Research activities within PROTECT. Luisa Ibáñez

Transcription

1 Research activities within PROTECT Luisa Ibáñez

2 PROTECT Work Package 2 Working Group 3

3 PROTECT: Pharmacoepidemiological Research on Outcome of Therapeutics by a European ConsorTium

4 PROTECT Project organization

5 Introduction of participants WP2 Co-leaders: Olaf Klungel...UU WG3 Robert Reynolds...Pfizer Participating institutions: European Medicines Agency(EMA), Danish Medicines Agency (DKMA), AEMPS (Spanish Medicines Agency), Utrecht University (UU), Ludwig Maximillian University-Munich (LMU-München), FICF, GP Research Database (GPRD),Glaxo-Smithkline (GSK), Novartis, Amgen, PGRx-Laser, Pfizer, CEIFE (Centro Español de Investigación Farmacoepidemiológica) Coordinators: Luisa Ibáñez...FICF Hans Petri...Roche Marieke Shoonen...Amgen Joan-Ramon Laporte...FICF Mònica Sabaté...FICF Elena Ballarin...FICF Pili Ferrer...FICF Joerg Hasford...LMU-München Joan Fortuny...Novartis

6 Objectives WP2 To develop, test and disseminate methodological standards for the design, conduct and analysis of PE studies, applicable to different safety issues using different data Objectives WG3 1. Build and update an invetory on drug consumption data sources: 1. National drug consumption databases 2. IMS Health 2. Evaluate validity of consumption data. 3. Estimate exposed population for each of the 5 selected key drug-adverse effect. 4. Perform a systematic review with/without meta-analyses on the selected key drug-adverse effects. It will serve to calculate the Population Attributable Risk and to identify discrepancies in results from clinical databases (WG1) and published studies. DRUG-ADVERSE EFFECTS OF INTEREST: Calcium-channel blockers-malignancies Antidepressants and Benzodiazepines-Hip fracture Antiepileptics-Suicide Antibiotics-Drug-induced liver injury Beta-2-adrenergics-Acute myocardial infarction

7 RESULTS

8 Inventory on drug utilization databases in Europe

9 DRUG CONSUMPTION DATABASES IN EUROPE WHAT IS THIS REPORT? This report is the result of reviewing, compiling and updating knowledge about European sources of data on drug utilization in the out- and inpatient health care sector. Information is available on Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Spain, Sweden and United Kingdom. It is a work in progress: further European countries will be included and the information is regularly updated. GOALS OF THE DOCUMENT It describes the characteristics of non-commercial drug consumption data providers in Europe, with special emphasis on pricing and reimbursement agencies. It reports the features of each country health policy systems and lists several pharmaceutical data sources. It includes a brief summary of data provided by Intercontinental Marketing Services (IMS Health). It provides an updated list of national drug consumption databases in selected European countries, describing their main characteristics and accessibility. It outlines the validity of these European national drug consumption databases. It explores the availability of inpatient drug consumption data at national level. WHO MAY BE INTERESTED IN IT? This inventory is a shared resource for all researchers interested in pharmacoepidemiology and drug utilization research in particular. Having this in mind, we encourage institutions and individuals within and outside the PROTECT project to critically review this report and make recommendations on change. If you have any queries, please contact Dr Luisa Ibáñez (li@icf.uab.cat) or Dr Hans Petri (hans.petri@roche.com)

