Sex, Drugs, and Commercial Speech: The Contested Discourse of Truvada
Joseph F. Lawless*
* Farnsworth Note Competition Winner, 2016. Ph.D. Candidate 2022, College of William & Mary, American Studies; J.D. Candidate 2017, Columbia Law School; B.A., University of Pennsylvania, 2012. The author thanks Professor Noa Ben-Asher of Pace Law School for her thoughtful comments on prior drafts and for her wonderful encouragement; gratitude is also extended to Professor Bernard E. Harcourt and Professor Patricia J. Williams of Columbia Law School, both of whom remain faithful interlocutors and generous mentors. Finally, the author offers the most heartfelt thanks to the editorial staff of the Journal of Law and Social Problems, with particular appreciation to Tara Raam, for their herculean efforts during the editing process.
In January 2016, Michael Weinstein, president of the AIDS Healthcare Foundation (AHF), a globally influential HIV/AIDS policy organization, urged the Food and Drug Administration (FDA) to take legal action against Gilead Sciences, manufacturer of the HIV-prophylactic medication Truvada, for violations of the Food, Drug, and Cosmetic Act (FDCA). The violations the letter enumerated were in reference to a Gilead-sponsored video advertising campaign that, per the allegations, misrepresented the proper usage regimen of Truvada. Under constitutional precedent governing commercial speech vis-à-vis pharmaceutical marketing, such misrepresentation of a drug’s constitutes “off-label” speech, a form of promotional advertising subject to criminal sanctions. This Comment explores the implications of AHF’s claims in the context of recent changes to commercial speech doctrine. It contends that should the FDA act upon the allegations contained in AHF’s letter it would require the agency to argue in favor of a significant misapplication of commercial-speech doctrine, particularly with regard to the branding provisions of the FDCA. Because the FDA continues to harden its stance on off-label use and speech, and in light of policy changes potentially encouraged by the new presidential administration, an examination of how the FDA might respond to allegations of FDCA violation is crucial. This Comment concludes by observing that the significance of this analysis is only heightened when the drug under legal scrutiny is one like Truvada — a prophylactic medication potentially able to drastically reduce the rate of HIV contraction if rendered more widely available.
In January 2016, Michael Weinstein, president of the AIDS Healthcare Foundation (AHF), the world’s largest and most influential HIV/AIDS advocacy organization,[fn id=”1″] wrote a letter to the Food and Drug Administration (FDA) urging the agency to take legal action against Gilead Sciences (Gilead), the biopharmaceutical company that maintains exclusive patent rights over the drug Truvada, for misbranding and promoting false information regarding the drug’s proper medical use.[fn id=”2″] AHF’s primary allegations referenced a video advertising campaign that, per the organization, misrepresented the proper usage regimen of Truvada, in violation of the Food, Drug, and Cosmetic Act (FDCA).[fn id=”3″] This misrepresentation would, under commercial-speech precedent vis-à-vis pharmaceutical drugs, constitute “off-label” speech, a form of promotional advertising subject to criminal sanctions.[fn id=”4″] A pharmaceutical company engages in off-label speech when it encourages the use of a drug in a manner inconsistent with that approved by the FDA and presented on the drug’s labeling.[fn id=”5″] Based on Gilead’s putative off-label advertising, AHF insisted the FDA admonish Gilead publically, mandate that Gilead correct the misinformation it has spread, and issue any and all legally permissible sanctions.[fn id=”6″]
This Comment will explore the implications of the claims AHF proffers in its letter to the FDA; if heeded by the agency, AHF’s call to action would require significant misapplication of commercial-speech doctrine by the FDA, particularly with regard to the branding provisions of the FDCA. As one of the most influential voices on HIV/AIDS advocacy globally, AHF is in a unique and potent position to propel or strain policy narratives based on their alignment with the organization’s political agenda. It is because of AHF’s position as a central actor within policy debates and legal discourse addressing HIV/AIDS that its demand for legal intervention against Gilead, however misled, cannot be dismissed as facile pandering or hyperbole. Indeed, as the FDA continues to harden its stance on off-label use and off-label speech under the new presidential administration,[fn id=”7″] the question of whether a drug as important as Truvada — a prophylactic medication able to drastically reduce the rate of HIV contraction — may be forcibly removed from interstate commerce is one that echoes throughout the nodal point of commercial speech doctrine and health law.
