By Molly Knobler and Tim McCormack
Two closely watched and much-debated court cases, Amarin and Caronia, have largely given pharmaceutical companies the green light to promote their drugs for uses not approved by the FDA -- also known as "off-label marketing." But in the end, this may prove to be a pyrrhic victory for big pharma. Neither decision permits false or misleading speech such as sales pitches that omit material safety information or misrepresent scientific findings. This activity remains actionable by the FDA as "misbranding" and has formed the basis for billions of dollars in False Claims Act recoveries (the lawsuits that truly strike terror into the hearts of pharmaceutical executives around the world).
In fact, many of the significant "off-label marketing" False Claims Act cases pursued by the government or whistleblowers over the last 15 years, have involved allegations of false or misleading statements about a drug's safety or efficacy. In these cases, the government's focus on a statement's off-label bent was often a simple evidentiary way to address speech that was also misleading in other respects. So while there is no question that courts have limited the government's ability to go after "off-label" marketing per se, the FDA should view this as an invitation to redirect their regulatory sights on the adequacy and veracity of the wide array of promotional speech undertaken by pharma companies.
In that vein, the FDA's recent actions to correct Kim Kardashian's representations on Instagram are promising. Kardashian, a paid spokesperson for Diclegis, posted a photo of herself with the drug to Instagram, counseling her followers that, "I felt a lot better and most importantly, it's been studied and there was no increased risk to the baby." The FDA objected to Kardashian's post, not on the grounds that it promoted Diclegis off-label (it is FDA-approved to treat morning sickness), but on the grounds that it failed to give a complete safety profile of the drug.
Unfortunately, misleading pharmaceutical marketing can be far more insidious than Kardashian's social media flub, and it is with these more serious transgressions that the FDA must keep a careful eye. For example, last week, reports of "mutant super lice" went viral. Major news outlets ran stories proclaiming impending doom from treatment-resistant lice. The furor -- which just happened to occur in the middle of back-to-school season -- was caused by two research scientists publicizing the results of a study they presented to the American Chemical Society. Based on their (as yet unpublished) study results, the scientists pronounced that over-the-counter (OTC) lice shampoos are no longer effective and much more expensive prescription products should be used instead.
Although the scientists' research was funded, in part, by Sanofi Pasteur, a drug company that makes one of these expensive prescription anti-lice treatments, there is no indication that the scientists have been paid directly to promote these prescription treatments. The nature of their media campaign against OTC alternatives is notable, though, because it mirrors the way that pharmaceutical companies often use limited, or scientifically questionable, studies to promote their drugs.
The authors of the study, Kyong Sup Yoon, Ph.D., a professor of biology and toxicology at Southern Illinois University, and John Clark, Ph.D., a professor of toxicology at the University of Massachusetts Amherst, have repeatedly claimed that OTC lice treatments simply do not work. Dr. Yoon even told U.S. News that treatment with OTC shampoos would probably make things "worse rather than better."
But it is far from clear that Yoon and Clark's research actually supports this conclusion. They report their study shows a high prevalence of lice with genetic mutations more likely to make them resistant to pyrethroids, the chemicals found in OTC lice treatments. But Remy Durand, PharmD, PhD, HDR, a researcher in the Department of Parasitology and Mycology at Hôpital Avicenne, points out that "[t]he relationship between clinical and genetic resistance is still debated." Even Dr. Yoon, in an earlier study, recognized that "the presence of [these genetic mutations] alone may not directly predict clinical failure."
Moreover, even if OTC treatments are declining in effectiveness, there may still be good reasons to keep them as the first line of defense. Specifically, they are generally safer (Dr. Yoon called them "enormously safe") and cheaper ($20 versus $300 per treatment) than the prescription alternatives. For these reasons, many doctors recommend OTC treatment before trying prescription drugs, even after hearing about Yoon and Clark's research. See here, here, and here.
Another problem with Yoon and Clark's media blitz is that they fail, in their more quotable moments, to emphasize a significant limitation of their study methodology. In their 2014 article they acknowledged that they did not take into account whether the lice were collected from patients who had already attempted OTC treatment. Accordingly, they warned that the "results should be interpreted cautiously in that the number of lice collected and analyzed [were biased] possibly to lice collected from subjects whose infestations had already been treated with permethrin or similar product." This means it is possible that some or all of the samples taken in the study were from patients who already killed off the non-resistant lice with OTC treatments. Even worse, it is possible that people who were infected with non-resistant lice were functionally excluded from the sample because OTC treatments worked. It is unclear whether they controlled for this in the 2015 study, but given their description of the 2015 study as a "follow-up" it seems likely they used the same collection processes. What is clear, though, is that this key issue was not discussed in the 2015 media tour.
This is the new battleground for FDA regulation: drug companies funding research relevant to their drugs, flogging the results of biased and limited studies to doctors and consumers alike, and attempting to cover their tracks with limited small-print disclosures that no one pays attention to while attractive spokespeople with big CVs give half the story. Let's hope the FDA is ready.