10 NON-COMMERCIAL DRUG CONSUMPTION DATABASES: DATA AVAILABLE AT FICF Country Data received Organization Type of data ATC/DDD methodology Denmark (Danish National Prescription Registry) Online The Danish Medicines Agency Outpatient (dispensed) Inpatient (sales) Yes DDD/1000inh/day Validity assessment Data Graphical description Yes Questionnaire received Yes France CNAMTS (ERASME) No (Declined collaboration) National Insurance Company AFSSAPS Yes AFSSAPS In- and Outpatient (sales) Outpatient (reimbursed) Yes --- No Yes DDD/1000inh/day DDD/100 admissions Yes Yes Germany (AOK database) No (waiting for the agreement WIDO- LMU_FICF) The Research Institute of the AOK Outpatient (reimbursed) Yes No No Italy (OsMed database) Incomplete,waiting for ATC 5 level The Italian Drug Agency Out-and inpatient (reimbursed+ims Health) Yes No Yes Norway (Norwegian Prescription database (NorPD) Poland (National Health Fund database) Online Norwegian Institute of Public Health Outpatient (prescribed and dispensed) Yes Yes Yes No National Health Fund Outpatient (reimbursed) Yes No No Sweden (The Swedish Prescribed Drug Register) Online National Board of Health and Welfare Outpatient (prescribed and dispensed) Yes Yes Yes Spain Yes Spanish drug and health products agency Outpatient (reimbursed) Yes Yes No The Netherlands GIP Online Healthcare Insurance Board Outpatient (reimbursed) Yes Yes Yes SFK No Foundation for Pharmaceutical Statistics Outpatient (dispensed) Yes No Yes United Kingdom (England and Wales) epact Yes NHS Prescription Services Outpatient (reimbursed) BNF/ADQ (ATC/DDD upon request) Yes No Data on Finland not requested

11 NON-COMMERCIAL DRUG CONSUMPTION DATABASES: DATA SOURCES 1 Dispensed medicines: licensed medicines supplied to a patient by a pharmacist or a doctor dispensing practice. These medicines might be prescribed or not; it includes OTC. 2 Prescribed medicines: licensed medicines that require a prescription by a health care professional and dispensed under the supervision of a pharmacist. 3 Reimbursed medicines: licensed medicines prescribed by a healthcare professional, dispensed under the supervision of a pharmacists and subsidized by the government.

12 DRUG CONSUMPTION DATABASES VALIDITY Premise: Checklist for evaluating validity of data (Vander Stichele et al. Br J Clin Pharmacol 2004;58(4): Variables related to measurement of drug exposure: Population coverage and definition of setting: in- and outpatient Drug-based information Patient information Prescriber information 13 questionnaires sent, 2 reminders sent, 8 responses received (61.5%) from Catalonia (VinCAT), Denmark, France (AFSSAPS), Italy, Norway, Sweden, The Netherlands (SFK and GIP).

13 DRUG CONSUMPTION DATABASES VALIDITY: questionnaire items POPULATION COVERAGE nationwide database/sample? SETTING DEFINITION what is classified as in- or outpatient drug use: medicines consumed in nursing homes and other long-term care institutions; prescriptions of specialists to outpatients, hospital drugs dispensed to outpatients? DRUG-BASED INFORMATION Type of drug records: sales, dispensed, prescribed or reimbursed. OTC Manually or electronically prescriptions (% of prescriptions not dispensed) Date of prescription, date of dispensation Quantity of drug dispensed Prescribed dose recorded Package description: package size, strength, form of dosage Duration of prescription or days of supply Indication for use Completeness of registration (% of prescriptions with a missing field) ATC/DDD methodology PATIENT-RELATED INFORMATION Variables recorded: age, gender, ethnicity, place of residence, education, income, social class. Linkage to other databases VALIDITY OF THE DATABASE How and how often the internal validity of the database is checked? ACCESSIBILITY

14 Conclusions TASKS TIME PERIOD RESPONSIBLE INVENTORY PUBLICATIONS Research WG on DU across Europe November 2011 FICF National DU data sources January 2011 FICF Hospital drug consumption review February 2011 FICF Antibiotic consumption in Europe: Analyses from data provided by IMS Health IDENTIFICATION OF DISCREPANCIES IN STUDY RESULTS. PUBLICATIONS November 2011 Patterns of use and exposed population antibiotics-acute liver injury October 2013 Amgen Public health impact of antibiotics on acute liver injury December 2013 Amgen Patterns of use and exposed population antiepileptics- suicidal attemp/suicide October 2013 FICF Public health impact of antiepileptics onsuicidal attemp/suicide December 2013 FICF Patterns of use and exposed population benzodiazepines and antidepressantship fracture October 2013 FICF and Novartis Roche Public health impact of benzodiazepines and antidepressants on hip fracture December 2013 Roche Patterns of use and exposed population B2-agonists-acute myocardial infarction October 2013 LMU-Munchen Public health impact of B2-agonists on acute myocardial infarction December 2013 LMU-Munchen Patterns of use and exposed population calcium channel blockers-malignancies October 2013 Novartis Public health impact of calcium channel blockers on malignancies December 2013 Novartis

