Amnog Early Benefit Assessment (EBA) in Germany - A Specific Challenge for Antidiabetics

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Objectives: To quantify the excess effect of diabetes mellitus (DM) on the healthrelated quality-of-life (HrQol) in community-dwelling elderly. Methods: In a matched cohort study, nested in a prospective randomized trial on the efficacy of the 13-valent pneumococcal vaccine in community-dwelling persons of ≥ 65 years, HrQol was assessed at the time of enrolment, using the EQ-5D-3L instrument, in 5,567 subjects with self-reported DM (i.e. DM-cohort) and 11,131 matched controls without DM (i.e. non-DM-cohort). Controls were matched to cases on age, sex, educational level, comorbidities other than DM, population density and region. EQ-5D-3L summary index (EQ-index) was derived using Dutch tariff. Stratification was conducted for sex, education, age, number of comorbidities and the use of insulin (DM cohort only). GP-data on diabetes status, available for 48.8% of DM-participants, were compared with the self-reported DM status.  Results: Participants had an average age of 72 years and 61.5% were males. DM-participants reported more problems in all five dimensions, and in particular in mobility, usual activities and pain/ discomfort where they reported 12.1%, 7.5% and 6.2% more problems than non-DM participants. Mean EQ-index was 0.88 and 0.91 for DM and non-DM-participants, resulting in 0.03 EQ-index loss attributed to DM. This effect between DM and nonDM-participants was larger in females than in males (0.04 vs 0.03), in low educated than in higher educated (0.03 vs 0.02), older elderly (i.e.,≥ 85 years) than younger elderly (i.e.,< 70 years) (0.04 vs 0.02), and in participants with several comorbidities than participants having only DM (0.04 vs 0.03). DM-participants with and without insulin had a 0.06 and 0.02 lower EQ-index than non-DM participants, respectively. For DM-participants self-reported DM status was confirmed in 94.8% by ICD-code in GP registries.  Conclusions: In community-dwelling elderly DM was associated with more problems in every dimension of the EQ-5D-3L, and a 0.03 lower qualityof-life than non-DM elderly.

DIABETES/ENDOCRINE DISORDERS – Health Care Use & Policy Studies PDB84 Quality of Life in Patients with Diabetes Mellitus II in Czech Republic Matisakova I, Bartosakova R, Bielik J Trencin University, Trencin, Slovak Republic

Objectives: The prevalence of Diabetes Mellitus II (DMII) in Czech Republic (SR) is about 800 000 cases. No study was published about the impact of DMII on quality of life (QoL) and work ability (WA) in patients with DMII in Czech Republic.  Methods: 140 patients were evaluted, 76 women and 64 men, with the average age being 58,87 years, weight – 79,1 kg and height – 170,7 cm. 51 patients were treated by PAD, 18 - PAD and insulin, 38 – insulin, 33 – intensive insulin therapy. Average duration of DMII was 7,4 years and patients visted a diabetologist 3,7 times per year. 76 patiensts had some type of complications. The own questionnaire consisting of 6 parts was used: A. Demography, B. Clinical part, C. Quality of life, D. Socio-economic part, E. EQ5DL. QoL and WA were evaluated on numeric scales from 0 - the worst to 10 - the best. T-test, Wilcoxon test were used in results evaluation.  Results: Significant statistical differences in QoL were found: in the time of best health - 8,96, without DM – 8,65 in the time of diagnosis – 6,94, in the time of full treatment – 7,36. Similar results were gained in WA: 8,89 vs 8,74 vs 7,11 vs 7,26. The results from QoL and WA were in strong correlation. Foreknowledge of disease (1-the worst, 5-the best) was 3,8, satisfaction with medical care – 4,2 and nursing care – 4,3. Willingness to pay for health without DM was 60 €  monthly by average monthly income 511 € . There were 33 disability days per year due to DM.  Conclusions: DMII has significant impact on patients‘ QoL and AW. There are significant differences in quality of life and work ability assessments in various stages of the duration of DMII. The treatment has positive impact on QoL and WA. PDB85 Real-World Treatment Pattern in Community Patients with Type-2 Diabetes: Evidence from Shanghai, China Gao Y1, Chen L2, Fang H2, Xu D2, Xuan J3, Liu B4 Centennial Scientific Ltd, Shanghai, China, 2Shanghai Minhang Center for Disease Control and Prevention, Shanghai, China, 3Sun Yat-Sen University, Guangzhou, China, 4Department of Health Economics, School of Public Health, Fudan University, Shanghai, China 1Shanghai

