We see so many cases alleging “illegal” promotion of off-label use that when we find one where the plaintiffs don’t make that sort of allegation, it makes us sit up and take notice. That’s the case with Meharg v. I-Flow Corp., No. 1:08-cv-184-WTL-TAB, slip op. (S.D. Ind. March 1, 2010). It’s a pain pump case – the allegations being that these pumps, which are used after shoulder surgery, continuously “infused” various types of anesthetics intended to (evidently successfully) reduce post surgical pain, but that the continuous exposure (or anything else a creative expert might come up with to blame on defendants) caused long-term deterioration (“chondrolysis”) of shoulder cartilage.

The pumps (which are FDA approved) are machines, and of course machines don’t care what you put in them – they’ll infuse it. Thus, the most interesting aspect of pain pump cases we’d seen prior to Meharg had to do with product identification. That is, plaintiffs have been trying to sue various drug companies without even being able to allege the the defendant’s drug was actually used. That’s a no-no, and it’s produced some favorable decisions reaffirming the rule that a plaintiff can only sue the manufacturer of a product s/he actually used. Timmons v. Linvatec Corp., ___ F.R.D. ___, 2010 WL 476661, at *3-4 (C.D. Cal. Feb. 9, 2010); Haskins v. Zimmer Holdings Inc., 2010 WL 342552, at *2 (D. Vt. Jan. 29, 2010); Gilmore v. DJO Inc., 663 F. Supp.2d 856, 860-61 (D. Ariz. 2009); Combs v. Stryker Corp., 2009 WL 4929110, at *2-3 (E.D. Cal. Dec. 14, 2009); Dittman v. DJO, LLC, 2009 WL 3246128, at *3 (D. Colo. Oct. 5, 2009); Sherman v. Stryker Corp., 2009 WL 2241664 at *5 (C.D. Cal. March 30, 2009). These pain pump cases are yet another reason why we like Twombly/Iqbal.

We expect that the pain pump litigation will continue producing decisions on weird points, because the plaintiffs will be suing the wrong defendants, the manufacturers of the drugs used in the pumps, over injuries that were caused, not so much by the drugs, but by how the drugs were continuously infused by the pumps – if there’s any causation at all, that is. In fact, we can almost guarantee it.

Why?

Preemption.

These pain pumps (at least in cases where we’ve seen it discussed) are Class III devices. That means the cases against the manufacturers aren’t very likely to succeed under Riegel v. Medtronic, Inc., 552 U.S. 312 (2008), and the manufacturers will either get out on preemption, e.g., Wolicki-Gables v. Arrow International, Inc., 641 F. Supp.2d 1270 (M.D. Fla. 2009), or they’ll settle out cheap and take their chances with more attenuated – but at least not preempted – claims against the drug manufacturers. That’s what looks like happened in Meharg. The court mentions that the medical device claims had been settled.  Slip op. at 3 n.4.

The claim in Meharg, which is essentially an attempt to blind-side a manufacturer with liability for an off-label use that it neither encouraged nor promoted, is one of those weird theories. But plaintiffs didn’t get very far.

Why?

The state of the art defense.

It appears from Meharg that the continuous infusion of these local anesthetics is a lot different than their occasional injection (or other application) on a one-shot (really bad pun) basis. Continuous infusion isn’t what these drugs were approved for, and since the off-label use wasn’t (even the plaintiffs agreed – which is saying something) anything the defendants made any attempt to encourage, the defendant didn’t know about side effects peculiar to off-label use.

Since it’s the state of the art defense, the key date is when the product was used.  Here that’s technically the drug, not the device, but it doesn’t matter (it might in other cases).  That date is February, 2006.  Remember that fact.

We haven’t posted a lot about the state of the art defense on this blog, but when we did, we did so thoroughly. For a general discussion of why it’s not a good thing to hold drug/device manufacturers liable for not warning of risks that were unknown or undiscovered at the time of use, see here.

In that post we included one of our 50-state surveys of the states that had adopted that state of the art defense in drug/device cases. We provided citations to cases from 42 states – check that – 40 states, Puerto Rico, and the District of Columbia. It so happens that Indiana was on that list:

Indiana: Ortho Pharmaceutical Corporation v. Chapman, 388 N.E.2d 541, 548 (Ind. App. 1979); Phelps v. Sherwood Medical Industries, 836 F.2d 296, 305-06 (7th Cir. 1987).

Meharg is an Indiana law case.  That’s why (one reason, anyway) the plaintiff in Meharg lost – umm … that is, because of the state of the art defense, not because we included Indiana in our blog post.

The court in Meharg went right to Chapman, and stated:

In Ortho Pharmaceutical Corp. v. Chapman, 388 N.E.2d 541, 548 (Ind. App. 1979), the Indiana Court of Appeals held that in the context of a prescription drug manufacturer, “the duty to warn. . .does not arise until the manufacturer knows or should know of the risk” and that “the standard of constructive knowledge is that of an expert in that particular field.”  In cases such as this one that involve an off-label use of a prescription drug that is not endorsed or promoted by the manufacturer, the requisite knowledge of the risk is two-fold:  the manufacturer must know (or be charged with knowledge of) both that the off-label use is occurring and that the off-label use carries with it the risk of the harm at issue–in this case, damage to cartilage.

Meharg, slip op. at 4.

By relying on Chapman, the court quite consciously avoided a legal thicket that exists with respect to the duty to warn in cases of off-label use.  Meharg, slip op. at 4-5 n.6. The courts have never really settled on an approach to off-label use generally, and the rationales run the gamut from no duty at all (on the theory the off-label use is a form of misuse) to no discernable difference from warning about labeled uses. The various approaches are well summarized in Blain v. Smithkline Beecham Corp., 240 F.R.D. 179, 194-95 (E.D. Pa. 2007), and if you want all the gory details, they’re in Bexis’ book at the end of §2.20[1].