15 ICPE Poster 2010

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17 ICPE Poster 2011

18 Objectives: FINDING NATIONAL DATABASES ON DRUG UTILIZATION INFORMATION ACROSS EUOPE M Sabaté, E Ballarín, P Ferrer, H Petri, J Fortuny, K L Goh, J Hasford, JR Laporte, S Yeboa and L Ibáñez To build up and update an inventory of European national drug consumption databases (DCDB). To facilitate their access to estimate the public health impact of adverse drug events. Those are part of the aims of the Work Package 2 of the PROTECT project (IMI/115004). Methods: Design: Descriptive study. Setting: 11 European countries selected taking into account their population (<30x10 6 ), participation in the PROTECT project, or data availability. Intervention: Electronic search on a)medline: Drug Utilization studies; b)european Union and Europe Medicines Agency websites; c)health care systems and national competent authorities regulating access, Pricing and reimbursement of drugs. And, interviews of experts. Main outcome: Description of the main characteristics of the national DCDB. Results: Table 1. Main characteristics of the selected European national drug consumption databases Table 2. Source of drug data in the selected national DCDB 1 Dispensed medicines: licensed medicines supplied to a patient by a pharmacist or a doctor dispensing practice. These medicines might be prescribed or not; it includes OTC. 2 Prescribed medicines: licensed medicines that require a prescription by a health care professional and dispensed under the supervision of a pharmacist. 3 Reimbursed medicines: licensed medicines prescribed by a healthcare professional, dispensed under the supervision of a pharmacists and subsidized by the government. PROTECT (Pharmacoepidemiological Research on Outcomes and Therapeutics by a European Consortium), IMI-JU (Innovative Medicines Initiative - Joint Undertaking) Conclusions: The major national DCDB in 11 European countries have been identified. Key features of such databases are presented in a structured and easy-to-read manner. Most of the databases collect outpatient drug consumption. There is a lack of information on dosage and indication for use. OTC use is only available in 3 national databases. This inventory is a practical starter point for researchers interested in drug utilization studies in Europe. A more comprehensive inventory on DCDB would be a highly valuable asset in the timely estimation of the public health impact of the use of medicines in the community, in terms both of benefits and adverse outcomes. Acknowledgements and statements:the research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/ ) for the Innovative Medicine Initiative ( under Grant Agreement n The research leading to these results was conducted as part of the PROTECT consortium (Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium, which is a public-private partnership coordinated by the European Medicines Agency.

19 ICPE Poster 2011 Potential population impact of antidepressant use on hip fractures rate in Denmark, Norway and The Netherlands Goldenberg et al. ICPE Abstract 2011 Potential population impact of benzodiazepine use on hip fractures rate in Denmark, Norway and The Netherlands Khuong et al.

20 Figure 1. Forest plot of relative risks for hip fractures and use of benzodiazepines versus non-use Squares represent the relative risk in each study, their sizes are proportional to their weights. Horizontal lines represent the 95% confidence intervals. The black diamond in the bottom represents the pooled relative risk (calculated with a random-effects model). Studies are ordered according to their weights. Kuong TP et al. Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States. (sent for publication August 2011)

