the Ouroboros

2014© Medscape staff surveyed physicians on ethical issues, finding less than half confessed to a weakness for a freebie. That’s encouraging to drug reps, since influencing just a few Key Opinion Leaders pays dividends. So long as the flock all think alike, this being exemplified by a disclosure. The practitioner failing to practice what he preaches!drugreps
Dr Justin Coleman boldly challenged pharma thru his official position with Royal Aust College of GPs, fronting a well-publicised ‘no reps’ in the surgery campaign which raised ire among his fellows. Seriously, who’d ever believe wealthy physicians could be bought with a Bic? A humour-laden registrar tutoring session blogged recently under ‘Uncertain Dealings’ raises doubts. “Thus, when a patient complains of a painful lower back, my eventual diagnosis, after a thorough history and examination, is ‘low back pain’…. And, as for assuming my intervention of massage or gabapentin directly causes the pain’s eventual resolution, well…call me Dr Doubt!” Bon mots over a patient suffering pain aside, this is revealing. Gabapentin is an anti-convulsant for epilepsy, which happens to also fix everything – if Pfizer’s offlabel marketing is to be believed. Fines for such of $430m in 2004, $142m in 2010, and $615m (including $325m class settlement) in 2014 were just incidental costs alongside their promotional budget. The best evidence from Cochrane states that less than half of those with postherpetic neuralgia or diabetic neuropathy will obtain pain relief. So uncertainty over cause leads to a stab (glad he didn’t become a surgeon) that the pain originates from damaged nerves, and an indirect consequence of a hundred Pfizer Aust pain presentations to doctors in the previous 6 months just happens to be a prescription for Neurontin. And a little rub down there, in case of a herniated disc perhaps.

There’s been 6 studies into gabapentin for nociceptive pain, ie hurting without malfunctioning nerves, and all the results were suppressed by the company. They weren’t published, because they were negative. This disturbed Kaye Dickerson sufficiently to inspire a 57 page dissertation on the subject, with a few hundred pages of supporting appendices.
The white knight * can offer no other assistance, and how did this come to pass? A letter from Pfizer Aust in 2003 prefaces the corporate strategy – avoid offlabel fines by investing in more approval trials. Dawn Carroll was recruited by Pfizer in ’07 and co-authored an updated Cochrane review in ’10, which was surprisingly favourable to their products gabapentin and pregabalin for chronic pain. All up, she’s published 50 articles with the Pain & Palliative Support group of Cochrane’s Editorial boardmember Prof Andrew Moore. Moore’s 2014 article for Jnl of the American Medical Association, ‘Antiepileptic Drugs for Neuropathic Pain and Fibromyalgia’ confirms that marketing-based medicine penetrates everywhere: “The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain and the National Institute for Health and Care Excellence recommend gabapentin and pregabalin as first-line treatments for neuropathic pain. These results support the recommendations.”

The future holds little promise, since a check of registered ANZ Clinical Trials of gabapentin for bad backs tells us Pfizer is comparing gabapentin against pregabalin for sciatica – which won’t offer us much of a choice (they’re related drugs having identical mechanisms). The obvious difference is that pregabalin is more expensive – the fine for offlabel promotional bribery was double that of its stablemate, at $USD2.3bn

I’d ridiculed medicine’s adoption of the caduceus previously. Perpetually going in circles makes the ouroboros – the snake eating itself, a more appropriate motif.

*Justin claimed in a memo that his example was an ironic motif, because he campaigns against industry influence on prescribers such as for gabapentin.  I value his opinion on popular culture as an illustrative means, and intend to  incorporate same next month. But perhaps the somewhat more socially critical Southpark, than the sagely Gandalf.

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2 Comments

  1. Prof Moore has responded and rightly points out that other than the referenced review (and ‘The Impact and Burden of Chronic Pain in the Workplace’ in 2012) all co-written articles were prior to Carroll’s employment by Pfizer. The final item of correspondence contributes positively, and is linked under Downloads.

  2. Dr Kaye Dickersin’s link has gone, but an excerpt sums it up: “With respect to Pfizer-supported studies of Neurontin in the areas of migraine, bipolar disorders, and pain, there is extensive evidence of reporting bias. Those that I observed, most of them many times over, included failure to publish negative results; selective outcome reporting where a secondary outcome or newly defined outcome was reported because the desired findings were not obtained for the primary outcome; selective analyses where, for example, patients were inappropriately excluded from or included in the analyses; multiple publication of desirable results; hiding of negative results in abstracts, letters to the editor, or other “grey literature”; and differential citation of Pfizer results to highlight actual or claimed positive findings. In addition, I observed extensive evidence of “reframing” or “spin” to make negative results appear positive. This was often accomplished by a “ghost author” working with a commercial company hired to accomplish Pfizer’s marketing goals related to its “publication strategy” (ie, the plan to successfully market Neurontin through selective publication of study results). There is also evidence that many of the studies were biased in their design, rendering their scientific value questionable.
    The documents I reviewed represent a remarkable assemblage of evidence of reporting biases that amount to outright deception of the biomedical community, and suppression of scientific truth concerning the effectiveness of Neurontin for migraine, bipolar disorders, and pain. Although each of the biases I observed has been individually reported and decried in the biomedical research literature, these biases have not typically been examined collectively as part of an overall “publication strategy” taken on by product sponsors. A publication strategy, meant to convince physicians of Neurontin’s effectiveness and misrepresent or suppress negative findings, is clearly spelled out and executed when one views the Neurontin documents as a whole. I find the behavior and actions visible through these documents highly unethical,harmful to science, wasteful of public resources, and potentially dangerous to the public’s health
    .”

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