The studies described in this protocol are all performed within the framework of PROTECT
(Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium)
Workpackage 2 (WP2) and Workgroup 1. The primary aim of these studies is to develop, test and
disseminate methodological standards for the design, conduct and analysis of
Pharmacoepidemiological (PE) studies applicable to different safety issues and using
different data sources. To achieve this, results from PE studies on 5 key adverse events
(AEs) performed in different databases will be evaluated. Therefore, emphasis will be on the
methodological aspects of the studies in this protocol and not on the clinical consequences
of the association under investigation. The standards to develop will contribute to
decreasing the discrepancies in results from different studies in the future and increase the
usefulness and reliability of these studies for benefit-risk assessment in the EU.
We propose to assess the association between antibiotics use and idiopathic acute liver
injury with different study designs (descriptive, cohort, nested case-control and case
crossover) across different primary care databases and to compare the results between
databases, across designs to evaluate the impact of design/database/population differences on
the outcome of the studied association.
Specific aims (in each database):
1. To describe characteristics, clinical features, and risk factors for acute liver injury
in patients exposed and unexposed to antibiotics.
2. To estimate the overall risk of acute liver injury associated with antibiotics exposure
(users and non-users) in each database
3. To estimate the risk of acute liver injury associated with various antibiotics classes
4. To estimate the risk of acute liver injury associated with specific individual
5. To assess the effect of dose and duration of use for specific individual antibiotics.
6. To compare the results of a case-control study with the results of a retrospective
cohort study and self-controlled case series study in the different databases
The proposed studies will be collected in populations from the following databases: The
General Practice Research Database [GPRD] (UK), Health Improvement Network [THIN] (UK), BIFAP
[Base de datos Informatizada para estudios Farmacoepidemiologicos en Atencion Primaria]
(Spain)- the Bavarian Claims Database (Germany), Mondriaan (Netherlands), and the National
Databases of Denmark.