Monday, July 6, 2009

Are Clinical Trials Rigged?

A news article by Ivanoe Medical news, accessible by the link in the title of this post, brings together some of the critical background information on results being skewed and summarizes some of the findings in a JAMA article.

The articles say's:
“Many medical journals are becoming marketing instruments for the drug companies," Sidney Wolfe, M.D., Director of Public Citizen's Health Research Group, said.

A new study finds 2 percent of scientists admit they have fabricated, falsified or altered data to improve the outcome at least once. About 35 percent admit to questionable research practices. A JAMA study reveals that 30 percent of the original research studied was either false or exaggerated. Problems include small study size, design flaws, publication bias and failure to publish negative results.

"A smart drug company -- maybe not an ethical one, but a smart one -- might decide to publish only those studies that put its drug or device in the best light," Dr. Lurie said."

But what can be done to protect patients/consumers? Some momentum is being gained to establish a data base were the results of all clinical trials, negative and positive results, can be queried.

We have posted many articles on this subject, which makes a strong case against preemption.

Knowing what we now know, can we afford to not do anything? I think not.

Any plan to overhaul our health care system has got to include a critical assessment of the FDA, medical associations and their guidelines including the guidelines for publishing clinical trial results.

We need to restore credibility and trust in our health care system.


  1. Thanks Former – Another in a long, long line of reports on the cunning manipulation by the pharmaceutical industry.

    How obvious it is that change is essential in the current pharma environment. I am sure that even industry leaders would agree with this. Attitudes, regulation, methods, relationships, transparency, communications have all been corrupted over time in favor of easier profit.

    Yet we see the focus of the industry leadership is not on correcting these obvious flaws but rather to protect them by kicking out the only remaining willing corrective leg left in the system - Product liability accountability (state tort).

    For those of us who have been watching this train wreck for a while it becomes obvious that in reality FDA Preemption is attempting to protect the current corrupted environment. FDA Preemption was invented by the industry and is now being defended by the industry in the most deceitful ways by using reasoning void of statistical data, innuendo, assumption, purposeful misdirection and purchasing influence.

    So therefore it is obvious that the intention of the industry leaders through preemption in reality is to maintain business as usual:
    • protect the attitude of profit over safety
    • eliminate or neutralize overseeing regulation
    • maintain the easy methods that lead to higher profit rather than relying on true science
    • neglect the relationship between the product producers and the consumers
    • fog transparency to allow surreptitious activity
    • halt communications between all the interconnected parties that serve to protect the public

    In reality something more that just the defeat of preemption will be required to fix this mess.

  2. JAMA has been part of the problem. The horse is out of the barn and they waited way too long to say anything. See: JAMA Editor Ignites Firestorm By Calling Critic a 'Nobody and a Nothing'_WSJ - | Google Groups

    How do we deal with (once) trusted journals that are, as Dr. Wolfe points out, “becoming marketing instruments for the drug companies?”

    Any ideas?

  3. FPME, I'm glad you posted that article. A couple interesting points:
    1) The first sentence states "Each year, $84 billion is spent on drug development." Note that this is 2x the entire budget for the National Institute of Health NIH and the National Science Foundation COMBINED!! This should give people a sense of the scale of R&D going on in the pharma industry.
    2) Negative studies ARE frequently published for major drugs. Don't you remember all the clinical flops of recent years? Here's a few major ones: Torcetrepib (Pfizers HDL raising drug), Rimonabant, Taranbant.
    These links will give you many more...
    Suggesting that these trials were rigged is almost laughable. Kindof like the bumbling thief that shot himself in the foot on his way out of the bank. It just doesn't make sense.
    3) I agree that trial results (raw data) should be publicly available to all. As we've discussed before, this is already happening and there is little resistance from the pharma industry. (note, as I've said many times, real PUBLICATION of negative results is sometimes not possible because journals are peer-reviewed - they only are interested in articles that advance science forward - not articles that illustrate a bunch of mistakes. I'm a chemist. There is no way I can publish a bunch of failed reactions in a journal.

  4. I have been actively exposing Purdue Pharma for their criminal marketing of OxyContin. My work for the past 7 years saw reward in the conviction of Purdue Pharma and its 3 CEO's Michael Friedman, Howard Udell and Paul Goldenheim in Federal Court for minimizing the addictive and abusive qualities of OxyContin. Recently I charged them with marketing for pregnancy pain and newborn and pediatric pain through the FDA -- action was taken against PP. I also have charged Purdue Pharma with utilizing bogus reports on their website -- also with success with the FDA. I am now involved in having the marketing phrase "undertreatment of pain" utilized by Purdue Pharma eliminated from their criminal marketing tools.
    Marianne Skolek
    Activist for Victims of OxyContin and
    Purdue Pharma - a criminally convicted pharmaceutical company

  5. Good remarks Nathan.

    It is hard for us to analyze the 84 billion dollar figure being used in the article, it may even include the money being spent by the NIH and others, as the article doesn't state if this is in pharma money only. The other factor is we do not know what the authors mean when they say drug development. For some people this is still a catch all phrase and may include things such as, Drug discovery / product development, pre-clinical research(microorganisms/animals) and Clinical trials (on humans). Few people still refer to the drug development as mere preclinical development. It may even include "Opportunity cost" which is the value of the next best alternative forgone as the result of making a decision. So we can not say that the 84 billion directly translates or is a good measure of the R&D being spent by Pharma.

    We are not suggesting the trials are rigged, but the article clearly states that the researchers themselves admitted to falsifying the data to some extent. What do you call that?

