Free Minds & Free Markets

The First Amendment Applies to the FDA Too

Can the government prevent drug firms from telling patients true facts about the medicine they prescribe?

Charanlak Suwannate/Dreamstime.comCharanlak Suwannate/Dreamstime.comIf you use a beta-blocker called Corgard to prevent migraine headaches, you are taking advantage of an important if obscure element of modern medicine: physicians' ability to prescribe approved medicines for purposes not explicitly sanctioned by the Food and Drug Administration (FDA). Corgard is approved for angina and high blood pressure only, yet migraine sufferers and their physicians know that it has other useful properties as well. These so-called "off-label" uses of drugs are perfectly legal, yet regulators make it all but impossible for manufacturers to inform doctors about such uses. No law or regulation explicitly forbids it, but the FDA treats it as misbranding or fraud. The government has prosecuted numerous drug makers for off-label promotion, with penalties and settlements in the billions of dollars.

But that could change soon. In the last few years, the agency has lost several cases in which federal courts have held that giving doctors truthful information about off-label uses is protected by the U.S. Constitution's First Amendment. And while prosecutors have continued to drag drug makers to court, new leadership at the FDA has finally signaled some willingness to obey the Constitution. In the waning days of President Barack Obama's administration, the agency issued a rule that reinforced its speech restrictions, but regulators are now reconsidering that position.

Before a drug can be sold in the United States, it must be certified by the FDA as safe and effective for a specific "on-label" use—to treat high blood pressure or a certain kind of leukemia, for example. But once a drug has been approved, physicians may legally prescribe it for any other purpose. There is typically a long lag between clinical research findings and FDA approval of a new use; journal articles and presentations at scientific conferences far outpace the agency's process. So off-label prescribing makes it possible for patients to benefit from the most up-to-date medical knowledge.

Off-label prescribing is ubiquitous in a number of medical specialties and, by some estimates, at least 20 percent of all prescriptions are written for off-label uses. A 2013 study, for example, found that about 30 percent of the prescriptions for oncology drugs were for off-label uses.

Needless to say, off-label prescribing must be done judiciously. "Guesses" about possible uses of drugs may have deleterious results, as illustrated by a 2011 safety review of the heart drug Multaq. The approved, on-label use of the drug is to treat people with transient atrial fibrillation (an abnormal heart rhythm). However, according to the FDA, the drug increases the risk of serious cardiovascular events, including death, when used by patients with permanent atrial fibrillation. Prescribing Multaq for the latter condition because it is safe and effective for the former would put patients at grave risk.

So doctors know they must continuously educate themselves about the risks and benefits of all the medicines they prescribe, for both on- and off-label uses. And drug manufacturers have a legal obligation to monitor the safety of their products long after they've been approved; whether they're promoting approved uses or off-label ones, the FDA has the authority to prosecute companies when they distribute false or misleading information. Similarly, drug companies can (and routinely are) sued by patients who believe some aspect of information is incorrect or misleading. Those are compelling reasons for manufacturers to continue to test their drugs long after approval, despite this rhetorical question posed by a former FDA official in the Washington Post, "If your drug is approved for X, why would you ever commit millions [of dollars] in additional testing to get approved for Y, when it's already legal to use it for Y?"

If the threat of agency action or private litigation weren't enough, there is yet another reason why drug companies continue to test the safety and effectiveness of their products for both on- and off-label uses. The overwhelming majority of drug sales in the United States are paid for by insurance companies and government health care programs, and they demand evidence that drugs are safe and effective before they agree to pay for new uses.

Medical professional societies, the FDA, or perhaps the National Institutes of Health or another agency could do more to keep track of and distribute scientific evidence about off-label uses. But drug makers will inevitably have the most comprehensive and up-to-date information about their products.

The FDA itself acknowledges that "off-label uses or treatment regimens may be important and may even constitute a medically recognized standard of care" and insists that drug companies are in the best position to understand the risks and benefits of their products. Nevertheless, regulators have aggressively exercised their authority over drug labeling and "promotion"—which is construed to encompass not just advertising but virtually any communication with health professionals or patients about the drug—to prevent manufacturers from disseminating information about off-label uses, even to doctors.

Until recent federal court decisions, drug firms were permitted only to engage in a severely limited range of so-called "educational" activities, such as speaking about research projects at medical conferences. Scientists working for drug firms, but not sales representatives, could answer questions about off-label uses posed directly to them by doctors. In some circumstances they were able to send peer-reviewed medical journal articles and excerpts from medical textbooks to physicians—but not if the firm had any financial ties to the underlying research.

Since most clinical research on medicines is funded, at least in part, by drug firms, this restriction cordoned off a huge fraction of published research from dissemination by manufacturers. And almost everything else appeared to be prohibited, although the FDA's regulations are so unclear that even legal and regulatory experts often had difficulty deciphering what was permitted and what was not.

