By Randall Osborne

Editor

It's either a beneficent way for physicians to get medicine into the hands and bodies of needful patients (and, not incidentally, for drug makers and their biotech partners to make extra money), or it's a dangerous practice that can lead to worsened illness or death, when pursued by eager or inexperienced doctors.

When the subject is off-label drug use, opinions on both sides are fiercely held.

Last summer, a federal court ruled the FDA's ban on pharmaceutical manufacturers sending medical studies of drugs for unapproved indications to physicians even those studies published in respected journals was unconstitutional. The FDA filed an appeal, and earlier this year another court ruling came down. That ought to have settled the matter, at least in the realm of everyday practice.

Apparently not.

A shady zone remains, and within it the battle continues squaring off drug firms aiming for bigger profits (who find unlikely comrades in hands-off political conservatives and the boosters of alternative medicine, as well as in free-speech advocates) against the FDA and some consumer watchdogs.

Drug firms say patients can't always wait for the FDA to approve an already marketed treatment specifically for their indication. They say physicians should be allowed to know every way the drug might be useful, even if the data come unsolicited from drug makers. The government, they say, has no business meddling once a treatment has been given the FDA's nod for any indication. It's too much like Big Brother.

The FDA says it only wants to guard an unwary public from greed on the part of overzealous pharmaceutical profiteers, which could lead to prescriptions that either do no good for the targeted, unapproved ailment, or that when given by practitioners without enough knowledge are downright harmful.

Larry Sasich, a research analyst with the consumer watchdog group Public Citizen in Washington, said the appellate decision probably didn't settle anything.

"It's not out of the courts," he said. "This is an intermission."

Taking up the war with the FDA on First Amendment grounds was the Washington Legal Foundation (WLF), which long had opposed the FDA rule on disseminating what it called "truthful" information on off-label uses, and which claimed victory in the appeals decision.

Although the court did not hand down an opinion on the free-speech issues involved, WLF said, it threw out the FDA's case, thereby leaving the first finding intact, "in substantial part."

WLF vowed to seek a citation of contempt against the FDA if it tries to evade the ruling by some arcane interpretation used to crack down on the free flow of accurate information.

"They're poised," Sasich said.

In the original court battle, the FDA said it needed to restrict promotional claims until they could be reviewed by the agency, but the court declared truthful commercial speech is guaranteed protection. Journal articles, textbooks and the like could not be considered false or misleading, just because the FDA had not examined them, the court said.

The court's injunction against the FDA let companies distribute bona fide peer-reviewed journals with advice on off-label uses. Firms also may send excerpts of legitimate textbooks that would support off-label uses. At the same time, the court let the FDA block material that it knows is false or misleading, or material internally produced by companies. The agency also may forbid drug makers from talking with physicians person-to-person about off-label uses, the court said.

It was a "paternalistic assumption" that the FDA needed to protect medical professionals from information, the judge in the case said. He said it was "constitutional blackmail" to require a supplemental application from manufacturers who want to distribute such data, and called the practice a "gross imposition on free speech."

The FDA has issued a guidance paper on the appeals decision. A source in the agency acknowledged the paper is confusing, and seems, to some readers, to say the court's decision more or less backs the FDA's original rules on sending out information related to off-label drug use. Further clarification of the guidance within the agency is yet to be made, the source said. Officials did not return calls.

Sasich said the original lawsuit had to do with FDA guidance documents, which dealt with continuing education and symposia. But the court didn't come to a decision until after the FDA Modernization Act (FDAMA) was passed. FDAMA contains a provision specific to promoting off-label drug uses.

"That muddied the waters," he said, so the FDA asked for clarification.

"Some [companies] felt that, with the original decision, they could send around reprints that are unsolicited," Sasich said. "With the appeals court decision, the way I read it, if the company wants a safe harbor for distributing information, they would have to use the FDAMA rules."

Others, such as WLF, read the decision differently, he added.

FDAMA requires the company to promise it will pursue a supplemental new drug application for the indication it wants to distribute information about, Sasich said.

"They have to submit the materials they want to distribute, and those are gone over by the FDA," he said. "[The paperwork to the FDA] has to clearly state the reprint discusses a use not approved for the FDA," and must include the drug label, as well as disclose any financial connection between the company involved and the author of the article, Sasich said.

The FDA must also be provided with a bibliography of other articles that discuss off-label use, and the agency has 60 days to review the material.

But that's not good enough for Sasich's group, co-founded several decades ago by activist Ralph Nader. Public Citizen believes drug companies should not be allowed to send unsolicited information to doctors in any circumstances.

"There's never been any prohibition about doctors going to the library, or going to the companies and requesting a reprint," Sasich said. "There, the physician is looking for information."

Late last year, Public Citizen filed litigation of its own, asking the FDA to provide it with materials submitted by companies distributing those materials under FDAMA rules.

"We had to sue them to get [the material]," he said. The lawsuit is ongoing. Sasich said the FDA's position was that the material is scientific information, until Public Citizen asked to see it at which point the agency (and companies) said the material was commercial and therefore private.

"They can't have it both ways," Sasich said. "This process should be totally transparent to the public, [along with any] safety and efficacy information that the companies had or the FDA has about an unapproved use."

Among the companies whose materials are sought in the Public Citizen lawsuit against the FDA are the biotech firms Chiron Corp., SuperGen Inc., Alza Corp., Agouron Pharmaceuticals Inc., as well as pharmaceutical giants Novartis, Merck and SmithKline Beecham, Sasich told Financial Watch.

"I'm trying to categorize them right now, to see what uses are being promoted, and if the FDA had any objections," he said, adding that the list is not yet complete. The case is expected be heard again late this month or early next.

Meanwhile, the other shoe could drop any day, if the FDA decides to restrict a company and a group such as WLF takes the case as a test of the most recent appeals court decision. The agency seems to believe it can do that, on the basis of the court decision, Sasich said. Opponents seem to believe it can't, on the same basis.

"Everybody thinks they're winners," Sasich said. "I don't know why."