ResearchBlogging.orgI’ve been having an internal debate about whether to write on this issue, not because it isn’t interesting, not because it isn’t important, but because it’s getting so much coverage and I’m not sure how much I can add to the conversation.

But it so infuriated me that I must blog. Science-based medicine relies on medical evidence. It relies on being able to grade medical evidence by its quality and strength, and to do this, there must be a certain level of transparency.

I’m only a little bit idealistic. I know that drug companies must fund clinical trials if we ever want to see new drugs. That is why we have “conflict of interest” statements included in most medical studies—so that we may view the data with a somewhat jaundiced eye, if necessary.

Until two days ago, I’d never heard of a “seeding trial”. Now I have, and I’m not happy.

Seeding trials are basically direct-to-doctor advertising. Instead of confining the trial of a new drug to one or two institutions, a study can be spread out among many investigators in the community. If a promising new medication is ready for widespread testing, doctors like me (but not me) out in the community can sign up to participate in the clinical trial. The pharmaceutical company will design the trial and a third party company will come out and make sure we are following the protocol correctly. This allows data to be collected from a diverse group of patients. It also allows a doc out in the community to participate in research, and perhaps make a little extra money.

It turns out that sometimes the research protocol comes not from the research department but directly from the marketing department.

You see, Merck isn’t run by fools. They (and apparently many other companies) figured out that these types of trials make really good advertising. They get a whole lot of doctors into the habit of prescribing a new medication not as a side-benefit of the trial but as its primary purpose.

In the latest Annals of Internal Medicine, and in-depth analysis of a seeding trial involving Vioxx (ADVANTAGE) revealed some very disturbing information. This document, obtained by the study’s authors, is one of many that shows how this study was not done in the name of testing the medication (later withdrawn for safety concerns), but as a giant marketing ploy.

The authors of the article specifically mention three problems with seeding trials that makes them “harmful to science and society”:

    Full informed consent is impossible, as the participants are not aware of the full purpose of the trial (as a marketing tool).
    Good research design is compromised for marketing goals. Spreading the study over as many practitioners as possible is good for business, but maybe not so good for research quality control.
    The study may be scientifically irrelevant. A more definitive study of Vioxx was being done simultaneously with the ADVANTAGE trial, rendering ADVANTAGE moot.

There are further problems. The existence of trials run by marketing departments creates distrust of scientific knowledge. We base our practice on data. Some data will always be problematic, but if the whole system of collecting data is called into question, clinical science-based practice can be set back decades.

While I’m not surprised that seeding studies exist, I am disgusted. Now that the practice has been brought into the light, we can be armed with another tool with which to interpret data, which is ultimately a good thing.

References
Kevin P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; and Harlan M. Krumholz, MD, SM (2008). The ADVANTAGE Seeding Trial: A Review of Internal Documents Annals of Internal Medicine, 149 (4), 251-258 (Link)

Comments

  1. #1 William Wallace
    August 20, 2008

    Science-based medicine relies on medical evidence.
    You keep saying this (and it sounds like a tautology), but you have failed to address the FDA’s admonition to not use ultrasound for keepsake videos, while, at the same time, you’ve chastised MDs who have warned about possible dangers in overuse of cell phones.

    Although there is no evidence that these physical effects can harm the fetus, public health experts, clinicians and industry agree that casual exposure to ultrasound, especially during pregnancy, should be avoided.–FDA

  2. #2 William Wallace
    August 20, 2008

    While looking for news articles on relatively recent study that purportedly showed humans have a common ancestor dating to the time of the flood (with no allegations that the researchers were young Earth creationists), I found this

    Blacks, whites and Asians have different ape ancestors – and did not come from Africa, claims scientist

    A public claim by a fellow of the prestigious Royal Geographic Society that humans did not all come from Africa — and that blacks, whites and Asians have different ape ancestors — has been dismissed by world experts as “dangerous”, “wrong” and “racist”.

    In a paper widely trumpeted and due for release in book form, Akhil Bakshi, the leader of a major 2006 scientific expedition supported by India’s prime minister, claims that “Negroid”, “Caucasian” and “Mongoloid” peoples are not only separate races but separate species, having evolved on different continents.