    There is much to be learned from failed trials and I would agree that not every failed trial result needs to be published. We are saying that both positive and negative trial results for the same drugs should be made available. As you yourself pointed out, we should also be able to access the raw data.

  6. Marianne,
    Thank you for your dedication; so sorry that it was fostered in the sad loss of your child. I think that a number of us here have had similar experiences and have come to realize that the tragedies we’ve experienced can so easily happen to others. We live in a world that we’ve found to be much less trustworthy and more dangerous than we ever realized it could be and hope to in some way warn others.

    Your latest quest against the marketing of the term “underteatment of pain” is similar to something that we’ve encountered in our fight against FDA Preemption. The term we’re accustomed to hearing from those that try to “invent” justification for preemption is “overwarning”.

    “Overwarning” is basically the same kind of scare tactic that causes one to believe that it really exists simply because it has been given a name. You can call it a weasel word. (see Wikipedia)

    Its intention is to claim that unless manufacturers are allowed to be free from product liability they will be forced to add many more warnings to their labels, thereby scaring the consumer and causing them to not use the product. The problem is there is no evidence that overwarning is or ever has been the case. The defenders of preemption just assume that it might be the case. Pretty flimsy evidence for elimination of the civil right to a day in court.

    Anyway I wish you much success in your fight. Keep us updated.

  7. change is essential in the current pharma environment.
    for the patient yes, for the Pharma Co. no change is essential

  8. short note--A guest speaker in my course last year, former exec at Squibb, asked my class, "What the heck is 'development'?"

    He made it clear that the "D" part of the R&D budget numbers as released usually include a great deal that most folks would consider essentially advertising.

  9. Good point Justice and attached is an article from Reuters - Dec 2008 -

    A quote from the article - "Direct-to-consumer promotion was the single worst decision for the industry," William Burns, the Swiss group's head of pharmaceuticals, told an FT conference in London on Tuesday.

    "When industry says we're spending all the money on R&D but actually it's spending it on TV advertising to preserve margins, it doesn't get much credibility," he added.

  10. Justice - please expound on that statement. I stongly disagree, and I'd like some details on what the speaker considered "development".

    The division between "research" and "development" is very clear within my circle of big pharma:
    "Research" refers to all preclinical and some early clinical work (phase I and maybe into phase II).
    "Development" refers to late stage clinical trials, regulatory submissions, manufacturing optimization, etc.

    There are HUGE expenses in the "development" phase that have nothing to do with product promotion.

    I'm guess what the speaker is refering to is some "grey" areas. For instance: If you want to show that your drug is good a new indication. If you want to show your drug is effective in pediatric populations. If you want to establish the superior safety/efficacy of your drug in comparison to your competitors. Those are all real R&D expenses -- but, yes, they do overlap (slightly) with marketing needs.

  11. This may be of interest to some of you: Derek Lowe has a new blog post today (link below) that illustrates that drug marketing expenditures have actually been DECLINING for years (as a % of drug sales) while R&D expenses have been increasing over the same time period. You can argue that marketing expenses are still too high -- but this data strongly suggests that the TREND is in the direction that most of you folks would like to see: More R&D and less marketing.

  12. So if I understand correctly (by the graph), sales and marketing are at about 40% of total sales and increasing and R$D is around 15% and slightly increasing while Manufacturing costs are drastically reducing and at 45%.

    I say we releave pharma of the sales and marketing cost burden and eliminate DTC. Can you imaging what doubling R&D could do?

  13. David,
    Two points:
    1) DTC ads are only a tiny fraction of total marketing costs. (~7% in 2004) See this link:
    2) Remember that the "40% line" is NOT just sales and marketing. It is "sales, marketing, and administrative costs". That includes IT, HR, infrastructure, etc along with the sales/marketing. Companies break down costs this way do to SEC regulations, I believe.

    That said, I would love to see my pharma R&D budget double. But eliminating DTC would only allow us to increase R&D by a fraction. Even so, it might only allow a temporary increase in R&D. Once DTC stops, sales would likely fall resulting in slashed R&D budgets.

    Of course I agree that there is no point in maintaining our sales unless the products we sell are actually benificial. I'd like to maintain my job, but certainly I hope I can do so by making a useful product - not a product that makes money simply because of slick advertising...

  14. Hi Nathan,

    My guess is that the speaker was referring to that "grey area" you mention. His style was a bit cryptic in general, so I can't add much that is specific.

    My earlier understanding of "development"--which is almost certainly incorrect or partial--was that it is the process in which a company takes a molecule from, say, a research center and does the additional work that makes it a viable drug. Thus, I folded development into what is essentially part of research--especially later trials, as you suggest. Here in Ann Arbor, for example, many claim to be part of the "development" of Lipitor, which intends something different than to be one of those who originally "discovered" (it that's the right word) the potential of the molecule. Rather, development, as I understood it, meant ushering it through the various stages that would demonstrate its potential--again, much the same as what most folks would call research.

    The speaker suggested that "development" _could_ mean whatever a company chose it to mean. And the suggestion was that this varied a good deal, depending on the company and drug in question.

    The overall point, I think, was that it was easy for "outsiders" to assume what such terms meant, without actually doing so.

  15. Here is perhaps another example, although I don't recall if the speaker specifically mentioned it.

    Certainly, it is often claimed that many phase IV trials have less to do with confirming a risk/benefit or even creating data for a new indication. Rather, the idea is to engage physicians, especially heavy prescribers of that company's products, with the use of a particular drug and provide them a sense of "ownership" in its future. Such phase IVs would combine what is simultaneously research, development, and promotion.

    I think that is consistent with the last category you wrote about.


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