Monday September 24, 2012, 11:33 am
Good summary of why it is so essential to identify the funding source(s) of any study, any affiliation the researchers and/or authors have/had with the funding source to illuminate the potentials of biased results and interpretation. So many research reports (both public and private) never see the light of day or public release if the findings are at odds with those desired by those with the power to quash (part of why some state contracts now permit independent professional publishing by research contractors after a period of time has passed).

Monday September 24, 2012, 12:01 pm


eboxetine is a drug I have prescribed. Other drugs had done nothing for my patient, so we wanted to try something new. I'd read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It's approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.

But we had both been misled. In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat, positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.

It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients' worth of data was left unpublished, and this unpublished data showed that patients on reboxetine did worse than those on other drugs. If all this wasn't bad enough, there was also the side-effects data. The drug looked fine in the trials that appeared in the academic literature; but when we saw the unpublished studies, it turned out that patients were more likely to have side-effects, more likely to drop out of taking the drug and more likely to withdraw from the trial because of side-effects, if they were taking reboxetine rather than one of its competitors.

I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.

Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us. These problems have been protected from public scrutiny because they're too complex to capture in a soundbite. This is why they've gone unfixed by politicians, at least to some extent; but it's also why it takes detail to explain. The people you should have been able to trust to fix these problems have failed you, and because you have to understand a problem properly in order to fix it, there are some things you need to know.

Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion.

In their 40 years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies - often undisclosed - and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it's not in anyone's financial interest to conduct any trials at all.

Now, on to the details.

In 2010, researchers from Harvard and Toronto found all the trials looking at five major classes of drug - antidepressants, ulcer drugs and so on - then measured two key features: were they positive, and were they funded by industry? They found more than 500 trials in total: 85% of the industry-funded studies were positive, but only 50% of the government-funded trials were. In 2007, researchers looked at every published trial that set out to explore the benefits of a statin. These cholesterol-lowering drugs reduce your risk of having a heart attack and are prescribed in very large quantities. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. They found that industry-funded trials were 20 times more likely to give results favouring the test drug.

These are frightening results, but they come from individual studies. So let's consider systematic reviews into this area. In 2003, two were published. They took all the studies ever published that looked at whether industry funding is associated with pro-industry results, and both found that industry-funded trials were, overall, about four times more likely to report positive results. A further review in 2007 looked at the new studies in the intervening four years: it found 20 more pieces of work, and all but two showed that industry-sponsored trials were more likely to report flattering results.

It turns out that this pattern persists even when you move away from published academic papers and look instead at trial reports from academic conferences. James Fries and Eswar Krishnan, at the Stanford University School of Medicine in California, studied all the research abstracts presented at the 2001 American College of Rheumatology meetings which reported any kind of trial and acknowledged industry sponsorship, in order to find out what proportion had results that favoured the sponsor's drug.

In general, the results section of an academic paper is extensive: the raw numbers are given for each outcome, and for each possible causal factor, but not just as raw figures. The "ranges" are given, subgroups are explored, statistical tests conducted, and each detail is described in table form, and in shorter narrative form in the text. This lengthy process is usually spread over several pages. In Fries and Krishnan (2004), this level of detail was unnecessary. The results section is a single, simple and - I like to imagine - fairly passive-aggressive sentence:

"The results from every randomised controlled trial (45 out of 45) favoured the drug of the sponsor."

How does this happen? How do industry-sponsored trials almost always manage to get a positive result? 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.

This is such a secretive and shameful situation that even trying to document it in public can be a fraught business. In 2006, a paper was published in the Journal of the American Medical Association (Jama), one of the biggest medical journals in the world, describing how common it was for researchers doing industry-funded trials to have these kinds of constraints placed on their right to publish the results. The study was conducted by the Nordic Cochrane Centre and it looked at all the trials given approval to go ahead in Copenhagen and Frederiksberg. (If you're wondering why these two cities were chosen, it was simply a matter of practicality: the researchers applied elsewhere without success, and were specifically refused access to data in the UK.) These trials were overwhelmingly sponsored by the pharmaceutical industry (98%) and the rules governing the management of the results tell a story that walks the now familiar line between frightening and absurd.

