Don't Fix What Ain't Broken--off-label Marketing, the Fda's Regulatory Regime, and the First Amendment

• Publication year: 2018

Don't Fix What Ain't Broken--Off-Label Marketing, the FDA's Regulatory Regime, and the First Amendment

Loren Jacobson

DON'T FIX WHAT AIN'T BROKEN—OFF-LABEL MARKETING, THE FDA'S REGULATORY REGIME, AND THE FIRST AMENDMENT Loren Jacobson^*

Introduction

In 1962, Congress passed the Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act (FDCA), requiring that drugs and devices be approved for safety and effectiveness for a particular use before companies could market them for that use. Prior to the amendments, once a manufacturer had a product approved for safety, it could market the product for any use whatsoever, regardless of effectiveness. The Congressional hearings leading up to the amendments demonstrated a pattern and practice of false and misleading promotion of drugs by the pharmaceutical industry.¹ These promotional practices encouraged physicians to prescribe drugs with very serious side effects for uses that were not proven to be effective. For example, Mellaril, which was reserved as a drug of last resort for schizophrenia because of its severe side effects and was pulled off the market in 2005 due to concerns that it increased the risk of cardiac arrhythmias and could cause sudden death,² was widely promoted for pregnant women with emotional symptoms in connection with childbirth, for chronic fatigue, insomnia, anxiety, apprehension, and vague digestive disorders.³ Diethylstilbestrol (DES) was marketed widely to prevent miscarriage, even in normal pregnancies. But DES caused a high rate of reproductive abnormalities in the children of women given DES, including a rare form of vaginal cancer in girls, and a later study of the drug showed it to be completely ineffective in preventing miscarriages.⁴ Without regulations requiring that drug companies prove their products to be safe and effective for a particular use before marketing them for that use, thousands of Americans suffered adverse consequences from drugs that were not even effective for the uses for which they were being promoted, often on the basis of anecdotal or other unreliable evidence.

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Yet ever since the Kefauver-Harris Amendments were put into place, pharmaceutical and device companies, whose ostensible purpose is to "work[] together for patients" and to "work together for a healthier world,"⁵ have sought to undermine the prohibition on marketing until safety and effectiveness have been established. The companies and their defenders claim that the system is broken because marketing restrictions prevent patients with few other alternatives from getting life-saving drugs and devices and that the clinical trials required to "satisfy the FDA's demanding standards" are expensive.⁶

The companies and their lobbyists have made some legislative in-roads. Last year, the state of Arizona passed a bill specifically allowing "a pharmaceutical manufacturer or its representative" to "engage in truthful promotion of an off-label use of a drug, biological product or device," and prohibiting state officials from prosecuting a pharmaceutical manufacturer or cooperating with federal officials in a prosecution or other action for off-label promotion.⁷ It remains to be seen what, if any, effect the bill will have, since Arizona likely already cooperates very little in prosecutions for off-label marketing since the state does not have a False Claims Act that would allow the state to recoup Medicaid payments made for prohibited off-label promotion, and in any case, the law is likely preempted by federal law.⁸ In March 2017, U.S. Congressman Morgan Griffith introduced the "Medical Product Communications Act of 2017," which seeks to amend the FDCA by allowing companies to make any communication about a product so long as it is "supported by scientifically appropriate and statistically sound data, studies, or analyses," which according to the bill, includes dissemination of scientific findings in "lay media" and "letters to the editor in defense of public

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challenges."⁹ The bill was referred to the Committee on Energy and Commerce, which held a hearing on it last July, but it has not made any further progress.¹⁰

But the pharmaceutical companies' main weapon has been the First Amendment, and the weapon landed a massive blow when the United States Circuit Court for the Second Circuit ruled, in United States v. Caronia,¹¹ that the prosecution of a pharmaceutical sales representative for misbranding—promoting a drug for unapproved uses—violated the First Amendment. The court held that, while the First Amendment did not protect false or misleading speech, "the government cannot prosecute the pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug."¹² The opinion is striking because before it, courts had generally considered misbranding prosecutions not to even implicate the First Amendment.¹³