21 Table 1. Benzodiazepine use (DDD/1,000 persons/day) in five European countries and the US, calculated using IMS MIDAS drug sales data (2009) Country Any benzodiazepine SAB LAB France Germany Italy Spain UK US DDD: WHO s Defined Daily Dose; SAB: short-acting benzodiazepines; LAB: long-acting benzodiazepines Table 2. Estimated population attributable risk (%) and its 95% confidence interval for hip fractures associated with benzodiazepine use in five European countries and the US Country Any benzodiazepine* SAB* LAB* France 7.4 (4.5 10) 3.7 ( ) 1.0 ( ) Germany 1.8 ( ) 0.8 ( ) 0.3 ( ) Italy 5.2 ( ) 2.5 ( ) 0.8 ( ) Spain 8.2 (5.1 12) 3.9 ( ) 1.5 ( ) UK 2.0 ( ) 0.7 ( ) 0.6 ( ) US 8.0 (4.9 11) 4.3 ( ) 0.6 ( ) Pe RR PAR% 1 Pe 1 RR 1 * 100

22 Antiepileptic ME Santander-Paredes 1,2, C Rafaniello 3, M Sabaté-Gallego 1,2,4, P Ferrer 1, E Ballarin 1,2,4, A Coma 5, C Zara 5, L Ibánez 1,2,4 1 Foundations Catalan Institute of Pharmacology, Barcelona, Spain. 2 University Hospital Vall D Hebron, Barcelona, Spain. 3 Second University of Naples Pharmacology Department 'L Donatelli', Naples, Italy. 4 University Autònoma of Barcelona, Barcelona, Spain. 5 Catalan Health Department. Esteve Terrades, Barcelona, Spain.

23 Main indication for use in epilepsy Other indications for use New antiepileptic drugs in the last decades There is no information on comparison of antiepileptic drug consumption between these 3 countries To describe antiepileptic drug consumption in the general population across the 3 European countries.

24 Data sources: Register of Medicinal Product Statistics. Danish Medicines Agency. Norwegian Prescription Database(NorPD). Norwegian Institute of Public Health. DATAMART database. Catalan Health Service Unit of measurement: Defined Daily Doses/1000 inhabitants/day (DID), by age and gender.

25 Total Antiepileptic Drug Consumption DID Var% 2008/2007 Var% 2009/2008 Var% 2009/ ,03 13,03 13,67 8% 5% 14% 12,04 12,82 13,40 7% 4% 11% 11,20 12,63 13,14 13% 4% 17%

26 DID Antiepileptic drug (AED) consumption in Catalonia by age and gender: Women Men

27 DID 30 AED consumption in Denmark by age and gender: Women Men

28 DID AED consumption in Norway by age and gender: Women Men

29 DDD/1000 inh/day NO3AX by gender and age (Catalonia 2009) Other antiepileptic drugs (N03AX): use by gender and age Catalonia 2009 Lamotrigine Topiramate Gabapentin Levetiracetam Zonisamide Pregabalin Lacosamide Women Women

30 DDD/1000 inh/day NO3AX by gender and age (Norway 2009) Other antiepileptic drugs (N03AX): use by gender and age Norway 2009 Lamotrigine Topiramate Gabapentin Levetiracetam Zonisamide Pregabalin Lacosamide Women Men

31 DDD/1000 inh/day NO3AX by gender and age (Denmark 2009) Other antiepileptic drugs (N03AX): use by gender and age Denmark 2009 Lamotrigine Topiramate Gabapentin Levetiracetam Zonisamide Pregabalin Lacosamide Women Men

32 First European comparison of antiepileptic drug consumption. Total antiepileptic drug consumption increases over the 3-year period across the 3 countries. N03AX is the most consumed antiepileptic drug group. Lamotrigine and pregabalin were the most used drugs in Denmark and Norway, whereas in Catalonia were Pregabalin and Gabapentin (year 2009).

33 In middle-aged adults Lamotrigine was the most consumed AED in Norway and Denmark. In Catalonia Topiramate was the most used AED (year 2009) by middle-aged adults. In older people, Gabapentin and Pregabalin are the most used AED in Catalonia and Norway. Gabapentin and Lamotrigine in Denmark. Lack of information on indication for use in these databases and the use of DDD as a unit of measurement hampers the interpretation of the results. (Funding: EU (FP7-IMI) Grant Agreement nº PROTECT consortium)