February 24, 2012 — Neurologists and epileptologists are banding together to urge the US Agency for Healthcare Research and Quality (AHRQ) to withdraw its report on antiepileptic drugs.
The American Academy of Neurology (AAN), the American Epilepsy Society (AES), the International League Against Epilepsy, and the Epilepsy Foundation have united to draw attention to their concerns about the potential misuse of the study, which they say could negatively affect patient care.
The new report compares efficacy, safety, and tolerability of newer versus older and innovator versus generic antiepileptic medications. The intent of the systematic review is to provide an evidence-based analysis.
However, leading neurologists and epileptologists argue that the work fails to take into account the complexities of epilepsy and the drugs used to treat. They are asking the agency to collaborate on a new research proposal.
“We are very concerned the report is sending a dangerous message,” Jacqueline French, MD, a spokesperson for the AAN and incoming president of AES, told Medscape Medical News. Dr. French is based at the New York University Comprehensive Epilepsy Center.
The report fails to recognize the different types of epilepsy and focuses on efficacy without considering individual drug characteristics, Dr. French said. “There are very good reasons we make certain drug choices.”
The study compares the effectiveness of old-line anticonvulsants with that of newer epilepsy drugs irrespective of epilepsy type and comes to inappropriate conclusions, Dr. French said.
Report to Stand
Jean Slutsky, director of AHRQ’s Center for Outcomes and Evidence, told Medscape Medical News that the researchers are not considering withdrawing the report.
“There are few high-quality research studies comparing various medications for treatment of epilepsy and different types of epilepsy. The report points out that this limitation precluded report authors from making strong conclusions about comparative effectiveness and risks of different medications,” Slutsky said. “However, one of the cornerstones of the Effective Health Care Program is the high priority it places on identifying future research needs. Our report cites examples of potential studies that could have significant impact on this field of research.”
During an interview, Edward Faught, MD, chair of the AES treatments committee and professor of neurology at Emory University in Atlanta, Georgia, said he strongly supports evidence-based medicine and comparative effectiveness research.
“This report provides a great deal of useful information. It’s over 50 pages long and will make a good reference. The problem is the final conclusions are not warranted by the data, and there is a risk future treatment decisions could be made based on economic factors alone,” said Dr. Faught.
The ability of an antiepileptic drug to stop seizures is just 1 of many considerations, he pointed out.
Those troubled by the report say they were given an opportunity to comment on a draft version in February 2011; however, they note that none of their concerns were taken into account in the final publication.
“I think this is a case where the statisticians are looking at the data and making conclusions that don’t match what we find in daily practice,” Dr. Faught said. “There is nothing statistically incorrect about the report, but the final conclusions are problematic.”
The report concludes that there are “no significant differences in the risk of maintaining seizure freedom” when newer antiepileptic medications are compared with carbamazepine, phenytoin, and valproate.
“It is possible to read the conclusions simplistically and to determine that there is little justification for not using carbamazepine or valproate first,” Dr. Faught said. He suggests that the study’s equivalent efficacy results between old and new drugs depend heavily on the inclusion of 2 drugs in the analysis that are less effective for new-onset seizures — gabapentin and vigabatrin. The first is known to be relatively inefficacious for these seizures, and the latter is a rarely used special-purpose anticonvulsant.
Medication side effects and potential drug-drug interactions are also given relatively little attention in the study, the specialists argue. Valproate has a well-documented increased risk for hepatotoxicity in children younger than 2 years and an increased risk for dermatological reactions in children.
Particularly disconcerting to the group is the absence of consideration of the teratogenic effect of this drug, which should be avoided when possible, owing to the risk for serious congenital malformations and cognitive outcome in children of women taking valproate during pregnancy.
Source: Medscape Medical News