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How Big Pharma’s Misleading and Fraudulent Marketing Leads to Mass Tort Claims

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Profits vs. Lives in the War Against Defective Drugs and Defective Medical Devices

Choice health or money. Caduceus and dollar signs on scales. 3d
Pills dollar symbol

I. Introduction to the Battle Against Defective Drugs and Medical Devices

This article focuses on the inherent problems associated with drug and device manufacturers’ misleading and fraudulent marketing practices.

Unlike the past, Big Pharma’s marketing now has less oversight over its promotional activities.

Significantly, the current lack of oversight and forceful guidelines may have contributed to countless mass tort cases and claims, record-breaking civil and criminal fines, . . . and countless patients who have been seriously injured or died.

Much of this article focuses on the risks and liabilities among three relationships: manufacturer-doctor; doctor-patient; and one relationship that is somewhat disconnected, which is manufacturer-patient.

Generally, the source of strain within these relationships originates from the battle between the Food and Drug Administration (FDA) and Big Pharma.  The spring board for this tug-of-war stems from the FDA’s policies regarding the safety and efficacy of drugs and medical devices versus manufacturers’ desire to introduce products outside the scope of the FDA’s original approval for those products.

In other words, the safety and efficacy of patients’ lives versus the mega-millions made by Big Pharma.

Notably, Big Pharma pursues its right to market its wares to doctors by leveraging its freedom of speech.  They say there is a need to provide free-flowing medical information.

However, that argument likely is pretext for the underlying motivation, which is to line their pockets.

Ultimately, this article will recommend that the FDA re-introduce a similar version of its prior prerequisites to manufacturers who promote off-label drugs and medical devices: the FDA should be required to review all off-label promotional materials intended to be submitted to prescribing physicians on a pre-approval or trial basis.

Based upon current regulations, patients’ rights to making an informed decision have been trumped by Big Pharma’s right to free speech.

Past FDA policies had the effect of a general rule that off-label materials sent to physicians was a violation, which was strongly imposed upon them. However, successful court battles by manufacturers asserting freedom of speech claims turned the tables in their favor.

Today, one can contend that the exception is now the general rule, as manufacturers may send marketing materials on off-label products with significantly less restrictions. This is the “new normal.”

Record-setting criminal fines of more than $1 billion by one drug manufacturer may be demonstrative of a failed effort to fight fraudulent promotion and unsafe products, and that a new approach may be successful on many levels.

Ultimately, a better approach could allow the agency to win the war against defective drugs and defective medical devices, and take advantage of the lost opportunities by the FDA to provide needed practical guidance.

II. Off-Label Prescription and Promotion: A Background

Doctor writing out RX prescription selective focus
Close crop of medicine cabinet filled with pill bottles, each labeled with a red question mark.

Before drugs and devices are approved by the FDA for general use, they undergo through clinical trials (also called “research studies”) to determine how well they comport with safety and efficacy.1 Specifically, the trials must prove that the drug: (1) works to treat a particular medical condition; (2) works the way in which it is expected; and; (3) is safe when used as instructed2.

Originally, the FDA focused solely on safety; however, after realizing that even snake oil could be safe, the agency added efficacy to its threshold of approval.3Following approval for safety and efficacy, the FDA works with the drug or device manufacturer to develop the “label.”4This “label” does not refer to the “label” on the side of a prescription bottle or medical device package5 . Rather, it is a report that provides information about the drug or device, such as the conditions it is approved to treat (“indications”) and dosage amounts.6

Drugs and medical devices may be used for purposes that are not approved, provided they are approved for some type of treatment.7 Those that are administered contrary to the FDA- approved label are called “off-label.”8

Types of off-label drug prescription include administering a drug for a different disease or a different manner of ingestion.9 However, unbeknownst to many patients, physicians do not have strict legal limitations when prescribing off-label. In fact, doctors may prescribe FDA-approved drugs and medical devices in any manner they believe is medically suitable, and may do so without FDA oversight.10 This is because the FDA lacks the authority to oversee doctors in this manner.

In particular, the Federal Food, Drug and Cosmetic Act (FFDCA) states, “Nothing in this Act shall be construed to limit or interfere with the authority of a healthcare practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate healthcare practitioner-patient relationship.”11 In essence, off-label use “is an accepted and necessary corollary of the FDA’s mission to regulate in this area without directly interfering with the practice of medicine.”12

This policy, which originates from the 1938 Food, Drug, and Cosmetic Act and is known as the “practice-of-medicine exception,” says that “once a drug is approved for marketing, FDA does not generally regulate how, and for what uses, physicians prescribe that drug . . . [and a] physician may prescribe a drug for uses or in treatment regimens or patient populations that are not listed in the FDA-approved labeling.”13

Off-label prescriptions are commonly pursued for non-experimental purposes, and the medical community is rife with examples that demonstrate their highly effective uses.14 Arguably, the most notable off-label use of a prescription drug could be that of Pyrimethamine, Famciclovir, and Ganciclovir, which are used for the treatment of AIDS, a condition which is treated with nearly 100% off-label prescriptions.15

This is a significant statistic that must be underscored. If an average of 40% of all prescriptions are off-label, it is not a great leap of logic to suggest that 40% of all revenues and profits come from off-label prescription. A figure which cannot be ignored by corporate executives reviewing cash flow and profit-and-loss statements—especially when designing strategic approaches to market the medications they have developed.

