What happens when one of the most powerful regulatory bodies in the country orders a business to violate the agency's own rules? If they don't want to make waves, company executives follow the order, cross their fingers and hope the regulators won't punish them later. But this month, one company will have the courage to go to court and tell the regulators they've gone too far.
On April 26 California-based drug manufacturer Allergan will seek a court ruling that the Food and Drug Administration may not ban the distribution of truthful information about safe and effective uses of medicines that the agency has already approved for other conditions. It could be years before the case is finally resolved, but an Allergan victory would be a huge boon for millions of American patients who rely on so-called "off-label" uses.
Before they can be sold in the U.S., every new medicine must be certified by the FDA as safe and effective for a specific, or "on-label," use. But, once approved, physicians may legally prescribe drugs for any safe and effective off-label indication.
Allergan's drug Botox has been approved for treating muscle spasms in the neck and eyes, as well as for its more popular cosmetic purposes. But it is widely used off-label to treat various other muscle spasticity conditions, as well as speech impediments and migraine headaches.
Last September the FDA ordered Allergan to send detailed safety updates to physicians who prescribe Botox for both on-label and off-label indications. But fully complying with the order could violate an FDA ban on promoting drugs for off-label uses. Ironically, doctors will have less information about patient safety if Allergan follows the FDA's off-label rules.
Botox isn't unique. By some estimates, at least 20% of all prescriptions written are off-label, and those uses often constitute the medically recognized standard of care. The practice is ubiquitous in cancer and cardiac treatment, where as many as half of all prescriptions are for off-label uses. If not for off-label prescribing, millions of patients would have fewer treatment options, and many would die.
Off-label prescribing is controversial with regulators and some politicians, who view it as a way to shortcut clinical testing and skirt the FDA approval process. But the American Medical Association says that "physicians have the training and experience to determine the best or preferred method of treatment," and that off-label prescribing should often be considered "reasonable and necessary medical care, irrespective of labeling." In fact, doctors can be subject to malpractice liability if they do not use drugs for off-label indications when doing so constitutes the standard of care.
Still, the FDA uses its authority over drug labeling and promotion to prevent manufacturers from disseminating almost any information about off-label uses, even to doctors. Drug firms may send peer-reviewed medical journal articles and excerpts from medical text books to physicians. And, in some circumstances, they can answer questions asked directly by physicians. Nearly everything else is forbidden.
The FDA and federal prosecutors take these restrictions very seriously, charging violators with both civil and criminal sanctions. In 2009 drug manufacturer Pfizer pleaded guilty to criminal charges and paid a record $2.3 billion to settle allegations of promoting 14 of its products for off-label uses. And Eli Lilly was forced to pay $1.4 billion for promoting its schizophrenia drug Zyprexa for off-label use.
Earlier this year the FDA even sent a warning letter to a Florida dermatologist for mentioning in interviews with Elle and Allure magazines and NBC's Today show that an anti-wrinkle drug she was testing had shown positive results and that "early data shows it may last longer and kick in faster than Botox."
You can see why Allergan was hesitant to comply with the FDA's order. Sending doctors information about patient selection, dosage and appropriate injection sites for off-label uses could subject Allergan to millions of dollars in fines and threaten the company and its employees with criminal penalties.
These restrictions raise serious constitutional questions, however. In 1999 a federal district court held that the FDA's near-blanket ban on the dissemination of truthful and non-misleading information about off-label uses was an unconstitutional restriction of commercial speech. The agency only avoided having its regulations totally invalidated by claiming that they did not really ban most forms of off-label promotion. Aside from the journal article exemption, though, the FDA won't tell anyone what is and is not permitted. And, in practice, the agency refuses to permit distribution of any other kinds of information about off-label uses.
That surely is why Allergan felt it had no other choice but to seek clarity from the courts. The company acknowledges that the FDA may forbid false or misleading claims, but has petitioned the court to hold the FDA's near total ban on truthful and non-misleading information unconstitutional. In a landmark 2002 case involving advertising by pharmacists, the U.S. Supreme Court concluded that the "First Amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good."
It is long past time for the FDA to admit that permitting truth in advertising really is the best medicine.