Bioethics @ TIU

The return of Carter’s Little Liver Pills?

Posted February 8th, 2013 by Joe Gibes

 

In 1868, a fellow named Carter formulated a patent medicine and named it after himself, the famous “Carter’s Little Liver Pills.”  It turned out, amazingly, that there were few human ailments these wonderful pills could not cure: sick headaches, biliousness, torpid liver, constipation and indigestion, sluggishness . . . the list went on and on. Truly Mr. Carter was a boon to humanity.

Except that, of course, the pills did little of what was claimed. They turned out to be pretty good laxatives; everything else was advertising hype. In 1959 the Federal Trade Commission (FTC) made the company drop the word “liver” from its name, considering it false and misleading advertising.

Today the Food and Drug Administration (FDA) does most of what the FTC did for Mr. Carter’s pills. It is apparently fairly easy to design a scientific-appearing study that will prove just about anything you want it to; as my father used to say, “Figures don’t lie, but liars figure.” Poorly-designed but impressive-sounding pseudo-scientific studies have been used to foist countless frauds on a public (and medical profession) that in general does not have the sophistication to tell a well-designed study from a sham (for an example, see the now thoroughly-discredited Wakefield study that purported to show a connection between the MMR vaccine and autism — and all the people, including medical professionals, that were taken in by it). Among other functions, the FDA strives to ensure that prescription drugs are supported by reliable studies showing that a medication’s benefits outweigh its risks for its intended purposes. Drug companies are not allowed to promote their wares for “off-label” indications, that is, maladies for which there is not good evidence that the drug in question does any more than a good sugar pill would.

But this consumer-protection function of the FDA is under attack. The February 6th JAMA relates the story of a drug company and its salesman who promoted their medication for numerous off-label uses, even claiming it was safe in elderly and pediatric patients, despite the label warning specifically stating that safety was not shown in those populations. They were investigated by the Department of Justice; the drug company pleaded guilty, the salesman didn’t and was convicted. He appealed his conviction on the basis of his FIrst Amendment right to free speech. The appeals court sided with the salesman.

This case will be appealed further, so there’s no telling how it will ultimately turn out. But it is conceivable, based on this verdict, that drug companies could start making marketing claims based on pseudo-scientific sleight-of-hand that physicians and their patients might have a hard time seeing through, all in the holy name of Free Speech.

But free speech used to make false claims about potentially dangerous substances should not be protected.  Nobody likes government regulation; but when dealing with medications with a great potential for harm as well as good, I would rather trust government-employed scientists charged with protecting the common weal than a bunch of slick salesmen charged with maximizing their companies’ profits.

9 Responses

  1. Cecile Soucie says:

    i wish i knew the original ingredients in the dodds liver pills as my mother took them in the 40’s and helped her tremendously she has phlebitis and sure this could be from colon problems but cleared the headaches and everything that was ailing her
    why do science has to tamper with something good
    they cant take that someone can do better

  2. Louise Hall says:

    Question: Is the current and available now ” Carter’s Little Pills” the same formula as the Old Carter’s Little Pills or did they change it???? We used this with the herding dogs to rid them of hair balls obstructing the bowels. It worked every time without harming the dogs. Hoping it is the exact formula.

  3. Joy Mills says:

    Are they out now, If so where can I find them .

    My mother and hers as well as my self,Believed in those little pills and they honstly helped with many symptoms we were having.we have wished several times that they were still around

    thank you, JOY

    • Joe says:

      Did you ever find your Carters pills? Can I ask what you use to take them for and other than as a laxative what ailments did they cure or help?

  4. Jon Holmlund says:

    As someone who has spent a career in oncology drug development in and around biotech/pharma, I would like to make some comments as someone who is biased: I do not believe that we are ALL purely evil. I’ll start with some comments that may be a bit more aligned with Dr. Gibes’ position then expand a bit.

    First, to be sure, FDA closely regulates the promotion of drugs–through the Office of Prescription Drug Promotion (OPDP), formely and famously known as “DDMAC” (the Division of Drug Marketing, Advertising, and Communications). To be honest, I am not a regulatory affairs professional who keeps the details of the relevant regulations at his fingertips, but I do believe that the regulations are detailed (including, for example, font size in print advertising).

    Second, as a clinical drug developer, I have tended to carry a certain antipathy toward the marketers, because, to be sure, there is no shortage of “clinical trials” that really are attempts to support marketing. Just to say it.

    Third, the relationship between industry and ODPD/DDMAC can be contentious–stories abound of some companies’ marketing executives believing that if they are not getting warning letters from this part of FDA, they are not pushing the envelope enough. Not a position I am sympathetic with.

    Fourth, the regulation is needed–there are clear and egregious examples of abuse. (I tried to include a link to my personal favorite, but I got a “spammy” message to I deleted it.)

    But that said:

    I don’t think I agree that ALL marketing is hype. It seems to me that legitimate, true claims for a product’s merit–including a drug’s–constitute acceptable marketing.

