Pharma Turns Up the Heat on Off-Label "Free Speech" Chilled by FDA - Implications for Social Media Marketing

"FDA’s regulations censor manufacturers," says the Medical Information Working Group (MIWG), an "informal" group of pharmaceutical companies that includes Allergan, Amgen, Boehringer Ingelheim USA, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Purdue Pharma, and sanofi-aventis U.S.

In a "friends of the court" brief to the court hearing the appeal  of the Caronia off-label promotion case (see here), the MIWG contends that a manufacturer that "speaks about the lawful off-label uses of its products subjects itself to potential enforcement action unless FDA and DOJ determine, in their sole discretion, that they will not treat the speech as evidence of an 'intended use' for the product. This creates a chill on manufacturers’ speech, which has serious potential consequences for physicians, patients, and the public health."

Because of FDA's regulations that "lack coherence and clarity," MIWG claims physicians will have difficulty obtaining "objective, balanced, and accurate information on important unapproved uses of approved products." Furthermore, MIWG contends that pharma companies are "uniquely positioned to provide physicians with such information."

That's rich, considering that the drug industry often has difficulty providing "objective, balanced, and accurate information" on APPROVED uses of drugs as evident from all the FDA warning letters, which address this difficulty (for a list of the most recent letters, see here).

Should the heat the drug industry is bringing against FDA's off-label authority succeed, I envision off-label "woolly mammoths" (aka, sales reps) breaking free of the chilly ice and running amok among physicians offering "objective, balanced, and accurate information" - all without any oversight!

Much has been written about this legal issue, which you can find here, here, and here. Aside from the "objective, balanced, and accurate" claim, what caught my attention in the language of the brief was the overlap in the arguments presented with arguments pharma (eg, Pfizer) has made about how FDA should (or should not) regulate the promotion of Rx drugs via the Internet and social media.

On page 10 of the brief, for example, the argument is made that so-called "safe harbors" (eg, FDA guidelines for distribution of off-label reprints; see "FDA's Good Reprint Practices Guidance") are "not the product of formal rulemaking" and are "in most instances explicitly 'non-binding'." This was the argument Pfizer made against FDA issuing social media guidelines (see "Pfizer Asks for New FDA Regulations, Not Guidance, for Social Media"). As part of that argument, Pfizer said that "for FDA to regulate in this sensitive area [social media] through guidance instead of rulemaking inherently raises First Amendment concerns because of the nature of the process used to develop guidance, and the nature of the Agency pronouncements that result." (NOTE: Both documents are written by some of the same lawyers.)

Another parallel appears on page 11 of the brief, which delves into "unsolicited requests." The brief noted that FDA allows pharma company representatives (eg, paid physician speakers) to provide off-label information in response to an "unsolicited request" (eg, a question from the audience; perhaps from a physician "planted" in the audience for that specific purpose?).

Recall that the FDA's 2011 guidance "agenda" called for the agency to issue guidance regarding "unsolicited requests" from any source, including the Internet. That particular guidance, says FDA, was part of its promised social media guidance (see "FDA Drops Social Media from Its 2011 Guidance Agenda"). Before FDA can do THAT, it has to contend with the legal issues raised by MIWG in its brief.

This push for an end to FDA's off-label marketing ban is the latest industry action that puts the FDA in a very weakened position viz-a-viz issuing any marketing guidance (and certainly NOT social media guidance) for the foreseeable future. The industry hopes the court case in question -- the Caronia off-label promotion case -- will end up in the Supreme Court. In the meantime, FDA is probably thinking "let's wait and see what happens before we issue any new guidance that 'lacks coherence and clarity'."

Do Women Take More Drugs Than Men Because They Need To or Because They Are Targeted by DTC Advertising?

Aside from Viagra, there's hardly a prescription drug I've heard of that women are NOT the major users of. Take, for example, this bit of information regarding Ambien as reported recently in the New York Times:

"According to IMS Health, a health care consulting firm in Danbury, Conn., the use of prescription sleep aids among women peaks from 40 to 59. Last year, the firm said, 15,473,000 American women between those ages got a prescription (overwhelmingly for Zolpidem, the generic form of Ambien) to help them sleep, nearly twice the number of men in that age group."

