Ad Nauseam

That’s because the U.S. is one of only two countries (the other being New Zealand) that allow direct-to-consumer advertising (DTCA) of pharmaceuticals. Since 1938, the U.S. Food and Drug Administration (FDA) has been responsible for regulating this type of communication, but industry, researchers, and practitioners are still debating whether the ads provide a service to consumers or unintentionally harm them.

Some believe advertising raises awareness, empowers patients to discuss treatment with their health-care providers and, theoretically, improves the doctor-patient relationship. Others argue that it leads to overdiagnosis, overtreatment, and higher drug prices (to cover the costs of advertising).

The American Medical Association (AMA) has taken the latter stance, and, in 2015, called for a complete ban of DTCA.¹ The organization argues that a growing number of pharmaceutical advertisements flooding consumer airwaves has the effect of “driving demand for expensive treatments despite the clinical effectiveness of less costly alternatives.” Pharmaceutical companies also are expanding beyond traditional print and television ads to find new ways to reach patients’ (or potential customers’) eyes and ears. Website ads, television episode sponsorships, and awareness campaigns are blurring the line between what is and isn’t considered an advertisement and where DTCA is and isn’t permitted.

In March 2018, the FDA announced that its Office of Prescription Drug Promotion (OPDP) is launching a research program to better understand how people interpret the risk-benefit profiles communicated in promotional materials, and how they affect patients’ and health-care providers’ behaviors.²

ASH Clinical News spoke with researchers to trace the history of DTCA, weigh its risks and benefits, and discuss the continuing debate about its regulation.

The History of Pharmaceutical Ads

In its early years, pharmaceutical advertising was directed toward physicians, as companies believed patients lacked the necessary background knowledge to evaluate such information. Congress seconded that notion and passed the Food, Drug, and Cosmetic Act (FDCA) in 1938, which increased federal authority over drugs and – for the first time – mandated that drugs be proven safe to receive FDA marketing approval.³

In the 1960s, Congress intensified its focus on physician-directed advertisements, largely in response to the realization that thalidomide, marketed in Europe and Canada as a sedative to treat morning sickness during pregnancy, caused birth defects in thousands of babies. In an attempt to prevent such tragedies from occurring in the U.S., legislators added the Kefauver-Harris Amendment to the FDCA, which transferred jurisdiction over prescription advertising from the U.S. Federal Trade Commission to the FDA.⁴ The amendments also stated that companies needed to prove that drugs were safe and effective; once a drug was approved, companies were required to report any adverse events to the FDA.

In 1969, the FDA settled on final regulations for prescription drug advertising. The ads must present a “fair balance” of information describing both the risks and benefits of a drug, include facts that are “material” to the product’s advertised uses, and include a “brief summary” that mentions every risk described in the product’s labeling.⁴

Though relatively broad, these guidelines were sufficient to ensure that the ads provided accurate information to health-care providers – at least until the 1980s, when some pharmaceutical companies began advertising directly to consumers through print ads in magazines and newspapers.

The agency became concerned that the existing guidelines could not adequately govern this new sphere of advertising and requested a moratorium on this type of communication from 1983 to 1985 while it reviewed its policies.³ In 1985, the FDA decided that DTCA should meet the same legal requirements as physician-directed advertising.

DTCA continued in print, but was scarce in broadcast media because it was expensive to purchase enough airtime to list every risk of a drug included in the not-so-brief summary. Recognizing this as an obstacle for advertising, the FDA relaxed those guidelines in 1997, requiring only “major risks” to be listed, along with resources for patients to find more information.³

“DTCA was basically non-existent before 1997 due to the FDA regulations surrounding risk disclosures,” Brad Shapiro, PhD, an associate professor of marketing at the University of Chicago Booth School of Business, told ASH Clinical News. Met with a friendly regulatory environment, companies increased their spending on DTCA year after year, into the billions of dollars in the early 2000s.⁵ That number fell slightly for the first time during the financial crisis of 2008, but rebounded and reached $5 billion in 2015.⁶

Regulating DTCA

The regulations for broadcast DTCA follow those originally outlined for health-care provider–directed advertising, with a few additional conditions to satisfy the FDCA’s “fair balance” requirement, depending on the format or intent of the advertisement. The agency characterizes three types of DTCA: productclaim ads, reminder ads, and help-seeking ads.