What may be more eye-opening is that doctors generally do not need to disclose that the drug or medical device has been prescribed for an off-label purpose during an informed consent discussion with the patient.16  Typically, a doctor is bound to discuss the potential complications associated with a drug or device.17 Yet, that is not necessarily the case with off-labels.

There are two approaches states apply to the question of whether a doctor should provide the patient with information about the potential side effects, complications, benefits, and history.18 The majority rule is the “reasonable patient standard,” which allows a jury to determine “whether a reasonable patient would have regarded the information as important.”19 Notably, expert testimony is not required here because there isn’t an expert at being a reasonable patient; it is an illusory figure.20 On the other hand, the minority approach applies an “actual patient standard,” which is a subjective approach that gives more weight to the actual patient.21

Notwithstanding, pharmaceutical companies have a history of rigid restrictions when promoting off-label drugs and medical devices. For example, marketing drugs and medical devices for unapproved purposes is forbidden in that it prohibits doctors and patients from making unbiased and informed decisions.22 This is based upon the FDA’s charge of regulatory oversight of protecting the general public from profit-focused pharmaceutical companies.23

If a non-FDA-approved use of a drug is included on a label, it is deemed “misbranded” and the manufacturer faces potential criminal and civil penalties.24 It is also a violation to release an “adulterated” product, one that is categorically problematic with respect to the product’s degree or level of toxicity, cleanliness, or sterility, how well it conforms to its label in terms of composition of ingredients and strength, and any issues with manufacturing quality control.25 Notably, a medical device may be deemed both adulterated and misbranded if promoted for a used not approved or cleared by the FDA.26


III. History of FDA’s Policy Decisions: Safety First, Efficacy Second

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Health Medication Healthcare Treatment Concept

The FDA’s policy is reflective of the background of the 1938 Federal Food, Drug, and Cosmetic Act (FDCA) and its amended 1997 Food and Drug Administration Modernization Act (FDAMA). The FDA initially focused on safety, then added the element of efficacy in 1962.27

The agency’s oversight authority is expressed in the Code, with the mandate that new uses for drugs outside of their scope of approval are to be tested and cleared by the FDA28 .The FDAMA provided strict limitations on the distribution of off-label use of drugs and medical devices, which included the following:

  • The drug manufacturer must provide the FDA with an application for new-drug use;
  • Any dissemination of data must not be abridged, false, misleading, or pose a significant health risk;
  • All information containing clinical research must be based upon the manufacturer’s work;
  • The drug manufacturer must provide the FDA with any data it will provide to doctors, and include prominent disclaimers clearly stating the drug’s non-FDA approved status regarding any off- Label prescription.29

Based on this construction, the FDA’s policies and restrictions arguably forbid drug manufacturers from distributing off-label uses. The FDAMA’s strict limitations on off-label marketing found in § 401 expired in 2006.

New guidance was announced on January 13, 2009, when the FDA released the Good Reprint Practice Guidelines that offered the FDA’s “current thinking” on how manufacturers may disseminate off-label uses of drugs and devices to physicians.30 Interestingly, these guidelines are non-binding and have no force of law. Thus, the guidelines without the standard note-and-comment format found in enacted legislation and promulgated regulations, do not serve as a reliable source of direction for manufacturers.

Also, when a manufacturer pursues off-label drug promotion within its guidelines, it need not provide a supplemental new drug application.

Finally, the manufacturer is not required to apply to the FDA for approval of off-label promotional materials prior to introducing the content to prescribing physicians, as this restriction is no longer in effect.

Given this background of toothless guidelines, it begs the following question: why do restrictions upon manufacturers for distribution of off-label drug and medical device uses exist? To what end?

The answer is twofold. First, they cannot be trusted to comply with federal or state guidelines regarding off-label marketing because they generate enormous sales from off-label revenue streams.31 Second, drug manufacturers have historically been motivated to support the medical community in pursuing reimbursement for such uses.32 The initial problem with reimbursement is that off-label use is not reimbursable by private insurance companies, such as Cigna and United HealthCare, or public health care programs like Medicare and Medicaid.33


  • 27 Significant Dates in U.S. Food and Drug Law History, U.S. Food and Drug Administration, (last visited January 3, 2016). Go Back
  • 28 21 U.S.C.A. § 355. This process starts with the manufacturer submitting a New Drug Application (“NDA”). Once approved, the manufacturer proceeds through the first phase of the NDA process, which typically entails animal testing and corresponding toxicity research. Ausness, supra note 19, at 1256. This is followed by clinical trials on humans. 21 C.F.R. § 314.50 (2007). Upon completion of these two phases, the manufacturer submits the updated NDA to the FDA that details “the drug’s ingredients, detailed chemical information, detailed biological information, summaries of clinical testing results, a summary of the risks and benefits of the drug, an environmental impact statement, marketing history, and proposed labeling.” Id.Go Back
  • 29 21 U.S.C. § 360aaa(b) (2000).Go Back
  • 30 Good Reprint Practices, supra note 27.Go Back
  • 31 Ausness, supra note 19, at 1253.Go Back
  • 32 id. Go Back
  • 33 id. Go Back

