PATIENT PRIORITIES FOR TREATMENT ATTRIBUTES IN ADJUNCTIVE DRUG THERAPY OF SEVERE HYPERCHOLESTEROLEMIA IN GERMANY: AN ANALYTIC HIERARCHY PROCESS.

OBJECTIVES: Severe hypercholesterolemia is a major cause of death in coronary heart disease. New adjunctive drug therapies have passed authorization processes and been launched recently. So far it is not known which properties of the new treatment options generate the highest benefit for patients. The aim was to evaluate patient priorities in the field of adjunctive drug therapy with apheresis. Therapy characteristics were examined as to their relevance to hypercholesterolemia patients. METHODS: To identify all potential patient-relevant treatment characteristics, a systematic literature review and ten interviews with patients were conducted. Seven key characteristics were identified from the patient perspective. Patients' priorities were elicited using an analytic hierarchy process (AHP). RESULTS: In total, N = 61 patients diagnosed with severe hypercholesterolemia and undergoing apheresis participated in the study. The analysis showed predominance for the attribute "reduction of LDL-C level in blood" (Wglobal:0.362). The "risk of myopathy" (Wglobal:0.164), "risk of neurocognitive impairment" (Wglobal:0.161) and "frequency of apheresis" (Wglobal:0.119) were ranked second, third and fourth. Subgroup analyses revealed that "frequency of apheresis" is of greater importance to younger patients, men and/or patients who indicated a reduction in quality of life due to apheresis. CONCLUSIONS: The essential decision criteria for optimal therapy from the patients' perspective were obtained. "Reduction of lipoprotein in blood" was ranked highest compared with the "mode of administration" and "side effects" characteristics. The study offers a transparent approach for the identification of patient priorities for adjunctive PCSK9-inhibitor therapy in apheresis-treated hypercholesterolemia. The project can be used by healthcare decision makers to understand the importance of each patient-relevant endpoint.

Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis.

BACKGROUND: There are a number of instruments that describe severity and progression of multiple sclerosis and they are increasingly used as endpoints to assess the effectiveness of therapeutic interventions. We examined to what extent the psychometric properties of two accepted instruments--EDSS and MSFC--meet methodological standards and the value they have in clinical trials. METHODS: We conducted a systematic literature search in relevant databases [MEDLINE (PubMed), ISI Web of Science, EMBASE, PsycINFO & PSYNDEX, CINAHL] yielding 3,860 results. Relevant full-text publications were identified using abstract and then full-text reviews, and the literature was reviewed. RESULTS: For evaluation of psychometric properties (validity, reliability, sensitivity of change) of EDSS and MSFC, 120 relevant full-text publications were identified, 54 of them assessed the EDSS, 26 the MSFC and 40 included both instruments. The EDSS has some documented weaknesses in reliability and sensitivity to change. The main limitations of the MSFC are learning effects and the z-scores method used to calculate the total score. However, the methodological criterion of validity applies sufficiently for both instruments.For use in clinical studies, we found the EDSS to be preferred as a primary and secondary outcome measure in recent studies (50 EDSS, 9 MSFC). CONCLUSIONS: Recognizing their strengths and weaknesses, both EDSS and MSFC are suitable to detect the effectiveness of clinical interventions and to monitor disease progression. Almost all publications identify the EDSS as the most widely used tool to measure disease outcomes in clinical trials. Despite some limitations, both instruments are accepted as endpoints and neither are discussed as surrogate parameters in identified publications. A great advantage of the EDSS is its international acceptance (e.g. by EMA) as a primary endpoint in clinical trials and its broad use in trials, enabling cross-study comparisons.

Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin.

OBJECTIVE: To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. METHODS: This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. RESULTS: A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. CONCLUSION: Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.

Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review.

BACKGROUND: Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH) the long-acting analogue insulin glargine (GLA) is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT) of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. METHODS: A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science) and DAHTA (Deutsche Agentur für Health Technology Assessment), and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP). RESULTS: A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY) gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER). The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI). CONCLUSIONS: The incremental cost-utility-ratios (ICER) show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK) is adopted, GLA is cost-effective in 4 of 6 cost utility analyses (CUA) included. Thus insulin glargine (GLA) seems to offer good value for money. Comparability between studies is limited because of methodological and country specific aspects. The results of this review underline that evaluation of insulin therapy should use evidence on efficacy of therapy from information synthesis. The concept of relating utility decrements to fear of hypoglycaemia is a plausible approach but needs further investigation. Also future evaluations of basal-bolus insulin therapy should include costs of consumables such as needles for insulin injection as well as test strips and lancets for blood glucose self monitoring.

