of which was the efficiency frontier approach. Subsequent health care reforms have led to changing objectives and strategies. Currently, price negotiations of newly launched drugs are based on an early benefit assessment of dossiers submitted by pharmaceutical manufacturers. Other reasons might be the presently very comfortable financial situation of the statutory health insurance system as well as a historically grown societal fear and discomfort towards what is perceived to be a rationing of medicinal products. For the time being, it remains open how long the German health care system can afford to continue neglecting the benefits of health economic evaluations for drug and non-drug interventions, and when it will be time to wake this sleeping beauty.

Cost-effectiveness analysis of coronary artery disease screening in HIV-infected men.

BACKGROUND: HIV-infected patients are at increased risk of coronary artery disease (CAD). We evaluated the cost-effectiveness of cardiac screening for HIV-positive men at intermediate or greater CAD risk. DESIGN: We developed a lifetime microsimulation model of CAD incidence and progression in HIV-infected men. METHODS: Input parameters were derived from two HIV cohort studies and the literature. We compared no CAD screening with stress testing and coronary computed tomography angiography (CCTA)-based strategies. Patients with test results indicating 3-vessel/left main CAD underwent invasive coronary angiography (ICA) and received coronary artery bypass graft surgery. In the stress testing + medication and CCTA + medication strategies, patients with 1-2-vessel CAD results received lifetime medical treatment without further diagnostics whereas in the stress testing + intervention and CCTA + intervention strategies, patients with these results underwent ICA and received percutaneous coronary intervention. RESULTS: Compared to no screening, the stress testing + medication, stress testing + intervention, CCTA + medication, and CCTA + intervention strategies resulted in 14, 11, 19, and 14 quality-adjusted life days per patient and incremental cost-effectiveness ratios of 49,261, 57,817, 34,887 and 56,518 Euros per quality-adjusted life year (QALY), respectively. Screening only at higher CAD risk thresholds was more cost-effective. Repeated screening was clinically beneficial compared to one-time screening, but only stress testing + medication every 5 years remained cost-effective. At a willingness-to-pay threshold of 83,000 €/QALY (∼ 100,000 US$/QALY), implementing any CAD screening was cost-effective with a probability of 75-95%. CONCLUSIONS: Screening HIV-positive men for CAD would be clinically beneficial and comes at a cost-effectiveness ratio comparable to other accepted interventions in HIV care.

Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia.

BACKGROUND AND PURPOSE: Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. METHODS: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). RESULTS: Predicted lifelong discounted costs were 33,837 for patients diagnosed by the 7-d-Holter and 33,852 by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 /QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. CONCLUSIONS: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness.

Cost of HIV and determinants of health care costs in HIV-positive patients in Germany: results of the DAGNÄ K3A Study.

OBJECTIVES: The aims of this study were to estimate the expenditure for HIV-care in Germany and to identify variables associated with resource use. DESIGN/SETTING: We performed an 18-month prospective multi-center study in an HIV specialized ambulatory care setting from 2006 to 2009. SUBJECTS, PARTICIPANTS: Patients were eligible for study participation if they (1) were HIV-positive, (2) were ≥ 18 years of age, (3) provided written consent and (4) were not enrolled in another clinical study; 518 patients from 17 centers were included. MAIN OUTCOME MEASURES: Health care costs were estimated following a micro-costing approach from two perspectives: (1) costs incurred to society in general, and (2) costs incurred to statutory health insurance. Data were obtained using questionnaires. Several empirical models for identifying the relationship between health care costs and independent variables, including age, gender, route of transmission and CD4 cell count at baseline, were developed. RESULTS: Average annual health care costs were 23,298 per patient from the societal perspective and 19,103 from the statutory health insurance perspective. Most expenses are caused by antiretroviral medication (80 % of the total and 89 % of direct costs), while hospital costs represented 7 % of total expenditure. A statistically significant association was found between health care costs and clinical variables, with higher CD4 count and female gender generating lower costs, while increased antiretroviral experience and injection drug use led to higher expenditures (P < 0.05). CONCLUSIONS: Expenditures for HIV-infection are driven mainly by drug costs. We identified several clinical variables influencing the costs of HIV-treatment. This information could assist policymakers when allocating limited health care resources to HIV care.

Are HIV patients undertreated? Cardiovascular risk factors in HIV: results of the HIV-HEART study.

