Pharmaceutical companies deliberately mislead doctors into prescribing useless and even harmful meds

Writing in the Guardian, Ben Goldacre reveals the shocking truth about the drugs that doctors prescribe: thanks to aggressive manipulation from the pharmaceutical companies and passivity from regulators, doctors often don't know that the drugs were ineffective (or harmful) in a majority of their clinical trials. That's because pharma companies set up their trials so that they the right to terminate ones that look unpromising (or stop them early if they look promising and report on the result partway through as though it reflected the whole trial), and to simply suppress the results of negative trials.

As a result, doctors -- even doctors who do their homework and pay close attention to the published trials, examining their methodology carefully -- end up prescribing useless (or harmful) medicines. And according to Goldacre, this is true of all doctors in every country, because every country's regulators allow pharmaceutical companies to cynically manipulate research outcomes to increase their profits. As Goldacre points out, a 2010 Harvard/Toronto study showed that "85% of the industry-funded studies were positive, but only 50% of the government-funded trials were" -- and in another analysis, industry-funded trials of statins "were 20 times more likely to give results favouring the test drug."

What's more, when scientists blow the whistle on this life-threatening criminality, they're smeared and hounded by the pharma companies, as happened when Danish scientists published a study critical of industry-funded trials in the Journal of the American Medical Association. After the study was published, Lif, the Danish pharmaceutical industry association, called for professional misconduct investigations into the researchers, though they couldn't provide any evidence of the alleged misconduct. Though the researchers were cleared of all wrongdoing, their employers were given copies of the accusations of scientific dishonesty, as did "the Danish medical association, the ministry of health, the ministry of science and so on."

This long piece is an excerpt from Goldacre's forthcoming book, Bad Pharma: How drug companies mislead doctors and harm patients.

Sometimes trials are flawed by design. You can compare your new drug with something you know to be rubbish – an existing drug at an inadequate dose, perhaps, or a placebo sugar pill that does almost nothing. You can choose your patients very carefully, so they are more likely to get better on your treatment. You can peek at the results halfway through, and stop your trial early if they look good. But after all these methodological quirks comes one very simple insult to the integrity of the data. Sometimes, drug companies conduct lots of trials, and when they see that the results are unflattering, they simply fail to publish them.

Because researchers are free to bury any result they please, patients are exposed to harm on a staggering scale throughout the whole of medicine. Doctors can have no idea about the true effects of the treatments they give. Does this drug really work best, or have I simply been deprived of half the data? No one can tell. Is this expensive drug worth the money, or has the data simply been massaged? No one can tell. Will this drug kill patients? Is there any evidence that it's dangerous? No one can tell. This is a bizarre situation to arise in medicine, a discipline in which everything is supposed to be based on evidence.

And this data is withheld from everyone in medicine, from top to bottom. Nice, for example, is the National Institute for Health and Clinical Excellence, created by the British government to conduct careful, unbiased summaries of all the evidence on new treatments. It is unable either to identify or to access data on a drug's effectiveness that's been withheld by researchers or companies: Nice has no more legal right to that data than you or I do, even though it is making decisions about effectiveness, and cost-effectiveness, on behalf of the NHS, for millions of people.

In any sensible world, when researchers are conducting trials on a new tablet for a drug company, for example, we'd expect universal contracts, making it clear that all researchers are obliged to publish their results, and that industry sponsors – which have a huge interest in positive results – must have no control over the data. But, despite everything we know about industry-funded research being systematically biased, this does not happen. In fact, the opposite is true: it is entirely normal for researchers and academics conducting industry-funded trials to sign contracts subjecting them to gagging clauses that forbid them to publish, discuss or analyse data from their trials without the permission of the funder.

Just read it. There's so much more. Paroxetine, a drug that was known to be ineffective for treating children, which had a risk of suicide as a side-effect, widely prescribed to children, because GlaxoSmithKline declined to publish its research data after an internal memo stated "It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine."

