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Editor: Robert Blanchard
Profession: Attorney at Law

Category: Ortho Evra Legal News

There is a pretty good decision from the 5th Circuit about adequacy of warnings being a jury issue. Off label use and other concepts are discussed as well.

5th Circuit: Jury Should Decide Adequacy Of Risk Warning; Off-Label Use Creates Duty
NEW ORLEANS - A jury should decide whether the label for Wyeth's gastroesophageal reflux disease (GERD) drug Reglan misled doctors about the risk of involuntary muscle conditions, a panel of the Fifth Circuit U.S. Court of Appeals ruled Aug. 22 (Sue C. McNeil v. Wyeth, et al., No. 05-10509, 5th Cir.).
The panel dismissed Wyeth's arguments that it need not warn doctors and patients about mere associations with adverse effects or about problems resulting from off-label use.
Sue C. McNeil was prescribed Reglan in August 2000 for treatment of GERD. Although the drug is approved for no more than 12 weeks' use, three doctors continued prescriptions for 14 months.
The pharmacology section of Reglan's label explained that it may produce "extrapyramidal reactions, although these are comparatively rare." The label also warned that Reglan may produce tardive dyskinesia, a severe form of extrapyramidal symptoms (EPS), marked by involuntary movements of the mouth and extremities and general agitation.

Tardive Dyskinesia
In October 2001, after taking Reglan for 14 months, McNeil was hospitalized and diagnosed with EPS and tardive dyskinesia.
McNeil sued Wyeth in Texas state court for failure to warn doctors and consumers of the increased risk of tardive dyskinesia from long-term use of Reglan. After Wyeth removed the case to federal court, the U.S. District Court for the Northern District of Texas granted summary judgment, finding that the label was adequate as a matter of law because it specifically mentioned the symptoms McNeil experienced.
McNeil appealed.
Risk Level Misleading
The Fifth Circuit panel agreed with McNeil that the District Court's reliance on Texas state case law is inapposite to her case. Although Reglan's label mentions the conditions of which McNeil complains, the panel said she does not claim that the warning is inadequate because the conditions are not mentioned but that the label is misleading about the "risk level" for the conditions.
Noting a lack of Texas case law on adequacy of warnings, the panel applied a default Texas rule that questions of adequacy go to a jury. It cited Texas law and the Restatement of Torts, noting that even if there is a learned intermediary, a manufacturer can be liable for an inadequate warning.
"Warning the learned intermediary of a much lower risk than the actual risk could render the warning not just misleading, but ineffective," the panel said. "When the risk described on the label is so low as to induce a doctor to undertake the risk, had he not done so if he were warned of the real risk, we cannot say that no reasonable jury could conclude that a warning was inadequate.
"Thus, if the manufacturer decides to label a risk as 'comparatively rare' and also to provide a numerical quantification of that risk, that number must be within a certain degree of accuracy."
Extended Use Well-Known
The panel rejected Wyeth's argument that it has no duty to warn of risks for use longer than the 12 weeks for which Reglan was approved.
"Wyeth was, or should have been aware that Reglan was prescribed routinely for long-term use," the panel said, citing expert testimony about Wyeth's market data showing long-term use by 84 percent of Reglan users.
"Because the widespread long-term use of Reglan suggests that Wyeth's indication for use for no more than twelve weeks was widely disregarded, a jury could infer that Wyeth's warning was ineffective and thus inadequate," the panel said. "Therefore, McNeil's suggested additional warning about long-term use would not be superfluous."
"Because Wyeth advertised that the risk of developing EPS is 'comparatively rare,' or that it is 0.2% for short term use," the panel said, "just noting that the risk is higher for long-term use may not put a physician on notice that certain studies have found that the risk could be a hundred times higher. That is, because the advertised risk is negligibly low, the mere statement that the risk increases with use does not put a physician on notice that the increase in risk is of a completely different order of magnitude and class of risk.
"Thus, a jury could find that the risk of developing EPS from long-term use was not just higher, but that it was 'significantly' higher, and that the label was therefore misleading and inadequate."
"In sum, because the widespread long-term use of Reglan suggests that Wyeth's indication for use for not more than twelve weeks was widely disregarded, a jury could infer that the warning was ineffective and therefore inadequate," the panel said. "It follows that Wyeth had a duty, under Texas law, [to] adequately warn the learned intermediary of known risks with long term use and not be misleading as to that risk."
Association Vs. Causation
The panel also rejected Wyeth's argument that the mere association of Reglan with a condition does not necessarily show causation that needs to be on the label. The panel noted that Food and Drug Administration regulations require labels to be revised to include warning as soon as there is an association of serious hazards and that a causation relationship need not be proved.
Although Texas law might not require the same warning as the FDA regulation, the panel said state law "does not absolve a manufacturer, as a matter of law, of a duty to warn on grounds that no existing studies or clinical trials prove actual causation."
The panel noted that one of McNeil's experts testified that drug manufacturers frequently change labels based on simple case reports, not actual clinical studies.
"Thus," the panel wrote, "it is not uncommon for drug companies to do precisely what Wyeth claims it cannot do: tell physicians that a certain use is contraindicated even if no clinical or epidemiological studies exist that confirm causation or degree of risk."
Duty Created By Off-Label Use
"Certainly, it is easier for a manufacturer to make an off-label use contraindicated when that use provides only a minimal amount of sales from that drug as opposed to when the off-label use provides the majority of its sales, as allegedly it is with Wyeth and Reglan," the panel said. "But it is precisely this fact - that off-label use allegedly provided a majority of Wyeth's sales - that would create Wyeth's duty to physicians not to be misleading about the risk of long-term use."

Circuit Judge Jerry E. Smith wrote the opinion for Circuit Judges Carolyn Dineen King and Fortunato P. Benavides.

Counsel
Coleman M. Cowan, John A. Jones and George C. Olson of Martin & Jones in Raleigh, N.C., represent McNeil. Michael R. Klatt, Susan E. Burnett and Kelly R. Kimbrough of Clark, Thomas & Winters in Austin, Texas, and Jeffrey R. Pilkington of David, Graham & Stuff in Denver represent Wyeth.