Comparison of treatment costs in inadequately controlled type 2 diabetes in Germany based on the APOLLO trial with insulin glargine.

OBJECTIVE: A cost analysis of once-daily insulin glargine versus three-times daily insulin lispro in combination with oral antidiabetic drugs (OADs) for insulin-naive type 2 diabetes patients in Germany based on the APOLLO trial (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment). METHODS: Annual direct treatment costs were estimated from the perspective of the German statutory health insurance (SHI). Costs accounted for included insulin medication, disposable pens and consumable items (needles, blood glucose test strips and lancets). Sensitivity analyses (on resource use and unit costs) were performed to reflect current German practice. RESULTS: Average treatment costs per patient per year in the base case were 1,073 euro for glargine and 1,794 euro for lispro. Insulin costs represented 65% vs. 37% of total costs respectively. Acquisition costs of glargine were offset by the lower costs of consumable items (380 euro vs. 1,139 euro). Sensitivity analyses confirmed the robustness of the results in favour of glargine. All scenarios yielded cost savings in total treatment costs ranging from 84 euro to 727 euro. CONCLUSIONS: Combination therapy of once-daily insulin glargine versus three-times daily insulin lispro both with OADs, in the management of insulin-dependent type 2 diabetes offers the potential for substantial cost savings from the German SHI perspective.

Resource utilisation and costs in patients with type 2 diabetes mellitus treated with insulin glargine or conventional basal insulin under real-world conditions in Germany: LIVE-SPP study.

OBJECTIVE: To assess and compare the total costs relevant to diabetes care in patients with type 2 diabetes mellitus (T2D) treated at specialised diabetes practices with either insulin glargine- or conventional basal insulin (neutral protamine Hagedorn [NPH])-based therapies from the German statutory health insurance (SHI) perspective. METHODS: The Long Acting Insulin Glargine Versus NPH Cost Evaluation in Specialised Practices (LIVE-SPP) study is an observational, retrolective, multicentre longitudinal cost comparison in adults with T2D. Costs were evaluated from the German SHI perspective based on official 2005 prices. Average total costs per patient for insulin glargine-versus NPH-based therapies were compared using multivariate general linear modelling. Sensitivity analyses were performed by varying the main cost factors by +/- 25%. RESULTS: Patients (n=1,024, 512 patients per cohort) were on average 62 years of age, with an average 8-year diabetes history at study start. The average unadjusted total annual costs per patient were euro 1,868.41 (95% CI 1,744.27-1,992.56) for insulin glargine-based vs. euro 2,063.72 (95% CI 1,922.91-2,204.54) for NPH-based therapies. Average adjusted total annual costs per patient between insulin glargine- (euro 1,241.13) and NPH-based therapies (euro 1,607.86) were statistically significantly different (p=0.0004). The economic advantage for insulin glargine-based therapies resulted mainly from fewer blood glucose measurements and other diabetes-related materials (e.g. needles). The savings remained stable in one-way sensitivity analyses. CONCLUSIONS: The LIVE-SPP study suggests that insulin glargine-based therapies may offer an economic advantage over NPH-based therapies.

Statin-associated myopathy. Assessment of frequency based on data of all statutory health insurance funds in Germany.