The decision, although from only one circuit court, seems to have chilled the ability or willingness of the federal Food & Drug Administration (FDA) to ensure that drug and device companies only promote their products for uses that have proven to be safe and effective. Since the decision, the Department of Justice has announced only three False Claims Act settlements involving unlawful drug promotion—one against Shire Pharmaceuticals that mainly settled claims relating to "false and misleading" promotion,¹⁴ another against Genentech Inc. and OSI Pharmaceuticals LLC related to "misleading statements

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about the effectiveness of the drug Tarceva,"¹⁵ and a third against Celgene for marketing two cancer drugs for unapproved uses.¹⁶ Moreover, most recent criminal prosecutions of pharmaceutical companies appear to be related to promotion of drugs that have not been approved at all.¹⁷ While it may be that pharmaceutical companies are engaging in less off-label promotion, the more plausible explanation for the paucity in the past five years of FCA settlements and prosecutions involving the off-label marketing of pharmaceuticals is the Caronia decision.¹⁸

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Nevertheless, on the eve of the change in administrations, the FDA released a Memorandum and two draft guidances on drug and device manufacturer communications and opened a public comment period for the draft guidances.¹⁹ The Memorandum provides a robust defense of the FDCA and a strong rebuttal to Caronia. While it is unclear what the current administration's position will be,²⁰ this essay posits that the current laws, regulations, and rules that control the marketing of drugs and devices for off-label use properly balance providing physicians reliable information so that they soundly exercise their discretion to assist their patients with protecting those patients from ineffective and dangerous products. Moreover, the regulatory system currently in place does not violate drug and device companies' First Amendment rights. The FDA has robust arguments for why Caronia was wrongly decided and the current system strikes the right balance under the First Amendment. Further, the fact that the FDA provides safe harbors to drug and device companies to provide information about off-label uses of their products and the recent amendments made to the FDCA by the 21^st Century Cures Act, which broaden these safe harbors, show that to the extent the FDCA constrains off-label marketing, such constraints are narrowly tailored to effectuate the compelling need to protect the public from harmful and ineffective drugs.

Thus, this essay posits that the FDA should protect the current regime put in place by the Kefauver-Harris Amendments and continue to prosecute drug and device companies and their employees for putting patient lives in danger by marketing their products for off-label use. The essay focuses on the pharmaceutical companies, but device companies are subject to the same regulations. In fact, in 2015, the Department of Justice filed charges, including

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claims for putting misbranded and adulterated products in interstate commerce, against two Acclarent executives, William Facteau and Patrick Fabian, for the promotion of a device approved as a sinus spacer for unapproved use as a steroid delivery system.²¹ Facteau and Fabian were convicted of misdemeanor misbranding and adulteration charges, and the case is still working its way through the judicial system.²²

In the meantime, as this essay makes clear, legislative efforts to allow broader off-label marketing are short-sighted, ignoring both the terrible consequences visited on patients prior to the Kefauver-Harris Amendments. The current regime rightly allows the pharmaceutical and device companies to provide reliable, accurate, and truthful information to physicians so that they can make the best decisions possible for their patients, while ensuring that drugs and devices are only marketed for uses for which they are scientifically proven to be safe and effective.

I. The Regulatory and Legal Background

A. The FDCA and Limits on Off-Label Marketing

The FDCA prohibits the "introduction or delivery for introduction into interstate commerce any . . . drug [or] device . . . that is adulterated or misbranded" and also prohibits "the adulteration or misbranding of any . . . drug [or] device . . . in interstate commerce."²³ A drug or device is misbranded if, among other things, its labeling does not bear "adequate directions for use,"²⁴ which include directions that allow a layperson to use the drug safely "and for the purposes for which it is intended."²⁵ The FDA considers the promotion of a drug or device for a use other than one that has been approved by the FDA—what is known as "off-label" promotion—to violate the misbranding proscriptions because when a drug or device is promoted for an unapproved use, the label contains no instructions about how to safely use the drug for the unapproved use.

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In order to market a drug for a specific use, a...