American Journal of Law & Medicine

The ban on "off-label" pharmaceutical promotion: constitutionally permissible prophylaxis against false or misleading commercial speech?

Critics of the Food & Drug Administration's ban on off-label promotion often claim that it violates the First Amendment because it suppresses pharmaceutical manufacturers' truthful speech about their legal--and beneficial--products. Characterizing the ban on off-label promotion in this way has more than rhetorical significance. Bans on truthful, non-misleading speech elicit special skepticism because of the belief that they "usually rest solely on the offensive assumption that the public will respond 'irrationally' to the truth." The legislative history of the provisions of the Food Drug and Cosmetic Act that underlie the ban on off-label promotion, however, reveals that Congress was concerned that physicians were responding rationally to false and misleading promotional claims. In this Article, I explore the doctrinal questions raised by conceiving of the ban on off-label promotion not as a ban on "truthful speech to physicians" but instead as a prophylaxis against false and misleading pharmaceutical promotion. I review the evidence that false and misleading claims were commonplace before the ban's adoption and persist today, along with the enforcement challenges the FDA confronted at that time and would confront were the ban lifted, and conclude the government likely could develop the factual record necessary to establish that Congress' rejection of an after-the-fact case-by-case approach to combating false and misleading prescription drug promotion is constitutional.

I. INTRODUCTION

In 1962, a physician named Miles Robinson testified before the House Committee on Interstate and Foreign Commerce about the advertising and promotion of prescription drugs, including the tranquilizer Mellaril, the side effects of which include both the serious movement disorder tardive dyskinesia and sudden death. Mellaril's manufacturer was promoting the drug to general practitioners to treat, in the manufacturer's words, "tense, nervous patients seen in everyday practice ... for chronic fatigue, insomnia, anxiety, and apprehension, vague digestive disorders, etc." (1) Dr. Robinson testified that he was "impressed with that 'etc.' It just tapers off into the wide, blue yonder where tranquilizers are claimed to be good for everything." (2)

Promotional abuses like those Dr. Robinson described were part of the impetus for Congress to amend the Food and Drug Administration's (FDA) organic statute, the Federal Food, Drug, and Cosmetic Act (FDCA), to require that a manufacturer demonstrate to the FDA's satisfaction that, in addition to being safe, a drug is effective for a given use before marketing it for that use. (3) The 1962 amendments to the FDCA (often termed the Harris-Kefauver Amendments after their congressional sponsors) require that manufacturers seeking agency approval of a new drug, or--importantly--of a new use for an already-approved drug, produce:

   evidence consisting of adequate and well-controlled investigations,
   including clinical investigations, by experts qualified by
   scientific training and experience to evaluate the effectiveness of
   the drug involved, on the basis of which it could fairly and
   responsibly be concluded by such experts that the drug will have
   the effect it purports or is represented to have under the
   conditions of use prescribed, recommended, or suggested in the
   labeling or proposed labeling thereof. (4)

This statutory language underlies the FDA's requirement that a drug undergo preclinical testing followed by clinical trials in humans before an indication, method of administration, patient population, or, in some circumstances, dose, is enshrined on the product's agency-approved label. (5) While physicians are free to prescribe a drug that has been approved for one use for any other use they deem appropriate, manufacturers may only promote it for its approved use or uses. (6)

The precise contours of the ban on off-label promotion derive from the Harris-Kefauver Amendments and the FDCA's misbranding provisions, as well as the FDCA's implementing regulations, court decisions, and various agency interpretations of the governing law. (7) While manufacturers are not permitted to promote their products for unapproved uses, multiple avenues for dissemination of information about such uses remain available to them. For example, manufacturers are not limited to the label when they engage in scientific exchange. (8) Their physicians and scientists can discuss research into off-label uses via medical journal articles, (9) and they can respond to physicians' requests for information about such uses. (10) Subject to certain limitations, manufacturers are also permitted to fund off-label continuing medical education programs for practicing physicians (11) and to provide physicians with, among other things, peer-reviewed medical journal articles discussing off-label uses. (12) These avenues notwithstanding, the disconnect between off-label use and the rules governing off-label promotion forces manufacturers to leave promising sales opportunities unexploited. Manufacturers also complain that the ban prevents them from providing physicians who are prescribing the manufacturers' products for off-label uses with important information about those uses.