II. AHF AND THE LEGAL ASSAULT ON GILEAD AND TRUVADA
A. THE HIV/AIDS EPIDEMIC AND PARADIGMS OF TREATMENT
In 1982, a crisis emerged that permanently altered the juncture at which queer male bodies and American law met. Throughout the first five months of 1982, physicians documented a constellation of physiological symptoms primarily affecting individuals in urban settings that bore no relationship to preexisting diseases.[fn id = “8”] Clinical reports stated that the symptoms from which these persons suffered engendered a complete disintegration of the immune system, leaving patients’ bodies susceptible to rare forms of cancer and serious infections.[fn id = “9”] Nearly all who presented this symptomatic mosaic self-identified as gay men, leading researchers to call the anomalous collective Gay-Related Immunodeficiency (GRID).[fn id = “10”] It was not until September 1982, as rates of infection continued to grow exponentially, that the Centers for Disease Control (CDC) named the cluster of mysterious and fatal symptoms intimately associated with queer death Acquired Immune Deficiency Syndrome (AIDS).[fn id = “11”] Subsequent epidemiological investigation revealed that the ailments symptomatic of AIDS were caused by sustained viral infection.[fn id = “12”] By May 1986, there was near-universal consensus among the international scientific community that the pathological agent causing AIDS was a virus; the International Committee on the Taxonomy of Viruses soon convened to confirm this consensus, naming the AIDS-causing pathogen the Human Immunodeficiency Virus (HIV).[fn id = “13”]
On the biopharmaceutical frontier, research for treatments of HIV/AIDS would remain reactive in nature until the publication of a 2010 multinational study that evaluated the efficacy of a once-daily oral antiretroviral treatment to proactively reduce the likelihood of HIV acquisition.[fn id = “14”] Named the Preexposure Prophylaxis Initiative (iPrEx), the study enrolled 2500 HIV-negative subjects across six countries,[fn id = “15”] each of whom received chemoprophylactic therapy in the form of an antiretroviral composite pill. The study concluded that, although “[t]he protective effect of [the composite antiretroviral] was . . . not as high as originally hypothesized . . .,”[fn id = “16”] ingestion of the once-daily oral pill “provided 44% additional protection from HIV [acquisition] among men . . . who have sex with men . . . .”[fn id = “17”] The discussion the iPrEx study began continued in 2011, when two additional studies confirmed the efficacy of the composite antiretroviral in reducing HIV acquisition.[fn id = “18”]
The composite pill would be named Truvada, and it was subsumed within the general preventative HIV treatment known as Pre-Exposure Prophylaxis (PrEP) as its bio-chemical component. Gilead, the biopharmaceutical company that maintained exclusive rights over the patents covering Truvada, immediately sought to introduce the medication into the United States market following the success of these international studies.[fn id = “19”] Although Gilead successfully petitioned the FDA to begin sales of Truvada in July 2012,[fn id = “20”] the medication immediately incited controversy. Truvada’s most vocal opponent was Michael Weinstein, president of the AIDS Healthcare Foundation. Both prior and subsequent to the FDA’s approval of Truvada, Weinstein employed AHF’s influential marketing apparatus to sustain a lobbying campaign intended to discredit Truvada as false science.[fn id = “21”]
B. AHF’S LETTER TO THE FDA AND THE THREAT TO TRUVADA
AHF’s campaign against Truvada took on a legal dimension in January 2016, when Weinstein wrote a letter to the FDA urging legal action against Gilead for misbranding Truvada and for promoting false information about the medication’s use through a video advertisement campaign.[fn id = “22”] The letter stated that, despite the restrictions on Truvada that the FDA clearly articulated, Gilead had “launched a brazen new ad campaign to promote situational use of the anti-retroviral as a ‘party drug.’”[fn id = “23”] It further alleged that Gilead’s advertisements “misleadingly impl[ied] that Truvada can be effectively used exclusively on a situational basis to prevent HIV infection on occasions when an individual decides to [be sexually active].”[fn id = “24”] AHF’s letter described with particular invective a moment in one of the three advertisements[fn id = “25”] wherein an actor stated that he “‘like[s] to party[ ]’ as the video shows him reaching for Truvada the morning after he presumably engaged in sex.”[fn id = “26”] Per AHF, because the campaign “entirely contradicts the scientific evidence for the drug’s effectiveness[, it] constitutes advertising for an unapproved and off-label use.”[fn id = “27”] AHF even expands its criticism of the videos beyond the boundaries of adherence to a regimen of Truvada use. As Weinstein comments:
It is also worth noting that the ad goes even further than promoting off-label usage of Truvada and essentially promotes illicit drug use as part of an “I Like to Party” lifestyle. At one point, one of the ads clearly shows the primary actor reaching for recreational drugs as he leaves his home for an evening of “partying.” It is precisely this cavalier attitude toward complying with the established PrEP regiment, consistent condom use, and regular testing that undermines the effectiveness of Truvada and expressly contradicts the approved usage of the drug.[fn id = “28”]
AHF found that the videos in question excluded “any references to the side effects associated with Truvada,” a transgression compounded by the absence of any reference to Truvada by its name.[fn id = “29”] The videos, AHF noted, concluded with a slate that made unmistakable the financial support of Gilead in the production of the advertisements, which AHF found to “clearly establish[ ] a link between the manufacturer of Truvada and the inappropriate off-label promotion of the drug.”[fn id = “30”] Because AHF believed that Gilead launched this campaign in purposeful contravention of statutes and regulations, its letter urged the FDA to take immediate action by halting Gilead’s off-label promotion, requiring Gilead to publically correct the false claims disseminated by its advertisements, and imposing any sanctions permissible under law.[fn id = “31”]
III. THE DOCTRINE OF COMMERCIAL SPEECH IN THE CONTEXT OF PHARMACEUTICAL EXPRESSION — SITUATING THE CONSTITUTIONAL BOUNDARY
AHF’s primary allegation in its letter to the FDA is that Gilead, by financially supporting the production of the aforementioned advertising videos, launched a campaign “to mislead viewers into believing that Truvada is safe and effective for use on a situational basis despite knowing that the drug is not approved for such use.”[fn id = “32”] Consequently, the advertisement campaign “constitutes impermissible off-label promotion” of Truvada contravening the FDCA and regulations the FDA has passed pursuant to its delegated power.[fn id = “33”] Because the FDA continues to vacillate on the policy position it will adopt with regard to the off-label promotion of pharmaceuticals,[fn id = “34”] the legal inquiry raised by AHF’s letter addresses more than its conflict with Gilead — it speaks to the continued viability of the constitutional proscription of commercial speech on behalf of drug manufacturers. The broader scope the AHF-Gilead conflict implicates sharpens in clarity when situated within the context of a January 2017 rule promulgated by the FDA,[fn id = “35”] which dealt directly with the threshold of liability required to hold a pharmaceutical company responsible for the promotion of off-label uses of FDA-approved medications.[fn id = “36”] In consideration of these issues, this Part will examine the interstices of overlap between FDCA law and commercial-speech doctrine as related to the regulation of pharmaceutical speech. This examination will provide a normative foundation upon which an analysis of AHF’s misbranding allegations and its subsequent request that the FDA restrict Gilead’s speech may be constructed.
