zoloft: beyond the approval II…

Posted on Tuesday 19 February 2013

And so to what was riding on those decisions along the way? An absolute fortune was riding on every single one of them – on the jury-rigged protocol 103, or the unreplicable protocol 104, on the relapse prevention protocol 320 with its massive drop-out rates, on Paul Leber’s F.D.A. N.D.A. speech, and on the deceptive marketing campaign that followed. An absolute fortune…

There’s little need to document Pfizer’s success in marketing Zoloft. Pfizer is the world’s largest pharmaceutical company [with the world’s largest sales force], and they know how to do sell drugs. Here’s what the Lawsuit has to say about their campaign:

After Pfizer was approved in 1991, Pfizer embarked on a massi ve campaign to promote Zoloft as an effective and reliable treatment for depression. The first arm of this campaign involved the "direct-to-prescriber" approach. Pfizer would "wine and dine" prescribing healthcare professionals to encourage them to prescribe Zolof!. Pfizer would pay prescribing healthcare professionals to attend various events, such as theater shows, sporting events, ski trips and pay for stays at luxurious hotels and meals at fancy restaurants. Pfizer also used a large sales force, long recognized as the largest sales force in the industry, to visit prescribing healthcare professionals on a routine basis to promote Zolof!. These sales representatives, who were typically young attractive people, would visit prescribing healthcare professionals and "brief’ them on how effective Zoloft was at treating depression. The sales representatives would leave behind free samples and various forms of product literature, all designed to give prescribing healthcare professionals the impression that Zoloft was a reliable and effective medication for depression

The second arm of Pfizer’s promotional campaign focused on media advertisements to prescribing health care professionals and consumers. These print and video advertisements gave the false and misleading impression that Zoloft was a tremendously effective drug for the treatment of depression. For example, in a 2005 medical journal, Pfizer published an advertisement directed toward prescribing healthcare professionals which read: Zo effective, Zo well tolerated, Zo trusted. Zoloft. Choose the #1 prescribed SSRI. In another advertisement, Pfizer claims "Zoloft has helped millions with depression." In comic strip format, the advertisement tells a story about "Denise" who, depicted as a balloon-cartoon, is a music conductor that felt "an octave lower" because she "was depressed" and "had to do something about it." However, before she went to the doctor, she "did some homework" and discovered that "Zoloft is the number oneprescribed brand for depression." So, Denise went to her doctor and he told her "it’s helped millions" just like Denise. In the next box, Denise "realizes that Zoloft was helping me at work and at home." Beneath the comic strip, the ad states: "Denise took comfort in the fact that Zoloft has helped so many people for so many years. Zoloft is safe and effective. It has treated more people with more types of depression and anxiety than any brand of its kind. So she asked her doctor about Zoloft. Zoloft. #1 for millions of reasons." This advertisement, much like others, carefully misleads consumers into believing Zoloft is more effective for treating depression than clinical data would suggest. Pfizer stresses that Zoloft has "helped millions" but that inference presupposes that Zoloft is what is causing the perceived benefit in consumers, not the placebo effect – a fact that is simply not supported by Pfizer’s own clinical research. The combination of direct-to-prescriber and direct-to-consumer promotion convinced consumers and prescribing healthcare professionals that Zoloft was particularly effective at treating depression. Pfizer’s promotion, however, never revealed that the majority of clinical trials showed that Zoloft was no better than placebo.
This graph is number of prescriptions written by year. Zoloft passed Prozac in 2000 [about halfway through its patent life], and it continued to dominate the market share until going generic in 2006 [when it was replaced at the top by generic Zoloft]. It was a $30 B drug:

In 2009, Pfizer paid out $2.3 B in fines, the largest pharmaceutical settlement to date, but it was for a host of drugs only including Zoloft in a long string [1 of 13]:
Pfizer to Announce Record $2.3 B Settlement
Would be the largest payout of its kind
Associated Press
By LeAnne Gendreau
September 2, 2009

Pfizer, the world’s largest drugmaker, will pay $2.3 billion in connection with illegal drug promotions. The pharmaceutical giant Pfizer will to pay a record $2.3 billion settlement for illegal drug promotion. Pfizer Inc. and its subsidiary Pharmacia & Upjohn will pay the settlement to resolve criminal and civil liability arising from the illegal promotion of several pharmaceutical products, according to the U.S. Justice Department.

