Source: https://www.law.cornell.edu/supct/html/06-1249.ZD.html
Timestamp: 2019-04-26 08:01:22+00:00

Document:
This case illustrates that tragic facts make bad law. The Court holds that a state tort jury, rather than the Food and Drug Administration (FDA), is ultimately responsible for regulating warning labels for prescription drugs. That result cannot be reconciled with Geier v. American Honda Motor Co., 529 U. S. 861 (2000) , or general principles of conflict pre-emption. I respectfully dissent.
Federal law, however, does rely on the FDA to make safety determinations like the one it made here. The FDA has long known about the risks associated with IV push in general and its use to administer Phenergan in particular. Whether wisely or not, the FDA has concluded—over the course of extensive, 54-year-long regulatory proceedings—that the drug is “safe” and “effective” when used in accordance with its FDA-mandated labeling. The unfortunate fact that respondent’s healthcare providers ignored Phenergan’s labeling may make this an ideal medical-malpractice case.3 But turning a common-law tort suit into a “frontal assault” on the FDA’s regulatory regime for drug labeling upsets the well-settled meaning of the Supremacy Clause and our conflict pre-emption jurisprudence. Brief for United States as Amicus Curiae 21.
Thus, a drug’s warning label “serves as the standard under which the FDA determines whether a product is safe and effective.” 50Fed. Reg. 7470 (1985). Labeling is “[t]he centerpiece of risk management,” as it “communicates to health care practitioners the agency’s formal, authoritative conclusions regarding the conditions under which the product can be used safely and effectively.” 71Fed. Reg. 3934 (2006). The FDA has underscored the importance it places on drug labels by promulgating comprehensive regulations—spanning an entire part of the Code of Federal Regulations, see 21 CFR pt. 201, with seven subparts and 70 separate sections—that set forth drug manufacturers’ labeling obligations. Under those regulations, the FDA must be satisfied that a drug’s warning label contains, among other things, “a summary of the essential scientific information needed for the safe and effective use of the drug,” §201.56(1), including a description of “clinically significant adverse reactions,” “other potential safety hazards,” “limitations in use imposed by them, … and steps that should be taken if they occur,” §201.57(c)(6)(i). Neither the FDCA nor its implementing regulations suggest that juries may second-guess the FDA’s labeling decisions.
Notwithstanding the statute’s saving clause, and notwithstanding the fact that Congress gave the Secretary authority to set only “minimum” safety standards, we held Geier’s state tort suit pre-empted. In reaching that result, we relied heavily on the view of the Secretary of Transportation—expressed in an amicus brief—that Standard 208 “ ‘embodies the Secretary’s policy judgment that safety would best be promoted if manufacturers installed alternative protection systems in their fleets rather than one particular system in every car.’ ” 529 U. S., at 881 (quoting Brief for United States as Amicus Curiae,O. T. 1999, No. 98–1811, p. 25). Because the Secretary determined that a menu of alternative technologies was “safe,” the doctrine of conflict pre-emption barred Geier’s efforts to deem some of those federally approved alternatives “unsafe” under state tort law.
The same rationale applies here. Through Phenergan’s label, the FDA offered medical professionals a menu of federally approved, “safe” and “effective” alternatives—including IV push—for administering the drug. Through a state tort suit, respondent attempted to deem IV push “unsafe” and “ineffective.” To be sure, federal law does not prohibit Wyeth from contraindicating IV push, just as federal law did not prohibit Honda from installing airbags in all its cars. But just as we held that States may not compel the latter, so, too, are States precluded from compelling the former. See also Fidelity Fed. Sav. & Loan Assn. v. De la Cuesta, 458 U. S. 141, 155 (1982) (“The conflict does not evaporate because the [agency’s] regulation simply permits, but does not compel,” the action forbidden by state law). If anything, a finding of pre-emption is even more appropriate here because the FDCA—unlike the National Traffic and Motor Safety Vehicle Act—contains no evidence that Congress intended the FDA to set only “minimum standards,” and the FDCA does not contain a saving clause.4 See also ante, at 18 (conceding Congress’ “silence” on the issue).
