Off Label Drug Use Should Be Regulated For Patient Safety

[Update: the American Medical Association recently posted an article about how "off-label" marketing is so pervasive that many doctors don't even know what the approved purposes of the prescription drugs and medical devices are, exposing them to malpractice liability.]

The pharmaceutical defense lawyers at Drug & Device Law, one of my favorite blogs to throw rocks at (we went Jersey Shore over the Wellbutrin litigation a year ago), are at it again, this time attacking a legal theory they refer to as ‘FDA regulatory informed consent.’ Although drug companies aren’t allowed to market drugs for any purpose other than those purposes approved by the Food and Drug Administration (it’s called “off-label marketing” and it’s blatantly illegal), the FDA permits individual doctors to prescribe FDA-approved drugs for any purpose, creating a disconnect between FDA approval and actual medical practice. The FDA doesn’t do anything to regulate what doctors prescribe; the closest it comes to informed consent are its regulations for clinical trials.

Under the theory of FDA regulatory informed consent, physicians should be required to tell patients if the physician is prescribing a medication for a use not approved by the FDA. Jim Beck at Drug & Device Law thinks it’s a bad idea, and wrote his post in response to a new law review article, “The Case For Legal Regulation Of Physicians’ Off-Label Prescribing,” 86 Notre Dame L. Rev. 649 (2011)(online copy here), by Philip M. Rosoff, a professor at Duke Medical School, and Doriane Lambelet Coleman, a professor at Duke Law School. As Beck notes, most courts don’t accept the explicit version of this — i.e., the requirement that a doctor specifically say the drug or medical device isn’t FDA-approved — but, as Beck doesn’t note, some courts get awfully close. See, e.g., DeNeui v. Wellman, No. 2009 U.S. Dist. LEXIS 114853, at *11–14 (D.S.D. Dec. 9, 2009)(“a jury must determine whether a reasonable person would attach significance to the off-label use of [the medical device] before deciding whether to undergo the surgery in this case”); In re Diet Drug Litigation, 384 N.J. Super. 525, 895 A.2d 480 (Law Div. 2005)(distinguishing Blazoski v. Cook, holding “While obesity is a serious condition, phen-fen is hardly its only cure. While phen-fen may have provided real benefits for those who took it, these patients were entitled to know of its risks. And it is certainly foreseeable that, if advised of the risks, they might well have chosen alternatives.”).

I’m unsurprisingly more on Rosoff and Coleman’s side. I’ll explain.

First, a little bit of background on the subject. As I’ve discussed before, intense lobbying by drug companies — including infiltration of the supposedly neutral legal research groups like the American Law Institute, which publishes the various Restatements — has whittled away at most of the potential claims against defective drug manufacturers. The law’s so hostile to patients that even doctors think it’s too protective of drug companies. (At the same time, those same companies have lobbied for absurd laws like the Prescription Drug User Fee Act that penalize the FDA if it doesn’t approve drugs quickly enough; unsurprising, that has made drugs less safe and more likely to be withdrawn.)

If you try to sue a drug company for inadequately testing or improperly designing a drug, the drug company will cite FDA approval and shout “pre-emption,” arguing that the FDA already signed off on the drug’s safety and efficacy and that the courts aren’t allowed to second-guess that — even if neither the FDA nor Congress said they meant to foreclose tort lawsuits. Defense lawyers call that dubious argument “implied pre-emption.”

Courts will too often buy those arguments; consider the lengths to which Judge Posner jumped to deny a toxic epidermal necrolysis / Stevens-Johnson syndrome victim a $3.5 million jury award. I’m not sure why he bothered with that long and winding factual argument, leaping from assumption to assumption and begging his own questions; he could have just said, “I’d prefer they lose” and be done with it.

In short: under a variety of names (“implied preemption,” “learned intermediary,” “unavoidably unsafe product,” etc) the drug manufacturers routinely claim that FDA approval is the be-all, end-all of drug safety, and so no injured patient should ever be allowed to sue the manufacturer of an FDA-approved drug. It’s thus more than a little hypocritical for them or their lawyers to now claim that FDA approval is irrelevant to patients. It’s the sole reason they believe they’re entitled to special legal immunities not granted to other manufacturers.

