CORNELIUS, N.C. - In the waning days of the Bush administration, the Food and Drug Administration issued new guidelines to make it easier for drug manufacturers to promote "off-label" prescription drug uses, which can be deadly for patients.
The move came despite criticism from Bush's own Department of Veterans Affairs, which said the change "favors business interests over public safety" and could lead to a "decline in drug safety." It also was crafted despite efforts by state and federal law enforcement experts to clamp down on off-label drug marketing.
The new guidelines were issued four years after Robin Briggs of Cornelius, N.C., buried her husband, Doug, who committed suicide on a chilly Christmas Day after taking a drug off-label.
Doug Briggs, a physician, had taken Neurontin, which the FDA had approved to treat epilepsy, to ease persistent back pain. It didn't much help his back, but Robin Briggs said the drug's risk of producing suicidal behavior led to his death.
As the Obama administration reviews all the midnight rules that the departing Bush administration issued, it will have to decide whether to try to modify or reverse this late change in the FDA's oversight of off-label drug marketing.
Congressional leaders from both parties criticized the guideline when it was proposed last year. Sen. Charles Grassley (R., Iowa), who has repeatedly investigated the FDA, said the proposal would legitimize something that "the FDA once considered evidence of unlawful marketing."
"A legislative fix may be in order," Grassley said last week.
Rep. Henry Waxman (D., Calif.), called the guideline a "long-coveted parting gift" for the pharmaceutical industry that "fundamentally undermines" the FDA's authority.
The use of drugs "off-label" - for reasons the FDA hasn't approved - has long been tolerated, and sometimes encouraged. For certain ailments including cancer it can be helpful.
But the practice also can be dangerous. Nearly every drug has side effects, some serious. Those risks can be worth the potential benefit that comes with an FDA-approved, on-label use. But with an off-label use, the risks remain but the benefits are less certain.
While it's legal for physicians to prescribe drugs off-label - often based on their reading of the latest medical research - it's illegal for drugmakers to push such uses.
Over the past five years, federal prosecutors and state attorneys general have brought more than a dozen cases against drugmakers for off-label marketing and won more than $6 billion in criminal and civil settlements, according to the Government Accountability Office and the U.S. Department of Justice.
In January alone, two of the nation's largest drugmakers - Pfizer Inc. and Eli Lilly & Co. - agreed to two of the biggest off-label settlements ever.
"The FDA has been abysmal policing this area," said Connecticut Attorney General Richard Blumenthal, who helped engineer a major off-label case against drug maker Cephalon Inc., in Frazer, Pa. "One reason the states have been more and more active is that the federal government has been asleep at the switch."
To increase its sales, Cephalon launched a "concerted plan to maximize revenue by the off-label marketing of drugs," according to the government's trial memorandum.
Cephalon's Actiq, for example, was designed for cancer patients with extreme pain. Cephalon told its sales staff to pitch the powerful drug to general practitioners, not just to cancer specialists.
It paid off. "The sales of Actiq quadrupled. Up to 80 percent of Actiq sales were off-label," said Laurie Magid, the acting U.S. attorney in Philadelphia.
Last September, her office announced that Cephalon would plead guilty to violating drug-marketing laws and pay $425 million in fines and penalties.
While Magid and other prosecutors cracked down, the FDA relaxed its stance.
In its final week, the Bush administration opened the door to some off-label marketing. In what's called a "guidance" document, the FDA specified how drug companies could hand out medical journal articles that highlight potential off-label drug uses.
The guidance was complicated, and the main players in the issue still disagree about what it means for FDA oversight of off-label marketing. The drug industry generally endorsed the guidance as helpful to doctors and patients.
But health advocacy groups, insurers and state prosecutors said the change would do more harm than good.
To be sure, doctors can find good information on new drug uses in medical journals. The screening process for medical journals, however, is rarely as rigorous as the FDA's drug approval process. Without proper oversight, drugmakers can pay for flimsy research on off-label uses and then use the results to promote their drugs.
The Bush FDA issued the new guidance over the objections of Bush's Department of Veterans Affairs, which pays for drugs taken by its health system patients.
"We urge the FDA to withdraw" the proposal, the VA wrote the FDA last year. "It will not improve drug safety and could very well result in a decline in drug safety."
"Second-rate 'studies' published in journals with questionable peer-review processes will be used to convince physicians to use drugs for an ever-increasing number of unapproved uses," the VA said.
The FDA's Jarilyn Dupont said the agency tried to strike a balance between patients' interests and the medical community's free-speech rights.
"Doctors have the ability to read these articles on their own," she said. "So the question is, does it change the article if they are given it by a drug representative or they read it in a medical journal? The article is still the same."
Drug companies have agreed to pay almost $7 billion in settlements that involve marketing drugs for uses other than those approved by the FDA:
* Examples of off-label uses; settlements may be specific to just one off-label use
NOTE: GAO defined an off-label settlement to be any civil and/or criminal settlement or disposition of a matter where a sponsor's promotion of a drug for a use not contained in FDA-approved labeling was investigated, regardless of whether that alleged conduct was the basis for the ultimate disposition; settlement amounts may include penalties for offenses not involving off-label promotion