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Proposed Changes to FDA Regulation Present a Dilemma

The Food and Drug Administration (FDA) is proposing a very interesting loosening of their regulations of pharmaceutical company marketing. The pros and cons of the proposed changes present an interesting dilemma, with legitimate points on both sides.

When the FDA approves a drug it is approved for a very specific medical indication. I have long thought that FDA approved indications for drugs were too narrow and restricting. For example, most anti-seizure medications are initially approved not for seizures but only for certain types of seizures – for example for adjunctive therapy (meaning it is meant to be added to another drug rather than used alone) for focal onset seizures (and not against primary generalized seizures – or ones that begin all over the brain at once).

Once approved physicians are free to use drugs as they see fit. If evidence shows that a new seizure medication is effective as first line treatment, then it is ethical good medicine to use it that way, even if it is not FDA approved for that use (this is called off-label use). FDA approved is not equivalent to science-based.

While physicians are free to follow the evidence and their clinical judgment, pharmaceutical sales representatives can only talk about the FDA approved indication for the drugs that they promote. They can only provide information (FDA approved information) for on-label uses. They are not supposed to even talk about off-label uses for their drugs.

If a pharmaceutical company wants to market a drug for an off-label use they must apply to the FDA and provide sufficient evidence to earn a separate indication for their drug.

The change being proposed now would allow drug companies to provide to physicians published studies about their drugs, even if they discuss off-label uses. This new policy is called the “Good Reprint Practice.” To balance this loosening of restrictions the FDA says, “This guidance also safeguards against off-label promotion.” They add further reassurance that articles will be restricted to those that are peer-reviewed, published by editorial boards, and not published in journals or supplements funded by the drug makers.

Now here’s the dilemma. Proponents of this new proposed change to the FDA imposed restrictions argue that companies are gagged from promoting uses for their drugs even when they are solidly evidence-based and life-saving. For example, a New York Times article on this issue reports that:

“The consequence of rapid disclosure of these benefits could be measured in lives,” said Dr. Scott Gottlieb, a former F.D.A. deputy commissioner.

Of course, physicians can get access to this information without the help of pharmaceutical companies. But considering the overwhelming amount of new scientific medical information published each year, any method of disseminating quality scientific information to physicians is useful.

Critics of the proposed changes also have a very legitimate point to make. Again, quoting the NYT article:

Representative Henry Waxman, Democrat of California, said the proposed rule “caters to the industry’s desire to market their products without adequate testing or review.”

But more to the point, if pharmaceutical companies can promote off-label uses for their drugs by providing published articles then that removes their incentive to fund and conduct sufficient studies to gain FDA approval. In general companies pay for expensive clinical trials of their products only to the extent that they are required to by regulation. Therefore the new regulations could mean less pharmaceutical company funded clinical research.

I don’t think there is a clear resolution to this controversy, because either choice is a trade-off. Restricting dissemination of legitimate scientific information about life-saving uses of drugs and medical devices will cost lives. But allowing companies to provide published studies on off-label uses will decrease their incentive to pay for further research.

I always find it ironic, however, that when people are discussing FDA regulation of drugs there is almost a universal failure to apply the same arguments to supplements, for which there is even less regulation. For example, by allowing supplement makers to sell their products with health claims (under DSHEA) without the need to provide any evidence or pass any FDA review process, there is absolutely no incentive for the supplement industry to conduct meaningful clinical research.

The dilemma between the protection of regulation and oversight vs the freedom to disseminate information and make claims without restriction exists throughout health care – it is not unique to drugs and medical devices. At the moment, in the US, this conflict is resolved very far to the regulation end of the spectrum for drugs and to the freedom end of the spectrum for supplements (even though supplements are often used as drugs). There is nothing in between. FDA approval is all or nothing – either you meet a very high bar of evidence or none is required.
Perhaps the solution is to provide different levels of FDA oversight. There should be a mechanism for the FDA to have expert panels review existing published evidence and then to approve those claims that are sufficiently science-based – without necessarily requiring millions of dollars worth of new research.

Such a review process could be applied to supplements – replacing the anything goes rules of the current regulations under DSHEA. Such a process could also be used for off-label uses of approved drugs.

It seems that that binary aspect of FDA approval is no longer adequate to deal with the complex world of health products. It has lead to our current situation of irrational regulations and unnecessary trade-offs.  My counter-proposal for the FDA is to institute mechanisms for one or more levels of science-based FDA review to handle the full spectrum of commercial health claims that are being made to the public. Until then we will be stuck with inadequate regulation and an unresolvable dilemma.

Posted in: Pharmaceuticals, Politics and Regulation

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