Thursday, July 19, 2007

The "RLS Gene" Story: Requip Ad Disguised as News on ABC

I couldn't believe my eyes and my ears last night when ABC News devoted significant air time to a story that it claimed "will put an end to criticism of Restless leg Syndrome" or something to that effect.

[I wish I had the video to prove to you that was exactly how this story was introduced. I need a TiVO if I am going to continue in this business!]

In reality, this "news" item was a direct to consumer ad (DTC) for Requip, except without the fair balance! Prominently featured in the opening segment of the ad, er, I mean "news story," were clips from the infamous Requip ads showing the specially-made green chair and a physician mouthing the single word "Requip."

Contrary to ABC News's prediction viz-a-viz shutdown of criticism, there is so much to criticize here that I am at a loss where to begin my renewed criticism! But I will give it a stab.

First, the story is about a scientific study published in the New England Journal of Medicine (NEJM) that claims to have found the gene for Restless Leg Syndrome (see "Restless Legs Scientists Find Sleep-Kicking Gene").

Follow the Money
Let's first follow the money to see if we can catch a "tricky dick" here.

The study, "A Genetic Risk Factor for Periodic Limb Movements in Sleep," was sponsored in part by the Restless Leg Syndrome Foundation, which, as I have pointed out before, is an "astroturf" non-profit established and virtually run by GlaxoSmithkline (GSK), the company that markets Requip for the treatment of RLS.

GSK and Boehringer Ingelheim (BI, maker and marketer of Mirapex, another RLS treatment) are "Gold Level Sponsors" of the Foundation (see "Restless Pharma Marketing"). These companies have an even more incestuous relationship with the RLS Foundation:
The first RLS Foundation Science Award went to Ronald L. Krall, MD, Senior VP of Worldwide Development at GSK! That's a first! Pipe money into a foundation and viola! you (or a VP in your company) gets an award!

Not only that, Dr. Richard Allen, a member of the RLS Foundation's Medical Advisory Board, proudly reveals in the press release that he had the "pleasure" of "collaborating" with the research team selected by Dr. Krall to do studies supposedly supporting the data on the prevalence of RLS in the US and in Europe.
Undoubtedly, the RLS gene study, which originated in Iceland, was one of those "collaborations." (See the RLS Foundation press release.)

OK, we have an industry-created and supported astroturf foundation laundering GSK and BI money to support RLS research in Iceland. It doesn't look good, but the researchers could still be independent and credible, right?

Wrong!

Here's the authors' conflict of interest statement at the bottom of the NEJM article:
"Dr. Rye reports receiving consulting fees from or serving on paid advisory boards for GlaxoSmithKline, Boehringer Ingelheim, Ortho-McNeill, and Sepracor and lecture fees from GlaxoSmithKline and Boehringer Ingelheim; Dr. Bliwise, receiving consulting fees from or serving on paid advisory boards for Takeda, Neurocrine, Sepracor, and Cephalon and lecture fees from Takeda and Boehringer Ingelheim. Dr. K. Stefansson is chief executive officer and Dr. Gulcher is chief scientific officer of deCODE Genetics, and both have equity in the company. The company has a financial interest in the results of this study, including diagnostic products and patents. No other potential conflict of interest relevant to this article was reported."
OK, so we can't trust some of the authors either. But, maybe the science is still OK.

Forgive me for not wishing to delve too deeply into the science, particularly about how strong the connection is between the newly discovered gene and RLS. Let's just say that I don't question the connection between a gene and the condition that the researchers actually studied, which was NOT RLS.

The study was initially done with 306 Icelanders who fit the criteria for RLS and who kicked their legs once they fell asleep -- an action known as periodic limb movements in sleep, or PLMS.

OMG, another acronym for a "real medical condition"!

They also studied 108 Americans in Atlanta.

Quite a convincing N, don't you think? And here I am criticized for my "unscientific" survey with N=145!

The researchers attached a gizmo to the legs of subjects and measured twitches during sleep. The ABC News report showed a graph of someone suffering from PLMS who twitched 60 times an hour during sleep. I am not sure where the cutoff is -- how many twitches per hour is considered "periodic" enough to be PLMS? This is the level of detail I refuse to sink to.

Anyhoo, what does PLMS have to do with RLS?

That's either the Archille's heel of this study or the genesis of a new indication for Requip and a whole new marketing campaign. I envision late-night DTC ads showing scantily-clad babes like that pictured above kicking in their sleep.
NOTE: The photo above is taken from the ABC News Web site version of the story. In the broadcast -- aired during family hours -- a decidedly less attractive woman in jammies and unsexy white socks(!) was used to illustrate what they dubbed "sleep-kicking."
A supposed physician ("docpiner") commenting on the ABC piece had this to say:
"This disease [RLS] has nothing to do sleep kicking. Kicking in sleep is NOT restless leg syndrome. Feeling an uncomfortable sensation in the legs and needing to consciously move the legs to get relief is what this [is] about. This howevere (sic) does not get you your snappy title. You do a disservice to your readers with this type of shoddy reporting."
Indeed, even physicians on GSK's and BI's payroll admit the same:
"It is not a gene per se for RLS, but rather for leg movements seen in individuals and families with RLS," said Dr. John Winkelman, medical director of the Sleep Health Center at Brigham and Women's Hospital. "Whether the same gene is associated with periodic leg movements in [other] contexts, we have no information from this study."

