Systematic Review and Meta-Analysis of the Efficacy and Safety of Metformin and GLP-1 Analogues in Children and Adolescents with Diabetes Mellitus Type 2.

Diabetes mellitus type 2 (DMT2) is one of the most frequent glucose metabolism disorders, in which serum glucose concentrations are increased. In most cases, changes in lifestyle and diet are considered as the first step in addressing its therapy. If changes in lifestyle and diet fail, drugs, such as metformin, must be added. Lately, apart from metformin or insulin, the FDA has approved the use of glucagon-like peptide-1 (GLP-1) analogues for children and adolescents. Little is known about their efficacy and safety at this young age. The main aim of this systematic review/meta-analysis was to assess the safety and efficacy of metformin and GLP-1 analogues, exenatide and liraglutide, compared with placebos or other antidiabetic drugs used for DMT2 in children and adolescents. Metformin did not seem to demonstrate pharmacologic superiority, while GLP-1 analogues were found superior to placebos. GLP-1 analogues may be considered a useful alternative for the treatment of DMT2 in children and adolescents.

Real world, big data cost of pharmaceutical treatment for rheumatoid arthritis in Greece.

INTRODUCTION: Rheumatoid Arthritis (RA) is a highly prevalent autoimmune disease associated with joint inflammation and destruction. Treatment for RA, especially with biologic agents (biologics), improves patient functionality and quality of life and averts costly complications or disease progression. Cost of RA pharmaceutical treatment has rarely been reported on the basis of real-world, big data. This study reports on the real-world, big data RA pharmaceutical treatment cost in Greece. METHODS: The Business Intelligence database of the National Organization for Healthcare Services Provision (EOPYY) was used to identify and provide analytics on patients on treatment for RA. EOPYY is responsible for funding healthcare and pharmaceutical care services for approximately 95% of the population in the country. ICD-10 codes were applied to identify patients with RA and at least one reimbursed prescription between 1 June 2014 and 31 May 2015. RESULTS: 35,873 unique patients were recorded as undergoing treatment for RA. Total reimbursed treatment cost for the study period was €81,206,363.70, of which €52,732,142.18 (64.94%) was for treatment with biologics. Of that cost, €39,724,489.71 (48.32%) accounted for treatment with anti-TNFs and/or methotrexate/corticosteroids. CONCLUSION: Real world, big data analysis confirms that the major driver of RA pharmaceutical cost is, as expected, the cost of treatment with biologics. It is critical to be able to match this cost to the treatment outcome it produces to ensure an optimal, no-waste, evidence-based allocation of healthcare resources to need.

Systematic review and network meta-analysis of approved medicines for the treatment of idiopathic pulmonary fibrosis.

Background: Clinical practice guidelines for the treatment of idiopathic pulmonary fibrosis (IPF) currently recommend pirfenidone and nintedanib. However, there is a lack of evidence from head-to-head comparisons. Objectives: To perform a systematic review and network meta-analysis (NMA) to access the efficacy and tolerability of two new treatments for IPF, pirfenidone and nintedanib. Methods: Randomized controlled trials (RCTs) selection (CENTRAL, MEDLINE, Embase), data extraction, risk of bias analysis, and GRADE assessment were carried out by two authors separately. Direct estimates were calculated using standard pairwise meta-analysis. A Bayesian mixed treatment comparison approach for NMA estimates, with 95% confidence intervals (CI), was used to compare the treatments, calculating odds ratios (OR) and number needed to treat (NNTB) or harm (NNTH). Results: The NMA on 10 randomized controlled trials showed that each drug had a positive effect on percentage of forced vital capacity (FVC) decline ≥ 10% (pirfenidone OR = 0.54 [95% CI = 0.37-0.80], NNTB = 9 [95% CI = 7-22]; nintedanib OR = 0.59 [95% CI = 0.41-0.84], NNTB = 9 [95% CI = 6-23]), but no significant differences were noted when comparing pirfenidone and nintedanib with respect to acute exacerbations, mortality, and serious adverse events (FVC decline OR = 0.91 [95% CI = 0.45-2.03]) or dropouts (OR = 0.75 [95% CI = 0.33-1.27]). Nintedanib showed an effect on dropouts, OR = 1.61 (1.13-2.28) and NNTH = 14 (8-61). Conclusions: Based on RCTs of 12 month duration in patients with IPF, a positive effect on FVC decline was noted for both treatments and on dropouts for nintedanib, but no significant differences were noted between treatments.

