Bridging Differences in Outcomes of Pharmacoepidemiological Studies: Design and First Results of the PROTECT Project

Abstract

Background:Observational pharmacoepidemiological (PE) studies on drug safety have produced discrepant results that may be due to differences in design, conduct and analysis.Purpose:The pharmacoepidemiology work-package (WP2) of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) project aims at developing, testing and disseminating methodological standards for design, conduct and analysis of pharmacoepidemiological studies applicable to different safety issues using different databases across European countries. This article describes the selection of the safety issues and the description of the databases to be systematically studied.Methods:Based on two consensus meetings and a literature search, we selected five drug-adverse event (AE) pairs to be evaluated in different databases. This selection was done according to pre-defined criteria such as regulatory and public health impact, and the potential to investigate a broad range of methodological issues.Results:The selected drug-AE pairs are: 1) inhaled long-acting beta-2 agonists and acute myocardial infarction; 2) antimicrobials and acute liver injury; 3) antidepressants and/or benzodiazepines and hip fracture; 4) anticonvulsants and suicide/suicide attempts; and 5) calcium channel blockers and malignancies. Six European databases, that will be used to evaluate the drug-AE pairs retrospectively, are also described.Conclusion:The selected drug-AE pairs will be evaluated in PE studies using common protocols. Based on consistencies and discrepancies of these studies, a framework for guiding methodological choices will be developed. This will increase the usefulness and reliability of PE studies for benefit-risk assessment and decision-making.

Inpatient Drug Utilization in Europe: Nationwide Data Sources and a Review of Publications on a Selected Group of Medicines (PROTECT Project)

“…All active pharmaceutical ingredients classified at ATC level five of these groups were included. The reason for the selection of these groups of medicines has been described elsewhere [9]. Antimicrobials, which are also included in the PROTECT project, were excluded because the reasons for the study of their consumption in hospital settings are well known [10,,14,15].…”

“…Therefore, the PROTECT project focuses on five pairs of drug-adverse events to explore the feasibility of using different types of DU data sources to provide accurate data for a benefit-risk assessment [9].…”

Electronic Health Data for Postmarket Surveillance: A Vision Not Realized

“…The published project design outlined five drug-adverse event pairs (for example, anticonvulsants and suicidal behaviors) [15]. The WP2 design called for the drug-adverse event pairs to be studied in six different European electronic record databases with common protocols that would evaluate different methods such as cohort, case control, and case crossover designs (similar to OMOP's self-controlled methods).…”

A methodological comparison of two European primary care databases and replication in a US claims database: inhaled long-acting beta-2-agonists and the risk of acute myocardial infarction

“…For example, pharmacoepidemiological (PE) studies may differ with regard to database characteristics (e.g., claims vs. GP database), inclusion criteria (age restrictions, comorbidities, co-medications), exposure (consideration of dosages), follow-up period, outcome (identification and classification of AMI) definition, and the confounders adjusted for in multivariate models (comorbidities, comedications, disease severity) [8,[10][11][12][13]. Whereas Zhang et al [8] defined AMI cases by using the General Practice Research Database (GPRD) and the national registry of hospital admissions in England, the analyses of Au et al [11] were based on patients included in a multicenter, randomized clinical trial.…”