An Off-Label Conundrum

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            The legal community is still buzzing about the Second Circuit’s decision in United States v. Caronia, ___ F.3d ___, 2012 WL 5992141 (2d Cir. Dec. 3, 2012) and what it bodes for the future.  Whatever its eventual implications, today, it is important to remember that the FDA bans off-label promotion and that there remains a lot of litigation about “illegal” off-label promotion.  That’s right, illegal.  Off-label promotion, even if scientifically sound, useful or even critical to physicians, is still breaking the law (at least outside the Second Circuit).  So our clients get sued, a lot, for allegedly doing it.              Fortunately, defendants have been fairly successful in defeating product liability claims based solely on off-label promotion because off-label promotion, while perhaps unlawful, is not a tort.  Without something more, such claims are simply an attempt to bring a private cause of action for off-label promotion violations of the FDCA.  Numerous courts have so held.  But it is still illegal.   So, even if private litigants can’t recover for off-label promotion, drug and device companies are still subject to suit by the government.  So, in general our clients are very sensitive and extremely cautious when it comes to saying or doing anything not FDA-approved.  And while that may protect against FDCA-based criminal actions, it leaves open the door to failure to warn claims.            Then the plaintiff’s allegation isn’t “you said too much” (off-label promotion) – it’s “you’ve said too little” (failure to warn).  Talk about walking a fine line.  Drug and device manufacturers are like Nik Wallenda balancing above Niagara Falls.  Harnessed or not, a fall from that height is heart-stoppingly scary.  So, what to do?  How much can you say to provide an adequate warning about an off-label use while not violating the FDCA?  That was precisely the conundrum faced by the defendant in Wells v. Allergan Inc., 2013 U.S. Dist. LEXIS 13191 (W.D. Okla. Jan. 31, 2013).  And the court left them damned if they do and damned if they don’t.            The product at issue was Botox that was used to treat pediatric limb spasticity – an off-label use.  Id. at *2.  The labeling history is important so here are a few details.  Based on studies and reports concerning the link between Botox and botulism, especially in pediatric use cases, Allergan twice proposed to FDA labeling that included a warning that in pediatric trials for cerebral palsy, “doses greater than 8 U/kg have not been adequately studied.”  Id. at 2-3.  The FDA rejected Allergan’s proposed warning because cerebral palsy “is not an approved use in the United States.”  Id.  at *3.  About one year later, the FDA began requiring a black box warning on Botox and distribution of a medication guide for patients.  “Neither the FDA’s new label warning nor the medication guide included Allergan’s previously suggested 8 U/kg language.”  Id. at *4.  The black box did provide a warning about the possibility of botulinum toxin effects, including that “[t]he risk of symptoms is probably greatest in children treated for spasticity . . . [and] have occurred at doses comparable to those used to treat cervical dystonia and at lower doses.”  Id.  This warning was in effect at the time Botox was prescribed to the plaintiff.  Id. at *5.              Years before the black box warning and before this plaintiff was ever treated with Botox, his prescriber requested information from Allergan about “maximum dosing levels for pediatric spasticity and information on cases of botulism following Botox use in children.”  Id. at *6.  In its response, Allergan did not include information about the 8 U/kg dosing level but did provide two post-marketing reports of pediatric botulism.  Id.   This is the crux of plaintiff’s failure to warn claim.            Not surprisingly, Allergan pointed to the FDA-required black box warning addressing the very risk sustained by plaintiff as proof that they provided an adequate warning.  But the court didn’t agree that that was enough.  Instead the court found that the adequacy of the warning was a fact issue for the jury based on “Allergan’s evasive response to Dr. Wright’s direct inquiry in 2007.”  Id. at 15.  Evasive?  What the court found as evasive, we would argue is more accurately a manufacturer attempting to comply with the FDA’s ban on off-label promotion.  Remember that tightrope – well how about this for a balancing act:  “Because this case involves an off-label use, Allergan should have been particularly forthcoming when asked information relating to a specific question by an individual doctor.”  Id. at *15-16.  Particularly forthcoming about an off-label use.  How is a manufacturer supposed to reconcile his FDCA obligations to not promote off-label uses with a state law requirement to discuss off-label uses in detail?  Sounds like conflict preemption to us, but we’ll get to what the court said about that in a minute.            Before we leave the adequacy of the warning discussion, we have to point out that the court and plaintiff are relying on information that was provided to the prescriber three years before he treated the plaintiff.  To the extent that information may have been lacking, it was superseded by an FDA-mandated black box warning about the very risk at issue.  In fact, the prescriber changed his informed consent to include the box warning about botulinum toxin.  Id. at *8.  It is difficult to understand how such a warning is not adequate as a matter of law.       So, we think on that point the court simply got it wrong and then went on to muddy the waters as to how much a manufacturer should say about off-label uses.            Now on to preemption.  While Wyeth v. Levine, 555 U.S. 555 (2009), doesn’t leave brand defendants a lot to work with, there are still arguments to be made.  Such as the fact that the FDA specifically rejected Allergan’s proposed warning that included 8 U/kg dosing information.  So any state law requirement that Allergan provide such information to doctors is in conflict with federal law and therefore preempted.  Not so says Wells, which distinguished this case from an earlier case from the same court – Dobbs v. Wyeth Pharmaceuticals, 797 F. Supp.2d 1264 (W.D. Okla. 2011).  We’ve discussed Dobbs here.  In Dobbs, the proposed warning was rejected because it lacked scientific support.  In Wells, the court rejected conflict preemption finding that the “FDA clearly explained that it rejected Allergan’s proposal [not because of science, but] because of fears of back-door off-label promotion.”  Wells, at *19-20.              How does that get around conflict preemption?  The FDA said you can’t discuss the dosing information because it is off-label promotion.  Off-label promotion violates federal law.  This court’s ruling would require Allergan to provide information that they have already been told by the FDA is impermissible off-label promotion.   There’s your conflict.   There’s your conundrum.              It is quite conceivable that the very language this court would require to defeat a failure to warn claim would give rise to criminal allegations by the FDA – regardless of the truth and accuracy of the statements.  That can’t be the answer.  Which  brings us full circle back to Caronia.  One of the possible implications of Caronia, as we’ve previously suggested, is that the FDA will have to abandon its off-label promotion ban in favor of First Amendment-compliant “time, place and manner” restrictions.  The hope is that this will help with conflict preemption – more requirements, more opportunities for common-law claims to conflict with them.  We certainly think that would help in this situation, at least to provide the manufacturers with true procedures for communicating accurate information to physicians.  Until then, we may be stuck with damned if you do, damned if you don’t.