The article, titled "Sleep medication: Mother's new little helper" (find it here), goes into detail why mothers -- as opposed to fathers -- are so dependent on sleep aids. One woman is quoted as saying "The minute I had children I was like the mother listening in the woods for the bear. I don’t know if men are less vigilant, but my husband doesn’t wake up in the middle of the night. He could sleep in a dunking booth.” Yes, mom, men can be as vigilant! As a father of grown children living at home, I am often up at 3 AM wondering where the heck they are!

Here are other examples of this women/drug user phenom:

• "Women are twice as likely to take anti-depressants than men (Overall, 40% of females and 20% of males with severe depressive symptoms take antidepressant medication says CDC). Actually, for all degrees of symptoms, women are 2.5 times more likely to take antidepressants than men" (see here).
• There seems to be a proliferation of "real" diseases that "primarily affect middle-aged women." That, for example, is how fibromyalgia is described (see here).

Forgive me, but I have problem with these articles trying to explain why women -- more than  men -- need drugs. Specifically, I don't buy the argument that women need more drug X to treat Y than do men because more women suffer from Y than do men.

Could it be that women feel they need more drugs than men because they are more targeted by direct-to-consumer (DTC) ads? That's a question I'd like to discuss during my next Pharma Marketing Talk LIVE podcast this Wednesday (see "How to Score With Women (as a Marketer) via Social Media").

Other questions to be discussed include:

• Who said "social media is all about women" and what does this mean for the pharmaceutical industry?
• What does it take to be an effective social media partner when comunicating with women?
• Let's talk about "moms" and not "Sex in the City" conspicious consummer of high-end goods type of women. What is pharma doing to woo moms via social media?
• While it is possible to imagine women having relationships with certain consumer brands via social media, is it possible for them to have similar relationships with health and/or drug brands?
• Is it even possible for pharma brands to establish relationships with women via social because of regulatory restrictions on pharma branded marketing?
• What are the best digital marketing strategies to create trust in mhealth?
• Do you think there will be a day where everybody will use mhealth devices in their daily basis?
• What sector of the population do you think is more reluctant to use mhealth devices?

You can join the discussion by calling in by phone (the callin number is 347-996-5894) or via chat on the BlogTalkRadio site (here; you must be a BlogTalkRadio member to join the chat).

FDA Moves the Cheese on Drug Approval Numbers

The FDA and the pharmaceutical industry are bragging about the number of "new" drugs approved in "fiscal year" 2011 (October 1, 2010 through September 30, 2011). In a report (find it on the FDA site here), FDA said it approved 35 "innovative drugs" during that period. PhRMA -- the drug industry's trade association -- said that 35 "new molecular entities" received FDA approval in fiscal year 2011.

One has to be careful about how you define a "new" drug in order to compare one year's performance to another. Also, there's the fiscal year numbers vs. the calendar year numbers.

For example, "new molecular entity" is a well-defined FDA term that even has an acronym: NME. FDA defines a New Molecular Entity as "an active ingredient that has never before been marketed in the United States in any form." NMEs go through a New Drug Approval (NDA) process.

In its report, FDA does NOT say there were 35 NDAs approved in FY 2011 as would be inferred from PhRMA's statement. Instead, FDA uses the term "innovative drug," which it does NOT define. It does, however, also refer to 35 "new drugs." Typically, FDA would use these terms to mean NMEs.

It's all a bit confusing to us mice trying to find the "cheese."

Let's look at the data on a calendar year basis.

FDA has new drug approval data available on its web site here. These data -- reported on a calendar year basis -- include NMEs (usually small, non-biological molecules) and BLAs (biologics license applications). The latest available data covers calendar year 2010 during which FDA approved 15 NMEs and 6 BLAs for a total of 21 total "new drugs."

Unfortunately, we cannot compare the number 35 for FY 2011 recently mentioned by FDA and PhRMA with the number 21 for calendar year 2010 to determine how much better the FDA/drug industry is doing. Obviously FDA wants to paint the rosiest of pictures in order to justify approval by Congress of new user fees being paid to the FDA by the drug industry to "expedite" the approval process.

So, how many NMEs and BLAs has the FDA approved so far this CALENDAR year? Well, on July 7, 2011, it was reported that FDA approved 20 "new drugs" as of that date, "just one short of the total for all of 2010, according to a top agency official" (see "2011 New Drug Approvals May Exceed 2010 Total, But...").

