Professionalism/Purdue Pharma and OxyContin

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In 1996, Purdue Pharmaceuticals released a new opioid painkiller called OxyContin. Due to Purdue's aggressive and deceptive marketing campaign, OxyContin was overprescribed, leading to a widespread abuse epidemic. In 2007, the company was fined over $600M to resolve multiple civil and criminal cases against it.[1]

Background[edit]

Purdue Pharma is a pharmaceutical company that specializes in pain medication. The company was founded by Dr. John Purdue Gray and George Frederick Bingham in 1892 as The Purdue Frederick Company. It was purchased in 1952 by Drs. Raymond and Mortimer Sackler. In 1972, Purdue developed the Contin controlled drug release system. MS-Contin, a morphine-based pain reliever, was launched in 1987. [2] The World Health Organization began to promote the treatment of cancer pain using opioid analgesics in 1986. By the mid-1990s many national pain-related organizations began to stress the importance of pain management, releasing treatment guidelines that included the use of opioids.[3] The oxycodone drug OxyContin was released in 1996.[2] OxyContin was about as effective as contemporary opioid painkillers, but differed from its competitors in that it used a controlled-release mechanism that slowly delivered the drug over a period of 12 hours.[4]

Marketing of OxyContin[edit]

The marketing of OxyContin has largely been characterized by its aggressive nature. In 2001 alone, Purdue spent an unprecedented $200 million on drug promotion, understating OxyContin’s potential for abuse and encouraging general use for chronic pain indications.[5]

Purdue's marketing strategy was primarily aimed at physicians. Most notably, it made use of advanced marketing data to profile and target physicians who were the most frequent opioid prescribers. The data, however, did not differentiate between physicians that carefully distributed OxyContin and those that did it carelessly. Purdue ingratiated itself with physicians by holding many all-expenses-paid symposia at resorts and distributing branded OxyContin items such as fishing hats, plush toys, and swing music.[6] Additional promotional strategies included extremely lucrative sales bonuses and the use of and patient starter coupons for a free 7- to 30-day supply.[6]

The number of OxyContin prescriptions for non-cancer related pain increased tenfold, from 670,000 in 1997 to 6.2 million in 2002.[7] Prescribing was particularly abundant in certain areas including Maine, Western Virginia, southwestern Virginia, and Alabama (up to six times the national average).[7]

Understating OxyContin's Addictive Potential[edit]

Throughout its promotional efforts to physicians, Purdue Pharma systematically minimized the risk of addiction to opioids. Purdue’s sales representatives were trained to carry the message that the risk of addiction was “less than one percent.” The company cited a study by Porter & Jick[8] which concluded that only 4 of 11,882 patients treated with opioids over a short period of time became addicted.[6] The study, however, reported no evidence of low addiction rates when opioids are used daily to treat chronic pain.

Prior to the marketing of OxyContin, most physicians were hesitant to prescribe opioid analgesics out of fear that their patients would become addicts. This attitude began to change as Purdue Pharma funded more than 20,000 pain-related educational programs and organizations which, in turn, advocated for long-term use of opioid analgesics in the treatment of chronic non-cancer related pain.[7] According to Van Zee, this “educational” campaign transformed the opioid prescribing patterns of physicians throughout the country.[6]

In 2007, Purdue plead guilty for the misbranding of OxyContin.[1]

FDA Oversight[edit]

Under the Federal Food, Drug, and Cosmetic Act (FD&C), the FDA is responsible for reviewing and approving new prescription drugs as well as their promotional materials. Purdue Pharma was not always forthright with the FDA about its promotional materials for OxyContin, however. In 1998, it distributed 15,000 copies of an OxyContin video to physicians without submitting the video to the FDA for review. After acknowledging this oversight, Purdue submitted the video to the FDA in 2001. One year later, the FDA concluded that the video minimized risks of OxyContin and had made unsubstantiated claims about the drug’s benefits.[6] By this time, the false information presented by the videos had already circulated among physicians for four years. The FDA may have been able to detect the original oversight and review the video much earlier if it had been appropriately staffed for the ever-increasing volume of prescription drug promotional materials.

