Alan Cassels is a drug policy researcher in Victoria, British Columbia and a regular contributor to HealthNewsReview.org. Follow his writings on Twitter @akecassels.
Last August, the drug company Amarin won a court case that essentially granted them a protected “free speech” right to promote their fish oil-derived product Vascepa for off-label purposes. And this week, Amarin’s free speech rights were further upheld in a settlement with the FDA and U.S. government over the same issue.
This means that Amarin can continue to promote Vascepa for off-label purposes. The drug is currently approved to treat people with severely elevated triglycerides, and the company sued to be able to “engage in truthful and non-misleading speech promoting the off-label use of Vascepa.” Essentially the company could say that “supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease,” but in that ruling the company also had to disclose that the FDA has not approved Vascepa to reduce the risk of coronary heart disease.
Extensive coverage – including stories in the New York Times, Bloomberg, Associated Press and ABC News, US News and World Report — delivers a lot of details on the freedom of speech issues this court case raises. But the stories mostly fail to dig into the crucial consumer impact of what constitutes “on-label” or “off-label” use of a drug — and whether it’s a good idea to let drug companies promote off-label uses.
Setting the stakes
That distinction can have life or death consequences, says Larry Sasich, a consultant pharmacist who works for PatientDrugNews.com. He is also a former staffer at US Public Citizen’s Health Research Group and a long-time analyst of FDA decisions around drug approval and marketing. For him, the court decision is potentially precedent-setting and he stressed that there is a high value in the information contained in FDA approval documentation. He emphasized that because the FDA posts the studies and other information used to gain approval on its website (whereas some other jurisdictions, such as Canada, don’t), this means that “the information is verifiable, because it’s transparent.”
In the debate over off-label promotion, it’s important to recognize that there are both disadvantages and possible advantages to off-label use.
One of the potential benefits is that it allows physicians to try out treatments on patients for whom approved drugs have been ineffective, and so the approach might be useful when there are specific patient populations that haven’t been studied. Clearly off-label use is good for the drug manufacturers’ bottom line, but there are disadvantages in addition to safety concerns and the potential for wasted spending on ineffective treatments. One researcher noted that off-label drug use could “diminish public expectation that drugs will be evaluated for safety and efficacy before use” and may be a disincentive for companies to do the studies they need to do to get FDA label changes. Why conduct an expensive new study if doctors are already prescribing the drug for the unapproved use?
The importance of FDA labeling
Why is FDA approval so critical? An FDA review and approval that allows “on-label” use means FDA experts have pored over the published and unpublished studies of a drug’s safety and effectiveness, and created medication guides and professional product labels (“on label”) which are thorough and rigorous.
It’s important for reporters to “give some context–and this is difficult for journalists because of space limitations–but a reader might have no idea what ‘off label’ means,” Sasich says. “Journalists should know that this means that there is no evidence of benefit, or studies have been done and the drug has failed to show benefit.”
People need to know if the drugs they are taking for their particular circumstance have been tested and found useful. Sometimes it happens that drugs are being prescribed “off label” in patients for whom the drugs are specifically contraindicated, such as the use of the antidepressant paroxetine in adolescents or children, Sasich noted. That drug is not approved for children and adolescents because of the increased risk of suicide–and it says so on the label–so prescribing it “off-label” is likely to increase the harm to children.
“Patients need to know that many of the drug tragedies that the public has suffered for years and years and years were from off-label uses of drugs,” Sasich said.
Bextra case illustrates perils
The key issue here is not necessarily whether drugs are used off label, but whether they are promoted for off-label uses. One example that illustrates the dangers of this is the Cox-II inhibitor drug Bextra, sister drug to Vioxx, the worst drug disaster in recent memory. Pfizer sales reps promoted this drug widely for uses beyond its label (where it was only approved for arthritis and menstrual cramps) including for the treatment of acute pain at higher-than-recommended dosages. Pfizer’s push to use Bextra in patients with acute pain, such as patients just getting out of surgery, led to many more adverse effects than if it had been used in only the patients it was approved for. Bextra was eventually removed from the market in 2005 because of cardiac and skin-related adverse effects and the company faced over $2 billion in fines for off-label marketing of Bextra and other drugs.
As some legal scholars have argued, “Off-label promotion—pharmaceutical manufacturers’ marketing of FDA approved drugs for unapproved uses—is considered a First Amendment right by some, a threat to the safety and effectiveness of pharmaceutical drugs by others.” “Off-label” promotion certainly widens the boundaries of what a company can say about their product, but the extent to which this ruling will change the behavior of companies remains to be seen. As health news site STAT reported, this decision is unlikely to cause a rush of off-label promotion, but if Pfizer’s past behavior is any indication, where gross examples of off-label marketing resulted in tens of billions in sales (but only a few billion in penalties), companies will clearly try to exploit a potential new loophole if they see one here.
This story is sure to continue: As one law firm crowed: “Off-label promotion is an evolving area of law fraught with opportunities and pitfalls, including substantial fines and criminal sanctions.”