“Product-claim ads” include the name and indication of the drug and make claims regarding its safety or efficacy. These materials must include a brief summary of the drug’s risk and are subject to the FDA’s most stringent regulations. “Reminder ads” name a drug but do not mention its indication, and “help-seeking ads” mention an indication but do not name a specific drug; neither are required to communicate information about a drug’s risks.⁷

A pharmaceutical company can submit drafts of an ad to the FDA for advance feedback but, for the most part, DTCA regulations only require that companies submit the materials to the FDA after they have been published or aired.⁸

The agency acknowledges that not all companies take advantage of the preliminary review. And, even when companies do submit their ads, the materials may run for months before the FDA has the opportunity to review them. Often, the FDA finds out about misleading advertisements from health-care providers, patients, or competing companies.⁸

When the agency does come across an advertisement that doesn’t abide by their guidelines – whether it suggests off-label uses for a drug, overpromises benefits, or doesn’t adequately address risks – officials typically send a warning letter or a notice of violation to the company. In rare cases, the FDA can choose to take other enforcement actions with more serious consequences, such as product seizures or criminal action. The agency has won lawsuits requiring GlaxoSmithKline, Abbott, Eli Lilly, and Pfizer to pay billions of dollars in penalties for miscommunicating information in DTCA.⁹

Reading Between the Lines

In March 2018, the FDA sent its first untitled letter (indicating a violation that does not meet the threshold for regulatory action) in three years to CSL Behring, citing misleading information in promotional materials for Idelvion, a recombinant coagulation factor IX concentrate to treat hemophilia B.¹⁰ The ad, which appeared on the product’s website, patient brochures, and sales aids, depicted a person jumping and heading a soccer ball, suggesting that patients taking the drug could safely participate in such activities. However, playing soccer, especially hitting the ball with one’s head, is dangerous for people with hemophilia, even if they are being treated with the drug. The FDA gave the company 10 days to update their materials with more realistic imagery.

“Disease-awareness campaigns sponsored by pharmaceutical companies “blur the line between advertising and a public health campaign.”

—Lisa Schwartz, MD, MS

A May 2018 review of 97 drug ads (representing 60 unique drugs) showed that few broadcast ads adhered to all the FDA’s guidelines.¹¹ Thirteen percent advertised off-label uses and, while the authors did not find blatantly false information, they noted that many of the ads made claims that were potentially misleading. Materials presented information about risks in conjunction with distracting images, so viewers were likely to focus more on the imagery than the list of risks. Only one-quarter of the ads studied provided quantitative information about the drug’s benefits and none provided quantitative information about its risks. Drug efficacy, however, was presented quantitatively in 26 percent of ads.

Although the FDA has been sending fewer warning letters every year, researchers suspect this may be related to increased review requirements within the agency, rather than improved compliance among pharmaceutical companies.⁵ Violations may go unnoticed by the public because the FDA lacks adequate funding and staff to respond to them: In 2008, as a result of staff shortages, only 35 percent of broadcast DTCA materials had been reviewed.⁵ Also, by the time everyone who needs to approve a violation letter has had time to review it, the advertisement or promotional materials may have been discontinued.

Finding New Loopholes

While the FDA may be struggling to keep up with reviewing traditional print and television ads, pharmaceutical companies are expanding their efforts and advertising in new ways, through internet ads and other “patient education” sponsorship opportunities.

In 2009, the FDA sent warning letters to 14 pharmaceutical companies regarding banner ads, which represent a large portion of online advertisements. Most ads were cited for omitting information about the risks of taking particular drugs, overstating the drug’s benefits, or suggesting off-label uses.¹²

Pharmaceutical companies have found ways around the DTCA regulations, though, like shifting their focus to the types of advertisements that do not require detailed information regarding a product’s risks and benefits: reminder ads that give a drug’s name but not indication, and help-seeking ads that describe an indication but do not name a drug.

