"Off-Label" -- And Out Of Bounds?

When drugmakers promote products for unproven uses, they may be courting trouble

On Oct. 5, Genentech Inc. (DNA ) disclosed that the U.S. Attorney's office in Philadelphia was investigating the marketing of one of its drugs. Neither the feds nor the company would provide details, but many observers believe the inquiry is focused on whether Genentech, led by CEO Arthur D. Levinson, improperly marketed the cancer drug Rituxan to combat cancers other than those approved for treatment by the Food & Drug Administration. Such ``off-label'' uses seem to be attracting increasing scrutiny these days. Johnson & Johnson (JNJ ) and Cephalon Inc. (CEPH ), too, are being probed for possible marketing violations believed to be connected to off-label uses.

On the face of it, using drugs to treat diseases they weren't designed and tested for seems risky -- yet another example of the overzealous marketing for which drugmakers are increasingly criticized. But the issue is more complicated than that. In an effort to help patients, doctors commonly try medicines in new ways, even if the drugs haven't been rigorously tested for those diseases. That raises real questions about whether patients are being used as guinea pigs and how drugmakers should spread the word about promising new treatments. The law bans them from actively marketing drugs for off-label uses. But with the lure of additional sales, companies have a powerful incentive to push the envelope. Here is a primer on the issue and the larger concerns it raises:

Why are drugmakers being investigated?

Genentech's drug Rituxan was approved only for patients with slow-growing non-Hodgkin's lymphoma who have relapsed or failed to respond to other drugs. Scientists have been testing Rituxan in other blood cancers, with some promising results, prompting doctors to prescribe it more widely. But if Genentech is actively promoting the drug for those new uses, it's breaking the rules. J&J is being investigated for off-label promotion and sales of several drugs, including Procrit, which is used to treat anemia.

But if a drug does work for other diseases, shouldn't doctors get the word?

Yes. Medicine clearly advances when researchers find new uses for drugs. And arguably, companies are well placed to spread the information. Currently, industry sales reps can give doctors copies of studies on unapproved uses if the reports appear in peer-reviewed medical journals.

So where's the problem?

Companies may push drugs for off-label uses harder than the evidence warrants. Even if they follow the rules and only hand out journal articles, drugmakers may be spreading half-truths, since they aren't bound to distribute less favorable studies. The industry has often flouted the rules. This year, Pfizer (PFE )-owned Warner-Lambert pleaded guilty to criminal charges that its Parke-Davis division illegally promoted its epilepsy drug Neurontin for a host of other disorders, turning it into a blockbuster. Among other dubious practices, the company paid doctors to give presentations and write articles heralding unproven uses. It agreed to pay $430 million in penalties.

Does the practice harm patients?

Potentially, and in two different ways. Individual patients can be hurt if a drug they're given doesn't work. Medical knowledge can also be a casualty. If companies can get docs to prescribe a drug for unapproved uses, the industry has little incentive to do the clinical trials that would prove whether it actually is effective.

What's the solution?

There are no easy answers. Some experts say regulators should ban dissemination of information about unapproved uses. Courts, though, have ruled that companies have a constitutional right to give information to doctors. While the FDA should make it easier for companies to perform the clinical trials needed to get approval for new uses, that won't resolve all the problems. Sometimes companies play a useful role, spreading the word about promising new uses of their drugs. Other times, they cross the line in their quest for fatter profits and need to be reined in by regulators.

By John Carey in Washington, with Amy Barrett in Philadelphia

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