Methods and Issues to Consider for Detection of Safety Signals From Spontaneous Reporting Databases: A Report of the DIA Bayesian Safety Signal Detection Working Group

Abstract

Spontaneous reporting (SR) adverse event system databases, large observational databases, large clinical trials, and large health records databases comprise repositories of information that may be useful for early detection of potential harms associated with drugs, devices, and vaccines. All of the data sources include many different adverse events and many medical products, so that any approach designed to detect "important" signals of potential harm must have adequate specificity to protect against false alarms yet provide satisfactory sensitivity for detecting issues that really need further investigation. Algorithms for evaluating potential risks using information from these sources, especially SR databases, have been described in the literature. The algorithms may seek to identify potential product-event associations without any prior specifications, to identify events associated with a particular product or set of products, or to identify products associated with a particular event or set of events. This article provides recommendations for using information from postmarketing spontaneous adverse event reporting databases to provide insight into risks of potential harm expressed by safety signals and offers guidance regarding appropriate methods, both frequentist and Bayesian, to use in various situations as a function of the objective of the analysis.

Statistical Practices of Safety Monitoring: An Industry Survey

“…As the statistical separation between pre-and post-approval monitoring diminishes, we will view spontaneous reports not as inferior to trial reports but as having greater uncertainties we must address. 19 In preparation for working with safety scientists, it is important to use the same safety terminology, which can have subtle differences regarding degree of drug association. CIOMS VI provides a list of terms that define "signal" and distinguish between causality gradients "probably," "possibly," and "likely."…”

“…As the statistical separation between pre- and post-approval monitoring diminishes, we will view spontaneous reports not as inferior to trial reports but as having greater uncertainties we must address. 19…”

Pharmacovigilance and Adverse Drug Reaction Reporting among the General Public in Lithuania: A Cross-Sectional Study

“…The method of pharmacovigilance that is most frequently utilized is spontaneous ADR reporting [ 1 , 2 ]. It is both a crucial element and a potent instrument of any nation’s pharmacovigilance system [ 3 ].…”

Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database

“…Our study data shows that the disproportionality statistic was higher in the pre-2017 period 27 , albeit with a wider confidence interval. Considering the large number of patients exposed to the drug every year, this small but significant disproportionality finding is important, but at the same time, this needs to be considered taking into account the inherent limitations of data obtained from adverse event databases such as FAERS used in the current study 15,28 . It is also to be noted that the results did not show increased reporting of acute pancreatitis, which is more likely to be drug-related, with TCZ.…”