A new analysis by the US Food and Drug Administration (FDA) of data from over 40 clinical trials did not show a link between statins, drugs used to lower cholesterol, and higher risk of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease often referred to as “Lou Gehrig’s Disease“. The FDA said there is no need to change prescribing practice.
The analysis is reported as a study in the 29 September issue of Pharmacoepidemiology and Drug Safety by FDA researchers.
ALS is a fatal neurodegenerative condition that affects about 1 to 2 per 100,000 people. Its incidence increases with age. ALS is a type of motor neurone disease where brain cells that control muscle movement gradually stop working and the person eventually loses the ability to move any part of the body apart from the eyes.
The FDA study is an example of the increasing use of an investigative method called data mining. Traditionally a tool of corporate knowledge management specialists, data mining is a systematic way of extracting data relevant to a specific topic or question from a collection of information sources originally produced for other reasons. Researchers are increasingly using this discipline to mine studies with a common theme to look for coherent patterns that suggest other things could also be happening in the data set.
The FDA wondered if such a pattern might be that statin use was in some way linked to an increased incidence of ALS because they were getting a higher than expected number of Adverse Event Reporting System (AERS) reports of ALS in patients on statins. They received 91 such reports in all, some from inside and some from outside the US.
First, two FDA neurologists individually reviewed all AERS cases of ALS reported in association with the use of a statin. Then they asked drug companies making the statins lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, cerivastatin, and rosuvastatin to tell them how many cases of ALS were diagnosed during all of their placebo-controlled statin trials that lasted 6 months or more.
The FDA investigators then reviewed the data from 41 placebo-controlled statin trials that lasted between 6 months and 5 years, totalling around 200,000 patient-years of exposure to a statin and about the same to a placebo. They found that 9 cases of ALS were reported in statin-treated patients and 10 cases in those treated with placebo.
They concluded that:
“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.”
One of the investigators, Dr Mark Avigan, director of the Division of Pharmacovigilance I, at the FDA’s Center for Drug Evaluation and Research, said:
“While the FDA finds the lack of an increase in the incidence of amyotrophic lateral sclerosis (ALS) in patients treated with statins in clinical trials reassuring, given the extensive use of this class of drugs and the serious nature of ALS, continued study of this issue is warranted.”
The FDA is waiting for the completion of a large study of ALS and statin use by Dr Lorene Nelson, Chief of the Division of Epidemiology at Stanford University School of Medicine, and colleagues from the Division of Research at Kaiser Permanente, which should finish in 6 to 9 months, and the agency is also considering carrying out further epidemiologic studies of its own.
Statins, or HMG-CoA-reductase inhibitors, are the most commonly-prescribed drug for reducing elevated cholesterol levels in the US.
“An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA’s spontaneous adverse event reporting system”
Eric Colman, Ana Szarfman, Jo Wyeth, Andrew Mosholder, Devanand Jillapalli, Jonathan Levine, Mark Avigan.
Pharmacoepidemiology and Drug Safety, Published Online 29 Sep 2008.
DOI: 10.1002/pds.1643
Source: FDA, journal abstract.
Written by: Catharine Paddock, PhD.