Doctor promoting drug

First Amendment Protects “Truthful, Non-Misleading” Off Label Promotion, NY Judge Rules

When Kim Kardashian West publishes photos on Instagram, she probably doesn’t expect a response from the US Food & Drug Administration. But that’s just what the reality TV star, wife of Kanye West and expectant mother received after she uploaded a photo promoting the benefits of Diclegis, America’s only drug approved for the treatment of morning sickness.

In a letter sent to Canadian drug manufacturer Duchesnay, the FDA wrote “the Kim Kardashian Social Media Post […] is false or misleading in that it presents efficacy claims for Diclegis, but fails to communicate any risk information.” Kardashian removed the picture, and all that remains is an error message:

Kim Kardashian Morning Sickness Drug Instagram

High standards: Kim Kardashian’s Instagram about Diclegis has since been removed.

No one would deny that this is a high standard to apply to a celebrity. But a recent court decision in New York may significantly loosen that standard for pharmaceutical manufacturers.

“Truthful” Off Label Promotion Protected As Free Speech, Rules New York Federal Judge

Connecticut’s Amarin Pharmaceutical manufactures Vascepa, an Omega-3 fatty acid drug used to lower triglyceride levels in patients with excessive fats in their blood. But it is approved only for patients with severely high triglycerides, above 500 milligrams per deciliter (ml / dL).

If a physician prescribes Vascepa to a patient with “persistently high” triglycerides, between 200 and 499 ml / dL, it is considered “off label use.”

Vascepa, Denied Approval Over Efficacy Doubts, Sparks First Amendment Dispute

Amarin has sought approval for this extended use, but was denied because, as Paul A. Engelmayer, District Judge for Manhattan’s Federal District Court writes, “recent scientific studies have left it unclear whether reducing the triglyceride levels of persons with persistently high triglycerides reduces cardiovascular risk.”

In other words, Amarin has failed to demonstrate that Vascepa presents any additional benefits over pre-existing treatments for patients with persistently high triglyceride levels, even though the drug has been shown to reduce overall triglyceride levels in these patients.

The FDA asked for more evidence, proof that Vascepa could improve cardiovascular outcomes in patients with high, but not severe, triglycerides. The agency then said that Amarin could be charged for “misbranding” a drug, if the company promoted Vascepa as being effective for the extended patient population.

So Amarin sued the FDA. Prohibiting it “from making completely truthful and non-misleading statements about its product to sophisticated healthcare professionals” violated the company’s First Amendment rights, Amarin argued.

Free Speech: Between Truth & Fraud

On August 7, 2015, a Judge in the US District Court for the Southern District of New York agreed, deciding that the FDA’s injunction against “off label” statements had, in this case, infringed upon a pharmaceutical manufacturer’s Constitutional rights.

Judge Engelmayer ruled that, insofar as Amarin’s statements are “truthful and non-misleading,” they are protected by the First Amendment. You can find a copy of Engelmayer’s decision here.

As the New York Times pointed out, what a sales representative leaves unsaid may be just as important as what is said. A company’s claims must be both truthful, supported by sufficient scientific evidence, and “non-misleading”; in Kim Kardashian’s case, this meant mentioning both Diclegis’ benefits and its risks.

While Engelmayer’s decision applies only to Amarin’s case, many in the legal and medical communities believe the FDA will appeal the ruling in the near future.

Update March 9, 2016 – FDA Will Not Appeal Amarin Decision, Allows Off-Label Promotion Of Omega-3 Drug

On Tuesday, March 8, Amarin announced that it had settled its case against the Food & Drug Administration, and the agency will not be appealing Judge Engelmayer’s ruling. FDA sources have downplayed the agreement, which will allow Amarin to continue promoting its Omega-3 drug Vascepa for unapproved uses, as long as the company’s statements are in line with current scientific research. “Narrow and specific” is how the FDA is framing the decision, according to the Washington Post; the settlement “does not signify a position on the First Amendment and commercial speech.”

