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Off-Label Marketing

 

One would hope that prescription drugs are rigorously tested before being used by physicians. However, it is common for doctors to use drugs for purposes that have not been approved by the FDA -- prescribing them "off-label." While such uses can be beneficial and advance innovation, there is also the potential for harm to patients.

It is legal for doctors to prescribe drugs to their patients for off-label purposes; it is illegal for drug companies to actively market such uses. But the profits from off-label uses of drugs can be huge, with some experts estimating that a fifth of all drugs are sold for off-label purposes. Drugmakers thus have huge incentively to market their drugs for such uses. In order to get around legal roadblocks, pharmaceutical companies have engaged in a variety of market strategies to promote drugs for off-label uses. For instance, they will hire the top doctors in a field to "discuss" their off-label uses of a certain drug with other doctors at company-sponsored educational events.

In recent years, nearly every major drug company has been been investigated for illegal off-label marketing and many have paid huge fines.

Pfizer

Pfizer agreed to pay $2.3 billion, the largest criminal fine ever paid  in the history of the Department of Justice and Health and Human Services, to resolve criminal and civil liability arising from the illegal promotion of four of its drugs, Bextra, Geodon, Lyrica and Zyvox. It was also charged with providing doctors with illegal kickbacks to induce them to prescribe Bextra, Geodon, Lyrica, Zyvox, Aricept, Celebrex, Lipitor, Norvasc, Relpax, Viagra, Zithromax, Zoloft and Zyrtec. Pfizer’s subsidiary, Pharmacia and Upjohn Company, Inc., agreed to plead guilty to illegally promoting the sale of its anti-inflammatory drug, Bextra, for off-label uses and paid a criminal fine of $1.195 billion and forfeited $105 million, for a total criminal resolution of $1.3 billion. Bextra was approved by the FDA in 2001 to treat arthritis and menstrual cramps, yet Pfizer sales representatives told doctors it could be used to treat acute and surgical pain if taken at levels significantly higher than the recommended doses.

In addition, Pfizer agreed to pay $1 billion to resolve allegations in a number of qui tam cases that it illegally promoted four drugs – Bextra; Geodon, an anti-psychotic drug; Zyvox, an antibiotic; and Lyrica, which treats nerve pain – and caused false claims to be submitted to Government health care programs for uses that were not medically accepted indications and therefore not covered by those programs.  Geodon (the brand name for ziprasidone), was approved by the FDA for treatment of schizophrenia and manic or mixed episodes of bipolar disorder for adults. According to the complaint, Pfizer promoted Geodon for a number of off-label uses, including for children and in much higher-than-prescribed levels of dosage.

Atypical Antipsychotics

The new generation of atypical anti-psychotic drugs (AAPs) surpassed cholesterol-lowering drugs this decade to become the nation's highest-selling category of medication, totaling $14.9 billion out of 2009's $300 billion market. This rise cannot, however, be separated from the darker side hidden behind the numbers. As children and the elderly continue to take these anti-psychotics in increasing numbers for uses often disapproved by the FDA, some of the country's largest pharmaceutical giants have been caught with orchestrating massive illegal marketing schemes. In the last three years, four companies alone have paid prosecutors over $2.7 billion in settlements over off-marketing tactics for their anti-psychotics. Many of these companies did the exact same thing: they pushed their drugs as cures for dementia instead of the approved use, namely for psychosisCoincidentally, it was also anti-psychotics that were the center of famous discoveries of medical conflicts-of-interest at numerous institutions and organizations, such as Harvard Medical School and NPR's "The Famous Mind," both of which helped directly influenced public debate on the use of depressants for children.

AstraZeneca and Seroquel

AstraZeneca became the third pharmaceutical giant since 2007 to plead admit to federal charges of illegal marketing of anti-psychotic drugs when it agreed to a massive $520 million settlement over charges that it marketed Seroquel for inappropriate uses. The company's marketing efforts were instrumental in the rise of  its prescription to children and the elderly for uses not approved by the FDA, which helped to boost Seroquel's sales to $4.9 billion in 2009.

