The First Amendment: Not One Size Fits All

• Publication year: 2016

The First Amendment: Not One Size Fits All

Caroline Poplin

THE FIRST AMENDMENT: NOT ONE SIZE FITS ALL

Caroline Poplin^*

Introduction

In the last twenty years or so, the Republican conservatives on the U.S. Supreme Court have relished overturning settled constitutional doctrine, particularly to benefit corporations at the expense of their customers, workers, investors, and ordinary people in general. The First Amendment has been one of their favorite tools.

The poster case for this successful effort is, of course, Citizens United, where the court majority overturned restrictions on corporate campaign contributions that had stood for almost a century.¹

Less well known, but still important, the Court has challenged the traditional restriction of First Amendment protection to political speech, and extended constitutional protection to "commercial speech", speech—such as advertising—by a business to promote a product to make money.² Or maybe the product itself is speech, or data. Speech is speech, the Court seems to say, and as long as it is truthful and not misleading, maybe there are people who want to listen and learn. The Supreme Court case is Sorrel v. IMS Health 131 S. Ct. 2653 (2011).

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In 2010, the Second Circuit went the Supreme Court one better, in United States v. Caronia, 703 F.3d 149 (2nd Cir. 2012).³ The case involved a pharmaceutical salesman, Alfred Caronia, who promoted Xyrem, a drug approved by the Federal Drug Administration (FDA) only for cataplexy in narcolepsy, and excessive daytime sleepiness in narcolepsy.⁴ Caronia was recorded telling a physician that Xyrem could be used for insomnia, fibromyalgia [a common but not well-understood pain syndrome], Parkinson's disease, chronic fatigue, obesity and other common problems.⁵ Also that neurologists use it for children between eight and ten, and patients over 65.⁶ "It's a very safe drug," said Mr. Caronia.⁷ The FDA prosecuted the salesman for "misbranding", the conviction was upheld by the District Court, and overturned by the Second Circuit.⁸

Speech, written or other material promoting a drug for a use not approved by the FDA, has always been considered good evidence of "misbranding," so prohibited by the Food, Drug and Cosmetic Act (FDCA).⁹ As "commercial speech," such promotion had never been entitled to any special protection: large pharmaceutical companies have paid billions of dollars in fines in recent years to settle Federal government allegations of misbranding evidenced by off-label marketing.¹⁰ Nevertheless, in Caronia the Second Circuit held that the drug representative's promotion of off-label uses of Xyrem was now protected by the First Amendment as long as it was "truthful and not misleading".¹¹

In August 2015, a judge in the Southern District of New York, following what he called "[the] modern First Amendment law" as set out by the Second Circuit in Caronia, upheld pharmaceutical manufacturer Amarin's constitutional right to promote its drug, Vascepta, for an off-label use,¹² since it

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found that Amarin's message was "truthful and non-misleading."¹³ Judge Engelmeyer noted in passing how common—and important—off-label use of drugs is: "And the therapeutic—indeed, sometimes life-saving—value of off-label uses of FDA approved drugs has been widely recognized".¹⁴ He apparently finds this sweeping proposition so intuitively obvious he offers no support for it.

One more point to keep in mind. Congress, the FDA and Department of Justice (DOJ) have always been clear that nothing in the FDCA, from its original passage in 1906 to the present day, constrains in any way a licensed physician's right and responsibility to prescribe any drug legitimately on the market for any condition he or she thinks appropriate.¹⁵ The Second Circuit uses this, though, as an argument to support off-label marketing—it helps 'educate' the physicians.¹⁶

Nevertheless, these decisions have caused great consternation in the medical community: anxious editorials have appeared in JAMA,¹⁷ the New England Journal of Medicine,¹⁸ and the Annals of Internal Medicine.¹⁹

Were the statements by Alfred Caronia about Xyrem, and later by Amarin about Vascepta, in fact "truthful and non-misleading"?

