FDA, Hospital at Fault in Levine Case, Not Wyeth

March 5, 2009

Yesterday's  big news was the fact that Wyeth Pharmaceuticals lost its appeal in the precedent setting Wyeth vs. Levine safety labeling case.

Yesterday's  big news was the fact that Wyeth Pharmaceuticals lost its appeal in the precedent setting Wyeth vs. Levine safety labeling case.

Apparently, back the 1988, after numerous attempts, Wyeth Pharmaceuticals had tried to make the warning label on its drug, Phenergan, more explicit to ensure that health care professionals would not inject the drug incorrectly.  FDA did not respond, then appeared to reject the proposed changes, advising the company to keep its current labeling.  It was just such a mistake, made by a physician’s assistant in a Vermont hospital emergency room, that cost Diana Levine, a professional violinist, her arm.

In this tragedy, it is completely understandable that Ms. Levine should want to sue anyone and everyone connected with it.  OK, suing FDA wouldn't gain very much, monetarily or otherwise. Ms. Levine did successfully sue the hospital and Wyeth, which was trying to appeal the verdict.  But this wasn’t Wyeth’s fault.

Even comments on musician discussion boards place the blame on the healthcare facility and the FDA.
The Supreme Court decided, in effect, that it was up to Wyeth to strengthen its drug safety warnings, whether or not FDA required it. Anyone who would argue this point doesn’t understand the relationship between pharma companies and FDA, which continues to be one of fear and defensiveness. “Whatever you say or we think you’re saying,” in effect, whether or not it even makes sense.

Consider drug information inserts…. An FDA initiative a few years back was designed to make them more “user friendly.”  They’re still basically written for the drug reviewer and physician, rather than the patient.

Until we finally have “personalized medicine,” given the number of potential side effects or potential administration errors for any medication today, labeling requirements could get complex and costly.  Shouldn’t FDA be the final arbiter of whether drug labeling is adequate? Couldn’t help but agree with Gregory Conko of the Competitive Enterprise Institute, who believes the Court botched the decision.  The Institute issued the following opinion brief today:

The Supreme Court handed down its decision this morning in the case of Wyeth v. Levine, ruling that federal law did not bar plaintiff Diana Levine from suing pharmaceutical maker Wyeth over allegedly insufficient drug safety warnings, even though the warnings had been approved by the Food and Drug Administration.

This case establishes the troubling precedent that a sympathetic jury can now supersede the expert opinions of drug makers, physicians and the FDA on what qualifies as adequate safety labeling. Ms. Levine lost an arm to gangrene after a physician’s assistant injected the Wyeth drug Phenergan in such a way that it came into contact with oxygen-rich arterial blood. Although the drug’s label explicitly warned that doing so posed a high risk of tissue damage, Levine claimed that the label should have instructed physicians not to use this intravenous “IV-push” method at all.

The Supreme Court held, by a 6-3 majority, that “Federal law does not pre-empt [plaintiff Diana] Levine’s claim that [the drug’s] label did not contain an adequate warning about the IV-push method of administration.” According to Justice John Paul Stevens’ majority opinion, “The history of the [Food Drug and Cosmetics Act] shows that Congress did not intend to pre-empt state-law failure-to-warn actions.” Although true, the Court failed to recognize that this is not a typical failure-to-warn case. As Justice Samuel Alito’s dissenting opinion notes, Ms. Levine conceded that, in 1988, Wyeth proposed a label change that “if followed, would have prevented the inadvertent administration of Phenergan into an artery,” but that FDA rejected that language.

Nevertheless, Ms. Levine alleged not only that the warning on Phenergan’s label wasn’t strong enough, but that Phenergan was “not reasonably safe for intravenous administration,” and that Phenergan’s label should have indicated that the drug “should not be used intravenously.” But, that poses a question regarding FDA’s approval of the product for that use, not Wyeth’s alleged negligence in drafting the label warning. Consequently, the decision reaches to the very core of FDA’s statutory competence.

FDA made a regulatory decision that the benefits of IV injection outweighed the risks, and the agency permitted the product to be labeled accordingly. Furthermore, there are no allegations that Wyeth hid any information about the risks of IV injection, nor that any new information regarding the risks of IV injection have arisen that would call that decision into question since FDA made it. So, letting a Vermont jury penalize Wyeth for not ruling out IV injection on Phenergan’s label is tantamount to letting a group of laymen over-rule FDA’s expert opinion regarding safety.

It would have been one thing if new evidence of risk had arisen since FDA approved the label, or if Wyeth were accused of hiding information from the FDA or mis-representing the data it did provide. In such a case, exposing a drug manufacturer to tort liability would not be over-riding FDA’s expert judgment. But that is decidedly not the case here. Indeed, the negligent act that actually caused Ms. Levine’s unfortunate injury was not an IV push injection into a vein, but the physician’s assistant’s negligent administration.

The physician’s assistant injected Phenergan in such a way that it came into contact with Ms. Levine’s arterial blood despite six label warnings against this very risk. The physician’s assistant also administered a dose twice as high as indicated on the drug’s label and continued to push in the plunger despite Ms. Levine’s protestations of pain, again in direct contravention of an explicit label warning. More or sterner warnings regarding the risks of intravenous injection would not have prevented Ms. Levine’s injury.

Thus, the Supreme Court could have and should have held in Wyeth’s favor with a narrowly tailored opinion confined to the facts of this case. Doing so would not have insulated wrong-doers from punishment, but would have recognized that Congress gave FDA statutory authority over questions of safety and efficacy because it believed that only a federal expert body could effectively balance the benefits and risks of new medicines.
As Justice Alito’s dissent makes clear, “the ordinary principles of conflict pre-emption turn solely on whether a State has upset the regulatory balance struck by the federal agency.” That is exactly what has happened here. So, not only is the majority’s decision bad policy, it’s also bad law.

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