Sunday, February 3, 2013

Big Pharma, Bad Medicine

Given the importance of rigorous, verifiable research in the practice of modern medicine, it seems a natural assumption that the doctors who treat us base their actions and recommendations on solid, irrefutable evidence. Evidence-based medicine, is, after all, the mantra that we as patients hear over and over again, especially when it comes to our inquiries into the implementation of alternative therapies that fall outside of the medical mainstream. More often than not we are told that there is simply no evidence for the effectiveness of this or that alternative therapy, and that rather than waste our time and energy on unproven and possibly dangerous unconventional remedies, we should stick to the tried-and-true, which almost always come in the form of pharmaceutical products produced by one of the giant multinational pharmaceutical firms, known collectively as “Big Pharma”.

The logic behind such thinking isn’t necessarily faulty. Untold millions of dollars are spent developing drugs and putting them through laborious clinical trials, the result of which is the evidence upon which “evidence-based medicine” thrives. Absent the data produced by this research model, the practice of medicine would be largely reduced to educated guesswork, based solely on the experiences and impressions of individual medical practitioners, which by definition would be limited in scope and might easily be skewed by subliminal prejudices and statistical aberrations physicians could encounter during the course of their careers. Relying instead on evidence amassed through years of rigid research encompassing thousands of patient hours makes deciding which medicine to prescribe or procedure to recommend an exercise in logic and intellectual reasoning, the cornerstones of all disciplines of modern science.

This all makes perfect sense, and indeed this very reasoning has fueled the rapid advances seen in many fields of medicine over the last half-century. However, if the evidence which is the foundation of evidence-based medicine becomes unreliable, or downright misleading, the entire edifice that is modern medicine stands in danger of collapse. To an extent that is almost incomprehensible, this is the very environment in which patients and physicians now find themselves operating, as the research published in scholarly journals and presented at medical symposiums appears to be increasingly biased in favor of the drugs being researched, to the point that physicians are now basing their treatment decisions on woefully incomplete data sets and trial results that conveniently leave out the negative while emphasizing the positive.

As is documented by British psychiatrist Dr. Ben Goldacre in his book “”Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients”, which was recently excerpted at Salon.com (click here), the trial evidence upon which doctors base their most important decisions is often misleading at best, and outright dishonest at worst. As more and more medical research is funded by the drug companies themselves, rather than by independent concerns such as foundations or government agencies, the results of that research appear to be becoming less and less reliable. Dr. Goldacre cites studies which show that research funded by pharmaceutical companies is far more likely to favor the drug being tested than studies funded by independent organizations.

One such study, conducted in 2007, looked at every published study investigating the effectiveness of statin drugs, which are commonly prescribed to lower cholesterol. The studies either compared an individual drug to another kind of treatment, or to a competing statin drug. In all, 192 studies were surveyed, and researchers found that pharmaceutical company funded studies were 20 times more likely to give results favoring the test drug than similar trials funded by independent concerns. Other studies looking at different bodies of research found discrepancies that weren’t quite so dramatic, but invariably found that industry funded studies were far more favorable to the drug being researched.

The reasons for this bias are many. Trial results can be manipulated by testing a drug against another drug given at a sub optimal dosage. Patient populations can be manipulated, so that only patients most likely to get better are used in the research. The researchers themselves, even those conducting studies that are properly designed, may be subconsciously biased by the knowledge that their paycheck is being funded by the pharmaceutical company whose drug is being tested. Whatever the reasons, the evidence appears to be irrefutable: the trial results upon which doctors base their treatment decisions are very often biased in favor of the treatment being tested.

To make matters worse – much worse – drug companies routinely fail to report negative research outcomes, never allowing them to see the light of day. The companies conduct many studies on a single drug, and only publish those studies whose findings are positive for the drug in question. Dr. Goldacre writes about a situation in which he did the very best he could as a doctor, only to later find that he had been misled by the very act of doing his due diligence. In deciding on an antidepressant drug on which to put a patient for whom other drugs had proven ineffective, Dr. Goldacre read every published study he could find on a new drug he was considering, which all showed it to be better than placebo, and as good if not better than competing antidepressant drugs. Later, Dr. Goldacre learned that, though he had read all of the available studies, he’d only received a tiny glimpse into the true research record of the drug he was investigating, Reboxetine.

