Big Pharma, are you ready for your close-up?

Blood MedicineIt’s movie awards season, and that reminds us that filmmakers are at work on new projects that might snag an award or two next year. And ever since the film Love and Other Drugs turned Jake Gyllenhaal into a Viagra sales rep, and director Steven Soderbergh‘s film Contagion made a vaccine researcher into a hero, Big Pharma’s a hot theme in the movie biz.

For example, a recent Reuters report says that Kathleen Sharp‘s book Blood Medicine (formerly Blood Feud) has just been optioned by the film production company, New Regency. This book is the true story of Mark Duxbury, a Johnson & Johnson drug rep-turned-corporate whistleblower. Duxbury repped for J&J’s biotech division Ortho, and was one of its top salespeople for its anemia drug Procrit – until he was fired, allegedly for warning that the drug could actually be harmful.

Here’s why this real-life script has suspense thriller written all over it.  Procrit (epoetin alfa, or EPO) seemed to be a miraculous blood booster, stimulating the bone marrow to make red blood cells. This anti-anemia medication was one of the first biotech wonder drugs, developed in the 1980s by a start-up company called Applied Molecular Genetics, or Amgen.

As the story opens, Amgen knows it has a potential blockbuster on its hands. The AIDS epidemic is sweeping the U.S.  At this time, there is no way to detect HIV-tainted blood, and any new drug which can reduce the need for blood transfusions has the potential to save countless lives. But Amgen needs capital to develop their new drug, and they enter into a partnership with pharmaceutical drug industry giant Johnson & Johnson to sell the drug under the brand names Procrit, Epogen, and Aranesp.

J&J sales rep Mark Duxbury champions this new product and believes in the technology behind it. Described by Sharp as “always at the ready with a joke and a smile”, his knowledge and passionate pitches set sales records and help him win company performance awards.

J&J allegedly provides Duxbury with a playbook of tactics known to convince physicians to write more Procrit prescriptions and at higher, more dangerous doses, all the while assuring them the drug is “as safe as mother’s milk.”

Doctors, as Sharp describes, are easily manipulated into prescribing more of this drug through J&J’s offers of rebates, speaking and consulting fees, research stipends, grants, rebates, free meals, secret discounts, honoraria, “continuing medical education” seminars at luxury resorts, and other kickbacks.

Procrit is heavily promoted as an instant cure for chemotherapy-related fatigue as well as for anemia in kidney dialysis patients. J & J starts running ads for Procrit. This ad campaign, which runs between 1998 and 2005, features the tagline “Strength for Living.” An FDA letter to J&J, however, warns that the ad is “misleading because it implies that Procrit improves strength and may improve survival, when the outcomes have not been demonstrated by adequate and well-controlled clinical trials.”

J&J also finances “The Fatigue Coalition”  – a patient-advocacy group that promotes off-label (unapproved) uses of the drug for cancer patients, despite studies* concluding: these agents  are effective in the management of cancer-related fatigue but also raises serious concerns about safety data and adverse outcomes associated with these agents. The review concludes that these agents should not be used for the treatment of fatigue in patients with cancer.” *

Kickbacks to doctors and hospitals buying Procrit become an integral part of the marketing strategy. For example, an internal company memo calculates that a physician who orders  $1 million of Procrit over 15 months would personally receive a kickback of $237,885 in return, or a 24% cash rebate.

The drugmaker also:

  • monitors doctors’ prescribing habits to determine the marketing strategies that will work best
  • violates patient confidentiality laws by encouraging sales reps to troll medical records for the best drug-testing candidates
  • uses study participation to get doctors to prescribe Procrit for dangerous off-label purposes.

Then the plot thickens.  The deaths of about a dozen high-profile European cyclists from a deadly condition called pure red cell aplasia (a total shutdown of the body’s red blood cell production) are linked to high dosing with the blood booster EPO (accessed via the black market).**

EPO has already been linked to illegal doping among elite athletes, and is banned as a performance-enhancing drug that claims to increase an athlete’s aerobic capacity and muscle endurance. (It also made headlines last year when U.S. cyclists Tyler Hamilton and Floyd Landis each claimed first-hand knowledge of disgraced seven-time Tour de France champion Lance Armstrong‘s use of the banned drug).***

Sharp writes that drug safety tests have not been conducted for Procrit, though such testing is  required by the FDA contingent on approval. Astonishingly, the FDA had decided that safety studies could be done after the drug was brought to market. She writes:

“Scientists knew that boosting red blood cells also thickened the blood, which increased the risk of clotting. Blood clots lead to strokes, heart attacks, and brain aneurisms. No one could be sure that Procrit was safe at even recommended doses, according to several sources.”