When pressed, FDA officials have occasionally acknowledged that truthful speech is protected by the First Amendment. But they have continued to prosecute manufacturers, even when company employees merely informed doctors about off-label uses the agency eventually approved. The agency's attitude, according to federal judge Royce Lamberth, was that scientific evidence about off-label uses should be considered false until the FDA says it is true. According to Lamberth, "the FDA exaggerates its overall place in the universe," inasmuch as the "First Amendment is premised upon the idea that people do not need the government's permission to engage in truthful, non-misleading speech about lawful activity."

The agency has gone to baffling lengths to defend its position. For example, prosecutors (from the Department of Justice, acting on behalf of FDA) have argued that the FDA policies do not prohibit constitutionally protected speech but merely unprotected conduct—that is, mislabeling a drug. Under the Food, Drug and Cosmetic Act, a drug's FDA-approved label must include safety information for the manufacturer's "intended use" of the product. The agency's theory is that off-label promotion renders a drug mislabeled because the promotion is evidence of another intended use not described on the product's label. Most courts have seen through this circular logic and have therefore concluded that that the FDA policies are unconstitutional.

In a 1999 case brought by the nonprofit Washington Legal Foundation, a federal district court held that the FDA's policy of restricting the dissemination of medical journal articles describing off-label uses was an unconstitutional restriction of commercial speech. On appeal, the FDA tweaked its argument and conceded that drug manufacturers do have some First Amendment rights, including the right to distribute journal reprints. That made the specific constitutional question moot, but in the intervening years the FDA has declined to say definitively what else is permitted. That lack of transparency is unfair both to industry and to patients.

Another legal milestone was the 2012 case U.S. v. Caronia, in which the federal Second Circuit Court of Appeals overturned the conviction of a pharmaceutical sales representative who told a doctor about off-label uses of Xyrem, a prescription drug manufactured by Orphan Medical, Inc. The court held that "the government cannot prosecute pharmaceutical manufacturers and their representatives under the [Food, Drug and Cosmetic Act] for speech promoting the lawful, off-label use of an FDA-approved drug." Conviction for off-label marketing that was not untruthful or misleading would infringe the defendant's First Amendment rights, the court found, although "of course, off-label promotion that is false or misleading is not entitled to First Amendment protection." The FDA opted not to appeal the decision to the Supreme Court, but said that the Caronia decision would not significantly affect its enforcement.

In 2015 a U.S. district court judge in New York handed the FDA another significant defeat, ruling again that the agency cannot bar truthful, off-label marketing without violating freedom of speech. That led to an agreement between the FDA and the plaintiff, Amarin, that the drug maker may promote one specific off-label use of Vascepa, a drug approved for lowering triglycerides, so long as the company uses "truthful and non-misleading" speech.

Those decisions by lower courts comport with U.S. Supreme Court rulings, which have held on several occasions, most recently in the 2011 case Sorrell v. IMS Health, that truthful speech used in pharmaceutical marketing is entitled to the same level of First Amendment protection as other forms of commercial speech.

Nevertheless, in 2016 the FDA secured a guilty verdict in a case, U.S. v. Facteau, against two medical device company executives, even though the judge informed the jury that off-label promotion "is not itself a crime." The judge bought the government's bogus argument that it was prosecuting the defendants not for their speech but for the "act" of mislabeling a medical device. That verdict may, of course, be overturned on appeal, but it suggests the FDA has not been chastened by the growing number of court decisions against it.

Photo Credit: Charanlak Suwannate/

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  • SIV||

    the FDA treats it as misbranding or fraud

    I wish the FDA would treat eggless vegan "mayo" and lab-grown and plant-based "meat" as misbranding and fraud because that's what it fucking is. Don't get me started on fat-free "half and half" and "sour cream".

    Better yet, abolish the FDA.

  • SQRLSY One||

    Why don't sellers get creative here? Its not soy milk or coconut milk, it's soy miilk or soy mulk or coconut milck? As if consumers think that soy milk might be cow's milk in the first place, come ON!!! WHO is gonna get confused if we label it "Vegan Mayo"? But then"vegan Mayu" to bypass the fuck-heads at the FDA should help! Come on, sellers, get creative!

  • Azathoth!!||

    the problem isn't labeling it 'Vegan Mayo', the problem is labeling vegan mayo 'Mayo'

  • BestUsedCarSales||

    I think this is easily handled by people without any need of a government agency defining things.

  • Quixote||

    Just as long as we all agree that the First Amendment does not apply to criminal "satire," contrary to outrageous "opinion" pieces such as this:

  • mtrueman||

    "the problem is labeling vegan mayo 'Mayo'"

    We are blessed to live in a time and place where folks can say this, in all seriousness, without embarrassment.

