A Cautionary Tale for Anyone Expecting FDA Social Media Guidelines Any Time Soon

A Cautionary Tale for Anyone Expecting FDA Social Media Guidelines Any Time Soon

If you think waiting over two years for FDA to issue guidelines it promised for regulation of "Promotion of Prescription Drug Products Using Social Media Tools," then you should take a look at the following timeline and weep.

This timeline documents the major steps in FDA's process of developing guidance for direct to consumer television (DTC) and radio ads; ie, "standards that would be considered in determining whether the major statement in direct-to-consumer television and radio advertisements relating to the side effects and contraindications of an advertised prescription drug intended for use by humans is presented in a clear, conspicuous, and neutral manner":

• 1 November 2005: FDA convenes a 2-day public hearing to discuss the issue (see "FDA DTC Hearings: Snippets from Day 1" and "DTC Pros and Cons Presented at Public Hearing"). Sound familiar?


• 21 August 2007: FDA announces it will conduct a study of "consumer evaluations of variations in communicating risk information in direct-to-consumer (DTC) prescription drug broadcast advertisements." It opens a 90-day period to submit comments regarding this study. This study used the latest cognitive science technique called Affect Misattribution Procedure (AMP), in which participants are asked not to judge the TV ads' imagery directly, but to judge whether or not a Chinese character shown to them afterward is positive or negative. I suggested FDA NOT use Chinese characters because that would be discriminatory, but they did not listen to me (see "FDA at a Mall Near You: The Manchurian Connection"). With regard to social media guidelines, the FDA has also announced it will do some studies before issuing guidance (see "FDA's Proposed Web Study Will Further Delay Social Media Guidelines"). Deja vu all over again!


• 29 March 2010: FDA finally publishes the draft guidance, more than 4 years after the public hearing (see Federal register ref: 75 FR 15376). FDA was goosed along by an act of Congress: the Food and Drug Administration Amendments Act of 2007 (FDAAA), which required that the major statement in DTC television or radio advertisements (or ads) relating to the side effects and contraindications of an advertised prescription drug intended for use by humans be presented in a clear, conspicuous, and neutral manner. FDA was forced into RULEMAKING mode rather than GUIDANCE mode, which is how the pharma industry wants the agency to approach the regulation social media drug promotion as well (see "Pfizer Asks for New FDA Regulations, Not Guidance, for Social Media").


• June 2011: FDA published an executive summary of a study of the methodology of the AMP study cited above entitled "A Supplementary Test of Distraction in DTC Advertising Using an Implicit Measure, The Affect Misattribution Procedure" (find it here). Maybe FDA read my comments after all!


• 27 January 2012: FDA announced that it added a document to the docket for the proposed rulemaking concerning a study entitled: "Experimental Evaluation of the Impact of Distraction on Consumer Understanding of Risk and Benefit Information in Direct-to-Consumer Prescription Drug Television Advertisements" (Distraction Study; see Docket No. FDA–2009–N–0582). This document reopened the comment period (extending the deadline to February 27, 2012) for the rulemaking proceeding to allow an opportunity for comment on the study as it relates to the proposed standards. Way back during the public hearing in 2005 I was unimpressed by research claiming that TV drug ads were designed to "distract" viewers from reading the fair balance (see op cit and "Ruth Day and the Bees Repeat Performance at House DTC Hearing" for an update on that).


• 23 March 2012: FDA reopens the comment period for a second time "in response to a request for more time to submit comments to the Agency." The new comment period will expire on April 9, 2012. According to the FDA, the "Pharmaceutical Research and Manufacturers of America (PhRMA) submitted a letter dated February 20, 2012, requesting an additional 15 days for interested persons to comment. FDA believes that an additional 15 days to comment on the Distraction Study as it relates to the proposed standards is appropriate."

What strikes me are the similarities between the evolution of these DTC guidelines/rules and the long-awaited social media guidelines.

First, there are the delaying studies and studies of studies. It's well-known that if you wish to halt progress, do a study.

Second, I sense that the drug industry pushed the FDA into RULEMAKING rather than issuing guidelines although it took an act of Congress to do that in this case. The drug industry may use the courts in the case of social media (another example of how an "activist" judiciary can work both sides of the aisle).

If it takes the FDA SEVEN or more years to complete this process for TV ads, I imagine it will take them 10 years to finalize guidance or rules (whatever!) for regulation of the use of social media for drug promotion. While TV has more or less stagnated during the seven years since 2005, social media will look completely different by the time those 10 years are up in 2019!

Voltaren "Adherence Email" Gets FDA Warning Letter: Is It Justified?

Voltaren "Adherence Email" Gets FDA Warning Letter: Is It Justified?

