In Wyeth, the Plaintiff, Diana Levine, claimed that she was injured by the inappropriate administration of Wyeth's antinausea drug
Phenergan, which caused her to develop gangrene and resulted in the amputation of a portion of her arm. In this case, a Vermont
jury found that the Phenergan label was inadequate and should have contained a stronger warning regarding intravenous push
administration because of the known risk of inadvertent intra-arterial injection and consequent development of gangrene. Wyeth
maintained that Levine's state tort claims were preempted because FDA had approved the Phenergan label without such a strong
The doctrine of federal preemption is based upon the Supremacy Clause in the Constitution, which states that the "Constitution
and the laws of the United States ... shall be the supreme law of the land [notwithstanding] anything in the constitutions
or laws of any state. …" (26). Federal law preempts state law where a federal statute contains specific language indicating
that federal law must control (express preemption), where federal law "occupies the field" (i.e., field preemption) or where
state law conflicts with federal law and thus making it impossible to comply with both (i.e., conflict preemption).
Wyeth argued that it would have been impossible for it to modify its labeling without violating federal law and that allowing
Levine's state tort claim was unacceptable because it would permit a state jury to override FDA's scientific judgment regarding
a product's labeling (27, 28). The Supreme Court rejected Wyeth's arguments, holding that state tort claims for injuries caused
by drug products were not preempted by the Federal Food, Drug, and Cosmetic Act, and that drug manufacturers have primary
responsibility for strengthening warnings in their labeling based on new information about adverse events. The Supreme Court
reasoned that Wyeth could have strengthened the warnings on the Phenergan label without prior FDA approval, and added that
Wyeth could not simply rely on its approved labeling when faced with new information of adverse events (29, 30).
The Supreme Court noted that FDA does not have sufficient resources of its own to enforce drug-product safety. FDA has historically
viewed state tort law as a supplementary form of drug product regulation. Ultimately, however, the responsibility for safety
of the product resides with the manufacturer (31).
The Wyeth decision put drug manufacturers on notice that they bear primary responsibility for their labeling, and they must be vigilant
in monitoring and evaluating adverse events associated with their drug products. Moreover, the evaluation of risk information
must be ongoing: an event that seems insignificant today may be quite significant a year from now, in light of other adverse
events. As shown in Matrixx, courts may not look solely to the concept of statistical significance in order to determine whether or not such adverse
events indicate causation. Instead, as reaffirmed by the Supreme Court, drug manufacturers must continue to evaluate multiple
sources of information when assessing the risks associated with their products.
While the Matrixx case made no mention of Wyeth, it seems that the two cases are consistent in requiring drug manufacturers to evaluate carefully any new information about
a drug product that trigger an obligation to act—whether to notify stockholders of material facts or to change the warnings
on a product's labeling. However, such cases merely illustrate that the courts, investors and federal and state governments
expect this obligation to extend well beyond mitigation of litigation risks and instead to include every aspect of pharmaceutical
product design, manufacture, and stewardship. Statistical significance, while still a valuable tool for assessing variation,
is only one of many considerations in the "total mix" of information available to drug manufacturers.
- S.T. Ziliak and D.N. McCloskey, The Cult of Statistical Significance (University of Michigan Press, Ann Arbor, 2008).
- R. Hooke, How to Tell the Liars From the Statisticians (Marcel Dekker, New York, NY, 1983).
- H.F Spirer et al., Misused Statistics, 2nd ed., (Marcel Dekker, New York, NY, 1998).
- C.Wang, Sense and Nonsense of Statistical Inference (Marcel Dekker, New York, NY, 1993).
Cathy L. Burgess is a partner in the Washington, DC, office of the law firm Alston & Bird LLP, tel. 202.239.3648, email@example.com
. Sean A. Simmons is a senior associate in the Atlanta, Georgia, office of Alston & Bird LLP, tel. 404.881.4576, firstname.lastname@example.org
. Lynn D. Torbeck is a statistician at Torbeck and Assoc., and a member of the Pharmaceutical Technology Editorial Advisory Board, tel. 847.424.1314, Lynn@Torbeck.org