On Nov. 4, 2008, the US Supreme Court heard arguments in Wyeth v. Levine, a drug-injury lawsuit with enormous implications for how product liability cases against pharmaceutical companies are handled.
On its face, Wyeth is about Diana Levine, a professional bass player and composer of children's music who lost her hand and forearm to gangrene after the IV push administration of the anti-nausea drug promethazine (Phenergan), which was being used to treat her migraines. Levine settled with the Vermont hospital where the injury took place — a fairly straightforward settlement, given that the hospital evidently failed to warn her about the known risks of gangrene when promethazine comes into contact with arterial blood.
But the issues being considered by the Supreme Court are far muddier, and far broader. Levine sued promethazine's manufacturer, Wyeth, in Vermont court, claiming that the drug's labeling was inadequate — it describes the risks of inadvertent intra-arterial injection and lists intramuscular injection as the preferred method of administration, followed by IV drip, and warns against IV push administration but does not specifically prohibit it. The Vermont trial court agreed and awarded her a $6.7 million verdict, which was upheld by a divided state supreme court in 2006.
DOCTRINE OF PRE-EMPTION
It is Wyeth's appeal of this verdict that has reached the Supreme Court. Wyeth claims that once the FDA approves a warning label for a drug, consumers can't sue drugmakers in state court claiming they were harmed by the drug in question. In its previous term, the Supreme Court upheld this doctrine of pre-emption in the case of medical devices — but the device law has a provision that prohibits states from imposing their own requirements. The Court found that that provision implicitly applies to private lawsuits as well, but a similar provision that does not appear in the federal Food, Drug, and Cosmetic Act.
On Levine's side, friend-of-the-court briefs were filed by 47 state attorney generals, 18 members of Congress, the New England Journal of Medicine, and two former FDA commissioners, David A. Kessler, MD, and Donald Kennedy, PhD. The AAN did not file an amicus brief in the case, and takes no official public position on it, said AAN General Counsel Murray Sagsveen.
“Drs. Kessler and Kennedy essentially said that the FDA is conscientious and hard-working and does the best it can, but it's not a fail-safe system for dealing with drug risk — far short of it,” said Richard Merrill, Daniel Caplin Professor of Law Emeritus at the University of Virginia School of Law, an expert in food and drug law. “If you take away tort law, you have one leg to stand on rather than two. Two people who ran the agency wrote a brief saying ‘You shouldn't trust us entirely.’”
Figure. DIANA LEVINE...Image Tools
The New England Journal (NEJM) editors argued that the FDA approval cannot be considered the final word, pre-empting lawsuits, when information on a drug's safety is frequently either discovered after its approval or, in some cases, withheld during the approval process by the manufacturer. “The drug companies have withheld key information from the FDA and ardently negotiated against stricter label warnings — all the while continuing to market their unsafe drugs to an unsuspecting public,” the NEJM editors wrote.
THE FDA CHALLENGE
“The FDA can't keep up with everything,” agreed Daniel Larriviere, JD, MD, assistant professor of neurology at the University of Virginia (UVA) School of Medicine and a member of the AAN Ethics Committee, who also teaches legal and ethical issues in the practice of medicine at UVA law school.
“They receive 11,000 applications a year. There will be things that companies find out in postmarketing analysis that may change what they told the FDA. Once a drug has been out there and a million people have taken it, you may see a side effect that you didn't know about before, because it's rare enough that you need more people to get exposed to the drug before you see it. In that case, if the Supreme Court said, ‘Once the FDA has spoken, you can't do anything,’ then the manufacturers have no legal incentive to come back to the FDA with the new data.”
Wyeth garnered support from the Pharmaceutical Research and Manufacturers of America, the US Chamber of Commerce, and the FDA itself (in the person of the US Deputy Solicitor General). About eight years ago, the FDA began to change its stance on pre-emption, said Merrill. “Beginning around 2000, the FDA shifted from a position of acceptance or indifference to private suits to one in which the agency appears in court on the same side as the defendant manufacturer.”
Along with the Solicitor General, Wyeth attorney Seth Waxman argued that upholding the state court's judgment would negate the FDA's balancing of the risks and benefits of making IV push available for patients who needed rapid administration of the drug. “In other words, Wyeth and Waxman argue that, when the FDA has specifically considered the risk involved and rejected the sort of warning that Diana Levine seeks, then the claim is pre-empted because it directly conflicts with the FDA's own determination,” wrote Dan Slater on the Wall Street Journal's law blog on Nov. 3.
There is a downside to determining that pre-emption does not apply, Dr. Larriviere noted. “Then every state could come up with its own standard based on lawsuits in state court,” he said. “Pretty soon, drug labels expand based on jury verdicts, not a 10,000-foot view of the landscape of risks and benefits. That gives you less of a public health standard and more of a litigation-driven standard in labeling.”
But neither side may get what it wants from the Supreme Court's ruling, Merrill suggested, at least not if the progress of oral arguments offers any hint as to how they're leaning. Although — unsurprisingly — justices Antonin Scalia and John Roberts seemed more sympathetic to Wyeth's position while Ruth Bader Ginsburg and David Souter's questioning appeared to lean more Levine's way, the overall course of the arguments seemed to point toward a more narrow reading of the case.
“If you read the oral arguments, I think that some justices were coming around to the view that there wasn't much of a gap between what the label actually said and what Mrs. Levine's lawyer claims it should have said,” said Merrill. “The FDA was aware of the risk, and the plaintiff's claim was that more should have been said, but if a majority of justices come out that there is not a major difference between what the plaintiff asked for and what the FDA provided, there's no basis for a finding of liability on the part of Wyeth. In this event, the hypothesized collision between federal and state law disappears — so, it's more possible than not that the claim of pre-emption won't be settled at all.”
That view was shared by several attorneys interviewed by a trade newsletter on FDA news, FDA Week. “Many of them had come to the conclusion that the resulting opinion might turn out to be disappointing, and much narrower than the litigants had assumed,” said Merrill.
Somewhat more optimistically, the Wall Street Journal suggested that the justices might find a middle ground. “Some justices seemed to be searching for a moderate position, whereby private lawsuits might be permitted in extraordinary circumstances. The justices seemed disinclined to permit private lawsuits to simply re-evaluate data that the FDA had fully considered.”