Some time after Goldacre prescribed Reboxetine for his patient, researchers did a comprehensive survey of all the trials that had ever been conducted on the drug, including those that had not been submitted for publication in academic journals by the drug company, collecting their data through numerous requests to manufacturers and regulating agencies. They found that seven studies had compared Reboxetine to placebo. Of those seven studies, only one found the drug had a positive result, the other six found Reboxetine to be no better than a dummy sugar pill. Only the positive study was published for review by physicians. The six failed studies were never submitted for publication. Trials comparing the drug to competing drugs showed a similar pattern. Three trials, totaling 507 patients, found Reboxetine to be more effective than a rival drug. However, other trials, which used data derived from 1657 patients, found that Reboxetine treated patients fared worse than those on other drugs. These findings were again left unpublished, shielded from the view of the physicians.

Tragically, this situation is typical of the industry. The fact that pharmaceutical companies can fund their own studies and decide to only publish positive data is unfathomable. Would we let, say, automobile manufacturers conduct their own safety tests, and without question accept their claims that the cars they make are the safest in the land? Of course not, yet this same practice has been allowed to flourish in an industry upon which the health of the world has come to rely. The situation is outrageous, but is so endemic that remedies are difficult to come by.

The British Medical Journal, a highly respected academic journal better known these days as BMJ, has, as of January of this year, announced that it will only publish studies that allow access to patient data from all of the studies conducted on the drug in question. The editors of the BMJ lay out their case for this action in a hard-hitting editorial published last October (click here). If only other academic journals would follow suit. The pharmaceutical giant GlaxoSmithKline announced in October 2012 that it will open up all research data for investigation by physicians and scientists (click here). While this is an admirable step, it comes only after GlaxoSmithKline was forced to pay $3 billion to the Federal Drug Administration to settle three charges of fraud levied against it (click here), one of which included holding back data and making unsupported claims regarding its diabetes drug Avandia.

Another of the charges in the GlaxoSmithKline settlement was that the pharmaceutical giant used inappropriate tactics to influence physicians to prescribe their drugs, tactics which included paying large speaking fees to doctors and providing them free access to high-priced entertainment. Couple the reality that pharmaceutical companies have been allowed to bury negative trial data with the fact that these companies routinely use their huge sales forces to court practicing physicians with offers of all-expenses-paid trips to “educational symposiums” in exotic locales, free gifts and lunches, and sponsored lectures, and we have what some cases amounts to a completely rigged system.

As circumstances currently stand, physicians find themselves faced with a situation in which they can’t trust the research published in academic journals (often their only resource for such vital information), and many find themselves subject to conflicting influences offered by pharmaceutical companies, the success of whose products lies completely in the hands of these same physicians. The end result can only be that patients in general, who trust their very lives to doctors, can only wonder about the motivation and correctness of the treatment decisions made on their behalf. For MS patients, whose drugs can cost tens of thousands of dollars a year and some of which carry potentially deadly side effects, the gravity of these questions is only multiplied.

It’s a situation that truly boggles the mind.

The below video is a presentation given by Dr. Ben Goldacre on some of these very same issues. It's really a must watch…
 


Enhanced by Zemanta

27 comments:

  1. Thank you so much for drawing attention to this. I've only had MS for 5+ years but have been on antidepressants and struggling with depression for 23 years. I had not heard the story of this particular antidepressant in England. We don't have it in the US (I guess the FDA decided it didn't meet their standards) but I have read similar stories about American prescribed antidepressants -- this has been a problem for years.

    Most of the ADs are statistically said to be almost no better than placebo in a clinical setting if you take into account all of the studies (which some people have discovered through use of the Freedom of Information Act).

    It really is frightening that pharmaceutical companies wield that much power in our world, isn't it?

    And what can we do if our own doctors don't have access to legitimate information? And imagine, as you said, what it's like with MS drugs (or any other autoimmune drugs for that matter). The MS treatment market alone is about $10 billion right now. Analysts expect it to grow to about 14 billion in 2015.

    Love your blog and always find it highly informative.

    ReplyDelete
    Replies
    1. Low Vitamin D3 can cause depression. Most people with MS have low Vit. D.

      Delete
    2. You are correct, it is very important for MS patients to monitor their vitamin D levels.

