A magazine ad for Boniva, fronted by actor Sally Field, generated the DDMAC (now the Office of Prescription Drug Promotion, or OPDP) Untitled Letter last year due to following phrase: “After one year on Boniva, 9 out of 10 women stopped and reversed their bone loss.” That didn’t jibe with the scientific data, DDMAC said in the letter, before requesting that all ads containing the phrase be removed from the campaign.

Genentech went a step further. In September of last year, the company began running corrective magazine ads addressing the overstated claim. The corrective ad states that the violative ad “may have given you the wrong impression.” It goes on to state that “Boniva has not been proven to stop and reverse bone loss in 9 out of 10 women and is not a cure for postmenopausal osteoporosis.” The corrective ads will run though April 2012.

Unlike their mild-mannered, Untitled Letter cousins, Warning Letters are considered more severe, and they typically mandate corrective ads to clear up any overstated claims or minimized risk information. Given that Genentech received the former communique and not the latter, it’s notable that the company chose to run corrective ads without a mandate.

After speaking with DDMAC about the Untitled Letter, Genentech worked with the agency to create and then “voluntarily” launch the corrective ads last September, according to Chris Vancheri, director, public affairs, at Genentech.

In a statement, Genentech said that in addition to the corrective advertisements – which are running in several women’s magazines, including Weight Watchers and this month’s WebMD the Magazine – “our clinical specialists have reached out to health care providers” to inform them about the corrective ads, which intend to “clarify the benefits and risks of Boniva in women suffering from post-menopausal osteoporosis.”

Sally Field was the face of Boniva beginning in 2006, but Vancheri says Field is “no longer engaged” on the campaign. GlaxoSmithKline signed a co-promotion deal with Roche on Boniva in 2001, but the companies broke the partnership in 2010.

Abram’s comments, made during a panel this morning at the Drug Information Association’s (DIA) annual meeting in Chicago, prompted audience members to probe Abrams, and his CBER colleague Lisa Stockbridge, branch chief of the Advertising and Promotional Labeling Branch, about specific policies governing online promotion. One audience member wondered whether unbranded, educational campaigns online could link to branded sites, or if that kind of activity would generate an enforcement letter. Abrams responded that his own question, in that instance, would be, “Why are you linking to a brand site?” if a campaign is designed specifically to educate about a disease, as opposed to a branded campaign designed to sell a product. When pressed, he said an educational or awareness campaign – which isn’t required to present risk information, since no drug is being promoted – linking to a brand site would “have to be considered on a case by case basis.” Industry has been browbeating DDMAC about issuing social media guidelines for years.

On FDA’s Bad Ad program, one audience member asked what sort of proof would be required to verify improper promotion by a sales rep, given that a discussion between a rep and a physician would likely be verbal and unrecorded. Abrams said that an extensive review of the complaint would happen before moving forward, and then a signed affidavit from the physician, testifying to what was said during a sales meeting, would most likely be required. John Kamp, executive director at the Coalition for Healthcare Communications, and moderator of the panel, wondered aloud about whether a sales rep making hundreds of calls a week would be able to recall exactly what was said during a specific detail. “Couldn’t a sales rep say, ‘I don’t remember what I said, but my training and common response in this situation would be X.’ Would that kind of [defense] fly?” asked Kamp. Abrams didn’t answer the question directly, but insisted that DDMAC was diligent in investigating complaints, and the circumstances surrounding a potentially illicit conversation.

Abrams also discussed a proposed update to Section 502(n) of the Federal Food Drug and Cosmetic Act (FDCA) dealing with “clear, conspicuous, and neutral” major statements, or legally-mandated statements on major risks associated with a given drug. The update was announced in March of last year, and deals with DTC advertising, specifically television and radio, said Abrams. One of the four proposals put forward by DDMAC would require that an “advertisement does not include distracting representations (including statements, text, images, or sounds or any combination thereof) that detract from the communication of a major statement.” Anyone who has seen a drug ad on television will recognize the target of this proposal; the last seconds of a DTC ad are typically used for a voiceover announcing a drug’s “major” risks, while simultaneously providing unrelated images associated with the actors or visual narrative of the commercial.

DDMAC is in the process of being elevated from a division to an office, a process that is “slow even by government standards,” joked Abrams. The new office will be separated into two divisions, healthcare professional and consumer, he said.

But the single most effective tool in the Bad Ad program’s toolkit, according to Arnie Friede, principal at Arnold I. Friede & Associates, and a former associate chief counsel at FDA, is fear. Or rather, in terrorem, a “Latin term that lawyers use” to mean frightening someone into compliance, says Friede.

When the program launched, FDA Commissioner Margaret Hamburg sent an explanatory letter to “more than 33,000” physicians, a fraction of the roughly 972,000 physicians in the US. Sales force management and reps themselves will have to decide if they are willing to play Russian roulette with a physician who may or may not be an informer. “FDA is trying to create the perception that the rep doesn’t know if the doctor is or is not a friend,” says Friede. “Accordingly, reps should be on the straight and narrow.” For FDA, the conversation between a rep and a doctor is one of the hardest areas to regulate efficiently, according to Friede. Creating in terrorem means prevention, he says.

