Are medicines safe for us and for our children? Americans once thought so. Now we aren't so sure.
It's been a shaky year for our faith in U.S. drug safety:
Heart safety questions led to the withdrawal of the arthritis drug Vioxx (search). Vioxx's sister drugs Celebrex (search) and Bextra (search) are reported to have heart safety concerns. The Food and Drug Administration releases heart warnings about the over-the-counter pain reliever Aleve. Antidepressant drugs now carry a new "black-box" warning (search) about suicide risk. The ADHD (search) drug Strattera (search) is associated with — in a very small number of patients — serious liver damage.
A maverick FDA drug reviewer told Congress that several drugs now on the market may not be safe. He acknowledged he did not speak for the FDA, which finds the drugs safe when used properly. The drugs (Crestor, Bextra, Meridia, Accutane, and Serevent) remain on the market.
A three-year-old study of the FDA's drug review process surfaced late this year. It shows that nearly one in five FDA reviewers felt pressured to approve a drug, and that two out of three FDA reviewers lack confidence in how the FDA monitors the safety of a drug once it is approved. The report, from the Health and Human Service's inspector general's office, concludes that "these findings present a significant warning signal."
Is our drug-safety system broken? Exactly what does it mean for a drug to be "safe?" How can you find out whether medicines put you or your family at risk? WebMD takes a look at these questions.
What's a "Safe" Drug?
No drug on earth is totally risk free. Every time you take a medication, you take a risk.
So what's a safe drug?
Balance, says William Comanor, PhD. Comanor is director of the UCLA program on pharmaceutical economics and policy and is professor of health services at UCLA and professor of economics at the University of California, Santa Barbara.
"Drug safety means finding the right balance," Comanor tells WebMD. "There is no other answer, unless you want to be an advocate or a politician."
By balance, Comanor means weighing a drug's risk against a drug's benefit. That's exactly how the FDA defines drug safety.
"The FDA's determination that a product is safe ... does not suggest an absence of risk," FDA spokeswoman Laura Alvey tells WebMD. "Rather, a product is considered to be safe if the clinical significance and probability of its beneficial effects outweigh the likelihood and medical importance of its harmful or undesirable effects. In other words, a product is considered safe if it has an appropriate benefit-risk balance for the intended population and use."
Large benefits make a large risk acceptable, says Marcia Angell, MD, for two decades the editor of The New England Journal of Medicine and now senior lecturer at Harvard University.
"When treating cancer we take all kinds of risk, because the benefits are so great," Angell tells WebMD. "Drug safety ought to be some relationship between benefit and risk. You ought to be able to take a risk that is commensurate with the benefit you get."
Note Angell's use of the word "ought." Drugs with very small benefits, she says, aren't worth any risk at all. Yet such drugs get approved as safe.
"If we are looking at drugs like Vioxx and Celebrex, neither should have been approved because they don't offer anything over pain relievers already sold over the counter," Angell says. "You don't want to accept any risk if there's no benefit over existing treatments."
But not everyone agrees with that stance. Safety concerns are exactly why arthritis specialist Stephen M. Lindsey, MD, says some patients truly need Cox-2 drugs such as Celebrex. Lindsey heads the rheumatology department at the Ochsner Clinic Foundation in Baton Rouge, La.
"I don't think we should be telling people to stop taking Cox-2 drugs," Lindsey told WebMD in response to the news that Celebrex was linked to heart attacks and strokes. "There is a high risk of bleeding ulcers and death with traditional arthritis drugs. We forget that 17,000 people die each year with ulcers due to arthritis drugs. So if somebody has a high risk of a bleeding ulcer and has arthritis, they are safer on Celebrex — unless they have serious heart disease, then all bets are off."
The bottom line is that drugs aren't free lunches. There's always a risk. Yet not everybody can benefit from every drug, says Clyde Buchanan, RPh, senior director of pharmacy services for Atlanta's Emory University Hospital.
"There certainly is a problem with consumers wanting every benefit from every drug whenever they want it, without any of the safety issues that go along with any medicine," Buchanan tells WebMD.
Is America's Drug-Safety System Broken?
No nation on earth has better drug testing and oversight than the U.S., says David B. Nash, MD, MBA, director of the office of health policy and clinical outcomes at Thomas Jefferson University Hospital. He points to the extensive clinical trials and intensive review process the FDA requires for drug approval.
Buchanan agrees that the FDA's approval process is rigorous.
"One of the strengths of the drug review system the FDA has had since the early 1960s is that pre-approval clinical trials are extensive and carefully reviewed," he says. "Not every country has an FDA. In those countries, drugs can be marketed more quickly. That often leads to difficulties with drug safety. But because of political pressure, the FDA has been moving drugs through the review process more quickly since the late 1990s."
In the late 1980s, AIDS activists frustrated by the FDA's approval process demonstrated in favor of more rapid drug approval. Joined by other patient-advocacy groups - and the pharmaceutical industry - this frustration led to the 1993 Prescription Drug User Fee Act (search). PDUFA, as it's called, changed the rules of the game. Under PDUFA, drug companies pay a hefty fee to submit new drugs for approval. That money is used to hire a new FDA reviewer. In return, the companies get much faster FDA action.
This is both good and bad, Comanor says.
"There are costs to our society from delaying the introduction of helpful drugs and testing them too thoroughly. Extra testing means delay. People die when there are delays," he says. "And there are costs to society from too rapid drug approval. Drugs are powerful things and we don't always know the results of giving them to very large numbers of people for a long time. People die as a result."
