Saturday, 12 June 2010
Does This Smell Nice?
On Saturday, 12 June the Dr. Mercola web site in the USA featured a video and long description concerning how major companies influence scientific research and used the system to their advantage. Inevitably, what applies to the major pharmaceutical companies applies just as much in other fields, notably those less regulated. It will certainly apply to household and cosmetic products and with even greater force to the companies making extensive use of fragrances.
Big Pharma’s Bald Faced Lies And The Destruction Of Health
Dr. Mercola – Saturday 12th June 2010
Dr. Golomb is one of those rare commodities. She has earned an MD and a PhD and, is an associate professor of medicine, and associate professor of family and preventive medicine at the University of California at San Diego. But she is a rare commodity because she has integrity, and has not sold out to the drug companies while most other researchers have.
"I was initially perplexed by the disparities I saw between the published evidence, review papers, guidelines, and follow-up papers after trials were published," she explains, when asked how she became interested in the topic of Big Pharma distorting scientific evidence.
She had been researching statins (cholesterol lowering drugs), and she was perplexed by how people could come to the conclusions they were coming to, based on the data. "I would ask my colleagues, how could they have read this paper and come to this conclusion?"
Over time, as she began examining the evidence relating to conflict of interest and published results, she discovered there were forces at play that lead to disparities between the evidence that was published, relative to the "truth" of that evidence, and the secondary representations of that evidence and the evidence that was published originally
"There is actually widespread evidence, even within the medical literature, showing that these forces can lead to qualitative differences in the conclusions relative to the fact," Golomb says.
A Perfect Example of Drawing the Wrong Conclusion from Published "Scientific Evidence"
Early in the interview Dr. Golomb cites a perfect example of the qualitative difference between the scientific facts amassed and the conclusions drawn.
"FDA analysts now have access to clinical trials whether or not they are published because of the clinical trial registries that some journals now require. (That doesn't actually require that those results then be published, but at least now there is opportunity for the FDA to get access to those studies, and sometimes to the evidence from the studies.)
So the FDA conducted an analysis of antidepressant drug trials and found that of 38 trials for which the evidence appeared favorable, 37 had been published. Whereas of 36 trials for which the evidence did not appear favorable toward antidepressant drugs, 22 were not published at all, and 11 were published in a way that misleadingly conveyed the outcome as though it was favorable.
So that research, the "published evidence," would be that over 90 percent of publications were favorable, relative to "truth" (at least as determined by the FDA analysts), which was about 50 percent.
So that's an example of how the evidence we see can be dramatically different from the evidence that was procured, and there are actually a number of mechanisms that lead the evidence that was procured to already have disparities, generally favoring treatment benefits, relative to truth."
Many of the critics against natural or alternative health claim that we have abandoned the scientific method, and I think nothing can be further from the truth.
I have enormous respect for the scientific method, and I think when it is done properly it can clearly provide us with profound and valid truths that can guide and direct our treatment protocols.
But what many people fail to appreciate is that much of the research published has been deeply influenced and severely tainted by tremendous conflicts of interest and profit-driven motives.
Dr. Paul Offit, for example, an infectious disease specialist at the Children's Hospital of Philadelphia, has been quoted as saying: "Science is not a democracy where people's votes decide what is right. Look at the data, look at science and make a decision based on science that has been published."
But what he is really advocating with this statement is blind faith in "facts" that may have been produced in the midst of, and sorely skewed by, massive conflicts of interest.
You Won't Find What You Purposefully Avoid Looking for
Dr. Golomb was previously the scientific director for the Department of Veteran Affairs and on the Research and Advisory Committee on Gulf War Veterans' illnesses. This experience also predisposed her to being more sensitive to issues that many other physicians are not attuned to.
"Part of the reason I got interested in the Gulf War area was because I was already concerned about the way inferences were drawn about that condition… I had seen the conclusions of the Institute of Medicine and the Presidential Advisory committee reports relevant to Gulf War illness at that time, and… inferences were basically absence of proof of a connection between organic factors and illness, which is interpreted as "proof of absence" of a connection.
