How drug companies get the clinical trial results they want

Every prescription drug (or over-the-counter medication) in your bathroom cabinet is there because it’s been evaluated in research called a clinical trial. For a basic introduction to clinical trials, let’s turn to former editor-in-chief of the prestigious New England Journal of Medicine, Dr. Marcia Angell, who wrote the following in her frightening landmark piece called “Drug Companies & Doctors: A Story of Corruption” (New York Review of Books, 1/15/2009):

“Before a new drug can enter the market, its manufacturer must sponsor clinical trials to show the Food and Drug Administration that the drug is safe and effective, usually as compared with a placebo or dummy pill.

“The results of all the trials (there may be many) are submitted to the FDA, and if one or two trials are positive – that is, they show effectiveness without serious risk – the drug is usually approved, even if all the other trials are negative.” 

But there’s an even bigger problem with clinical trials, according to Dr. Richard Smith (editor of the British Medical Journal for 25 years). He explained the problem in his Public Library of Science journal article called “Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies”:*

“A much bigger problem lies with the original studies, particularly these clinical trials published by medical journals.

“Far from discounting these, journal readers see randomized controlled trials as one of the highest forms of evidence.

“A large trial published in a major journal has the journal’s stamp of approval, will be distributed around the world, and may well receive global media coverage, particularly if promoted simultaneously by press releases from both the journal and the expensive public-relations firm hired by the pharmaceutical company that sponsored the trial.

“For a drug company, a favourable trial is worth thousands of pages of advertising, which is why a company will sometimes spend upwards of a million dollars on reprints of the trial for worldwide distribution.”

Here’s an example of what Dr. Smith is talking about: a study published in the Journal of the American Medical Association reported that the drug giant Merck had hired medical ghostwriters to draft dozens of flattering ‘research’ papers about their now-discredited pain drug Vioxx. They then lined up well-known doctors who agreed to fraudulently claim to be the actual authors for submission to journals.**

The New England Journal of Medicine sold 929,400 reprints of a single Vioxx-friendly ‘research’ article it had published  – mostly sold directly to the drug’s own manufacturer, Merck, in fact. Merck’s sales reps then distributed these reprints to physicians on their daily call routes as part of their  aggressive Vioxx sales campaign.

Reprint orders from this one ghostwritten Vioxx article brought in more than $697,000 in revenue for the NEJM.

Medical journal editors who don’t want to bite the Big Pharma hand that feeds them apparently learn to hold their noses and accept this. And as Dr. Smith explains:

“The doctors receiving the reprints may not even read them, but they will be impressed by the name of the journal from which they come.

“The quality of the journal will bless the quality of the drug.”

Consider also the systematic review published in the British Medical Journal comparing the outcomes of studies funded by the pharmaceutical industry with outcomes of studies funded from other sources.***

Researchers found that 13 of the 16 clinical trials or meta-analyses studied had outcomes favourable to the drug companies that funded the studies. In fact, studies funded by a company were four times more likely to have results favourable to the company than studies funded from other sources. In the case of five studies that looked at economic evaluations, the results were favourable to the sponsoring company in every case.

The evidence is strong, warns Dr. Smith, that drug companies are generally  getting exactly the results they want from the clinical trials they pay for, and this is especially worrisome because between two-thirds and three-quarters of the trials published in the major medical journals (Annals of Internal Medicine, Journal of the American Medical Association, Lancet, and New England Journal of Medicine) are funded by industry.

But how is it possible that these companies are getting such bizarrely predictable favourable results?

Dr. Smith suggests that they’re not fiddling with the research results, which he claims would be far too crude and possibly detectable by peer review, but rather are simply asking the “right questions”.

But how to accomplish this? Dr. Smith advises this primer for Big Pharma:

Methods Used by Pharmaceutical Companies to Get the Results They Want from Clinical Trials

  • Conduct a trial of your drug against a treatment known to be inferior.
  • Trial your drugs against too low a dose of a competitor drug.
  • Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
  • Conduct trials that are too small to show differences from competitor drugs.
  • Use multiple endpoints in the trial and select for publication only those that give favourable results.
  • Do multi-centre trials and select for publication only those results from centres that are favourable.
  • Conduct subgroup analyses and select for publication only those that are favourable.
  • Present results that are most likely to impress – for example, reduction in relative rather than absolute risk.