Concerns about the Bad Ad program being abused by competing brands seem to be unfounded. According to FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC), only 4% of the complaints that came in since last May were anonymous. Friede says complaining to DDMAC about competing brand messages is not something new, to be facilitated by the Bad Ad program. “There are plenty of channels for competitive complaints with DDMAC,” says Friede. Companies wishing to complain about marketing materials anonymously can simply do it through a law firm, Friede says, adding that “people that live in glass houses shouldn’t throw stones.”

Of the 328 submissions to the Bad Ad program, 188 came from HCPs, 116 from consumers, and 24 were submitted by industry representatives. The program will be expanded this year, according to DDMAC, to include a “web-based continuing education program,” and a new focus on med students and early career HCPs. FDA will also seek collaborations with medical, pharmacy and nursing schools to “enhance student education.”

The stated aim is to assist FDA’s Division of Drug Marketing, Advertising, and Communications (DDMAC) in its efforts to deter promotional activities. DDMAC examines promotional pieces submitted to the agency, scans ads and TV commercials informally, and monitors drug company exhibits and programs at medical meetings. An important source of information is all the complaints the division receives are from industry competitors who see another company getting away with off-label promotion or unfair comparisons. It’s impossible for DDMAC to catch everything, and certainly not what’s said in meetings between doctors and sales reps or at sponsored dinner programs.

To kick off the Bad Ad program, which was announced last month, DDMAC staffers will give talks and distribute educational materials to providers at medical conventions and society meetings. A brochure advises doctors on how to recognize misleading promos: omitting risks, overstating effectiveness, promoting off-label uses, or making misleading comparative claims. FDA is making it easy for doctors to squeal about objectionable messages by establishing a special call-in number and email address.

It’s not yet clear if the campaign will generate a lot of finger-pointing—or if it does, how DDMAC will deal reports that are vague and undocumented (anonymous calls are okay). Marketers fear that doctors will file complaints based on misunderstandings and personal prejudices. Supporters of the program anticipate that marketers and sales reps will modify their pitches if they think that their audience is taking a much closer look at what they say. But free-speech advocates like the Washington Legal Foundation fear it will chill open exchange of health information, which can be useful.

The Bad Ad campaign fits FDA’s effort to step up enforcement, as Commissioner Margaret Hamburg promised a year ago. The agency has issued 186 warning letters so far this year, putting it on track to meet last year’s record of 570 enforcement missives, according to BNet Pharma. And more of those are coming from DDMAC, which doubled its warning-letter rate to 41 in 2009, vs. 21 the year before. Many recent letters challenge Internet marketing, an activity that remains on FDA’s radar screen. In April, DDMAC sent a long warning letter to Novartis challenging the company’s use of Web sites to promote unapproved uses and to make unsubstantiated claims for Gleevec. FDA plans to develop guidelines on Internet promotion and use of social media by drug marketers, but it’s proving to be a complicated business.

FDA wanted to find out what people really think of the risk information printed on the back of pharmaceutical advertising. Surprise, people tend to absorb far less information from the giant blocks of text printed in drab language.

DDMAC social science analyst Amy O’Donoghue explained FDA’s recent study results to an audience of marketers at Drug Information Association’s annual meeting, yesterday.

“We recognize the current situation where pharma can just reproduce risk information written to doctors in print ads,” O’Donoghue said. So, we looked at current format and different ways of presenting the information and what format.”

The first study examined how people use the current brief information to determine if risk info and med condition affect the time people spend reading the ad, the comprehension of the info, the selection of topics, and the intention to ask a doctor.

FDA created a fake drug called Oncazil, which they used to treat asthma, high cholesterol, excess weight and produced low risk ad or high risk ads for each disease state.

Of the 800 people that saw the ad, most of the, were more worried about the heart valve damage risk in the high-risk advertisement. The average reader spent 26 seconds reading the promotion page and 41 seconds reading the brief summary.

“The conclusions we reached are that the presence of a serious risk did not change the time spent on either page,” O’Donoghue said.

In another study, FDA only looked at overweight drugs. They studied the different formats of brief summaries to see which format presents risk info in the most digestible manner.

• Traditional summary has risk info buried in a giant mix of text in three columns, on back page.
• Q&A format has less info and is more of a dialogue.
• Highlights section is more reader-friendly.
• The drug facts box version was designed similar to the OTC brief summary.

This was a mall intercept campaign and was computer administered, however the screen was the size of a magazine page. 300 people were interviewed.

FDA found no difference in reported intention to ask doctor or differences in risk/benefit tradeoff. Self-efficacy differed by format and people who saw the drug facts box were more confident that they understood the risk information than on the traditional summary.

Most people were positive about the drug facts ad box and the traditional received the lowest marks. People had a significantly more positive attitude towards the highlights and drug facts (54 percent).

