FDA Concerned About Product (eg, Lyrica) Ads That are Too "Educational"

FDA Concerned About Product (eg, Lyrica) Ads That are Too "Educational"

In a recent Federal Register notice (find it here), FDA outlined a study it plans to do to determine if disease awareness information in branded ads confuses consumers; i.e., if consumers confuse educational information about a disease with specific product claims approved by the FDA. As usual, FDA will only study print ads -- not Internet-based ads.

"Sponsors [pharmaceutical companies] may choose to include disease information in their full product promotions," says FDA. "Such information is designed to educate the patient about his or her disease condition. However, in some cases a full description of the medical condition may include information about specific health outcomes that are not part of a drug’s approved indication... When broad disease information accompanies or is included in an ad for a specific drug," says the FDA, "consumers may mistakenly assume that the drug will address all of the potential consequences of the condition mentioned in the ad by making inferences that go beyond what is explicitly stated in an advertisement."

FDA cites as an example a hypothetical ad that mentions "diabetic retinopathy," which is damage to the eye's retina that occurs with long-term diabetes. "...the mention of diabetic retinopathy in an advertisement for a drug that lowers blood glucose may lead consumers to infer that the drug will prevent diabetic retinopathy, even if no direct claim is made. The advertisement may imply broader indications for the promoted drug than are warranted, leading consumers to infer effectiveness of the drug beyond the indication for which it was approved."

I couldn't find a diabetes-related print drug ad that mentioned "diabetic retinopathy," but I did find one in today's Parade magazine that informed me that "Diabetes Damages Nerves." That ad (shown below) promotes Pfizer's drug Lyrica, which is indicated for the treatment of "Diabetic Nerve Pain." It is NOT indicated to prevent nerve damage caused by diabetes.

What I see when quickly glancing at this ad is "DIABETES DAMAGES NERVES" (all caps), then "PAIN," (also all caps) and, finally, "LYRICA" (also all caps). If I were a typical consumer with diabetes, I might think that LYRICA prevents damage to my nerves, which would be an incorrect assumption.

BTW, the ad also says "Lyrica is believed to work on these damaged nerves." What does that mean? Does Lyrica work on repairing the nerves? or does it work on shutting down the nerves so you don't feel pain? And, what does "believed" mean? It's all very mysterious!

This ad probably is not the best example of an ad that FDA has in mind -- it was just the best example I could find at the moment. I'll have to buy a few more consumer magazines to find other, more relevant examples. If you know of one, please point it out to me.

Pfizer Responds, But Did I Get an Answer?

Pfizer Responds, But Did I Get an Answer?

On the urging of a FaceBook friend, I behaved like a "journalist" and contacted Pfizer directly about an issue I raised regarding a Lyrica print DTC ad. For background, see here and here.

Pfizer did respond to me in a timely manner, which I appreciate given the current state of media frenzy regarding the resignation -- I mean retirement -- of Kindler, Pfizer's CEO. I'm not sure if Twitter facilitated the process or if my multiple phone calls/voicemails to various media people at Pfizer were responsible. Within a couple of hours, however, Chris Loder, Pfizer's Head of US Media Relations, gave me a call and said he needed some time to research the issue, but promised someone would followup soon.

After Chris called, I sent him this email so Pfizer could respond to a specific issue I was interested in:

Thanks for getting back to me regarding a Lyrica DTC ad in the December 2010 issue of Prevention Magazine ("What's causing your chronic widespread MUSCLE pain?"). I know you have seen my main blog post about this but I'd like to call your attention to this comment I received because it gets to the heart of the matter:

"... you can't make up an indication based on your MOA or preclinical data, and I do believe that Lyrica is trying to expand its indication beyond diabetic neuropathic pain and fibromyalgia (which cannot accurately be described merely as chronic muscle pain). There are other non-opioid agents now receiving chronic musculoskeletal pain indications, and I think Lyrica is trying to muddy the waters and gain some additional share of that market without bothering to do the hard clinical research and face the enormous placebo effect that comes with any pain studies."

About 4 hours after that I got an email from Victoria Davis, Senior Manager, Media Relations at Pfizer. Read what Davis had to say and then tell me your opinion.

In regards to your questions regarding the Lyrica ad, please find our statement below.

“The DTC campaign is designed to educate patients about the symptoms of fibromyalgia and encourages patients to have a discussion with a healthcare provider about their symptoms. Through illustration, the ads show how overactive nerves may cause the chronic widespread muscle pain that is characteristic of fibromyalgia. The ads also highlight how Lyrica is believed to work by calming these overactive nerves to provide relief from fibromyalgia pain.

“The elements included in the print ad were included in pre-clearance with the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC).