Objectives: Researches have demonstrated the value of community based, protocol driven care in the management of diabetes; however, real-world evidence describing treatment pattern of type-2 diabetes in primary healthcare setting in China lacks. We aim to investigate the real-world treatment pattern for those diagnosed with type-2 diabetes in Chinese community population.  Methods: A retrospective database study was conducted. Data were obtained from the Minhang community-based EMR database, which cover medical encounter records from community clinics/hospitals in the Minhang district of Shanghai, China. Patients aged over 18 and diagnosed with type-2 diabetes between 2010 and 2014 with 6 month treatment naive period before first diagnosis and 1-year follow-up after first prescription of anti-diabetic medication were included in the study. Patient baseline characteristics, treatment pattern including switching were collected. Descriptive statistics were used for data analysis.  Results: A total of 32,363 patients were identified. Mean age was 69.9, 81.6% over 60. Male accounted for 44.7%. Median BMI was 24.0. 11.9% patients smoked and 4.0% were heavy smoker. 16.7% patients drunk and 31.0% were heavy drinker. Mean systolic blood pressure (BP) measured 147.4; mean diastolic BP measured 89.1. Hypertension and dyslipidemia ranked top co-morbidities, with 85.2% and 46.7% patients respectively. Sulfonylureas was the top initiation medication (58.3%), followed by biguanide (34.6%) and α -glucosidase inhibitors (18.4%). 70.8% patients started with one oral antidiabetic drug (OAD). 75.2% patients experienced antidiabetic therapy switch during 1-year follow-up period, with 85.0% switched from OAD to other OAD and 5.10% from OAD only to insulin. 10.1% patients started with insulin, with premixed human insulin accounting for 99.0%. We also observed 6.6% insulin to OAD(s) switch, which would require

further investigation.  Conclusions: Our findings outlined the type-2 diabetes treatment pattern in Chinese primary healthcare setting, which provided scientific insight for real-world diabetes treatment in China. Note: Co-1st-author: Yue Gao, Linli Chen; Corresponding-author: Bao Liu. PDB86 Impact of Cardiovascular Outcome Trial (CVOT) Data on EU5 Access for New Type 2 Diabetes Drugs DiModica L1, O’Connor E2 Resources Group, Burlington, MA, USA, 2Decision Resources Group, London, UK

1Decision

Objectives: Empagliflozin was the first glycemic-lowering therapy to demonstrate a reduction in cardiovascular (CV)-related mortality in a dedicated CV outcome trial (CVOT), the EMPA-REG OUTCOME study. Liraglutide has subsequently demonstrated CV benefit in the LEADER CVOT. Lixisenatide and sitagliptin have shown non-inferiority for CV events in patients with a history of CV disease (CVD). We sought to determine the impact of CVOT data on EU5 pricing and reimbursement (P&R) decisions and access for T2D drugs.  Methods: In January 2016, 270 endocrinologists and general practitioners across the EU5 were surveyed regarding their views on current and expected T2D prescribing and the extent to which it is impacted by payer policy. Additionally, 15 payers who influence national/regional reimbursement were interviewed.  Results: Surveyed physicians indicated that the potential target population for empagliflozin far exceeds the number of patients currently treated with sitagliptin (28-33% vs. 3-8%, respectively). However, respondents anticipate that national or local coverage, patient eligibility requirements, and budgetary factors may limit empagliflozin access, likely in earlier lines of therapy. Nevertheless, 37-61% of respondents would prescribe empagliflozin as the second-line therapy of choice behind metformin in high-risk CVD patients. More respondents would switch GLP-1-treated patients to an in-class agent showing CV benefit (38-58%) than would increase prescribing of lixisenatide based on its non-inferiority data from the ELIXA CVOT (12-23%). Physicians’ anticipated prescribing suggests that reductions in CV events and mortality seen with liraglutide in the LEADER CVOT will drive its increased use in T2D. Interviewed payers report that positive effects on hard clinical outcomes such as CV-related mortality will improve new T2D drugs’ chances of favorable findings on health technology assessment.  Conclusions: Primary research with EU5 payers and physicians suggests that T2D drug developers that demonstrate CVOT benefit may use this as a lever to more favorable P&R terms and market uptake. PDB87 Increase Hospital Physicians’ Awareness of Expenditure Generated by Their Prescription in the Ambulatory Sector: Learning from the Experience of the 37 Public Hospitals of Paris in Diabetology Bocquet F1, Fusier I1, Cordonnier A1, Lechat P2, Paubel P1 1AP-HP, AGEPS, Paris, France, 2COMEDIMS AP-HP, Paris, France