[According to ABC News, Dr. Winkelman "has reported receiving financial support for research, as well as consulting and lecture fees, from Boehringer Ingelheim and GlaxoSmithKline."]
The RLS Foundation, however, has no qualms about playing up the connection between RLS and PLMS:
"PLMS are present in about 90% of people with RLS and are considered a typical expression of RLS."
The Foundation doesn't cite its source for this tidbit of information.

It's interesting that the gene associated with PLMS is found in 65% of all Icelanders and maybe as many Americans.

Whoa boy! Imagine Requip having an new indication for PLMS! Is that a marketer's wet dream or what?!

New Requip Ads Coming Soon?
But new indication or not, I envision new Requip TV ads showing more twitching in sleep than twitching during dinner at a restaurant. GSK already has the YouTube video prototype out there (see "GSK's YouTube Disease Awareness Sponsorship"). Will FDA allow this in branded advertising? Inquiring minds want to know.

Meanwhile, this study sets the stage for the greatest off-label promotion scandal to come. I am sure GSK and BI sales reps and/or Medical Science Liaisons will be out there talking this up to physicians who undoubtedly will be led to equate PLMS with RLS.

Another commenter to the ABC News story shows how easy it will be to confuse RLS with PLM:
I too agree with docpiner it is not sleep kicking. I have had RLS since my last child was born (19 years ago) and it is very annoying. I hated to see evening come. As soon as I would sit or lie down for the evening my legs would start. I finally found Requip about 3 years ago and has provided me with relief so that I could get to sleep. It wears off for me around 6am. My legs get me awake then I have to get up. My legs ache (from the knees down) and also wonder if other RLS sufferers have the same problem.

6 comments:

  1. Anonymous1:45 PM

    As a long term "put up with-er" of RLS/PLMS I am grateful for any advance in the treatment or explanation of this disorder or whatever label you want to put on it. I don't care where the advance comes from or who funds it or who profits from it. I wish all you naysayers of the advertising, research, and the existence of RLS would just go rain on your own parades.

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  2. I am not raining on your parade! Parade away you dough on Requip as much as you want!

    My comments are limited to marketing practices and the relationships it spawns. We all have a right to know who funds the research. If anything, I'm raining on THAT parade!

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  3. Anonymous3:00 PM

    We all have a right to know who funds the research.

    Thanks, John. I think we all have a right to know when PR is disguised as "new science." Since MSM seems unable to do this, your efforts are doubly appreciated.

    --Melody

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  4. Neil Gray3:08 PM

    John:

    I remember months ago when I said the Requip campaign focusing on restless leg syndrome was the one that put me over the edge relative to DTC advertising. I think I was right then...as you are now. Tangential and moderately causal relationships in science are to be guarded against. Correlation doesn't always mean causation. For an interesting comment on same, see Clifford J. Rosen, MD, chair of the FDA advisory committee on rosiglitazone, in NEJM, (10.1056/NEJMp078167) at www.nejm.org, August 8, 2007. It shouldn't be restless leg that should worry us, it should be foot in mouth.

    Regards,

    Neil

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  5. Anonymous9:56 PM

    John -

    Thank you for your article! I suffer from RLS -- sometimes it's really quite horrible. Just trust me on that. Anyway, I'm not writing about RLS, but about how grateful I am to learn more about who's behind the RLS Foundation.

    A story for you: I just received an e-mail from the RLS Foundation criticizing and ad from Consumer Reports. Here's an excerpt...

    "We wanted to apprise everyone on our mailing list of some bad press for RLS. We want to encourage you to 'fight back'.

    "A video on consumerreports.org promises 'relief from restless legs hype.' The RLS Foundation is taking a tough stand against this type of bad press for RLS.

    "Click here [blogs.consumerreports.org/health/2007/11/index.html] to watch this extremely sarcastic and insulting video for yourself. Then, click here [www.rls.org/NETCOMMUNITY/Document.Doc?&id=829] to read the RLS Foundation's response to this video.

    "The RLS Foundation is calling for drastic measures to respond to this video. We aren't concerned that they are reporting on a drug. We are concerned that they are mocking a condition that so many people live with everyday. We encourage you to respond to this advertisement immediately. If you are a subscriber of Consumer Reports, we encourage you to cancel your subscription...."


    So, I showed this to my wife -- who's much brighter than I am -- and she said, "Hmmm. I don't see anything wrong with the Consumer Reports ad. And, hey, y'know the RLS response doesn't sound like a non-profit's response -- I didn't think that non-profits went around attacking each other for protecting consumers. I wonder if we could find out if RLS Foundation has any corporate sponsors..."

    So, I Googled 'rls foundation sponsors requip' and found your article. When I read it to my wife, she did a little celebratory jig. ;-)

    We were both delighted to find that you'd done some research and were able to help us learn that there IS a connection b/t the RLS Foundation and the RLS drug makers.

    What to do next, I don't know -- my Mirapex is a real life-saver -- but I was certainly glad to learn about the connection.

    Thank you, thank you.

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  6. John,

    I have just stumbled upon your blog, and wish I had found it sooner. I recently posted a paper I wrote for a freshman English class in regards to DTC marketing and it's downfalls. I recieved a comment from an anonymous user (imagine that!) directing me to the RLS.org website to prove to me it was a real disease that affects as many people as alzheimers.

    Sure.

    I'm pretty sure that Glaxo makes plenty of donations to this "organization". Of course, it's for the good of the population, right?

    Let me hop off my soapbox and say you have now been favorited and I look forward to reading more.

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