WEUKBRE5557: IMI PROTECT(Work Package 2): Antiepileptics & Suicide

NCT01607333 | Completed

• 2 other identifiers: 115737WEUKBRE5557
• Study Type: observational
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Epilepsy

Keywords

Antiepileptics; suicidality

Outcome Measures

Primary Outcomes (1)

• Suicide attempt including completed suicide identified in GPRD from Read codes and cause of death; and ICD-9 codes and cause of death from Death Registry in Danish database

  Up to 13 and a half years following drug exposure

Secondary Outcomes (2)

• Completed suicide only identified in GPRD from Read codes and cause of death; and ICD-9 codes and cause of death from Death Registry in Danish database only

  Up to 13 and a half years following drug exposure

• Completed suicide, suicide attempt, and including preparatory acts toward imminent suicidal behavior, suicidal ideation plus indeterminate or potentially suicidal events (wide definition) in GPRD only

  Up to 13 and a half years following drug exposure

Study Arms (3)

Completed suicide

Patients who completed suicide

Drug: Lamotrigine use

Suicide attempt

Patients who have attempted suicide, or performed preparatory acts toward imminent suicidal behavior, suicidal ideation plus indeterminate or potentially suicidal events

Drug: Lamotrigine use

Not completed suicide

Patients who have not completed suicide

Drug: Lamotrigine use

Interventions

Lamotrigine use DRUG

Lamotrigine prescription during the study period

Completed suicide; Not completed suicide; Suicide attempt

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

For the descriptive studies that compare six European databases: All patients with at least one prescription of an AED between January 1, 2000 and December 31, 2009 from the following databases: National Databases (Denmark), General Practice Research Database \[GPRD\] (UK), Health Improvement Network \[THIN\] (UK), the Mondriaan database (Netherlands), BIFAP \[Base de Datos para la Investigación Farmacoepidemiologica en Atencion Primaria\] (Spain), and the Bavarian health-insurance database (Germany). Additional descriptive and analytic studies comparing the study populations from GPRD and Danish data sources: study cohorts consisting of patients who have received a first prescription to at least one AED on July 1, 1996 or later to December 31, 2009.

You may qualify if:

• patients with at least one prescription to an AED between January 1, 2000 and December 31, 2009
• patients who fulfill the quality criteria of the respective database
• patients who have received a first prescription to at least one AED at July 1, 1996 or later in the UK or Denmark
• patients who are an age of 15 years and older at the index date
• patients who have a registration history of at least 6 months prior to the index date (first date of AED prescription)
• patients who have fulfilled research data criteria in GPRD

You may not qualify if:

• patients without a prescription to an AED between January 1, 2000 and December 31, 2009
• patients who do not fulfill the quality criteria of the respective database
• patients without a first prescription to at least one AED at July 1, 1996 or later in the UK or Denmark
• patients younger than age of 15 years at the index date
• patients who do not have a registration history of at least 6 months prior to the index date (first date of AED prescription)
• patients who have not fulfilled research data criteria in GPRD
• patients with records of coded suicidality (wide definition, including suicidal ideation) in the six months prior to the index date

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Epilepsy; Suicidal Ideation

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 30, 2012
• Study Start: December 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: March 27, 2015

Record last verified: 2015-03