Aim of the study was to assess the incidence of statin-associated myopathy (SAM) under real-life conditions in Germany. DATABASE: Administrative data (master data, diagnoses, prescriptions) for all individuals in Germany insured with the Statutory Health Insurance. Basic population: individuals 18 years and older who have been insured continually from 2009 to 2011 (52.9 million; 29.9 million men, 23.9 million women). Data access is provided by the German Institute of Medical Documentation and Information, DIMDI) according to the Data Transparency Regulation of 2012. Statins: identification with the ATC-Codes: C10AA, C10BA and C10BX. STUDY POPULATION: incident statin users in 2010 with a diagnosis of lipid disorders (ICD-10-GM E78, excluding patients with: E78.1, E78.3, E78.6 in eight quarters before index prescription. Definition of SAM: documentation of myopathy (ICD-10-GM G72.0, G72.8; G72.9, M60.8, M60.9, M79.1) in the first statin prescription quarter or in one of the three following quarters. The first event is considered for the incidence estimate. The daily doses included in a package were classified as "days under therapy" (by assuming one DDD) and taken as exposition time. SAM was found in 1.9% of 531 672 incident statin users. The percentage differs according to the patterns of statin use: the lowest incidence is observed in those with only one prescription (1.3%), the highest incidence with 5.0% is observed in those who not only stopped the treatment within 365 days, but who also had their statin changed. Administrative data including diagnoses from ambulatory care provide a realistic estimate of SAM frequency in every day practice.

Treatment Preferences in Germany Differ Among Apheresis Patients with Severe Hypercholesterolemia.

BACKGROUND: Severe hypercholesterolemia is a major risk factor of death in patients with coronary heart disease. New adjunctive drug therapies (proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors) have gained approval in Europe and the USA. OBJECTIVE: In this empirical study, we documented preferences regarding adjuvant drug therapy in apheresis-treated patients with severe familial hypercholesterolemia. METHODS: We conducted a systematic literature search to identify patient-relevant outcomes in patients with severe hypercholesterolemia currently undergoing apheresis. Data were used to generate a semi-structured qualitative interview that enabled seven patient-relevant characteristics with three levels each to be identified. For the discrete choice experiment, an experimental design (7 × 3) was generated using NGene Software that consisted of 96 choices divided into eight blocks. The survey was conducted between November 2015 and April 2016 using computer-assisted personal interviews. RESULTS: The survey was completed by 348 patients (64.9% male). The random parameter logit estimation showed predominance for the attribute 'reduction of LDL-C (low-density lipoprotein cholesterol) level'. 'Risk of myopathy' and 'frequency of apheresis' dominated next. Within the random parameter logit estimation, all coefficients were significant (P ≤ 0.01). The latent class analysis identified three patient groups. The first group (126 patients) found 'reduction of LDL-C level in blood' to be most important. This group focused solely on this treatment outcome independently of apheresis frequency or additional injections. The second group (106 patients) focused on three attributes: 'frequency of apheresis', 'risk of myopathy', and 'reduction of LDL-C level in blood'. Respondents clearly considered a high frequency of apheresis to have a negative impact. The third group (116 patients) demonstrated the highest preference for apheresis. These patients have adjusted to apheresis for > 10 years. CONCLUSION: Regarding patient preference, clinical efficacy seems to dominate. Hence, 'reduction of LDC-C in blood' was ranked highest above patient-relevant modes of administration and adverse effects. In the patient groups identified, reduction of apheresis was important for only a subsegment (30%) of patients. Another 30% wanted effective LDL-C reduction by whatever means necessary. Most strikingly, another 30% preferred higher frequencies of apheresis.

Utilization of lipid-modifying therapy and low-density lipoprotein cholesterol goal attainment in patients at high and very-high cardiovascular risk: Real-world evidence from Germany.

BACKGROUND AND AIMS: Elevated low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for cardiovascular (CV) events. European guidelines recommend reducing LDL-C as the primary lipid target to reduce CV risk, using lifestyle modifications and lipid-lowering therapy (LLT). Many European patients do not achieve guideline-recommended LDL-C levels. The present database analysis aimed to assess LLT treatment patterns and LDL-C threshold attainment in Germany in a large, real-world cohort of patients. METHODS: Patients from the Cegedim Longitudinal Practice Database in Germany who met selection criteria were included: (a) LDL-C measurement in 2013; (b) ≥20 years of age; (c) high or very-high CV risk conditions: recent acute coronary syndrome (ACS), other coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) (atherosclerotic cardiovascular disease [ASCVD]) or diabetes mellitus (DM) (non-ASCVD). LDL-C threshold attainment was assessed based on LDL-C targets from 2011 European guidelines. RESULTS: 42,767 patients met the inclusion criteria; 35% received current statin treatment, and 30% achieved guideline-recommended LDL-C targets. Attainment of LDL-C goals among ASCVD hierarchical categories was 46.7% for recent ACS, 35.8% for ischemic stroke, 34.9% for other CHD, and 26.9% for PAD. Among patients in the non-ASCVD group with DM, 23.6% achieved LDL-C goals. Similar results were observed when patients were grouped by prevalence (patients assigned to every risk group for which they qualified). CONCLUSIONS: In this high/very-high CV risk population in Germany, statin utilization was low; suggesting that LLTs are not prescribed as per European guidelines. These results highlight the need to increase LLT use among high-risk patients.

Prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia.

INTRODUCTION: Hypercholesterolemia is a causal risk factor for cardiovascular diseases, which is recommended to be treated at least in high-risk patients. Yet, currently there is a lack of epidemiological data on the number of high-risk patients in Germany who do not respond adequately to high-dose statin monotherapy or statin therapy in combination with other lipid-lowering agents. METHODS: Of a total of over 2.6 million patient records from general practitioners in the IMS Disease Analyzer database, all high-risk cardiovascular patients with hypercholesterolemia who did not reach target low-density lipoprotein-cholesterol (LDL-C) levels despite at least 12 months of maximum lipid-lowering therapy and optimal medication supply (medication possession rate≥80%) were selected over a defined period. RESULTS: On the basis of the practice data, a total of 602 133 patients with a high cardiovascular risk who were treated with statin monotherapy or statin combination therapy with optimal medication supply (medication possession rate≥80%) for at least 12 months were identified. Of them, 49 406 patients received high-dose statin therapy, and 51 869 patients received statin therapy in any dose in combination with another lipid-lowering agent. A total of 79 848 high-risk patients did not reach the target LDL-C level of 70 mg/dl or less despite consistent lipid-lowering therapy; of them, 12 808 had a documented LDL-C level of at least 130 mg/dl. CONCLUSION: The prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia is substantial in Germany.

[Analysis of Secondary Data to Determine the Prevalence of Cardiovascular High Risk Patients with Hypercholesterolemia and Refractory Course of Treatment]. / Sekundärdatenanalyse zur Ermittlung der Prävalenz von kardiovaskulären Hochrisiko-Patienten mit Hypercholesterinämie und therapierefraktärem Behandlungsverlauf.

Background Hypercholesterolemia plays a causal role in the development of cardiovascular diseases. Patients are affected differently. There is a lack of epidemiological data about the frequence and characteristics of patients in Germany, especially about those who do not respond sufficiently to high intensity statins with or without other lipid modifying therapies. Methods From more than 2.6 million patient records of office based general practitioners, patients with hypercholestrolemia and high cardiovascular risk, who do not reach their individual LDL-C goal despite a best supplied twelve month maximum lipid lowering therapy (MPR ≥ 80 %), were extracted from the database. Results 5791 909 statutorily insured German patients are extrapolated with hypercholesterolemia (95 % CI: 5787 368 - 5796 454). 602 133 (95 % CI: 600 620 - 603 650) patients with high cardiovascular risk were treated with high intensity lipid modifying therapy (medication possession rate ≥ 80 %) for at least 1 year. 49 406 (95 % CI: 48 972 - 49 843) of them got mono-therapy with high intensity statins, 51 869 (95 % CI: 51 425 - 52 317) received statins in any dose combined with other lipid lowering drugs. 79 848 (95 % CI: 79 313 - 80 385) high risk patients did not reach LDL-C < 70 mg/dl despite optimal lipid treatment. 12 808 (95 % CI: 12 589 - 13 030) high risk patients even had LDL-C values ≥ 130 mg/dl. Discussion To classify patient's therapy refractory, they must have maximal drug therapy over a sufficient period of time. Usually statins are prescribed as first line therapy. Due to adverse events or contraindications statins are often prescribed in submaximal doses. Therefore patients with statins at lower dose combined with another lipid lowering drug were also included in the analysis. For patients missing the LDL-C target of ≤ 130 mg/dl despite optimal lipid lowering therapy there is a high medical need for innovative therapies.

'Knowing what matters in diabetes: healthier below 7': results of the campaign's first 10 years (part 1): participants with known type 2 diabetes.