.

* Smith R. Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies. PLoS Med 2(5): e138. 2005. doi:10.1371/journal.pmed.0020138

** Joseph S. Ross, MD et al. Guest Authorship and Ghostwriting in Publications Related to Rofecoxib: A Case Study of Industry Documents From Rofecoxib Litigation. JAMA. 2008;299(15):1800-1812

*** Lexchin J, Bero LA, Djulbegovic B, Clark O (2003) Pharmaceutical industry sponsorship and research outcome and quality. BMJ 326: 1167–1170.

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10 thoughts on “How drug companies get the clinical trial results they want

  1. I only read the brief statement given when I opened the mail but I had no wish to torture myself by reading the gruesome details. My comment: Why does this not surprise me? Given everything else I’ve learned from you about the pharmaceutical companies, nothing would surprise me now. They are just unbelievably corrupt and very good at helping others become corrupted – another piece of evidence that money wins over everything. And I mean EVERYTHING. It makes me sick.

    But please don’t anyone suggest a medication to treat my sickness!

    (Well, not unless it’s cookies, cake, dark chocolate candy, or – well, you catch my drift.)

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    • Hi Bev – I’m down at Stanford attending the Medicine X conference here, and I’m pretty sure I heard one of the doctors here say that cookies, cake, chocolate are all good drugs . . .

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    • There is simply too much money at stake here to expect industry (and the scientific journal editors who are complicit in publishing industry-funded studies) to simply stop doing what they’re doing unless forced to do so. Conflict of interest disclosure is not enough.

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  2. The system we have for demonstrating the safety and efficacy of drugs isn’t perfect and has been gamed and defrauded, but it is far better than any system we have for testing any other product.

    What would happen to the auto industry if every new car was required to undergo four years of trials under real world conditions, with every single repair, accident, paint chip, or broken window written up as an “adverse event”? Where are the FDA-approved, company funded trials of vitamin supplements or herbal medicines? For that matter, where is the inspection that proves there is even a vitamin in your vitamin supplements? Where is the evidence that Windows 7 is safe and effective?

    The FDA was established in part to regulate the drug industry, and it is paid for by putting up huge cash barriers for entry into the US drug market. It is also putting up huge regulatory hurdles, in an attempt to ensure that when we take a drug, we have good information about both the risks and the potential benefits of taking the drug. The information may not be perfect, but again, it is better than the information we have available about any other product.

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  3. Thanks for sharing your perspective here, Mike. The issue here, however, is that my car’s paint chips or Windows 7 flaws do not affect my body. The fistful of cardiac meds I now take daily do. My concern is that the “good information” about risks and benefits of those meds is likely to be bought and paid for by Big Pharma.

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    • Paint chips and pixel misalignment may not affect your body and mind, but brake failures and backdoors that allow hackers to empty your bank account certainly do. Occasional slight fevers or mild drymouth also do not affect your body to a great extent, but are required to be publicly reported anyway.
      The bar for acceptable information required by FDA may be low, but the information the FDA requires to be submitted for a new drug is still far higher than that required for anything else we as consumers ever use.

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  4. Mike, I can’t disagree with your argument that this country requires intensive testing and reporting, but when that reporting hides a well known side effect called DEATH, reviewed and also hidden by the drug company’s MDs in the appropriate field, then I think it’s time the drug companies are stopped in their tracks and put in the slammer. They probably won’t die in there. Or we could just have them come in for their daily or whatever is recommended of their own death-prone drug. I would call that a fitting consequence. If they die? Oh well………. (I actually am a person who doesn’t believe in killing anyone who isn’t threatening actively to kill someone else, but this consequence sure comes to mind for someone who behaves in such a reprehensible way!)

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    • Hi Carolyn

      Thanks for allowing us to ‘nick’ some of your work. Keep kicking butt. You have a great blog and we will be sign posting people in your direction in the future. So much of the science that rules and influences our lives is bent, and has been bought and paid for.

      Keep up your great work.

      Good luck and health to you and yours.

      Eddie

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  5. Pingback: Dr. Joe Kosterich

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