A surveillance method for the early identification of idiosyncratic adverse drug reactions.
BACKGROUND
Pemoline is a CNS stimulant that was introduced in 1975 in the US and was used to treat children with attention deficit hyperactivity disorder. Pemoline was withdrawn from the market 30 years later because of fatal hepatotoxicity associated with its use.


OBJECTIVE
To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle.


METHODS
All case reports of acute liver failure associated with pemoline and reported to the US FDA from 1975 through 1999 were reviewed. All published articles on pemoline-induced hepatotoxicity were reviewed, and the Naranjo adverse drug reaction probability scale was applied. The incidence rate of idiopathic acute liver failure was estimated from the published literature. The data were analyzed using Fisher's Exact test and relative risks (RR) were calculated.


RESULTS
As early as 1978, there was a significant signal indicating that pemoline was associated with acute liver failure, with an RR of 24.08 (95% CI 4.67, 124.10; p < 0.05). With an increased number of cases, the significance of the association had been steadily increased.


CONCLUSIONS
This method enables researchers, clinicians, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier than they currently are in the course of marketing and thus quantify serious adverse events.
Etwel
Fatma A
FA
Department of Medicine, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.
Rieder
Michael J
MJ
Bend
John R
JR
Koren
Gideon
G
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D017723:Drug Utilization Review / Q000706:statistics & numerical data; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced*; D010389:Pemoline / Q000009:adverse effects* / Q000627:therapeutic use; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D013607:Tablets; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
D000697:Central Nervous System Stimulants; D013607:Tablets; D010389:Pemoline