The drugs don't work: a modern medical scandal


  1. “… pharma companies set up their trials so that they the right to terminate …”

    I think there might be a missing or misplaced word in the “that they the right” part of the sentence.  (Then again, I am zoned-out enough to have originally left “word” out of my own sentence, so maybe there isn’t anything missing and I’m merely confused.)

      1. Topiramate is probably one of the most prescribed drugs for a list of US FDA off-label usage: essential tremor, bulimia nervosa, obsessive-compulsive disorder, alcoholism, smoking cessation, idiopathic intracranial hypertension, neuropathic pain, cluster headache, migraine headache, cocaine dependence, and Borderline Personality Disorder. It also got Ortho McNeil to cough up millions in fines by the FDA for promotion of off-label usage that they did not apply for. Makes ya wonder why the US even has an FDA since off-label usage is so prevalent.

        1. I was exposed to it on recommendation from an MD for migraine illness, as a prophylactic. Not worth it even if it could be shown to be mildly effective; it has earned the nickname Dope-a-max.

          1. Indeed. I’m beginning to think that one of the reasons why US Healthcare is in the state its in is because of the lack of evidence and accountabilty across the healthcare delivery spectrum.  

          2. The “dopey” side effects wore off for me after a few months. But if you can’t afford the luxury of being dopey for two months, then? I did lose my Iphone during that time. Oh well, the drug has been nothing short of amazing for me.

        2. The off-label usage problem is probably the largest issue in the pharmaceutical wars right now.  This is where the drug reps do the real dirty work.  A drug is approved for one thing and one thing only, so the literature lists only that use.  But the drug reps scuttle from office to office pushing the off-label uses.

          I’m also convinced that there’s some Jekyll/Hyde thing depending on the audience.  We had inservices to nursing staff from drug reps all the time, and they were generally really useful and informative.  And then the same rep skitters down to the doctor’s office and turns into a scam artist.

        3. It’s a wonder drug as far as I’m concerned. I can’t live without it. I am surprised that it is used for so many things. I know that for many people the side effects are too much to handle. One man’s trash is another man’s treasure.

  2. Decades ago in the US it was illegal for the pharmaceutical industry to advertise their products in mass media. Now look at their 10K’s as to where their expenses go to.  It also goes to show how much regulatory capture occurs within the governments that only forces the most dangerous drugs off the market when the lawsuits for bad drugs threaten their profits, and at the same time allow patents to be issued against the active metabolites of existing drugs, increasing their monopoly. 

  3. I’ve heard about this many times before, in various articles. And I’m just some dude who reads the newspaper. It would seem that a doctor who has been “doing their homework” on drug companies and doesn’t know about this is not actually doing their homework.

    1. Next time you visit your doc, ask him how many times he’s been visited by ‘detailers’.  And just as important, how many times has he sent them packing. 

  4. Cory, to describe this knowledge as “the shocking truth” is a bit strange and belated. Any good drug pusher knows that he or she must get everyone loaded all the way down the line, from buyer to middle man, to importer, to manufacturer…a stoned covert Capitalism is the best form of covert Capitalism

    A person would really have to be deluded to think that prescription drugs (oops, I mean MEDICATIONS) are any different than non-sanctioned drugs such as crystal meth, pure heroin or PCP. When I was growing up we were rarely given anything stronger than Bayer aspirin. Now, every friend I know has a medicine cabinet full of Vicodin and other assorted mind-altering drugs.

    1. Here’s something for you to chew on:  back in the late 1980s in the US, the most prescribed drugs were not related to mental health; today the drugs prescribed for mental health are the majority of prescriptions in the US.  They were also the same class of drugs that the US Government went after Big Pharma for various forms of ‘mis-application’. 

  5. I believe I encountered a horrible case of corruption in a veterinary study that my vet participated in. Pet owners with a flea infestation that didn’t respond to the normal topical treatments were given a new “safe” flea treatment, then filled out a diary.  (It was one of those very-last-stage-before-market public trials, so no problems were expected.)

