The FDA Amendments Act (FDAAA), which was signed into law in 2007, requires that the FDA issue new regulations regarding the presentation of risk information in broadcast (TV and radio) drug ads directed to consumers (DTC ads). On March 29, 2010, the FDA published the proposed regulations in the Federal Register (see here). FDA had issued guidance relating to presentation of risk information previously and most experts agree that the proposed regulations pretty closely resemble that guidance (see “Draft Guidance on Presenting Risk Information in Prescription Drug and Medical Device Promotion“; pdf file).

Specifically, the regulations focus on determining whether a drug ad’s “major statement” (ie, disclosure of the major side effects and contraindications of the drug) is presented in a “clear, conspicuous, and neutral manner” as required by FDAAA. FDA says that a major statement would be considered to be presented in this manner if:

  1. Information is presented in language that is readily understandable by consumers;
  2. Audio information is understandable in terms of the volume, articulation, and pacing used;
  3. Textual information is placed appropriately and is presented against a contrasting background for sufficient duration and in a size and style of font that allows the information to be read easily; and
  4. The advertisement does not include distracting representations (including statements, text, images, or sounds or any combination thereof) that detract from the communication of the major statement.

FDA’s Kristin Davis, deputy to Tom Abrams, head of FDA’s Division of Drug Marketing, Advertising and Communication (DDMAC), reminded attendees of a recent industry conference that the FDA is “using the principles of the draft guidance virtually every day in both pre-reviews and Warning Letters,” according to John Kamp, Executive Director, Coalition for Healthcare Communication.

I was curious to learn if recent Notice of Violation (NOV) letters (aka “warning letters”) issued by DDMAC actually cited violations of one or more of the 4 rules for the presentation of the major statement in DTC ads. I looked at all of the 16 NOV letters that DDMAC issued in the first quarter of 2010. Of these, only 10 included violation warnings related to consumer promotional pieces/ads.

Many NOV letters include warnings about several different types of violations, including

  • Broadening of Indication
  • Failure to State Full Indication
  • Failure to Submit Under Form FDA-2253
  • Minimization of Risk Information
  • Omission of Material Facts
  • Omission of Risk Information
  • Overstatement of Efficacy
  • Promotion of an Unapproved Drug
  • Unsubstantiated Claims
  • Unsubstantiated Comparative Claims
  • Unsubstantiated Effectiveness Claims

I counted a total of 22 such violations concerning promotional pieces intended for consumers and/or patients in the ten letters.  These promotional pieces included print and TV ads, web sites, videos, patient brochures, waiting room signs, and co-pay brochures. That is, not all of these were “broadcast” print and TV ads, which is the focus of the draft guidance and proposed regulations. In fact, ONLY 4 letters included violations relating to broadcast DTC ads!

These 4 letters included 6 such violations, only 33.3% (2) of which were about risk communication. One concerned Cymbalta, a drug promoted by Eli Lilly. The FDA letter stated:

“We note that the Print Ad contains the statement, ‘See left page for Important Safety Information, including Boxed Warning.’  at the bottom of the page and that risk information is presented on an adjacent page, but this is not sufficient to provide appropriate qualification or pertinent information for the claims made in the body of the ad or to mitigate the overall misleading presentation. This risk information is placed in a single column in a single-spaced paragraph on a page with unrelated advertisements or magazine content. It appears unconnected to the main body of the Print Ad and is not likely to draw readers’ attention.”

This seems to violate “rule” number 3 above (ie, “Textual information [should be] placed appropriately and is presented against a contrasting background for sufficient duration and in a size and style of font that allows the information to be read easily”).

The second broadcast DTC risk-related violation concerned Truvada, a drug marketed by Gilead Sciences, Inc. The FDA letter stated:

“The Print Ad is false or misleading because it fails to present the risks associated with Truvada with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of the drug. Factors impacting prominence and readability include typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis. In the Print Ad, claims pertaining to efficacy and benefits of Truvada are conveyed through headlines, colorful text, illustrations, bullets, and eye-catching graphics and images. In contrast, the risk information is presented in several long, single-spaced paragraphs in small font/text type in a single column along one side of the Print Ad.”

Again, a violation of “rule” number 3.

At least one letter cited language in an OraVerse patient brochure that “presents efficacy claims for OraVerse in language that is easily understandable to consumers, it presents risk information using complex medical terminology that is not likely to be comprehended by the same audience.” This would violate “rule” number 1 above, except that patient brochures are not “broadcast” media and hence are NOT covered by the newly proposed rules.

Even when you look at ALL the 52 violations cited in ALL 16 letters, only 34.6% (18) are concerned with risk information. So, FDA may not be overly focused on risk. It is, however, focusing on much more than broadcast TV and print ads in its warning letters. Increasingly, FDA is focusing on Web-based promotions, for which there is no guidance and no proposed rules.