Original Report

An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA's spontaneous adverse event reporting system†

  1. Eric Colman MD1,*,
  2. Ana Szarfman MD, PhD2,5,
  3. Jo Wyeth PharmD4,
  4. Andrew Mosholder MD, MPH4,
  5. Devanand Jillapalli MD3,
  6. Jonathan Levine PhD6,
  7. Mark Avigan MD, CM4

Article first published online: 29 SEP 2008

DOI: 10.1002/pds.1643

Issue

Pharmacoepidemiology and Drug Safety

Pharmacoepidemiology and Drug Safety

Volume 17, Issue 11, pages 1068–1076, November 2008

Additional Information

How to Cite

Colman, E., Szarfman, A., Wyeth, J., Mosholder, A., Jillapalli, D., Levine, J. and Avigan, M. (2008), An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA's spontaneous adverse event reporting system. Pharmacoepidemiology and Drug Safety, 17: 1068–1076. doi: 10.1002/pds.1643

Author Information

  1. 1

    Division of Metabolism and Endocrinology Products, United States Food and Drug Administration, Silver Spring, MD, USA

  2. 2

    Division of Cardiovascular and Renal Products, United States Food and Drug Administration, Silver Spring, MD, USA

  3. 3

    Division of Neurology Products, United States Food and Drug Administration, Silver Spring, MD, USA

  4. 4

    Office of Surveillance and Epidemiology, United States Food and Drug Administration, Silver Spring, MD, USA

  5. 5

    Division of Biometrics VI, Office of Biostatistics, Office of Translational Sciences, United States Food and Drug Administration, Silver Spring, MD, USA

  6. 6

    Office of Critical Path Programs, Center for Drug Evaluation and Research and Office of the Commissioner, United States Food and Drug Administration, Silver Spring, MD, USA

*Division of Metabolism and Endocrinology Products, Office of Drug Evaluation II, Center for Drug Evaluation and Research, United States Food and Drug Administration, White Oak Office Building 22, Room 3360, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

  1. †

    All authors report no potential conflicts of interest.

Publication History

  1. Issue published online: 23 OCT 2008
  2. Article first published online: 29 SEP 2008
  3. Manuscript Accepted: 29 JUL 2008
  4. Manuscript Revised: 22 JUL 2008
  5. Manuscript Received: 27 JAN 2008

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Keywords:

  • data mining;
  • statins;
  • amyotrophic lateral sclerosis;
  • AERS

Abstract

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).

Purpose

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. Copyright © 2008 John Wiley & Sons, Ltd.

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