    I gave my torbie cat Tanookie a fractional dose, as I’m extremely wary about any kind of drug I haven’t dealt with before.  Several days later, we took her in to have a minor procedure in which she’d be sedated (not knocked out), then treated and sent home ten minutes later.  Short story is, she had repeated strokes (despite having no heart anomalies) and then systemic shutdown despite the ER vets doing everything possible, and we had to let her go.  The ER couldn’t get ahold of the vet during all of this, though he had never failed to return their calls before.

    In shock, we left messages with the vet clinic to ask where we should mail the journal or if we should give it to him, but never got a response. I don’t know if the drug played any role in Tanookie’s death, but I wish I’d known what company was holding the trial so I could’ve contacted them.  (In case anyone is concerned: the fleas are now almost gone, as our new vet introduced us to the safe use of food-grade diamocetaceous earth on carpets.)

  6. I’m not sure if this excerpt is just from the introduction or what, but there are two other books that are already available that are much better written.

    The first is The Truth About Drug Companies, by Marcia Angell. She was the former editor of the NEJM.

    The second is Overdosed America, by John Abramson.

    IIRC they were written in 2004 and 2008 respectively, but very little (other than some superficial stats) has changed since then. And plus they both focus on the US medical system and the FDA, whereas Goldacre may or may not focus more on the NHS.

  7. It’s things like this that make me more sympathetic to homeopathy. OK, they’re full of shit and promote a bogus theory… but at least they only peddle sugar pills instead of stuff that can get you addicted (Oxycontin), destroy your liver (Tylenol), or increase your risk of dementia (statins, if you stop taking them).
    In re: Oxycontin, it is amazing to me that they were able to promote it on the same basis that morphine and heroin were first pushed, back in the day: each was supposed to be far less likely to cause addiction than its predecessor opiate.

    1.  Turns out that that the drug that Oxycontin is based on was first developed in something like 1914 or thereabouts. It was so strong (think heroin) that it was never prescribed all that much. That all changed somewhere in the ’90’s  when a version was developed that was time released. New patent, new drug. And, golly! Safe for everyone!!

      1. And what diabolical mind could possibly conceive of crushing/chewing the pill to defeat the timelapse? Oh, right, everyone, that’s who.

        And @ Boris, agreed about the relative harmlessness of homepathy. Reminds me of the Northern Exposure episode where the Native American receptionist woman was giving something to people with a bad flu and it worked for them, and Joel the doctor wanted to have it analyzed to see if it was a quack cure. The point was it really didn’t matter much since the people were cured, even if it was psychosomatic. “The human body is an amazing self healing machine”, as they put it.

        1.  Drug companies aside, homeopathy is not harmless. The remedies themselves are, but when people are delaying from treatments known to work, in favour of sugar pills and tea tree oil, harm is often done. Ignoring all of the tools at out disposal because of some bad prescriptions is foolish. And a TV show does not equate in any way to real life.

    2. Oxycontin, it is amazing to me that they were able to promote it on the same basis that morphine and heroin were first pushed, back in the day: each was supposed to be far less likely to cause addiction than its predecessor opiate.

      Hilarious, since oxycodone and hydrocodone are more addictive.  They are really useful, however, since they make many people slightly speedy, meaning that you can function when you’re taking them.

      1. That’s funny – out of the opiates I have taken, oxycodone made me feel the groggiest, even more so than heroin. That’s why I didn’t really care for it; I like being able to function. I’ve never tried hydrocodone, though.

        In any case, they should just stop trying to market new opiates as “less addictive” – most of the time they aren’t, and even if the risks are a bit lower, the withdrawals can be an unpleasant surprise to the unprepared. Painkillers are life-savers for people with serious pains, but no one should be deluded into thinking that there isn’t any (and in Oxycodone’s case, BIG) potential for addiction. I’ve heard of many people who were prescribed opiates or benzos without being fully informed of the risks.