A. THE CONSTITUTIONAL TERRAIN OF COMMERCIAL SPEECH IN THE PHARMACEUTICAL CONTEXT
The FDCA empowers the FDA to police the “introduction . . . into interstate commerce . . . any . . . drug . . . that is adulterated or misbranded.”[fn id = “37”] A drug is misbranded if it lacks “adequate warnings . . . against unsafe dosage . . . as are necessary for the protection of users . . . .”[fn id = “38”] The misbranding provision ties intimately to the labeling mandate of the FDCA; when a pharmaceutical company submits a New Drug Application (NDA) for evaluation, it must include “the labeling proposed to be used for such drug” so the FDA may evaluate the label’s accuracy.[fn id = “39”] The FDCA defines “labeling” as “all labels and other written, printed, or graphic matter . . . accompanying such [drug].”[fn id = “40”] This provision has been broadly interpreted so as to include information entirely separated from the medication itself as supplementary labeling.[fn id = “41”] What the FDA legally approves, then, is not the drug itself, but the drug’s specific medical use, known as the drug’s “indication.”[fn id = “42”] For a label to be sufficient, it must dictate the proper conditions under which the drug should be prescribed. A label that does not focus on a specific treatment or on a narrow constituency of patients might fail to meet this high threshold, thereby precluding the drug from entering interstate commerce.[fn id = “43”] Once a product is approved to enter interstate commerce, however, a physician may prescribe such medication to treat any illness.[fn id = “44”] Thus, because doctors may speak about off-label uses and promote medications for such uses while pharmaceutical companies cannot, two forms of drug-related speech begin to circulate — on-label speech and off-label speech.[fn id = “45”]
Despite its legal prohibition against the off-label marketing of medication, the FDA does not regulate the prescription of medication by doctors for off-label purposes.[fn id = “46”] In fact, once the FDA approves a drug for a specific treatment, the use of that drug in alternative and unconventional contexts is left to the discretion of the prescribing physician.[fn id = “47”] Further, restrictions on the dissemination of scientific literature discussing off-label uses apply only to the commercial entities that manufacture the medication; a physician’s request for such literature is inoculated against legal indictment.[fn id = “48”] An asymmetry of permissible speech thus materializes, the axis of which separates the physician, whose charge is the treatment of the individual patient, from the FDA, whose statutory purpose is to protect public health.[fn id = “49”] When challenged as improper or unconstitutional, this asymmetry triggers the protections offered by the First Amendment.[fn id = “50”] Specifically, such challenges are filtered through the doctrine of commercial speech, as they ask whether it is permissible to proscribe drug manufacturers from disseminating information regarding off-label uses for their medication,[fn id = “51”] and whether the labeling requirements of the FDCA are too onerous for even the largest of biopharmaceutical companies to meet.[fn id = “52”]
Although the seminal case establishing the doctrinal analysis of commercial speech regulation is Central Hudson Gas & Electric Corporation v. Public Service Commission of New York,[fn id = “53”] the questions of off-label commercial speech and FDA proscriptions on that speech were first prominently addressed in a series of D.C. Circuit cases now taken as a significant authority on these inquiries.[fn id = “54”] Thus, while Central Hudson provides the overarching normative framework for commercial-speech constitutional analysis, the decisions issued by the D.C. courts in the Washington Legal Foundation cases illuminate how Central Hudson’s structure should be applied in the context of FDA-based restrictions on manufacturers’ speech.