But no one had looked, and therefore no one had "proved" that the exposures they had received were related to their illness. They then concluded that there couldn't be a relationship. But you couldn't conclude there was "no relationship because there was no evidence" because nobody had looked, or even asked if it was biologically possible and therefore merited more inquiry."
This seems to happen more frequently than you might think. Absence of proof of a connection between a toxic exposure and disease tends to morph into "proof of absence of a connection." But in reality, the absence of proof is oftentimes little more than a refusal to investigate the matter in any serious way.
"It was clear that some of the exposures Gulf War veterans had, had strong biological plausibility as precipitants for their illness, and I outlined… a research plan that would help to evaluate whether in fact there was a cause of relationship.
I suggested that we look at the genetic variants of the enzymes that detoxify some of the chemicals they were exposed to, on grounds that if these chemicals were causally linked to illness, [then] people who have sluggish variants of these detoxifying chemicals should be more likely to be ill, and sure enough, they are. And people who had higher levels of exposure to these chemicals would be more likely to be ill, and sure enough, they are."
Why is There so Little Independent Research When We Know Profit Motives Drive Conclusions?
Not surprisingly, based on Dr. Golomb's investigations into statin drug studies, ALL of the large randomized control trials of statin drugs have been funded by drug companies. And when you consider that the pharmaceutical industry makes about half a trillion dollars annually, it's easy to see how statin drug research may have been clouded by conflict of interest.
So why is there not more independent research being done?
"It's very expensive to do those studies," Golomb explains. "The only other source of funding for reasonable sized studies is the National Institutes of Health (NIH).
We approached the NIH to conduct a study to see whether coenzyme Q10 might mitigate muscle side effects of statins, and we were told by NIH officers that they wouldn't even consider to do the study unless we ask the drug company to supply the statin.
So I contacted the NIH and I said, "I'm really trying to have a career free of drug company conflict of interest, would it be such a problem to have one study that doesn't have a drug company involved in it?"
And they said, somewhat reasonably, that their interest is in leveraging their funding and therefore, no, they would not consider an application unless we asked the drug company to supply the drug, which of course already set some level of conflict of interest."
So, unfortunately, the need of the government to leverage their investment has the unfortunate side effect of also producing ties to industry. Clearly, a pharmaceutical company is not going to jump at the chance to give their drug to an independent researcher who may find that the drug has significant problems.
If they voluntarily supply the drug, they're naturally going to want to have a say in what results are published at the end.
How the Publication Process Can Easily Add to the Problem
But looking at the funding, and hence the potential for direct conflict of interest, of the research in question is not the only problem we face when trying to decipher the truth of any given study.
Once the data has been collected, there's a whole other set of variables that come into play, with respect to submitting them to peer-reviewed journals. "We've already alluded that there are funding disparities, and that less favorable studies – if they are drug company funded – are less likely to be submitted for publication. And then there are issues at the level of the journal.
It would be nice to think of medical journals as these bastions of truth and light that have no bias, but in fact, they're businesses, and they make their money, in many cases, from drug company advertisement, and also from sales of the glossy reprints of the drug favorable articles to industry.
And interestingly, several former editors and chiefs of major medical journals, Richard Smith of the BMJ (British Medical Journal), Richard Horton of the Lancet, and also a couple of former editors-in-chief of the New England Journal of Medicine have written books and opined heavily on the favorable impact of drug company influence on medical publishing.
There are strong conflicts by the journal to publish drug company favorable articles in order to reap those hundred thousand dollars or so in reprint sales for the favorable articles, and also to keep the drug companies happy so that they continue to get drug company advertising."
This is an important point that I don't want you to miss: There are drug reps whose sole responsibility is to "educate" physicians about new drugs, and one of their primary tools is to provide reprints of favorable studies. This is not something that they can simply photocopy in their office, because that would be copyright infringement. So they actually have to pay for that reprint from the journal, and that's exactly what Dr. Golomb refers to here as "reprints."