Legal experts, however, have taken a slightly different position, saying the FDA’s willingness to settle, and thus allow Amarin’s off-label promotion, may open the door for other manufacturers hoping to “negotiate” with the regulatory agency.

Other observers have questioned the very definition of “truth” in this context, since numerous studies have found that pharmaceutical manufacturers routinely “game” clinical trials to inflate the benefits and minimize the risks of their products.

A case in point may be the US Department of Justice’s recent case against GlaxoSmithKline, manufacturer of Zofran.

“Off Label” Promotion: GlaxoSmithKline & Zofran

In 2012, patients across the country were shocked to learn that the US Department of Justice (DOJ) had filed criminal and civil charges against GlaxoSmithKline, claiming the pharmaceutical manufacturer had promoted several drugs unlawfully.

In a wealth of court documents soon made public, the Federal Government said Glaxo had marketed Paxil, Wellbutrin, Advair, Lamictal and Zofran for unapproved (or “off label”) uses, in violation of the Food, Drug and Cosmetic Act.

In a press release accompanying Glaxo’s eventual settlement agreement, the DOJ described the practice of “off label” promotion like this:

“Under the provisions of the Food, Drug and Cosmetic Act, a company in its application to the FDA must specify each intended use of a drug. After the FDA approves the product as safe and effective for a specified use, a company’s promotional activities must be limited to the intended uses that FDA approved. In fact, promotion by the manufacturer for other uses – known as ‘off-label’ uses’ – renders the product ‘misbranded.’ “

According to Federal allegations, GlaxoSmithKline:

  • promoted Paxil, an anti-depressant, for use in patients under the age of 18, despite the fact that the FDA has never approved it for pediatric patients,
  • promoted Wellbutrin, an anti-depressant at the time only approved for Major Depressive Disorder, as a treatment for sexual dysfunction, substance abuse and Attention Deficit Hyperactivity Disorder (ADHD),
  • promoted Advair, an asthma medication approved solely as a secondary treatment after initial options have been exhausted, as a “first-line therapy for mild asthma patients,”
  • promoted Lamictal for neuropathic pain management, in spite of its approval only covering patients with epilepsy.

That these allegations were leveled by America’s main criminal enforcement organization only helped substantiate their accuracy in the eyes of many industry watchdogs. But public outcry may have been strongest around the drug Zofran.

Promoting Off Label Was Glaxo’s “Corporate Strategy,” Says Federal Government

A potent “anti-emetic,” or anti-nausea drug, Zofran has never been approved for any patients other than those being treated for cancer with chemo- and radiotherapies, as well as those undergoing operative anesthesia.

Notwithstanding a total lack of clinical evidence demonstrating Zofran’s safety (or effectiveness) in treating pregnancy-related nausea, the US Federal Government charged GlaxoSmithKline for promoting the drug directly to obstetricians and gynecologists as a safe and effective morning sickness remedy.

The sheer number of drugs implicated in the Government’s “off label” allegations could lead a critic to think that unapproved marketing may be a common practice among GlaxoSmithKline’s sales representatives. Indeed, the DOJ frequently referred to Glaxo’s “off label” promotions not as the work of isolated individuals, but as a “corporate strategy” (as seen here, p. 20).

Truth May Be Key, But Who Decides?

Ben Goldacre, a physician and academic, has suggested that pharmaceutical companies systematically misrepresent the risks and benefits of their products, both in marketing materials intended for physicians and direct-to-consumer advertising (which is only legal in the United States and New Zealand). We covered Goldacre’s findings extensively in our article “Science For Sale: How Big Pharma Controls Drug Research.”

But with the recent Court decision’s emphasis firmly on the “truthfulness” of a drug company’s “off label” claims, Goldacre’s suggestion that manufacturers design and publicize even clinical trials to inflate the benefits of their products becomes particularly distressing.

We have to ask an important question: how do we know that a manufacturer’s “truth” is actually the truth?