    Unfortunately, I never found the articles on the genetic study initially referenced above, but oh well. The article I did find illustrates clearly that scientists are not guided only by evidence, but are also guided by politically correct ideology.
    Whether or not humans descended from different apes (and clearly, I do not think they did) is not important. What is interesting is the reactions, and the reasons for these reactions.

  3. #3 Steve
    August 20, 2008

    Jesus Fucking Christ! I can’t put into words how infuriating this is.

  4. #4 William Wallace
    August 20, 2008

    comment-1060721 was not intended for this blog entry, but for Helpful hints for Creationist Cults–not sure what happened. My apologies–please delete it.

  5. #5 Francois
    August 20, 2008

    “clinicians and industry agree that casual exposure to ultrasound, especially during pregnancy, should be avoided.”

    The key word here is CASUAL. “keepsake videos” are thus made ONLY during the context of pertinent and justified prenatal care visits. They SHOULDN’T be the purpose of the visit.

    Nothing mysterious there. PalMD has not failed to address anything. You just failed to read the FDA statement correctly, an especially ingrained habit of yours.

  6. #6 Francois
    August 20, 2008

    “Whether or not humans descended from different apes (and clearly, I do not think they did)”

    Everybody knows that extra-terrestrial beings seeded Planet Earth 54,792 years ago. The apes come from a different, albeit very similar genotype.

    There is speculation as to why these beings did such a thing. A somewhat reasonable hypothesis posit that God ordered them to do so.

    C’mon William! Tell us something new for a change.

  7. #7 bi -- IJI
    August 20, 2008

    Regarding “seeding trials”:

    I find it particularly interesting that the Merck folks are using the word “trial” to denote both clinical trials and market research.

    Reminds me of how climate inactivist Tom Harris used the phrase “information sharing” to denote wholesale propagation of talking points (I blogged about this), and then later switched to a more benign sense of the phrase — exchanging intelligence about climate regulation proposals etc.

    Natural language is a wonderful thing. :)

    – bi, International Journal of Inactivism

  8. #8 Bill
    August 20, 2008

    “Until two days ago, I’d never heard of a “seeding trial”.”

    Seriously? That surprises me. Let me preface this with the disclaimer, I am not a doctor. I own an assisted living facility.

    I received a telephone call a couple of years ago from a Dr. ______ that wanted to stop by and tell me about a fantastic new study regarding an Alzheimer’s medication. It could be a huge step forward in the treatment of dementia. I agreed for the doctor to stop by the next week. Over lunch, he spelled out the terms of what he was offering. My ACLF residents that had a diagnosis of Alzheimer’s type dementia would be given the opportunity to participate in the study of a new medication that was showing great promise.

    To make a long story short, I took a second look at this gentleman’s business card. His name didn’t end with an MD. It ended with PhD. Turns out he works as a third party putting together these studies for an MD that was conducting a study for the marketing department of XYZ pharmaceuticals. This MD would review information collected by Mr. PhD and prescribe my residents medication based on that information without ever having seen the patients.

    I paid for my own lunch and thanked him for his time.

  9. #9 William Wallace
    August 21, 2008

    Francois,

    Before you break your arm patting yourself on your back, please note that cell phones are most often used in a casual (non-necessary) manner.

  10. #10 LanceR
    August 21, 2008

    Yes, cell phones are used in a “casual manner”. You also receive more RF radiation driving past a radio station transmitter than you do using your cell phone. Also, RF radiation is non-ionizing. That’s a concept you should look up. Radio frequency radiation is completely harmless at doses lower than what you would pick up sitting in front of a large transmitter every day all day.

    Learn something before you open your mouth. It might make you appear less stupid.

    “Light travels faster than sound. This is why some people appear bright until they speak.”

  11. #11 mandrake
    August 21, 2008

    William:
    there is a difference between a developing fetus and a full-grown human. It is well known that many, many things that can effect a fetus will not negatively effect a full grown human (or even a child) at all.

  12. #12 William Wallace
    August 21, 2008

    LanceR,

    Also, RF radiation is non-ionizing.

