Professionalism/Eli Lilly and Zyprexa

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Zyprexa[edit]

Zyprexa (olanzapine) 10 mg tablets

Zyprexa (olanzapine), a product of the pharmaceutical giant Eli Lilly & Co, was introduced in 1996 as an atypical antipsychotic [1]. Approved by the FDA for the treatment of Schizophrenia and Bipolar Mania, Zyprexa accounted for almost one-third of annual revenue for Eli Lilly since the drug's introduction, with global sales exceeding $4 billion dollars in 2006 [1]. Zyprexa has been prescribed to nearly 26 million people since 1996 [2].

Marketing Strategy[edit]

Eli Lilly is widely criticized for employing irresponsible marketing strategies that down-played the risks and promoted "off-label" usage of Zyprexa.

Off-label Marketing[edit]

While only approved for schizophrenia and bipolar mania, the drug was marketed to doctors and patients for a wide range of unapproved and questionable treatments. For example, Eli Lilly established a "Viva Zyprexa" campaign that promoted the use of Zyprexa for symptoms including agitation, hostility, aggression, depression, and sleep or mood disturbances [3]. No specific clinical studies had been performed to examine Zyprexa's effect on these symptoms.
Eli Lilly also specifically targeted the elderly suffering from dementia and Alzheimer's [4]. Leaked documents show that Eli Lilly instructed pharmaceutical salespeople to make dementia the first message for primary care physicians, since Schizophrenic patients were typically reported to specialists [1]. Similarly, other documents show Eli Lilly claiming that Zyprexa is a safe choice for treating agitation and confusion. The sales slogan "5 at 5" was allegedly used by salespeople to promote 5mg of Zyprexa at 5pm to help the elderly sleep. However, Zyprexa had not been approved for any such treatments and, in fact, suggested harmful side effects during clinical trials [3].

Down-played Risks[edit]

Concerned that sales of the drug might suffer if they were more forthright, Eli Lilly instructed sales representatives to down-play the risks of Zyprexa. Clinical trial documents showed that 16% of patients gained more than 66 pounds within a year of use. Moreover, the effects of the drug on diabetes risk were extreme [3]. In 2001, the American Medical Association published a study reporting that patients taking Zyprexa had a ten times higher risk of developing diabetes. Similar cases have been identified for Ketoacidosis and Pancreatitis [5][6]. Researchers also discovered that the elderly were twice as likely to suffer stroke or fatal injury while on Zyprexa. Although the FDA and regulatory agencies in the UK and Japan all warned that Zyprexa might lead to diabetes, Eli Lilly failed to disclose this information [4].

Legal Consequences[edit]

Through 2008, Eli Lilly had paid out over $1 billion to settle more than 32,000 Zyprexa lawsuits. In 2009, Eli Lilly entered a guilty plea with federal prosecutors of the Pennsylyvania Federal court for illegally marketing Zyprexa [3]. While doctors hold the authority to prescribe drugs for conditions that they haven't been approved for, it is strictly illegal for pharmaceutical companies to promote off-label usage of their drugs. Eli Lilly, guilty of these actions, was forced to pay $1.42 billion for its misdemeanor violation of the Federal Food, Drug and Cosmetic Act in addition to other state level lawsuits [3].

The terms of the plea agreement also include compulsory compliance in a corporate integrity agreement with the Office of the Inspector General (a division of the U.S. department of Health and Human Services) [4]. This includes an external compliance program that will be in effect for five years, Although very similar in protocol to the internal compliance policies existing at Eli Lilly, this program includes third-party review for all systems, processes, policies, procedures, and practices.

General Pharmaceutical Misconduct[edit]

Such actions are widespread in the pharmaceutical industry. Of the top 10 pharmaceutical manufacturers in the world, all 10 have been involved in similar deceitful behaviors. Pfizer, the largest pharmaceutical manufacturer in the world, has been found guilty of falsely advertising and deceiving doctors about its prized possession, Lipitor. Lipitor is the best-selling prescription substance in the world [7]. Novartis, the second largest pharmaceutical manufacturer in the world, in 2010, paid over $200 million for off-label marketing [8]. Sonafi, the next largest manufacturer, paid $100 million for similar activities in 2009 [8]. Similarly, Merck, the manufacturer of Vioxx, faced billions of dollars in lawsuits for falsely advertising its blockbuster drug [9].