Many researchers claim that anti-psychotics often lead to weight gain, which increases the risk of diabetes in patients. AstraZeneca denies these claims -- though, in a 1997 email uncovered from the investigation, it was discovered that the company had "buried" a study that showed that patients had gained an average of 11 pounds on the drug, replacing it with a study claiming participants had lost weight.

Eli Lilly and Zyprexa

Eli Lilly an approximately $1.4 billion global criminal, civil, and administrative settlement to resolve allegations that it illegally marketed its antipsychotic drug Zyprexa, a powerful drug for schizophrenia and bipolar disorder. Under the civil settlement agreement, Lilly agreed to pay the Federal Government $438.2 million and participating states up to $361.8 million to resolve False Claims Act allegations that it marketed Zyprexa for certain unapproved uses and caused false claims for payment to be submitted to Federal health care programs, such as Medicaid, from September 1999 to the end of 2005. Lilly paid a criminal fine of $515.0 million and forfeited assets of $100 million. 

In its plea agreement, Lilly admitted that from September 1999 to March 31, 2001 it promoted Zyprexa for unapproved uses in elderly populations as treatment for dementia and encouraged primary care physicians to use the drug on children with no signs of either of its two approved uses. In a rare insight into industry back-dealings, then-executive John C. Lechleiter wrote an email to other executives that appeared to advocate for the use of Zyprexa in non-approved ways: "The fact that we are now talking to child psychs and peds and others about Strattera (a second Lilly psychiatric drug) means that we must seize the opportunity to expand our work with Zyprexa in this same child-adolescent population." According to Anne Nobles, the vice president for corporate affairs, patients who have seem to have dimentia may actually have schizophrenia that could worsen if gone untreated. Several psychiatrists, in response to Lilly's claims, strongly disagreed, claiming that the two illness should never be confused. The drug was Lilly's best blockbuster, with sales of $4.2 billion in 2005, almost 30% of company profits.

Philip Dawdy, a former journalist of the Seattle Weekly and author of the popular mental health blog Furious Seasons followed the Zyprexa story quite closely, and has been kind enough to post to host PDFs of internal memos that sought to downplay the drug's risks.

Bristol-Myers Squibb and Abilify

One wonders how a company can expect to commit fraud on a company-wide level without one of its employees succumbing to their conscience (or lured by qui tam profits) and turning their employers over to federal prosecutors. Enticed by the track record of federal prosecutors in Massachusetts, several employees from Bristol-Myers Squibb decided to expose the company's massive illegal marketing scheme for its AAP Abilify (aripiprazole), resulting in a massive $515 million settlement. Like the three above examples, BMS also illegally marketed its AAP for pediatric use and dementia. Even after the FDA forced boxes of Abilify to carry a black box warning against the use of the drug for dementia, the drug company's sales force still targeted nursing homes to sell the drug!  According to an official Department of Justice press release, BMS employees provided illegal kickbacks to doctors to encourage them to sell their drugs through financial gifts and trips to luxurious resorts.

Johnson & Johnson and Risperdal

Documents uncovered by federal officials revealed that Johnson & Johnson, having been told in 1999 that the company was skewing the harms and benefits of its AAP Risperdal, crafted a business plan the very next year aiming for sales of over $300 million by increasing the drug's market share for elderly dementia sales, a blatant off-label use. Louisiana officials cited the documents in recent court hearings against the drug giant for charges of off-label marketing of its best-selling antipsychotic, claiming it was proof that the pharmaceutical company purposely pushed the drugs on patients unaware of the drug's risks. J&J has been sued by 10 states over marketing practices, though it has yet to put aside an amount for a settlement. The drug netted J&J a cool $4.5 billion in 2007 before it lost patent protection.