The type-2 diabetes drug manufactured by Glaxo-SmithKline, is the most recent poster child for drug safety hysteria. A meta-analysis published last May by a noted cardiologist fueled concern and headlines over possible cardiovascular side effects from the drug (rosiglitazone maleate), forcing the FDA to revisit Avandia’s labeling in the absence of any new, convincing clinical trials. The result: GSK’s agreement in mid-November to expand Avandia’s existing black-box warning with confusing language saying “a risk of an increase in myocardial ischemic events was not confirmed or excluded in three long-term clinical trials.”
It is that kind of decision-making in the absence of facts that the Food and Drug Administration Amendments Act (FDAAA) of 2007 aims to help eliminate. The bill is a political steroid shot in the arm to the beleaguered FDA, long considered a 98-lb. weakling. As a result, its Center for Drug Evaluation and Research (CDER) will flex new muscles in 2008. But don’t expect CDER to become Hulk Hogan overnight, if ever. In many ways, despite its size and provisions, the legislation is hardly radical. generic cialis soft tabs
“It is not a rewrite of authority; [nor] is it a huge addition the way the 1962 amendments were,” explains Bill Hubbard, who left the FDA in 2005 as Associate Commissioner. He now serves as senior advisor to the Coalition for a Stronger FDA.
“It is a tweaking, but a big tweaking,” he says.
The bill gives the FDA authority to impose restrictions on the distribution of new drugs that have significant benefts—like Avandia—but whose safety hasn’t quite been buttoned down at the time of approval (again, like Avandia). Those up-front agreements are called Risk Evaluation and Mitigation Strategies (REMS).
The agency will be able to force companies to perform post-approval clinical trials to pin down unresolved safety problems. If those trials turn up troubling information, the FDA will be able to act quickly to force a label change. None of this had happened with Avandia.
Concerns about Avandia hit the headlines last spring when Steven Nissen, M.D., chairman of the Department of Cardiovascular Medicine at Cleveland Clinic and immediate past president of the American College of Cardiology, dropped a bomb. The meta-analysis he published in the New England Journal of Medicine in May 2007 combined the results of 42 previously completed small studies to show that Avandia posed a 43% increased incidence of heart attacks. At the FDA’s insistence, GSK had added additional language about heart attacks to Avan-dia’s warning label 15 months earlier. canadian pharmacy cialis
The Nissen meta-analysis, however, implied that the company was soft-pedaling the risk—even though he conceded that, his meta-analysis was “less convincing” than a clinical trial, even though the New England Journal of Medicine itself had seconded the fuzziness of the doctor’s analysis in an accompanying editorial, and even though FDA Commissioner Andrew von Eschenbach, M.D., had noted “serious concerns.” He said that patients taking Avandia and their health care providers were confused about the drug’s safety because of media reports surrounding the journal article. Confusion and hysteria are what Congress hopes to eliminate in 2008 and beyond with the provisions of the FDAAA A more accurate title for the bill might have been “The No More Vioxx, Ketek, Avandia canadian, et al., Act of2007.”
The legislation weighs in at more than 400 pages of technical verbiage and contains at least 200 provisions. Many of these provisions have deadlines for implementation and are identified within the bill itself.
Although the bill’s drug safety provisions were the subject of numerous headline-producing congressional battles, they were actually an add-on to legislation reauthorizing the FDA to collect user fees from drug companies for the five years starting in fiscal year 2008, which began on October 1, 2007. Those user fees, although controversial, are a critical component of the CDER’s budget.
In fiscal year 2008, according to Alan Goldhammer, Deputy Vice President of Regulatory Affairs of Pharmaceutical Research and Manufacturers of America (PhRMA), companies will pay a total of $459 million in user fees. These fees will account for 62% of the CDER’s budget. The $459 million is an increase of nearly 50% over the $305 million the companies paid in 2007, and it will increase in each of the next four years over the five-year term of the reauthorization. Most of that money has been, and will continue to be, used for the review of new drugs. However, the bill sets aside $54 million for drug safety activities in fiscal year 2008; that figure will also increase steadily over the next five years, and much of the $54 million will be used to hire staff in the area of postmarketing surveillance.
By the end of2008, the CDER’s staff will have grown by about 500 employees, a 20% increase. Congress expects to see a bigger, stronger, better-staffed CDER win more wrestling matches with pharmaceutical companies over drug safety, but the companies aren’t so sure that a larger CDER will necessarily mean fewer drug safety headlines.