As of April 15, 2010, FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) sent out 5 "notice of violation" (aka "warning") letters to drug companies regarding various promotional pieces. One letter is of interest because it concerns a direct-to-consumer (DTC) adherence "wave 5 e-mail" ("Adherence Email") for Voltaren, an NSAID topical gel marketed by Novartis. This may be the FIRST FDA warning letter issued for an email promotion. But is it justified?

Among other violations, the letter cites "minimization of risk information." The letter (find it here) states:

"The Adherence Email prominently presents efficacy claims in large bolded font size and in colorful text and graphics surrounded by a significant amount of white space. In contrast, the risk information is relegated to the bottom of the email and is presented below the indication for use in extremely small black font, and in single-spaced paragraph format that makes the information very difficult to read. Furthermore, while the Adherence Email presents efficacy claims for Voltaren Gel 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 (e.g., “cardiovascular thrombotic events” and “hematological effects”). The overall effect of this presentation undermines the communication of important risk information, minimizing the risks associated with Voltaren Gel, and misleadingly suggesting that Voltaren Gel is safer than has been demonstrated."

"For me, that is a little out of left field," said Mark Senak over at EyeOnFDA Blog. "To my knowledge," said Senak, "FDA/DDMAC has not issued any standards on how to do this [present risk information] aptly." I disagree with Senak. The FDA has issued "standards" about presenting risk information.

In my previous analysis of DDMAC warning letters (see "An Analysis of DDMAC Warning Letters Regarding Risk Information in Broadcast Drug Ads"), I noted that 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, specifically) 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.

The Voltaren Adherence Email (find it here) seems to violate "rules" #1 and #3 above. That is, it would violate those rules IF it were in the category of "broadcast" DTC. FDAAA requires FDA to enforce "clear and conspicuous" risk information in TV and radio ads that are broadcast to a mass audience. The Voltaren Adherence Email does not seem to fit in that category of ad because it was not a TV or radio ad and it was likely sent to a select group of consumers, not a mass audience.

However, in the draft guidance mentioned above, FDA states: "Unless otherwise specified in this draft guidance, the principles set forth below apply to all promotional pieces, regardless of the medium used or the target audience."

So I am a bit confused as to whether or not, in the case of the Voltaren letter, the FDA has overstepped the authority given it by Congress to regulate risk information in non-broadcast media. What do you think?

An Analysis of DDMAC Warning Letters Regarding Risk Information in Broadcast Drug Ads

An Analysis of DDMAC Warning Letters Regarding Risk Information in Broadcast Drug Ads

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.

Is This Juvederm XC DTC Print Ad "Fair and Balanced?"

Is This Juvederm XC DTC Print Ad "Fair and Balanced?"

Take a look at the Juvederm XC ad, which I found in this week's New Yorker Magazine, which (coincidentally) includes an article about treatment of wrinkles ("Face It: The Truth About Wrinkles"). The article does not mention Juvederm and hardly has anything at all to say about injection of gels into the skin.

Do you think this ad is "fair and balanced"; ie, presents risk information that is "comparable in depth and detail with the claims for effectiveness or safety" as required by the Federal Food, Drug, and Cosmetic Act?

FDA issues "notice of violation (NOV)" letters to drug companies when it feels that promotional pieces overly minimizes risk information.

Should FDA send a NOV letter to Allergan, which markets Juvederm?

"Promotional materials are misleading," said FDA in a recent letter to Meda Pharmaceuticals regarding an Astelin promo piece (see "FDA Warns Meda Pharmaceuticals that Astelin Isn't Approved as a Cure for House Cleaning!"), "if they fail to present information about risks associated with a drug with a prominence and readability reasonably comparable with the presentation of information relating to the effectiveness of the drug."

With regard to the Astelin promo piece, FDA noted "the only risk information contained on the sign (a disclosure of common adverse events) is presented at the bottom of the sign after the indication for the drug in extremely small font size and in a single-spaced format that makes this information very difficult to read."

Clearly, the Juvederm ad also presents risk information in hard to read "mouse typeface." But let's take a more scientific, quantitative approach. I compared the area devoted to risk information versus benefit information in both the Astelin and Juvederm ads. My thesis is that there is a similar quantitative de-emphasis of risk information in the latter as in the former and that Allergan should also receive a letter from the FDA.

I've collected benefit vs. risk information data for a number of print DTC ads and have found that, on average, Rx drug print ads devote 65.3% to benefit information (includes image area) and 11.8% to risk information (not including information on back of the ad). See "Print DTC: How Does It Measure Up?: A Quantitative Analysis of Risk vs. Benefit Information." Clearly BOTH the Astelin and Juvederm ads devoted MUCH less of the ad space to risk information than the AVERAGE print DTC ad.

I don't know if the FDA will send a letter to Allergan or not. FDA has sent letters regarding violations that seem as trivial as this one may be. I'll be keeping an eye out.