Dec 07 2012

Promoting Off-Label Use of Drugs

The off-label use of prescription drugs is often misunderstood by conflating it with the non-evidence-based use of drugs. I actually don’t have an issue necessarily with using drugs off-label. A distinct issue is whether or not drug companies can promote off label uses, and how they can advertise their drugs at all. A recent court decision may loosen restrictions on the pharmaceutical industry (and by extension the supplement industry and the marketing of any health product).

In a case that could have broad ramifications for the pharmaceutical industry, a federal appeals court on Monday threw out the conviction of a sales representative who sold a drug for uses not approved by the Food and Drug Administration. The judges said that the ban on so-called off-label marketing violated the representative’s freedom of speech.

The ongoing battle between regulation and free speech rages on. First for some background, in the US the FDA regulates the marketing of drugs, which are defined as a substance that is used to treat or modify any disease. Supplements are now defined as substances use to enhance or improve some structure or function in the body, but cannot be claimed to treat any specific disease. So these categories are based, for regulatory purposes, on the kinds of claims that are made for them.

Pharmaceutical companies must apply to the FDA for the right to study a potential new drug in humans, to meet the requirement for evidence of safety and effectiveness to get the new drug on the market. A drug cannot be sold at all unless it has been approved by the FDA for at least one indication. Once a drug is approved (and again, that approval is tied to a specific disease indication) it can be sold on the market. The drug company, however, can only market the drug for the approved indication, and only to doctors in a relevant specialty. They can also now advertise the drug directly to the public.

Any use of the drug for something other than its precise indication is considered “off label.” The FDA does not regulate medical practice, however, only drug companies, so doctors can use approved drug in any way they feel is appropriate. (There are other regulatory mechanisms to maintain the standard of care in terms of what doctors do in practice.)

Drugs often have multiple and complex effects on the body. This means they always have some side effects, but it also means they can have multiple beneficial effects as well. Also, diseases may share features or mechanisms and therefore one drug may be effective for multiple conditions. Drug companies may seek approval for additional indications, but the only reason for them to do this is if they think it will expand the market for the drug. This is therefore a marketing decision, not a scientific one necessarily. Drug companies have tried to skirt the rules by promoting off-label use in he past, sometimes resulting in mutli-billion dollar fines from the FDA.

There are times, however, when there is solid published evidence supporting off-label use of a drug, and in fact such use of the drug may be life-saving or cost effective (in other words, good medicine). Some have argued that restricting drug company promotion of off-label but evidence based use of certain drugs harms consumers and public health.

I have taken the position that congress should explore new rules for the FDA that will allow them to approve off-label promotion of drugs based upon a review of existing published peer-reviewed research (therefore the drug company does not have to spend millions of dollars on new research just for the FDA). But (and here is the key, relevant to the new development) – there needs to be an official review of the evidence to determine which claims are sufficiently evidence based.

The basic concept here is that it is the FDA’s role to protect the public not only from unsafe drugs and health products, but also from false or misleading corporate claims or advertising. ¬†(The Federal Trade Commission also shares this latter responsibility, although the FTC is restricted to post-market regulation.) How can they do this if not by reviewing claims?

Now we get to the crux of the recent court decision. This was an appeals court decision resulting from a case brought against a drug company sales representative who was promoting off label use of the company’s drug. He argued that doing so was protected free speech. He was simply relaying the results of scientific research, and the FDA does not have the right to essentially muzzle him from discussion public information. Further, off label use of drugs is not illegal, so he was not promoting any illegal activity.

Two of the three judges in the case decided that the FDA did not have the power to restrict free speech that was essentially promoting an evidence-based and legal activity. The one dissenting judge, however, pointed out that this will create a precedent that will effectively neuter the FDA in terms of regulating drugs sales. I would add that this precedent will extend beyond drugs to supplements and any health care product or service, and will not only neuter the FDA but the FTC as well. (Orac wrote about this topic yesterday and made the same point. )

I tend to agree with the dissenting opinion in this case. Freedom of speech does not give people carte blanche to make whatever commercial speech they desire. Looked at another way – I am a big believer in the free market, but markets are constructs and they are constructed of rules and regulations. In the marketplace of medicine, unrestricted claims and marketing, in my opinion, lead to chaos. The consumer will be overwhelmed by complex claims that are very difficult to assess because they involve understanding the scientific literature in a thorough and nuanced way. There needs to be at least a basic filter in place to weed out patently false claims and give a minimal reassurance that health claims are reasonable – and then let the public decide among legitimate claims. In an unregulated marketplace, however, legitimate claims will be overwhelmed by slick but false or misleading claims. I give as evidence for this the supplement industry.

There is a balance between freedom and open markets, and also regulations to assure at least a basic level of honesty, fairness, and safety. Just citing freedom of speech on one side of the equation ignores this balance.

I don’t necessarily think we are currently at the optimum balance. We are too far to the freedom end with some things, and the regulation end with others. I do think, as I stated above, that it would be reasonable to have more efficient and less expensive review processes to approve the marketing of off-label use of drugs, and for specific health claims for supplements – as long as there is some review process. Otherwise it is left to the FTC to clean up the mess after the fact, and they are already overwhelmed.

Hopefully this decision will spur meaningful discussion on this issue. Let’s not get bogged down in accusations of evil government regulators or evil big pharma. There is a rational compromise in the middle.


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