From Jim Mittler, Medical Director, PhD, Palio

We’ve all seen bad drug advertisements – confusing concepts, poorly written or too much copy, disconnected visual elements, etc. The FDA is now stepping up their monitoring for bad ads, but not for the creative aspects or connection to the brand. (Although, in some cases I wish there was an organization that could pull poorly executed creative.)

Last week, the FDA announced the launch of the “Bad Ad Program,” which is an educational outreach effort to encourage physicians to do what the Division of Drug Marketing, Advertising, and Communications (DDMAC) can’t necessarily do – monitor what is communicated during face-to-face interactions with pharmaceutical representatives. Traditionally, DDMAC reviews promotional materials developed by pharmaceutical companies (eg, journal ads, TV commercials, sales aids, or slide kits) to ensure that information is on-label and accurately portrays the efficacy of a drug while clearly stating the potential risks so that physicians can make informed prescribing decisions. Through the Bad Ad Program, DDMAC will seek to educate HCPs on what constitutes inappropriate promotional activities and will encourage HCPs to report possible violations. So not only is the content of promotional materials monitored, but by using HCPs as their agents, how these materials are used and the information articulated can also be monitored by DDMAC.

What this means is that verbal communications that occur in promotional settings such as sales representative office visits and industry-sponsored dinner and speaker programs could be under scrutiny. In the current conservative environment, sales reps are careful not to discuss off-label use or overstate the efficacy of a drug. Now, glancing over the safety data in a sales aid or the Important Safety Information slide during a presentation is frowned upon, as it should be. However, the increased scrutiny by HCPs could deter sales reps from deviating from a predetermined script and they could lose meaningful conversations out of fear that they could misspeak or be misinterpreted, and subsequently be reported to DDMAC. It may be difficult for DDMAC to determine what was discussed in a private meeting; however, according to FDA officials, if there is systematic misrepresentation, FDA reviewers will be able to spot similar complaints about a drug coming from multiple doctors, which would signal DDMAC to investigate.

The question remains if HCPs will take the time to report anything they feel is misleading or inappropriate. Additionally, will this enhanced surveillance lead to increased enforcement? The FDA has gotten tougher on promotional materials developed by drug marketers. Issuance of enforcement letters is higher than it has been in the past, with 31 warning letters already issued by DDMAC through May 2010 (which is on pace to exceed the 41 letters issued in 2009 and tops the 21 letters issued in 2008). However, if a high volume of complaints arise, there are questions regarding how the FDA will be able to investigate and issue timely corrective action due to the limited resources within the FDA. Regardless, even if DDMAC enforcement is logistically problematic, the Bad Ad Program could be a deterrent and improved compliance to DDMAC regulatory principles on the part of the pharmaceutical companies is sure to follow.

By Randy Glasbergen

From Tim Phalen, Medical Writer, Palio

Controversies surrounding prescription drugs are permanently on the media radar these days. This is not surprising given the huge and receptive audience for news about drug safety and effectiveness. The ever increasing availability of new drugs, and a populous generation reaching the age when more healthcare and prescription medications are needed has contributed to the increase of that audience. According to the Centers for Disease Control, nearly half of Americans report using at least one prescription medication and 63% of Americans 65 and older report taking 3 or more medications. However, despite a growing dependence on medications and an expectation for new and better therapies, there is also a high level of distrust of the pharmaceutical industry and its products among this audience.  This distrust may have been established and fed, in part, by several high profile media stories in recent years about concerns with commonly used prescription drugs. While there were legitimate questions of safety and efficacy being addressed, some of the coverage approached sensationalism, and the stories became less about the risks posed to patients and more about the motives of the pharmaceutical industry or problems with the prescription drug approval and regulation process in general.

The controversy surrounding Vioxx in 2004 set the bar for media coverage of prescription drugs. The release of studies showing an increased risk of heart attack and stroke with long-term use of the widely prescribed painkiller, and subsequent withdrawal from the market caused a panic. Some follow-on stories strayed from the specific safety issue with Vioxx and posed questions drug safety in general, and asked if there could be “other Vioxx’s.” There were also several, “what did they know, when did they know it?” type stories.

A few years later in 2007, when questions arose about an increased risk of heart failure with the widely prescribed diabetes drug Avandia, it was dubbed as ,“the next Vioxx,” in many media reports well before the issue got a full vetting. This nickname implies less about the nature of safety risk than it does about the media frenzy that was expected to, and did, ensue. It should be noted that the evidence for this risk was enough to necessitate a “black box” warning and further study. However unlike Vioxx, it is still on the market and being used by many, albeit far fewer patients, and the recommendation by the FDA to physicians is for patients to continue using it if it is still working for them. This ongoing inquiry into the cardiovascular safety may finally be resolved after a comparison of Avandia and Actos, a member of the same drug class is completed, which could be very soon.