    3. ” OK, they’re full of shit and promote a bogus theory… but at least they only peddle sugar pills”

      Sorry, but homeopathy is such a kluge of non-science that you can’t trust it to be harmless. Putting the magic words “homeopathic” on something in the US essentially gives it a free pass from regulation, and not all homeopathic remedies are ultra-diluted into nothingness, as people who may have lost their sense of smell due to “Homeopathic” Zicam have found out. Zicam contains ” slightly diluted zinc acetate (2X = 1/100 dilution) and zinc gluconate (1X = 1/10 dilution);[2]” something is safe because it says “homeopathic” on it is a fools game.

  8. This seems to be a case where shoddy evidence and demagoguery are obscuring some of the reasonable points he has.  It’s true that not all studies are published and that they should be.  But some of the other points are misrepresentations of the laws or regulations about clinical trials.  -The comparison that’s required for a new drug in a certain class is vs. standard of care.  In some cases, yes, that is a sugar pill, because there is no effective treatment- those are the areas we should be encouraging development.  But in other cases, say statins, if you have a new cholesterol lowering drug you don’t get to compare it to a sugar pill just because you feel like it, you have to compare it to the most similar most effective drug and you have to show some improvement (less side effects, better dosing schedule, or more significant effect) or your drug is not approved.
    -It’s quite common to try to identify a sub-population in which a drug is effective, especially with it becoming more common these days to sequence study participants.  There’s nothing nefarious about this, it’s the whole “personalilzed medicine” that people were excited about 10 years ago- this is what it looks like.  You still need to have enough people in the subpopulation to achieve statistical significance, and usually you have to have some kind of biomarker to decide when treatment is appropriate (one of the most commonly known ones is breast cancer Her2 receptor expression, detected with the Herceptest that decides whether someone receives Herceptin.)  So you can’t just run a trial, find one subject who responds, and declare that 40 year old men named Bob are your target.  Now, once a drug is approved, it’s true that doctor will prescribe it off-label outside the defined population, sometimes under pressure from patients, sometimes under illegal marketing by companies.  The latter is a real problem where companies are breaking the law, but again the good point is being obscured by the overwrought claim about cherry picking responders.
    -As far as stopping clinical trials early, a lot of that is ethics.  When a trial is stopped early due to success, the control/standard of care arm is switched to the new treatment because it’s unethical to withhold from a control group a drug that’s shown to be effective just because you want to complete the study to see how many more people die under the old treatment.  Similarly with stopping due to failure- if there is an adverse event that’s shown to be linked to the drug, you can’t keep running the trial just because you want to know exactly how toxic the drug really is. Phrasing this as “companies have the right to stop the trial” is misleading, they are required to stop the trial if success or failure is evident before it is over.  Imagine how Goldacre would describe it if trials were run to completion even after success was obvious partway through- “The Evil pharma industry is withholding a known cure from patients just to get their statistics more significant so they can have better marketing materials.  We thought this was over after Tuskegee but apparently it continues to this day…”
    As I said, unfortunate that he’s going for the big headline by twisting some of the facts because he also points out things that really should be fixed.

    1. ‘You still need to have enough people in the subpopulation to achieve statistical significance’…

      Yes, but if you try with enough subpopulations, you can achieve (what looks like) statistical significance by happenstance. And then not publish all those boring results from the other subpopulations.
      Anyway, ‘evergreening’ or repatenting of existing compounds is another big semifraudulent practice on the part of the drug companies. Nexium, OxyContin, and Adderall off the top of my head – all compounds first synthesized long ago, then given very minor tweaks so as to be patent protected once more. Of course in these cases you can also blame the doctor for not seeing through the scheme…

      1. W.r.t. your first point, I don’t think you could. If a population is small enough to show results ‘through happenstance’, chances are the confidence interval is going to be big enough to include the null value, and there is no statistical significance.

