title: Bayesian model selection in logistic regression for the detection of adverse drug reactions.
abstract: Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, the analysis of such databases requires statistical methods. In this context, disproportionality measures can be used. Their main idea is to project the data onto contingency tables in order to measure the strength of associations between drugs and adverse events. However, due to the data projection, these methods are sensitive to the problem of coprescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. On different examples, this approach limits the drawbacks of the disproportionality methods, but the choice of the penalty value is open to criticism while it strongly influences the results. In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis-Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well-established approaches on a reference dataset, and obtains better rates of positive and negative controls. However, many signals (i.e., specific drug-event associations) are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance. Code implementing the proposed method is available at the following url: https://github.com/masedki/MHTrajectoryR.
authors.affiliation: Inserm, UMR 1181 B2PHI, Institut-Pasteur and Université Versailles St-Quentin, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Marbac
authors.affiliation: Inserm, UMR 1181 B2PHI, Institut-Pasteur and Université Versailles St-Quentin, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Tubert-Bitter
authors.affiliation: Inserm, UMR 1181 B2PHI, Institut-Pasteur and Université Versailles St-Quentin, France. mohammed.sedki@u-psud.fr.|Faculté de médecine, Université Paris-Sud, France. mohammed.sedki@u-psud.fr.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Sedki
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016015:Logistic Models; D017891:Pharmacoepidemiology / Q000379:methods*; D060735:Pharmacovigilance
keywords: Bayesian Information Criterion; Binary data; Logistic regression; Metropolis-Hastings algorithm; Model selection; Pharmacovigilance; Spontaneous reporting