    In the case cited, United States vs Caronia, the brief JAMA discussion states that clearly false statements were made by the defendant. How far these may be protected as “free speech” is a matter of law that I won’t try to address in detail, but it seems to me that we do rightly regard fraudulent claims as punishable, so I agree that we should worry about the court decision as described.

    A longer discussion of this case appeared in the New England Journal of Medicine and is available for free online: http://www.nejm.org/doi/full/10.1056/NEJMp1214926 It raises the question whether FDA’s regulation of off-label marketing extends to “data mining” by pharmaceutical companies. I guess that remains to be determined.

    While FDA regulates (prohibits) the off-label promotion of drugs, it does not regulate the off-label USE of drugs by physicians. That means that doctors are exploring these all the time. In fact, much medically accepted drug therapy is in fact off-label–particularly in oncology. (That means, Dr. Gibes, that I disagree with your blanket characterization of an “off-label” use as a “malad[y] for which there is not good evidence that the drug in question would do any more good than a sugar pill would.”) Public and private payors decide whether to cover that use by looking at what is in the medical literature–involving a complex decision about what is “scienfically” valid and what is not. (Think about Avastin for breast cancer for one example. I think it’s still paid for–even though the label claim was withdrawn, and, IMHO, it doesn’t work for that indication.)

    FDA in fact takes pains to be sure that this off-label activity is physician-driven, not unduly influenced by industry. I suppose we can debate industry involvement in clinical trials designed to support a “compendial strategy” for reimbursement. And I suppose we can debate how effective FDA’s efforts are–but see for example FDA’s final guidance on industry support for scientific or educational conferences (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070072.pdf) and its draft guidance on how industry should handle requests for off-label information from individuals, websites, etc.: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM285145.pdf). This is a complex area, and people can and do differ about the dissemination of off-label information, but I submit we might do well to define our science and psuedo-science, the sources of its generation and interpretation, and the actions taken on it, carefully.

    For my part, I get steamed at the claims for things like nutritional supplements, which are less heavily regulated (as in, “these statements have not been evaluated by the Food and Drug Administration,” etc, etc).

    At this point, I will leave it to the practicing physicians to confirm what steps they take to protect themselves from being flummoxed by slick salesmen selling pseudo-scientific claims that they, the physicians, have a hard time seeing through. IMHO, again, there is little excuse for a physician claiming not to be able to “see through” bad data. The public–that’s another matter. I believe that many physicians simply refuse to see detail people (a good call, I think). But I submit if you are a doc using a drug off-label for your patient, you better know the data.

    I’ve gone on enough.

    • Joe Gibes says:

      Jon,
      Thanks for clarification of my generalizations. Yes, not ALL marketing is hype, but much of it uses hype even for the legitimate uses you point out. Also, thanks for the clarification re. the difference between a drug company promoting the off-label use of a drug vs. a physician using a drug off-label. I agree wholeheartedly and then some with your disgust at the claims made for nutritional supplements. I will disagree, however, with your point about physicians understanding bad data. I sometimes take part in weekly meetings with physician faculty at a major research university who have been trained in statistics and epidemiology and research methods, reviewing studies for validity, applicability, etc. The vigorous discussion and disagreement by people who know a lot more about this than I, the subtle but important points that turn out to be hidden in the table on page 857, the nuances of a of a non-inferiority study, a 1-sided alpha level, a Pearson correlation, and a whole lot of other statistical minutiae that ain’t in the abstract (which is where I am afraid many doctors, myself included, start and end when reading mounds of journals), all lead me to conclude that it takes a lot of time and specialized sophistication to understand and evaluate data — time and sophistication that docs like myself just don’t have in large amounts. That isn’t to say that one shouldn’t try to understand it, especially when using drugs for off-label indications. But the enormous complexity makes it easy to make bad data look good, and thus the necessity for folks trained in statistical and research methods to separate the wheat from the chaff, and the need to prevent salespeople from dressing up chaff to look like wheat.

      • Jon Holmlund says:

        Both rejoinders are well put. Specifically regarding the second one, about statistics used in the service of obfuscation, one can only plead sympathy. I guess different clinical specialties have different levels of familiarity with the common statistical issues involved; oncologists live with these off-label discussions as a matter of course, while they might be rather less prominent in the life of other specialists. Then again, when there is big controversy about the data, then one has to decide just how clear the results must be to convince one to adopt something as acceptable practice. Even then, the controversies can be thorny.

  5. Susan Haack says:

    Two comments come to mind:
    First, “What is truth?”
    Second, concerning your comment that drug companies could start marketing based on pseudo-scientific claims, it is already happening, if not explicitly, by implication and inuendo. That is the very nature of marketing.

    • Joe Gibes says:

      Susan,

      To your first comment: I don’t think of scientific studies, whether of drug efficacy or anything else in medicine, as providing “truth;” rather, they merely quantify our uncertainty. To your second comment: Yes, marketing is always hype, and hype is lies. But I think that if there are not some controls on the quality of data upon which drug companies can base their claims, the danger to patients from unscrupulous marketing will increase exponentially.

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