BACKGROUND: Antiretroviral therapy improved the survival of patients with human immunodeficiency virus (HIV) infection. With increased life expectancy, HIV-infected patients increasingly are experiencing comorbidities, most notably cardiovascular risk factors (CRFs) and coronary heart disease (CHD). DESIGN: This study utilized a prospective, cross-sectional multicentre long-term design. METHODS: In 803 patients (82% male; mean age 44.2 ± 10.3 years) we evaluated the prevalence of CRFs and 10-year risk of CHD using the Framingham risk model. The presence of a risk factor was determined based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), and the German Society of Cardiology. RESULTS: The most common CRFs were smoking (51.2%), high triglycerides (39.0%), low high-density lipoprotein cholesterol (27.5 %) and high blood pressure (21.4%). In total, 60.3%, 21.6%, and 18.1% of patients were categorized as being at low (<10%), moderate (10-20%), and high (>20%) 10-year risk for CHD, respectively. In patients with hypertension, at least one antihypertensive drug was given in 91/163 (55.8%) patients. The percentage of patients on treatment with diabetes mellitus was 23/41 (56.1%). Anti-platelet therapy was prescribed to 42/102 (41.2%) patients with known CHD or CHD equivalent. In patients of moderate or high CHD risk there were more than 50% and 30% for LDL cholesterol and more than 60% and 40% for total cholesterol untreated. CONCLUSIONS: The prevalence of CRFs remains high in an HIV-infected population. CRF management of HIV-infected patients deserves further improvement.

Treatment costs and indirect costs of cluster headache: A health economics analysis.

BACKGROUND: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (eCH) or chronic cluster headache (cCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. METHODS: Treatment costs (direct costs) due to healthcare utilisation, as well as costs caused by disability and reduction in earning capacity (indirect costs), were obtained using a questionnaire in CH patients treated in a tertiary headache centre based at the University Duisburg-Essen over a 6-month period. RESULTS: A total 179 patients (72 cCH, 107 eCH) were included. Mean attack frequency was 3.5 ± 2.5 per day. Mean direct and indirect costs for one person were €5963 in the 6-month period. Direct costs were positively correlated with attack frequency (r = 0.467, p < 0.001). Burden of disease measured with HIT-6 showed a significant correlation with attack frequency (r = 0.467, p < 0.001). Twenty-four (13.4%) of the participants were disabled and not able to work. CONCLUSION: CH leads to major socioeconomic impact on patients as well as society due to direct healthcare costs and indirect costs caused by loss of working capacity.

Lipodystrophy - a sign for metabolic syndrome in patients of the HIV-HEART study.

BACKGROUND: After the introduction of antiretroviral therapy, the life expectancy of HIV patients has increased to more than 30 years after initial diagnosis. Cardiovascular disease now is an important cause of death in HIV-infected patients. PATIENTS AND METHODS: In the multicenter, prospective HIV-HEART study, 222 (38 %) patients suffered from lipodystrophy. Women were more often affected than men (41.5 % vs. 25.3 %). Patients with lipodystrophy were on average 5 years older and had been infected longer (10.4 vs. 6.6 years) then patients without lipodystrophy. RESULTS: Lipodystrophy in HIV patients was a clinical sign of cardiovascular risk factors like hyperlipidemia (total cholesterol 19 mg/dl higher, HDL 2.8 mg/dl lower, triglycerides 53 mg/dl higher) and type 2 diabetes (11.3 % vs. 2.8 %). Patients with lipodystrophy were more likely to be co-infected with hepatitis B (34.7 % vs. 28.8 %, p = 0.122) or C (13.1 % vs. 9.3 %, p = 0.16) than patients without lipodystrophy. The quality of life was reduced in patients with lipodystrophy. In 6 of 8 scales of the SF-36 questionnaire, patients with lipodystrophy had lower scores. CONCLUSIONS: Lipodystrophy syndrome is an early warning system for a number of illnesses which reduce life expectancy. Dermatologists must help insure that HIV-infected patients receive treatment for these disorders.

[BNP in HIV-infected patients]. / Wertigkeit des Biomarkers BNP bei HIV-infizierten Patienten.

BACKGROUND AND PURPOSE: HIV-infected patients exhibit an increased rate of cardiac diseases, due to an elevated rate of cardiac risk factors and side effects of antiretroviral therapy. The aim of the present study was to analyze the impact of B-type natriuretic peptide (BNP) in this patient population. PATIENTS AND METHODS: The HIV-HEART (HIV infection and HEART disease) study is a prospective and multicenter cohort study. Outpatients with a known HIV infection were included over a 20-month recruiting period. BNP values were determined by a standardized laboratory test at study inclusion. RESULTS: 802 HIV-infected patients (male: 83.4%, mean age: 44.2 +/- 10.3 years) were included. The BNP concentrations (median 11.3 pg/ml; BNP < or = 100 pg/ml: 96.2%) were associated with echocardiographic parameters and with the right ventricular diameter (p = 0.02) and the systolic pulmonary arterial pressure (p = 0.01). Patients with a BNP concentration of > 50 pg/ml had a significantly higher rate of heart failure (p < 0.001), cardiomyopathy (p < 0.001), and coronary artery disease (p < 0.001). CONCLUSION: The data demonstrate that BNP is suitable for the detection of cardiac disorders in HIV-infected subjects. Therefore, BNP could be an appropriate tool for a screening program for HIV-associated disorders in this patient population.