INTRODUCTION: During the 'Knowing what matters in diabetes: healthier below 7' diabetes campaign, more than 30 000 randomly participating individuals underwent an occasional, voluntary diabetes risk check between 2005 and 2014. METHODS: This campaign aimed to inform individuals in Germany about diabetes mellitus and its complications, the established risk factors for development of type 2 diabetes (T2D), their prevalence and management in the real-life population, the quality of risk factor control and actual disease management in participants with a history of established diabetes mellitus [people with diabetes (PWD)]. Besides demographic characteristics (e.g. sex, age) and anamnestic information (antihypertensive treatment, history of elevated plasma glucose levels, genetic disposition), risk factor assessment included BMI, waist circumference, and lifestyle (physical activity, nutritional habits). The requested information was complemented by direct measurements of blood pressure (BP) (routine), plasma glucose, and HbA1c (voluntary). Between 2005 and 2014, more than 31 000 individuals participated in 45 single campaigns in numerous German cities. Here, we report on the results of the subgroup of participants with known diabetes mellitus. RESULTS: Among the 26 522 individuals with a completed questionnaire participating in the years 2006-2014, 21 055 participants (79.4%) did not have a history of diabetes and 5098 individuals (19.2%) reported being diagnosed with T2D, 369 (1.4%) with type 1 diabetes. The proportion of participants with T2D increased markedly over the years from 13.3 (2006) to 21.7% (2014). The age group older than 64 years was the largest within this subgroup (67.3%), 48.4% men and 51.6% women. The prevalence of overweight or obesity was found in 78% and 69.2% of the PWD. More than 40% of individuals with T2D had no regular physical exercise and more than 15% had unfavorable nutritional habits. In all, 69.9% of participants with T2D had elevated BP as assessed during the campaign or reported treatment with antihypertensive drugs at any time. On average, almost half of PWD (46.3%) had an HbA1c above 7.0%; a significant trend toward higher values over the 10-year period was observed. CONCLUSION: The analysis of PWD participating in the 'Knowing what matters in diabetes: healthier below 7' campaign showed that despite huge efforts in the past, important aspects for progression and complications of T2D mellitus are still not well controlled. This includes lifestyle habits as well as pharmaceutical treatment. Although the participants in this study cannot be considered a representative sample of the German population and occasional measurements without standardization further limit firm conclusions, the BP, plasma glucose, and HbA1c results indicate that a major proportion of PWD have insufficient metabolic and BP control. The marked increase in the proportion of T2D among all participants over time is consistent with the increasing prevalence of T2D mellitus found in many other countries worldwide in the recent decades. Our findings underline the importance of an optimized therapy for further improvement of disease management in those already diagnosed with this common chronic, progressive disease.

Early discontinuation and related treatment costs after initiation of Basal insulin in type 2 diabetes patients: a German primary care database analysis.

AIMS: The aim was to compare early discontinuation and related treatment costs in type 2 diabetes in primary care after initiation of insulin glargine or human basal insulin (NPH). METHODS: Overall, 2765 glargine and 1554 NPH patients from 1072 general practices were analyzed (Disease Analyser). Early discontinuation was defined as switching to a different basal insulin or another insulin treatment regimen within 90 days after first basal insulin prescription (index date, ID). Treatment costs were assessed 365 days prior and post ID in both groups. Propensity score matching and linear regression was used to adjust cost differences (post vs prior ID: discontinued vs continued patients) for age, sex, diabetes duration, antidiabetic comedication, diabetologist care, disease management program participation, costs before ID, and Charlson Comorbidity Index. RESULTS: Within 3 months after ID, 13% of glargine patients switched to other insulin treatment regimens (NPH: 18%; P < .05). After propensity score matching, adjusted cost differences in 146 discontinued versus 1342 continued glargine patients were calculated (NPH: 146 vs 1342). Diabetes-related prescription costs were lower among persistent glargine patients compared to persistent NPH patients (EUR-49 [19]; P = .0109). Mean cost difference for diabetes-related prescriptions was lower among those who persisted on glargine compared to those who switched to other treatment regimens (EUR-74 [42], P = .0780). CONCLUSIONS: Treatment persistence within 3 months after basal insulin initiation was significantly higher under insulin glargine compared to NPH. Diabetes-related prescription costs were significantly lower among patients who adhered to insulin glargine compared to persistent NPH patients.

Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis.

AIMS: To compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin. METHODS: In the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008-2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan-Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance. RESULTS: In BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31-1.87; NPH vs. glargine: 1.22; 1.07-1.38). Heart failure (1.39; 1.16-1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98-0.99), metformin (0.61; 0.54-0.69), and sulfonylurea co-medication (0.86; 0.77-0.97) were associated with lower discontinuation. CONCLUSIONS: In BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.

Predictors of hypoglycaemia in insulin-treated type 2 diabetes patients in primary care: a retrospective database analysis.

AIMS: To investigate the frequency and predictors (diabetes care and treatment, comorbidity) of documented hypoglycaemia in primary care patients with insulin-treated type 2 diabetes. METHODS: Data from 32,545 patients (mean age: 70 (SD 11) years, 50.3% males) from 1072 practices were retrospectively analyzed (Disease Analyzer database Germany: 09/2011-08/2012). Logistic regression (≥1 documented hypoglyemia) was used to adjust for confounders (age, sex, practice characteristics, diabetes treatment regimen). RESULTS: The prevalence of patients (12 months) with at least one reported hypoglycaemia was 2.2% (95% CI: 2.0-2.4%). The adjusted odds of having hypoglycemia were increased for renal failure (OR; 95% CI: 1.26; 1.16-1.37), autonomic neuropathy (1.34; 1.20-1.49), and adrenocortical insufficiency (3.08; 1.35-7.05). Patients with mental disorders including dementia (1.49; 1.31-1.69), depression (1.24; 1.13-1.35), anxiety (1.18; 1.01-1.37), and affective disorders (1.80; 1.36-2.38) also showed an increased odds of having hypoglycemia. Location of the practice in an urban area was associated with a lower odds ratio (0.74; 0.68-0.80). CONCLUSIONS: Both individual patient characteristics (e.g. comorbidity) and regional factors (practice location) have a substantial impact on hypoglycaemia in primary care patients with insulin therapy.

Predictors of insulin initiation in metformin and sulfonylurea users in primary care practices: the role of kidney function.

The aims were to investigate predictors of insulin initiation in new users of metformin or sulfonylureas in primary care practices, in particular, its association with decreased renal function. Data from 9103 new metformin and 1120 sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90 ml/min/1.73 m(2) from 1072 practices were retrospectively analyzed (Disease Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score matching was used to adjust for confounders (age, sex, practice characteristics, comorbidity). Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years (P < .001). Kaplan-Meier curves (propensity score matched patients) showed that the metformin group was at a lower risk of insulin initiation compared to sulfonylurea users throughout the study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m(2)) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users. New users of sulfonylurea monotherapy in primary care practices in Germany were about 3-fold more likely to start insulin therapy than those with metformin. Kidney function decline was associated with earlier insulin initiation in metformin but not in sulfonylurea users.

Relevance of indirect comparisons in the German early benefit assessment and in comparison to HTA processes in England, France and Scotland.

Early benefit assessment in Germany under the legislative framework of AMNOG (Arzneimittelmarktneuordnungsgesetz) requires direct comparisons of the new drug with appropriate comparators determined by the Federal Joint Committee (G-BA). In case no head-to-head studies are available for direct comparisons, the submission of indirect comparisons is permitted to assess the additional benefit of the new drug. However, the Institute for Quality and Efficiency in Health Care (IQWiG) states a clear preference for head-to-head trials and defines strict requirements for indirect comparisons to be considered in the benefit assessment. Similar requirements also exist in other countries with mandatory health technology assessments (HTA), like France, England and Scotland. Our evaluation shows that a comparison of the different HTA regarding indirect comparisons is difficult. Overall, external preconditions and methodological requirements are demanding and hardly to fulfill by pharmaceutical companies for implementation of indirect comparisons in early benefit assessment. The determination of the appropriate comparators, outcomes, patient subgroups and study choice are the main target within indirect comparisons for the future. To compare and assess submitted indirect comparisons it would be desirable that a transparent process was established, including the mandatory publication of HTA-reports within Europe and international guidelines, accepted by a large number of HTA-agencies.

