Wednesday, March 4, 2009

I Wonder Whether Mr. Eakeley will bring THIS Case to the Attention of Judge Cavanaugh!

On and off, over the past few months, lawyers at the firms of Lowenstein, Sandler and Dechert, LLP have been peppering Judge Cavanaugh with letters advising him of other federal court rulings, mostly related to arguments supporting the notion of preemption (by FDA drug approval). Note that Congress has provided this form of preemption should apply to devices.

That leaves them in the rather unfortunate position of having to now let Judge Cavanaugh know that the nation's highest court disagrees with those earlier arguments (Wyeth v. Levine, SCOTUS No. 06-1249, Argued November 3, 2008 -- Decided March 4, 2009). Hilarious. [I think Judge Cavanaugh already knows about this one, boys.] This is the passage of the majority's (6-3) opinion Douglas Eakeley, of Lowenstein, Sandler ought to quote, by subsequent letter, to federal District Court Judge Cavanaugh (Cavanaugh is presiding over the current bolus of 145 lawsuits against Schering-Plough) -- if he truly wishes to keep the judge abreast of the developing path of the law of FDA preemption (as his earlier letters suggested):

. . . .Wyeth’s cramped reading of the CBE regulation and its broad reading of the FDCA’s misbranding and unauthorized distribution provisions are premised on a more fundamental misunderstanding. Wyeth suggests that the FDA, rather than the manufacturer, bears primary responsibility for drug labeling. Yet through many amendments to the FDCA and to FDA regulations, it has remained a central premise of federal drug regulation that the manufacturer bears responsibility for the content of its label at all times. It is charged both with crafting an adequate label and with ensuring that its warnings remain adequate as long as the drug is on the market. See, e.g., 21 CFR §201.80(e) (requiring a manufacturer to revise its label “to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug”); §314.80(b) (placing responsibility for post-marketing surveillance on the manufacturer); 73 Fed. Reg. 49605 (“Manufacturers continue to have a responsibility under Federal law. . . . to maintain their labeling and update the labeling with new safety information”).

Indeed, prior to 2007, the FDA lacked the authority to order manufacturers to revise their labels. See 121 Stat. 924–926. When Congress granted the FDA this authority, it reaffirmed the manufacturer’s obligations and referred specifically to the CBE regulation, which both reflects the manufacturer’s ultimate responsibility for its label and provides a mechanism for adding safety information to the label prior to FDA approval. . . .

Note that, on January 23, 2008, FDA warned Schering-Plough that the Vytorin label would be "misleading" if not updated for the non-superiority outcome in ENHANCE. Schering apparently waited until it had "stocked out" of the old labels to revise them. Interesting -- in light of today's decision.


Anonymous said...

I noticed the very same paragraph when I read the decision.

What I found particularly interesting is the following statement:

“to include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug"

The question then is what is a reasonable associatiion?

With regards to Vytorin and cancer some people seem to interpret this as a requiring the same level of statistical rigor as showing that a drug is efficacious. This is clearly a ridiculous standard as no drug study for is designed that way and thus no side effects detected in development studies could ever meet that standard. On the other hand companies will include reports or rare single cases in labeling for drugs.

Thus it seems to me that the the high incidence of cancer with Vytorin especially in the face of additional biologic plausibility (which would not be needed) seems to me to meet the standard of a REASONABLE ASSOCIATION, (i.e. it need not be proved).


Condor said...

I am inclined to agree, Salmon.

Thanks for the keen insights -- as always.

Time will tell whether Schering-Plough has made a fundamental mistake -- in choosing not to proactively warn about cancer, voluntarily, in its label-copy, post SEAS.

That seems to be one of the emerging object-lessons from the Wyeth v. Levine opinion: be proactive with your drug-warnings, oh you pharma players.

Time will tell.


Anonymous said...

Per my previous comments on the level of statistical rigor needed. Well Dave Graham made the exact same comments in his Senate testimony on Vioxx.

Do read if you're interested.