The settlement, which was announced Wednesday, is the biggest ever paid by a drug company for such activity, the Philadelphia Inquirer reports. Pfizer is accused of breaking U.S. Food and Drug Administration rules by marketing drugs for unapproved uses and paying kickbacks to doctors in entertainment, cash, travel and meals to promote and prescribe certain medications, according to Connecticut Attorney General Richard Blumenthal. The allegations involved 13 Pfizer drugs, including Bextra, Geodon, Lyrica, Viagra, Lipitor and Zoloft
Looking back, we have to ask ourselves if what Dr. Leber said back in 1991 is enough. Is it a reasonable standard? or too minimalist to be viable? Knowing now what happened, is this the best we can do?
"I think it should be understood that all comparisons are probably odious. We do not have a comparative efficacy/safety drug law, although, clearly, clinicians using drugs are interested in determining relative efficacy, relative safety and relative utility – whatever that means. I think you have to understand that when we face an application from a regulatory perspective, we are asked to face what the law requires us to do. We are obligated to approve an NDA unless our review finds that the drug is unsafe for use; that inadequate testing has been done to show that the drugs is safe. We are required to approve the drug unless we find that the tests submitted failed to contain substantial evidence of efficacy. That means more than one investigation which adequate and well controlled which would allow experts – experts by experience, training and background – to reach a conclusion that the drug is effective. And we are obliged to approve the drug unless we find that the labeling is false or misleading in some particular…"
And is having a higher standard for F.D.A. approval really the place to intervene? With financial incentives like $30 B, is there anything we can do to add some checks and balances to this out-of-control system?
  1.  
    Bernard Carroll
    February 19, 2013 | 6:36 PM
     

    Mickey, your series on sertraline (Zoloft) does a fine job summarizing the corruption of the past 20+ years in neuropsychopharmacology. The Pharma-commissioned and ghostwritten articles were carefully planned. They were the end result of commercially strategic clinical trials that aimed to promote the product in a market niche. For these the term experimercial is used. It is no accident that this term was added to our lexicon in connection with a Pfizer trial of Zoloft. When we get beyond the hand waving, the data manipulation, the selective analyses, the cherry picking, the special pleading over trivial effect sizes, and the other tricks, then “like the Cheshire cat’s smile, the only evidence that sertraline was there is the disembodied p value, grinning in statistical space, with no connection to clinical reality” (PubMed ID 15169734).

  2.  
    berit bj
    February 19, 2013 | 7:33 PM
     

    “…strategic clinical trials that aimed to promote the product in a market niche.”
    And that “market niche” grew to enormous proportions in step with WHO consulting the oracle of Delphi, one may presume, giving psychic illness/ depression top spots in charts of global ill health burden, accompanied by Big Pharma commercials and global promotion. The “antidepressants” and the “antipsychotics” grew to blockbusters in the top drug division of around 30 billion dollars each a year. What a niche. What frauds. What a racket.

  3.  
    February 19, 2013 | 7:34 PM
     

    “Something has changed in our conceptual paradigm when a drug can be described as “effective” for depression but the patients do not endorse that their lives are any better with respect to vitality or social functioning or emotional role functioning or mental health. Like the Cheshire cat’s smile, the only evidence that sertraline was there is the disembodied p value, grinning in statistical space, with no connection to clinical reality. That is not quite what Percy Bridgman had in mind when he introduced operationalism in science. Lewis Carroll, on the other hand, would have appreciated the irony.

    Bernard Carroll, 2004
    in response to a Sertraline in geriatric depression paper…

  4.  
    February 26, 2013 | 10:13 AM
     

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