Legal Librarian, Thomas M. Cooley Law School

There is a whole horde of issues surrounding the off-label use of prescription drugs. Forget the medical malpractice implications for a moment—whether off-label prescribing can fall within the standard of care or be used as evidence of negligence. Forget the argument that if the FDA restricted off-label uses for FDA approved medications, it would take on significant de facto authority over the practice of medicine. And even though I am interested in a drug company’s ability to promote their products for off-label uses, forget the inherent False Claims Act issues and Constitutional freedom of commercial speech issues entirely. On February 20, 2008, the FDA released a draft Guidance for Industry that will potentially change the current restrictions imposed on drug companies with regard to the dissemination of information regarding off-label uses for their products. Currently, drug manufacturers are barred from any sort of marketing of their products for unapproved uses; however, the FDA’s recent draft Guidance now purportedly recognizes “the important public policy reasons for allowing manufacturers to disseminate truthful and non-misleading medical journal articles and medical or scientific reference publications on unapproved uses of approved drugs and approved or cleared medical devices to healthcare professionals and healthcare entities.” Sounds good, right? We always like the free flow of information to doctors; a knowledgeable doctor is a good doctor. Doesn’t more info always mean better care? Well . . . sometimes. Doesn’t it also matter who is funding the research and promoting the results? Is it possible that this proposed change could open the floodgates to profit-motivated abuse? No one can argue the fact that some drugs have valuable off-label uses. However, the FDA approval process is a long and complex beast. It usually takes more than eight years for a newly discovered compound to navigate its way through the FDA’s rough waters and come out the other side in a little amber bottle with a safety cap on top. There is also no denying that this is an expensive process. However, the process is in place for a reason. For all of its shortcomings, the FDA approval process has the goal of protecting people. One criterion that the FDA uses when reviewing new drugs is the overall risk-benefit ratio. Essentially, the FDA wants to know whether the drug will cause more harm than good; however, when making that determination, there is always a specific pathology involved. Weighing a compound’s adverse effects against its benefits for someone with a terminal condition is completely different than doing the same for someone with the common cold. If the current regulations are changed to allow drug companies to promote their products for off-label uses, isn’t there a possibility that drug companies will gain FDA approval based on a lower standard than that for which the drug will eventually be marketed and from which most of the return on investment will be had? One example that comes to mind is a little company called Biopure that has diligently been trying to get FDA approval for its oxygen therapeutic product. At one time, Biopure sought FDA approval for its product as a blood substitute that would not need to be typed, would not need refrigeration, and could be manufactured from cow’s blood. The potential market for such a product is obvious. However, trying to show that your product is better than the current alternatives, such as whole blood transfusions, is a pretty tough standard. Luckily for Biopure, their product had another saving grace. Biopure claims that the oxygen delivery vehicle in its product is many times smaller than the red blood cells of real blood, and as such, it can be useful in situations in which an artery is partially blocked and will not allow oxygen rich red blood cells to pass (think: heart attack and stroke), hence the new designation as “oxygen theraputic.” Don’t get me wrong. I like Biopure. I am rooting for their success. But if they are able to gain FDA approval for their product as an oxygen therapeutic, under the proposed change, what would stop them from marketing it again as a blood substitute through the use of journal articles and reference publications that spoke to that off-label use? And if they did, would that really be so bad? Was the FDA’s standard too high when it came to a blood substitute that could potentially find its way onto battlefields and accident scenes in the hands of medics and first-responders? And if this potential change would be a good thing with regard to Biopure’s product, will there be other situations that will fall on the other side of the line? In the words of Saul Bellow, “A great deal of intelligence can be invested in ignorance when the need for illusion is deep.”