IV. The FDA Approval Process for New Drugs

Pursuant to the FDCA, a “new drug” must be approved by the FDA prior to being introduced into commerce.34 This starts with the manufacturer submitting a New Drug Application (“NDA”).35

Once approved, the manufacturer proceeds through the first phase of the NDA process, which typically entails animal testing and corresponding toxicity research—followed by clinical trials on humans.36 Upon completion of these two phases, the manufacturer submits the updated NDA to the FDA that details “the drug’s ingredients, detailed chemical information, detailed biological information, summaries of clinical testing results, a summary of the risks and benefits of the drug, an environmental impact statement, marketing history, and proposed labeling.”37

Provided the drug obtains approval by the FDA, the labeling information follows. “The FDA requires that a drug’s label include information necessary for safe and effective use, warnings, precautions, clinical pharmacology, indications, contraindications, and information about adverse reactions.”38

FDA-approved drug labels, geared for physician and medical staff use, is provided in the Physicians Desk Reference and enclosed within the medication’s packaging.39

A. Exceptions for Drugs

In the event that an individual is presented with a life threatening situation, there is an emergency use exemption available that permits the prescription of an Investigational New Drug (IND).40 This exemption is defined as “the use of an investigational drug or biological product with a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is not sufficient time to obtain IRB approval.”41 The IRB has the authority to approve, disapprove, and modify research on IND’s.42

B. Marketing of Drugs

The FDA’s Office of Prescription Drug Promotion oversees the marketing of prescription drugs, including television, radio, print, and online advertising, as well as materials provided to physicians and patients by pharmaceutical sales representatives.43 Company marketing materials are to be provided to the Office contemporaneous with its original dissemination of publication.44

C. Pre-Market Clearance Process of Medical Devices

One avenue that a manufacturer may pursue in order to get a medical device on the market is by pursuing a 510(k) clearance.45 This pre-market submission to the FDA is a demonstration by the manufacturer that a device is minimally as safe and effective – or substantially equivalent – to a device that is legally marketed, which is not subject to pre-market approval.46

Companies wishing to obtain clearance of medical devices must refer to the Medical Device Amendments of 1976 (”MDA”), which divides devices into three classes in order to properly regulate them.47

Class I is for devices that must abide by the FDA’s “general controls” guidelines.48 Class II is for devices in which “the general controls by themselves are insufficient to provide reasonable assurance of the safety and effectiveness of the device.”49 Class III is for devices that: (1) lack sufficient data to determine whether the general controls and special controls provide reasonable assurance of safety and efficacy; and (2) are for life sustaining-based, impairment-based, or have unreasonable risk of illness or injury.50

Class III devices also have strict guidelines. The device maker must complete the following:

  • A Pre-market Approval Application prior to introducing it into interstate commerce.
  • A complete detail of safety and effectiveness of the device.
  • A complete detail of what components, properties, and how the device operates.
  • A complete detail of manufacturing facilities, controls, methods, processing, packaging and implanting procedures, where necessary.
  • Any additional information discussing safety and efficacy evaluations that should be known or that should reasonably be known.
  • Proposed labeling for the device.51

D. Exceptions to Class III Devices

There are three general exceptions to pre-market approval: (1) in the event the device was marketed before the MDA was passed and contemporaneously, there was no requirement for pre-market approval;52 (2) if a “substantially equivalent” predecessor device existed prior to the MDA,53 and; (3) when human testing on the device is involved under an “Investigational Device Exemption.”54

E. Marketing Approval for Medical Devices

Another avenue a manufacturer may pursue to legally market a medical device within the United States is to submit a Pre-market Notification (PMN) under § 510(k) of the FDCA55. Here, the manufacturer must notify the FDA within 90 days of any intent to promote the device56. This allows accurate identification and classification of new, first-time introduction of devices that are entering the marketplace, as well as those being reintroduced with major modifications such that safety and efficacy are affected.57

V. Potential Claims for Violations of Off-Label Promotional Use

There are many claims that apply to violations of the FDA’s off-label marketing guidelines for drugs and medical devices. These can implicate federal and state laws that impose civil and criminal violations.

A. Fraud on the FDA

When a manufacturer makes a material misstatement to the FDA that results in a pre-market approval, and the drug or device subsequently injures an individual, a “fraud on the FDA” claim may arise58.

According to a fraud on the FDA claim, “but for” the fraudulent marketing of a product a person’s injuries would not have occurred, and the manufacturer is thus liable regardless of whether the product was defective59. This is traditionally a federal claim, and the FDA’s policy is that such claims remain under its exclusive authority, thus preempting state laws and civil litigants60.

