Sunday, December 04, 2011

Corrupted Research (Repost)

This is a repost from May 2009.

When a former editor-in-chief of The New England Journal of Medicine, says:
"It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine."
It's worth paying attention.

That quotation is by former NEJM editor Dr. Marcia Angell from her review of three recent books which (including one she authored herself) shine a light on the influence businesses, in this case drug companies, have on research that appears in even the most respected, peer-reviewed science and medical journals ... and how businesses influence the behavior of medical professionals, in all fields - healthcare, research, academia, and government.

Here's her review:
Drug Companies & Doctors: A Story of Corruption, New York Review of Books, January 2009.

I'll list the books she was reviewing because I think their titles help tell the story:
  • "Side Effects: A Prosecutor, A Whistleblower, And A Bestselling Antidepressant On Trial"
    by Alison Bass

    This is the story of pharmaceutical giant GlaxoSmithKline, who "buried evidence that its top-selling antidepressant, Paxil, was ineffective and possibly harmful." GSK agreed to settle charges of consumer fraud for $2.5 million - their cost for doing business, since Paxil continued to bring in about $3 billion a year.

  • "Our Daily Meds: How The Pharmaceutical Companies Transformed Themselves Into Slick Marketing Machines And Hooked The Nation On Prescription Drugs"
    by Melody Petersen

    The story of how drug companies engage in "disease-mongering," convincing prospective patients and their doctors "that they have medical conditions that require long-term medical treatment." Here, Pfizer pled guilty for illegally marketing Neurontin, laying out $430 million to resolve the charges. Again, this was just the cost of doing business, since Neurontin, which was initially approved to treat epilepsy, continued to bring in billions annually - for precisely the off-market uses Pfizer illegally advanced, "bipolar disease, post-traumatic stress disorder, insomnia, restless legs syndrome, hot flashes, migraines, tension headaches, and more."

  • "Shyness: How Normal Behavior Became A Sickness"
    by Christopher Lane

    This is another story of disease-mongering: Drug makers creating diagnoses for which drug intervention is not indicated (e.g. the diagnosis of "social anxiety disorder" for shyness), let alone adequately researched, yet proceeding to aggressively market their drugs anyway.

Selling Pills On Inference Instead Of Science

The field of psychiatry is particularly vulnerable to disease-mongering since diagnoses are largely subjective. However, Senator Charles Grassley, who exposed damaging conflicts-of-interest in the psychiatry field, has shifted his attention to the cardiology field - where cocktails of powerful drugs are being peddled without the backing of convincing published scientific evidence. (The polypill for heart disease comes to mind. It's an untested pill containing a statin, ACE inhibitor, diuretic, aspirin, and others.)

Ways Industries Corrupt Research

There are many ways that industries influence research. One is by suppressing unfavorable results of industry-sponsored studies. Here's an example using antidepressants:
"Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive."
- Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy, NEJM, 2008
Other ways include:
  • Setting up trials that are all but certain to show market worth, e.g. by comparing your drug to a placebo instead of to another similarly-classed drug.

  • Writing a paper that shifts focus away from a drug's poorly substantiated primary effect to a peripheral effect that appears more favorable.

  • Reanalyzing data from published studies, that is, performing a "meta-analysis," where included studies can be cherry-picked, or statistical analyses performed to deemphasize negative findings (i.e. broadening confidence intervals).
Dr. Angell says that "many reforms would be necessary to restore integrity to clinical research and medical practice. ... Many would involve changes in the FDA." I hope the new FDA Commissioner makes these reforms part of her agenda.


Anonymous said...

Thanks for re-posting this. I wish every physician would take it to heart.


Bix said...

I think the SATURN statin study (Lipitor vs. Crestor) fits the bill here, as corrupted research. Why on earth would you set the bar so high for serious side effects? 5 times normal? Unless you wanted to promote a potentially harmful drug?

Anonymous said...

I agree that there's some shenanigans going on. I also think the FDA is somewhat between a rock and a hard place, wrt people wanting even laxer regulations for alternative mediine, etc. Similar to the police ignoring drug dealing in my 'hood to focus on violence, yet preventing it in nicer 'hoods. (A friend buying a house called the police to ask, was really told this)

Bix said...

I agree with you about the FDA being caught between a rock and a hard place. There are some smart, hard-working people in that organization. I've read some outstanding documents from them. But people, well, some people, expect them to guarantee a perfectly safe food supply on a shoestring. (There's the whole issue of industrial lobbying and revolving door appointments too ... that affect how they operate. But, if I look at the glass as half-full, at least we have them.)

Angela and Melinda said...

Thanks for reposting. I couldn't remember which journal it was, as I mentioned before. I really appreciate it.

Anonymous said...

I definitely like the way you share yor ideas. You express the public opinion. Aren't you afraid of that?

Bix said...

Interesting question. Yes, in fact.