Help-seeking ads take advantage of an important loophole in “disease-awareness” materials: When a consumer clicks a help-seeking banner ad, he or she is directed to a website dedicated to a particular company or brand of drug, providing the information that would typically classify it as a product-claim ad.

Because an estimated 60 percent of internet users search for medical information online, the potential audience for these advertisements is vast.¹³ Consumers might be redirected to a website that includes information about a drug’s risk, but it is rarely found on the homepage. In other cases, pharmaceutical company–funded websites containing product claims masquerade as grassroots advocacy sites.¹⁴ These websites don’t plaster the name of a drug across the homepage, but may include editorial content, podcasts, or videos featuring experts recommending the drug for a particular indication.

The growing use of social media also presents a unique challenge to regulating DTCA. Social media allows pharmaceutical companies to interact directly with consumers on their own Facebook pages, YouTube channels, and Twitter profiles. Companies can produce both branded and unbranded content that, in turn, consumers can share with their personal networks. In addition, paid spokespeople can share content that isn’t obviously connected to the sponsoring company.¹⁴

Social media and online advertisements have also paved the way for DTCA in countries where it has been banned. Even if the target audiences are residents of the U.S. or New Zealand, for example, there are no barriers that prevent residents of other countries from viewing the ads.

“Use of the internet, social media, and mobile technology by firms to promote their prescription drugs has grown substantially in the last decade and continues to rapidly expand,” an FDA spokesperson told ASH Clinical News. “The FDA is taking the opportunity to work on guidance that considers new technologies and includes information about social science research to better reflect the agency’s current thinking on these issues.”

A Very Special Episode

In a move that some researchers consider even stealthier, drug companies have started using promotional tactics previously employed by disease advocacy organizations and public health initiatives to communicate their message.

A recent episode of the sitcom “Black-ish” raised concerns about this new type of pharmaceutical sponsorship. Series star Anthony Anderson was diagnosed with Type 2 diabetes in real life, a disease that can go undiagnosed for years and is common among African-Americans. Mr. Anderson is the face of a Novo Nordisk–backed awareness campaign called “Get Real About Diabetes” that encourages patients to talk to their doctors about managing the condition.

In a special episode of “Black-ish,” the character he plays receives a diagnosis of Type 2 diabetes, raising awareness about the disease among viewers. The episode specifically mentions that the disease disproportionately affects African-Americans, but this is no ordinary awareness campaign. Rather than working with a disease-awareness organization, Mr. Anderson partnered with Novo Nordisk to produce the episode.¹⁵

Disease-awareness campaigns are intended to empower patients, not to expressly sell a pharmaceutical product, so the FDA has no authority over them. This type of content “blurs the line between advertising and a public health campaign,” according to Lisa Schwartz, MD, MS, co-director of the Center for Medicine and Media at The Dartmouth Institute, who studies pharmaceutical marketing.¹⁶ Since there is no mention of company sponsorship in the television episode, she argued, viewers may lack a healthy skepticism about the information presented.

DTCA also is now headed to the stage: In July 2018, the pharmaceutical company BioMarin announced that it is producing the first-ever musical about bleeding disorders, “Breaking Through!”¹⁶ BioMarin is working with Believe Limited, a creative agency specializing in educational and inspirational content for people living with bleeding disorders, to host a three-day workshop in which performers will work with professional composers, facilitators, and therapists to create an original, six-song musical. The material will eventually be turned into “educational and inspirational videos and shorts to be distributed more broadly,” according to a press release announcing the program.

While consumers may benefit from an increased awareness of relatively common diseases thanks to these efforts, what happens when entertainment is sponsored by a company that manufactures drugs for a rarer disease?

“DTCA promotes use of higher-cost medications when cheaper, generic alternatives that work equally well are available.”

—Joseph Ross, MD, MHS

In a 2017 episode of the soap opera “General Hospital,” doctors diagnosed a patient with polycythemia vera, but the writers did not make this decision on their own. Incyte, a pharmaceutical company whose only FDA-approved drug (ruxolitinib) is indicated to treat the disease, asked the show’s writers to introduce the disease into a plotline to raise awareness.¹⁷ The producers complied, and, without naming the drug, the fictional doctor suggested that leaving disease symptoms untreated would put the patient in danger.