Circuit Courts, however, had been split over whether such claims were preempted by the FDA until Buckman Co. v. Plaintiff’s Legal Committee61. There, the plaintiff’s asserted that manufacturer AcroMed Corporation and its consultant, Buckman Company misled the FDA by obtaining clearance for fixation implant devices (“screws”) as “substantially equivalent” devices to be used in leg and arm bone surgeries62.

In reality, the manufacturers in Buckman intended to market the screws primarily as spinal implant or fusion devices63. In effect, the manufacturers evaded the lengthy and expensive pre-market approval process.

B. Fraudulent Misrepresentation

Patients have also pursued claims against drug and medical device manufacturers for fraudulent misrepresentation. This cause of action requires six elements be proven by a clear and convincing standard: (1) a representation; (2) which is material to the transaction at hand; (3) made falsely, with knowledge of its falsity or recklessness as to whether it is true or false; (4) with the intent of misleading another into relying on it; (5) justifiable reliance on the misrepresentation; and (6) the resulting injury was proximately caused by the reliance64.

The anti-depressant medication Zoloft is illustrative of such a claim, and Miller v. Pfizer Inc. (Roerig Division)65 demonstrated the difficulty of establishing the elements of reliance and causation with such assertions. Here, the plaintiff’s defective marketing action was based upon the assertion that the manufacturer had “gone to great lengths to reassure doctors that the violence and suicide problems that they ha[d] heard about, mainly with its chief competitor Prozac, would not occur with Zoloft, and to assuage patient’s concerns over the initial adverse effects which are frequently harbingers of tragedy.”66

Evidence supporting this claim came from a Pfizer employee who “advised the representatives to communicate information about Zoloft to high-prescribing physicians and told them not to discuss suicide unless a physician asked about it.”67 If someone did inquire about the suicide risks, they were instructed to reassure them of Zoloft’s safety by stating that the drug had a low risk of suicide.68

Unfortunately for the plaintiffs, establishing the elements of reliance and causation proved to be the Achilles heel in their action. The United States District Court in Kansas granted Zoloft a partial summary judgement, and on two of the four claims held that (1) the prescribing physician did not rely on supposed material misstatements by Zoloft, and (2) the plaintiffs did not show medical causation.69

C. Failure To Warn

Manufacturers of drugs and medical devices have a duty to provide adequate warnings regarding inherent dangers associated with the normal use of their products that are outside the scope of knowledge of an ordinary user70.

In Knowlton v. Deseret Medical, Inc.71, a plaintiff went into heart surgery in which a device composed of a catheter-and-needle combination was used72. The special catheter, called an Intracath, was used off-label to transfer Nitroprusside (Nipride) to the patient’s heart73.

However, the drug leaked from the catheter, made contact with the patient-victim’s chest and abdominal walls, and resulted in “extensive and intensive chemical burns74. The trial court found in favor of the plaintiff regarding the manufacturer’s failure to warn claim, and the First Circuit Court of Appeals affirmed76.

Specifically, the trial court held that FDA approval for the device was for venipunctures, which is when a needle goes into a vein77. Yet, evidence showed that the manufacturer of Intracath knew that its product was being used as an off-label vehicle to transport drugs during heart surgery78.

Moreover, corporate insiders admitted their knowledge of the high risk involved in such procedures because the product’s tubing could be sliced or otherwise compromised under these surgical conditions79.

The court also held that a reasonably prudent cardiovascular surgeon would have been unaware of the inherent danger involved in such a procedure, thus recognizing the valid failure-to-warn claim.80

i. Overpromotion As A Defense To Failure-to-Warn

It is possible for a plaintiff to still maintain a failure-to-warn claim in the event the drug or device maker “diluted the effect of the warning81. A common example is that of a pharmaceutical sales representative making inaccurate statements about FDA-approved warnings within the products label.

In this instance, anyone with a financial or beneficiary tie with the pharmaceutical company would be equally as liable. However, courts are split on the viability of such a claim when the physician understands that the representative’s comments are contrary to the label’s warnings82 Love v. Wolf83.

In Love v. Wolf, a doctor prescribed chloromycetin, an antibiotic frequently used for off-label purposes84. The prescription was refilled several times by the patient, who was provided the medication to treat a gum infection and subsequently suffered severe aplastic anemia84. This is a condition in which the bone marrow fails to generate enough red blood cells.

Meanwhile, “[l]etters were dispatched intended to reach all physicians in the United States stating these warnings in great detail85. The warning letters to doctors were considered “over promotion,” and that prevented the defense of learned intermediary doctrine86, an exception to the duty to warn which many courts have recognized in situations where the product is recommended or prescribed to the consumer by a learned third party, such as a physician. This is discussed in detail below in Section VI-A.

D. False Claims Act

The False Claims Act offers an additional source for fraud-based claims. Courts have defined such claims as “a demand for money or for some transfer of public property87.

