Wednesday, February 04, 2009

Taking Trust With a Grain of Sodium

I was rather intrigued when a drug company representative showed up at my institution with some literature on a medication called Vaprisol manufactured by Astellas Pharma. This drug is one of a class of drugs called vasopressin receptor antagonists (VRA's) and is used to treat low blood sodium levels (also called hyponatremia).

I may be the worst philistine in academia but to me, Vaprisol is a so-so solution in search of a problem. Hyponatremia is typically treated by first identifying its underlying cause. Once that cause is determined, treating it generally makes the hyponatremia go away or at least improve. And guess what? Even if the problem can't be cured, the chronically low sodium that results rarely causes serious problems by itself.

That said, I can imagine rare scenarios whereby drugs such as Vaprisol may be useful. Obviously, attempting to be helpful, the rep left a reprint of a paper from the reputable American Journal of Medicine. It summarized some expert panel recommendations regarding the diagnosis and treatment of this condition.

I was surprised however to find that of the articles eight pages of text regarding the actual treatment of hyponatremia, half were devoted to VRA's. This may have been appropriate for a review of developments in the field but this was ostensibly a guideline for current management practice.

I encounter hyponatremia frequently but I've never seen nor known of a physician using this drug or any drugs in its class. I hardly think that the use of VRA's is generally accepted by the medical community. Which brings me to the title of my reportage. Are the recommendations of this guideline really trustworthy? Curious, I immediately flipped through the reprint to find the authors' financial relationships disclosure which had been dutifully reported.

I wasn't the least bit surprised that of the five authors, all five had financial ties to one or more of the companies selling VRA's:
Joseph G. Verbalis, MD, has served as a consultant and member of advisory boards and Speakers’ Bureau for Astellas Pharma US, Inc.; as a consultant and member of advisory boards for sanofi-aventis, and as a consultant to Otsuka.

Stephen R. Goldsmith, MD, has served as a consultant and member of advisory boards for Astellas Pharma US, Inc.

Arthur Greenberg, MD, has served as a member of advisory boards and Speakers’ Bureau for Astellas Pharma US, Inc., and as a consultant to sanofi-aventis.

Robert W. Schrier, MD, has served as a consultant to Otsuka.

Richard H. Sterns, MD, has served as a member of advisory boards and Speakers’ Bureau for Astellas Pharma US, Inc.
Now don't get me wrong. I myself haven't done an exhaustive search of the literature to determine whether or not these drugs are in fact any good. For all I know, they're magic bullets that should be put in the water supply to treat and prevent all current and future cases of hyponatremia.

But that's not my point. The problem is that even before checking out this particular drug's usefulness, I'm already starting from a position of mistrust. With such an undeniable "appearance of impropriety" how can I truly rely on these experts to give me the unvarnished truth? It's one thing to report hard facts. It's something entirely different to render an opinion which is what a guideline is.

Surveys of physicians have shown that most believe that the clinical judgment of other physicians can be influenced by financial encumbrances. However, those same doctors also believe that they themselves wouldn't be. What does this tell us?

Should any of us in medicine have unerring faith in the fairness and objectivity of our profession's opinion leaders and can we as patients trust that our doctors have access to the best information available? Perhaps we all need to read Dr. Daniel Carlat's 2007 New York Times article on his transformation from honest clinician to drug company shill (and back again).

It seems to me that we're getting to the point where we have to get away from the very concept of having clinical guidelines (not to mention FDA Advisory Committee reports) formulated by opinion leaders altogether. It may be far better to simply convene skilled but generic clinicians, epidemiologists, and statisticians with no ties to the pharmaceutical industry to create recommendations based only on a nonbiased, critical reading of the existing medical literature.

As drug reps are being increasingly isolated from prescribing physicians due to practice group and academic institution policies, pharmaceutical companies are shifting more of their advertising budgets towards cultivating (financial) relationships with academia's clinical gurus. No one can deny the moral hazard associated with this trend.

Understand that I am not impugning the integrity of the authors of the above-mentioned guideline but truthfully, I have no a priori reason to trust them either.

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