At issue in Washington Legal Foundation were FDA policies articulated within Guidance Documents the agency had published, which concerned “manufacturer distribution of reprints of medical textbooks and peer-reviewed journal articles . . ., and manufacturer involvement in continuing medical education seminars and symposia . . . .”[fn id = “55”] The Washington Legal Foundation (WLF), a public-interest law firm whose mission is “to preserve and defend America’s free-enterprise system by litigating, educating, and advocating for free-market principles,”[fn id = “56”] sought a declaratory judgment that the FDA policies expressed in the Guidance Documents violated rights under the First Amendment. Specifically, the interest group argued that the portions of the Guidance Documents (1) restricting the distribution of medical textbooks and peer-reviewed journal articles and (2) narrowing the permissible scope of manufacturer involvement in medical educational symposia unconstitutionally burdened pharmaceutical companies’ speech.[fn id = “57”] Such materials and actions, the FDA contended, must generally aim to “strike the proper balance between the need for an exchange of reliable scientific data and information within the health care community[ ] and the statutory requirements that prohibit companies from promoting products for unapproved uses.”[fn id = “58”] When the content of materials or the information provided at a medical symposium is heavily influenced by drug manufacturers, their scientific accuracy risks adulteration and thus, per the FDA, necessarily becomes subject to increased scrutiny.[fn id = “59”]
The pivotal Washington Legal Foundation case, decided in 1998 at the district-court level, characterized the threshold inquiry demanding resolution as “how to classify the ‘speech’ at issue [in the instant case],”[fn id = “60”] that is, whether the speech in question is ultimately more properly taxonomized as “pure speech or commercial speech.”[fn id = “61”] Commercial speech, the court noted, is typically “authored and/or uttered directly by the commercial entity that wishes to financially benefit from the message.”[fn id = “62”] With regard to the prescription drug industry, the “dissemination of scientific research results [represents] an especially important and prevalent marketing tool,”[fn id = “63”] leading manufacturers to “want to get scientific information demonstrating the efficacy of their products in the hands of physicians”;[fn id = “64”] statements meant to market pharmaceuticals therefore present the question of whether academic speech articulated in the service of commercialism dilutes the level of First Amendment protection to which the speech is entitled.[fn id = “65”] The Supreme Court first articulated a doctrinal framework to determine whether the communication under scrutiny constitutes commercial speech in Bolger v. Youngs Drug Products Corporation, the three prongs of which are: (1) whether the speech is “conceded to be [an] advertisement[ ]”;[fn id = “66”] (2) whether the speech makes “reference to [the] specific product”;[fn id = “67”] and (3) whether the speaker “has an economic motivation” for the speech that would “turn [it] into commercial speech.”[fn id = “68”] In its application of each of the Bolger factors to both manufacturers’ influence over medical symposia and the dissemination of medical journal articles by pharmaceutical companies, the district court in Washington Legal Foundation held that such speech “is properly classified as commercial speech” and thus subject to the four-part test articulated in Central Hudson.[fn id = “69”]
In Central Hudson, the Court described its constitutional analysis of commercial-speech restrictions as follows:
At the outset, we must determine whether the expression is protected by the First Amendment. For commercial speech to come within that provision, it at least must concern lawful activity and not be misleading. Next, we ask whether the asserted governmental interest is substantial. If both inquiries yield positive answers, we must determine whether the regulation directly advances the governmental interest asserted, and whether it is not more extensive than is necessary to serve that interest.[fn id = “70”]
Although the district court in Washington Legal Foundation was, at the time of its decision, applying the full scope of jurisprudential precedent then available,[fn id = “71”] the Supreme Court has since intervened in the domain of commercial pharmaceutical communications.[fn id = “72”] This intervention has resulted in a multilayered constitutional analysis that has been modeled by the Second Circuit Court of Appeals and a district court within its jurisdiction.[fn id = “73”] These three cases — Sorrell v. IMS Health Inc., United States v. Caronia, and Amarin Pharma, Inc. v. FDA — illustrate the more robust analysis now expected of federal courts considering restrictions on commercial pharmaceutical speech. Of importance in Sorrell was the Supreme Court’s articulation of the relationship between the First Amendment and pharmaceutical marketing: “[s]peech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment. As a consequence, [statutory restrictions on such speech] must be subjected to heightened judicial scrutiny.”[fn id = “74”] This determination would undergird the reasoning articulated in both Caronia and Amarin and as well as propel a shift in the FDA’s regulatory regime in 2017.[fn id = “75”]
B. CONSTELLATING THE EFFECTS OF SORRELL IN THE SECOND CIRCUIT — UNITED STATES V. CARONIA AND AMARIN PHARMA, INC. V. U.S. FOOD & DRUG ADMINISTRATION
AHF’s letter alleges that Gilead’s video campaign, the contents of which will be discussed infra, misleads “viewers into believing that Truvada is safe and effective for use on a situational basis despite [Gilead’s] knowing that the drug is not approved for such use.”[fn id = “76”] Such promotion, AHF argues, is proscribed by the FDCA.[fn id = “77”] This question of the FDCA’s proscriptive jurisdiction was left unanswered in Sorrell, as the object of the Court’s consideration therein was the constitutionality of a state statute.[fn id = “78”] However, in United States v. Caronia, the Second Circuit Court of Appeals addressed directly “whether . . . prosecution . . . under the FDCA only for promoting an FDA-approved drug for off-label use [could be] constitutionally permissible.”[fn id = “79”] While the FDCA criminalizes misbranding or conspiring to misbrand a drug, the statute and its corresponding regulations do not explicitly proscribe off-label promotion. Instead, 21 C.F.R. § 201.128, which addresses how a manufacturer’s intent may be evinced during a prosecution pursuant to the FDCA’s misbranding provisions, emphasizes an objective evaluation that “may, for example, be [buttressed] by labeling claims, advertising matter, or oral or written statements by such persons or their representatives.”[fn id = “80”] Such analysis of the mens rea element of the misbranding offense necessarily implicates speech, which, as the Caronia court acknowledged, raises significant First Amendment concerns.[fn id = “81”]
