The Role of Disproportionality Analysis of Pharmacovigilance Databases in Safety Regulatory Actions: a Systematic Review.

Abstract

Disproportionality analysis (DA) of adverse drug reactions spontaneous reporting (SR) databases is used to identify signals of disproportionate reporting (SDR). The objective of this study was to identify the generation of SDR in the published literature and whether it led to regulatory action. A systematic literature search in MEDLINE and Cochrane Central Register for Controlled Trials (CENTRAL) in a 10-year period, from 2005 to 2014, was conducted, to identify studies designed to detect drug safety signals through the use of disproportionality measures applied to spontaneous reporting databases of adverse drug reactions. Seventy three studies were included. The number of publications has been rising over the study time period. Forty nine studies focus on drug-event combinations. Large international and smaller national or regional databases were identified. The disproportionality measures applied included frequentist and Bayesian methods and some studies used more than one method. SDRs were identified in more than ninety percent of the studies. Ten studies were found to be confirmatory of previous regulatory decision. It was not found any safety signal issued by drug regulatory agencies exclusively generated by DA. More research devoted to this issue is needed, since the value of these methods on drug safety signaling and their impact on drug regulation actions remains to be established.