End-of-Life Health-Care Cost of Patients With Lung Cancer: A Retrospective Study.

INTRODUCTION: Lung cancer exerts a significant societal and health-care-related economic burden and chemotherapy drugs constitute a major factor of total direct cost. The aim of the present study was to assess the direct health-care cost of lung cancer in Greece by conducting a retrospective analysis on the last 6 months of life. METHODS: The present study was based on both the medical data and costs of treatment of deceased adult patients who suffered from terminal stage IIIB/IV lung cancer (non-small cell lung cancer and small cell lung cancer) during the last 6 months of their life. The study's protocol was approved by the Hospital's Research Ethics Committee. Costs included outpatient (outpatient services) and inpatient (inpatient services) costs. Descriptive statistics were mainly used for statistical analysis. RESULTS: The files of 144 patients were analyzed. The total cost of health-care services for the study population during the last 6 months of life was attributed by 57% to inpatient services, whereas chemotherapy costs (74%) comprised the largest proportion of the total inpatient cost. The highest expenditure for outpatient services was attributed to concomitant medication (59%), followed by the cost of tests (21%) and radiotherapy (20%). CONCLUSIONS: The results of our study indicate that both inpatient and outpatient costs were substantial. The main inpatient and outpatient cost drivers were chemotherapy and concomitant medication, respectively. A more comprehensive nationwide study would be useful to validate our results and to include also indirect costs of cancer care in Greece.

Exploring knowledge and perceptions on generic drugs of final year pharmacy school students in Greece.

Objectives: The economic crisis in Greece has triggered an extensive public debate about the use of generic drugs (generics). Despite their cost-saving potential, generic market penetration remains very low. This raises questions on awareness of, perception on and preference for generics by health-care professionals and patients. This is a descriptive study on the level of knowledge and attitudes towards generics of final year pharmacy school students in Greece. Methods: An electronic questionnaire was distributed to 173 senior pharmacy school students in three Universities in Greece. Responses were submitted electronically. Results: The majority of students knew that generics contain the same active ingredient as the originator products and are cheaper. Students were somehow concerned with safety and efficacy of generics. The majority of students agreed that pharmacists should probably recommend the use of generics, and indicated that prescribing and dispensing practices would largely depend on the profit margin. Despite more than half of the students expressing a positive attitude towards generics, they were inadequately educated on their features. Conclusion: It is critical to improve knowledge of and preference for generics amongst health-care professionals from early on if to build the trust required to increase generic market penetration and achieve measurable savings in pharmaceutical expenditure.

CURRENT ENVIRONMENT FOR INTRODUCING HEALTH TECHNOLOGY ASSESSMENT IN GREECE.

OBJECTIVES: The aim of this study was to describe the current regulatory environment in Greece to evaluate the potential introduction of health technology assessment (HTA) for medicinal products for human use. METHODS: Data sources consist of national legislation on pricing and reimbursement of health technologies to identify the potential need of establishing HTA and its relevant structure. RESULTS: The pricing procedure regarding medicinal products for human use is based on an external reference pricing mechanism which considers the average of the three lowest Euorpean Union prices. Currently, a formal HTA procedure has not been applied in Greece, and the only prerequisite used for the reimbursement of medicinal products for human use is their inclusion in the Positive Reimbursement List. To restrict pharmaceutical expenditure, a variety of measures-such as clawback mechanisms, rebates, monthly budget caps per physician, generics penetration targeting-have been imposed, aiming mainly to regulate the price level rather than control the introduction of medicinal products for human use in the Greek pharmaceutical market. CONCLUSIONS: Greece has the opportunity to rapidly build capacity, implement, and take advantage of the application of HTA mechanisms by clearly defining the goals, scope, systems, context, stakeholders, and methods that will be involved in the local HTA processes, taking into account the country's established e-prescription system and the recently adapted legislative framework.