Recognizing that construing the FDCA as criminalizing the mere promotion of a drug’s off-label use would pose a grave constitutional difficulty, the court offered a narrow interpretation of the statute as, pursuant to the doctrine of constitutional avoidance,[fn id = “82”] “not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs.”[fn id = “83”] The court began its analysis by considering the two-step inquiry articulated in Sorrell, wherein a court is first to consider “whether the government regulation restricting speech [is] content- and speaker-based”[fn id = “84”] and then “whether the government ha[s] shown that the restriction on speech [is] consistent with the First Amendment under the applicable level of heightened scrutiny.”[fn id = “85”] Importantly, the Sorrell Court did not flesh out the contours of this “heightened scrutiny,” instead noting only that the state statute in question would be “unconstitutional even under the lesser intermediate standard set forth in Central Hudson.”[fn id = “86”] Though the Supreme Court appeared to indicate that its abridged analysis could supplant the four-prong test developed in Central Hudson, the Caronia court offered an ordinal and merged interpretation of the doctrinal frameworks, beginning with Sorrell’s two-step inquiry to determine whether a constitutional violation based on viewpoint-discrimination exists and ending with Central Hudson’s less rigorous examination to consider whether the government can justify its criminal proscription of off-label promotion.[fn id = “87”]
A determination of content-based discrimination turns on whether the FDCA “distinguishes between ‘favored speech’ and ‘disfavored speech on the basis of the ideas or views expressed.’”[fn id = “88”] Under the government’s proffered construction, speech about government-approved uses of drugs would be permissible while speech about off-label uses would necessarily remain prohibited, even if off-label use was not prohibited per se. This interpretation would have the express purpose of diminishing “‘the effectiveness of [off-label drug] marketing by manufacturers,” strongly suggesting that the FDCA’s regulation of commercial speech was content-based and therefore presumptively unconstitutional.[fn id = “89”] That this construction would effect speaker-based discrimination was facially manifest — as the court noted, “it targets one kind of speaker — pharmaceutical manufacturers — while allowing others to speak without restriction.”[fn id = “90”] The court leveraged the Sorrell analysis to repudiate the government’s construction of the FDCA, and, after rejecting this reading of the statute, it turned to Central Hudson to determine whether the government could nevertheless pursue criminal sanctions under an alternative reading of the FDCA. Insofar as the government’s position advocated the criminalization of off-label promotion, it could not be squared with its curious acquiescence in the dissemination of information regarding off-label use when requested by physicians;[fn id = “91”] accordingly, the court concluded that the government’s “criminal ban on off-label promotion by pharmaceutical manufacturers [was] more extensive than necessary to achieve [its] substantial interests.”[fn id = “92”] The court ultimately construed the FDCA’s misbranding provisions “as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved drugs.”[fn id = “93”]
A year prior to the decision in Caronia, Amarin Corporation (Amarin), a biopharmaceutical company, sought FDA approval for a single use of Vascepa, a drug it had developed to address cardiovascular health issues.[fn id = “94”] Subsequent to the FDA’s authorization of Vascepa’s intended use, Amarin sought in 2013 an additional approval for Vascepa to treat a derivatively related cardiovascular condition; the FDA, however, denied Amarin’s application, stating that the clinical trials Amarin conducted failed to yield sufficient data to support the medical benefits of this second usage.[fn id = “95”] In response, Amarin stated that it wished at minimum to include the results of those clinical trials on Vascepa’s label to better ensure that physicians were aware of the drug’s positive indication for multiple cardiovascular conditions.[fn id = “96”] In 2015, the FDA issued a letter refusing Amarin’s request and further stated that, should the company market Vascepa for any usage other than the one approved by the agency, the company would expose itself to criminal liability for “misbrand[ing] under the FDCA.”[fn id = “97”] Ten days after FDA’s implicit threat of prosecution, Amarin filed a civil suit in the Southern District of New York, claiming that “FDA’s threat of a misbranding action [was] chilling it from engaging in constitutionally protected truthful speech”[fn id = “98”] and seeking “an injunction that would prohibit the FDA from bringing a misbranding action against [the company] for its truthful and non-misleading statements to doctors regarding Vascepa . . . .”[fn id = “99”]
In granting Amarin’s application for preliminary injunctive relief, the district court rooted its analysis squarely in the precedent set by Caronia. In order to establish the intent (mens rea) and act (actus reus) elements of a misbranding action, the FDA argued at trial that it could “use Amarin’s statements regarding Vascepa’s [second usage] as objective evidence of Amarin’s intent to promote [Vascepa] for [an] off-label purpose” and cite any “truthful and non-misleading statements about that use” made by Amarin as evidence of the act of misbranding itself.[fn id = “100”] However, the court noted that, “under Caronia, the FDA may not bring such an action based on truthful promotional speech alone, consistent with the First Amendment.”[fn id = “101”] The Caronia majority presented the issue as “whether a misbranding prosecution that identified a defendant’s speech alone as the proscribed conduct [could be] constitutionally permissible,” and the ensuing analysis held categorically that the FDCA’s misbranding provisions were not to be construed as reaching truthful speech promoting off-label use.[fn id = “102”] Caronia is thus to be understood as a case of statutory construction that turned not on the mens rea requirement of the misbranding provision but rather on the actus reus requirement of that provision, and, because the court read the FDCA did not reach truthful, non-misleading speech promoting off-label uses, the FDA could not constitutionally pursue its threatened prosecution.[fn id = “103”]
IV. CONTESTING TRUVADA — CONSIDERING PHARMACEUTICAL SPEECH POST-CARONIA AND THE FDA’S NEW REGULATORY CALCULUS
A. A “BRAZEN NEW AD CAMPAIGN” — DETAILING THE CONTENT OF THE GILEAD-SUPPORTED VIDEO ADVERTISEMENTS
The AHF’s letter to the FDA regarding Gilead’s putative misbranding of Truvada, now written just over one year ago, has not yet incited a legal response from the agency. Although the president of AHF, Michael Weinstein, addressed the letter to Stephen Ostroff, the then-Acting Commissioner of the FDA, there is no evidence the document was routed to the FDA’s Office of Prescription Drug Promotion (OPDP), the branch of the FDA charged with the review and surveillance of drug advertisement materials and thus the proper addressee.[fn id = “104”] The FDA marshals the OPDP to run its “Bad Ad Program,” the purpose of which is “to increase the effectiveness of OPDP’s surveillance . . . especially with regard to curtailing inappropriate promotional activities” by allowing any individual to report misleading prescription-drug promotion.[fn id = “105”] Assuming, arguendo, the AHF’s letter to the FDA can be taken as a form of reporting to the Program, the central investigative inquiry facing an OPDP reviewing officer would be whether the speech cited by AHF — three online videos, the production of which was financially supported by Gilead — encourage a use of Truvada inconsistent with the FDA’s approved usage. A review of the videos produced for the advertising campaign is therefore useful in proceeding with the below analyses.