    Neither are ultrasonic waves, so you haven’t actually made a valid point. But, since you’re so obviously and arrogantly ignorant, why not look up “dielectric heating”, and “thermal hypothesis”.

    mandrake,

    I agree. I think that is one of the points of the good MD who warned against cell phone use, especially by minors. It’s prudent.

    But PalMD is against prudence when it comes to cell phones, and silent so far on the unscientific prudence of the FDA when it comes to ultrasound.

    In my case, I think both warrant caution.

    In PalMD’s case, he seems to think that cell phone use should be presumed safe unless scientifically proved dangerous, but is silent when the FDA cautions against unnecessary exposure to ultrasound waves.

    It is that kind of thinking (presumed safe in the absense of scientific evidence) that led to xray facial hair removal machines in the 20s or 30s, and xray machines at shoe stores.

  13. #13 LanceR
    August 21, 2008

    Another “I know you are, but what am I” gambit!! Amazing!

    Dielectric heating. Being too close to a STRONG source of radio waves can cause burns, in exactly the way that a microwave oven heats food. Hence my point when I said you would have to sit too close to a powerful transmitter. The RF from a cell phone is almost nonexistent when discussing heating effects. If you had any clue what you are talking about, you would know this. The FDA has cautioned doctors about unnecessary ultrasounds because there has been some evidence of harm to the extremely fragile fetus when exposed to excessive ultrasound.

    To wrap up the idiocy completely, can you tell us the main difference between RF and ultrasound?

    PalMD did not suggest that cell phones “should be presumed safe unless scientifically proved dangerous”. Cell phone usage *is* safe, at least with regard to RF energy. Driving off the road while chatting is still possible.

    Get a clue, Wally.

  14. #14 MarkH
    August 21, 2008

    We have almost a century of experience with RF radiation at non-ionizing frequencies. Yes, some frequencies are dangerous because they cause vibrational excitation of water molecules like those used in microwave ovens. But hints to negative effects of such waves include that burning painful sensation of your skin being cooked – surely our intelligent designers prepared us well for such challenges.

    RF is safe until proven otherwise. Bombarding a fetus with high-powered sound waves? Also probably safe. But we are reasonably cautions because if anything is going to be harmed by such an intervention, it will be a fetus.

    Comparing the two? Pure idiocy. RF is safe, get over it. It’s not just the two decades of cell-phone use but the near-century of RF communication use in dozens of different capacities all over the world. Even if the “dangers” described are real it’s an insignificant increase in risk compared to other daily activities we find perfectly acceptable. If your risk of a benign acoustic neuroma went from 0.0001 to 0.0002, big freaking deal (if it’s even real). This compared to the 3000 fold increase in risk in lung cancer with exposure to cigarettes over a lifetime and we see what a real environmental hazard is.

    Please ignore the thread hijack from the luddite troll.

  15. #15 William Wallace
    August 22, 2008

    A luddite? Note that I am using a computer and probably knows more about EM fields and radiation than most of you, given my education and career.

    Another clue for PalMD’s clueless wonder boy: heat doesn’t need to burn to be dangerous (consider a high grade fever).

    For anybody that cares more about science than name calling (obviously not MarkH and LanceR) you might want to take a look at, for example, Evidence for Stress Response (Stress Proteins).

  16. #16 minimalist
    August 22, 2008

    Willy Wally:

    Unfortunately, I never found the articles on the genetic study initially referenced above, but oh well. The article I did find illustrates clearly that scientists are not guided only by evidence, but are also guided by politically correct ideology.

    So you don’t know what his evidence even is, but you’re certain that the mainstream scientists’ reaction to it is “politically correct ideology.” Could you stop to consider for a second that these are your own prejudices at work?

    Consider, for example, your presumption that Bakshi’s work is “genetic”, though there is zero indication for that in the Times article. In fact, here is his “paper” in toto:

    http://film-india.com/expdtn/Paper%20on%20Continental%20Drift.htm

    Start to finish, it’s built solely on the author’s own ignorance of the present evidence, and chock full of erroneous assumptions (“Why would hominid populations bother to migrate?” he asks, as though environments never change). In fact, the sole nod to genetics is to deny all the genetic evidence in the second to last paragraph! “BAH!”, he snorts with a wave of his hand, “Scientists have been wrong before!”