  • Griffin3||

    I don't see what the problem is. Look at the crap Kraft has been marketing as "Sweet and Sour" sauce for years.

  • SQRLSY One||

    Well, ya know, we have to have Government Almighty PROTECT us all from ignorant consumers, who might casually glance at the big fat label on a product, ignoring the finer print... And then WHO KNOWS WHAT might happen!

    Suppose, for instance, that I see a "Soy Milk" label, and then assume that the cows have been drinking or eating "Soylent Green", to make this milk... And "Soylent Green is PEOPLE", ya know, and then I might panic, pick up some guns, take revenge on the supposedly-people-eating "mad cows", shooting up the cows, and THEN who knows what would happen after THAT?!?

    Maybe "cows take revenge", as in "Cows with Guns", see ...

  • SQRLSY One||

    Here we are, more than a year after Trump takes power and is supposedly "cleaning out the swamp", and absolute CRAP like this ain't fixed yet?!?! WTF?!??!

    Some bright young genius needs to bypass Government Almighty, and put up a web site for doctors and pharmaceutical companies. Post up instructions on this web site, for computer weenies to see how to use TOR or TunnelBear or other VPNs to post content. Police the content a tad... And locate the server in Iceland or other nation away from USA snoops and power-piggies and thought-control police... Iceland has a LOT of this kind fo freedom, I think...

    And invite ANONYMOUS sources (like, inside sources at pharmaceutical companies, as well as doctors) to post content, to include white papers and PDF files, ALL about off-label uses. One killer web site for this, that is power-pigs proof, would ROCK!!!. I bet they could sell advertising for pharmaceutical companies, at the same time as they accept anonymous donations of content, from "leakers"! Wikileaks leaks a lot of stuff about other stuff; WHERE is our web site for "leaks" about pharmaceuticals?!?!?!

  • Robert||

    It's called Medline.

  • WoodChipperBob||

    "Here we are, more than a year after Trump takes power and is supposedly "cleaning out the swamp", and absolute CRAP like this ain't fixed yet?!?! WTF?!??!"

    I'm guessing you missed the second to last paragraph, where it said, "In early January 2017, during the Obama administration's final few days, the FDA issued a rule on "intended uses" that reiterated its view that off-label promotion renders a drug or medical device criminally mislabeled. The incoming Trump administration put a hold on that and all other new regulations, choosing to implement some and reverse many others. The FDA's intended-use rule was among those chosen for additional review, suggesting that the new administration may not let it go forward—and may, in fact, rewrite the document to clarify what kinds of off-label promotion will be considered legal. A final decision is expected sometime this month," Cleaning out the swamp actually takes time, if you want to avoid throwing a whole lot of babies out with the bath water. And while I'm not convinced that the Trump administration really intends to clean out the swamp, I haven't seen any evidence that they don't.

  • C. S. P. Schofield||

    ""the FDA exaggerates its overall place in the universe,""

    Why should it be any different from any other government agency?

  • Frank White||

    The most powerful off-label drug info I know: Want to avoid heart disease? Drop the statin and take low dose Viagra.

  • Ben of Houston||

    I have to say that I can't fully stand behind this.In fact, I believe that it is taking precisely the wrong tactic.

    Why? Airborne. A compound that is demonstrably useless, makes billions of dollars a year through what is essentially fraudulent advertisement. Homeopathy, a "science" that is essentially peddling of magic potions, runs rampant. People are being actively defrauded here.

    The restrictions on advertisement of medicine to what has been actively proven is a strong protection of the people. The problem isn't the ability to publish uncertain results. It's the FDA's ludicrous standards that make it a Herculean feat to prove water is wet. Reduce these to reasonable standards of evidence, and you can have the protection of the people without enabling the snake oil salesmen.

  • Robert||

    But the Homeopathic Pharmacopoeia of the US is included statutorily as among "official drugs", largely because US senator Royal was a homeopathic physician. FDA's just doing what Congress says.

  • Robert||

    As usual, I don't fault FDA in this, but Congress & the courts. (It'd be the same at the state level were cases to come up there.) Nearly all regul'n of classes of products by state & federal gov't is based on intended uses of the products, which inextricably ties restrictions on marketing to communication. As bad as it is concerning off-label use of drugs, what about the many products which FDA or att'ys gen'l go after as misbranded drugs of medical devices which aren't labeled for medical use at all? There it's all about inferences of unstated but supposedly intended uses. Lawmakers have long treated off-label use as a loophole by which a marketer can slyly get around all sales restrictions, effectively vitiating the restrictions & their supposed consumer protection entirely—for what would stop someone from marketing a product in the knowledge that it would be used as a drug (or any other regulated product class) without getting the product licensed as a drug (etc.) at all, putting no instructions on the label? Eventually 3rd-party payers would catch up to that new reality, doing their own research on the effectiveness of products.


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