Off-Label Promotion and the U.S. Constitution

You would think these ten simple words are clear enough: "Congress shall make no law...abridging the freedom of speech..." Apparently not. Congress did, of course, pass a law prohibiting pharmaceutical companies from promoting off-label uses for drugs and put the FDA in charge of that enforcement. Never mind that off-label prescribing is widespread, legal, and helps American patients. Never mind that Congress itself, Medicare, the Department of Veterans Affairs, the National Cancer Institute, and the National Institute of Health actively encourage off-label prescribing.

A drug's "label" is the drug's FDA-approved prescribing information--the package insert. Any approved use is considered on-label, while any use not listed on the insert is considered off-label, even though the off-label use may effectively treat a medical condition and reflect the best medical practices. Although the FDA tolerates off-label usage, it forbids companies from promoting such uses. Promotion is really just communication and communication is speech. So the FDA is in direct violation of the First Amendment. Something has to give.

This is not some academic issue, as pharmaceutical companies have been pressed into paying almost $12 billion in fines over the last decade. In fact, just today GlaxoSmithKline announced that it settled its case for a whopping $3 billion.

In other news today, pharmaceutical companies are mounting a concerted legal effort to overthrow or weaken this and similar rules. Their case got a boost this summer when the U.S. Supreme Court cited the First Amendment in striking down a related Vermont law. In its decision, the court wrote that speech used in drug marketing is a form of expression protected by the Free Speech Clause of the First Amendment. It's good that someone is actually reading the Constitution.


Off-label prescribing may help patients in some cases, but it also harms patients and there is a reason the FDA forbids marketing for off-label indications. Think Infuse. Surgeons all over the U.S. have been using it at dosages that are off-label and as high, and often higher, than that offered by Amplify... a substance which FDA denied approval for because of a significant increase in the incidence of cancer among those who received it. I, for one, am glad I am not one of the thousands of patients who received off-label high-dose Infuse and do not have to constantly worry about what the future holds for me as a result.

If companies have an indication they'd like to market a drug for, they can run the studies and apply for approval. There's no one saying they can't do that. Pushing off-label prescribing is a way to get around the expense of running scientific studies to prove that a drug actually works and is safe for an indication. If you'd like to go back to the Snake Oil days when anyone could sell anything for any condition, you're welcome to. But don't force it on me. I'd rather be at least semi-confident that the drug I'm taking has gone through at least minimally rigorous (though likely pharma-sponsored) scientific analysis.

Let's review a hypothetical case and see if we really would return to the days of snake oil sales.

Disaster strikes and you are diagnosed with HER2 over-expressing breast cancer. Around this same time, AstraZeneca starts to promote Crestor (rosuvastatin) for this type of breast cancer. (This is not true, of course, but I'm using it as a hypothetical example.) Anyway, the AstraZeneca sales representative has a sales call with your physician and recommends that he/she try Crestor for breast cancer patients. Your physician would say, "You're kidding, right? What data do you have? What's the mechanism of action? Is this a joke? What other doctors have used it that way and can I talk to them?" To this, the AstraZeneca sales rep has no good response.

Now imagine that this physician makes a huge mistake and prescribes Crestor for your breast cancer anyway. How will he/she tell you what dose to take when there's no supporting data? You leave perplexed but go to the pharmacy to fill your prescription. Your insurance company rejects the claim because it only pays for Crestor for hyperlipidemia and dyslipidemia, two cardiovascular conditions.

Now imagine your insurance company makes a huge mistake and allows the claim. Your pharmacist then flags this prescription as suspect and tells you there has been a mistake. Your pharmacist calls your doctor to report the problem.

In addition to all these protections, we can add the general press (TV, newspapers, magazines such as Consumer Reports, and newsletters such as Berkeley Wellness Letter) and the industry press, which all say that Crestor doesn't treat breast cancer. And then there is the Susan G. Komen website where breast cancer victims give each other advice. Women on that site will tell you that you should have gotten Herceptin (trastuzumab) instead of Crestor.

Let's say all these protections fail and you take Crestor and your breast cancer worsens, you can sue AstraZeneca and your doctor. You will win and receive millions of dollars, as will other women across the country.

Now imagine that you work at AstraZeneca. Would you decide to spend limited company resources promoting Crestor for breast cancer instead of the home run of hyperlipidemia? Even if you did, your boss or your boss’ boss would override your decision. It would be an astonishing company to make such a bad decision.

I hope you can see that we would not return to the days of snake oil sales.

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