    It’s shoddy crankwork, and presents zero original scholarship (no references) or research.

    (Yes, yes, feeding an incredibly dumb troll incapable of logic, but the ape in me just can’t resist swatting at the low-hanging fruit.)

  17. #17 William Wallace
    August 23, 2008

    Yawn.

  18. #18 Lab Lemming
    August 24, 2008

    Couldn’t doctors participating in these surveys tell by the protocol that they are dodgy? If in fact they are?

  19. #19 minimalist
    August 24, 2008

    Yawn.

    Nothing makes Wally’s mind shut down faster than the risk that he might actually have to use it. For something other than spinning elaborate conspiracies of “genetic studies” and “politically correct” atheist conspiracies out of a single, ambiguously-written news piece, that is.

    Why, I can’t possibly imagine why nobody tries to engage him in serious conversation anymore.

  20. #20 William Wallace
    August 25, 2008

    minimalist….keep typing…

    You do more for your cause than you know.

    I posted a link to a paper with scientific conclusion backing up my point of view, but you all just name call.

    Scienceblogs should be ashamed.

  21. #21 PalMD
    August 25, 2008

    pourquoi?

  22. #22 minimalist
    August 25, 2008

    Yep, just as I thought, Wally didn’t comprehend a single word I said.

    If Denialism has any reason to be ashamed, it should be for not banning your useless butt, the way Pharyngula, Panda’s Thumb, and who knows how many others have.

  23. #23 William Wallace
    August 25, 2008

    Keep typing minimalist. You’re a classic denier.

  24. #24 minimalist
    August 25, 2008

    More terms to throw on top of the Big Pile of Words Wally Doesn’t Understand:

    “paper”
    “scientific”
    “news article”
    “denier”/”denailist” (sic)

  25. #25 LanceR
    August 25, 2008

    Reading for Comprehension? You’re doing it wrong. Re-read the paper you linked to, Limp Wally. Then look up RF and ELF. Learn to read, you great blathering git.

    Stop beating your wife yet?

  26. #26 Dan
    October 3, 2008

    The Human Injury of Lost Objectivity

    If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials would be at the top of the list. Pharmaceutical companies manipulate the trials they sponsor because of their power to control others involved in the process largely absent of regulation. This is a matter of requiring authenticity and, more importantly, assuring the safety of the public health.

    Decades ago, clin ical trials were conducted in academic settings that focused on the acquisition of knowledge and the completely objective discovery of novel medicine. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit sites, called Contract Research Organizations (CROs), which are composed of community research sites with questionable investigators void of necessary experience or quality regarding their research purpose and ability. Since they are for-profit, the trials conducted at CROs are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor’s medication. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit the collusive relationship between the site and the sponsor.

    Further disturbing is that once the trials are completed, the medical articles are then written by ghostwriters, who are not identified and acknowledged by the sponsor, and are not trained in clinical research overall, as they are simply freelance writers. How often ghostwriters are utilized by pharmaceutical companies remains a mystery. This activity removes accountability and authenticity of the fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor.

    To have the trial published, the sponsor pays a journal, along with the promise of purchasing thousands of reprints of the study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the industry. So benefits of medicine studied in such a malicious way can potentially harm patients and their treatment options. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers — your doctor.

    Such misconduct impedes research and the scientific method with frightening ethical and harmful concerns. Our health care treatment with medications is now undetermined in large part in such situations, as well as the objectivity that has been intentionally eliminated regarding the trust in the scientific method in this type of activity illustrated in this article. More now than ever, meds that are removed from the market are given black box warnings. Now I understand why this is occurring.

    The pharmaceutical industry needs transparency and disclosure in order to correct what we have historically relied upon for conclusive proof — the scientific method. More importantly, research should not be conducted in a manner that the sponsor can interfere in the ways I described in this article. We should call for independent sites with absolutely no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health. Knowledge is power, and is also possibly a lifesaver.

    Ethics and Science need to shake hands.
    – Richard Cabot

    Dan Abshear (published on: http://www.brainblogger.com)

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