      2. Boris:  It’s called a type II error, and we define an alpha and beta value a priori to reduce the risk of that error.

        And, for your “try with enough subpopulations” point, it is called multiple comparisons for which there are statistically-valid adjustments for multiple comparisons that can greatly reduce your odds of seeing a significant effect by chance, and my experience has been that weaker adjustments (Bonferroni) have largely been abandoned for stronger ones (Tukey’s).

    2. Ben Goldacre’s generally good but in this case he’s selling a book, so I would suspect that he’s going overboard on some issues. It’s also worth mentioning that there has been a fair amount of work into statistical methods for early stopping of trials, a quick Google search turned up this:
      and this review (available freely online):

      1.  “so I would suspect that he’s going overboard on some issues.”

        Citation needed.

        You admit he’s good and then diss him with no evidence.

    3.  Thanks for pointing out that equipoise must be maintained, I was going to do so myself. I am a bit annoyed he diluted some of his mostly good, it would seem, material with that point.

    4. Very good post, glad to see this. I think people who are not familiar with clinical research just have this notion of “good science” but don’t have a good grasp of human subjects rights. 

  9. I keep thinking, it is 2012, and there is sexual, racial, and economic equality, and that advances in psychology and healthcare have made huge steps in reforming outmoded forms of prejudice, violence and greed, and improved general well-being to a massive extent, and advances in technology have dispensed with the need for the plastics and petrochemical industries. 
    Then I remember… it’s 1972.

    Oh. Wait a minute. I already posted this in the Archie thread.

    Oh well. Here is a video to cheer everyone up, while remembering that DMT is part of human DNA already. 

  10. “It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile net profit of paroxetine.”

    There. Fixed that for ya.

  11. The funny thing is, the next time Ben writes an article condemning “alternative” quackery, He’ll be accused of being in the pay of big pharma.

  12. My infant son was prescribed Cisapride while hospitalized after birth. It was an off-label use of the drug for stomach acid and reflux but here’s the thing: The drug is a powerful neurological agent and had little effectiveness for this use.

    We were lucky, he is fine, many children died from the use of the drug and some of the families were accused of harming their children (Munchausen by proxy syndrome) with little evidence. One doctor had six mothers he accused of harming their children in a single year. Think of the almost statistical impossibility of that. The  very good documentary Mama/M.A.M.A. covers the fallout ,and lawsuits.

  13. Okay this is kinda technical but a bit about evergreening: when I was helping write a formulary for our organization, for the “antidepressants” section I wanted to exclude escitalopram on the premise that it’s virtually the same drug as citalopram, and it’s still on-patent and manyfold more expensive than citalopram. The psychiatrists on the committee pointed out that there are studies pointing to the superiority of escitalopram over citalopram, so we really couldn’t, in the name of evidence-based medicine, exclude escitalopram (it’s the s-enantiomer of citalopram).

    So I critically appraised the articles finding superiority of escitalopram over citalopram. ALL of them were sponsored by Lundbeck, the manufacturer of escitalopram, and also the maker of the brand name of citalopram before its patent expired. The patent expiry of brand-name citalopram (Celexa) coincided with the release of this “new” drug, escitalopram.

    One of the psychiatrists on my committee contacted me privately to say that I was right; that the endpoints in trials of antidepressants are based on many subjective outcome measures so it’s kinda sticky to say one antidepressant is marginally “better” than another. But if we excluded escitalopram, and a pt we substituted citalopram attempted suicide, we’d be vulnerable from a litigation POV, given the data finding superiority for escitalopram, nevermind the data finding an association between SSRIs and suicide.

  14. The vast majority of drug development activities do not involve criminal activity.  Fraud and the other crimes mentioned here should be punished like any other crime.  If we set aside the assumption that all motives are sinister, then there are other insights to be gleaned.