Again, Comanor argues, it comes down to a question of balance.
"Striking exactly the right balance between timely approval and safety is a task for Solomon — it is splitting the baby," he says. "I think the FDA does a pretty good job. But that doesn't mean their task is always done perfectly."
Baloney, says Angell.
"Our system is broken in all kinds of ways," she says. "Drug companies pay user fees, but those are used to speed drug approval. Not much is used for safety. And the FDA is underfunded by Congress. So you see rapid growth in the part of the FDA that approves drugs, and shrinking of the part that ensures safety, good manufacturing standards, and truth in advertising. If we spent more on safety and less on rapid approval, you would restore balance."
Angell's recent book, The Truth About Drug Companies: How They Deceive Us and What To Do About It (search), argues that the growing political clout of drug companies has overwhelmed FDA regulation. She says that the FDA has all the power it needs to insist on extensive safety testing, but "sits on its hands" instead of acting in the public interest.
"The FDA is captured by the industry it is supposed to be regulating," Angell says. "Congress is in the pocket of the pharmaceutical industry, too, and the FDA has to answer to Congress. You have this unholy chain in which industry tells Congress what to do, and Congress tells the FDA what to do."
Nash could not disagree more. He says it's nonsense to think that the drug industry has somehow captured the FDA. Those who think the FDA is powerless, he says, don't understand how the system works — and how drug companies tremble when the FDA issues warning letters that threaten the products on which their profits depend.
Buchanan takes a more moderate approach than Angell or Nash.
"I wouldn't say the system is broken, but it needs a tune-up," he says. "We have a conflict of interest with the drug companies actually paying for drugs to be processed through the FDA. That just doesn't make sense to me. It would take more tax money, maybe, but the public deserves a more objective approach to drug safety before marketing."
A tune-up, at least, is in the works. FDA officials say their agency is committed to safety and public health. Yet there's clearly room for improvement. To that end, FDA Acting Commissioner Lester Crawford, MD, last month announced four initiatives to improve safety:
—The FDA has asked the independent Institute of Medicine to evaluate the U.S. drug safety system. A major focus of the study will be on how best to monitor the safety of approved drugs after they reach the market.
—The FDA intends to begin a program that will referee differences of opinion among FDA staffers.
—The FDA will speed its search for a director of its Office of Drug Safety within the Center for Drug Evaluation and Research. That position is currently empty.
—The FDA will hold workshops and advisory committee meetings over the next year to bring together experts — from federal agencies, universities, the pharmaceutical industry, and the medical community — to discuss drug safety issues.
What You Can Do About Drug Safety
"We don't think the current situation is a reason to panic," Buchanan says. He urges patients NOT to stop taking any prescribed drug without first talking to their doctor. Pharmacists, he says, can answer many drug safety questions.
Every expert who spoke with WebMD agrees on one thing: Patients can do much to protect themselves.
Buchanan has a short list of questions to ask your doctor when he or she prescribes a drug:
—What is this drug used for?
—How long do I have to take it?
—What dose should I take?
—How often should I take it?
—Are there any side effects I should be aware of? If I have any of these side effects, what should I do about it?
Angell advises patients to be wary of new drugs. If an older drug will do the trick, she says, use it before trying a newer, more expensive, and possibly less safe new drug. Her advice:
Try not to take a drug that has been on the market for less than three years. If your doctor prescribes a newly approved drug, ask if there isn't a generic or older drug that would be just as good.
If your doctor says, "No, you need this new one,' say "How do you know? What are you basing this on?"
"People have to give their doctors permission not to give them a prescription whenever they walk out of the office," Angell says. "Ask your doctor, 'Are you giving me a prescription or a free sample just to get me out of the office? Or would it be better to talk with me about changing my lifestyle?'"
"Patients have a responsibility to understand their medicines," Paul Barach, MD, MPH, associate dean of the University of Miami medical school and director of the University of Miami/Jackson Memorial Hospital, tells WebMD. "Ask your doctor, your nurse, your pharmacist. Use the Internet. Just as checking with Consumer Reports is a good idea when you're going to buy a stereo or a car, you should check out the drugs you buy. Consumers need to take more responsibility on their shoulders for drug safety."
By Daniel DeNoon, reviewed by Michael Smith, MD
SOURCES: Laura Alvey, spokeswoman, FDA. Marcia Angell, MD, senior lecturer, department of social medicine, Harvard Medical School. Paul Barach, MD, MPH, associate dean, School of Medicine, University of Miami; medical director, Jackson Memorial Hospital; director, center for patient safety, University of Miami/Jackson Hospital, Miami. Clyde Buchanan, RPh, senior director of pharmacy services, Emory University Hospital, Atlanta. William Comanor, PhD, professor of health services, UCLA; director, UCLA research program on pharmaceutical economics and policy; professor of economics, University of California, Santa Barbara. David B. Nash, MD, MBA, director, office of health policy and clinical outcomes, Thomas Jefferson University Hospital, Philadelphia. FDA Review Process for New Drug Applications: A Management Review, HHS Office of Inspector General, March 2003. FDA. Angell, M. The Truth About Drug Companies: How They Deceive Us and What To Do About It, Random House, 2004. Stephen M. Lindsey, MD, head of the rheumatology department, Ochsner Clinic Foundation, Baton Rouge, La.
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