When respondent was injured in 2000, Phenergan’s label specifically addressed IV push in several passages (sometimes in lieu of and sometimes in addition to those discussed above). For example, the label warned of the risks of intra-arterial injection associated with “aspiration,” which is a technique used only in conjunction with IV push.12 The label also cautioned against the use of “syringes with rigid plungers,” App. 390, which are used onlyto administer the drug via IV push. As respondent’s medical expert testified at trial, “by talking plungers and rigid needles, that’s the way you do it, to push it with the plunger.” Id., at 53 (testimony of Dr. John Matthew). Moreover, Phenergan’s 2000 label devoted almost a full page to discussing the “Tubex system,” see id., at 391, which, as noted above, is used only to administer the drug via IV push.
As noted above, when the FDA approved Phenergan’s label, it was textbook medical knowledge that the “antecubital fossa” creates a high risk of inadvertent intra-arterial injection, given the close proximity of veins and arteries. See supra, at 13–14; see also The Lippincott Manual of Nursing Practice 99 (7th ed. 2001) (noting, in a red-text “NURSING ALERT,” that the antecubital fossa is “not recommended” for administering dangerous drugs, “due to the potential for extravasation”).13 According to the physician’s assistant who injured respondent, however, “[i]t never crossed my mind” that an antecubital injection of Phenergan could hit an artery. App. 110; see also ibid. (“[It] just wasn’t something that I was aware of at the time”). Oblivious to the risks emphasized in Phenergan’s warnings, the physician’s assistant pushed a double dose of the drug into an antecubital artery over the course of “[p]robably about three to four minutes,” id., at 111; id., at 105, notwithstanding respondent’s complaints of a “ ‘burn[ing]’ ” sensation that she subsequently described as “ ‘one of the most extreme pains that I’ve ever felt,’ ” id., at 110, 180–181. And when asked why she ignored Phenergan’s label and failed to stop pushing the drug after respondent complained of burning pains, the physician’s assistant explained that it would have been “just crazy” to “worr[y] about an [intra-arterial] injection” under the circumstances, id., at 111.
Second, the Court today distinguishes Geier because the FDA articulated its pre-emptive intent “without offering States or other interested parties notice or opportunity for comment.” Ante, at 21; see also ante, at 24. But the Geier Court specifically rejected the argument (again made by the dissenters in that case) that conflict pre-emption is appropriate only where the agency expresses its pre-emptive intent through notice-and-comment rulemaking. Compare 529 U. S., at 885 (“To insist on a specific expression of agency intent to pre-empt, made after notice-and-comment rulemaking, would be in certain cases to tolerate conflicts that an agency, and therefore Congress, is most unlikely to have intended. The dissent, as we have said, apparently welcomes that result … . We do not”), with id., at 908–910 (Stevens, J., dissenting) (emphasizing that “we generally expect an administrative regulation to declare any intention to pre-empt state law with some specificity,” and that “[t]his expectation … serves to ensurethat States will be able to have a dialog with agencies regarding pre-emption decisions ex ante through the normal notice-and-comment procedures of the Administrative Procedure Act” (internal quotation marks omitted)). Indeed, pre-emption is arguably more appropriate here than in Geier because the FDA (unlike the DOT) declared its pre-emptive intent in the Federal Register. See 71 Fed. Reg. 3933–3936. Yet the majority dismisses the FDA’s published preamble as “inherently suspect,” ante, at 21, and an afterthought that is entitled to “no weight,” ante, at 25. Compare Lohr, supra, at 506 (opinion of Breyer, J.) (emphasizing that the FDA has a “special understanding of the likely impact of both state and federal requirements, as well as an understanding of whether (or the extent to which) state requirements may interfere with federal objectives,” and that “[t]he FDA can translate these understandings into particularized pre-emptive intentions … through statements in ‘regulations, pre-ambles, interpretive statements, and responses tocomments’ ”).
Third, the Court distinguishes Geier because the DOT’s regulation “bear[s] the force of law,” whereas the FDA’s preamble does not. Ante, at 24; see also ante, at 19. But it is irrelevant that the FDA’s preamble does not “bear the force of law” because the FDA’s labeling decisions surely do. See 21 U. S. C. §355. It is well within the FDA’s discretion to make its labeling decisions through administrative adjudications rather than through less-formal and less-flexible rulemaking proceedings, see SEC v. Chenery Corp., 332 U. S. 194 (1947) , and we have never previously held that our pre-emption analysis turns on the agency’s choice of the latter over the former. Moreover, it cannot be said that Geier’s outcome hinged on the agency’s choice to promulgate a rule. See ante, at 19, 24. The Geier Court relied—again over the dissenters’ protestations—on materials other than the Secretary’s regulation to explain the conflict between state and federal law. Compare 529 U. S., at 881, with id., at 899–900 (Stevens, J., dissenting), and ante, at 1–2 (Breyer, J., concurring).