It is not surprising, then, that the ban on off-label promotion is controversial. Its critics argue that it is also unconstitutional. Specifically, they claim that the ban violates the First Amendment because it suppresses pharmaceutical manufacturers' truthful speech about their legal products. (13) The manufacturer in a recent constitutional challenge to the ban, Allergan v. United States, pointedly limited its complaint to the ban's effect on "truthful speech to physicians." (14)

Characterizing the FDA's requirement that a drug that is approved for one use may not be promoted for another as a "ban[] against truthful, nonmisleading commercial speech" has more than rhetorical significance. (15) Such bans elicit special skepticism because of the belief that they "usually rest solely on the offensive assumption that the public will respond 'irrationally' to the truth." (16) By contrast, regulations targeting false and misleading speech merit much more relaxed review, because "[w]hen a State regulates commercial messages to protect consumers from misleading, deceptive, or aggressive sales practices, or requires the disclosure of beneficial consumer information, the purpose of its regulation is consistent with the reasons for according constitutional protection to commercial speech...., (17) The legislative history of the Harris-Kefauver Amendments reveals that one of Congress' principal concerns was that physicians were responding--rationally--to false and misleading promotional claims. (18) This Article explores the doctrinal questions raised by conceiving of the ban on off-label promotion not as a ban on "truthful speech to physicians" but instead as a prophylaxis against false and misleading pharmaceutical promotion.

The Article proceeds as follows. In Part II, I review the circumstances under which the government can adopt a prophylactic rule that targets false and misleading commercial speech but incidentally sweeps in some truthful, non-misleading speech. I also review the discussions of false and misleading prescription drug promotion in Washington Legal Foundation v. Friedman, the highly-influential district court decision invalidating the ban on off-label promotion as applied to continuing medical education courses, medical textbooks, and peer-reviewed journal articles, and Thompson v. Western States, (19) in which the Supreme Court invalidated restrictions on pharmacists' promotion of drug compounding. Notably, while the WLF Court used broad freedom-of-speech favoring language, the injunction it adopted was "narrowly applicable" (20) and incorporated requirements--for example that companies could only distribute reprints of articles that originally appeared in bona-fide peer-reviewed journals--that without doubt excluded truthful, non-misleading speech from constitutional protection. In Part III, I analyze a number of prophylactic bans of other types of commercial speech that have withstood constitutional challenge and point to commonalities they share with the promotion of pharmaceuticals to physicians. Finally, in Part IV, I review the extant empirical evidence of false and misleading prescription drug promotion, as well as the enforcement challenges the FDA confronted before the adoption of the ban on off-label promotion and would confront were the ban lifted. I conclude that the government likely could develop the factual record necessary to establish "that in fact [off-label promotion] is subject to abuse" and, thereby, establish that Congress' rejection of an after-the-fact case-by-case approach to policing such promotion is constitutional. (21)

II. COMMERCIAL SPEECH DOCTRINE, FALSE OR MISLEADING SPEECH, AND THE BAN ON OFF-LABEL PROMOTION

To determine whether commercial speech regulation comports with the Constitution, courts apply the familiar test set forth in Central Hudson Gas Electric Corp. v. Public Service Commission. (22) The test's first prong is "whether the expression is protected by the First Amendment." (23) Speech that concerns unlawful activity or is false, deceptive, or misleading is unprotected and thus the analysis ends. (24) If "truthful and nonmisleading expression will be snared along with fraudulent or deceptive commercial speech," (25) a court must move to the Central Hudson test's second prong, "whether the asserted governmental interest is substantial," third prong, "whether the regulation directly advances that interest," and fourth prong, "whether the regulation is more extensive than necessary to serve the asserted interest." (26) The government bears the burden of demonstrating that its regulation meets the Central Hudson test and if it can "achieve its interests in a manner that does not restrict speech, or that restricts less speech, [it] must do so." (27)

A. THE SUBSTANTIAL GOVERNMENT INTEREST IN ENSURING THE ACCURACY OF PRESCRIPTION DRUG PROMOTION

In Washington Legal Foundation v. Friedman, the court determined as a preliminary matter that the off-label information contained in the continuing medical education courses, medical textbooks, and peer-reviewed journal articles at issue was true, or, at least, not always or necessarily false. (28) In response to an argument from the FDA that the FDCA "prescribes a specific system for determining the 'truth' of claims about drugs and devices"--making off-label promotion per se false or misleading--the court famously wrote that the agency "exaggerate[d] its overall place in the universe. …

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