Biologic treatment for rheumatic disease: real-world big data analysis from the Greek country-wide prescription database.

OBJECTIVES: To directly assess the prevalence of inflammatory rheumatic disease under treatment with biologic disease modifying anti-rheumatic drugs (b-DMARDs) and compare treatment patterns between rheumatoid arthritis (RA) and spondyloarthropathy (SpA), including psoriatic arthritis. METHODS: The obligatory country-wide prescription electronic database covering 10.223.000 Greek citizens (95.1% of the population, 99.5% Caucasian), all of whom with fully reinbursed access to b-DMARDs, was used to retrospectively capture all patients under b-DMARDs for RA/SpA between June 2014-May 2015. Age, gender and medications for RA/SpA and co-morbid classical cardiovascular risk factors (hypertension, dyslipidaemia, diabetes) were retrieved and analysed. RESULTS: A total of 9.824 RA (61.2±14.0 years, 79% women) and 9.279 SpA patients (51.4±13.1 years, 41% women) using pharmacy-dispensed prescriptions for b-DMARDs were identified (overall prevalence 0.19%). Tumour necrosis factor inhibitors were used in 73% and 99% of RA and SpA patients, respectively. B-DMARD monotherapy (RA: 18.71%, SpA: 52.11%), b-DMARD switching during 12 months (RA: 7.73%, SpA: 6.26%), and use of methotrexate (RA: 50.25%, SpA: 27.35%) and corticosteroids (RA: 55.8%, SpA: 23.63%) differed between the two patient subgroups. In both subgroups, women received more often than men methotrexate, leflunomide, hydroxychloroquine and corticosteroids, and less often b-DMARD monotherapy. After adjustments for age, gender and concomitant drugs, the probability for anti-hypertensive and lipid-lowering drug prescription was higher in SpA than RA [OR=1.41 (95%CI: 1.29-1.54) and 1.24 (1.14-1.36), respectively, p<0.001], whereas for anti-diabetics it was similar. CONCLUSIONS: In the first country-wide study that examines the characteristics of rheumatic disease patients under b-DMARD we show that their exact prevalence is 0.19%, with RA patients being older by 10 years, only slightly more numerous, and less likely to receive treatment for hypertension and dyslipidaemia than their demographically matched SpA counterparts. Longitudinal studies should assess the implications of these novel findings on the differential financial burden of rheumatic diseases, as well as on cardiovascular morbidity and mortality of these patients.

The prevalence and treatment patterns of diabetes in the Greek population based on real-world data from the nation-wide prescription database.

AIMS: Epidemiological data regarding diabetes in Greece are based on regional, small-scale studies. We aimed to identify all citizens with prescribed pharmacological treatment for diabetes, to further explore type 1 diabetes prevalence and describe pharmacological treatment patterns in type 2 diabetes. METHODS: The electronic prescription database of the National Organization for Health Care Services Provision was used to identify individuals who received at least two prescriptions with an ICD-10 code relevant to diabetes, dispensed between June 1st, 2014 and May 31st, 2015. Type-1 diabetes was defined in those receiving at least two fully-reimbursable insulin prescriptions with an ICD-10 code of E10 (insulin-dependent diabetes). RESULTS: The study population consisted of 10,222,779 individuals, accounting for 95% of the Greek population. Prevalence of medication-prescribed diabetes was 7.0% (720,764 individuals), ranging from 0.08% in children and adolescents, to 8.2% in adults, and 30.3% in those ⩾75years old. Prevalence of type 1 diabetes was 0.24%, with a clear male predominance and more than half of cases developing after 14years of age. Metformin was the most frequently prescribed medication (77.4%) in type-2 diabetes followed by DPP-4 inhibitors (44.8%) and sulphonylureas (34.5%), while insulin was used by 19.4% of patients. CONCLUSIONS: This nation-wide real-world data analysis on medication-prescribed diabetes demonstrates that the current prevalence in Greece is 7.0%, with wide age variation and high figures in older adults. Identification of pharmacological patterns among patients with type 2 diabetes is a valuable guide in policy-makers' efforts to balance a cost-effective, quality-acceptable disease management.