The problem is well illustrated by the labels borne by “vesicant” drugs, many of which are used for chemotherapy. As a class, vesicants are much more dangerous than drugs like Phenergan,15 but the vast majority of vesicant labels—like Phenergan’s—either allow or do not disallow IV push. See Appendix, infra. Because vesicant extravasation can have devastating consequences, and because the potentially lifesaving benefits of these drugs offer hollow solace to the victim of such a tragedy, a jury’s cost-benefit analysis in a particular case may well differ from the FDA’s.
1 Indeed, respondent conceded below that Wyeth did propose an adequate warning of Phenergan’s risks. See Plaintiff Diana Levine’s Memorandum in Opposition to Wyeth’s Motion for Summary Judgment in Levine v. American Home Products Corp. (now Wyeth), No. 670–12–01 Wncv (Super. Ct. Washington Cty., Vt.), ¶7, p. 26. Specifically, respondent noted: “In 1988, Wyeth proposed language that would have prevented this accident by requiring a running IV and explaining why a running IV will address and reduce the risk [of intra-arterial injection].” Ibid. See also id., at 24 (“Although not strong enough, this improved the labeling instruction, if followed, would have prevented the inadvertent administration of Phenergan into an artery …”). The FDA rejected Wyeth’s proposal. See App. 359.
2 Moreover, in the trial judge’s final charge, he told the jury that “the critical factual issue which you must decide” is whether Phenergan’s FDA-mandated label reflects a proper balance between “the risks and benefits of intravenous administration and the potential for injury to patients.” Id., at 220. See also ___ Vt. ___, ___, 944 A. 2d 179, 182 (2006) (recognizing that respondent’s argument is that Phenergan’s “label should not have allowed IV push as a means of administration”).
3 Respondent sued her physician, physician’s assistant, and hospital for malpractice. After the parties settled that suit for an undisclosed sum, respondent’s physician sent her a letter in which he admitted “responsibility” for her injury and expressed his “profoun[d] regre[t]” and “remors[e]” for his actions. 1 Tr. 178–179 (Mar. 8, 2004) (testimony of Dr. John Matthew); see also App. 102–103 (testimony of physician’s assistant Jessica Fisch) (noting that her “sense of grief” was so “great” that she “would have gladly cut off [her own] arm” and given it to respondent). Thereafter, both the physician and the physician’s assistant agreed to testify on respondent’s behalf in her suit against Wyeth.
4 To be sure, Congress recognized the principles of conflict pre-emption in the FDCA. See Drug Amendments of 1962, §202, 76 Stat. 793 (“Nothing in the amendments made by this Act to the Federal Food, Drug, and Cosmetic Act shall be construed as invalidating any provision of State law … unless there is a direct and positive conflict between such amendments and such provision of State law”). But a provision that simply recognizes the background principles of conflict pre-emption is not a traditional “saving clause,” and even if it were, it would not displace our conflict-pre-emption analysis. See Geier v. American Honda Motor Co., 529 U. S. 861, 869 (2000) (“[T]he saving clause … does not bar the ordinary working of conflict pre-emption principles”); id., at 873–874 (“The Court has … refused to read general ‘saving’ provisions to tolerate actual conflict both in cases involving impossibility and in ‘frustration-of-purpose’ cases” (emphasis deleted and citation omitted)).
5 The FDA cited numerous articles that generally discuss the costs and benefits associated with IV push. See, e.g., Nahrwold & Phelps, Inadvertent Intra-Arterial Injection of Mephenteramine, 70 Rocky Mountain Medical J. 38 (Sept. 1973) (cited in App. 314, no. 14); Albo, Cheung, Ruth, Snyder, & Beemtsma, Effect of Intra-Arterial Injections of Barbituates, 120 Am. J. of Surgery 676 (1970) (cited in App. 314, no. 12); Corser, Masey, Jacob, Kernoff, & Browne, Ischaemia Following Self-administered Intra-arterial Injection of Methylphenidate and Diamorphine, 40 Anesthesiology 51 (1985) (cited in App. 314, no. 9); Correspondence Regarding Thiopental and Thiamylal (3 letters), 59 Anesthesiology 153 (1983) (cited in App. 314, no. 11); Miller, Arthur, & Stratigos, Intra-arterial Injection of a Barbituate, 23 Anesthesia Progress 25 (1976) (cited in App. 315, no. 19).