“The statements that ‘fibromyalgia is chronic widespread muscle pain thought to be caused by overactive nerves,’ and that ‘Lyrica is believed to calm these nerves’ are scientifically supported. Data supporting these and similar statements have been published in many peer-reviewed journals, including Nature Clinical Practice Rheumatology (now re-titled Nature Reviews Rheumatology) and Epilepsy Research.”

Please let me know if you need anything else.

I am particularly concerned with the FDA "pre-clearance" statement made by Davis. This implies that the FDA gave its OK when, in fact, FDA does not commit to approving ads BEFORE they are run. It can still cite ads for violations AFTER they have been submitted on Form 2253. FDA requires these submissions to be made " . . . at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product." Companies can choose to submit materials BEFORE initial dissemination of the ad and get some "opinions" from the FDA. But FDA does not APPROVE any ads BEFORE they are run. Here's the DDMAC FAQ on that:

Does FDA "approve" advertisements and promotional labeling before use by the company?

No, except in rare instances, when FDA may require pre-approval of promotional materials as part of an enforcement action. However, DDMAC provides opinions on proposed advertisements and labeling pieces before use upon request by an applicant. Note that accelerated approval products are under a "presubmission" requirement. The accelerated approval regulations require that applicants submit to FDA copies of all promotional materials prior to the intended date of dissemination or publication.

In any case, I do not think that Pfizer's response was sufficient to answer my question, which asked for SPECIFIC references to support the claim that Lyrica "calms" over-active nerves. I have responded by email to Davis asking for these specific references.

----------
FOLLOWUP: I sent Davis this followup email:

Thanks for your response. However, I was hoping for something more specific, ie, specific references to the medical studies that support the claims. Can you tell me, for example, if these claims are also made in marketing materials provided by Pfizer to physicians? If so, wouldn't those materials include specific references? If not, why not (ie, why are these claims not made in physician promo materials)?

To which she responded:

"Here are the references.

Staud, R. and Rodriguez, M. “Mechanisms of Disease: Pain in Fibromyalgia.” Nature Clinical Practice: Rheumatology. (2006), Vol. 2, No. 2

Taylor, C. et al., “Pharmacology and mechanism of action of pregablin: The calcium channel (alpha2-delta) subunit as a target for antiepileptic drug discovery.” Epilepsy Research (2007), doi: 10.1016/j.eplepsyres.2006.09.008

The last paper supports the claim that Lyrica "calms" over-active nerves. The abstract states: "The preclinical findings to date are consistent with a mechanism that may entail reduction of abnormal neuronal excitability through reduced neurotransmitter release." But this is a review and not a clinical study and it is not concerned with the mechanism of action, but only "addresses the preclinical pharmacology of pregabalin, and also the biology of the high affinity binding site, and presumed site of action." Furthermore, the author is a Pfizer employee who works at the "Department of CNS Biology, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. charles.taylor@pfizer.com"

This is the end of the road for me as far as investigating the validity of the claims made in the Lyrica ad. I leave it up to you and the FDA to determine if Pfizer has made its case in support of the claims made.

Pfizer's Latest Lyrica DTC Ad Should Be Cited By FDA as Misleading

Pfizer's Latest Lyrica DTC Ad Should Be Cited By FDA as Misleading

Do you have "chronic widespread MUSCLE pain?" That's the question asked in a Lyrica direct-to-consumer (DTC) print Ad in a recent issue of Prevention magazine (see image below). "The answer may be over-active NERVES," says the ad. The implication is that Lyrica treats "muscle pain" caused by "over-active nerves."

Yet Lyrica is officially approved by the FDA "to treat Diabetic Nerve Pain, Pain after Shingles, and Fibromyalgia. LYRICA is also indicated to treat Partial Onset Seizures in adults with epilepsy who take 1 or more drugs for seizures." Neither "widespread MUSCLE pain" nor "Over-active NERVES" is mentioned in the approved labeling for Lyrica. And the National Institutes of Health (NIH) says that the causes of fibromyalgia are "unknown."

Pfizer even includes a diagram (left) showing how Lyrica "calms" the nerves, which "can provide significant relief from Fibromyalgia pain."

I think that all this is speculative hocus pocus that is not based on any reputable science at all! This is shameful coming from a company and an industry that promotes itself as being "science-based."

I'd like to see (1) references to scientific data, trials, etc. that supports Pfizer's hypothesis that fibromyalgia, aka "widespread muscle pain", is caused by "over-active NERVES" and (2) data to support the claim that Lyrica "calms" over-active nerves.

FDA "warning letters" often state that "Promotional materials are misleading if they suggest that a drug is useful in a broader range of conditions or patients than has been demonstrated by substantial evidence or substantial clinical experience." If Pfizer has no data to support the claims made in this ad, then the FDA should cite it as being misleading. That's my opinion. What do you think?