An Indication For Change

If you go to the Lyrica web site, a drug made by Pfizer, it says that Lyrica is "the first and only FDA-approved treatment that can help relieve fibromyalgia pain." This is a true statement, but there are plenty of other drugs physicians have been using to treat fibromyalgia pain. A similar example from a few years ago is the TV commercial for Zyrtec (now over the counter) which stated that it was the only drug approved for both indoor and outdoor allergies. Again, true, but in medical school I learned that in response to allergy the body didn't release different kind of histamines for indoor allergies and outdoor allergies, and that there was only one type of antihistamine that would work on both.

Why the confusion? The reason has to do with a product's indication. When a product is approved by the FDA as being both safe and effective, it is only approved for a specified indication. A good example of an indications would be age. When GSK first approved Advair (the #1 selling asthma drug), it was indicated for adults or children over 12 years of age. The reason for this indication is that the studies that GSK submitted to the FDA for approval were only done in children 12 years and older. But what if you are a 10 year old asthmatic that could really benefit from Advair? Your physician, if he or she felt comfortable could still prescribe it because a physician can use any approved drug for any patient in whom he or she feels is appropriate. The difference is that the drug companies can only promote their products to patients and physicians for its indicated use. In fact many drugs are used for "off-label" indications. This is especially true in Pediatrics, where it might take years before the company does the studies to get approval in younger children (Advair is now approved for 4 and up). In fact, drug companies will often use their indications for a competitive advantage over similar drugs that may not have that indication (like Zyrtec and Lyrica).

Going back to fibromyalgia, before Lyrica, many physicians (myself included) used Neurontin (indicated for seizures) for fibromyalgia pain (Lyrica and Neurontin are similar drugs), and it is still used today, though it use is considered off-label. In fact Pfizer (who also makes Neurontin) settled a case regarding Neurontin in 2004 for $430 million. The crime: promoting Neurontin for off label use. The FDA has been cracking down on drug companies to ensure that they are only marketing their drugs for their specificied uses. However, off-label promotion continues to be a common occurence.

This may be about to change.

As reported in the Wall Street Jounrnal today, the FDA announced it is considering lifting some of its restrictions on drug companies for off-label promotions to physicians. Specifically, drug companies through their representative may now be allowed to give a physician an article published from a peer-reviewed journal on their drug, even if the drug has not been approved for that indication. According to the FDA:

"Articles that discuss unapproved uses of FDA-approved drugs and devices can contribute to the practice of medicine and may even constitute a medically recognized standard of care," said Randall Lutter, FDA deputy commissioner for policy. "This guidance also safeguards against off-label promotion."

Off-label use can be very important for certain drugs where an approved treatment does not exist. In fact many discoveries regarding drugs were made initially using the drugs off-label. If physicians want to be up to date on the latest information, it would be important for them to know about studies on a product, even if the use is off-label. It may take years before the company gets approval for the indication that is clearly effective based on published research. In fact, many times the company does not even seek the indication because the cost of the approval process is quite high, and (especially if there are good studies to support its use) doctors will often start using drugs for off-label indications well before the product gets approved for that use.

On the other hand, allowing drug companies to promote their products for uses that have not been approved by the FDA as being safe and effective is risky business. This may lead to inappropriate use of the drug. The measure proposed by the FDA has the potential advantage of allowing only good studies (peer-reviewed, published) to be used for off label promotion and not other data (non-published, not peer reviewed). Both types of data are currently used for off-label promotion by drug company representative despite this practice being against the policies of most major drug companies. Critics will argue that even these "good" studies are inherently biased. If the new policy is approved, it will be interesting to see whether this promotes scientific discussion and learning, or inappropriate use of medications. (Optimistically, I think it will do the former, but realistically I think it will do both).

One of the main issues is not so much whether to allow drug companies to show publically available articles to doctors regarding the off-label use of their drugs (if a study is published in the New England Journal of Medicine, why shouldn't a rep bring this to a physician's attention?). The real issue is the way studies on drugs are done and the way physicians learn about appropriate use of medications. Most studies done on pharmaceuticals are sponsored by the drug companies. All of the major medical journals that publish these studies are supported by advertising revenue from the drug companies. If a physician wants to learn more about a drug, they can go to live meetings, dinner programs, web programs, etc. which are (you guessed it) funded by the drug companies.

This is not a criticism of the drug companies. They have an obligation to their share holders to promote their products for their indicated use. In addition, the information they provide to physicians can be valuable for patient care. The problem is that their is very few ways for physicians to get truly unbiased information. The NIH or government does not fund many therapeutic trials. At the NIH, there is no Institute for Primary Care whose mission is to educate primary care physicians about evidence based treatments. If we as a society want to ensure that there is no conflict of interest in the research on therapeutic agents that improve our health, as well as the promotion of this research and information to the physicians that prescribe these products, then we are going to have to start paying for this. The drug industry has and will continue to fill this void, and at this point it doesn't look like our society is willing to spend the money on this when so many Americans still don't have health care coverage.