Resource consumption and costs of treatment in patients with type 1 diabetes under intensified conventional therapy under German real-life conditions.

INTRODUCTION: The aim of this study was to compare, from the perspective of the statutory health insurance, resource consumption and the associated adjusted treatment costs of intensified conventional therapy (ICT) with long-acting insulins in patients with type 1 diabetes mellitus (T1DM). METHODS: We identified patients with T1DM who started ICT with either insulin glargine or neutral protamine Hagedorn (NPH) insulin between July 2000 and February 2008 using a representative German database (IMS® Disease Analyzer). The variables age, gender, insurance status, diabetes duration, hemoglobin A1c level, body mass index, and geographic region and specialization of practice were collected. Resource consumption was evaluated over a time period of 12 months and included the quantities of applied basal and bolus insulin, blood glucose test strips, lancets and needles, physician visits (general practitioner, specialist), hospitalization, and antihypoglycemic therapy (intravenous glucose/glucagon). RESULTS: A total of 2297 patients with T1DM were included; 1079 received ICT with insulin glargine and 1218 with NPH insulin. After adjustment, annual cost savings in favor of insulin glargine amounted to €423.94 compared with NPH insulin (p = .3019). DISCUSSION: The adjusted results show that an ICT with insulin glargine results in lower annual costs than ICT with NPH insulin (this difference was not statistically significant). However, in the context of glucose-lowering effect and a lower hypoglycemia rate, insulin glargine is preferred to NPH insulin for patients with T1DM undergoing ICT.

Predictors for the initiation of a basal supported oral therapy (BOT) in type 2 diabetic patients under real-life conditions in Germany.

OBJECTIVE: To assess the predictors for the initiation of a basal supported oral therapy (BOT) in type 2 diabetic patients under real-life conditions in Germany. RESEARCH DESIGN AND METHODS: A historical cohort study based on representative German real life data (IMS(®) Disease Analyzer) was performed. The study included patients with type 2 diabetes who started an oral antidiabetic drug (OAD) treatment between 01/1995 and 12/2011. Patients with consecutive treatment data for at least 12 months before the initiation of an OAD treatment were eligible for the analysis. The time-dependent rate of patients starting an insulin therapy with a long-acting insulin was calculated by use of the Kaplan-Meier method. Multivariate Cox regression analyses were applied to identify associated factors. RESULTS: The study included 194,967 patients with type 2 diabetes mellitus being on OAD therapy. 24,964 patients were switched to BOT during the observational period. The probability of switching to insulin therapy was associated with three main predictors such as (1) poor metabolic control, (2) midlife age and (3) number and type of the OAD before insulinization. The variation of the HbA1c threshold to HbA1c≥7.5 leads to comparable outcomes with significant HR. CONCLUSION: The highest probability of initiating a basal supported oral therapy (BOT) under real life conditions was found for patients with poor metabolic control, midlife age and pre-treatment with specific OADs such as SU, GLI or AGI before initiation of insulin therapy.

Amputation rate and risk factors in type 2 patients with diabetic foot syndrome under real-life conditions in Germany.

AIMS: To determine the risk of amputation and the influencing factors for amputation for patients with type 2 diabetes with diabetic foot syndrome. METHODS: Longitudinal data from general practices in Germany (Disease Analyzer database, IMS Health) were analyzed. 3892 type 2 diabetes patients (mean age: 66.0 (SD: 10.9 years), 39.1% female) with a first-time diagnosis of diabetic foot syndrome between 01/200 and 12/2004 and at least 5 year follow-up documentation in the practices were included. The analyses of amputation-free survival were carried out using Kaplan-Meier curves and log-rank tests. A multivariate Cox regression model was fitted with the incident of diabetes-associated amputations as the dependent variable and adjusted for clinical and demographic characteristics. RESULT: The cumulative incidence of diabetes-associated lower limb amputations was 18.2%. Amputations are independently associated with higher age, male gender, higher HbA1c value and longer diabetes duration but also some other diabetes complications. DISCUSSION: The diabetic foot syndrome can but must not lead to a lower limb amputation. Due to the great medical and economic burden on the health system caused by diabetic complications, early therapeutic intervention is essential for patients with diabetic foot syndrome.