      Delete
  2. Marc, thanks for keeping your critical light shining on Big Pharma. It may take a long time, but I think change will eventually come as long as we keep the issue on the front burner.

    ReplyDelete
    Replies
    1. Hey, it's a dirty job but someone has to do it. Actually, I can't say I am all that confident that things will change as long as Big Pharma keeps on earning its billions. We are cutting government budgets, and leaving more to the private sector. In some areas this may be prudent, but medical research cannot be driven by the profit motive, there are just too many conflicts of interest.

      Delete
    2. Marc we've never met but you have no idea how much I appreciate your existence. Not to mention the power of science and it's undeniable truth.

      Delete
  3. Awesome Marc! Only wish you had included some of the ill practices that have come to light with the MS DMDs of late...

    ReplyDelete
    Replies
    1. So many grievances, so little time. There are Big Pharma outrages wherever you look…

      Delete
  4. Thank you Marc for keeping Big Pharma's feet to the fire. You are doing a great service for everyone. It is sad indeed when we must be our own doctor.

    ReplyDelete
    Replies
    1. Indeed we must. It's so important for patients to self educate, and I know far too many who are resistant to do so. Maybe they're better off, ignorance is bliss…

      Delete
  5. No surprise, then, that I usually find news about drugs in development on the business page. Treating sick people as a profit center is just so wrong.

    ReplyDelete
  6. Nice work, Marc. I would add another note to your points. Since I have been diagnosed with MS I have had wonderfully well-informed, conscientious, and compassionate doctors, but once upon a time many of the symptoms I now know to be the result of MS were attributed to mental illness--specifically, depression and PTSD. One psychiatrist I saw during that time period prescribed "Big Pharma" meds like they were Tic Tacs. At one point, I had an entire cabinet shelf full of different types of antidepressants that the psychiatrist insisted I "try." Now that I know that many of the symptoms I was having are MS-related--problems walking when I was stressed, depression itself, muscle spasms that came and went unpredictably, etc.--and not mental illness, I am appalled by what seems to me to be that psychiatrist's problematic reliance on Big Pharma's products.

    Along those same lines, there is an interesting (and related) piece in today's New York Times. http://www.nytimes.com/2013/02/03/us/concerns-about-adhd-practices-and-amphetamine-addiction.html?hp

    Thanks again for a great piece!

    ReplyDelete
    Replies
    1. That New York Times piece was amazing. Incredible how many doctors are simply prescription machines, especially psychiatrists.

      My experience was similar to yours, the first neurologist I saw when I started having symptoms told me that I probably needed to start taking antidepressants. I told her I'd been on them for 17 years…

      Delete
  7. Thank you for your voice in the wilderness. May it help us emerge someday to see the unencumbered light of day.

    ReplyDelete
    Replies
    1. Thank you, but far too many either don't care or won't care. Meanwhile, the pharmaceutical companies are gradually making sure that every individual is on some kind of medicine. They've taken to inventing diseases. Low T? Used to be called getting older…

      Delete
  8. Have you heard of LDN and the book "Up a Creek with a Paddle" as well as Honest Medicine?
    I just started taking it. The patent on it has run out and so it's effectiveness with MS patients is not largely known or studied. There are some studies that began in 2012. Let me know if you have tried it or what you think. JMD

    ReplyDelete
    Replies
    1. I tried LDN back when I was first diagnosed, but it didn't do a thing for me. I'm not a good person to use as an example, though, since my disease is so atypical that it might not even be MS. I do know many patients who claim that LDN has helped them, but full clinical trials will never be undertaken because there's no money to be made marketing an old, off patent drug like naltrexone…

      Delete
  9. I still marvel at the fact that most MS research is done on mice who do not get MS at all. Instead, the symptoms are induced in the mice who then are treated with the meds that become the blockbusters for Big Pharm. It appears that the treatments don't seem to work on people as well as the mice. Or, am I being too cynical?Oh yes, I forgot, the mice also die sooner.
    Also, since MS is reputed to be "different" for each person, how then can these trials have any validity when the so called "control" group is so markedly diverse?

    Bottom line once again is not finding cures, helping the suffering person have quality of life, or even pretending to be honest in the data......it is SHOW ME THE MONEY BABY!!!!



    ReplyDelete
    Replies
    1. The problem is that nobody is really searching for the root cause of MS, and all the drugs they are coming up with are really just sophisticated symptom managers. An out of whack immune system is a symptom of something deeper going on, but all of the MS drugs either modulate or suppress the immune system.

