Endotoxin-like reactions with intravenous gentamicin: results from pharmacovigilance tools under investigation.
OBJECTIVE
To apply two data mining algorithms (DMAs) to Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) reports that involved endotoxin-like reactions with intravenous gentamicin to determine whether a signal of disproportionate reporting of these events would have been generated concurrently with surveillance based on clinical observation.


METHODS
Multi-item gamma-Poisson shrinker (MGPS) and proportional reporting ratios (PRRs) were used. Data used for data mining consisted of an extract of the FDA AERS database. Previously published details of clusters of endotoxin-like reactions to intravenous gentamicin were used to select adverse events for data mining.


RESULTS
The first signal of disproportionate reporting with any relevant event occurred in 1998, the year in which the outbreak was identified and evaluated by the Centers for Disease Control and Prevention and the FDA. In 1997, there were only 6 reports of rigors in the AERS; this jumped to 68 in 1998. In 1998, a signal was generated for endotoxic shock with PRRs but not with MGPS, based on one case.


CONCLUSIONS
The two DMAs generated signals concurrently with the influx of reports. It would have been difficult for safety reviewers to ignore an increase in rigors by traditional methods of safety surveillance; therefore, DMAs might not have had a great deal to offer in this instance. If data mining were considered as a second-line defense to diligent clinical observations under similar circumstances, simple disproportionality methods such as PRRs might be more useful than DMAs such as MGPS when commonly cited thresholds are used.
Hauben
Manfred
M
Risk Management Strategy, Pfizer Inc., New York, New York 10017, USA.
Reich
Lester
L
D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001499:Bayes Theorem; D005839:Gentamicins / Q000009:adverse effects*; D006801:Humans; D016247:Information Storage and Retrieval; D007262:Infusions, Intravenous; D017891:Pharmacoepidemiology; D016012:Poisson Distribution; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D012772:Shock, Septic / Q000139:chemically induced*; D014481:United States; D014486:United States Food and Drug Administration
D000970:Antineoplastic Agents; D005839:Gentamicins