The purpose of the Act is to reduce “fraudulent claims” by applying liability to those who defraud the government88 one of these violations.. Under the Act, liability arises when an individual “knowingly presents, or causes to be presented, to the United States Government a false of fraudulent claim for payment or approval”; when the person “knowingly makes, uses, or causes to be made or used, a false record or statement to get a false or fraudulent claim paid or approved by the Government;” or; when a person “conspires to commit” one of these violations89.

Liability could include damages between $5,000 and $10,000 for each false claim provided to the government90.

Under the Act, “knowingly” is defined as any individual who “(1) has actual knowledge of the information; (2) acts in deliberate ignorance of the truth or falsity of the information; or (3) acts in reckless disregard of the truth or falsity of the information91. Thus, innocent mistakes and negligence could act as a defense.

In United States v. Krizer92, the U.S. filed a civil suit against a doctor and his wife for falsely billing Medicare and Medicaid patients, in which the billing mechanism included numeric codes that corresponded to certain procedures and respective billable times93 with medical personnel.

The doctor asserted that his “bundled” approach was comprised of one-on-one time with the patient combined with time reviewing files and consultation with medical personnel94. Conversely, the government asserted that a strict “face-to-face” approach was the correct application of the parameters of the program95.

The D.C. Circuit held that the code was ambiguous and that the doctor took a reasonable interpretive approach96. However, the doctor lost on one of the claims, as the court held that he fell within the third aspect of the “knowingly” standard of the False Claims Act, as the statute was designed to prevent the “ostrich-with-the-head-in-the-sand.” This was evident in light of the fact that he allowed his wife to make inaccurate assumptions of time with the patient per corresponding numeric code97.


RICO, the Racketeer Influenced and Corrupt Organizations Act98  which allows treble damages, was passed in 1970 to stop legitimate companies from being forced to deal with organized crime syndicates. The Act allows for claims based upon fraudulent promotional schemes in the marketing of drugs and medical devices, and the elements of a RICO claim include: (1) any person who invests funds from racketeering activities (2) in an enterprise (3) through a pattern (4) of racketeering activity.

Clear and convincing proof of these elements can subject a defendant to civil penalties with treble damages99.

F. Negligence Per Se Violations of the FDCA

Generally, a negligence per se action in common law is appropriate when a plaintiff demonstrates that “(1) a duty, recognized by law, requiring the defendant to conform to a certain standard of conduct; (2) a breach of that duty; (3) a causal connection between the defendant’s conduct and the resulting injury; and (4) actual loss or damage100.

Interestingly, plaintiffs pursuing this claim likely take the stance that the drug and device manufacturers who violated FDA or FDCA rules are liable under state negligence per se laws for damages proximately caused by such infractions101dangers are not evident.. The problems for claimants here have been two-fold: either the jurisdictions do not recognize the claim or causation has been difficult to prove.

VI. General Defenses to Off-Label Promotions Claims


There are several defenses to off-label marketing violations. Freedom of speech has proved to be a powerful defense, which will be detailed later in this article. Other defenses for negligence- based claims include assumption of the risk, contributory negligence, and comparative negligence; those typically are not as well-documented.

On the other hand, the most commonly used defense appears to be the learned intermediary doctrine, which is discussed next.

A. The Learned Intermediary Doctrine

As mentioned above, manufacturers have a general obligation to warn patients about the inherent dangers of their products in the event such dangers are not evident102 provide an adequate warning. However, the “learned intermediary doctrine” is an exception to the rule by allowing a warning originating from the patient’s prescribing doctor to act as a proxy for the warning, as long as the doctor did in fact provide an adequate warning103.

So, while the manufacturer is typically responsible for warnings lacking adequacy to the patient, a patient’s physician can preclude an inadequate warning claim by providing acceptable warnings directly to the patient104.

Thus, the claim will fail if the physician—who is acting as a learned intermediary—was cognizant of the inherent dangers, because the physician’s duty to warn eliminates the “but for” argument regarding the patient’s injury.105

There are a number of reasons people advocate for off-label promotion. Among the more popular are that the FDA’s approval and clearance process: (1) is too slow and cumbersome; (2) delays the availability of potentially life-saving medical advances to thosein need; and (3) precludes the exchange of relevant treatments and complications of drugs and devices.

The typical response to these arguments focuses on the manufacturers’ continuous violations of FDA protocols for selling, marketing, and distributing drugs and devices, especially for off-label uses.

The violations suggest that manufacturers simply cannot be trusted, as the pursuit for profits outweighs the ramifications of failing to comply with FDA policies of safety, efficacy, and regulations effectuating policy.

A. Freedom of Speech vs. Incentive for Profit

On one hand, physicians do not have restrictions on prescribing drugs and devices for off-label purposes106 definition of “education.. Yet, for years, manufacturers generally have been barred by the FDA for promoting their products for off-label uses, because of a fundamental mistrust by FDA for manufacturers. However, the FDA’s approach has changed, and it now permits a manufacturer to distribute reprints of non-solicited, peer-reviewed medical journal articles detailing off-label prescriptions, pursuant to the Good Reprint Practices Guidelines.

Here, such unsolicited distribution of materials falls under the FDA’s definition of “education107.