    Drug companies do all the clinical trials on their new chemical entity (NCE) because they hold the patent and will make all the money if the drug works.  Why would anyone want to do research on someone else’s product?

    Drug company scientists and physicians are often co-authors and co-investigators on clinical trials because they are the world experts on the molecule and on all the animal and human data gathered on the NCE to date.  This also means they have some say in any manuscripts the same way academic collaborators have a say.

    Studies sponsored by drug companies generally support the NCE efficacy for reasons that are not necessarily sinister:

    1) The company only publishes studies from drugs that work and it wants to sell.  An academic researcher will publish all the good and bad data about all 20 compounds she tested.  An industry researcher tests 2000 NCEs in one assay, tests two of those in another assay, tests for safety in humans, tests for preliminary human efficacy, and, after all of that data comes back positive, tests for full human efficacy and finally publishes it.  If the NCE had failed any of those preliminary steps, nothing would be published, or, to put it another way, the chance that the NCE was going to fail in the end is much lower after going through this process.

    2) Academic and government researchers don’t start working on the new drug until after it is on the market and they have some reason to doubt its efficacy or to test it against other drugs or off-label.  All of these lines of investigation have a relatively low odds of success with regard to supporting the new drug’s efficacy.  These lines of research are not biased against the new drug, they are just asking questions that aren’t nearly as slam dunk as the approval process.

    3) Medical journals also influence new drug publications based on the drug’s novelty, performance versus standard of care, and/or the response of the disease or disorder to previous treatments (if any).  Weaker studies on a hot medical topic have an advantage in the review process, and drug companies focus their discovery efforts on hot medical topics for the most profit.

    There are bad actors in any industry or area of work, and those bad actors may give us a really bad impression of their whole industry.  It may help to take a step back, look how the responsible parts of the industry operate, and maybe have a different take-away message.

    Then again, there is that saying about not wanting to know how sausage is made or else you will never want to eat it again!  At least it isn’t criminal sausage (dibs on this as a band name!).

    1. The vast majority of drug development activities do not involve criminal activity.

      That’s a faith-based statement. The financial incentives to only look at data that supports the drug in which you’ve just invested a fortune mean that the whole system is fraud-bait. And drug companies have repeatedly proven their willingness to act unethically. They have motive and opportunity.

      1. Actually, I have first hand knowledge from working at two different pharmaceutical companies with colleagues at several others (cue dismissing all insiders as liars…).  You are taking individual cases and extrapolating them to the whole industry based on 3rd hand knowledge (I suspect).

        The two cases I know of where this kind of fraud occured, those responsible were a small group within the organization operating without the knowledge of management.  Since these crimes cost the company hundreds of millions to billions, our ethics education programs only got more hardcore over the years.

        I could make your same extrapolation about non-profits or churches where criminal activity has taken place repeatedly.  Small businesses have the same incentive to commit arson and insurance fraud because they can’t afford to lose all the money they invested in the business.  This criminal activity happens a lot, but the whole small business system is not fraud bait.

        Financial incentives exist for ALL criminal activity, but it is all exactly that – criminal activity.

  15. No matter what, it seems I am always on the *wrong* side of the argument. I spent years trying to treat my illness with every natural treatment, herb, homeopathy that I could find. I spent thousands of dollars. Heck, I was on this blog and others defending these natural treatments and talking about how evil pharma is. Well, they never really worked in the long run and I finally gave in. 
    Finally, I went to a regular doctor and I am taking two medications made by evil  pharmaceutical companies and I am feeling better than I have ever felt. I have finally found the combination of drugs that I needed. There will be side effects but I won’t be wasting my entire life searching for an answer while suffering as I have for years and years. I can now be present  and well in my life, finally. Thank you pharma.

  16. Added to the to-read list, thank you! I’ve watched doctors in Germany and the USA claim not to be compromised by drug rep information or bennies, yet clearly be swayed.

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