The FDA and Purdue Pharma both claimed that they did not believe users would crush OxyContin pills in order to immediately obtain the full dose of the drug. The reasoning was that MS-Contin, a drug released by Purdue prior to OxyContin, had not seen widespread abuse and therefore they could not have anticipated that OxyContin would. This logic is flawed for many reasons. MS-Contin is an opioid intended to treat chronic pain. However, MS-Contin has distinct differences that should have prevented it from being used to predict outcomes for the new drug[4]. OxyContin contains pure oxycodone while MS-Contin is a morphine-based drug. Morphine has only half the potency of the active ingredient in OxyContin[3]. Morphine also carries the social stigma of a precarious narcotic that is only prescribed to the terminally ill. This stigma prevented MS-Contin from gaining the popularity that OxyContin would go on to have. The relatively small number of MS-Contin users was not a large enough sample size to use for making predictions regarding the widely used Oxycontin[4].

The FDA also made errors in approving the initial label for OxyContin. The FDA allowed Purdue to state that the delayed absorption mechanism that OxyContin employed reduced the abuse liability of the drug despite having no scientific evidence to support the claim. In 2001, after reevaluating, the language was removed [6]. The original label also contained a warning that crushing or chewing the pill would result in a rapid release of the drug. This served as an unintended advertisement that may have made users aware of ways to abuse the drug [3]. As Sam Quinones points out in Dreamland: The True Tale of America's Opiate Epidemic, “This was like an invitation to a junkie.” [9]

Abuse of OxyContin[edit]

Soon after its release, recreational users discovered that OxyContin could be crushed to receive nearly the full dose of oxycodone immediately. Purdue Pharma seemingly was aware of this as OxyContin was undergoing FDA review. Preliminary tests conducted by Purdue indicated that would-be-recreational users could receive 68% of the oxycodone immediately by crushing the pill[4].

Rising levels of abuse and addiction became evident in the late 1990s. From 1995 to 2001, the number of patients seeking help for opioid abuse in Maine increased 460%. Over this period, Eastern Kentucky saw a 500% increase in the number of patients entering methadone maintenance treatment programs.[7] Nationally, the opioid overdose death rate increased by 300% from 1999 to 2011. The unprecedented abuse of opioid pain relievers grew so rampant that the Centers for Disease Control and Prevention called the crisis the “worst drug overdose epidemic in US history.”[7]

Historical Cases of Prescription Drug Abuse[edit]

In 1933, a Benzedrine inhaler was released by Smith, Kline and French in America. The inhaler was intended to be used as a decongestant. However, users learned the inhaler could be broken open to expose a piece of filter paper containing 100 mg of Benzedrine carbonate. The paper could then be dissolved in a warm liquid allowing users to access the entire dosage in a short amount of time.[4] The drug became popular with the military during World War II exposing it to nearly 16 million Americans. By 1945 it was being abused by over half a million civilians as well.[10]

The FDA approved an analgesic called pentazocine in 1967 under the commercial name Talwin. By the late 1970s, users had discovered that the drug could be dissolved, filtered and then injected intravenously.[4] The drug became a popular substitute for heroin particularly in the Midwest. Reactions to the drug included muscle spasms, seizures, diaphoresis, nausea, and other symptoms.[11]

Lessons in Professionalism[edit]

Regulatory[edit]

Although the OxyContin case resulted in serious harm to millions of consumers, it resulted in no significant legal changes to the way controlled drugs could be marketed. According to the FDA, "Federal law generally requires that prescription drugs in the U.S. be shown to be both safe and effective prior to marketing."[12] There are restrictions on the marketing of controlled substances prior to FDA approval, but if the restrictions are not acted upon for years, their usefulness seems limited.

The FDA budget appropriation increased by approx. 400% between 2000 and 2016.[13][14] Although not all of this funding goes to prescription drug oversight, this represents significant growth in the FDA's ability to field sufficient staff to oversee pharmaceutical advertising. Although not all problems can be solved with more funding, this approach seems helpful in this case, as insufficient staffing directly enabled the OxyContin epidemic.

Medical[edit]

The responsibility of medical professionals is to provide effective and safe care for their patients; a responsibility which many failed during the OxyContin crisis. However, it is difficult to place blame for this on doctors, when they were intentionally misled by Purdue and let down by the FDA's oversight. It is absolutely the responsibility of prescribers to understand the drugs they prescribe, but it is not their responsibility to distinguish between genuine, reliable research and fraudulent research; it was reasonable for them to trust the FDA to fulfill that role.

However, the doctors prescribing or over-prescribing OxyContin are not without some blame in this crisis. OxyContin's marketing campaign focused heavily on prescribers. By providing them with merchandise, hosting conferences, and otherwise generating goodwill indirectly, OxyContin swayed the opinions of many doctors. Doctors must impartially judge the merits of medical techniques based on scientific data; when many failed to maintain their impartiality regarding Purdue, they failed the standards of their profession.