      Credit where credit is due, many patients do find a tremendous amount of relief from some of these drugs. But none of the drugs does absolutely anything in the way of curing the disease, and I'm not so sure that tinkering with the immune system long-term will not lead to some unforeseen outcomes…

      Delete
  10. Ben Goldacre is an enthusiastic showman and columnist and has done a great job at highlighting the priorities of big pharma.
    Ultimately though, they're just companies primarily in the business of making money, making patients' lives better would seem to feature further down the priority list than shareholder's profits.
    How can we separate money from healthcare?
    Iain Chalmers' Testing Treatments is a fantastic title that the authors felt was so important in allowing the public to more fully understand the trial process that he's made it available as a freely downloadable pdf http://www.jameslindlibrary.org/pdf/testing-treatments.pdf
    So, even if we can't take money out of the process of patching people up at least we can be better aware of what's being done 'for our own good'.

    Really worth a read.

    ReplyDelete
    Replies
    1. Thanks very much for the link,I will definitely check it out.

      You are very right that the pharmaceutical companies are only doing their job, making money for their shareholders. That's the problem, the flaws are built into the system, they are insidious and pervasive. Which means that there are no easy solutions.

      Despite the antigovernment spending predilections of the current United States political environment, there really are some things that government does better than the private sector, medical research being a primary example. Thankfully, there are some organizations, like the Myelin Repair Foundation, that are trying to come up with a better model…

      Delete
  11. I'd add one more to your list of ways Big Pharmaceuticals can skew data, seasonality of symptoms. I have been trying for a few months to get Patientslikeme.com to give me access to their records of patient reported new symptoms. I saw a study last year which looked at 2 different (small) groups of MS patients. It looked at them on different days and published the results saying the patients on the hotter day had more cognitive impairment. Every MS patient and researcher I've shared the stufy with has the same response, "Duh! They spent money/time to come to that conclusion?"

    The thing is this seasonal adjustment should be a part of every MS study, and probaly other conditions as well. I tried to get access to the data, because I already have seasonal adjustment measures programs for other studies at my work. I want to look at all of the MS drugs and categories of symptoms to see how seasonal the results are and can be.

    If I were a pharmaceutical company and got to pick, I would schedule my MS drug trials to begin in July and end 18 months later, in the winter. Then I could claim any improvement as the result of my drug, and a stable result as a good one even if it masked the worsening condition at the 12 month mark.

    In any event, thank you for your post. This information should be widely available. I'm just thankful the fed does now require and post a listing of all proposed studies and their results.

    ReplyDelete
    Replies
    1. The drug companies can and do take advantage of things like the seasonal cycles of MS. There are just so many ways to "cook" the numbers, and yet these companies still bury the results of negative study outcomes.

      I'm also concerned that most of these drugs only go through two or three years of testing, and patients are expected to be on them for far longer periods of time. Who knows what problems will crop up after patients have had major portions of their immune systems suppressed or eradicated for five or 10 years? Hopefully, there won't be too many nasty surprises in the future…

      Delete
  12. What I find hard to beleive is too many are oblivious to so many bad drugs that have killed . Too many in UK are being dosed up on many bad MS drugs luckily have never took any and lived longer than ones who have am living proof in UK lots

    ReplyDelete
    Replies
    1. As I stated befor very frightening side effect profiles, they also do improve the quality of life for many people who take them. I know many patients who have been so positively effected by Tysabri that they refuse to go off of the drug even when they start testing positive for the JC virus. They'd rather take the chance of PML then go back to experiencing a relentless series of relapses. Desperate times call for desperate measures, I suppose…

      Honestly, if I were presented with a drug that had a 50% chance of making the "normal", and a 50% chance of killing me, at this point I think I'd grab it…

      Delete
  13. Some of the research done to improve health is not always celebrated. Here is some good research I found.

    IL6 antibody has a wide range of biological effects, and is an important function in the immune system and acts as both a pro-inflammatory and anti-inflammatory cytokine responses. IL6 antibody is pertinent to curing many diseases such as diabetes, depression, prostate cancer, Alzheimer's Disease, systemic lupus erythematosus etc. Thank you for the article anyway, its helped me with my research.

    ReplyDelete