In total, Gilead appears to have sponsored the production of three videos by Public Health Solutions, a nonprofit organization based in New York City,[fn id = “106”] all of which addressed the question of whether Truvada was the right choice for an individual or a couple. In the first video, an actor is seen collecting condoms and a small plastic bag of unidentifiable pills before heading out to a bar.[fn id = “107”] The actor states that he “like[s] to party” while dancing at the bar. In the following scene, he is seated at home, looking at his cellphone, which provides him with a reminder to take his daily dosage of Truvada.[fn id = “108”] As the reminder appears on the screen, the actor states that he also “like[s] to be safe.”[fn id = “109”] In the second video, a man is seen on his cellphone, facilitating a casual sexual encounter with another user of a cellphone application.[fn id = “110”] After the two enter the man’s bedroom, he states to his paramour: “Hey . . . I’m on PrEP.”[fn id = “111”] When his partner admits to complete ignorance regarding Truvada, the man is shocked.[fn id = “112”] The screen then cuts to a slide that offers a hyperlink for viewers to learn more about the medication.[fn id = “113”] The third video is a series of crosscut interviews among several couples, all of whom are serodiscordant in HIV status.[fn id = “114”] Each couple speaks about the multiple reasons why one might use Truvada or instead depend on condoms as the means of prophylaxis.[fn id = “115”] One couple discusses the side effects of Truvada, after which an individual describes the three-month testing regimen for HIV status, as well as testing for kidney and liver health, that is medically necessary when taking Truvada.[fn id = “116”] Perhaps most notable is when one member of a couple plainly states that he does not believe that Truvada is for everyone, as it requires an individual to have educated herself about HIV/AIDS and make the personal choice about what role she expects the medication to play in a serodiscordant relationship.[fn id = “117”]
B. THE VIABILITY OF AHF’S ALLEGATIONS AFTER CARONIA AND AMARIN
A determination of misbranding turns on a drug’s labeling; as mentioned, the FDCA defines “labeling” as “all labels and other written, printed, or graphic matter . . . accompanying [a drug].”[fn id = “118”] At the outset, then, AHF’s linkage of the videos to Truvada’s labeling is legally sound. Nevertheless, the primary allegation in AHF’s letter — that Gilead engaged in the purposeful misbranding of Truvada through Public Health Solutions’ video campaign — seems unsustainable upon a plain review of the three videos’ content. In the letter’s concluding paragraph, AHF President Michael Weinstein characterizes the video campaign as misleading viewers into believing that Truvada “is safe and effective for use on a situational basis,” a point the letter earlier supports by reference to the content of the first video.[fn id = “119”] The letter suggests that the small plastic bag the actor takes as he leaves his home contains recreational drugs, and, because the use of recreational drugs is assumed to be metonymic with a “cavalier attitude toward complying with the established PrEP regiment, consistent condom use, and regular testing,” the video necessarily “undermines the effectiveness of Truvada and expressly contradicts the approved usage of the drug.”[fn id = “120”] While the suggestion that recreational drug use is integrated into certain sites of queer male culture is not without merit,[fn id = “121”] the chain of inferential reasoning the letter proposes is incoherent. First, the conclusory statement that recreational drug use bears a relationship to an individual’s ability to adhere to a specific medical regimen is without support; second, the statement is intentionally written in bombastic fashion to veil the weaknesses of AHF’s legal arguments, which require the presence of misleading speech within the video and thus cannot be sustained.
As explained in Amarin, Caronia held that “the FDCA’s misbranding provisions cannot constitutionally criminalize, and therefore do not reach, the act of truthful and non-misleading speech promoting off-label use.”[fn id = “122”] This conclusion necessarily followed from the Supreme Court’s prior observation that “[s]peech in aid of pharmaceutical marketing . . . is a form of expression protected by the Free Speech Clause of the First Amendment” and thus cannot be restricted absent a failure to satisfy the four parts of the Central Hudson analysis.[fn id = “123”] AHF’s claim that Gilead promotes the situational use of Truvada as medicinally effective would, if before a court, likely be addressed under Central Hudson’s first prong, which queries whether the commercial speech under scrutiny is “more likely to deceive the public than inform it . . . .”[fn id = “124”] The court in Caronia reiterated the axiom that “the First Amendment does not protect false or misleading commercial speech,” and the court’s construction of the FDCA affords no protection to the manufacturer who employs misleading communications in the promotion of an off-label use.[fn id = “125”]
The content of the first promotional video, though potentially referencing illegal substance use, certainly does not bind this provocative possibility to its representations of how Truvada is properly used. The actor states that his enjoyment of socializing does not compromise his commitment to sexual safety, a message that the ringing of his cellphone’s daily reminder to take Truvada daily reiterates, a schedule clearly aligned with the medication’s prescription regimen. Indeed, it may be that “partying” and “safety” are placed in such purposeful juxtaposition to demonstrate that the two are not irreconcilable — an individual can pursue autonomous sexual choices while remaining committed to bodily health and integrity. Of equal consequence is that, in the context of the other two videos that constitute the advertising campaign, the messages presented in this first video appear intended to acknowledge the frank reality both of HIV/AIDS and of a strong desire to pursue enjoyment without sacrificing one’s sense of bodily care.
