Bridging differences in outcomes of pharmacoepidemiological studies: design and first results of the PROTECT project.
BACKGROUND
Observational pharmacoepidemiological (PE) studies on drug safety have produced discrepant results that may be due to differences in design, conduct and analysis.


OBJECTIVE
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.


CONCLUSIONS
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.
Victoria
V
Abbing-Karahagopian
Xavier
X
Kurz
Frank
F
de Vries
Tjeerd P
TP
van Staa
Yolanda
Y
Alvarez
Ulrik
U
Hesse
Joerg
J
Hasford
Liset van
Lv
Dijk
Francisco J
FJ
de Abajo
John G
JG
Weil
Lamiae
L
Grimaldi-Bensouda
Antoine C G
AC
Egberts
Robert F
RF
Reynolds
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082 3508 TB Utrecht, The Netherlands. o.h.klungel@uu.nl.
Olaf H
OH
Klungel
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D016208:Databases, Factual / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D006801:Humans; D017891:Pharmacoepidemiology / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods