Advertising is a crucial component of pharmaceutical industry marketing around the world and plays an important role in educating physicians and other prescribers about new drugs. However, there is concern that physician exposure to advertisements increases prescribing of advertised drugs and critics have raised concerns about the quality of the information presented in these physician-directed advertisements, including a focus on relative, not absolute, benefit and poor referencing.
The Food and Drug Administration (FDA) through its Division of Drug Marketing, Advertising and Communications (DDMAC), regulates physician-directed pharmaceutical advertising in the United States. However, ensuring advertisement adherence is challenging and FDA resources dedicated to this task are limited. DDMAC’s fiscal year 2008 budget of $9 million is dwarfed by the pharmaceutical industry’s $58 billion marketing budget.
“The limited resources of DDMAC are a major barrier to successful regulation of the pharmaceutical industry’s multi-billion dollar marketing budget,” said lead author Dr. Deborah Korenstein of Mount Sinai School of Medicine.
While the FDA can require that companies change or remove non-adherent advertisements, given DDMAC’s size and the volume of marketing materials it regulates, it would be unreasonable to expect each individual pharmaceutical advertisement to be reviewed.
Acknowledging this regulatory challenge, the FDA has recently asked physicians to report non-adherent or misleading advertisements through its ‘‘Bad Ad’’ program, explaining that ‘‘With your valuable assistance, FDA can be more effective in limiting the number of misleading promotional messages directed to health care professionals.”
Despite the recent efforts of this program to identify grossly misleading advertisements, there has been no systematic assessment of the adherence of physician-directed advertisements to FDA regulations in the last 20 years and none to current standards, which were last updated in 2001.
As a result, authors from a recent study published in PLoS sought to determine adherence rates to the 2001 FDA guidelines among current print advertisements directed at physicians within biomedical journals and to describe content important for safe prescribing.
The study found that from a small sample that “nearly half of physician-directed advertisements fail to adhere to at least one FDA guideline regulating content.”
Study Design and Methods
The authors performed a cross-sectional analysis of November 2008 advertisements for prescription pharmaceuticals in top biomedical journals published in issues over a single month and hypothesized that rates of non-adherence to FDA guidelines would be high and that many advertisements would not present complete information important for safe prescribing. The authors excluded advertisements for devices, over the counter medications, and disease awareness.
The authors also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. The authors’ advertisement assessment tool included items based on FDA Prescription Drug Advertising Guidelines. FDA guidelines describe 21 unique items used to classify advertisements as ‘‘false, lacking in fair balance, or otherwise misleading.” The authors categorized advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. Advertisements were considered:
- Adherent if they contained none of the 21 features used by FDA to classify advertisements as misleading,
- Non-adherent if they contained one or more of the features used by FDA to classify advertisements as misleading, and
- Possibly non-adherent if there were no features clearly defining a misleading ad but at least 1 of those items for which information was incomplete.
Prior to initiating the reviews, the authors examined advertisements which had received FDA warning letters in 2008 (of which none was in our sample) to determine the approach of FDA to the regulations. All advertisements were reviewed between January and December of 2009.
All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. The final sample included 89 unique advertisements for 82 products. Thirty-six manufacturers advertised products in our sample, with a median of 3 advertisements (range 1–21) and 2 unique advertisements (range 1–7) per company.
Adherence to FDA guidelines
Among the 83 unique full advertisements:
- 15 (18.1%) were fully adherent to FDA guidelines,
- 41 (49.4%) were non-adherent to at least 1 FDA mandated item, and
- 27 (32.5%) were possibly nonadherent due to incomplete information
Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification.
There were statistically significant differences in non-adherence rates to FDA guidelines by item content. Nine (10.8%) advertisements were non-adherent to at least 1 FDA item focused on safety, whereas 18 (21.7%) advertisements were non-adherent to at least 1 FDA item focused on efficacy, 16 (19.3%) to at least 1 FDA item focused on references, and 23 (27.7%) to at least 1 FDA item focused on other issues.