Economics of the Pharmaceutical industry[edit]

To fully understand the ethical misconduct at hand, it is important to first examine why these major pharmaceutical companies behave in such a manner. Similar to any other business, large pharmaceutical companies are driven by profit incentives. PhRMA and the IFPMA, two major lobby groups for the pharmaceutical industry, state that the main objectives of the pharmaceutical industry are to deliver safe and effective pharmaceuticals to patients while also maintaining profitability for its investors [10] [11] . It is this latter part of this agenda that is often responsible for pharmaceutical misconduct.

The Drug Development Process[edit]

In the United States alone, $300 billion dollars is spent annually on prescription drugs [12]. With the promise of such a large market, pharmaceutical companies actively attempt to establish a larger market presence. Over the past 20 years, nearly 1900 new pharmaceuticals have been granted approval by the FDA[10]. With a very low chance of success, the development of each one of these medicines involves significant monetary and time commitments by pharmaceutical manufacturers. Pharmaceutical companies begin with a pool of over 10,000 compounds of interest. After approximately 10 years of product testing and clinical trials, a handful are selected for in vivo evaluation. Of these handful, one or two are tested on human volunteers, with a single compound from the initial 10,000+ moving into end stage studies before being submitted for regulatory review and approval. This process requires exorbitant financial investments. Nearly $800 million is spent on average on R&D alone to bring a single new drug to market[10]. In 2009, PhRMA estimated that nearly $65.3 billion on R&D by the research-based pharmaceutical industry[10].

Questionable Practices[edit]

To recoup the R&D costs and generate profits from their discoveries, pharmaceutical manufacturers rely on patents. Currently, manufacturers of pharmaceuticals like Zyprexa have approximately 8-10 years of effective market exclusivity due to patent expirations and competition from generics [11]. Due to this limited period of exclusivity, pharmaceutical companies have adopted many questionable strategies to maximize profits. These strategies include competitive practices with generic manufacturers, finding loopholes in the patent system, and ghostwriting. However, the practice that raises the greatest ethical issues is advertising to medical professionals and consumers. Over $11 billion is spent annually by pharmaceutical companies to promote and market their products [13]. In 2009, the top 20 proprietary pharmaceutical companies spent around 30% of their total revenues on marketing [14]. A majority of this expenditure is in the form of gifts and sponsored events for physicians. Physicians often use these company sponsored events, such as the Continuing Medical Education (CME) programs to learn about new medicines [15]. As these events are sponsored and conducted by the pharmaceutical manufacturers, they provide an opportunity for these companies to falsely advertise their products. With large investments at stake and investors demanding returns, the pharmaceutical industry often exaggerates the scope and safety of their products. These false claims frequently lead to improper prescribing practices by medical practitioners and, as has been the case for Zyprexa and many other blockbuster pharmaceuticals, hundreds of thousands of injuries and deaths to patients.

Similar Cases[edit]

Professional ethical misconduct is not limited to pharmaceutical companies. Such examples are present in every field where a professional's actions resulted in untold damages to those who depended on them. Frederic Whitehurst and the FBI and the Enron scandal are two such examples. In the first case, Frederic Whitehurst was an FBI agent who discovered and exposed illegal evidence manipulation in the FBI crime lab. Likewise, Enron was an energy company that duped its investors out of billions of dollars by falsely reporting its finances. The consequence for the professionals in these instances is the loss of trust and, accordingly, the loss of autonomy not only for themselves but also for other professionals in their field. In the case of Eli Lilly this was demonstrated by a drop in sales of Zyprexa after the scandal broke [16]. Not only do these decreased sales show a lack of trust in Lilly, but also in the doctors prescribing this drug and the FDA, who approves it for general market sale. Similarly, Eli Lilly is now subject to supervision by the Office of the Inspector General as they were no longer deemed trustworthy to ethically regulate their actions. For the FBI, the loss of autonomy played out in the form of investigation and accreditation by the American Society of Crime Laboratory Directors while the consequences for Enron and Arthur Andersen were far more severe. Both companies were virtually run out of business. Moreover, their actions led to the enactment of many laws regulating auditing practices nationwide. Companies that had no part in this scandal felt the backlash.

