In early January, the U.S. House Committee on Energy and Commerce [3] began investigating celebrity endorsements in television ads for brand-name drugs. The investigation was sparked by Pfizer [4]'s commercials for its best-selling cholesterol drug Lipitor [5]. These direct-to-consumer (DTC) ads [6] feature Dr. Robert Jarvik, a pioneer in the development of the artificial heart. Viewers are not told that Jarvik is not a cardiologist, nor is he licensed to practice medicine. His presentation as a trusted expert, Pfizer presumably hopes, is enough to persuade viewers to ask their doctors for Lipitor by name. And that would help erode the increasing competition from generic alternatives.

DTC ads have been controversial since the Food and Drug Administration [7] (FDA) loosened the rules governing pharmaceutical marketing in 1997. Before Lipitor made headlines, there was Viagra. Pfizer's "Viva Viagra!" campaign was criticized by the FDA and organizations including the AIDS Healthcare Foundation, who said the DTC ads encouraged recreational use of the erectile dysfunction drug. One print ad suggested that Viagra be used to "celebrate" events such as the Super Bowl or New Year's Eve.

While troubling, DTC ads represent only 14 percent of pharmaceutical companies' marketing budgets. By the time a 30-second drug commercial airs, the company has conducted months of segmentation studies, held dozens of meetings to define the "communication target" (typically a woman, usually a mother, and of a certain income), and spent millions of dollars to develop the drug's brand and its market. This strategic marketing, which represents the remaining 86 percent of drug promotion expenses, should receive at least as much attention from regulators and lawmakers as DTC ads.

Targeting doctors

While DTC ads seek to change patients' behavior, pharmaceutical companies are more interested in changing doctors' behavior. Drug marketers work hard to persuade doctors to prescribe their branded drug over generics and other competitors, and to change other medical practices that limit company profits.

To cultivate medical professionals, drug companies may retain a doctor as a spokesperson, position friendly medical "thought-leaders" in the media, or organize free events at posh resorts and expensive hotels to "educate" doctors about a new disease state (think Restless Leg Syndrome) or their latest drug. In 2000, the biggest 10 pharmaceutical companies spent $1.9 billion on promotional events alone.

Then there is the pharmaceutical industry's holy grail of marketing -- the relationship between their sales representatives and medical doctors. To maintain this relationship, often called "detailing," pharmaceutical companies spend a whopping $8,290 per doctor. The average family doctor receives 28 visits each week from drug reps, who provide free samples, explain new findings from company-sponsored drug trials, and demonstrate the latest innovation in their company’s medical devices.

Some doctors, reporters and public health advocates have long decried the pharmaceutical industry's seemingly endless attempts to buy goodwill among medical professionals. But insidious marketing campaigns seeking to rebrand medical conditions as lifestyle choices, and the patients who suffer from them as consumers, have received little scrutiny.

Turning patients into consumers

How are patients turned into consumers? The rebranding of Prozac, pharma giant Eli Lilly [8]'s top-selling antidepressant, as Sarafem illustrates the process.

Sarafem and Prozac are chemically identical. The only differences between the two drugs are branding -- Prozac is yellow and green, Sarafem is pink and purple -- and what each is prescribed for. Prozac is used to treat an array of symptoms associated with depression, while Sarafem is used to treat a highly contested and little recognized condition known as premenstrual dysphoric disorder (PMDD).

By going back to the FDA and getting approval to use Prozac to treat a new set of symptoms, Eli Lilly won big. The company now has two separate markets to sell to, and it stymied potential generic competitors to boot. Sarafem hit the market in late 2000, just months before Eli Lilly's patent on Prozac ran out. Sarafem's introduction effectively extended the patent on Prozac.

Rebranding is a highly effective marketing strategy. First of all, the process is mostly hidden from the "communication target": the person looking at a drug ad. Ads for a rebranded drug don't mention that the only thing "new" about the drug is the color of its coating. In addition, expanding the drug's FDA approval to cover new, ill-defined medical conditions allows the pharmaceutical company to decide who might benefit from their product. Not surprisingly, their definitions tend to be wide ranging, even including what are usually considered normal experiences. For example, Eli Lilly includes among its symptoms of PMDD [9] "irritability, mood swings, tension as well as breast tenderness and bloating" in the week before a woman’s menstrual period. "Left untreated, [PMDD] can get worse with age," warns the drugmaker. At least until menopause, that is.

Rebranding isn’t just for pills -- medical devices are a hot area for this marketing technique. Medical devices refer to everything from wheelchairs and contact lenses to artificial hips and breast implants. Also included in this category are the new skin "fillers," which are injected under the skin to smooth out wrinkles.

The market for injectable fillers has exploded since 2003, after the FDA approved Restylane™ for use under the skin between the nose and mouth, to smooth out smile lines. Since then, at least 13 more injectable fillers have hit the market, with several more in clinical trials. All are promoted as non-surgical alternatives to facelifts or as longer-lasting wrinkle treatments than the injectable neurotoxin Botox™ [10].

Non-surgical cosmetic procedures represent an enormous market potential. According to the American Society of Aesthetic Plastic Surgery (PDF) [11], in 2006 Americans spent close to $12.2 billion on elective cosmetic procedures. That same year, the number of cosmetic plastic surgeries decreased for the first time since 1997, while non-surgical procedures increased nearly eight-fold. Non-surgical procedures account for 83 percent of the 11.5 million cosmetic procedures done in the United States alone, and injectable fillers are second only to Botox™ as the most popular cosmetic procedure performed on the face.

