Why Drug Companies Promote Off-Label

Recently, the Archives of Internal Medicine published an article about the off-label prescribing of drugs by physicians (see "Off-label Prescribing Among Office-Based Physicians"). Here's the data:

In 2001, there were an estimated 150 million (95% confidence interval, 127-173 million) off-label mentions (21% of overall use) among the sampled medications. Off-label use was most common among cardiac medications (46%, excluding antihyperlipidemic and antihypertensive agents) and anticonvulsants (46%), whereas gabapentin (83%) and amitriptyline hydrochloride (81%) had the greatest proportion of off-label use among specific medications. Most off-label drug mentions (73%; 95% confidence interval, 61%-84%) had little or no scientific support. Although several functional classes were associated with increased off-label use (P<.05), few other drug characteristics predicted off-label prescription.

According to an article is USA Today ("Study: Off-label drugs often prescribed"), the authors were not sure why certain drugs were prescribed more often than others:

It's not clear why some drugs and types of drugs were more likely to be prescribed for unsupported off-label uses than others. The age of the drug, direct-to-consumer advertising or the company that made it made little difference, researchers said.

One explanation might be that "both physicians and patients have misunderstood the role of the FDA," Stafford says. "I think there's sort of a presumption that if a drug has made it onto the market, the FDA has vouched for its safety and efficacy for all of its potential uses."

Market Influence on Off-Label Prescribing
Too bad the authors didn't consider the influence of the market on off-label prescribing -- especially when the market is smaller than the one anticipated by the marketers.

Take for example, the case of Lilly's drug Evista, which is approved by the FDA for the prevention and treatment of osteoporosis in post-menopausal women. Back in December, I posted information about the case that the DOJ brought against Lilly for the illegal off-label promotion of this drug (see "Lilly's Off-Label Promo Shenanigans"). In that case, to which Lilly pleaded guilty, Lilly was pressured to promote off-label use of Evista because the on-label sales just were not meeting their expectations:

According to the information provided by DOJ, unrealized Evista sales forecasts spurred Lilly's new off-label promotion business plan.

"...the first year's sales of Evista in the U.S. were disappointing compared to Lilly's original forecast. According to the information, in October of 1998, the company reduced the forecast of Evista's first year's sales in the U.S. from $401 million to $120 million." [DOJ press release]

I don't expect that you can use this to predict what the next class of drugs will be subject to off-label promotion abuses, but if I had to guess, I would say it will be the erectile dysfunction (ED) class of drugs (Viagra, Levitra, Cialis). And it may already be happening.

The market for ED drugs is not nearly what the drug marketers in these companies thought it would be (see "ED Drug Sales Limp"). Perhaps responding to that fact, you are seeing more ED drug ads that are focusing on diabetes and high blood pressure as potential causes of ED. I notice in the Levitra ads, for example, men with diabetes and high blood pressure express concern that they did not know their medical conditions could result in ED. These men do not say, however, that they have experienced the problem. Now they are concerned about developing ED.

One might interpret the message of such ads as: "If you have diabetes or high blood pressure, you are in danger of developing ED. You should talk to your doctor about Levitra." That borders on off-label promotion because none of the ED drugs is approved for pre-emptive treatment to prevent ED (for more on this topic, see "Pre-emptive Drug Marketing?").

Another piece of evidence I have that there may be more off-label promotion of ED drugs comes from the book "Selling Sickness." The author points out that a prominent urologist -- a paid consultant to Pfizer -- said he was a "strong believer" in taking Viagra on a daily basis to "prevent impotence."

Professor Irwin Goldstein of Boston University, Massachusetts, said at a recent continuing medical education event (sponsored chiefly by the drug's manufacturer, Pfizer) that he was a "strong believer" in taking sildenafil on a daily basis to "prevent impotence."

Before a large audience of primary care doctors and others attending a sexual function update at New York University in December, Professor Goldstein said he had "hundreds of men" using Viagra for prevention: "If you would like to be sexually active in five years' time, take a quarter of a pill a night---we have data to show that will facilitate and prolong nocturnal erections."

His comments were made during a panel session, in response to a question from one of the event's directors, Dr Natan Bar-Chama, a urologist from the Mount Sinai School of Medicine, New York, who also told the meeting "I'm a strong advocate of proactive prevention as well." [reported in BMJ]

A Rose is a Rose is a Rose
Several industry conferences are devoted to off-label promotion by pharmaceutical companies. The term "promotion," however, has now been dropped in favor of "usage" as in the "5th Annual Off-Label Usage Conference." This reflects the fact that a lot more attention will be focused on off-label promotion these days by OIG, FDA, and individual states attorney generals (see, for example, "Off-label Marketing: Next State Issue").

Whenever the pressure is high to meet sales numbers -- especially to meet Wall Street expectations -- there will be a danger of crossing the line into illegal off-label promotion, even if it is called by another name.