Although every defective drug lawsuit these days alleges a variety of claims like strict liability, negligence, breach of warranty, and violations of consumer protection laws, in the end most of the prescription drug lawsuits tend to boil down to one type of claim: the “failure to warn” of a certain side-effect or problem with the drug. The Supreme Court held in Wyeth v. Levine that failure to warn cases could go forward, so patients’ lawyers have held on to that will all their might. All the big prescription drug cases these days — Accutane, Actos, Chantix, Darvon-Darvocet, Depakote, Fosamax, Plavix, Topamax, Yaz — are primarily failure to warn cases. The Accutane plaintiffs allege that Roche failed to warn about side effects like inflammatory bowel disease and birth defects. The Actos plaintiffs allege that Takeda failed to warn about an increased risk of bladder cancer. The Chantix plaintiffs allege that Pfizer failed to warn about the risk of depression and suicidal thoughts. Et cetera.

Lurking under the surface of many of these cases is the scourge of off-label marketing. You wouldn’t know it from Beck’s critique, but doctors and medical researchers have long fretted about off-label prescription. One study in 2006 found over 150 million off-label mentions by physicians each year — totalling over one-fifth of overall prescriptions — and found that three-quarters of those off label prescriptions had “little or no scientific support.”

Worse, many patients don’t know that doctors are allowed to prescribe drugs for unapproved and unsupported uses: “A 2006 poll suggests that much of the U.S. public is confused and ambivalent about off-label prescribing, with about half the respondents believing that physicians are permitted to prescribe drugs only for on-label indications and about half believing that physicians should be prohibited from prescribing drugs for off-label indications.” (Source).

In attacking the Rosoff–Coleman article, Beck goes into a long discussion about the bone screw litigation, an example Rosoff and Coleman raise, arguing there wasn’t any harm by the off-label use of the pedicle screws and concluding:

If Rosoff et al. couldn’t do their homework well enough to avoid branding well-established (no longer) off-label uses as “experimental,” we have zero confidence that, in practice, lawyers litigating cases (or judges adjudicating them) would be any more careful.

Bone screws aren’t my forte, but I happen to know something about the prescription drug litigation. Let’s take two of those drugs on my list above, Topamax and Depakote, both of which are anti-seizure and migraine medications known to cause birth defects.

Topamax was approved as an anti-epileptic drug, but not as psychiatric drug. That didn’t matter much to Ortho-McNeil Pharmaceutical, a Johnson & Johnson subsidiary, which:

[P]romoted the sale of Topamax for off-label psychiatric uses through a practice known as the “Doctor-for-a-Day” program. Using this program, Ortho-McNeil hired outside physicians to join sales representatives in their visits to the offices of health care providers and to speak at meetings and dinners about prescribing Topamax for unapproved uses and doses.

That’s from the Department of Justice’s press release announcing an $81 million settlement with the company. Topamax is still on the market, though, and so doctors can prescribe it for anything — including weight loss. Do I really need to explain why it’s bad for doctors to prescribe a Pregnancy Category D drug known to cause birth defects as a diet drug? Is it crazy to think that a woman in her child-bearing years might, just might, take into consideration the fact that the drug isn’t FDA-approved for weight loss when considering whether or not to take it?

Depakote similarly was approved to treat seizures, not psychiatric conditions (except for acute mania in bipolar disorder), yet Abbott Laboratories allegedly marketed it “as a treatment for agitation, aggression in the elderly and other uses not approved by the Food and Drug Administration.” “Allegedly” may only be the case for a few more weeks: the company reported a $1.5 billion charge to cover a potential settlement with the government over the off label marketing. Depakote is still routinely used to treat a variety of conditions like anxiety, post-traumatic stress disorder, obsessive compulsive disorder, and alcohol & drug addiction — despite not being approved for any of that.

These aren’t isolated incidents. Pfizer paid $2.3 billion to settle off-label claims relating to Bextra and other drugs. Eli Lilly paid $1.4 billion for Zyprexa marketing. AstraZeneca paid $520 for Seroquel. And on and on. Modern pharmaceutical companies are more marketing ventures than research endeavors. (Follow the money.)