Greek National E-Prescribing System: Preliminary Results of a Tool for Rationalizing Pharmaceutical Use and Cost.

BACKGROUND: In Greece, due to the ongoing economic crisis a number of measures aiming at rationalising expenditure implemented. A new e-prescribing system, under a unified healthcare fund was the main pillar of these reforms focus on monitoring and auditing prescribing patterns. OBJECTIVE: Main objective of this study was to document the Greek experience with the new national e-prescribing system. METHODS: We analyse the dispensed prescriptions over the period 2013-2014, stratified into four levels: therapeutic subgroup, patent status, physician's specialty and geographical region. RESULTS: Data analysis offered a comprehensive insight into pharmaceutical expenditure over the timeframe and revealed discrepancies regarding composition of spending, brand-generic substitution within certain therapeutic subgroups, physicians' prescribing behaviour based on medical specialty, therapeutic subgroup as well as regional per capita measures. CONCLUSIONS: E-prescribing system is a valuable tool providing sound information to health policymakers in order to monitor and rationalize pharmaceutical expenditure, in value and volume terms.

Drug Utilization Patterns and Costs of Erythropoiesis-Stimulating Agents in an Outpatient Setting in Greece.

UNLABELLED: Anemia in the elderly is often related to a higher prevalence of chronic diseases such as chronic kidney failure, arthritis, and malignancy. Erythropoiesis-stimulating agents (ESAs) have been used for years to effectively treat anemia and when used appropriately can substantially improve the health status and quality of life of older adults. Following the 2008 recession in Greece, the government introduced ESA price control restrictions, but no prescribing restrictions, in an effort to reduce drug expenditure. OBJECTIVE: ESA prescribing patterns and treatment costs were analyzed to determine inappropriate or appropriate use of these agents and related health care resources in Greece. METHOD: A retrospective register-based drug utilization study was carried out using data from prescriptions dispensed at the public pharmacy of the largest social insurance fund (IKA-ETAM), for patients receiving ESAs over a six-month period. For each patient, demographic data, ESA dosage regimen, treatment indication and cost, prescriber specialty, and prescription origin were recorded. RESULTS: A total of 14,387 prescriptions from 6,074 patients (median age 74 years) were reviewed. A substantial number of patients (13.5%) were treated for off-label indications, for which the average cost per patient per indication was higher. ESA dosage/frequency of administration varied but was in accordance with recommendations. The percentage of patients who received innovator and biosimilar erythropoietin (EPO) was 88% and 12%, respectively. CONCLUSION: For the optimization of ESA utilization and the reduction of treatment costs, strict ESA prescription monitoring, development of registries, and criteria for off-label indications and biosimilar use in naive patients under the umbrella of risk-sharing agreements should be proposed.

Reducing patient copayment levels for topical and systemic treatments in plaque psoriasis as a case for evidence-based, sustainable pharmaceutical policy change in Greece.

AIM: Psoriasis is a chronic inflammatory skin disease that requires treatment to manage co-morbidities and improve patient quality-of-life. This study estimated the budget impact to National Organization for Health Care Services Provision (EOPYY) of changing reimbursement of psoriasis treatment with topical and systemic, non-biologic, agents (75%) to bring it on par with that of biologic agents (100%) in Greece. METHODS: The Business Intelligence database of EOPYY was used to identify and provide analytics on patients with plaque psoriasis. Permission for use of anonymized data was obtained by the administration of EOPYY. EOPYY is responsible for funding healthcare and pharmaceutical care services for ∼95% of the permanent population in the country. Pre-defined ICD-10 codes were applied to identify patients with plaque psoriasis and at least one reimbursed prescription between 1 June 2014 and 31 May 2015. Age, gender, medications, and cost were recorded for these patients. RESULTS: Of the 45,581 unique patients identified through completely anonymized data on the e-prescription system, 72% were on treatment with topicals only and accounted for 5% of EOPYY psoriasis expenditure. Another 9% of patients were on methotrexate or a per os (POS, orally administered) systemic agent and accounted for 2.35% of total expenditure. Approximately 12% of total patients were on treatment with a biologic-containing regimen and accounted for almost 90% of psoriasis expenditure. Patients on biologics were younger than patients on topical and systemic treatments. The burden to EOPYY of adjusting reimbursement levels for topical and systemic, non-biologic, treatments to 100% of their cost was estimated at €2.05 per patient per month for topical treatments (monotherapy) and an additional €9.5 per patient per month for treatment with methotrexate, POS systemic agents, and their combinations with topical agents. This additional cost is expected to be offset by averting 200 earlier than clinically necessary switches from topical and systemic, non-biologic, treatments to expensive biologics a year. CONCLUSION: In circumstances of severe funding constraints for social health insurance in Greece, bringing patient copayment levels for psoriasis treatment on par with each other may aid proper clinical management of the condition, whilst achieving adequate treatment outcomes at optimal cost.

