By Rita Rubin, USA TODAY
If anyone has the right to say "told you so," it's Mirta Millares and her colleagues at Kaiser Permanente's Drug Information Services.
Based on advice from the staff of specially trained pharmacists, Kaiser never added Vioxx, the arthritis drug, or Tysabri, a multiple sclerosis drug, to its formulary, the list of covered prescription drugs.
In both cases, safety and cost-effectiveness concerns kept the drugs off. Doctors could prescribe them only if they believed there was no alternative.
And then, no one could get the drugs. Merck stopped selling Vioxx in September 2004, nearly five years after the Food and Drug Administration approved it. And Biogen Idec pulled Tysabri in February 2005, four months after approval.
A Merck study found patients with colon polyps who took Vioxx had twice the heart attack or stroke risk as those on a placebo. And two people in a long-term Tysabri study came down with progressive multifocal leukoencephalopathy, or PML, a rare neurological disease. One died.
Clearly, newer drugs are not always better drugs, although they're usually promoted more and pricier. Still, Arthur Levin, head of the Center for Medical Consumers in New York, cites "a cultural mindset, even among physicians, that new is an improvement on old."
A 2002 study of more than 42,000 patients found generic diuretics were not only cheaper but also more effective than newer, brand-name drugs in lowering blood pressure.
For the first year after the results came out, diuretic prescribing did rise, says lead author Curt Furberg. But since then, "it's been fairly flat." He says scientists simply can't compete with brand-name drug makers' efforts to put a positive "spin" on unfavorable findings.
When the study came out, Furberg estimated treating high blood pressure with diuretics instead of brand-name drugs could save the U.S. health care system up to $10 billion a year. Some of the brand-name drugs are now available as generics, but they're still not as effective as diuretics, and as many as half of candidates for diuretics, aren't on them, he says.
FDA's role in approval
In theory, at least, most Americans want the most effective drug, according to a USA TODAY/ABC News/Kaiser Family Foundation poll conducted Sept. 7-12. Insurers should not cover expensive new treatments unless they've been proven to be more effective than cheaper treatments, 72% of respondents said. The margin of error for that question was plus or minus 4 percentage points.
Increasingly, critics of the FDA and of the drug industry are advising doctors and patients to avoid the newest drugs when there are older, equally effective drugs.
"It is a widely held misperception that FDA approval of a new drug denotes a guarantee of safety and certainty about its risk-benefit profile," a special Institute of Medicine panel reported last month. "In fact, eliminating all uncertainties prior to approval could cause considerable delay in new products reaching patients in need."
The panel recommended Congress amend the Food, Drug, and Cosmetic Act to require new drugs carry a special symbol on their labels for their first two years on the market. The marking would alert patients and prescribers there might be uncertainties about risks and benefits.
In those first two years, panel members said they would favor a ban on direct-to-consumer advertising, although it's not clear such a move would be legal. And the FDA should review all new data about drugs after five years on the market, they said.
In last week's Archives of Internal Medicine, Furberg, Levin and three other current or former members of the FDA's Drug Safety and Risk Management Advisory Committee said the agency should be able to grant "conditional approval" for new drugs that "have clear benefits but unanswered questions regarding serious adverse events."
Conditional OK recommended
Conditional approval would press drug makers to do and report postmarket safety studies requested by the FDA, the authors wrote. For now, companies aren't doing the studies "because there is no consequence if they fail to do so," says Furberg, professor of public health sciences at Wake Forest University in Winston-Salem, N.C.
Alternatively, the FDA should re-review all drugs two to four years after initial approval, Furberg and his co-authors wrote. He says the most worrisome drugs are taken for chronic diseases over a period of years, usually far longer than pre-market clinical trials.
Spokesman Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America, the main industry trade group, says stigmatizing new drugs could cause patients and doctors to shun beneficial treatments.
"Clearly, there are going to be drugs that come through the system that pose very little in terms of a risk to the patient," he says. "To single these out for special attention seems to us to be unwise."
On paper, Goldhammer says, conditional approval looks like a good way to speed promising drugs to market, but the industry is concerned insurers might not cover drugs lacking full approval.
Meanwhile, the FDA gave Biogen Idec permission to resume selling Tysabri in June. The drug's new label is topped with a black-box warning, the FDA's strongest warning, about PML.
In response to an FDA advisory committee, Biogen Idec has set up a program limiting distribution of the drug.
Whether Tysabri should now be added to the Kaiser formulary is under review.