6 See Webb & Lampert, Accidental Arterial Injections, 101 Am. J. Obstetrics & Gynecology 365 (1968) (cited in App. 313, no. 5).
7 See Hager & Wilson, Gangrene of the Hand Following Intra-arterial Injection, 94 Archives of Surgery 86 (1967) (cited in App. 313, no. 7); Enloe, Sylvester, & Morris, Hazards of Intra-Arterial Injection of Hydroxyzine, 16 Canadian Anaesthetists’ Society J. 425 (1969) (hereinafter Enloe) (noting “recent reports” of “the occurrence of severe necrosis and gangrene following [administration of] promethazine (Phenergan®)” (cited in App. 314, no. 15)). See also Mostafavi & Samimi, Accidental Intra-arterial Injection of Promethazine HCl During General Anesthesia, 35 Anesthesiology 645 (1971) (reporting a case of gangrene, which required partial amputation of three fingers, after Phenergan was inadvertently pushed into an artery in the “antecubital” area); Promethazine, p. 7, in Clinical Pharmacology (Gold Standard Multimedia Inc. CD–ROM, version 1.16 (1998) (noting that “[i]nadvertent intra-arterial injection [of Phenergan] can result in arteriospasm … and development of gangrene”)).
8 Hager and Wilson noted that the most common reactions to intra-arterial injections of drugs like Phenergan include “[i]mmediate, severe, burning pain,” as well as “blanching.” 94 Archives of Surgery, at 87–88. The FDA required Wyeth to include Hager and Wilson’s observations on Phenergan’s label. See App. 311 (requiring the label to warn that “ ‘[t]he first sign [of an intra-arterial injection] may be the patient’s reaction to a sensation of fiery burning’ ” pain and “ ‘[b]lanching’ ”).
9 See Enloe 427 (discussing hydroxyzine—an antihistamine with chemical properties similar to those of Phenergan—and suggesting its “temporary” benefits can never outweigh the risks of intra-arterial injection); see also Goldsmith & Trieger, Accidental Intra-Arterial Injection: A Medical Emergency, 22 Anesthesia Progress 180 (1975) (noting the risks of intra-arterial administration of hydroxyzine) (cited in App. 315, no. 18); Klatte, Brooks, & Rhamy, Toxicity of Intra-Arterial Barbituates and Tranquilizing Drugs, 92 Radiology 700 (1969) (same) (cited in App. 314, no. 13). With full knowledge of those risks, FDA retained IV push for Phenergan, although the agency required Wyeth to incorporate observations from the Enloe article into Phenergan’s label. Compare Enloe 427 (arguing that “every precaution should be taken to avoid inadvertent intra-arterial injection,” including the use of “an obviously well-functioning venoclysis”), with App. 312 (FDA’s 1987 changes to Phenergan’s label). In contrast, at some time around 1970, the FDA prohibited all intravenous use of hydroxyzine. See id., at 79 (testimony of Dr. Harold Green). The FDA’s decision to regulate the two drugs differently—notwithstanding (1) the agency’s knowledge of the risks associated with both drugs and (2) the agency’s recognition of the relevance of hydroxyzine-related articles and case reports in its regulation of Phenergan—further demonstrates that the FDA intentionally preserved IV-push administration for Phenergan. See also Haas, Correspondence, 33 Anesthesia Progress 281 (1986) (“[Hydroxyzine’s] restriction does not lie with the medicine itself, but in the practice and malpractice of intravenous techniques. Unfortunately, the practitioner who knows how to treat injection technique problems is usually not the practitioner with the intravenous technique problems”).