Using Big Data to Assess Prescribing Patterns in Greece: The Case of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is one of the top leading causes of death and disability, and its management is focused on reducing risk factors, relieving symptoms, and preventing exacerbations. The study aim was to describe COPD prescribing patterns in Greece by using existing health administrative data for outpatients. METHODS: This is a retrospective cross-sectional study based on prescriptions collected by the largest social insurance fund, during the first and last trimester of 2012. Selection criteria were the prescription of specific active substances and a COPD diagnosis. Extracted information included active substance, strength, pharmaceutical form and number of packages prescribed, diagnosis, time of dispensing, as well as insurees' age, gender, percentage of co-payment and social security unique number. Statistical analysis included descriptive statistics and logistic regression. RESULTS: 174,357 patients received medicines for COPD during the study period. Patients were almost equally distributed between male and female, and age above 55 years was strongly correlated with COPD. Most patients received a long-acting beta agonist plus inhaled corticosteroid combination (LABA +ICS), followed by long-acting muscarinic agonist (LAMA). 63% patients belonging in the 35-54 age received LABA+ICS. LAMA was prescribed more frequently among males and was strongly correlated with COPD. CONCLUSION: The study provides big data analysis of Greek COPD prescribing patterns. It highlights the need for appropriate COPD classification in primary care illustrating the role of electronic prescribing in ensuring appropriate prescribing. Moreover, it indicates possible gender differences in treatment response or disease severity, and the impact of statutory co-payments on prescribing.

Monitoring of subcutaneous dalteparin in patients with renal insufficiency under intensive care: an observational study.

OBJECTIVE: The objective of this study was to investigate the pharmacodynamic parameters of dalteparin in patients with renal insufficiency under intensive care. MATERIALS AND METHODS: In this open, nonrandomized, nonblinded, prospective, single-dose observational study, 10 critically ill patients with renal insufficiency (mean creatinine clearance = 29.5 +/- 6.42 mL/min) were administered a single 5000-IU subcutaneous dose of dalteparin. RESULTS: Dalteparin blood levels were estimated indirectly over a 12-hour period by measuring anti-Xa activity and by performing a clotting assay known as the ATHU (AHEPA Thrombosis and Hemostasis Unit) test. Maximum anti-Xa activity (ie, 0.42 +/- 0.13 IU/mL) was achieved 4 hours after administration (in 8 of 10 patients). Adequate anticoagulant activity was maintained throughout the 12-hour dosage interval in all study patients. However, at time 0 hour of the study, 36 hours after the administration of a previous dose of dalteparin, considerable anti-Xa activity (ie, 0.39 +/- 0.11 IU/mL) was measured in 6 patients. A good correlation was found between anti-Xa activity and the results of the ATHU test. CONCLUSIONS: The presence of medium/severe edema and the concurrent administration of 1 to 3 inotropic drugs appear to contribute to a decrease in the rate of elimination of dalteparin, resulting in a greater-than-expected (as a result of decreased renal function) prolongation of its pharmacologic activity. We recommend that care be taken with repeated dosing of dalteparin in intensive care unit patients taking inotropic drugs until observed results can be confirmed.