For 16 of the 44 trials, the sponsoring company got to see the data as it accumulated, and in a further 16 it had the right to stop the trial at any time, for any reason. This means that a company can see if a trial is going against it, and can interfere as it progresses, distorting the results. Even if the study was allowed to finish, the data could still be suppressed: there were constraints on publication rights in 40 of the 44 trials, and in half of them the contracts specifically stated that the sponsor either owned the data outright (what about the patients, you might say?), or needed to approve the final publication, or both. None of these restrictions was mentioned in any of the published papers.

When the paper describing this situation was published in Jama, Lif, the Danish pharmaceutical industry association, responded by announcing, in the Journal of the Danish Medical Association, that it was "both shaken and enraged about the criticism, that could not be recognised". It demanded an investigation of the scientists, though it failed to say by whom or of what. Lif then wrote to the Danish Committee on Scientific Dishonesty, accusing the Cochrane researchers of scientific misconduct. We can't see the letter, but the researchers say the allegations were extremely serious - they were accused of deliberately distorting the data - but vague, and without documents or evidence to back them up.

Nonetheless, the investigation went on for a year. Peter Gøtzsche, director of the Cochrane Centre, told the British Medical Journal that only Lif's third letter, 10 months into this process, made specific allegations that could be investigated by the committee. Two months after that, the charges were dismissed. The Cochrane researchers had done nothing wrong. But before they were cleared, Lif copied the letters alleging scientific dishonesty to the hospital where four of them worked, and to the management organisation running that hospital, and sent similar letters to the Danish medical association, the ministry of health, the ministry of science and so on. Gøtzsche and his colleagues felt "intimidated and harassed" by Lif's behaviour. Lif continued to insist that the researchers were guilty of misconduct even after the investigation was completed.

Paroxetine is a commonly used antidepressant, from the class of drugs known as selective serotonin reuptake inhibitors or SSRIs. It's also a good example of how companies have exploited our long-standing permissiveness about missing trials, and found loopholes in our inadequate regulations on trial disclosure.

To understand why, we first need to go through a quirk of the licensing process. Drugs do not simply come on to the market for use in all medical conditions: for any specific use of any drug, in any specific disease, you need a separate marketing authorisation. So a drug might be licensed to treat ovarian cancer, for example, but not breast cancer. That doesn't mean the drug doesn't work in breast cancer. There might well be some evidence that it's great for treating that disease, too, but maybe the company hasn't gone to the trouble and expense of getting a formal marketing authorisation for that specific use. Doctors can still go ahead and prescribe it for breast cancer, if they want, because the drug is available for prescription, it probably works, and there are boxes of it sitting in pharmacies waiting to go out. In this situation, the doctor will be prescribing the drug legally, but "off-label".

Now, it turns out that the use of a drug in children is treated as a separate marketing authorisation from its use in adults. This makes sense in many cases, because children can respond to drugs in very different ways and so research needs to be done in children separately. But getting a licence for a specific use is an arduous business, requiring lots of paperwork and some specific studies. Often, this will be so expensive that companies will not bother to get a licence specifically to market a drug for use in children, because that market is usually much smaller.

So it is not unusual for a drug to be licensed for use in adults but then prescribed for children. Regulators have recognised that this is a problem, so recently they have started to offer incentives for companies to conduct more research and formally seek these licences.
**** Continue reading at Visit Site***

By Ben Goldacre, Guardian UK and RSN

Monday September 24, 2012, 2:07 pm
Kit; thanks for the article.... keep the info coming .. if you will... I have a personal interest...