Industrial[edit]

Responsibility for the damage caused by OxyContin falls most squarely on the marketers and executives who mislead consumers. Certain Purdue executives were criminally convicted for their actions[cite]. Company president Michael Friedman, top lawyer Howard Udell, and medical director Paul Goldenheim each plead guilty to misbranding (specifically off-label promotion, in violation of the False Claims Act) and the three were fined $34.5 Million in total.[1] In addition, each was given three years probation and ordered to perform 400 hours of community service. However, none received prison time.[15]

However, in light of the incredible profits gained by Purdue Pharma in the years prior to the conviction, it is not clear if these fines are sufficient to deter such action in the future. The United States does have an interest in not outright bankrupting a major pharmaceuticals company, which could temporarily impede medical care. However, various agents of the company, including its marketers, almost all lawyers, and almost all executives, escaped their activities legally unscathed.

Eliot Spitzer, former New York Attorney Genera, stated regarding a similar case, "What we're learning is that money doesn’t deter corporate malfeasance. The only thing that will work in my view is C.E.O.'s and officials being forced to resign and individual culpability being enforced."[16] Spitzer was referring to a case against GlaxoSmithKline, which was fined over $3 billion for charges including pharmaceutical fraud. In order to prevent cases like this in the future, deliberate misbranding for controlled substances must be punished harshly, and the individuals responsible must be jailed. Pharmaceutical fraud causes much more severe harm than similar false promotion of, say, entertainment devices, and must be punished with according severity.

References[edit]

  1. a b c Meier, B. (2007). In Guilty Plea, OxyContin Maker to Pay $600 Million. New York Times.
  2. a b Purdue Pharma. About Purdue Pharma. Retrieved from http://www.purduepharma.com/about/#&panel1-2
  3. a b c United States General Accounting Office. (2003). Prescription drugs: OxyContin abuse and diversion and efforts to address the problem. Washington, DC: U.S. Government Printing Office.
  4. a b c d e f Griffin, O. H., & Spillane, J. F. (2012). Pharmaceutical regulation failures and changes: Lessons learned from OxyContin abuse and diversion. Journal of Drug Issues, 43(2), 164-175.
  5. Gellad, Z. F., & Lyles, K. W. (2007). Direct-to-consumer advertising of pharmaceuticals. American Journal of Medicine, 120(6), 475-480.
  6. a b c d e f Van Zee, A. (2009). The promotion and marketing of oxycontin: Commercial triumph, public health tragedy. American Journal of Public Health, 99(2), 221-227.
  7. a b c d e Kolodny, A., Courtwright, D. T., Hwang, C. S., Kreiner, P., Eadie, J. L., Clark, T. W., et al. (2015). The prescription opioid and heroin crisis: A public health approach to an epidemic of addiction. Annual Review of Public Health, 36(1), 559-574.
  8. Porter, J., & Jick, H. (1980). Addiction rare in patients treated with narcotics. New England Journal of Medicine, 302(2), 123.
  9. Quinones, S. (2005). Dreamland: The true tale of America's opiate epidemic. New York, NY: Bloomsbury Press.
  10. Rasmussen, N. (2008). America’s first amphetamine epidemic 1929-1971: A quantitative and qualitative retrospective with implications for the present. American Journal of Public Health, 98, 974-985.
  11. De Bard, M.L., & Jagger, J.A. (1981). T's and B's-midwestern heroin substitute. Clinical Toxicology, 18 (9), pp. 1117–1123.
  12. FDA (2017). Unapproved Prescription Drugs: Drugs Marketed in the United States That Do Not Have Required FDA Approval. https://www.fda.gov/drugs/guidancecomplianceregulatoryinformation/enforcementactivitiesbyfda/selectedenforcementactionsonunapproveddrugs/default.htm
  13. American Society for Microbiology (2001). Food and Drug Administration - FY 2001 Testimony. https://www.asm.org/index.php/publicpolicy-2/statements-testimony?id=2192
  14. FDA (2016). Budget Exhibits - Appropriations History. https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/BudgetReports/UCM488478.pdf
  15. Meier, Barry. (2007). 3 Executives Spared Prison in OxyContin Case.
  16. Thomas, Katie. (2012). Glaxo Agrees to Pay $3 Billion in Fraud Settlement. New York Times.