Significantly, doctors lacking a financial conflict of interests are not barred from communicating the uses and benefits off-label prescription of drugs and devices to their patients and the public. This creates the dilemma of one prescribing doctor with financial ties to a company introducing the same truthful data about off-label successes as a non-paid physician.

In that instance, the first could face criminal and civil charges, while the second could be celebrated as a leader in the medical field.108

B. Safety, Efficacy, and Mistrust

There are three policy reasons for the FDA’s strict limitations on off-label marketing: “protecting public health through its certification of drug and medical device safety, preserving the integrity of the drug and device approval process, and ensuring that physicians and patients do not receive inaccurate or biased information that may influence prescribing decisions109.

The core of the argument favoring manufacturer limitations is that off-label use already generates a significant stream of revenue—and in some cases the primary source of sales—such that without the limitations there would be little motivation to seek FDA approval110.

The logic is simple: why endure a lengthy and expensive approval process for a particular purpose when a manufacturer can realize the same results (i.e., sales) without going through the headache and delay?

Reflection on the mindset of Big Pharma should help one easily arrive at the answer. In the same light, it does not take much research to lend credibility to the FDA’s implied argument that the private interests of profits can interfere with the public’s interests for safety and effectiveness.

C. Proof of Mistrust and Enforcement of Violations

In 2013, sales from the biggest pharmaceutical manufacturers made an astronomical $501.8 billion in sales, based upon annual reports. By the same token, over the years, they have also tallied some impressive penalties and fines, both criminal and civil, for tortious conduct in off-label promotion. Consider the following more notable examples:

Johnson & Johnson:

After generating $1.45 billion in sales from Risperdal in 2012, the Johnson & Johnson was fined $2.2 billion. There were close to 240,000 violations, mostly for not detailing the drug’s risks and deceptively marketing the drug as being safer and better than its competition.111


With sales of well over $5 billion in 2012 from Lyrica, Zyvox, and Bextra, the Pfizer was fined $2.3 billion.112

The company’s Pharmacia & Upjohn subsidiary offered a guilty plea following a felony criminal violation for misbranding Bextra with intent to defraud or mislead. This included the biggest criminal fine to date of $1.195 billion113.

Coupling the $105 million criminal resolution with another $1 billion for illegal drug promotion, as well as the false claims, the total comes to a staggering $2.3 billion114.

The company’s conduct concerning Bextra was the most egregious of the violations. In late 2001, the FDA “approved small dosages of Bextra for treating the symptoms of a limited number of conditions115. Yet, following this approval the company marketed and sold Bextra throughout the U.S. touting it as an effective morphine-sparing analgesic after knee surgery.

The drug was not approved for post-surgery pain and was pulled from the market in 2005.116 The company also continued to fund “medical education programs that were used to promote Bextra for off-label uses…and sponsoring articles that promoted off- label uses.117


With over $11 billion in sales in 2012 for drugs including Advair, Flovent, and Paxil, the GlaxoSmithKline was fined $3 billion. The reasons for the hefty penalty included failing to report safety information to the FDA (a criminal fine), promoting drugs for off-label/non-covered uses, paying kickbacks to physicians, and making false and misleading statements.118

Some of the other major fines and settlements include Abbot ($1.6 billion), Eli Lilly ($1.415 billion), Merck & Co. ($950 million), and Amgen ($762.1 million).

For some of these pharmaceutical giants, the enormous profits are a drop in the bucket relative to the fines imposed. And this is somewhat recent history.

The FDA may be quick to remind the public of the risk of “snake oil salesmen peddling approved products for off-label uses with unproven, exaggerated, or fraudulent health claims,” and how “eliminating the ban would open the floodgates for such objectionable conduct119.

VIII. Landmark Cases Lead the FDA towards Easing Off-Label Promotion Restrictions

A. Washington Legal Foundation, the FDCMA, and Good Reprint Packages Guideline

During the 1990’s, the Washington Legal Foundation (WLF) alleged that the FDA’s policy based upon the Food and Drug Administration Modernization Act of 1997 regarding off-label promotion via sponsored article reprints was a violation of the First Amendment120.

In particular, one important dispute involved the FDA’s stance on circulation of “independent medical and scientific publications concerning the off-label uses of their products,” and ”manufacturer support for Continuing Medical Education (CME) programs for doctors that focus on off-label use121.

The D.C. District Court analyzed this under the four-prong Central Hudson Test to determine whether commercial free speech restrictions are in violation of the First Amendment122. That standard directs the court to determine whether: (1) the particular speech is not misleading or unlawful123; if the speech comports with this benchmark, it is within the scope of the First Amendment and the court can proceed to determine (2) if there is a substantial government interest in regulating the speech; (3) if the regulation advances the government’s substantial interest; and finally (4) if the regulation is more extensive than necessary to serve or advance the State’s interests124.

The first question regarding the lawful and truthful activity was satisfied because off-label prescription by doctors is legal, and circulation of data by manufacturers was not a misleading activity125. This threshold question was affirmatively answered and allowed for the analysis to continue, where the court determined that a substantial government interest in regulating this speech existed, and the FDA’s regulation of the speech furthered that interest126.