I. Some Background

The story of medicinal pills, powders, and potions is colorful, and doubtless goes back to the beginning of human history. Sick people are desperate and vulnerable, they want to be cured, many will try anything. In the U.S., the market has always responded: in the nineteenth century, the wild west

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was not just along the frontier. All kinds of concoctions were peddled as miracle cures: this is when the term "snake oil" became a synonym for a product fraudulently offered as a cure-all. Many of these drugs were ineffective, some were dangerous: Mrs.Winslow's Soothing Syrup, for example, sold to comfort crying babies, was compounded with morphine.²⁰

The first national law to protect consumers from such practices, the Pure Food and Drug Act of 1906, required that the active ingredients of medicinal compounds be listed on the label, and meet purity standards.²¹ Each major subsequent revision of the law was passed in the wake of a preventable tragedy.²²

In 1937, to make a liquid preparation of the early antibiotic sulfanilamide, Massengill, a pharmaceutical manufacturer, dissolved the chemical in the solvent diethylene glycol. You might know a closely related compound, ethylene glycol, a potent human toxin used today for antifreeze. Massengil checked its product for appearance, taste and fragrance, but not for safety— that was not required by the 1906 law.²³ In short order, over 100 people died, including 35 children.²⁴ Congress quickly amended the law in 1938 to require manufacturers to demonstrate the safety of their drugs to the FDA before they could legally market them.²⁵

In 1962, Congress tightened the FDCA again,²⁶ this time in response to the thalidomide disaster, which readers of a certain age will remember well: thalidomide, a non-barbiturate sedative, was thought to be so safe it was marketed over the counter in Europe to everyone, including pregnant women for morning sickness. It was widely taken up. As the world found out to its

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horror, however, thalidomide is a potent teratogen: more than 10,000 children were born with serious, often fatal, birth defects before the drug was taken off the market. (A determined FDA officer, Francis Kelsey, kept it out of the U.S.)²⁷ Within the year, Congress amended the FDCA to require manufacturers to demonstrate safety and effectiveness, based on adequate and well-controlled clinical studies, conducted by qualified experts, to the FDA for each use for which they planned to market a drug.²⁸

Congress understood that just because a drug was safe and effective for one condition did not mean it was safe and effective for a different one. To give a notorious recent example, the FDA found a powerful anti-psychotic, Risperdal, safe and effective for schizophrenia (its first indication), under certain conditions for Bipolar I disorder, and for irritability associated with autistic disorder.²⁹ It is not, however, safe and effective for dementia-related psychosis, even though it was widely marketed and prescribed for that purpose: patients died.³⁰ DOJ prosecuted Johnson & Johnson for illegal off-label marketing; the FDA added a black box warning against this use to the label for Risperdal.³¹

Therefore, Congress designed the 1962 amendments—in particular, the definition of a "new drug"—explicitly to prevent a sponsor from getting a new drug on the market for an easy, narrow indication, then marketing it off-label for wider, more lucrative, but more problematic, uses. Senator Kefauver, a sponsor of the amendments, noted that if a manufacturer were not required to demonstrate safety and effectiveness for each use, "the expectation would be that the initial claims would be quite limited." However, once the drug received its initial approval, "the sky would be the limit and extreme claims of any kind could be made. . ."³²

II. Modern Medicine

Starting in the years after World War II, and accelerating with passage of Medicare, American medicine has undergone tremendous transformation and

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expansion. Scientists developed whole new classes of more powerful and better targeted drugs, new laboratory tests and imaging equipment, more detailed understanding of the physiology of health and disease down to the molecular and genetic level. At the same time, scientists and physicians developed appreciation for what has come to be called "evidence-based medicine" and in particular, the importance of randomized, controlled clinical trials (RCTs).

When a doctor prescribes a new medication for a very sick patient, and the patient dies, the doctor has no way of knowing whether the patient died from the disease or the medication—there is almost nothing in medicine that is 100%. If the patient recovers, it may be the effect of the medication, or the condition resolved spontaneously, as many do. That's why clinical trials need decent numbers of subjects—and a control arm.

Far more often than we expected, treatments that seemed logical, intuitive even, turned out to be ineffective, even dangerous. For example, physicians assumed for...