Saturday, April 5, 2008

More Deja Vu, and Genetic Tests for Fun and Profit

In the previous post, I mentioned Morton Mintz's 1965 book, The Therapeutic Nightmare. In the process of exposing how many drugs were then being heavily marketed, with little or no evidence of providing any patient benefit, Mintz stopped for a minute to describe the questionable role of the AMA.

In the early 1960s, Sen. Estes Kefauver (D-TN) was holding hearings and trying to push through legislation to strengthen the FDA's hand, demanding proof of both efficacy and safety before a new drug could be released to the market. Eventually this legislation became a slam-dunk because of the thalidomide disaster; but before that event, the legislation looked to be going nowhere. The Kennedy White House was lukewarm at best on the subject, and the FDA itself saw no reason why it should drop its comfy pro-industry posture.

In the middle of all this the AMA, with a delegation of its biggest bigshots, arrived in town to tell Congress that it opposed giving the FDA any new powers over drugs. The position argued by the bigs was: the only person who can decide what drug to use for which patient is the physician at the bedside. The physician knows what drug to prescribe because of his experience with this and similar patients in his practice. The physician might or might not, as he sees fit, take into account large-scale scientific trials of drug actions. But it was absolutely essential that the physician's prescribing liberty not be limited by having the Federal government play a role in deciding what drugs should or should not be on the market. If the individual physician, in his infinite wisdom, decides to prescribe arsenic for Mrs. Jones, then no government agency should be standing in his way by saying that arsenic is too dangerous or too ineffective to be sold.

The AMA was led to take this extreme position because it was caught in its own rhetorical trap, having been so strongly opposed for so long to anything that even vaguely looked like "socialized medicine," which translated into any government involvement in any aspect of medicine whatsoever (the AMA was then gearing up for its big fight against Medicare). In condemning more powers for the FDA, and demanding proof of efficacy for new drugs, the AMA leadership was turning its back on the advice of its own, highly respected Council on Drugs (which was being phased out in any event because it was increasingly an impediment to the AMA's getting maximum bucks from the industry for ads in its journals).

Fast forward now to the present day (thanks to Dr. Barney Carroll of the Pacific Behavioral Research Foundation for this tip). A company called Genelex (according to its website of the same name, a privately held corporation in Washington State) is busy marketing its gene test for CYP450, and recently (April 3) issued a statement disputing a comment made in Science. The statement made by Genelex, which they accuse Science of misquoting, is: Paxil (paroxetine) is metabolized through CYP2D6. Pharmacogenetic testing of this pathway serves as an anchor for the intense personalization required to effectively prescribe Paxil and other antidepressant medicines.

Genelex then states its position: Individuals have a right to learn their genotype and control who accesses this confidential information. Excessive regulation will impede the already slow adoption of DNA testing in medical management.... Randomized trials are in progress that will add to our knowledge. In the meantime clinicians and patients who find this information [gene testing] useful should have access to it. Physicians don't prescribe without knowing the patient's age, sex, and medical history, and often CYP genetics are more important than all these factors combined.

So, what have we here? Apparently a return to the AMA's position in the early 1960s, in which individual freedom is elevated to sacrosanct status as a medical goal. These randomized trials that are here described as sort of optional, by-the-way factors might show physicians, first, whether the genetic testing actually works to improve real patient outcomes; and second, exactly how to use the results of the gene tests in a practical clinical protocol so as to adjust the dosages (or whatever) of antidepressants. Idiots, Genelex imagines, might want to sit on their hands and wait for the results of those trials. But obviously, smart doctors are not going to want to sit on their hands; they will want to know right away. So if any government agency, like the FDA, sticks its nose in and demands proof that this technology really provides any patient benefit, they should be slapped down because they are interfering with the physicians' and patients' God-given rights. And meanwhile, one imagines, Genelex goes to the bank with the proceeds.

Let's step back and see what has happened with the use of the newer (serotonin-reuptake-inhibitor and mixed type) antidepressants. First, the industry sold physicians on these drugs by saying that they were as effective as the old tricyclic antidepressants, but had many fewer side effects. It took us many years to find out that the reasons these drugs had so few side effects is that the industry either looked the other way deliberately, when conducting drug trials, so as not to observe or measure any side effects; or when studies showed side effects despite their best efforts, simply not to publish the studies. (Along with suppressing all the studies that showed the notable lack of effeciveness of these drugs.) Now, at long last, the word has leaked out. For example, after years of denial that there is any withdrawal syndrome associated with Paxil, most physicians have figured out that it can be a real deterrent to the use of that drug.

So now the commercial marketing message seems to be--okay, so we admit that these drugs have more problems than we let on. But the answer is in our genes. All we need to do is do genetic tests and we'll know how each individual patient metabolizes these drugs, allowing us to "personalize" our treatment and eliminate all those nasty side effects. (Of course, if we truly believed in "personalized" treatment, we might take the time to sit down with Mrs. Jones and talk with her about why she feels depressed and what she's doing about it. But that cannot be allowed, as it might demonstrate that most cases of mild to moderate depression actually respond well to psychotherapy and don't need drugs at all. And that would be terrible for the bottom line, wouldn't it?) And while we are at it, not only will we sell you all these expensive drugs, but we'll also sell you these expensive gene tests. So don't get in the way of our business plan by grousing that these gene tests are actually quite experimental and we haven't the foggiest idea what the results really mean for patient care.

1 comment:

Bernard Carroll said...

Dr. Brody, your reprise of the AMA position in the 1960s is right on. One of the comments made in the statement from Genelex is "Putting what we know into practice would prevent more disease than worshiping at the altar of randomized trials." John Concato, MD, Yale University."

That is a standard rhetorical technique called proof surrogate: suggesting that there is evidence or authority for a claim without actually citing such evidence or authority.

It is time for the truly responsible professional societies to develop position statements on these newly marketed genetic tests, now that the genie seems to be out of the bottle. Genelex charges $250-$1400 for its "extended drug reaction panel." Dr. John Kelsoe at UC San Diego has a company called Psynomics that charges $399-$750 for allegedly "diagnostic" gene tests for bipolar disorder and predictive tests for drug responsiveness.

To say that the evidence is thin for any of these claims would be charitable.

Bernard Carroll.