However, the final question regarding whether the regulation was too extensive to further the government’s interest was found against the FDA: “They fell short of satisfying the final part of the Central Hudson test, however, because the policies restricted considerably more speech than necessary to encourage manufacturers to achieve this objective127r request for an injunction. As a result, the District Court found in favor of the plaintiffs and granted their request for an injunction128.

But the story does not end there. During the litigation process, the Court obtained guidance from the Food and Drug Administration Modernization Act of 1997 (FDAMA), which allowed for the circulation of “enduring materials129. These were defined as unedited copies of peer-reviewed medical journal articles and studies that included certain stipulations, such as a disclaimer that off- label usage was not approved130.

The decision’s effect was later rendered meaningless for guidance, as the FDA took a different position. The Court of Appeals dismissed the FDA’s appeal and vacated the district court’s decisions and injunctions to the extent that they ruled the FDAMA and the CME Guidance unconstitutional131. Thus, an opportunity for direction lost.

In January 13, 2009, the FDA released the Good Reprint Practice Guidelines that eased limitations of off-label promotion. However, there were issues with it. First, the guidelines would have no force of law and act as a true source of guidance for manufacturers132. Second, providing a supplemental new drug application when a manufacturer pursues off-label promotion is not required133. Third, the manufacturer need not provide its marketing materials to the agency before circulation134.

B. U.S. v. Caronia135

This case shows the conflict between free speech and “misbranding,” which is the promotion of a drug or device outside of its approved indications.

In this case, a pharmaceutical sales representative was promoting off-label usage of Xyrem, a drug approved in 2002, to treat narcolepsy patients with weak muscles and daytime sleepiness136. Due to heightened safety issues with the drug, a “black box” warning was required by the FDA, and only one pharmacy in the United States could carry the drug137.

In 2005, the government initiated a sting operation against the manufacturer. Its sales representative Caronia was recorded discussing Xyrem for off-label purposes with a government informant posing as a physician138. Caronia argued that the criminal misbranding-related charges violated his First Amendment right to free speech139. The district court was not persuaded, and denied his motion to dismiss the charges140.

On appeal, the Second Circuit vacated the criminal sanctions under the guise that the FDCA “and its accompanying regulations do not expressly prohibit or criminalize off- label promotion141. As to whether government prosecution under the FDCA was constitutional, the Court first determined that Caronia was being prosecuted for speech142. However, the government failed in its argument regarding restricting manufacturers marketing activities under a strictly scrutinized application of the Central Hudson test.

“Accordingly, even if speech can be used as evidence of a drug’s intended use, we decline to adopt the government’s construction of the FDCA’s misbranding provisions to prohibit manufacturer promotion alone as it would unconstitutionally restrict free speech. We construe the misbranding provisions of the FDCA as not prohibiting and criminalizing the truthful off-label promotion of FDA-approved prescription drugs. Our conclusion is limited to FDA-approved drugs for which off- label use is not prohibited, and we do not hold, of course, that the FDA cannot regulate the marketing of prescription drugs. We conclude simply that the government cannot prosecute pharmaceutical manufacturers and their representatives under the FDCA for speech promoting the lawful, off-label use of an FDA-approved drug143.”

B. United States v. Harkonen144

In 1990, a California-based drug company named InterMune received FDA approval for the medication Actimmune which treats childhood immune disorder and childhood osteoporosis145. However, about 12 years after its approval, the former CEO of the company, Dr. W. Scott. Harknonen, began promoting the drug for other uses.

On August 28, 2002, he issued a press release that stated, “Actimmune also demonstrated a strong positive trend in increased survival in the overall patient population.” The statement was made under the premise that it constituted a scientific debate with First Amendment protections146.

However, Harkonen was aware that the drug lacked therapeutic value by failing to reduce disease progression and that it was not approved for that purpose147. There was a significant inference made by the district court regarding Harknonen’s charge of intent to fraud, when it detailed how “the release states in its third paragraph InterMune expected that the results of the GIPF–001 study would ‘lead to peak sales in the range of $400–$500 million per year148.

Harkonen was subsequently hit with a wire fraud charge for making allegedly false statements in his news release, which was affirmed by the Ninth Circuit149. The free speech argument became moot, as the “First Amendment did not protect defendant’s fraudulent press release150.

The case does, however, demonstrate the abusive possibilities available if the door opens too wide for off-label promotion.

C. Where We Are Today

There is a clear rift between opponents and advocates regarding the free-flow of information for off-label use between the manufacturer and the doctor.

The arguments are evident by a review of the positions of those who support and those who reject the FDA’s new principles. On one hand, allowing more flexible off-label promotion “could weaken FDA’s overall influence in promoting efficacy and safety practices151. This comes at the expense of safety to society, as government oversight has decreased in an area fraught with profit-minded executives that are willing to introduce inaccurate information.

The Caronia decision finally brings a degree of clarification on how the Constitution affects the FDA’s ability to enforce its stance on off-label promotion by manufacturers152. In fact, prior to the conclusion of the case, the FDA’s recent guidance on circulating printed materials to physicians was released.

