Terra Sigillata

$29 billion/year industry thrives despite negative clinical trial outcomes

Posted by Abel Pharmboy on October 25, 2006
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Frequent commenter, anjou, just sent along a link to a MSNBC article by Robert Bazell entitled, “Ignoring the failures of alternative medicine.” The article is subtitled, “The U.S. spends millions testing popular supplements. It’s a futile effort.”

Bazell is chief science and health correspondent for MSNBC. Most striking about Bazell’s article is that the mainstream media has generally remained quiet on criticizing the alternative medicine industry. In contrast, the scientific community has long questioned both the legitimacy of NIH’s alternative medicine-focused center, NCCAM, and their priorities. Bazell’s article represents the first clear critique of these efforts that I have seen in the higher-profile lay press.

His arguments are based on two key theses:

1. US consumers continue to buy supplements despite the repeated lack of efficacy of a great many in clinical trials

2. Medical and media “personalities” are complicit in the propagation of this industry.

I’ve argued in the past that the rush to prove efficacy of dietary supplements in NIH-funded studies often lead to oversights on the quality of the product being used. This would be tantamount to a drug company embarking on a large, Phase 3 clinical trial before doing careful Phase 1 pharmacokinetic studies – a formula for disaster and a waste of money. By setting up trials for failure, one can equally question whether the supplement in question doesn’t work, whether the supplement tested even contained adequate amounts of a bioactive substance, or whether it was simply not dosed at a high enough level. This poor clinical trial design hurts all researchers who are conducting legitimate research on the potential efficacy of naturally-derived substances.

Bazell also takes to task some high-profile alternative medicine advocates with direct financial interests in the products they hawk. This issue was nicely discussed in the Jan/Feb 2006 issue of Nutrition Action Healthletter in an article entitled, “Supplementing Their Income: How Celebrities Turn Trust Into Cash — What You Should Know Before Handing Your Credit Card to Larry King, Dr. Phil or Dr. Andrew Weil” (513KB PDF)”

Bazell follows with a similar argument:

Marketers often sell them under the guise of a mom-and-pop alternative to big pharma. Yet the $29 billion-a-year dietary supplement industry wields such power that it got Congress to pass a law in 1994 that basically frees it to peddle almost anything that doesn’t kill people with claims of medical benefit that need not be proven.

No doubt some of the thousands of products sold as dietary supplements work well, but the industry that sells them has neither motivation nor desire to know which ones work and which don’t.

Neither do many of those who advocate their use, such as the guru of alternative medicine Dr. Andrew Weil.

In the end, all remedies with adequate preliminary data suggestive of their efficacy should be prioritizied and tested fairly and equally, all within the constraints of the current NIH budget. A burden for testing should also fall on this $29 billion industry. But having two sets of rules for drug products and supplement products seems to fuel an industry that appeals partly to mistrust and ideas of government or industrial conspiracy.

I am reminded of an excellent quote from an article co-authored by former editor of New England Journal of Medicine, Dr Marcia Angell, by no means a “pharma-shill” as judged by the content of her book, “The Truth About the Drug Companies”:

“There cannot be two kinds of medicine – conventional and alternative. There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work. Once a treatment has been tested rigorously, it no longer matters whether it was considered alternative at the outset. If it is found to be reasonably safe and effective, it will be accepted.”
– Angell M, Kassirer JP, Alternative medicine–the risks of untested and unregulated remedies. N Engl J Med 1998;339:839

Note added in proof: Prof Tara Smith has a post up today at Aetiology on this very article, covering some points I missed as well as a more extensive comment thread

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Comments

  1. #1 quitter
    October 25, 2006

    NCCAM isn’t so bad. Yeah, they publish a bunch of negative data, but it’s not a waste of money. People are taking these altie remedies and even negative results will give docs information that’s useful and relevant for patient care.