The time in which a drug company could credibly argue that they just make medicines that doctors then independently decide to give to patients is long, long gone. As explained by the seminal case on the ‘learned intermediary’ doctrine — another effort by pharmaceutical companies to wash their hands of any responsibility — Perez v. Wyeth,

Our medical-legal jurisprudence is based on images of health care that no longer exist. At an earlier time, medical advice was received in the doctor’s office from a physician who most likely made house calls if needed. The patient usually paid a small sum of money to the doctor. Neighborhood pharmacists compounded prescribed medicines. Without being pejorative, it is safe to say that the prevailing attitude of law and medicine was that the “doctor knows best.”

Pharmaceutical manufacturers never advertised their products to patients, but rather directed all sales efforts at physicians. In this comforting setting, the law created an exception to the traditional duty of manufacturers to warn consumers directly of risks associated with the product as long as they warned health-care providers of those risks.

For good or ill, that has all changed. Medical services are in large measure provided by managed care organizations. Medicines are purchased in the pharmacy department of supermarkets and often paid for by third-party providers. Drug manufacturers now directly advertise products to consumers on the radio, television, the Internet, billboards on public transportation, and in magazines. For example, a recent magazine advertisement for a seasonal allergy medicine in which a person is standing in a pastoral field filled with grass and goldenrod, attests that to “TAKE [THE PRODUCT]” is to “TAKE CLEAR CONTROL.” Another recent ad features a former presidential candidate, encouraging the consumer to “take a little courage” to speak with “your physician.” The first ad features major side effects, encourages the reader to “talk to your doctor,” and lists a brief summary of risks and contraindications on the opposite page. The second ad provides a phone number and the name of the pharmaceutical company, but does not provide the name of the drug.

The question in this case, broadly stated, is whether our law should follow these changes in the marketplace or reflect the images of the past. We believe that when mass marketing of prescription drugs seeks to influence a patient’s choice of a drug, a pharmaceutical manufacturer that makes direct claims to consumers for the efficacy of its product should not be unqualifiedly relieved of a duty to provide proper warnings of the dangers or side effects of the product.

The same is true of off label prescriptions: for better or worse, we live in a new world in which pharmaceutical companies spend billions of dollars manipulating consumers and physicians into using prescription drugs for unapproved purposes. You can’t drive a car that isn’t approved by the Department of Transportation — why should patents unknowingly be prescribed drugs for unapproved purposes?

Moreover, like with all tort law, we should weigh the benefits of liability versus the costs of non-liability. What is so difficult about having doctors spend ten seconds on their computer before the patient visit (or ten seconds on their smartphone during the visit) to confirm what the FDA approved uses are and reveal those to the patient? The Epocrates app is free. The Medscape app is free. Don’t have an iPhone? Just Google the drug’s name: Google will automatically put a direct link to the Library of Medicine’s PubMed page on that drug at the top of the list.

There’s evidence that the more information a patient receives, the safer a choice they will make, like this study from last month in the Archives of Internal Medicine. Of course, a patient could do the same thing — but patients aren’t trained for years, licensed by the state, and then paid to advise themselves on their own medication.

That’s the doctor’s job. The doctor can do it right. That’s what they swore they would do, way back in medical school. No amount of pharmaceutical company lobbying should interfere with that.

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  • http://thoughts4thesoul.wordpress.com Moshe Sharon

    I believe that doctors can prescribe drugs for off-label use with impunity because as long as he can testify that he did so in good faith in the hope of curing or slowing down the progression of a disease, there is no liability. The legal status of permitting doctors to prescribe any drug for any purpose is an indictment of the FDA’s drug approval process. The efficacy and side effect studies are all shamefully biased being funded and controlled by the manufacturers who are highly motivated to show results that will win FDA approval.

  • http://www.facebook.com/people/Tom-Sharon/748286406 Tom Sharon

    The for the most part, doctors have a great deal of latitude in prescribing for off-label use. But, when a doctor prescribes a drug or medical device, he/she still has to check the label for contraindications and other warnings and he has to be able to demonstrate that he prescribed said drug for said off-label use in good faith. There has to be some logical reason for prescribing the off-label use, like a study published in a peer review journal or reports of a beneficial side effect like the hair-growing effect of Minoxidil discovered in the 1970′s. These are the kinds of issues that attorneys should address when considering a lawsuit for damages arising from off-label prescribing.