Comparison of two drug safety signals in a pharmacovigilance data mining framework.
Since adverse drug reactions are a major public health concern, early detection of drug safety signals has become a top priority for regulatory agencies and the pharmaceutical industry. Quantitative methods for analyzing spontaneous reporting material recorded in pharmacovigilance databases through data mining have been proposed in the last decades and are increasingly used to flag potential safety problems. While automated data mining is motivated by the usually huge size of pharmacovigilance databases, it does not systematically produce relevant alerts. Moreover, each detected signal requires appropriate assessment that may involve investigation of the whole therapeutic class. The goal of this article is to provide a methodology for comparing two detected signals. It is nested within the automated surveillance framework as (1) no extra information is required and (2) no simple inference on the actual risks can be extrapolated from spontaneous reporting data. We designed our methodology on the basis of two classical methods used for automated signal detection: the Bayesian Gamma Poisson Shrinker and the frequentist Proportional Reporting Ratio. A simulation study was conducted to assess the performances of both proposed methods. The latter were used to compare cardiovascular signals for two HIV treatments from the French pharmacovigilance database.
Inserm, CESP Centre for Research in Epidemiology and Population Health, Biostatistics, Villejuif, France Univ Paris Sud, Villejuif, France pascale.tubert@inserm.fr.
Pascale
P
Tubert-Bitter
Inserm U657, Univ. de Bordeaux, Bordeaux, France.
Bernard
B
Bégaud
Inserm, CESP Centre for Research in Epidemiology and Population Health, Biostatistics, Villejuif, France Univ Paris Sud, Villejuif, France.
Ismaïl
I
Ahmed
D019380:Anti-HIV Agents / Q000009:adverse effects; D001499:Bayes Theorem; D057225:Data Mining; D016208:Databases, Factual; D005602:France; D006801:Humans; D009203:Myocardial Infarction / Q000139:chemically induced; D019888:Nelfinavir / Q000009:adverse effects; D060735:Pharmacovigilance; D012372:ROC Curve; D019258:Saquinavir / Q000009:adverse effects; D012680:Sensitivity and Specificity
D019380:Anti-HIV Agents; D019888:Nelfinavir; D019258:Saquinavir