Objectives: The expenditure generated by drugs prescribed by French hospital physicians dispensed to treat out-patients (drugs Prescribed in Hospital for OutPatients or PHOP) exceeds those generated by drugs prescribed for in-patients. Currently, French hospitals must comply with two regulatory rates on drugs-PHOP in 2016: an annual growth rate in volume (+4%) and a generic prescribing rate (44%). This study analyzes expenditures of antidiabetics prescribed by hospital physicians in the 37 Public Hospital of Paris (AP-HP).  Methods: Based on data provided by the French Public Health Insurance, the Committee on Medicinal Products of AP-HP analyzed expenditures generated by antidiabetics-PHOP by International Nonproprietary Names (INN), the annual growth rate in volume and the generic prescribing rate of PHOP-antidiabetics in AP-HP and in France over the 2014–2015 period, and the number of patients treated by antidiabetics by AP-HP hospitals in 2015.  Results: The expenditure generated by antidiabetics-PHOP in AP-HP were € 17.22 million in 2015 and € 17.29 million in 2014 (more than 100.000 patients treated annually). Spending were € 0.97 and € 0.87 million for in-patients these two years. The 2015–2014 annual growth rate in volume for antidiabetics-PHOP in AP-HP was +2.4% (lower than the national rate of +5.8% and than the regulated target rate of +4%). In 2015, the generic prescribing rates by INN were higher than the regulated target rate of 44% and similar to the national average. Heterogeneity between AP-HP hospitals in terms of drug costs per patient was highlighted for insulin glargine (63 to 279 € /patient), sitagliptin+metformin (28 to 187 € /patient) and metformin (6 to 32€ /patient). Such differences could be explained by varying duration of the prescriptions, dosages and patient profiles.  Conclusions: No lever to regulate the expenditure generated by antidiabetics-PHOP has been identified, but the duration of the prescriptions could be explored to calculate daily costs of antidiabetics-PHOP per patient in AP-HP hospitals. PDB88 Amnog Early Benefit Assessment (EBA) in Germany - A Specific Challenge for Antidiabetics Bleß H1, Mathes J2, Kotowa W2, Lübker C3 1IGES Institut GmbH, Berlin, Germany, 2IGES Institut GmbH, Nuremberg, Germany, 3IGES Institut GmbH, Hamburg, Germany

Objectives: A remarkable majority of antidiabetics could not prove an additional benefit (AB) during EBA in Germany resulting in low reimbursement prices and, therefore, in a great amount of market withdrawals. To investigate more detailed the amount of antidiabetics with no or any AB and of market withdrawals as well as the specific obstacles for antidiabetics during EBA and their effects on medical care, a retrospective analysis of EBA was conducted.  Methods: 27 EBA and entailing 78 patient groups (PG) of 23 medicinal products (MP) finalized until 31 May 2016, and the insulin consumption at the expense of the statutory health insurance (SHI) were analyzed.  Results: An AB vs. the appropriate comparator could not be proven for 91% of PG. A minor AB could only be proven for 9% of PG, exclusively on the basis of less side effects. A considerable or a major AB could not be proven. 48% of