The crystallization of Caronia’s jurisprudential legacy as articulated in Amarin may have suffered partial erosion in mid-2016, when the Second Circuit Court of Appeals issued its decision in U.S. ex rel. Polansky v. Pfizer.[fn id = “126”] The court there asserted in a footnote that its holding in Caronia, though having avoided the constitutional question presented by the FDCA’s potential implication of the First Amendment, had nevertheless “left open the government’s ability to prove misbranding on a theory that promotional speech provides evidence that a drug is intended for a use that is not included on the drug’s FDA-approved label.”[fn id = “127”] A textual examination of Caronia, however, suggests that the court’s misrepresents the Caronia dicta. The court in Caronia did not decide but rather assumed that a drug manufacturer’s promotional speech could be marshaled as evidence to prove that manufacturer’s intended use of a drug, a determination that would then support a criminal prosecution for mislabeling or misbranding.[fn id = “128”] Although this difference in language is ostensibly minute, it effectively circumscribes the reach of Caronia’s holding. Caronia is characterized as a case about simple promotional speech that does not seek to furtively supplant the particular use of a drug that the FDA specifically approved; this retrospective gloss once again opens the possibility of pharmaceutical marketing and speech to function as evidence of a criminal act.[fn id = “129”]
The essentially unanswered question of whether promotional speech may serve as the basis of a criminal prosecution or as partial evidence supporting a criminal prosecution leaves Gilead and, by necessary implication, Truvada in a precarious position. Should AHF’s allegations be taken seriously, the nuanced rereading of Caronia in Polansky could allow the FDA to marshal the video campaign as a piece of criminalizing evidence — one of many that AHF has worked to compile and provide.[fn id = “130”] Unsurprisingly, the FDA has taken notice of the jurisprudential ripples effected by Caronia. In September 2015, the FDA issued a proposed rule that included amendments to the agency’s regulations regarding “intended uses.”[fn id = “131”] In January 2017, the agency promulgated the rule in its final version, and the commentary accompanying the rule in the Federal Register offers useful insight into how the FDA will pursue misbranding allegations in the wake of Caronia.
C. POTENTIAL EFFECTS OF RECENT FDA RULEMAKING PROCEEDINGS AND THE JANUARY 2017 “INTENDED USES” FINAL RULE
In September 2015, the FDA initiated a rulemaking proceeding that had as one of its objectives the amendment of the agency’s “Intended Use” regulations.[fn id = “132”] To better elucidate its position on the types of evidence that are permissibly considered in an intended-use determination, the agency then recommended the deletion of the final sentence of 21 C.F.R. § 201.128,[fn id = “133”] which stated:
But if a manufacturer knows, or has knowledge of facts that would give him notice, that a drug introduced into interstate commerce by him is to be used for conditions, purposes, or uses other than the ones for which he offers it, he is required to provide adequate labeling for such a drug which accords with such other uses to which the article is to be put.[fn id = “134”]
When first promulgated, the regulation sparked significant criticism from pharmaceutical companies because the final sentence, when literally read, appeared to hold that “a manufacturer’s mere knowledge of an unapproved use of its approved drug automatically triggers requirements for new labeling that in turn render distribution of that approved product unlawful . . . .”[fn id = “135”] The FDA’s proposed deletion of that sentence intended to clarify that a manufacturer’s knowledge of physicians’ off-label use of a drug it had manufactured would not, by itself, trigger the FDCA’s labeling provisions.[fn id = “136”] After reviewing the comments submitted in response to the proposed rule, the FDA ultimately decided to forego deletion of the sentence in favor of a detailed re-articulation that would “better reflect” how the agency has consistently applied its intended-use regulation.[fn id = “137”] The final rule excised the former’s focus on manufacturer knowledge and articulated instead that an evaluation of “the totality of the evidence [can] establish[ ] that a manufacturer objectively intends that a drug . . . be used for conditions, purposes, or uses other than ones for which it is approved . . . .”[fn id = “138”]
Several comments to the proposed rule asserted that the FDA was constitutionally required to contract its proposed definition of “intended use” because of recent court rulings, including Caronia and Amarin. The FDA’s response to these comments emphasized the agency’s express disagreement with “the assertion that the current case allow allows FDA to consider speech as evidence of intended use only when it is false or misleading,”[fn id = “139”] as articulated in Caronia. The agency buttressed its claim with a citation to Polansky, quoting the language of the very same footnote that undermined the scope of the Caronia decision.[fn id = “140”] Interestingly, after the Polansky court stated that Caronia left intact the government’s ability to prove misbranding through reliance on promotional speech as evidence, the court then cited the final sentence of 21 C.F.R. § 201.128, the FDA’s intended-use regulation, as analogous support for its argument.
