Study Protocol for Drug Utilization Study WP4 – Primary Care Antibiotic ARPEC Prescribing for Common Childhood Security: CO A 2009-11-01 Infections Author(s): Sandra de Bie, Katia Verhamme, Version: 1 1/32 Miriam Sturkenboom (all EMC) ARPEC Antibiotic Resistance and Prescribing in European Children ARPEC Project A 2009-11-01 Protocol for Drug Utilization Study WP4 – Primary Care Anti-infective agent prescribing for Common Childhood Infections Version 1 © Copyright 2011 ARPEC Study Protocol for Drug Utilization Study WP4 – Primary Care Antibiotic ARPEC Prescribing for Common Childhood Security: CO A 2009-11-01 Infections Author(s): Sandra de Bie, Katia Verhamme, Version: 1 2/32 Miriam Sturkenboom (all EMC) Contents DOCUMENT INFORMATION .................................................................................................. 3 DOCUMENT HISTORY ............................................................................................................. 3 DEFINITIONS .............................................................................................................................. 4 ABBREVIATIONS ....................................................................................................................... 5 DISEASE CLASSIFICATION SYSTEMS USED BY THE DATABASES ............................ 6 INTRODUCTION......................................................................................................................... 7 1. BACKGROUND ...................................................................................................................... 7 2. STUDY OBJECTIVE ............................................................................................................... 7 3. STUDY DESIGN .................................................................................................................. 10 4. SOURCE DATA .................................................................................................................... 10 5. STUDY PERIOD ................................................................................................................... 12 6. STUDY POPULATION ........................................................................................................... 12 7. FOLLOW-UP PERIOD ........................................................................................................... 12 8. DATA COLLECTION ............................................................................................................ 13 OUTCOME MEASURES .......................................................................................................... 14 POPULATION LEVEL ................................................................................................................... 14 PERSON LEVEL USE ANALYSES ................................................................................................... 15 DISEASE LEVEL .......................................................................................................................... 16 PRESCRIPTION LEVEL ANALYSES ................................................................................................ 17 ANALYSES OF ANTIBIOTIC USE ........................................................................................ 19 TIMELINES ................................................................................................................................ 20 APPENDIX 1: STUDY DRUGS ................................................................................................ 21 © Copyright 2011 ARPEC Document Information Grant Agreement A 2009-11-01 Acronym ARPEC Number Full title Antibiotic Resistance and Prescribing in European Children Project URL http://www.arpecstudy.eu EU Project officer Deliverable Work package WP4 Delivery date Contractual n/a Actual n/a Status Draft final Nature Report Prototype Other Dissemination Public Confidential Level Authors Sandra de Bie, Katia Verhamme, Miriam Sturkenboom (Partner) Responsible Miriam Sturkenboom Email [email protected] Author Partner EMC Phone +31-10-7044123 Document History Name Date Version Description Miriam Sturkenboom, Katia 13-10- 1 Verhamme and Sandra de Bie 2011 3 Definitions . Associated partners of the ARPEC are referred to herein according to the following codes: SGUL St George‟s University of London United Kingdom ESPID European Society of Pediatric Infectious Diseases ASIC PENTA Paediatric European Network for Treatment of AIDS PEDIANET Paedianet database Italy FIHBHGM EMC Erasmus University Medical Center Netherlands SERMAS Servicio Madrileño de Salud Spain UT NKUA National and Kapodistrian University of Athens Greece CVBF Consorzio per le Valutazioni Biologiche e Farmacologiche Italy UKL-FR UMCL UA University of Antwerp Belgium UMIL Universita Degli Studi Di Milano Italy VUCH Vilnius University Children Hospital Lithuania . Grant Agreement: . Project: . Work plan: . Consortium: . Consortium agreement: . Foreground: . Background: 4 Abbreviations The following abbreviations are used in this report: . ATC – anatomical therapeutic chemical classification system . DDD – defined daily dose . GP – general practitioner . ICD-9-CM – international classification of disease, 9th rev., clinical modification . ICD-10-GM – international classification of disease, 10th rev., German modification . ICPC – international classification of primary care . IPCI – Integrated Primary Care Information Project . THIN - The Health Improvement Network . Rx - prescription . WP – work package 5 Disease classification systems used by the databases IPCI – ICPC BIFAP– ICPC PEDIANET database – ICD-9-CM THIN database – READ codes 6 INTRODUCTION 1. Background The study Antibiotic Resistance and Prescribing in European children (ARPEC) is an initiative by the European Society of Pediatric Infectious Diseases (ESPID) to improve the evidence base for antibiotic prescribing in European Children. The overall aim of the project is to improve antimicrobial prescribing in hospitals and in the community, by obtaining up-to-date, clinically relevant data on variation in clinical management and antimicrobial resistance rates and then to feed this back via a number of educational initiatives, to paediatricians in-training and in clinical practice, across Europe. For this study, we will build on existing paediatric infectious diseases networks, including PENTA, ESPID and TEDDY. The project uses established methodologies from ESAC and EARSS and existing community prescribing databases to develop a prospective surveillance system to monitor rates of antibiotic prescribing and resistance in European children The project has been funded by the Executive Agency for Health and Consumers (EAHC) through DG SANCO. The current document describes the design of the drug utilization study within the context of the WP4 – Primary Care Antibiotic Prescribing for Common Childhood Infections of the ARPEC project; leader Erasmus University Medical Center (EMC). The purpose of this drug utilization study is fourfold. First, patterns of anti-infective drug use will be analyzed, in terms of prevalence, incidence, volume and dose of use on a population level. Secondly, the volume and duration of use on a person level will be analyzed. Thirdly, the volume of use for the most common childhood infections will be analyzed. Fourth, and last, the data will be analyzed on a prescription level. A common data protocol will be produced to prepare standardized input files to study prescription patterns in Italy (IT), The Netherlands (NL), Spain (ES) and the United Kingdom (UK), making use of the Pedianet database (IT), the Integrated Primary Care Information (IPCI) database (NL), the Health Improvement Network (THIN) (UK) and the BIFAP database (ES) respectively. All include the complete automated records of primary care doctors, with information on patient demographics, prescription data (including indication of use) and diagnosis. Using these databases, person time of follow up for each child can be calculated and stratified by calendar year and age group. All anti-infective agents prescribed in children during the follow up will be retrieved from prescription data and grouped on the basis of the WHO ATC System. Age and country specific prevalence rates for individual anti-infective agents will be calculated and linked to the indications of use. 2. Study Objective The aim of this drug utilization study is to describe anti-infective drug utilization on four levels Population level 7 a) Prevalence of use during the study period by country, age groups, gender, type of anti- infective (class and ATC7-level), and calendar time (year or month or week) (see appendix for which drugs are considered study drugs) Several age group classifications will be considered: o Based on the ICH categories . 0 - < 2 years . 2 - ≤ 11 years . 12 - < 18 years o Based on the „Blue book‟ . 0 - < 1 years . 1- < 5 years . 5 - < 12 years . 12 - < 18 years o One year categories . 0 - < 1 years . 1 - < 2 years . etc. Monthly prevalence is defined as the number of users per 1,000 person-months. Yearly prevalence is defined as the number of users per 1,000 person-years. A user is defined as a child with at least one prescription of the drug of interest in the period of interest (month or year) b) Total volume of use (prescriptions per month, person time of exposure) by country, age group, gender, type of antibiotic (class and ATC7-level), and calendar time. DU90% methodology stratified by country: how many