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Key Problems With the FDA
• Problem: Pressure From the IndustryThere's pressure to speed decisions, and there's pressure to soft-pedal problems. That means drugs may go on the market without adequate vetting -- or follow-up. Critics of the FDA like to say it's the best agency the pharmaceutical industry can buy. That's a political jab, and agency advocates say it's unfair. "The extraordinary efforts of these committed staff members are the very reason further catastrophic food-and-drug events have been averted," an otherwise scathing review by the FDA's Science Board concluded last November.
But most agree that there's at least a problem of perception, and perhaps more than that, caused by the growing chunk of the agency's budget that comes directly from drug companies. Industry dollars now pay for more than half of the FDA's drug-review budget; in five years, that proportion is expected to jump to 70 percent.
Called user fees, this $400 million a year is designed to speed decisions on applications for new drugs. "User fees seem to save taxpayers money," says Susan Wood, PhD, the former assistant commissioner for women's health at the FDA and now a professor of public health at George Washington University. "But they undermine public confidence in the FDA's independence and impose time pressures that could end up costing lives."
Faster approval of drugs, of course, is a very good thing if you need a lifesaving medicine. Many patients are clamoring for that speed. Review times have been cut from 27 months to less than a year. Vioxx was fast-tracked in just six months. But some argue that the pendulum has swung too far. "A lifesaving drug should be sped along," says Steven Nissen, MD, chair of the department of cardiovascular medicine at the Cleveland Clinic and a frequent advisor to the FDA. "But with user fees, we've pressed the accelerator on all drugs, and that's a mistake."
Here's the danger: "The easiest way to make those deadlines is not raise too many questions and just accept what the drug companies say about safety," says former FDA drug reviewer David Ross, MD. Too often, Dr. Ross says, reviewers tell their FDA supervisors that a drug doesn't work or has a major safety problem and "managers come up with contrived reasons to approve the drug anyway." He says the standards of safety and efficacy have slipped to the point that the drug reviewers "can end up approving almost anything."
No one can say that moving drugs more quickly from the laboratory to the pharmacy always puts Americans at risk. But there is a smoking gun: an alarming spike in adverse drug reactions reported to the FDA recently, from 267,000 in 2000 to over 471,000 in 2006. And the number of reported deaths has nearly tripled, from 5,519 to 15,107. That's only part of the story: The agency estimates that it learns of fewer than one in ten drug reactions.
Janet Woodcock, MD, the FDA's deputy commissioner and chief medical officer, flatly denies that user fees and sped-up approvals compromise safety. "The FDA is legendarily tough -- our requirements are viewed as a really tough bar to get over."
"The review standards have not changed one bit since the introduction of user fees," says Alan Goldhammer, PhD, deputy vice president for the Pharmaceutical Research and Manufacturers of America, the drug industry lobby. "We've been careful never to compromise the independence of the FDA. Congress would not permit it."
Nevertheless, says Dr. Woodcock, "I understand that there's a perception problem."
What's Being Done
Congress slightly increased the FDA's drug safety budget last year but accomplished that mostly by boosting user fees once again. To help offset that influence, and enable the FDA to tackle all its other responsibilities, reformers say Americans should pay 3 cents a day to fund the agency, rather than the 1.5 cents we now pay. The agency's Science Board argues, "That's a great price to pay for the assurance that our food and drug supply is, indeed, the best and safest in the world."
• Problem: Safety of New Drugs
When the FDA approves a drug or medical device, staff scientists must, in effect, make a judgment call about its safety. They're relying on industry studies that usually follow between 600 and 3,000 people, often for just a few months. Those small clinical trials are designed to measure a drug's safety and effectiveness in a targeted group of patients -- not the dangers the drug might pose when it's taken by people with a wide variety of backgrounds and health conditions. "If it kills one in 2,000 people, or makes one go blind, you may not see that in the trial," says Drummond Rennie, MD, a deputy editor of The Journal of the American Medical Association (JAMA) and a professor of medicine at the University of California, San Francisco. "You start adding that up, and that's ten in 20,000 going blind, and that's a lot of people."
Those risks are revealed only after a medicine goes on sale and has been used for months or years by hundreds of thousands or even millions of people. Keeping track of those reactions is called post-market surveillance, and experts say it's one of the most important phases of drug testing. Historically, user fees were not allowed to go toward checking the safety of drugs once they were on the market. And until now, those follow-up reports haven't been mandatory. A 2006 report found that 65 percent of the studies that drug firms promised to conduct in recent years hadn't even begun.
What's Being Done
Congress authorized the FDA to spend $25 million from user fees this year to improve drug safety. But agency insiders say that's not nearly enough. "You've still got a mismatch," says Hubbard, who is now a senior advisor for the Alliance for a Stronger FDA, a group that includes seven former agency commissioners and three former Secretaries of Health and Human Services. "You still have all this effort going into getting the drugs on the market, and not much going into making sure they're safe once they're out there."
On that issue, Congress got tough last year. The FDA can now require companies to trace the long-term effects of their drugs. If firms renege, they face stiff fines, up to $10 million for repeat offenses.
Another crucial reform: Companies can no longer treat the results of clinical trials as trade secrets. Until this year, a manufacturer could cherry-pick what it revealed -- publishing a favorable study in a medical journal and sticking less rosy findings in a drawer. A report in the January New England Journal of Medicine revealed that one-third of antidepressant drug trials are not published, which can mislead doctors into thinking the drugs are more effective than they really are.
Here, too, Congress has drawn the line: Companies must post results of clinical trials on a public database, ClinicalTrials.gov, within one year of their completion. Independent experts should soon be able to evaluate the findings and better inform doctors and consumers about what the studies mean. Unfortunately, companies can wait three years to post summaries written for the general public.
That new measure of openness draws kudos from Dr. Woodcock, the FDA deputy commissioner. "People volunteered for those trials, and their lives may have been altered as a result," she says. "They deserve to know that their information has contributed to society." Having such full disclosure about a treatment or device is the only way to know what medical research means for all of us.
• Problem: Sloppy Record Keeping
For an organization whose core function is gathering and analyzing crucial facts quickly, the FDA's partially computerized database "is like something that came off the ark," says Dr. FitzGerald, the Penn pharmacologist and agency advisor.
Companies are required to tell the FDA about any severe reactions they learn of, and do so within 15 days if the injuries are life-threatening. And the agency operates a website called MedWatch (www.fda.gov/medwatch), where doctors (and patients) can download a form to report problems. But few physicians bother to use it. The result: Only a small fraction of adverse reactions get passed on. Even more important, the FDA doesn't have the time or money to make sense of the information it does receive.
The agency is notified of half a million problems each year, a third of them serious, says Dr. Woodcock. Most of those reports arrive via paper fax and have to be sorted by hand. More worrisome, the FDA's skeleton staff of 35 report analysts have only eight minutes to read even the most serious case, says Hubbard, who tracked such things as associate commissioner.
"We've never had enough resources to really do the job and hire the staff," says Dr. Woodcock, who has been at the FDA for two decades. "And it's not that we didn't try."
What's Being Done
Congress has responded, telling the agency to invest several million dollars to connect to large medical-records databases run by the Veterans Health Administration, Medicare and HMOs. Using these databases will allow the FDA to better track and analyze adverse drug side effects. That means the FDA will know much sooner if a newly marketed drug needs to be relabeled or pulled off the market, even whether one medication works better than another. And thanks to Congressional intervention, the agency will now be able to make label changes quickly, without prolonged negotiations with the drug companies.
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