On FDA's Drugs@FDA, you can search for "Original New Drug Approvals (NDAs and BLAs) by Month," which includes all applications approved for the first time during the selected month including New Molecular Entities (NMEs) and new biologics (note: "Not all biologics are in Drugs@FDA"). Anyway, accessing these data, I come up with 23 "new drugs" (NMEs). Or maybe it's 25, which includes two "drugs already marketed, but without an approved NDA." In any case, calendar year 2011 is shaping up better than calendar year 2010.

FYI, I've plotted the yearly data from 1994 through 2010, which clearly distinguishes between NMEs and BLAs (see chart below).

Chantix May Be More Dangerous Than Smoking!

Reuters reports (here) that Chantix is "eight times more likely to be linked with a reported case of suicidal behavior or depression than other nicotine replacement products, such as the nicotine patch," as reported by authors of a recent study (see "New study says Chantix raises suicide risks"). Here are more details as reported by Reuters:

The new study relies on adverse events from the FDA's Adverse Event Reporting (AER) System from 1998 through September 2010. They analyzed 3,249 reports of serious self-injury or depression linked to Chantix (varenicline), GlaxoSmithKline's Zyban (bupropion) antidepressant that was approved for smoking cessation and nicotine replacement products. They found that 2,925 cases, or 90 percent, of suicidal behavior or depression reported to the FDA were related to Chantix, even though the drug was only approved for four of the nearly 13 years of data included in the study. By comparison, there were 229 cases of suicidal behavior or depression related to bupropion and 95 cases related to nicotine replacement products.

The authors also looked at an antibiotic comparison group and found that adverse event reports of suicidal/self-injurious behavior or depression were otherwise "rare in a healthy population receiving short-term drug treatment."

I looked at the data in the study and carved out the data relating only to "completed suicides" and "suicide attempts" reported in the AEs studied. I figured these were the most serious adverse events. Here's a pie chart showing how Chantix compares with the competition:

In words: 88% of reported completed and attempted suicides among this group of products were found in Chantix AERs (595 Chantix cases vs. 75 Zyban cases and 6 nicotine cases). NOTE: 77% of the AERs were submitted to FDA directly by pharma companies; 40% originated with healthcare professionals and 60% originated with consumers.

This seems to be quite an increased level of risk to accept compared to the slightly better benefits of Chantix vs. the competition.

In its promotion of Chantix (among the TOP 10 DTC advertised drugs in 2010; see "Double Dip in DTC Spending Plus 33% Drop in Internet Display Ad Spending!"), Pfizer cites studies that show 44% of Chantix users were "quit during weeks 9 to 12 of treatment (compared to 18% on sugar pill)." As the authors of the PLoS study point out, however, the picture is not so rosy after 52 weeks: "by 52 weeks a large majority in all groups had resumed smoking -- only approximately 25 - 27%of varenicline [Chantix] patients had remained largely abstinent compared to 17 - 19% of bupropion [Zyban] patients and 9 - 12% of the placebo group." No wonder the authors conclude "The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation."

Pfizer is using patient testimonials in its DTC advertising and positioning Chantix against nicotine treatment products as shown in this Chantix Web site creen shot:

If I were "Herb," I'd wouldn't be so "intrigued" by "non-nicotine" Chantix if I realized that I was 88 times more likely to attempt suicide or actually kill myself while on Chantix than if I used a nicotine patch/gum/whatever. Besides, at Herb's apparent age, stopping smoking is not likely to improve his health outcomes -- his years of smoking probably have already limited his life expectancy. Why add possible suicide to the mix?

Chantix on Facebook?
P.S. I once thought Pfizer woud be smart to use social media to help people quit smoking while on Chantix (see "Chantix: Opportunity for Social Marketing Lost?"). Seeing this data, however, I don't believe Pfizer could do it because it would be swamped by adverse event comments, especially now that Facebook requires comments to be turned on for all FB pages, including pharma-sponsored pages.

Speaking of that, I found THIS Chantix FB page (content copied from wikipedia) that does NOT have comments turned on! What's up with that?

Google to Shutter Sidewiki on December 5, A Day That Will Live Famously!

Yesterday, Google sent out an email (see here) informing users of its sidewiki service that it will close the service on December 5. Sidewiki allows users to post and read comments linked to specific web pages. It was launched in September, 2009, and I was one of the first people to use sidewiki to attach comments to a drug.com website (see "Google's Wacky Wiki is Whack! Pharma Should Demand Ability to Block It!").