“People who like a format more might spend more time on the ad and get more out of it,” O’Donoghue said. “FDA hasn’t outlawed any format, but additional studies will be done to determine content of brief summary forthcoming.”

A Sanofi Aventis employee complained about the 14 warning letters and asked why the practice of purchasing sponsored links on search engines, without fair balance information, was allowed to go on for so long if it was wrong and what else should companies be looking at that they might not know is wrong.

“If you do not know, of if you are not sure [if an ad is okay], submit a proposal for advisory comments,” said Kristin Davis, deputy director, DDMAC. “We have limited resources – the fact that you didn’t hear from us, just like the fact that you went 15 miles over the speed limit on your way to work – doesn’t mean that it’s okay. It just means that the cops weren’t on the road that day. Unless you have advisory comments indicating our opinion, you are not insulated from enforcement action. Especially if you are exploring some new tool and you are not exactly sure, I really encourage that you submit for advisory comments. We prefer that to sending out enforcement letters.”

Davis made it clear that the sponsored link letters were for ads where the pharma company has control of the content, so that the organic search results from Google’s search algorithms are not what FDA is looking at. FDA is targeting sponsored ads on sites like Google and Yahoo where the company has purchased a link space and created a message to be submitted on a Form 2253.

Another audience member commented that the link ads are more like the front cover of a brochure, in that the pharma company’s intent is not necessarily for that sponsored link to be the end, but to be the beginning.

“If you go to a physician’s office and you see the different brochures, you look and see which one you want to take,” she told the panel. “I looked at a lot of those sponsored links that got a letter, and when you click on them, it’s like turning a page.”

What she was referring to was the “one-click rule” that many companies felt was an unwritten rule allowing them to have risk/benefit information within one click of the sponsored link ad.

“It is the Internet, so you can’t turn a page, but you can click through,” a third person argued. “I’m just trying to figure out the guidance now, because it was 14 letters – Where do we go from here.”

Davis replied that only a fraction of the audience ever clicks through to the link page and never sees the risk/benefit information, therefore they should be considered standalone ads.

“Because you are on the Internet, you can’t forget all the regulatory requirements that apply, whether it’s labeling or advertising on a pen,” Davis said. “You’re not going to be putting your indication and think you are somehow exempt from the requirements to disclose risk information. If you can fit in some benefit statement, you can incorporate risks. If you can’t because you are limited by the amount of characters you can include, don’t only convey the positive without the negative.”

She restated that FDA’s regulations are clear on what pharma can and cannot do in terms of failing to disclose some of the required information.

The panel said that FDA is considering social media guidelines and that the topic is a priority.

In related news, the DDMAC user-fee program will not be coming back any time soon. It was not covered because it never went into effect. The voluntary program to get TV ads reviewed within 45 days lost its authority and won’t be revitalizing the program any time soon, one panel member said. Instead, Congress appropriated fundings for DTC advertising activities and created an additional review group within DDMAC.

Regulatory guidelines require pharma to attach related risk information to all. There is, however, one exception to this rule: Reminder ads or ads that provide consumers with the drug’s name, but no indication for use—because it’s assumed that the consumer is familiar with the drug. So where is the line drawn for pharma?

It turns out that the line is drawn with a cursor pointed to a link reached with the click of a mouse. The ads that were subject to the warning letters were not considered reminder ads, and thus showed up on FDA’s radar. We found a few examples of these letters posted online, with some interesting opinions by Porter Novelli Director of Global Health Care Peter Pitts. Check it out on his blog, http://drugwonks.com.

While I’m not 100 percent positive, it looks like this might have been the first time FDA actually name-dropped a social networking service in a warning letter. Which poses the question: Is FDA watching YouTube, and what does this mean for pharma?

Ignite Health’s Fabio Gratton told me that this ramification could go one of two ways. Pharma could view it as the feds are now treating YouTube with the same degree of importance as television and other media outlets, thereby validating the online service. Or it could scare pharma away from posting videos on YouTube, because that could warrant a warning letter.

So where does FDA stand?

I sent an email to FDA spokesperson Felicia Stewart with one question: Are you guys watching YouTube for pharma ads?

She missed the deadline for the article, but lo and behold, this morning I got a nice, concise answer from the feds.

DDMAC has been and continues to monitor the many vehicles that companies use to promote their prescription drug products. Our monitoring includes magazine ads, TV ads, promotional exhibits at medical conferences, Internet, sales brochures, journal ads, and consumer mailers and brochures. Internet monitoring includes promotion done by or on behalf of drug companies such as companies’ own product Web sites and their placement of promotion on others Web sites. The action addressing promotion by the company on YouTube is one example. Another example is the action addressing Pfizer’s promotion on cnn.com for Viagra.

There you have it. FDA is watching YouTube, and boy, do I wish I was the guy or gal being paid to troll the Web all day looking for errant pharma ads or remixes of the Rozerem beaver singing the Tay Zonday classic “Chocolate Rain.”