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 and Workgroup 1. 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 five 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.
In the present project, investigators use Columbia Classification Algorithm of suicide
assessment (C-CASA) definitions as a basis to specify the operational definitions of the
different aspects of suicidality. The focus of the main analyses is on attempted suicide
including completed suicide. This is due to statistical power issues. However, investigators
will apply two additional outcome definitions in sensitivity analyses: 1) completed suicide
only and 2) completed suicide, suicide attempt, preparatory acts toward imminent suicidal
behavior, suicidal ideation plus indeterminate or potentially suicidal events. Investigators
will not include terms which clearly indicate an accidental event, or self-injurious behavior
without a suicidal intent. These definitions are listed in the statistical analysis plan
together with lists of terms from the dictionaries used in the different databases.
The objectives of this study are to 1) Compare the study results which are based on two data
sources (he UK General Practice Research Database (GPRD) and Danish registries) and different
designs and evaluate the impact of design and population differences on the outcome of the
study results (the UK database 'The Health Improvement Network' (THIN) may be included in
these analyses as well); 2) Evaluate the strengths and weaknesses of the two data sources to
study a possible association of antiepileptic drug (AED) use and suicidality, in particular
the specific outcomes of death from suicide, hospitalization due to suicide attempt, and
reports of the aspects of suicidality by the patients; 3) Estimate risks of completed
suicide, completed suicide and attempted suicide, and completed suicide, suicide attempt,
preparatory acts toward imminent suicidal behavior, suicidal ideation plus indeterminate or
potentially suicidal events overall for all AEDs and by individual AEDs prescribed in UK and
Denmark; and 4) Describe the patterns of AED prescribing in six European databases (GPRD and
THIN, UK; Danish registries; Mondriaan, Netherlands; Bavaria, Germany; Base de Datos para la
Investigación Farmacoepidemiologica en Atencion Primaria (BIFAP), Spain).