Monday September 24, 2012, 2:12 pm
Doctors have lost their ways... looooooong time ago. The "sickness industry" is too powerful, they succumbed to money. Only us, everyone of us can make a difference by modifying our thoughts and behaviors. For me, just my humble opinion, going to a doctor's visit is just as unreliable as going to the car mechanic. They supposedly hold all the knowledge in their hands so they've corrupted their profession.

Monday September 24, 2012, 2:36 pm

So very true, and the more we turn to any profession as being the sole answer to our problems the less we depend on ourselves and our community. Considering the vast number of prescription medications it's highly unlikely that any doctor would be able to read all the materials and keep up with a practice and a home life.

Monday September 24, 2012, 2:37 pm
I would think that if everyone took the time to read the information on warnings/side effects that come with all Rx drugs, that it would be enough to make you throw them in the trash. Better yet, just don't fill the Rx in the first place.

Monday September 24, 2012, 2:50 pm
Gee that one WAS LOOONG, but I read all the way through it. Although shocking, it comes as no big surprise-
haven't we all long known about the widespread huge fraud Big Pharma is involved in. And to call this a "modern medical scandal" is a typical British understatement.
One commentor to the article said it well:
"Research, as currently done, is a vast enterprise enriching corporations and publicizing authors. It is not designed... to advance truth."
Thx Kit-and folks, please seek the looongest detour on the way to any doc !

Monday September 24, 2012, 2:55 pm

Yes, it is a long article, but I really think it's worth the time to read it all. Far too many people from 50 on up are taking medications and have no idea what they are for nor the side effects.

Monday September 24, 2012, 2:58 pm
We have the best corporate medicine that our corporate government will permit us to have. They sell us poisons that don't work, have horrible side-effects, cause the illnesses that they are intended to treat...but don't use that plant that seems to treat everything...because that's against the law. Waging war on medicinal plants should be against the law!

Monday September 24, 2012, 3:01 pm
BTW -the image says it all, love it. And GSK was the company that had the monopol to provide thet flu vaccine some years ago. It later turned out a hoax, only to promote their vaccine, people did NOT show of for vaccination, the predicted epidemic never occurred and the stuff remained piled up in doctor's offices and had to be destroyed after all because storage life had passed.

Monday September 24, 2012, 3:03 pm

Do you know who owns the patents on cannabinoids, which do cure cancer? The US government, and have owned them since the turn of the century, this century.

Monday September 24, 2012, 3:27 pm
Wiki says: "On June 12, 2012, KannaLife Sciences, Inc. signed an exclusive license agreement with National Institutes of Health – Office of Technology Transfer ("NIH-OTT") for the Commercialization of U.S. Patent 6,630,507, "Cannabinoids as Antioxidants and Neuroprotectants" (the "'507 Patent"). The '507 Patent includes among other things, claims directed to a method of treating diseases caused by oxidative stress by administering a therapeutically effective amount of a non-psychoactive cannabinoid that has substantially no binding to the NMDA receptor. Cannabinoids are any of a group of related compounds that include cannabinol and the active constituents of cannabis (marijuana).

Monday September 24, 2012, 3:37 pm

Yep, it's been shown to be an effective treatment in many diseases...wonder what we are waiting for? Using the cannabinoids is not done by smoking, rather by extracting the cannabinoids from the leaves, though even those who wish to just get high would find a better high by not smoking. Most commonly the method of preference is called juicing - yep, putting the leaves into a juicer and making a drink, though NOT legal in most states.

Monday September 24, 2012, 3:40 pm
Even in the states where medical use has been approved, patients still face persecution by the federal government.

Monday September 24, 2012, 3:47 pm
Big Pharma at its' best - to a point I agree with Olivia - if you read the side effects you would throw out the Rx but there are some meds that I take but the minimum and the side effects are minimal - I hate that I take them - but am hospital material if I don't.

Monday September 24, 2012, 3:53 pm
Good point, Val...though there is much to distrust about many of our modern medicines, it would be unwise to throw them all out.

Monday September 24, 2012, 5:26 pm
Thanks.

Monday September 24, 2012, 8:53 pm
Why do physicians prescribe drugs for something when they are most definitely meant for something else?

