Is the Era of Off-Label Promotion Over?

The question arises in the wake of yesterday’s news that the government and GlaxoSmithKline settled a string of lawsuits charging the company with illegal promotion of prescription drugs for unapproved uses. The $3 billion settlement represented just a small fraction of the sales to patients for whom the off-label prescriptions either caused harm or did little or no good.

Glaxo’s chief executive Andrew Witty, in a prepared statement, assured the public that his company has “fundamentally changed our procedures for compliance, marketing and selling in the U.S. to ensure that we operate with high standards of integrity.”

Judging by the number of seminars and conferences over the past few years designed to help companies meet the legal requirements for promoting drugs, there would certainly appear to be a lot more attention being paid these days to staying within the law. There have been 165 settlements between the government and drug companies over the last two decades, and the more recent settlements — $2.3 billion from Pfizer and $1.4 billion from Eli Lilly — have achieved blockbuster status (a word usually reserved for drug sales above $1 billion). While that is affordable for the highly profitable industry, settlements of that size do tend to capture the attention of top company officials and begin to tip the risk-reward ratio for illegal activity toward better compliance with the letter of the law.

Ah, but there’s the rub. Just because companies like Glaxo are operating within the law doesn’t mean they’ve stopped promoting the off-label use of drugs. There is still a small army of salespersons (called detailers in the trade) who are out there visiting physician offices, delivering free samples and pizzas, and dropping off articles that have appeared in the medical literature. Those articles offer peer-reviewed evidence that this or that drug works for a patient population, even though that use hasn’t been approved by the Food and Drug Administration. There may not even be an application pending at the FDA for approval of that use.

These activities follow guidelines published by the FDA in January 2009, which replaced the rules set by the 1997 FDA Modernization Act that opened the floodgates to off-label promotion. The latest guidelines require that physicians ask for the information first, and that the distributed articles come from peer-reviewed journals (not industry-funded journal supplements) that have clear conflict-of-interest disclosure policies.

Those guidelines are inadequate, argued Bruce Psaty of the University of Washington and Wayne Ray of Vanderbilt in a 2008 Journal of the American Medical Association article (subscription required), which appeared when the guidelines were still in draft form:

While peer review provides some important safeguards, the system was not designed to manage major financial conflicts or to withstand the relentless promotion of commercial interests. Unlike the NDA (new drug application) process, in which the FDA supervises every phase of a trial and scrutinizes the resulting data, editors and manuscript reviewers are not generally aware of critical details of the trial design and conduct. They often do not and cannot know about potentially biased adjudication of end points, concealed adverse effects, or unreported changes in the primary outcomes, and they usually have no method of knowing about the presence of ghost authors or other published studies. The peer-reviewed literature cannot ensure high-quality off-label promotion of medications. . .  or to withstand the relentless promotion of commercial interests.

The result is that even though companies are more careful these days about how they train detailers to promote drugs, there is still a tremendous amount of off-label promotion going on. And a lot of that is for uses that will no doubt one day be exposed as having been not only not useful, but unsafe.

Merrill Goozner has been writing about economics and health care for many years. The former chief economics correspondent for the Chicago Tribune, Merrill has written for a long list of publications including the New York Times, The American Prospect, The Washington Post and Financial Times. You can read more pieces by him at GoozNews, where this post first appeared.