The new rules FDA proposes would allow drug and device makers to provide doctors with copies of medical journal articles that discuss product uses that have not been vetted or approved by the F.D.A. The rules also say that drug companies do not have to promise to adequately test the unapproved use discussed in the article.
Under the proposed rule, the agency would let drug and device companies pass out articles to doctors if the articles were peer-reviewed and came from a journal with an expert editorial board. The article must be accompanied by a prominent warning that the use described is not approved or cleared by the F.D.A.
The agency abandoned the requirement that drug and device makers must provide the studies to the F.D.A. beforehand or promise to seek approval of the discussed use.
This, according to many critics like Congressman Henry Waxman, Chairman of the House Committee on Oversight and Government Reform (and Clemens basher), "would carve a large loophole in the law and create a pathway by which drug and device manufacturers can promote unapproved (off-label) uses of their products without first obtaining FDA approval..." (see his letter to FDA commish Dr. von Eschenbach here).
Under the old law -- which expired in 2006 -- drug companies could distribute journal articles discussing off-label uses of drugs only if they promised that they intended to do controlled studies on the off-label use and submit an application to the FDA for approval for that use.
Critics worry that without this promise, drug companies have no incentive to seek such approval for new uses of their drugs and they will just promote off-label by showering docs with reprints.
It would be totally feasible under the proposed new guidelines for drug companies to sponsor small "investigator-initiated" trials on off-label uses and get these studies published in peer-reviewed journals so that they can distribute the reprints to physicians. Often such studies are in small populations and do not meet the rigorous requirements FDA has for approving drugs for new uses.
There are other issues raised by FDA's proposal that I'd like to explore further. Through this post and an associated online SURVEY I hope to get your opinions and then follow-up with a more in-depth article for publication in Pharma Marketing News.
The SURVEY I put together asks how strongly you agree or disagree with the following statements:
- Under NO circumstances should drug companies be permitted to hand out off-label information -- including peer-reviewed journal articles -- to physicians and other health care professionals.
- As in the old rule, a drug company should be permitted to hand out such information IF the information is first reviewed by the FDA and the company declares that it intends to submit an application for FDA approval of the off-label use (ie, perform clinical trials).
- FDA is forced to relax the rules because not to do so is an infringement of commercial free-speech rights.
- The new rule will stop pharmaceutical companies from underwriting expensive trials to confirm new drug uses.
- Because the FDA is so slow in assessing drug and device benefits, it is imperative that drug companies be able to hand out medical journal articles so that doctors can learn immediately about life-saving uses.
- Doctors have many other sources of information about off-label use of drugs -- the Internet and their own journal subscriptions, for example -- and do not require that pharmaceutical companies provide this information to them.
- Since the FDA admitted that it did not really enforce the old requirements, it is also not likely to enforce the NEW requirements (ie, use of peer-reviewed articles only, warning label on articles). Consequently, this gives the drug industry virtual free reign to do off-label promotion.
What I think: There clearly are circumstances where I think drug companies should be able to do this such as in peer-to-peer, physician-to-physician discussions; ie, using Medical Science Liaisons (MSLs; see "Give Docs What They Want"). Drug companies have been doing this for years. Why not set up a secure online network for physicians to supply reprints in electronic format? I have a problem with sales reps handing out off-label information to docs -- clearly they are positioned to promote the benefits of their products and may be tempted to use the off-label reprints as part of their promotional sales pitch -- in fact, they would be dumb NOT to do that! Overall, I would have to say that I disagree somewhat with this statement. What do you think? Answer here.
What I think: I don't see the logic of this. First of all, the FDA cannot possibly track this. It's similar to the situation in which drug companies make promises about doing post-marketing surveillance trials in return for faster approval. About 65% of the time it just never happens and the FDA is virtually powerless to do anything about it (see "Spinning Bad News about FDA & Drug Safety"). So I would have to say that I strongly disagree with this statement. What do you think? Answer here.
What I think: Bingo! FDA doesn't think it can win in court or, at least, it has had a change of heart on this issue after Dr. von Eschenbach took over. A legal gray has been cast over limitations FDA previously placed on distribution of reprints by pharma companies. Clearly, FDA's new guidance is based on a court decision regarding a first-amendment case brought by the Washington Legal Foundation (see "WLF Decision and Its Implications"). So I would have to say that I strongly agree with this statement. What do you think? Answer here.
What I think: Waxman said in his letter to von Eschenbach, "the draft guidance may create a disincentive for drug and device manufacturers to seek approval for unapproved uses." This argument would have more merit if sales of drugs depended solely upon promotion to physicians. Pharma companies also want to promote new uses for their products to consumers. They could do this -- and DO do this -- via PR, which gets stories in the press about unapproved uses of drugs, but it's much more efficient and effective to use DTC advertising, which in no way allows for the promotion of off-label uses. Still, it is estimated that 21% of prescriptions are for off-label use and that is a big source of income for the industry. Anything that would increase off-label use would be a windfall. Overall, I would have to say that I disagree somewhat with this statement. What do you think? Answer here.
What I think: I forget who used this argument -- it could have been Ken Johnson over at PhRMA. If doctors want to learn immediately about life-saving uses of drugs, they should subscribe to and read the medical literature and take their continuing medical education more seriously. Also, pharma companies have other ways to get this information to docs -- ie, by sponsoring continuing medical education! So, I would have to say that I strongly disagree with this statement. What do you think? Answer here.
What I think: This is a corollary of the previous statement or maybe even redundant -- but what the heck, let's treat it as a separate issue. As I have said before, physicians can easily learn about new drugs and off-label uses of old drugs from a myriad of sources -- especially the Internet (see "The Professor's Straw Man Free Lunch for Physicians Argument"). Maybe they prefer the nice, glossy reprints given to them by sales reps as gifts. Anyway, I would have to say that I strongly agree with this statement. What do you think? Answer here.
What I think: According to a NY Times article, "An F.D.A. official said the agency did not really enforce those [old] requirements anyway." Logically, if that is true, then it is also true that the FDA would not enforce the new requirements, which would open up a lot of possibilities for the drug industry to abuse the privilege -- especially, as I noted above, if sales reps are in charge of handing out reprints. So, I would have to say that I agree somewhat with this statement. What do you think? Answer here.