Safe Prescribing Content
Many advertised drugs in the sample presented potential risks to patients, with 31 (37.3%) containing black box warnings and 33 (39.8%) placing patients at risk for death or serious morbidity. However, when evaluating advertisement content important for safe prescribing, the study found that many physician-directed advertisements lacked important information. The majority (57.8%) did not quantify serious risks and 24 (28.9%) failed to present appropriate numbers to quantify benefits. Thirty-six advertisements (43.4%) referenced ‘‘data on file’’ and 40 (48.2%) lacked verifiable references, due either to an absence of any references or to the presence of references only to ‘‘data on file’’ or the product’s package insert.
Discussion
Based on the above findings, the authors noted that, “physician-directed advertisements contained bias with regard to a wide variety of issues across content areas addressed by FDA guidance.” The authors also asserted that, “advertisements do a poor job of conveying basic information necessary for safe prescribing, with the majority failing to quantify serious risks, more than one quarter failing to quantify benefits and nearly half providing no verifiable references.” Accordingly, the authors maintained that their study provides a context to inform the FDA’s new ‘‘bad ad’’ program.
However, the authors recognized that, despite the high rates of FDA non-adherence, “the mean number of biased features in each advertisement was low and most advertisements we reviewed satisfied the majority of FDA guidelines despite a general absence of content important for safe prescribing.”
Nevertheless, the authors noted that although FDA guidelines are detailed, they do not target many of the ad features most important for providing prescribers with useful information. For instance, FDA emphasizes avoiding frankly false information and balancing efficacy and safety information but does little to encourage the presentation of useful and accurate information. An advertisement containing no specific efficacy claim, no quantification of drug safety and no verifiable references would adhere fully to FDA guidelines, despite presenting no practical information for clinicians.
Consequently, the authors maintained that, “physicians should ensure that their prescribing is informed by the clinical literature and not by marketing materials.” This means more interaction and more CME. They added that, if “FDA is truly committed to improving prescribing and protecting the health of the public it should demand that content important for safe and effective prescribing be consistently presented in physician-directed advertisements.”
In addition, the authors recommended that FDA update and simplify its guidelines for physician advertisements to facilitate the review process. They noted that, updated FDA guidelines should be straightforward and objective, and should include requirements that physician advertisements present clear risk quantification, absolute benefit information, description of the appropriate population to receive the drug, and verifiable references, either to the peer-reviewed published literature or to studies registered within federally-sponsored internet sites such as ClinicalTrials.gov in the case of unpublished data.
The authors noted that these new guidelines might be applicable only to physician-directed advertisements, with separate guidance for DTC material, with greater focus on safety issues. Additionally, they asserted that new objective requirements would serve to enhance prescribing and public health by improving the quality, accuracy and transparency of advertisements, simplify at least part of the FDA review process, and facilitate physician participation in reporting ‘‘bad’’ advertisements.
Study Limitations
The authors noted that a major challenge of the study was performing advertisement evaluations given the subjectivity of the current FDA guidelines. For instance, the FDA describes that advertisements are misleading if they use ‘‘a quote or paraphrase out of context to convey a false or misleading idea’’ or ‘‘headline, subheadline, or pictoral or other graphic matter in a way that is misleading’’, without providing explicit definitions. Another limitation was the subjectivity of determinations of adherence.
The study was also limited because the sample of advertisements was from a single month in 2008, so they cannot comment on trends in advertisement characteristics over time. The authors also focused on high-impact biomedical journals publishing original research, excluding lower-impact and more narrowly focused publications and those publishing clinical reviews, which may also be frequently read among clinicians.
Conclusion
In the end, the authors noted that FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information. This change is necessary according to the authors because current FDA guidelines are subjective and challenging to enforce and do not emphasize transparency and the inclusion of basic information relevant to prescribing.
But as John Kamp, Executive Director of the Coalition for Healthcare Communication noted, no one knows for sure what’s compliant until the FDA says so, most often in a FDA warning letter. This serves no one including doctors, patients, FDA and industry. Everyone loses under the current standards because the rules prevent good communication and subject the industry to unwarranted criticism from the press, politicians and medical professionals and uneven, unpredictable enforcement from FDA. Accordingly, Kamp argued that, “better regulations would enable better informed patients and doctors, thus better patient care.”