Recently, the Center for Business Intelligence (CBI) held an Evidenced Based Marketing and Promotion conference. One presentation was given by Arnie Friede, Former FDA Associate Chief Counsel, and former Senior Corporate Counsel for Pfizer, Inc.
In the first part of Mr. Friede’s presentation, he discussed the scope of the jurisdiction the Division of Drug Marketing, Advertising, and Communications (DDMAC) has over pharmaceutical and medical device manufacturers. He first went over the difference between disease awareness and promotional claims. Mr. Friede noted that mixing disease awareness claims with product claims in the same piece is likely to be interpreted as a claim that the product addresses all aspects of the disease.
Next, Mr. Friede explained how DDMAC is now applying concepts from a May 2009 Draft Risk Disclosure Guidance, which discusses minimization of risk due to accessibility, placement, and conspicuousness in advertisements. For example, he noted the failure of promotional video to include any risk information during audiovisual portion.
Accordingly Mr. Friede asserted that companies must be sure to include warnings and precautions in advertising and not omit any risk information. Additionally, he noted the importance of putting risk and benefit information in consumer friendly language (not just benefit), and for such information to be integrated together. He also pointed out that companies should not understate the likelihood of side effects.
With respect to social media, he noted that a widget that allows for shared content on Facebook, must have risk information and that this is particularly problematic for a black box drug with a REMS. He noted that a hyperlink to risk information is not adequate and that risk information must be in each part to qualify the claims. Mr. Friede asserted that the “one click rule,”—meaning one click from the page takes you to the risk information—does not exist. Consequently, he noted that many of these issues have significant implications for social media guidance.
Additionally, Friede explained that patient videos/testimonials will be considered by DDMAC as making representative claims about product attributes. As a result, he noted that substantial evidence must support the claims, even if the video/testimonial accurately reflects the individual’s experience. He also noted how FDA may read depictions as making comparative superiority claims, which also require substantial evidence by way of comparative head-to-head trials.
Friede also explained that quality of life claims require substantial evidence such as patient reported outcomes data consistent with FDA’s PRO Guidance—example: claims that a drug “leaves one feeling very much alive” and “bring life into balance” require valid PRO data. In addition, he noted that advertisements that go beyond specific disease parameters to make general behavioral claims are not permitted, and that such claims need substantial evidence for support.
He also pointed out that comparative pharmacoeconomic claims, not directed at formulary decision makers, need to be supported by substantial evidence. Also, Friede noted that verbal statements by representatives at medical meetings are actionable by DDMAC. He also discussed how next generation/subtle superiority claims require head-to-head comparative trials. Friede touched on:
- Clinical Significance of In VitroData.
- Use of Rating Scales That Are an Aggregation of Multiple Measures But That are Used to Call out a Single Attribute.
- Guarantee Claims—i.e. Guarantee That You Will Reach Blood Pressure Goal—Overstates Efficacy Based on the Clinical Data. Implied Comparative Superiority.
Broadening of Indication/Off-Label Promotion
During this part of Friede’s presentation, he pointed out that DDMAC can take action on a company for broadening a products indication when the company fails to include specific qualifiers from approved indication. He also noted that inconspicuous qualifying information is not sufficient to save the claim. In addition, unqualified comparisons to other drugs suggest that the advertised drug is approved for all uses that the comparator drug is approved for, which therefore broadens the indication/off label.
Friede also explained that inclusion of the actual indication for the advertised drug does not qualify the claim, presumably unless the actual indication is conspicuously stated. He noted that claims of first line use when the drug is only approved for second or third line are off label.
Misleading By Omission
On this topic, Friede noted that DDMAC can bring actions against companies for omission of material fact by failure to include contextual information. There can also be misleading by a company having a contradiction between PI labeling and representations in advertising, including how the dosing works in practice and concentration of drug at site of interaction. Friede pointed out that misleading claims can also arise from failure to submit 2253 and/or to submit advertising for accelerated approval drug 30 days early. This is particularly problematic for purported disease awareness advertising that FDA recharacterizes as promotional.
On this point, Friede discussed FDA’s recent warning Letter to Novartis on two unbranded websites that FDA recharacterized as promotional communications. Specifically, he noted during these examples that FDA does not have regulatory jurisdiction over disease awareness communications that do not promote a specific product.
Disease Awareness Communications
Friede recognized that disease awareness communications effectively amount to scientific speech that is protected by the First Amendment and is beyond the scope of FDA’s jurisdictional reach. The implication of finding that a communication by a drug manufacturer is promotional versus disease awareness is that FDA has oversight of affirmative representations in terms of substantial evidence. Friede pointed to what FDA has already said about how to distinguish between disease awareness communications and promotional speech, including FDA/DDMAC’s June 2004: Draft “Guidance for Industry, „Help-Seeking‟ and Other Disease Awareness Communications By or on Behalf of Drug and Device Firms”.
Friede also pointed out that FDA has acknowledged that disease awareness communications are not subject to requirements of the Federal Food, Drug, and Cosmetic Act.
Consequently, he explained that Disease Awareness Communications are those communications that discuss a particular disease or health condition, but does not mention any specific drug and does not make any representation or suggestion concerning a particular drug. Accordingly, Friede described situations where FDA may find that a supposed disease awareness communication is promotional.
First, he noted “Bookending,” which is when a company combines disease awareness information with a reminder advertising or product claim promotion. Proximity may cause audience to perceive the two together (i.e. to link them), particularly if the two are perceptually similar, thereby making each ―promotional. Friede went on to explain that FDA views perceptual similarity as similarity in terms of themes, such as story lines, or other presentation elements, such as colors, logos, tag lines, graphics, distinctive visual elements, common narrator or background music (other elements of motif).
Additionally, Friede noted that “one product companies” are not automatically disqualified from disease awareness communications, but they have heightened scrutiny. Friede also recognized that the presence of a company’s name on the disease awareness piece may, depending on overall meaning and context, be enough for FDA to consider it promotional.
Products class communications, particularly if only one product in the class, may be deemed promotional depending on overall meaning and context. Consequently, FDA has substantial discretion, which is difficult to challenge unless the company is willing to risk enforcement action in court and let the court decide the question. Friede discussed examples from two recent incidents where FDA, applying the concepts from the Draft Disease Awareness Guidance, concluded that company web sites in fact implicitly made a representation or suggestion about a specific drug and thereby effectively promoted it.
Finally, Friede discussed the “Bad Ad Program,” a new program administered by DDMAC, to insure truthful prescription drug advertising and promotion. He explained how DDMAC began exhibiting the new program at major medical conferences starting in May 2010 to educate prescribers.
Essentially, Friede noted that FDA is enlisting prescribers to recognize and report possible advertising violations or put differently: FDA is deputizing doctors to serve as FDA advertising investigators in the field at the point of interaction between detailer and doctor (i.e. in the office, at medical meetings, at speaker presentations). “Depending on your perspective, another way to characterize it: FDA is turning doctors into unpaid informants.”
The program provides HCPs with an easy way to report to FDA what they think are violations of promotional rules and complaints can be reported anonymously. However, as Friede noted, in doing so, FDA is expanding its jurisdictional reach substantially. Criteria remain relatively ambiguous. He asked whether you can provide useful information to patients without even a hint of product-specific communication.