In many cases, these reprints can amount to income in the six figures, over and above the income the journal generates from the drug company's advertisements in the journal. This profit-driven motive to publish shoddy studies of dangerous drugs creates a major conflict of interest within the journal itself.
"The evidence that this has an impact comes from several sources," says Golomb. "One was the Annals of Internal Medicine that, some years ago, published an article on the impact of drug company advertising on physician behavior and the article was not flattering to drug company advertising.
Somebody tracked the impact on the Annals revenues before the article, and after the article, and they estimated that they lost $1-1.5 million in advertising revenue over the ensuing several years as an apparent consequence of having published that unflattering article. And there is direct evidence now as well, of drug companies rejecting unfavorable articles -- articles unfavorable to industry, based on factors other than article quality."
Two additional problems that have flourished within scientific publishing are the issues of ghostwriting, and duplicate publications. I expounded on both of these issues in this previous article. Although it is considered a serious ethical breach to publish the same clinical trial more than once, this is in fact what has happened with some drug trials, which Golomb discusses in this interview.
Why is this problematic?
Because, for example, if you were to do a meta-analysis, where you review all available studies on a particular drug, you'd be mislead to believe that there are far more favorable studies than there really are. And if that republished study was flawed or the results manipulated through conflicts of interest to begin with, then what you end up with is essentially scientific fraud.
Then there's the process of gaining favorable reviews by other experts, another area fraught with potential conflicts of interest. To learn more about the ins and outs of the peer review process, I urge you to listen to the interview in its entirety, or read through the transcript.
In it, Dr. Golomb discusses the policies in place regarding conflict of interest; why these policies so often fall short; and how pharmaceutical companies manage to circumvent these policies to still publish their sometimes downright imaginary findings.
Some of her stories detail the devastating collapse of the entire system that occurs far more often than anyone could possibly imagine. But she also discusses the potential for reforming the system. Part of rescuing the honor and validity of the scientific method is to put an end to the indoctrination by pharmaceutical companies that occur from day one in every medical school.
"Most of the physicians who are doing the training are conditioned by the existing literature and the existing "expertise," which is influenced by all the factors that we've just mentioned. So they legitimately believe the benefits of these drugs often to a degree that's not even supported by the published randomized trial evidence, because it will also be supported by the follow-on review papers, commentary expertise, and guidelines.
But medical students have actually been on the vanguard of trying to make change and the American Medical Student Association actually developed a policy of trying to rate the impact of conflict of interest in the classroom.
My understanding is that this was motivated initially by a medical student at Harvard who had listened to their lecture on statins, and somebody in the classroom had raised their hand and asked the question about statin adverse effects and it was answered in such a derisive and dismissive way that this other student looked up the lecturer online and discovered that he had all these conflicts of interest with statin industry. That ended up prompting the student group to try to take action."
Isn't that always how real change starts? With just one person, asking the right questions, expecting answers, and being willing to look deeper rather than accept something as "truth" at face value. It's unfortunate, but the science based system we currently have has some fatal flaws.
It's virtually impossible to expect a publicly traded pharmaceutical company, which has a major obligation to its stockholders, to simultaneously have the patient's best interest at heart. As Golomb says, the two are fundamentally incompatible. And yet this is THE source of the vast majority of the funding for all our science-based evidence.
Remember, the end consumer here is you, if you take any type of drug. So although these issues may seem far removed from your life, they absolutely affect a vast majority of you, every single day. The decisions about what drugs to prescribe are being made based on the research published. Oftentimes individuals will decide they want to take a specific drug based on a TV advertisement they just saw, which also spouts claims derived from this scientific process.
Knowing what you know now, after listening to this interview, how comfortable do you feel about taking Paul Offit's advice to just "make a decision based on science that has been published"? Hopefully, this interview will cause you to think a little deeper about the process of the scientific model in general, and how to evaluate scientific evidence in particular.