Thursday, February 21, 2008

The FDA's New Rule on Off-Label Marketing--Bad Idea

Previously I have offered opinions on why "off label" is a widely misunderstood category, and is often wrongly vilified:

So that must mean that I am OK with the FDA's proposed rules change...

...that would allow companies to start marketing drugs off label if they:
  • Distribute to physicians only peer reviewed medical journal articles describing the proposed off label use
  • Accompany any such article with a clear statement that the use described is not FDA approved

Right? Well, not exactly.

The point I tried to make in my earlier post is that even though many off label uses of drugs are quite defensible and are in the patient's interest, we need to be very wary of any specific rules change in the companies' favor, given their past ability to drive huge trucks through even the tiniest regulatory cracks.

The defenses for the new FDA policy, as summarized by Gardiner Harris in the NY Times, basically all amount to the same thing-- if there's scientific evidence that a drug works even off label, isn't it a good thing that docs see this scientific evidence as soon as possible? The answer is NO, not this way at least, for a bunch of reasons.

  1. The most basic reason--if docs are too busy and harried to read the journals assiduously, why should they, as professionals, turn to a for-profit industry to help them? Why not develop a more professionally responsible and less commercially biased way to disseminate information quickly? (As in fact is now happening more widely.)
  2. Why worry about for-profit bias? Often a single study will tell only a small piece of the story. For every study that shows a good outcome there might be one showing a bad outcome. How much can we rely on the industry to circulate both sorts of studies equally? Fat chance.
  3. Now, the more subtle concern. We have seen mountains of evidence (HOOKED could have been twice as long had I included more of it) of companies fudging research results in more ways than you could name, to make a study come out as if the drug performed well and was safe, when the real data would show quite the opposite. The industry claims: we would never do that; we are scientific drug firms; we live or die on our spotless reputations; it is contrary to our commercial interests to put our names on garbage research. These claims have now been proven many times over to be bull. The companies can get away with garbage research because they know that the same busy docs that are too busy to read the journals carefully, are also too busy to read the entire article; they will be lucky to read the abstract. Spin the abstract so that the drug looks good, and you can have table after table of damning data in plain sight in the rest of the article, and most docs won't notice. Now, if the company knows that a research paper is going to be published in an obscure journal, where hardly any doc is going to see it, there is a certain amount of incentive both to fund the research in the first place, and to spin it in the second place. But if the company knows that its detail reps have free rein to push this article about off-label use under every doctor's nose, then the incentive to fund garbage research, and to spin it further, goes way up.

The new FDA rule proposal, therefore, is not a tiny crack through which the clever industry can drive the proverbial Mack truck. The opening is Mack-truck-sized from the get go.

Harris G. F.D.A. seeks to broaden range of use for drugs. New York Times, Feb. 16, 2008.


Bernard Carroll said...

The stated justification for this step – saving lives – is humbug and fear-mongering. A truly important new drug or new off-label application will sell itself through long-established professional communication channels among physicians. The hubris of the pharmaceutical corporations in claiming to be the essential conduit of life-saving information is breathtaking.

As for the F.D.A., they would require that the promotional off-label articles be peer-reviewed and come from a journal with an expert editorial board. This veneer of objectivity might sound good to the F.D.A. but it won’t fool anybody else. Pharmaceutical corporations have a long history of co-opting key opinion leaders (KOLs) in academic medicine to publish corporate infomercials in even the very best journals.

A detailed case study of the systematic deceits used by KOLs and corporations to promote off-label drug use by corrupting first-tier medical journals is available on the Health Care Renewal blog for 16 January 2008 ( ) and a companion case study of corruption in continuing medical education appeared on 22 January ( The principal KOL in these cases, a member of the Institute of Medicine no less, has a long history of ethical controversy.

Thus, the safeguards the F.D.A. proposed for this new plan were broken long ago. All in all, this is a very, very bad idea.

Anonymous said...

The FDA, the industrie's main client instead of the public, was somewhat expected, along with medical device manufacturers exonerated from any wrongdoing.

Such rules that benefit these industries furter corrupts the unregulated atonomy reps. already have with physicians.

Anonymous said...

This is just an end run around the proposed restrictions for CME--which can discuss off label uses. Note: reps can't distribute CME materials. So pharma will be taking CME dollars and putting it into pub plans--off-label AND rep distribution. Plus no trail. If a journal publishes a lousy article, they get the heat, as opposed to a CME accrediting institution. Win-win, some would say--or at least pharma companies and med ed groups that develop the articles.

Anonymous said...