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analyzed MP belonging to above EBA were withdrawn from the market. Especially, the demand for patient-relevant endpoints, the non-recognition of surrogates, low absolute risks of severe events occurring only in the far future, limited duration of studies for antidiabetics as long-term therapeutics, and low reimbursement prices of generics as appropriate comparators were identified as obstacles for antidiabetics in EBA. The insulin consumption at the expense of the SHI increased by 149% from 1997 to 2014.  Conclusions: The higher insulin consumption might be a consequence of the uncertainty of physicians concerning the medical prescription of new antidiabetics due to EBA in addition to previous control tools, and associated market withdrawals. Thus, a reliable consensus on the potential importance of new antidiabetics under consideration of restricted possibilities for the proof of required evidence, the notably high need for efficient antidiabetic therapy just as the necessity of economic actions is indispensable. PDB89 Insulin Degludec in Clinical Practice: A Systematic Review of Japanese Real-World Data Kaku K1, Wolden ML2, Hyllested-Winge J3, Nørtoft E2 1Kawasaki Medical School, Okayama, Japan, 2Novo Nordisk A/S, Søborg, Denmark, 3Novo Nordisk Pharma Ltd, Tokyo, Japan

Objectives: This systematic review evaluated the real-world clinical effectiveness of switching to insulin degludec (IDeg) in Japanese patients.  Methods: Studies were identified from Japanese Diabetes Society (JDS) abstracts (2014-2015) and PubMed (2012 onwards). Inclusion criteria were: Japanese population, > 15 participants and only studies switching patients from basal or basal–bolus insulin regimens to IDeg. Randomised controlled trials and case reports were excluded. Weighted mean changes in safety and effectiveness endpoints were calculated using the number of patients in each study. Statistical significance: p≤ 0.05.  Results: A total of 81 JDS abstracts and 5 manuscripts met the search criteria, representing 4238 patients (1028 T1D, 602 T2D, 2608 not specified). HbA1c was reported in 93% of studies and was improved in 84% (51% significant, 33% numerical), unchanged in 12% and worse in 4% (3% numerical, 1% significant). Across all studies the weighted mean actual change in HbA1c was –0.25%. Basal insulin dose was reported in 57.5% of studies and was lower in 60% (30% significant, 30% numerical), numerically unchanged in 26% and higher in 14% (2% significant, 12% numerical). The weighted mean change in basal insulin dose was –4.81% and –3.72% for all studies and for significant-only studies, respectively. The weighted mean change in basal dose based on all studies was –8,9%, –5.5% and –2.9% for T1D, T2D and unspecified populations, respectively. Hypoglycaemia was recorded in 28.1% of the studies. After switching, 54.8% of studies reported decreased hypoglycaemia, 29.0% no change and 16.1% an increase. Quality of life (QoL) was measured in 11.1% of studies. 81.8% reported improved QoL after switching, 18.2% reported no change in QoL.  Conclusions: Switching from a conventional basal insulin to IDeg has the potential to improve HbA1c with a lower insulin dose. Switching to IDeg may also provide a reduced risk of hypoglycaemia and improvement in QoL. PDB90 A Population Based Diabetes Drug Utilization Analysis in Chinese Community: A Retrospective Database Study Wang K1, Gao Y2, Chen Y1, Jiang X1, Xuan J3, Liu B4 1Lilly Suzhou Pharmaceutical Company, Ltd., Shanghai, China, 2Shanghai Centennial Scientific Ltd, Shanghai, China, 3Sun Yat-Sen University, Guangzhou, China, 4Department of Health Economics, School of Public Health, Fudan University, Shanghai, China