Monday September 24, 2012, 9:09 pm
$$$$$ AMA $$$ BIG PHARMA $$$$ See?

Tuesday September 25, 2012, 3:47 am
An excellent find Kit, very comprehensive regarding the trial 'studies' done by who else, the drug manufacturers themselves. Mostly skewered, altered, slanted results where anything negative about the drug or effects or efficacy is hidden by the drug corp., so the FDA or whoever then will just rubber stamp the drug for public use.
Same with psychiatric drugs as with regular medical drugs.
I fear most of the general population are sheeple, who do NOT think for themselves, leave it all up to someone else to decide for them, plus any 'professional' who has a nice office, degrees on the wall, wears a nice suit or lab coat, 'trained for years',and is covered by insurance and funded by gov't. MUST know what they're doing and talking about.
There is an old human fault which is letting someone else decide for you and so if anything goes wrong they are responsible whereupon you can then blame them. However, there's the little point of you having been the effect of their bungling with your health.
Plus most people cannot (or do not) want to credit the placebo effect as having any validity in making a person feel better. Did you know that an 'active placebo' is one where a sugar pill has been given a tiny amount of some substance that for example causes a dry mouth only, which of course mimics some real drugs, and this increases it's efficacy to make people feel better! In other words still no actual medicinal value to the drug, the patient is FOOLED into thinking it's making them better, and does!
..

Tuesday September 25, 2012, 4:52 am
all about the MONEY......

Tuesday September 25, 2012, 4:53 am
Great article Kit, Thanks.I passed this on to several friends from my academic days.Being a student of Social Work/Psyche and taking tons of classes on Research,Method, and Design..and designing my own research taught me soooooooo much about critical thinking,stats,etc...it taught me to think and process info..differently.Reading this article, was quite disturbing but it fit right into some of the other Pharm. scams and BS. After working Substance Abuse and Mental Health for far too many yrs, this info gets added to the pile.This needs to change.

Tuesday September 25, 2012, 9:09 am

My mother is most reluctant to use a computer so when she returns from the doctor she reads me the scripts and I look them up on line. Well over 90% of the scripts are for anti-depressants, though she is not depressed, she does have allergies, some back pain, but does not take pain pills, so the answer must be to give a bogus script then the task is done.

Tuesday September 25, 2012, 12:51 pm
The big pharmas will do Anything to steal a buck. They peddle death in secret darkness, then wonder why people don't trust them even on vaccines!

Tuesday September 25, 2012, 2:54 pm
(Noting is working sporadically for me today). Thanks, Kit. Although the article specifically mentioned children, I didn't notice it specified anything about geriatric patients. I learned several years ago, when my grandmother was prescribed various drugs, that geriatric medicine is vastly different as well. Many drugs should be prescribed in lower doses, and some--not at all. Another thing I learned is that many elderly people don't drink enough fluids...esp. when taking these pharmaceuticals. We bugged my grandma constantly to stay hydrated.

Tuesday September 25, 2012, 6:49 pm
The "pill people"are no different from monsanto and friends.ALWAYS looking to make money.If one pill makes you sick,they`ll give you a different one.

Wednesday September 26, 2012, 3:26 am
Pharmakeia φαρμακεια is the Greek word for pharmacy, which is the practice and making of medication and vitamins.[citation needed] It also refers to the making of spell-giving potions, or alchemical potions (or elixirs) believed to have transforming powers, such as the power to extend life, boost energy, or enhance the mind. It also refers to any substance used to poison someone, to prevent or treat disease (or, for that matter, to cause it), or to gain control of someone's behavior. [1][unreliable source?] Pharmakeia and its related word forms pharmakeus, pharmakon, pharmakos and pharmakoi are the words from which we get the modern English words pharmacy, pharmaceutics, pharmaceutical, pharmacist, pharmacopia, pharmacology, pharmaceuticalist and pharmaceuticalism. The modern transliteration of pharmakeia is pharmacia ---- ALL of which is bulldust, just moneymaking...