The FDA and Its Damaging Lack of Citizen Protection

The Food and Drug Administration originated in its primitive form several decades ago to ensure the health and safety of the citizens of the United States. However, their focus seems to have changed the past few decades, as they appear to have formed a pathological alliance with the pharmaceutical industry. An example is the large amounts of money the industry gives the FDA for various reasons- amounts so large that this accounts, according to some, for about half of the FDA’s income, upon information and belief. An example of funds received is due to the prescription drug user fee act, which began in 1992. Basically, the drug industry has been authorized and required to pay the FDA for faster approval of their pending medications. Results of this relationship between the drug industry and the FDA, one could posit, could be a contributing factor the progressive and recent approval of unsafe drugs and lack of regulation and monitoring of the pharmaceutical industry that the FDA is obligated to perform. Yet the FDA continues to validate what has been posited through their support from the drug industry, in ways that seem reciprocal, and as a consequence, have possibly neglected the health of the public as best as they should.
The presumed intimacy between these two organizations does in fact seem to continue to worsen. For example, and recently, a new proposal by the FDA has been introduced that would allow the pharmaceutical industry’s drug sales reps to discuss their products with prescribers off-label, which means that the FDA may allow and accept the industry with their approval to possibly creating harm to patients with this proposal due to uncertainty associated with unapproved uses of a drug promoted in this way. Yet the FDA claims that this proposal would enhance the education and knowledge of the prescriber by the pharmaceutical representative, and this is rather delusional, to say the least.
A prescriber, upon their own discretion, can in fact prescribe a drug off-label, but historically, however, representatives from the pharmaceutical industry have been prohibited from suggesting this type of activity. In fact, it is a federal offense for such reps to speak off-label about the drugs they promote, and more pharmaceutical companies are being penalized for this behavior in the past in the form of monetary settlements with the Department of Justice. The drug companies that have allowed such criminal offenses, through vicarious liability at times, perhaps, and rarely admit guilt as part of such settlements.
This FDA protocol described and proposed is called, “Good Reprint Practices”, would require pharmaceutical sales representatives to use what may not truly exist, which is truthful and authentic clinical trials when and if they do speak off-label to prescribers. This in itself lacks etiology for such discussions by drug reps, as many clinical trials may be flawed due to the trials being possibly manipulated by the pharmaceutical companies of the meds involved in such trials, such as by a third party. Additional trial deception involves ghostwriting and invalid authors of such trials, and this is one of many concerns of this FDA protocol. These facts can be validated and have been discovered by others, so it appears the FDA did not take this into consideration.
Furthermore, this proposal is flawed in that most pharmaceutical reps lack clinical training and the ability for most drug representatives to analyze the unique statistical data regarding this issue with accuracy and meaning is unlikely, for the most part, I surmise. Remember that most drug reps have no medical or clinical training in any objective way, and, in my experience, have no interest in such training. So this seems to further complicate the idea of this off-label concept due to the ignorance of the reps of the complexities of these once reliable and dependable methods of proof. In addition, the relaxation of previous restrictions regarding off-label promotion could prove to be a catalyst for reps to embellish statements to prescribers for their own benefit in regards to their promoted meds. So, our previous safety association, the FDA, appears to be evolving into a possibly harmful association by suggesting such practices as this with deliberate intent and reckless disregard for public health, so it seems. Yet this situation of the FDA proposal mentioned appears to be of most benefit for the drug companies. It’s unbelievable this proposal ever came into existence, with the delusional fallacy that it would be of benefit to patient health, most likely. Furthermore, this may complicate existing patient medication errors, such as in the elderly or dosing for children, complicated by the fact that many are unable to understand label instructions on their med. So there are enough problems with prescribing, and adding this FDA proposal would just make the situation worse. We as citizens are no longer the concern of the FDA, one could conclude.
However, there is freedom of speech. Perhaps another alternative would be to have clinically trained people discuss such issues with prescribers, instead of the drug reps, who, unlike those academically enriched, have the objective of increasing the market share of their promoted meds with no regard to the science behind these meds, in large part. Because historically, medications have in fact proven to be beneficial for other disease states other than what a certain med was initially indicated for upon approval. Regardless, awareness needs to happen by the citizens involving tactics that are possibly deceptive such as this and many more activities by the pharmaceutical industry that one could argue are in fact somewhat covert and tacit. As citizens, we have the right to insist of the pharmaceutical company to maintain focus on the interest of others besides themselves, which could be the case now with the FDA. And the health of the public is that interest we as citizens demand, and should be enforced than it appears to be presently.

“As far as we can discern, the sole purpose of existence is to kindle a light in the darkness of being.”
---- Carl Jung

Dan Abshear