Eventually, Mark Duxbury comes to the horrifying conclusion that up to half a million people may have died as a result of this drug. He tries to stop some of the ruthless marketing practices, but is fired by J&J. Then he attempts to warn the public about the drug’s dangers in any way he can: by testifying in a secret arbitration, joining a class action effort, and, finally, filing a whistleblower lawsuit.

In the spring of 2007, the Food and Drug Administration slaps a black box warning on the label of the drug (sold as Procrit, Epogen and Aranesp), and the U.S. Congress calls a hearing about the illegal promotion of these anti-anemia drugs.

The drug’s packaging insert now includes this ominous warning:

“INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE.”

Physicians are still prescribing Procrit.  As of June 2011, the FDA’s warning to patients now simply reads:

“Using PROCRIT can lead to death or other serious side effects.”

Stay tuned for release date information as the Blood Medicine film production begins.

Meanwhile, watch this interview with Kathleen Sharp about what convinced her to write her book, Blood Medicine.

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*  Minton O, Richardson A, Sharpe M, et al: Drug therapy for the management of cancer-related fatigue. Cochrane Database Syst Rev 7: CD006704, 2010.

**   Nicole Casadevall. Pure Red-Cell Aplasia and Antierythropoietin Antibodies in Patients Treated with Recombinant Erythropoietin.  N Engl J Med 2002; 346:469-475 February 14, 2002

***  U.S. Anti-Doping Agency official charges, June 12, 2012: “Erythropoietin (EPO), also known as E, Po, Edgar or Edgar Allen Poe, among other names. EPO is used by athletes to increase the number of red blood cells in their circulatory system which are available to carry oxygen. … Even after the EPO urine test was developed and implemented in sport in late 2000 EPO was difficult to detect and the Respondents [Lance Armstrong, a team director, team captain and team doctors] implemented a number of means to avoid detection of EPO use, including: micro-dosing (i.e., using smaller amounts of EPO to reduce the clearance time of the drug), intravenous injections (i.e., injecting the drug directly into the vein rather than subcutaneously to reduce clearance time), saline, plasma or glycerol infusions (described below) and various effort to avoid testing by drug testers at times that EPO might still be detectable in the riders’ urine. … Multiple riders with firsthand knowledge will testify that between 1998 and 2005 Armstrong personally used EPO and on multiple occasions distributed EPO to other riders.”

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9 thoughts on “Big Pharma, are you ready for your close-up?

  1. Thanks for that post, Carolyn. But why am I not surprised? Sigh.
    I recently watched the movie Contagion and am trying to learn how to drink coffee or other beverages using my elbows!!

    ***Physicians are still prescribing Procrit. ***
    Just like Yaz is continued to be sold.

    ***“Using PROCRIT can lead to death or other serious side effects.”***

    What? What’s more serious than death? (insert black humor emoticon here)

    Like

  2. Wow!!! What amazing kickbacks! Any way I can get in on this? I’ll go door to door and tell everyone if they’re tired, whether just after waking up to after a big work-out at the gym, to beg their doctor to give them this energy boosting new medication! After all, don’t we all deserve to feel great? (How about sarcasm emoticons? Got any of those around?)

    Seriously, to everyone being prescribed to take this drug:

    ASK YOUR DOCTOR IF HE OR SHE WOULD TAKE THIS DRUG UNDER ANY CIRCUMSTANCES?!!!!

    Not that they could depend on an honest reply….

    I guess I still haven’t heard of enough of this level of horrifying behavior by marketing of anything at all to be numb. For our government, our physicians, or our drug companies to be willing to risk our lives absolutely horrifies me. I am stunned.

    How can anyone participating in this go to sleep at night? Do they say prayers before they go to sleep, begging for forgiveness for what they’ve done AND plan to continue to do?

    Carolyn, considering how cooperative our government is in promoting new drugs, see if they’ll give you the right to have access to every email address in the U.S. so you can send this Nag out as a warning to all. Just tell them you have an “informational drug” which is sure to save lives and increase performance in sports and in anemia-causing illnesses. I doubt you’ll even have to justify your claim, even being an honest one, but be ready to give a kickback to the FDA or anyone else who might argue with you. Everyone else seems to be susceptible to those.