10 See also Engler, Freeman, Kanavage, Ogden, & Moretz, Production of Gangrenous Extremities by Intra-Arterial Injections, 30 Am. Surgeon 602 (1964) (“Accidental arterial injection most often occurs in the antecubital region because this is a favorite site for venopuncture and in this area the ulnar and brachial arteries are superficial and easily entered” (cited in App. 313, no. 6)); Engler, Gangrenous Extremities Resulting from Intra-arterial Injections, 94 Archives of Surgery 644 (1966) (similar) (cited in App. 314, no. 16); Lynas & Bisset, Intra-arterial Thiopentone, 24 Anaesthesia 257 (1969) (“Most [anesthesiologists] agree that injections on the medial aspect of the antecubital fossa are best avoided” (cited in App. 314, no. 8)); Waters, Intra-arterial Thiopentone, 21 Anesthesia 346 (1966) (“The risk of producing gangrene of the forearm by accidental injection of sodium thiopentone into an artery at the elbow has been recognised for many years” (cited in App. 314, no. 10)); see also Hager & Wilson, 94 Archives of Surgery, at 88 (emphasizing that one of the best ways to prevent inadvertent intra-arterial injections is to be aware of “aberrant or superficial arteries at the antecubital, forearm, wrist, and hand level”); Mostafavi & Samimi, supra (warning against antecubital injections).
11 See App. 311 (requiring Phenergan’s label to warn that practitioners should “ ‘[b]eware of the close proximity of arteries and veins at commonly used injection sites and consider the possibility of aberrant arteries’ ”).
12 “Aspiration” refers to drawing a small amount of blood back into the needle to determine whether the needle is in an artery or a vein. Ordinarily, arterial blood is brighter than venous blood—but contact with Phenergan causes discoloration, which makes aspiration an unreliable method of protecting against intra-arterial injection. See id., at 282. Therefore, the label warned that when using IV push, a medical professional should beware that “[a]spiration of dark blood does not preclude intra-arterial needle placement, because blood is discolored upon contact with Phenergan Injection.” Id., at 390.
13 In addition, respondent’s own medical expert testified at trial that it is a principle of “basic anatomy” that the antecubital fossa contains aberrant arteries. See 2 Tr. 34–35 (Mar. 9, 2004) (testimony of Dr. Daniel O’Brien); see also ibid. (noting that Gray’s Anatomy, which is “the Bible of anatomy,” also warns of arteries in the antecubital space).
14 Thus, it is not true that “this Court has long” applied a presumption against pre-emption in conflict pre-emption cases. Ante, at 9, n. 3 (majority opinion). As long ago as Gibbons v. Ogden, 9 Wheat. 1, 210 (1824), the Court inquired whether a state law “interfer[ed] with,” was “contrary to,” or “c[a]me into collision with” federal law—and it did so without ever invoking a “presumption.” See also Davis, Unmasking the Presumption in Favor of Preemption, 53 S. C. L. Rev. 967, 974 (2002) (noting that many of the Court’s early pre-emption cases “resulted in almost automatic preemption of concurrent state regulation”). In subsequent years the Court has sometimes acknowledged a limited “presumption against pre-emption,” but it nonetheless remained an open question—before today—whether that presumption applied in conflict pre-emption cases. See Crosby v. National Foreign Trade Council, 530 U. S. 363 , n. 8 (2000) (“We leave for another day a consideration in this context of a presumption against preemption”). Moreover, this Court has never held that the “presumption” applies in an area—such as drug labeling—that has long been “reserved for federal regulation.” United States v. Locke, 529 U. S. 89, 111 (2000) . See also Buckman Co. v. Plaintiffs’ Legal Comm., 531 U. S. 341, 347–348 (2001) .
15 Vesicants may cause “blistering, severe tissue injury, or tissue necrosis” upon extravasation—even if the drug is not injected into an artery. See, e.g., Schulmeister, Administering Vesicants, 9 Clinical J. of Oncology Nursing 469, 469–470 (2005). See also ante, at 4 (majority opinion) (noting that Phenergan is labeled as an “irritant”); cf. Brief for Anju Budhwani et al. as Amici Curiae 15 (suggesting Phenergan should be considered a “vesicant”).
16 FDA, Oncology Tools Product Label Details, online at http://www.accessdata.fda.gov/scripts/cder/onctools/labels.cfm?GN=meclorethamine,%20nitrogen%20mustard (as visited Mar. 2, 2009, and available in Clerk of Court’s case file).
18 The same is true of FDA’s regulation of hydroxyzine. See n. 9,supra.

References: v. 
 §201
 §201
 v. 
 §355
 v. 
 v. 
 §202
 v. 
 v. 
 v. 
 v. 
 v.