Next was the cholesterol-lowering drug Vytorin. The 2008 controversy surrounding Vytorin was a bit more complicated and was focused on questions of efficacy, reporting of clinical trial results, and the overall drug approval process. Vytorin is actually a combination of two drugs, and when the results of a clinical trial (the ENHANCE trial) showed that Vytorin didn’t cause an improvement in a surrogate marker for cardiovascular health when compared to one of its component drugs (and a cheaper alternative), the need for an expensive drug like Vytorin was called in to question. Nothing was really answered by this trial, but it did spur the initiation of longer-term trials that should determine if there is a cardiovascular benefit with Vytorin. A controversy like this one is not as fear-inspiring as one about the sudden discovery of a safety risk, but it certainly got a great deal of attention. Had the stage not been set by Vioxx and Avandia, it may not have made headlines.

So, what’s the big deal about the media raising alarms and making headlines out of prescription drug controversies? The public can’t be blamed for turning their attention to such stories, nor should the media not be expected to ignore an issue that affects so many people. However, as was seen with each of these controversies, there was panic, confusion, and some anger among patients, which tended to perpetuate the coverage with stories about the reaction to the news instead of the primary issue at hand. In the midst of this panic, many patients immediately stopped taking whichever drug was in the news as well as other unrelated prescription medications before consulting with their doctor. While these patients may have thought they were protecting themselves, it’s just as likely that they were harming their health by avoiding their prescribed medications.

Much of this sensationalism and ensuing panic could be avoided if a couple of things were emphasized when prescription drug controversies or safety warnings surface.

First, all prescription and OTC medications carry some level of risk with them. There is no perfectly safe drug. Some are associated with very significant risks, others are relatively benign when used correctly. In every case it’s a matter of balancing the benefit with the risk. A drug with a high risk potential may be acceptable if it offers an even greater potential to benefit the patient, or if it’s only one of a few options for a serious disease. Also, as is often the case, a drug may not pose a risk to all patients with a particular disease, only certain groups. This type of risk/benefit evaluation is best handled by trained physicians, and is outside the scope of most media reports.

Second, pharmaceutical companies are subject to incredibly stringent regulations and oversight by the FDA, and billions of dollars are spent in clinical trials and in postmarketing studies to detect and determine safety risks. When a safety risk is found it’s documented, evaluated, and communicated to physicians and patients through multiple channels. Many times, the evidence that raises concerns about a drug’s safety comes from studies that don’t meet the strict criteria of the FDA for drug approval, and is found after it has reached the market. This type of evidence provides a reason for additional study, but it’s usually not enough to conclusively determine how serious that risk may be. It can take years before that’s established.

There will undoubtedly be more prescription drug controversies to come. When another one does make headlines, the public will be best served by a presentation of the facts and a reminder that any decisions people make about their medications should be done in consultation with a healthcare professional.

From Peter Hopper, VP, Account Services, Palio

Just the other day, in my local newspaper, there was a front page story about how the local police authorities are stepping up patrol of a main expressway heading into the city due to a significant increase in “aggressive driving.” Not to suggest that aggressive driving is appropriate behavior in any context, but obviously drivers are on notice: this particular stretch of road is going to be that much more on the radar screen, so to speak.

The appropriate response is to be mindful of the increased vigilance and ensure you are extra cautious to avoid getting pulled over and suffer the consequences: a ticket, extra points on your license, increased insurance, legal fees, perhaps even your name in the newspaper.

What about the duck?

For our industry, the name in the paper was Novartis, its oncology product Gleevec, and two disease-awareness Web sites actually registered to Novartis AG. The two sites’ disease-state content and clinical data were specific to the Gleevec indication. The FDA Warning Letter cited, along with other evidence, that the unbranded Web sites were “perceptually similar” to the Gleevec brand by look and feel, each included the Novartis Oncology logo, and each presented well-known facts that the medical community would easily recognize as referring to the branded product: if it looks like a duck….

In addition to blurring the lines between disease awareness and product promotion, the letter noted the omission of risk, as well as the inclusion of unsubstantiated dosing claims.

It is not news that DDMAC has substantially increased its resources to scrutinize branded and unbranded communications in the marketplace, and that those resources are good at their job. The FDA has posted over 30 letters specific to promotional materials to date in 2010, already eclipsing the entire count for 2008. This latest letter demonstrates the agency’s prowess, and every letter posted reinforces its determination, regardless of anyone’s opinion about how clearly defined, or not, the rules are.

One of our jobs as professional marketers is to seek out the appropriate opportunities and venues for our clients’ communications plans – and to offer sage advice on how best to leverage those opportunities – and, just as importantly, to keep our clients out of the unfortunate headlines.

From Ian DeMeritt, Senior Medical Writer, Palio

“What’s in a name? That which we call a rose by any other name would smell as sweet.” – Romeo and Juliet (Act II, scene II)

What if that rose didn’t have a name, yet claimed that it smelled sweet?

Late last week, DDMAC issued several regulatory letters to pharmaceutical companies, bringing the total number of letters it has issued so far in 2010 to 22, already topping the 21 letters sent in 2008. Of interest was a letter addressed to GlaxoSmithKline for an unbranded, single-page ad (also shown above) placed in the Journal of Clinical Oncology last December.