Wednesday September 26, 2012, 8:58 pm
One reason of many why I prefer meds that have been on the market over 10 years

Wednesday September 26, 2012, 9:18 pm
Big Pharma criminality no longer a conspiracy theory: Bribery, fraud, price fixing now a matter of public record

GlaxoSmithKline pleads guilty to bribery, fraud and other crimes.

It what is now the largest criminal fraud settlement ever to come out of the pharmaceutical industry, GlaxoSmithKline has pleaded guilty and agreed to pay $1 billion in criminal fines and $2 billion in civil fines following a nine-year federal investigation into its activities.

Wednesday September 26, 2012, 9:43 pm
When Half a Million Americans Died and Nobody Noticed

Was the US drug Vioxx responsible for far more deaths than has been acknowledged so far?

Wednesday September 26, 2012, 10:07 pm

15 Dirty Big Pharma Tricks That Rip You Off and Risk Your Health for Profit.

Even during a recession, pharma is still the nation's third most profitable sector. Here are some of the dirty tricks it employs to stay on top.

Even during a two-year recession with people losing their homes and jobs, pharma is still the nation's third most profitable sector. How does it do that? In part by cheating the government, misrepresenting science, bribing doctors, patients and pharmacies, and squeezing the FDA. Other than that, the industry plays completely fair. Pharma has often been criticized for lack of creativity in developing new drugs. But these dirty tricks show its creativity is alive and well when it comes to putting the public at risk just to turn a profit.


15 Dirty Big Pharma Tricks That Rip You Off and Risk Your Health for Profit

Wednesday September 26, 2012, 10:18 pm
Common Medical Uses for Cannabis (Marijuana)

Wednesday September 26, 2012, 10:19 pm
Kit thank you for sharing this eyeeee-opening information with us - it's alot to take in but basically I get 'it' !
Pharma fraud is nothing new. What I find shameful is the fact that 'some' doctors write a script for medication without really taking the time to research the medication to see if in fact the patient would benefit from it!
etc. etc.
I guess 'ethics' no longer are a consideration ! Sad ....

Anyways I wanted to share the news post offered by Dandelion
Cannabis, Cancer, Rick Simpson of Nova Scotia.....Important Film

Wednesday September 26, 2012, 10:57 pm
This excellent article spells out how it is that genuinely caring, responsible and ethical doctors end up prescribing poison that causes far worse "side effects" than the symptoms they are trying to treat. Big Pharma really has had it all sewn up. We need to continue to promote these stories, talk to every one we know, question professionals and celebrate the victories until this unethical greed machine is completely reorganised and regulated properly. There are times that medicine is needed in life. The people who research and make this medicine need to be trustworthy and their practices entirely unhidden.

Monday October 1, 2012, 5:25 pm
I wish I had realized and known how many pills my Father was taking, but unfortunately it wasn't until near the end that I found this out. As I looked over all his bottles, with fairly current dates, I brought them home to look up their side effects, most of them said, "could cause depression" given to a man who had just lost his wife a year before. Is no wonder he never could pull out of it, even if he was trying his best these medications were going against him.

Due to learning, the hard way, on my Father I paid a lot closer attention to my Mother and at age 90 she is on one blood pressure pill....and that is it! She said she also learned from my Father, for even though they had divorced he was still close to my Mom so she and I together were trying to help him. She also saw the pills and has will not just take anything thrown at her, however with a bit of dementia coming on, I had to be certain that this would be a continuation. They did have her on too many by the time I moved from Florida back north to help her, now without all the pills she is looking better, feeling better, and more clear headed.

I wish I could get my Aunt, her sister to listen, but she is one of the bought and sold hook line and sinker that the Doctor wouldn't give it to her if she didn't need it and he knows what is best. I asked her to at least seek another opinion on matters, as she feels no better years later and just gets more pills thrown at her. She is also on pills to stop the side effects of other pills.