Objectives: Comprehensive approach managing overall cardiovascular risk factors (i.e. blood glucose, blood pressure, and cholesterol level) is a core part of diabetes care; however, evidence describing type-2 diabetes (T2D) treatment in primary healthcare setting in China lacks. We aim to investigate the real-world drug utilization for T2D in a Chinese community population.  Methods: A retrospective database analysis was conducted. Data were obtained from Minhang community-based electronic medical record database, covering medical encounter records from community clinics/hospitals in Minhang district of Shanghai, China. Patients aged 18 or older, with T2D diagnosis or T2D medication prescription were included. Their demographics and drug utilization information between 1st July 2014 and 30thJune 2015 were analyzed using descriptive statistics. Results: Totaling 41,186 T2D patients were identified, with mean age 67.3 (SD= 10.3), 44.3% male, mean BMI 24.4 (SD= 3.3) kg/m2. Around 87.0% patients received anti-diabetic medications. Among them, sulfonylureas ranked top oral antidiabetic drug (OAD) (54.1%), followed by biguanide (33.6%) and α -glucosidase inhibitors (29.4%). Nearly 15.8% patients were on insulin, where premixed dominated (99.4%, 6,473/6,512). Hypertension (69.3%) and dyslipidemia (20.9%) ranked top co-morbidities, with 18.1% patients having both. Regarding comorbidity management, 46.9% patients were on anti-hypertension therapy, with 60.1% (11,602/19,314) on renin-angiotensin system inhibitor and 55.0% (10,624/19,314) on calcium antagonists; 8.5% were on anti-dyslipidemia therapy, with 93.1% (3,273/3,516) on statins. Around 43.7% T2D patients were on both anti-diabetes and anti-hypertension treatments, 8.0% on both anti-diabetes and anti-dyslipidemia treatments, and 5.4% on all three. Among T2D patients with hypertension, 32.3% were not receiving anti-hypertension treatment; among those with dyslipidemia, 59.2% were not receiving anti-dyslipidemia treatment; and among those with both, 26.8% were receiving neither.  Conclusions: Among Chinese T2D patients in community hospitals under study, sulfonylureas and premix are primary choices of OAD and insulin, respectively. Hypertension and dyslipidemia are top comorbidities, but with insufficient management. Co-1stauthor: Ke Wang, Yue Gao. Corresponding-author: Bao Liu. PDB91 Improving the System of Healthcare Provision for Patients with Diffuse Toxic Goiter in Ukraine Vadziuk Y

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Ivan Horbachevsky Ternopil State Medical University, Ternopil, Ukraine

Objectives: To assess medical technologies in order to increase efficiency and reduce the cost of thyroid disease treatment.  Methods: We made the retrospective analysis of 52 patients’s medical records with diffuse toxic goiter that were hospitalized to the endocrinology department of Ternopil University Hospital (Jan-Dec 2012). The cost of thyrostatic therapy, which was preferred in practice, was analyzed. We also checked the appropriateness of diagnostics and specialist consultations according to the Protocol of medical care for patients with endocrine system disorders.  Results: The result of retrospective analysis of 52 patients’s medical records with diffuse toxic goiter showed that all patients received thyrostatic therapy by thiamazol. Among them 13 patients were treated with drugs of Ukrainian production while 39 patients were taking medicine of foreign manufacturer. The cost of pharmacotherapy with foreign medicines was 275% more expensive compare to Ukrainian drugs. When comparing diagnostics and specialists consultations with a Protocol of medical care for patients with endocrine system disorders we have established compliance. However, given the prevalence of complications of underlying disease by cardiovascular system disorders (in 100% of patients), we consider it necessary to add cardiologist consultation to Protocol.  Conclusions: It is advisable to use domestic drugs in pharmacotherapy of diffuse toxic goiter. Cardiologist consultation should be added to Protocol of medical care for patients with diffuse toxic goiter. PDB92 Characteristics of Patients with Type 2 Diabetes Mellitus Initiated on Basal Insulin Regimens: Retrospective Analysis of Electronic Health Record Data Lee LK1, Liebert R2, Hallissey B3 1Kantar Health, Foster City, CA, USA, 2Kantar Health, New York, NY, USA, 3Kantar Health, Horsham, PA, USA