The simple ad announced that a “New Treatment Option for Refractory Chronic Lymphocytic Leukemia (CLL)” was “NOW APPROVED.” A footnote clarified the treatment was for CLL “refractory to fludarabine and alemtuzumab,” and a disease-specific Web-site address (www.cllinformation.com) and the GSK logo were included on the bottom of the page. That’s it. No efficacy data were included, no overt promotional claims were made, and no fancy images of happy people walking along a beach were present.

Most importantly, however, no safety information was contained in the ad, despite its unbranded nature.

Even though the name of the treatment was not provided, DDMAC considered the ad misleading because “the characteristics of the product promoted in the ad can only describe Arzerra,“ the only drug recently approved by the FDA to treat refractory CLL. Because the promotional material could only apply to a single product, the ad was effectively considered a branded advertisement requiring full disclosure of safety and risk information.

In our line of work, the response to what we perceive as unfair feedback from a client’s regulatory team is often jokingly along the lines of “can’t we just turn this into an unbranded campaign?” thinking that by simply removing the branding elements, the regulatory requirements will also magically disappear.

However, one of the important lessons to be learned from this letter is that a pharmaceutical brand comprises more than just a logo and color pallete. The totality of the message being conveyed must also be considered a key branding element, especially in the eyes of the FDA.

This latest DDMAC letter provides a useful reminder that failing to call a rose by its name doesn’t make it any less of a rose.

From Ian DeMeritt, PhD, Senior Medical Writer

As printed promotional materials are continually being replaced by flashier electronic detail aids and on-line content, it is not surprising that DDMAC continues to cast a regulatory eye on digital presentations of pharmaceutical advertisements. Last April, DDMAC fired a resounding shot across the bow of the pharma world that sent a clear message that it was well aware of the goings-on in the digital realm and that it meant to enforce on-line media as diligently as that in print form. The more recent FDA hearings on social media, the FDA’s new “transparency blog,” and the recently-launched “FDA basics” Web site demonstrate a growing commitment to their online presence.

The watchful on-line eye of the FDA was again demonstrated just recently when DDMAC warned 2 pharmaceutical Web sites for making false and misleading claims. While these new letters do not contain any new or groundbreaking information regarding DDMAC’s interpretation of the advertising laws as they apply to Web-based content, they do serve as a useful reminder of some pitfalls to avoid when designing Web sites for a pharmaceutical product. In addition to the familiar “Unsubstantiated Claims” castigations, warnings related to speciously presentated risk information were a key component of each letter.

Both products cited (Isovue and Visipaque) are intravascularly administered contrast media indicated for imaging of the cardiovascular system. Both product labels contain boxed and bolded warnings cautioning against a laundry list of severe and frightening risks including death, convulsions, cerebral hemorrhage, coma, paralysis, and brain edema, among others.

Despite these warnings, the GE Healthcare Web site describing Visipaque boasted an “excellent safety profile” and declared that it was “designed for patient safety and comfort.” The only risks listed on the Visapaque Web site were general cautions against blood clotting, thromboembolic events, and use in certain patients. While the Isovue Website (which presents the results of a head-to-head clinical study against Visipaque) did mention the possibility of severe reactions, the potential for fatal adverse events was not disclosed. This stark omission of important risk information did not escape the notice of DDMAC reviewers and these letters serve as a reminder that all relevant risk information, regardless of the implications to the brand, must be presented to balance promotional claims.

Furthermore, these letters reiterate that the placement and presentation of risk information is just as important in electronic format as it is in a printed piece. The Visipaque risk information was located at the very bottom of a long page of text, hidden below the references. Despite headlines heralding “Product Highlights” and “Product Description,” the risk information was not marked in any way to indicate to the reader that it was either present or important. Similarly, the risk information on the Isovue Web site was portrayed in a smaller font size than the promotional copy and without any headers to indicate its importance or presence.

It should be noted that both Web sites contained a link to the full prescribing information. However, as previous Warning letters have demonstrated, DDMAC is no fan of the so-called “one-click rule.”

While these new letters reveal no momentous changes in DDMAC policy concerning Web-based content, they do reinforce several lessons to keep in mind when creating, designing, reviewing, or reading pharmaceutical-based Web content:

Lesson 1. Safety Information must be clearly labeled as such and be given prominent placement on a Web page

Lesson 2. Risk information must be presented in a similar font size and appearance as promotional messages

Lesson 3. The FDA does not consider any pharmaceutical product with a boxed or bolded warning to be “safe” and any promotional messages to this effect are at risk

Lesson 4. All relevant risk information must be presented, regardless of how scary it might sound or the potential implications for the brand

Lesson 5. A “Please see…” line and/or a link to the PI is not sufficient to replace missing risk information

Lesson 6. The “one-click rule” is still dead

Most marketers and brands live with a beleif that FDA involvement = bad. Marketing communications that take full advantage of a brand’s label = good. So, what happens when the big “bad” FDA comes calling when an ad or other promotional effort crosses that grey line?