IX. Arguments Supporting and Objecting to the Good Practice Guidelines

A. Supporters of the FDA’s Guidance

Beyond the free speech argument, support stems primarily from the interest in the exchange of data between the manufacturers and the patient-consumer153.

According to advocates, the FDA has been an obstacle in the efficient flow of information, and the easing of off-label promotional limitations lowers the governmental barrier154. Thus, modern medical technological advances on drugs and devices can be shown to prescribing doctors, which allows for up-to-date treatment options for patients without FDA interference by way of claims of misbranding155.

B. Dissenters to the FDA’s Guidance

The leading argument against the FDA’s Guidance is that it no longer requires manufacturers to apply for new drug approval when circulated materials mention off-label uses—the requirement once mandated by the now expired § 401 of the FDAMA156. It is not a big leap to suggest that without such a process, there is a disincentive to obtain approval for new uses for a drug or device.

Another argument is that “off-label prescribing of drugs that have not been proven safe or effective for the prescribed use drives up the cost of health care and exposes patients to unnecessary risks157.

Finally, there is an argument that the new Guidance offers the potential for manipulation of data from the manufacturer to the doctor and finally to the consumer. Circulation of off-label uses may not ensure the right balance of safety and efficacy, and pushing the information into the hands of large groups of patients could have aggravating effects, as nearly all drugs have complications, many of them serious and even lethal158.

C. Ironic Pitfalls of Opening the Gates to “Accurate Information”

It is debatable whether drug and device manufacturers are circulating factually accurate and trustworthy peer-reviewed medical journal entries based upon scientifically-based data, pursuant to the new FDA Guidance159. This creative approach to evading the FDA’s weakened oversight comes from manufacturers giving attribution to credible sources for the materials they circulate, only to later discover that a predominant source originated from unacknowledged authors.

Further, the effects of unsafe off-label promotion based on misleading information should not be forgotten. One merely need to examine the “fen-phen” debacle.

That case involved the use of Fenfluramine, Deexenfluramine, and Phentermine, which were FDA approved as appetite suppressants160. Unfortunately, many patients experienced heart valve damage after prolonged use: the extended use and interaction of the medications was contrary to the approved label161.

However, “safety of Dexenfluramine beyond 1 year of use had not been established by clinical trials162. To take this one step further, informed consent from the physician could be absent163. This begs the following question: Amid publication and distribution of inaccurate and unreliable data, is there really such a thing as “informed” consent for off-label products?

X. Conclusion

Big Pharma is making money hand over fist. In fact, “profits of the ten drug companies on the Fortune 500 list in 2002 were greater than the combined profits for the other 490 businesses164.”

Drug and device manufacturers are businesses, and the economics of the pharmaceutical industry centers on profits along with healthcare for society. Understandably, manufacturers are unlikely to test off-label uses of their products unless the FDA orders them to do so due the added expense that cuts into their profits165.  Arguably, a lack of off-label testing leads to mass tort claims.

What’s more, it is not helpful that federal health care programs often do not reimburse health care providers for off-label therapies—effectively eliminating the opportunity to use medication for those who could benefit from these treatments the most.

An authoritative review of off-label materials being sent to prescribing physicians, combined with evidenced-based substantiation of those uses is desperately needed166.

Several of the decisions examined in this article provide a framework for the type of federal regulation that is required for off-label medications. There is much more that can be done.

Under the current FDA Good Reprint Practices era, Big Pharma has set record-breaking violations surpassing $1 billion accompanied by hundreds of thousands of individual violations and corresponding health complications.

Unless the FDA looks to now be a profit center for the federal government, a more collaborative approach to guidance that allows substantiated statements could save lives and prevent more record-breaking violations. And help put an end to this other drug war against defective drugs and defective medical devices.

  • 164 Margret Z. Johns, Informed Consent: Requiring Doctors to Disclose Off-Label Prescriptions and Conflicts of Interest, 58 Hasting L.J. 967, 973 (2007).Go Back
  • 165 See Ausness, supra note 19, at 1319.Go Back
  • 166 The State Bar of Texas Advertising Review Committee of the State Bar of Texas provides an excellent roadmap. Take Rule 7.07(b): “a lawyer shall file with the [Committee], no later than the first dissemination of an advertisement in the public media, a copy of each of the lawyer’s advertisements in the public media.” TX ST RPC Rule 7.07(b), Filling Requirements for Public Advertisements and Written, Recorded, Electronic, or Other Digital S. Under Rule 7.07(d), “[a] lawyer who desires to secure an advance advisory opinion, referred to as a request for pre-approval . . . may submit to the [Committee], not less than thirty (30) days prior to the date of first dissemination, the material” to be sent to physicians. TX ST RPC Rule 7.07(d). And Under 7.07(f) “[i]f requested by the Advertising Review Committee, a lawyer shall promptly submit information to substantiate statements or representations made or implied in any advertisement in the public media and/or written solicitation communication.” TX ST RPC Rule 7.07(f).Go Back

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