Objectives: To examine characteristics of patients diagnosed with type 2 diabetes mellitus (T2DM) initiated on three basal insulin regimens: long-acting basal insulins (LABI), ultra-LABI (ULABI), and LABI combined with any oral antidiabetic medications (LABI+OAD), using real-world clinical data.  Methods: This retrospective study used data (current to March 2016) from a US ambulatory electronic health records (EHR) database to identify patients ≥ 18 years old with International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes for T2DM who initiated ULABI (insulin glargine 300 mg or degludec; n= 3,718), LABI (insulin glargine 100 mg or detemir; n= 11,417), or LABI+OAD (insulin glargine 100 mg or detemir + OAD; n= 4,922) ≤ 1 year prior to March 2016. Demographics and clinical characteristics were extracted from EHR ≤ 2 years prior. A multinomial logistic regression predicted ULABI and LABI+OAD vs. LABI treatment from patient characteristics and clinical characteristics at or prior to treatment initiation.  Results: Overall sample (N= 20,057) age was 62.49; 49.7% female; 67.7% white. Significant (two-tailed, p< 0.05) predictors of ULABI vs. LABI use included younger age (odds ratio [OR]= 1.02), male gender (OR= 1.11), white vs. black (OR= 1.60) and unknown/ other race (OR= 1.94), overweight (OR= 1.22) and obese (OR= 1.31) vs. normal/underweight BMI, sleep apnea (OR= 1.25), hypertension (OR= 1.29), and higher prior HbA1c level (OR= 1.04). Significant predictors of LABI+OAD vs. LABI included younger age (OR= 1.01), unknown/other race vs. white (OR= 1.70), overweight (OR= 1.32) and obese (OR= 1.38) BMI, and absence of dyslipidemia (OR= 1.33), hypertension (OR= 1.11), depression (OR= 1.22), sleep apnea (OR= 1.29), and microvascular (OR= 2.19) and macrovascular (OR= 1.35) disease.  Conclusions: Higher prior HbA1c levels, overweight and obese BMI, and presence of sleep apnea and hypertension were associated with ULABI vs. LABI treatment. Overweight or obese BMI and absence of apnea, depression, and common diabetic comorbidities (dyslipidemia, hypertension, microvascular/macrovascular disease) were associated with LABI+OAD vs. LABI treatment. Findings may help inform physicians in deciding on the newer ULABI treatments in T2DM. PDB93 The Mosaic Study: Regional Variation in Treatment Patterns Associated with Progression from Initial Insulin Regimen Bae J1, Curtis BH2, Rogers JR3, Linetzky B1, Ali AK1, Tsoukas M4, Beshyah S5, Matsuba I6, Araz M7, Magalhaes Montenegro R8, Kim S9 1Eli Lilly and Company, Indianapolis, IN, USA, 2Eli Lilly, Indianapolis, IN, USA, 3Brigham and Women’s Hospital, Boston, MA, USA, 4McGill University, Montreal, QC, Canada, 5Medical Institute, Abu Dhabi, United Arab Emirates, 6Matsuba Medical Clinic, Kawasaki, Japan, 7Gaziantep University Hospital, Gaziantep, Turkey, 8Universidade Federal do Ceará, Fortaleza, Brazil, 9Harvard University Brigham Women’s Hospital, Boston, MA, USA

Objectives: The MOSAIc study is a 2-year prospective observational study of patients with type 2 diabetes treated with insulin across 18 countries in 5 geographic regions. Insulin use patterns vary by region. This analysis describes treatment regimen changes from baseline to the end of study by region.  Methods: Patients with type 2 diabetes, aged ≥ 18 years, and taking insulin for ≥ 3 months were included. Clinical, demographic, psychosocial, and health system data were collected within the routine course of care in each country. Treatment regimens at baseline and the end of study were compared, and the proportion of patients adding or switching treatments were analyzed by region, with emphases on basal (N= 1,463) and premixed insulin (N= 959) groups.  Results: During follow-up, 78% of the basal group patients continued the same therapy, with regional variations from 66% in the Middle East (ME) to 83% in Latin America (LA). Adding different insulin was observed in 6% overall but was 4% for Europe (EU) and 9% for North America (NA) (p= 0.04). In addition, 18% added a noninsulin therapy, ranging from 11% in NA to 27% in ME (p< 0.01). In the premixed group, 79% of patients continued the same therapy, with regional variations from 73% in ME to 93% in EU. Adding different insulin was observed in 6% patients overall but was 4% in EU and 9% in LA and ME. In addition, 16% added a noninsulin therapy, with regional variation from 4% in EU to 18% in ME and Asia (p< 0.01).  Conclusions: These data confirm differing patterns of insulin use by region and a relatively higher reliance on noninsulin therapy