When the character asks, “But this protocol sounds like you are treating the symptoms of this cancer; how do we beat it?” he suggests initiating the standard treatments for the disease (anticoagulation and phlebotomy). According to clinicians and researchers, this dialogue “may constitute subtle promotion of ruxolitinib.”¹⁸

Successful campaigns increase viewers’ awareness of a disease and, after watching the show, viewers may get tested for the publicized condition. If the disease’s diagnosis is not always definitive, as is the case with polycythemia vera, an awareness campaign could lead to overdiagnosis and overtreatment.

The Ups and Downs of DTCA

Many doctors and researchers fear that the costs of DTCA outweigh any benefits. When the AMA voted to recommend a full ban on DTCA, it argued that this move could help curb the rising costs of drugs.¹

“Today’s vote in support of an advertising ban reflects concerns among physicians about the negative impact of commercially driven promotions and the role that marketing costs play in fueling escalating drug prices,” said AMA Board of Trustees Chair-elect Patrice A. Harris, MD.¹ “DTCA also inflates demand for new and more expensive drugs, even when these drugs may not be appropriate.”

Joseph Ross, MD, MHS, a professor of medicine and health policy at the Yale School of Medicine, agreed. “Because we rarely, if ever, see advertising for drugs available as generics, DTCA promotes use of higher-cost medications when cheaper, generic alternatives that work equally well are available,” he told ASH Clinical News.

Dr. Ross also claimed there is little evidence that advertising helps properly inform patients. On the contrary, the evidence suggests that the practice is associated with overdiagnosis and inappropriate treatment.¹⁹ Along with minimal information about risks, the ads rarely provide sufficient evidence to inform patients about how likely they are to experience a benefit from the medication. “My opinion is that all of these issues together contribute to lower-quality, more expensive care for patients,” Dr. Ross added.

However, other researchers believe that DTCA plays an important role in public health and patient empowerment.

In an FDA survey conducted in 2004 (a decade before the AMA called for the ban), many doctors (73%) agreed that because a patient saw DTCA, he or she “asked thoughtful questions during the visit.” Also, 72 percent agreed that DTCA increased awareness of possible treatments.²⁰ Still, 60 percent of respondents thought that the ads did not convey information about risks and benefits equally. Most believed that patients understood the possible benefits of the drug “very well or somewhat,” compared with 40 percent who believed patients understood the possible risks.

In addition, about 75 percent of physicians surveyed believed that DTCA caused patients to think that the drug works better than it does, and 22 percent of physicians felt some pressure to prescribe when patients mentioned seeing DTCA. Overall, though, the report authors stated “doctors believe that patients understand that they need to consult a health-care professional about appropriate treatment.”

Dr. Shapiro, whose research focuses on antidepressant advertisements, contended that the public health benefits of DTCA balance out the costs. He offered the following example: Pharmaceutical companies spend up to $32 million annually on DTCA for medications to treat depression – a condition that has massive economic consequences in the form of missed workdays and decreased productivity. More DTCA “leads to $770 million in wage benefits from increased labor supply,” he explained. If the FDA were to ban all DTCA, “you would lose much more in benefits than you would save in costs.”²¹

The jury is still out about whether pharmaceutical DTCA is satisfying the “fair-and-balanced” requirements originally outlined in FDA guidance for promotional materials, but it is clear that the system needs to evolve with the advertising. Some researchers who spoke with ASH Clinical News suggested that increasing funding for the FDA would allow the regulatory agency and its OPDP to keep a more watchful eye on – and respond more quickly to – misleading advertisements.

Or perhaps the U.S. could adopt the European Medicines Agency’s model of bringing in third-party companies (separate from drug companies and regulatory agencies) to develop unbiased educational materials about treatment options. Others, like Dr. Ross, had a more straightforward solution: “DTCA should be illegal in the U.S.” —By Emma Yasinski