    Besides, it could be a lot worse. Basically NCCAM was started because Dan Burton is obsessed with altie remedies (and also believes vaccines cause autism, sigh). The money was thrown at NIH to set up this agency, and they put serious scientists at work studying altie treatments. We should be thankful, if they had decided to put a altie-advocate/quack in charge the results could be very different.

    In the first years of NCCAM the leadership of the agency found out something unfortunate, if they came out and aggressively criticized an altie treatment they would be viciously attacked by altie-advocates, and their hero Dan “Clinton is a scumbag” Burton. After all, these scientists are essentially attacking the religion of a fairly large subset of Americans. Subsequently they learned to take a “just the facts” approach. This may be unsatisfactory to scientists but that doesn’t change the reality on the ground. The money will get spent because of its advocates in congress. The research will be negative but negative data, if collected correctly, can still be very interesting and useful for medical practitioners. Finally, we should be very thankful that the agency is being run by serious scientists who care about finding the truth about these drugs.

    So, don’t worry that the agency doesn’t change altie minds. That’s impossible, they simply don’t believe in science. But it is good to have a record for real scientists and doctors about various altie treatments, their efficacy, their side-effects, typical dosages, pharmacology etc., because people will use them no matter what.

  2. #2 Joe
    October 25, 2006

    AbelPharmBoy

    “[You]‘ve argued in the past that the rush to prove efficacy of dietary supplements in NIH-funded studies often lead to oversights on the quality of the product being used.” But, then you posted this:
    “The best objective herbal medicine information for less than $100 per year”
    http://scienceblogs.com/terrasig/2006/07/the_best_objective_herbal_medi.php
    You (rhetorically) asked “”Where can I buy an herbal product that has shown efficacy in a placebo-controlled, randomized trial that has been published in a major peer-reviewed journal?” Let’s take the Ginkgo example above. … the product used was called EGb 761 … “

    Since the active ingredient (if there is one) is unknown, the specification (EGb 761) means nothing (unless it coincidentally includes the putative drug entity). So the accurate answer to your question is “I don’t know.” Quality control is impossible absent knowledge (not speculation, such as employed by Varro Tyler) of the active ingredient(s).

    Therefore, databases you advocate, including the “Natural Medicines Comprehensive Database” (NMCD) and the German commission, have little basis in fact. However, the NMCD is commended for listing unwanted ingredients (e.g., heavy metals).

    My point is, the whole field of “herbal medicine” overlooks “the quality of the product being used.” The focus needs to be identification of active ingredients.

    BTW- quitter,

    Although I hate to write anything seeming to favor Rep. Dan “The Loose Cannon” Burton (R, IN); Sen. Tom Harkin (D, IA) is probably more culpable for saddling us with the NCCAM.

  3. #3 quitter
    October 25, 2006

    I’m not surprised there’s more than one in there. The inside stories I hear from the NIH though are that Dan Burton is the bigger pain in their ass (and dumb as a brick).

  4. #4 Abel Pharmboy
    October 25, 2006

    quitter raises some very good points, namely, the one espoused by Bazell: no matter what science comes out of the best of these studies, true “believers” will continue to practice their consumerism as they might feel that they are among the few people who gain benefit from such remedies, regardless of whether the benefit is placebo or not.

    btw, quitter, happy first anniversary on your blog.

    Joe takes me to task on some of my previous recommendations of reference sources. My response is that I am doing the best in making fact-based recommendations driven by independent information sources. Unfortunately, these sources do not even come close to the standards of basic, translational, and clinical medicine that we associate with prescription pharmaceuticals. I also cannot speak for Purdue’s Dr Varro Tyler, who left this world over five years ago.

    The EGb761 discussion I have had before relates to a remedy that is indeed standardized for ginkgolide A, ginkgolide B, ginkgolide C, and bilobalide. Granted, even such products that exhibit clinical efficacy inone published study still suffer from the lack of oversight that subsequent products from the same manufacturer might not have the same chemical composition.

    I stand by my recommendation of the Natural Medicines Comprehensive Database – it is compiled and updated regularly by an excellent team led primarily by PharmDs who scour the domestic and international literature. To clarify Joe’s commment, I am not a fan of the German Kommission E reports since they have not been updated regularly and are poorly referenced, often relying on proprietary, manufacturer-supplied data.

    Finally, I would argue against the statement that, “the whole field of “herbal medicine” overlooks “the quality of the product being used.’” Most herbalists could give two rats’ behinds about the work I do, but I still I consider myself part of the herbal medicine community who does indeed subscribe to Joe’s goal: “The focus needs to be identification of active ingredients.” I couldn’t agree more.

    As for the politics, I am well aware of Burton’s role in the establishment of NCCAM and its predecessor, the NIH Office of Alternative Medicine (OAM). However, I am not clear as to what political pressure keeps it afloat. Interestingly, the NCCAM budget has been rather flat for the last three years.

  5. #5 Orac
    October 25, 2006

    Interestingly, the NCCAM budget has been rather flat for the last three years.

    That’s only because the NIH budget as a whole has been flat. Moreover, I note that the NCCAM budget more than doubled when it became NCCAM in 1998 and then more than doubled again between 1999 and 2003.

  6. #6 Joe
    October 26, 2006

    “Joe takes me to task on some of my previous recommendations of reference sources.”
    >I agree that those are the best sources, I simply find them inadequate as far as clinical results are concerned.

    “I also cannot speak for Purdue’s Dr Varro Tyler, who left this world over five years ago.”
    >Considering (the late) Tyler a leader in the field, I figured his speculation concerning “active ingredients” to be the state of the art. In most cases he would point to a compound that was characteristic of the plant and opine that it carried the activity attributed to the plant. This is unsupportable. For example, in the case of ginkgo, it does not matter if the products on standardized on certain components, unless they are proven to have the medicinal activity of the prep (if any).

    “To clarify Joe’s commment, I am not a fan of the German Kommission E reports …”
    >Sorry about that. In fact, your opinion on that is good to know.

    “Finally, I would argue against the statement that, “the whole field of “herbal medicine” overlooks “the quality of the product being used.’” …”
    >You are right, my words were overreaching. I was thinking only of the consumer side; where people buy ground-up shrubbery. For the thousands of products on the shelves, lack of control begins with lack of adequate clinical study and ends with lack of active-ingredient based quality control.

    “However, I am not clear as to what political pressure keeps it afloat.”
    >I suspect that the quack lobby is quite generous, and that there is a notion that NCCAM must have been established for a reason- so let it ride. Proponents get a lot out of the NCCAM- money and the appearance of legitimacy. Opponents don’t get anything for their work; in fact, their other professional work can suffer if they are active. So the push to shut down NCCAM has little effect.

  7. #7 Abel Pharmboy
    October 26, 2006

    Joe, thanks for the discussion – I think that The Haworth Press is struggling with how to revise Tyler’s books (although it looks like Dennis Awang will be involved with one) but I would expect them to be far heavier on chemistry and pharmacology than in the past. Part of the problem, but also part of the appeal, of Tyler’s The Honest Herbal and Herbs of Choice is that they are very approachable for the specialized lay reader. It is agreed that for technical folks like us, they are somewhat lacking, even with the excellent additions by co-author Steven Foster in the most recent editions.

    Opponents don’t get anything for their work; in fact, their other professional work can suffer if they are active.

    This raises a bigger point when something is found active: how do you market it without the patent protection of novel pharma molecules? Under DSHEA, it cannot be marketed for disease treatment or prevention lest you break federal law.

    From the research standpoint, the not-so-funny thing is that garnering research support from NCCAM has become even more competitive than from other NIH funding entities. So many people submit grant applications to NCCAM because they are considered “easy money” but the truth is the Centers covers so much ground with so little relative financial appropriation ($120-ish million pales in comparision to the overall $25-ish billion NIH budget) that it is difficult to compete for their funding. The funding of prematurely-supported clinical trials sucks up a lot of this funding and, as Orac points out, their budget has been just as flat as the rest of NIH’s.