Photography by Nicholas Eveleigh

U.S. consumers have been buffeted by bad news about the safety of the prescription drugs they take. One shock was the revelation of serious heart risks from the pain reliever Vioxx. Then “black box” warnings about an increased risk of suicide in young people were slapped on all antidepressants.

A leader of the Food and Drug Administration’s drug-safety office has told Congress that the agency and its once-vaunted Center for Drug Evaluation and Research are “broken.” The FDA is currently the object of several investigations, including one initiated at its own request.

A Consumer Reports investigation has now found that tens of millions of people may unknowingly have been exposed to the rare but serious side effects of a dozen relatively common prescription-drug types. Collectively, the drugs, sold in 140 brand-name or generic versions, accounted for some 266 million prescriptions in the U.S. and almost $25 billion in sales during the 12 months ending in September 2005, according to NDCHealth, an Atlanta-based health-care-information company.

 

	CR Quick Take
		Consumer Reports has identified 12 relatively common prescription-drug types linked to serious risks--including an increased likelihood of heart attack, stroke, cancer, or suicide--that were undetected or underestimated when they were approved for use. Many of those drugs are still being advertised, and some lack a “black box” warning that our chief medical adviser says is needed. Indeed, the nation’s drug-safety system has extensive weaknesses that put users of prescription medicines at risk: • Rush to approve. Working under tight deadlines and with sometimes skimpy, unrepresentative data, the Food and Drug Administration reviews drugs at a pace that may make sound decisions difficult. Some FDA scientists say that their bosses have pushed them to approve medications despite their reservations about safety. • A powerless FDA. The agency lacks the power to compel companies to complete studies after drug approval, force doctors to report adverse reactions, or dictate new warning labels. Its Office of Drug Safety assesses risks that emerge after approval, but it’s understaffed and is not permitted to make the final decision about those risks. • Risks hidden. Some companies have withheld studies showing unexpected risks or poor efficacy, which might limit use of a drug. And our analysis of FDA letters to drug firms indicates a broad spectrum of misleading promotions, which have continued unabated through September 2005; such ads swell demand for new drugs before their risks are fully known. • Reforms needed. Despite recent signs of improvement at the FDA, extensive reforms are needed in the drug-approval process, the monitoring of risks that emerge after approval, and the regulation of drug ads (see our January 2006 Viewpoint). For information on what you can do to protect yourself, see What you can do. We also offer vital information to help you weigh medical treatments--both benefits and risks.

Almost all of the drugs are used to treat relatively common conditions that are not usually crippling or life-threatening, such as acne, eczema, and head lice. None is the only drug option. Among the 12, which are made by a wide range of manufacturers, are the pain reliever celecoxib (Celebrex), a close cousin of Vioxx, linked with heart attack and stroke; the cholesterol reducer rosuvastatin (Crestor), which may cause muscle breakdown and kidney damage; and the eczema drugs pimecrolimus (Elidel) and tacrolimus (Protopic), which may increase the risk of cancer. (For a complete list and guidance on what to do if you take one of the 12 types, High-risk drugs.)

The 12 drug types we have identified are not a “dirty dozen.” There are plenty of others with worse risks, such as those used to treat cancer or severe rheumatoid arthritis. And each of the 12 types has legitimate medical uses, especially when other treatments fail.

But their known or possible adverse effects--which include heart attack, stroke, kidney failure, irreversible bone loss, and cancer--were undetected or underestimated when the FDA approved them for use. Some still don’t carry a black-box warning--the most serious label alert--that our chief medical adviser says they should.

Even a perfect drug-safety system might miss some of the adverse effects of medicines before they hit the market. But our investigation has identified serious flaws in both the initial drug-approval process and the monitoring of products after they reach the market, which have almost surely delayed the detection and public disclosure of adverse reactions of many widely sold medications. Indeed, our investigation suggests that our list of 12 is not exhaustive.


An absence of leadership

The problem with the drug-safety system starts with the FDA. The agency’s regulatory might has been undercut by constraints on its enforcement power, limited resources, dependency on drug-company fees to help finance the approval process, and what critics claim is a lack of will to enforce tough requirements.

In a statement by e-mail, Susan Cruzan, an FDA spokeswoman, said, “Drug safety has been and will continue to be a top priority for us.” Cruzan added that “a recent internal audit showed that our professional staff spends about one-half its time addressing safety issues.”

But at a time when strong leadership is most needed, the FDA has had only temporary, acting commissioners for three of the past five years. At press time the agency still had no permanent commissioner to replace Lester Crawford, D.V.M., Ph.D., who resigned in September 2005 after less than three months on the job.

The inspector general of the Department of Health and Human Services is investigating Crawford’s departure. Crawford could not be reached for comment on published reports saying that financial conflicts may have contributed to his decision to leave. In an interview posted on Forbes.com on September. 28, 2005, he said the reports are untrue. Crawford’s attorney, Barbara Van Gelder, declined to answer our questions, except to say that he “retired” from the FDA.

Compounding the safety problem, drug companies have often failed to conduct the studies needed to identify risks that often emerge after approval. Wide distribution of newly approved drugs before their long-term safety has been established, plus immediate, heavy, and sometimes misleading advertising, may increase the chance of harm.

Consumer Reports’ exclusive, ongoing analysis of consumer-drug ads identified a wide range of inaccurate information about safety and efficacy, including what the FDA deemed misleading claims for some brands of every high-risk drug we identified, except the malaria and head-lice medications. Our analysis further suggests that the FDA’s regulation of drug ads has weakened considerably since the late 1990s, although we found some improvement in the past two years.

Some companies have withheld publication of studies that found serious risks, or have failed to conduct post-approval studies that they promised to the FDA. Such studies are crucial for promptly detecting adverse reactions that surface when large numbers of consumers start to use new medications.

The safety system’s failings were illustrated in October 2005. A study released first on the Web site of the Journal of the American Medical Association (JAMA) reported that the diabetes drug muraglitazar, which an FDA advisory committee had recommended approving six weeks earlier, appeared to double the risk of heart attack, stroke, or death. Some analysts expected the drug to be a billion-dollar seller, but now drugmaker Bristol-Myers Squibb says it’s talking with Merck, its cosponsor, about scrapping the application or conducting more studies.

That report averted “a potential catastrophe,” says Steven Nissen, M.D., medical director of the Cleveland Cardiovascular Coordinating Center. Nissen, lead researcher of the JAMA study, said in a phone interview that “the advisory panel just dropped the ball completely.”

An accompanying editorial in JAMA reported that the study results were presented to the FDA in ways that may have fostered an “illusion of safety.” Tony Plohoros, a Bristol-Myers Squibb spokesman, said by e-mail that the company’s analytic methods “are widely used and have been validated by the scientific community.” The FDA would not offer specific comments while a decision on the drug was pending.