Many of these new gels and fillers were initially developed and approved for medical applications, such as in dissolvable sutures, to relieve joint pain or to repair eye damage. Then, they were rebranded for cosmetic applications. Two of the fillers still have FDA approval for medical applications only: Silikon 1000® [12] for retinal treatments, and Sculptra® [13] to treat facial fat loss in HIV-positive patients on anti-retroviral drug therapies. But both are marketed to consumers and doctors for "off-label," or unapproved, cosmetic purposes.

The FDA does not regulate off-label use of drugs or medical devices. The agency sees its role narrowly as a regulatory body, and believes off-label practices help foster medical advances. It is illegal to promote off-label uses in DTC advertisements, but off-label uses are marketed in other, more subtle ways. The ad for Restylane, for example, cannot mention its off-label applications, but marketers continually promote these unapproved uses. The off-label marketing of drugs and medical devices raises serious questions.

Turning medical necessities into consumer choices

The December 2007 issues of the women’s fashion magazines Allure and Harper's Bazaar both featured multi-page spreads on non-surgical cosmetic procedures, including the array of injectable wrinkle fillers. The articles outlined the pros and cons of each filler, evaluating injection pain, cost per injection (most run between $500 and $800 per shot), and how long each lasts.

Dermatologist and anti-aging cream entrepreneur Dr. Patricia Wexler [14] is featured prominently in the Bazaar story. Her remarks about each injectable reflect the marketing language of the brands themselves. When she is discussing Sculptra®, for instance, she describes how the product acts as "a trellis on which the collagen can grow" -- a line marketers use to describe how the device works. She also repeatedly suggests what are off-label, unregulated product applications, such as using injectable fillers in the eye area, in the temples, in the jawline, on the cheekbones, and in the fine lines surrounding the mouth.

Much like Dr. Jarvik's pitches for Lipitor, Dr. Wexler's injectable filler promotions are especially credible among the target audience. Wexler regularly discusses non-invasive, anti-aging procedures on the "Oprah Winfrey Show," the "Today Show," and "Good Morning America," and in the pages of Vogue and Marie Claire. The big pharma companies that make the injectable fillers likely dream of doctors touting their products and suggesting off-label uses for them in popular women's magazines. As the saying goes, they couldn't buy such good press -- but they probably did.

These articles, as well as the latest DTC television ad for Restylane™, clearly encourage off-label use of injectable fillers. Since the FDA has not approved these uses, they haven't been properly tested in clinical trials. For example, Sculptra was only tested in one trial, on 279 white, HIV-positive men. The filler has never undergone clinical trials on HIV-negative people, on people of color, or on anyone's hands or foreheads. People who use the fillers in these ways are effectively acting as guinea pigs. Not surprisingly, there have been reports of adverse affects in people with healthy immune systems. Earlier this month, USA Today [15] reported that the FDA is now warning patients [16] who use off-label Botox injections that they risk serious adverse side effects, including death.

While the FDA officially considers off-label use as spontaneous, observation-driven and innovative medical practice, the truth is that promoting off-label applications is a calculated marketing tactic to increase sales. With the injectable fillers, these semi-covert promotions have been quickly accepted by doctors and the general public, making off-label use the norm. Such marketing efforts are increasingly blurring the distinction between medical innovations and sales pitches. Worse, the trend is seriously undermining the regulatory authority of the FDA.

It's not surprising that profit-driven, cutting-edge marketing techniques have outstripped the government agency established to guide them. What is surprising is that public health advocates haven't made pharmaceutical rebranding and off-label promotions of drugs and medical devices major issues. In December, the advocacy group Consumers Union sent a letter (PDF) [17] to the FDA requesting tighter DTC advertising regulations on medical devices. That's a good first step, but much more must be done.

References

• Bonnie Goldstein, "Dr. Robert Jarvik, Pitchman [18]," Slate.com, Jan. 10, 2008.
• Stephanie Saul, "Drug Ads Raise Questions for Heart Pioneer [19]," The New York Times, Feb. 7, 2008.
• Matthew Herper, "Best-Selling Drugs in America [20]," Forbes, Feb. 26, 2006.
• "Pfizer's 'Viva Viagra' Ads Promote Party Use, Says AHF [21]," Backchannelmedia.com, July 24, 2007.
• "FDA Warns Pfizer About Celebrex Ad Claims, 27 Minute Infomercial Mentioned [22],” Backchannelmedia.com, Jan. 13, 2005.
• Stephen McGuire, "Statin Market Roiled as Generic Zocor Bites Lipitor," Medical Marketing & Media, October 2007.
• Val Brickates Kennedy, "Pfizer's profit plunges on generic competition [23]," MarketWatch.com, July 18, 2007.
• Julie Donohue, Marisa Cevasco, and Meredith Rosenthal, "A Decade of Direct-to-Consumer Advertising of Prescription Drugs [24]," New England Journal of Medicine, Vol. 357:673-681, Aug. 16, 2007.
• Jesse Vivian, "What’s In a Name? [25]" U.S. Pharmacist, Sept. 13, 2002.
• Rita Rubin, "Off-label Botox linked to serious side-effects [15]," USA Today, Feb. 11, 2008.
• Amy Newburger, "Cosmetic Medical Devices and their FDA Regulations," Archives of Dermotology, Vol. 142:225-228, Feb. 2006.
• Consumers Union, "Prescription for Change: Detailing," Consumers Union, March 2006.
• Marc-André Gagnon and Joel Lexchin, "The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States," PLoS, Vol. 5(1) Jan. 2008.
• FDA warning letter to Eli Lilly concerning DTCA of Sarafem [26], Nov. 11, 2000.

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Mary Ebeling is an Assistant Professor of Sociology in the Department of Culture and Communication at Drexel University in Philadelphia, Pennsylvania. Her research focuses on emerging technologies and the construction of technological markets.