Common drugs, hidden dangers, hidden risks 1/06

In this report: Overview; FDA: Watchdog to lapdog?; Misleading ads; Hidden risks; What you can do; High-risk drugs

January 2006

Failure to disclose In “just three days,” patients with irritable bowel syndrome can end “30 years of debilitating” symptoms with a treatment from Novartis, claims this print ad. But in June 2003, the FDA asked Novartis, maker of Zelnorm, an irritable-bowel drug on our list of high-risk medicines, to withdraw the ad because the main part failed to disclose any risk information and overstated the efficacy of medication. “Novartis complied with the FDA’s request and discontinued dissemination of the ad,” says Megan Thomas Humphrey, a company spokeswoman."

Hidden risks

It’s not just the advertising that may be misleading. Companies have sometimes reported only the positive findings of drug studies and suppressed the disappointing or worrisome ones. That “has a huge distorting effect on what we know about drugs,” says Nissen, lead author of the muraglitazar study.

In April 2002 GlaxoSmithKline submitted three studies to the FDA to support an application for approval of children’s use of its antidepressant Paxil. Two studies failed to show that the drug was effective against depression; the combined results of the three studies suggested an increased risk of suicidal thinking and behavior. But the company published only the single positive study, in the July 2001 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

In June 2003, about a year after receiving the studies about increased risk, the FDA issued a statement on its Web site saying that although it had “not completed its evaluation of the new safety data,” it was recommending against prescribing Paxil for children and adolescents. Another 16 months passed before the FDA requested a strong suicide-warning label for Paxil and all other antidepressants.

Mary Anne Rhyne, a spokeswoman for GlaxoSmithKline, says the FDA-requested label changes were “implemented immediately.” But by that time, although Paxil was never approved for pediatric use, doctors had written an estimated 2.1 million “off label,” or unapproved-use, prescriptions for children.

A lawsuit filed by New York’s attorney general in June 2004 charged the drug giant with concealing information about Paxil and misrepresenting the research to its own sales representatives, telling them that the drug had “remarkable efficacy and safety in the treatment of adolescent depression.” GlaxoSmithKline admitted no wrongdoing but resolved the lawsuit by agreeing to pay New York $2.5 million “to avoid protracted litigation.”

Rhyne confirmed that the company faces similar lawsuits from Paxil users as well as suits claiming attempted or actual suicide. She added that “access to the full clinical trial reports” is now available at the company’s Web site (www.gsk.com).

In congressional hearings in September 2004 about disclosure of test results, lawmakers grilled executives from GlaxoSmithKline as well as Forest Laboratories, Pfizer, Wyeth Pharmaceu-ticals, and others. “I don’t understand why a drug company wouldn’t want to put every possible bit of information out on the table,” said Rep. Greg Walden, R-Ore. Later in the hearings David Wheadon, GlaxoSmithKline senior vice president, responded, “That certainly is the goal and that is what we are working toward.”

To end selective reporting, legislation known as the Fair Access to Clinical Trials Act has been introduced in Congress to require registration of virtually all pending clinical drug trials on a government-run public Web site. It would also mandate posting the results on a database accessible to doctors and patients. The American Medical Association has recommended that the Department of Health and Human Services establish a comprehensive drug-trials registry. And the editors of 13 top medical journals have agreed to publish only trials listed on an acceptable registry.

PhRMA has launched a voluntary registry of members’ clinical trials at the government’s current, limited registry, where companies would also post summaries of the results. “The PhRMA membership is committed to the plan,” Goldhammer says. But federal rules already require that trials involving “serious or life-threatening” diseases be registered at the government site. Yet companies listed only 35 percent of some 690 such trials during nine months in 2002, according to an FDA analysis published in 2005.

DOCTORS FAIL TO REPORT

Physicians are supposed to voluntarily report any serious drug reactions to the FDA’s MedWatch program, where researchers look for signals that a medication might be causing problems. But only 1 to 10 percent of such incidents are ever reported, various studies have estimated. An FDA analysis found that pharmacists and, to a lesser extent, consumers each filed far more MedWatch reports than did physicians in fiscal 2004. Nurses filed about as many as doctors.

The FDA’s drug-safety and risk-management advisory committee has recommended that the agency actively search databases for signs of trouble. Until now, the FDA has consistently “underinvested” in such high-tech information gathering, reported Scott Gottlieb, M.D., the FDA’s deputy commissioner for medical and scientific affairs, in the July/August 2005 issue of Health Affairs.

Safety