    To all who are considering taking Procrit, legally or not:

    You can’t win your return to health nor an Olympic Gold Medal if you’re dead, right?

    By the way, Carolyn, any studies out on how to know if a doctor practices ethical medicine or not?

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    • Hi Bev
      Personally, I think it’s preferable NOT to feel “numb” by hearing stories like this one that Kathleen Sharp tells about Procrit marketing. Not sure how to answer your last question, given that there seems to be wide variation in individual doctors’ interpretations of what’s “ethical” or not in medicine.

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  3. Beneficence vs. Nonmaleficence

    Beneficence:

    Definition: Beneficence is action that is done for the benefit of others. Beneficent actions can be taken to help prevent or remove harms or to simply improve the situation of others.

    Clinical Applications: Physicians are expected to refrain from causing harm, but they also have an obligation to help their patients. Ethicists often distinguish between obligatory and ideal beneficence. Ideal beneficence comprises extreme acts of generosity or attempts to benefit others on all possible occasions. Physicians are not necessarily expected to live up to this broad definition of beneficence. However, the goal of medicine is to promote the welfare of patients, and physicians possess skills and knowledge that enable them to assist others. Due to the nature of the relationship between physicians and patients, doctors do have an obligation to:
    1) prevent and remove harms, and
    2) weigh and balance possible benefits against possible risks of an action. Beneficence can also include protecting and defending the rights of others, rescuing persons who are in danger, and helping individuals with disabilities.

    Examples of beneficent actions: Resuscitating a drowning victim, providing vaccinations for the general population, encouraging a patient to quit smoking and start an exercise program, talking to the community about STD prevention.

    Non-maleficence:

    Definition: Non-maleficence means to “do no harm.” Physicians must refrain from providing ineffective treatments or acting with malice toward patients. This principle, however, offers little useful guidance to physicians since many beneficial therapies also have serious risks. The pertinent ethical issue is whether the benefits outweigh the burdens.

    Clinical Applications: Physicians should not provide ineffective treatments to patients as these offer risk with no possibility of benefit and thus have a chance of harming patients. In addition, physicians must not do anything that would purposely harm patients without the action being balanced by proportional benefit. Because many medications, procedures, and interventions cause harm in addition to benefit, the principle of non-maleficence provides little concrete guidance in the care of patients. Where this principle is most helpful is when it is balanced against beneficence. In this context non-maleficence posits that the risks of treatment (harm) must be understood in light of the potential benefits. Ultimately, the patient must decide whether the potential benefits outweigh the potential harms.

    Examples of non-maleficent actions: Stopping a medication that is shown to be harmful, refusing to provide a treatment that has not been shown to be effective.

    Balancing Beneficence and Non-maleficence:

    One of the most common ethical dilemmas arises in the balancing of beneficence and non-maleficence. This balance is the one between the benefits and risks of treatment and plays a role in nearly every medical decision such as whether to order a particular test, medication, procedure, operation or treatment. By providing informed consent, physicians give patients the information necessary to understand the scope and nature of the potential risks and benefits in order to make a decision. Ultimately it is the patient who assigns weight to the risks and benefits. Nonetheless, the potential benefits of any intervention must outweigh the risks in order for the action to be ethical.

    From:
    http://missinglink.ucsf.edu/lm/ethics/Content%20Pages/fast_fact_bene_nonmal.htm
    © 2008 by the Regents, University of California

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    • Thanks Cave for sharing this crash course (courtesy of UCSF) on beneficence and non-maleficence (which are clearly NOT the same thing, apparently!) Very appropriate for this topic, particularly the examples of non-maleficent actions, which sound like they could have been lifted directly from this Procrit story.

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  4. I was kidding, Carolyn. Sorry that wasn’t at all clear. I couldn’t see how anyone could know if someone else was ethical. Cave has added to the body of general knowledge, though. Thanks, Cave.

    And yes! Not being numb is definitely better! Better to pay close attention, as well as to just still be alive and in the game!

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  5. Doctors getting kickbacks for prescriptions? Where have I been? It is certainly against the Hippocratic Oath, and should be a violation of the AMA Code of Ethics. I guess if they will not police themselves, we need to pass a law, either to have multimillion dollar fines to pharmaceutical companies or take away the medical licenses from doctors that accept cash rebates.

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