In my presentation at the November, 2009, public hearing at FDA regarding Promotion of FDA‐Regulated Medical Products Using the Internet and Social Media Tools, I famously called on Google to "tear down this Sidewiki" (it was the anniversary of the fall of the Berlin Wall; see transcript).

Google spent a lot of effort defending sidewiki in comments it submitted to the FDA after the November hearings, saysing "The service uses an algorithm to identify the best comments, based in part on user ratings, and seeks to display only comments that are judged to be of high quality."

I said it before (see here) and I'll say it again: Google... what a maroon!

Are Pharma Reps Important to Docs or Not?

Back in March, 2011, I reviewed a PhRMA sponsored survey of physicians the results of which PhRMA claimed shows that "nearly eight out of 10 physicians view pharmaceutical research companies and their sales representatives as useful sources of information on prescription medicines" (see "New PhRMA Survey of Physicians: Are Sales Reps as "Useful" as PhRMA Wants Us to Believe?"). If you look at a chart of the relevant data (see below), however, you see that the 80% mentioned by PhRMA includes 53% of physicians who find sales reps only "somewhat useful." Only 26% of physicians surveyed found reps "very useful."

Yesterday, I came across the Wolters Kluwer Health Point-of-Care survey of physicians, part of which looked at where physicians receive information to make decisions about diagnoses, treatment and ongoing patient care (see press release and executive summary here). This study asked physicians: "How often do you use the following sources to gain information used to diagnose, treat and care for patients?" The results are shown in the following chart:

The trends are comparable (eg, prof'l journals are rank near the top and sales reps rank near the bottom in both surveys), but you can't group the Wolters Kluwer categories "frequently" and "occasionally" together as well as you can group together PhRMA's "very useful" and "somewhat useful" categories. Because of the way PhRMA designed it's study -- using categories that can easily be combined -- they were able to spin the results favorably, whereas no such spin of the data is possible in the Wolters Kluwer survey.

So, looking at ALL the data, IMHO, the best that can be said in answer to my question is that most physicians find pharma sales reps among the least important sources of information they use to help them diagnose, treat and care for their patients.

P.S. (27-MAR-2012) I just came across another study attempting to answer the question "Do physicians find sales reps useful?" The study comes from Cegedim Strategic Data (CSD), a provider of integrated healthcare market research. CSD analyzed physician-reported diary entries of recent sales calls. Results from over 30 countries showed that overall 93.8% of physicians worldwide, both GPs and specialists, "find sales representative calls useful and of value to their practice, based on over 5.6 million product detailing mentions" (find more details here).

I believe CSD's methodology asks physicians to evaluate recent sales calls. This technique eliminates physicians who did not receive any sales calls, which skews the data to favor physicians who like sales reps to begin with. The CSD study does not compare usefulness of reps compared to other sources of information.

In any case, it's amazing how many studies are out there and how difficult it is to get a straight answer to a simple question.

Lipitor Won't Go Gentle Into that Good Generic Night

Today's Wall Street Journal reports that "Pfizer Inc. isn't rolling over and conceding the market for its cholesterol-lowering drug Lipitor after the blockbuster brand loses its U.S. monopoly at the end of the month" (read the article here). Pfizer has an aggressive co-pay card/PBM discount plan that it hopes will allow Lipitor to maintain a 40% share of the combined market for Lipitor and its generic equivalents for at least 6 months after generic brands are launched.

This has prompted me to man-handle Dylan Thomas's famous poem as an ode to Lipitor and its fight against patent expiry:

Do not go gentle into that good generic night,
Patent expiry should burn and rave at close of day;
Rage, rage against the dying of the innovator's right.

Though wise marketers at patent end know generic is right,
Because their words had forked no lightning their Rx brands
Do not go gentle into that good generic night.

Good Rx brands, the last wave by, crying how bright
Their frail market share might have danced in a greener pasture,
Rage, rage against the dying of the innovator's right.

Wild marketers who caught and sang cholesterol numbers in flight,
Learned, too late, Lipitor's fate, they grieve it on its way,
Do not go gentle into that good generic night.

Grave Rx brands, near death, that see with blinding sight
Off-patent drugs could blaze like meteors and be gay,
Rage, rage against the dying of the innovator's right.

And you, my Lipitor, there on the sad market height,
Curse, bless, your loyal patients now with your fierce tears, I pray.
Do not go gentle into that good generic night.
Rage, rage against the dying of the innovator's right.