Diminishing Professional Trust[edit]

All of these examples are from situations that, on the surface, are vastly different from each other, yet share a common theme. In each, there existed a group of professionals, organizations like Lilly, the FBI, and Enron, trusted by the public and, subsequently, given a certain autonomy. In each situation, these professionals failed in their duties to serve the public, resulting in deaths, wrongful convictions, or loss of billions of dollars. However, these consequences extend beyond these casualties. Such actions lead to a complete loss of trust and, therefore, autonomy for these companies and the associated professionals. From these cases it is evident that autonomy is an important, perhaps even fundamental, element of being a professional. But if this power is abused it will quickly be revoked. To keep this autonomy, professionals must be trusted. Therefore, maintaining trust is an essential part of being a true professional.

References[edit]

  1. a b c Berenson, Alex (2007). Lily Settles with 18,000 over Zyprexa. The New York Times http://query.nytimes.com/gst/fullpage.html?res=9f00e5db1430f936a35752c0a9619c8b63
  2. Lilly Resolves Investigations of Past Zyprexa Marketing and Promotional Practices (2009). Eli Lilly and Company. http://newsroom.lilly.com/releasedetail.cfm?ReleaseID=359242
  3. a b c d e Eli Lilly Zyprexa Settlement: Drug Maker to Pay Record $1.42 Billion (2009). Find Law. http://commonlaw.findlaw.com/2009/01/eli-lilly-zyprexa-settlement-drug-maker-to-pay-record-142-billion.html
  4. a b c Eli Lilly profit drops sharply on Zyprexa generics (2012). Reuters. http://www.reuters.com/article/2012/01/31/us-elililly-idUSTRE80U0R020120131
  5. Zyprexa: hyperglycemia and diabetes (2011). 1 Boring Old Man. http://1boringoldman.com/index.php/2011/03/26/zyprexa-hyperglycemia-and-diabetes/
  6. Zyprexa side effects (2005). Van Der Ginst Law, P.C. http://www.zyprexa-lawsuit.net/zyprexa-side-effects.shtml
  7. Edwards, Jim (2010). Lawsuit Claims Pfizer Deceived Doctors Into Prescribing Its Cholesterol Drug Lipitor. CBS. http://www.cbsnews.com/8301-505123_162-42844207/lawsuit-claims-pfizer-deceived-doctors-into-prescribing-its-cholesterol-drug-lipitor/
  8. a b Lucy, C (2010). Big Pharma Lawsuits – Who Got Hit with the Biggest Settlement?. Lawyers and Settlements. http://www.lawyersandsettlements.com/blog/big-pharma-lawsuits-who-got-hit-with-the-biggest-settlement-05310.html
  9. Wilson, Duff (2011). Merck to Pay $950 Million Over Vioxx. The New York Times. http://www.nytimes.com/2011/11/23/business/merck-agrees-to-pay-950-million-in-vioxx-case.html
  10. a b c d Pharmaceutical research and manufacturers of America (2011). http://www.phrma.org/sites/default/files/159/phrma_2011_annual_report.pdf
  11. a b International federation of pharmaceutical manufacturers & associations: corporate brochure (2010). http://www.ifpma.org/fileadmin/content/About us/1 Welcome/IFPMA_Corporate_Brochure_LowRes[1].pdf
  12. Huges J, Moore M, Snyder E (2002). Napsterizing Pharmaceuticals: Access, innovation, and consumer welfare. 2002 NBER Working paper
  13. Wazana A (2000). Physicians and the pharmaceutical industry. Is a gift ever just a gift? JAMA, 283, pp. 373–380
  14. Glasgow, L J. (2001). Stretching the Limits of Intellectual Property Rights: Has the Pharmaceutical Industry Gone Too Far?, 41 IDEA 227, 250-251
  15. Gagnon MA., Lexchin J. (2008). The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States. PLoS Med 5(1):e1.doi:10.1371/journal.pmed.0050001
  16. Brickates, Val (2007). Lily CEO: Zyprexa Sales Flat. MarketWatch http://articles.marketwatch.com/2007-03-14/news/30734464_1_zyprexa-eli-lilly-lilly-ceo