The plaintiffs, it turns out, didn’t have much to support the weird unpromoted off-label use cause of action. That’s not to say they didn’t try, but in the end their own expert – the ubiquitous Suzanne Parisian – slit their throat. She (or rather the plaintiffs’ lawyers who undoubtedly spoon feed their experts the only things they’re allowed to look at) was unable to find anything in the medical literature before the product use in this case.

There were some very generalized statements about infusions of other products. Meharg, slip op. at 5-6. Not helpful, with this defendant.  As we pointed out earlier, liability must be defendant (and thus drug) specific.  There were two pre-use studies that also didn’t help, because neither study’s authors suspected that the drug was implicated in the injury.  Id. at 6.  One of those studies, we note, the manufacturer probably couldn’t even have been disseminated to doctors under 21 C.F.R. §99.101(b)(v), because it only involved “one case.”  This is off-label use land, remember, and the rules are different (but more on that later).  In short, both of the studies that Dr. Parisian’s Declaration brought to the court’s attention reinforced the defendant’s point that nobody suspected the risk in question at the relevant time.

But that pales to what else Dr. Parisian stated. She expressly said in her declaration that the defendant should have taken steps to warn after it received certain specific “spontaneous reports.”  Slip op. at 7. However, as the court pointed out, that was “something that occurred on June 9, 2006, after Meharg’s surgery.” Id. at 8 (emphasis original).

Oops. Dr. Parisian (or maybe counsel) really walked into one there.

That something was the state of the art defense.  It’s nice, in litigation to have a ruling early on that the state of the art defense applies as a matter of law on a date certain – if you’re a defendant, that is.

Dr. Parisian tried to salvage things by putting on her lawyer hat (which she shouldn’t be allowed to do at all, but that’s another story), and concocting an even weirder theory.  She claimed there should be a duty to warn about possible risks of possible off-label uses.  So, even if you’re not promoting an off-label use, Parisian would impose a duty to research them.  The number of possible off-label uses is nigh on infinite, but of course that doesn’t bother a plaintiffs’ expert.  It did, however, bother the court.  Thus, we have this nifty language in the closing footnote of the opinion:

This “duty” does not exist under Indiana law. . . .  Dr. Parisian urges a far broader duty–a duty to warn physicians that there might be a risk, but we don’t know yet because we (and the scientific community at large) haven’t studied it yet.  Requiring such warnings regarding an off-label use in the absence of a known risk would be highly inefficient:  it would drain the resources of drug companies; it would cause physicians to be inundated with such pseudo-warnings and risk distracting them from heeding warnings of actual risk; and it would add very little to the fact that physicians already know that if a use is omitted from a prescription drug’s label that use has not been tested sufficiently to demonstrate that it is safe and effective.  Further, the Court notes that [plaintiff] expressly disavows the position that “simply saying that the use was not approved satisfies [defendant]’s duty,” and argues instead that [defendant] was required to provide “[a] clear cautionary statement setting forth the exact nature of the dangers involved.”  The problem with that argument is the fact that the “exact nature of the dangers involved” simply was not known prior to Meharg’s surgery.

Slip op. at 8 n.9 (emphasis original) (various citations omitted).  So if you need a ringing rejection of a duty-to research claim – here it is.  A plaintiff should not be allowed to slip the bounds of the state of the art simply by arguing a duty to conduct research.  At some point the real world is simply the real world.

And now the preemption point – it isn’t in the opinion, but it came to us while we were writing about it.  It goes back to the off-label angle. It so happens that the FDA is notoriously picky about what it allows manufacturers to say about off-label uses. We’ve written lots of First Amendment posts on that.  Ordinarily, a drug’s labeling is strictly limited to statements about its labeled uses.  There is, however, an equivalent to the CBE requirement for strengthening off-label warnings. It’s found in 21 C.F.R. §201.57(c)(6)(i):

In accordance with §§314.70 and 601.12 of this chapter, the labeling must be revised to include a warning about a clinically significant hazard as soon as there is reasonable evidence of a causal association with a drug; a causal relationship need not have been definitely established. A specific warning relating to a use not provided for under the “Indications and Usage” section may be required by FDA in accordance with sections 201(n) and 502(a) of the act if the drug is commonly prescribed for a disease or condition and such usage is associated with a clinically significant risk or hazard.

(Emphasis added). Note the specific “may be required by FDA” language where widespread off-label uses are discussed. Where off-label use is concerned, the FDA wants to keep tight control of the labeling. If it were possible to add or “strengthen” off-label warnings CBE-style – that is, without prior FDA approval, there would be no reason to include the highlighted sentence in §201.57 at all.

Further, aside from warnings, the FDA has a whole section, 21 C.F.R. Part 99, that severely limits what manufacturers can legally disseminate about off-label uses, and it expressly requires prior FDA approval of this type of material.

In light of the FDA’s promulgation of a slew of formal regulations restricting drug (and device) manufacturers’ off-label statements we think, with respect to off-label uses, the sort of warning claim seen in Meharg implicates Levine’s caveat, “we have no occasion in this case to consider the pre-emptive effect of a specific agency regulation bearing the force of law.”  Wyeth v. Levine, 129 S. Ct. 1187, 1203 (2009).  The “specific” FDA regulations governing what a manufacturer can say about off-label uses expressly require prior FDA approval in all circumstances, and under Levine, that’s enough to make a pretty good preemption argument.