 |
WASHINGTON - The government's watchdog agency is investigating whether the Food and Drug Administration's drug-review process cleared two medications without sufficient proof of their safety or effectiveness.
Senator Charles Grassley said yesterday the Government Accountability Office will study a much-debated method for approving drugs used to clear GlaxoSmithKline PLC's diabetes pill Avandia and Merck & Co. and Schering-Plough's cholesterol drug Vytorin.
The Iowa Republican requested the investigation after recent studies suggested the drugs may not lower the risk of heart attack and artery-clogging plaque, as assumed by millions of patients and doctors.
FDA cleared Avandia because it helped control blood sugar, which many doctors believe decreases diabetics' risk of heart attack. But the agency came under fire last year when an analysis showed Avandia could actually increase heart attack risk.
FDA argued that it has never required diabetes drugs to show lower heart attack risk, and that lowering blood sugar alone is important.
The agency approved Vytorin, which combines Schering-Plough's Zetia with Merck's older cholesterol drug Zocor, based on its cholesterol-lowering capability. But a study released earlier this year showed Vytorin was no more effective at limiting plaque buildup in neck arteries than Zocor alone, which is now available as a low-cost generic.
At issue now is whether FDA should approve drugs based on biological measures, like cholesterol, without evidence they improve more meaningful measures like survival.
FDA's director for medical policy Robert Temple said the agency has used several alternate study goals, called surrogate endpoints, to approve drugs for decades. For example, HIV drugs are cleared based on their virus-lowering power, an effective predictor of survival.
Drug industry advocates favor shorter study goals because they involve smaller, less expensive, and faster trials.
Longer trials, they say, may actually jeopardize patients.
"It's probably unethical to do an overall survival study where you're going to have HIV patients taking a placebo for 10 years," said Alan Goldhammer, vice president with the Pharmaceutical Research and Manufacturers of America.
But those who criticize FDA's handling of Avandia and Vytorin say surrogate endpoints aren't the problem. Rather, it's when FDA doesn't demand follow-up studies to prove drugs delivered on the predicted benefits.
"These studies are often never done, so we're left without the knowledge we need to use these drugs wisely," said Dr. Steve Nissen, chairman of cardiovascular medicine at the Cleveland Clinic.
Nissen wrote the analysis that showed Avandia raised the risk of heart attack. Last year FDA said the drug's risks were still unclear and asked GlaxoSmithKline to study its effect on the heart. Results are expected in 2014.
Schering-Plough and Merck are working on a study to determine if Vytorin extends patients' lives.
When the agency does require follow-up studies, its track record is poor for making sure companies complete them. A 2006 investigation by the Health and Human Services Department inspector general concluded FDA could not readily identify what progress companies made on the studies.
In its most recent report, FDA said 900 of more than 1,200 studies required of drug makers had not even begun.
© Copyright 2008 Globe Newspaper Company.