The FDA’s citation to the Polansky footnote in its final rule curiously omitted any reference to court’s inclusion of the intended-use regulation — a somewhat glaring excision insofar as the agency altered the text of that very sentence. The effect of Polanksy’s subtle circumscription of Caronia here becomes manifest, as the FDA was implicitly able to cite itself as judicial authority through its purposeful tailoring of the Polansky court’s footnoted text. This reassertion of the evidentiary value of pharmaceutical speech further corrodes the protection afforded by Caronia. Despite clearly addressing the constitutional complexities of off-label promotion throughout the text of the final rule, the FDA described the legal issues as sufficiently complex to merit a separate examination,[fn id = “141”] which the FDA initiated in September 2016.[fn id = “142”]
The newly altered version of 21 C.F.R. § 201.128 ostensibly provides some legal protection for drug manufacturers against discretionary enforcement actions for off-label promotion, but the FDA’s continuous equivocation in responses to comments on the rule’s proposed form suggests that the agency will not easily abandon its use of speech as prosecutorial evidence. AHF’s assault on Truvada, though amenable to being categorized as politically reactionary, may function as an unexpected symbol of the entropic policy adjustments now characteristic of the current federal political climate. Although the FDA took pains to describe its alteration of the intended-use regulation’s last sentence as a simple clarification of longstanding policy, a totality-of-the-evidence standard may, by virtue of the subjectivity involved in such an assessment, promote greater arbitrariness in the enforcement of FDCA prohibitions. AHF is a powerful advocacy organization whose capacity to ignite unexpected sociopolitical change cannot be discredited,[fn id = “143”] and thus its sustained criticism of Truvada as the potential site of a second AIDS epidemic may tap into an internalized reservoir of AIDS-phobia potent enough to exploit the plasticity of the FDA’s purportedly “consistent” regulatory position.
V. OSSIFYING REGULATIONS OF OFF-LABEL SPEECH — CONCLUDING THOUGHTS ON THE IMPERILING OF TRUVADA AND COMMERCIAL SPEECH
On January 18, 2017, two days before the Trump administration took office and the regulatory ethos of the executive branch would begin to undergo substantive change, the FDA released an official agency document (entitled a “memorandum,” thereby reducing the scope of its regulatory significance to possibly nil) wherein it staked out its position on the First Amendment questions pertaining to off-label commercial speech.[fn id = “144”] This document, which breaks years of agency silence on the specific question of the scope of First Amendment protection to which biopharmaceutical companies are entitled in the off-label marketing of approved drugs, suggests an attempt by the agency to place its views “on the record” before the change in administration results in an alternative approach; indeed, the memorandum may function to undercut the viability of any substantive change in the FDA’s position on off-label marketing, as significant changes in agency policy adversely affect the scope of deference afforded such changes.
The position the FDA articulates in its memorandum reflects the longstanding, implicit stance it has taken on off-label promotion: that the “government’s multi-faceted interests in the public health are substantial and . . . the relevant FDA Authorities directly advance many of those interests.”[fn id = “145”] While it is certainly worthwhile to retain the rigorous standards of examination to which new medical drugs are subjected prior to their approval for placement within the national market, the FDA’s cursory dismissal of the legal questions addressed by the courts in Caronia and Amarin cast doubt on the FDA’s attempt at a reasonable, evidence-based analysis of the public-health concerns those cases raised. The concern of heavily politicized bias within the domain of the FDA’s health policy determinations, augmented by the publication of the aforementioned Memorandum, led an organization of pharmaceutical companies and biotechnology corporations to file a petition to stay the implementation of the FDA’s Final Rule on intended use.[fn id = “146”] According to the industry groups’ petition, the new standard the FDA will employ in its determination of a drug’s intended use, completed under a “totality of the evidence standard,” would allow anything to “be considered to establish a product’s intended use,”[fn id = “147”] thereby allowing the FDA “to rely even on non-promotional scientific exchange as evidence of intended use.”[fn id = “148”] The chilling effect of such a standard is difficult to comprehensively imagine, as any kind of speech a pharmaceutical corporation engages in could be marshaled as evidence that the firm intended to misrepresent the manner in which the drug is approved to be used.
This new standard and the recalcitrance of the FDA to offer a more nuanced position on the relationship between the rights the First Amendment protects and the effects of those rights on commercial speech must be considered in contexts beyond those to which the FDA blithely alludes, such as those in which biopharmaceutical corporations seek the First Amendment as a shield to veil their exploitative efforts.[fn id = “149”] A medication such as Truvada, which serves communities subject to multiple forms of social disqualification, is particularly vulnerable to the kind of attacks the FDA’s policy would allow — a concern that is undoubtedly aggravated in the new political context portended by the Trump administration. The question here is thus not whether the FDA should or should not relax its standards regarding the proliferation of off-label speech; rather, it is whether the broad stroke the current policy effects may prove hazardous to continued access to drugs capable of changing the destruction experienced by communities that remain vulnerable to systemic exposure to illness and disease. Further, this question must consider whether the FDA’s position may offer the new administration a sword against which to assault those biopharmaceutical companies not engaged in off-label speech, as conventionally envisioned, but engaged in providing medication and information to communities otherwise imperiled by lack of access to medical information and drug availability.