An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA's spontaneous adverse event reporting system.
BACKGROUND
We detected disproportionate reporting of amyotrophic lateral sclerosis (ALS) with HMG-CoA-reductase inhibitors (statins) in the Food and Drug Administration's (FDA) spontaneous adverse event (AE) reporting system (AERS).


OBJECTIVE
To describe the original ALS signal and to provide additional context for interpreting the signal by conducting retrospective analyses of data from long-term, placebo-controlled clinical trials of statins.


METHODS
The ALS signal was detected using the multi-item gamma Poisson shrinker (MGPS) algorithm. All AERS cases of ALS reported in association with use of a statin were individually reviewed by two FDA neurologists. Manufacturers of lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, cerivastatin, and rosuvastatin were requested to provide the number of cases of ALS diagnosed during all of their placebo-controlled statin trials that were at least 6 months in duration.


RESULTS
There were 91 US and foreign reports of ALS with statins in AERS. The data mining signal scores for ALS and statins ranged from 8.5 to 1.6. Data were obtained from 41 statin clinical trials ranging in duration from 6 months to 5 years and representing approximately 200,000 patient-years of exposure to statin and approximately 200,000 patient-years of exposure to placebo. Nine cases of ALS were reported in statin-treated patients and 10 cases in placebo-treated patients.


CONCLUSIONS
Although we observed a data mining signal for ALS with statins in FDA's AERS, retrospective analyses of 41 statin clinical trials did not reveal an increased incidence of ALS in subjects treated with a statin compared with placebo.
Colman
Eric
E
Division of Metabolism and Endocrinology Products, United States Food and Drug Administration, Silver Spring, MD 20993, USA. eric.colman@fda.hhs.gov
Szarfman
Ana
A
Wyeth
Jo
J
Mosholder
Andrew
A
Jillapalli
Devanand
D
Levine
Jonathan
J
Avigan
Mark
M
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000453:epidemiology; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors