The Generic Drug Witch Hunt

CNS News has already achieved a certain degree of infamy in this blog for its subsidiary, CME Zone, an industry-funded CME factory. In a prior posting, I reviewed one article that masterfully tweaked information on anxiety disorders in order to promote Shwarz Pharma's Niravan, a orally-disintegrating version of Alprazolam (Xanax).

Now, unfortunately, CNS News is back on our radar screen for having commissioned an article bad-mouthing generic medications. You can find it as an insert in the November 2007 issue. The title is "Generic Antiepileptic Drugs: An Update," and the author is Andrew Wilner, M.D., a prominent neurologist with his own website.

Dr. Wilner's article is a biased article against using generic epilepsy drugs. He points out that the FDA allows generics to vary from 80% to 125% of the original drug's bioequivalence. But he ommits the crucial clarification that in actuality, generics vary from brand name by an average of only 3.5%, according to the most recent FDA analysis. He cites surveys of neurologists showing that most of them have seen breakthrough seizures when patients have been switched from brand name to generic formulations. But he fails to discuss how unreliable survey data like this can be. Response rates are low, and the physicians who have seen problems with generics are precisely those who are most likely to respond to a survey about possible generic drug dangers.

Dr. Wilner ends the article with an admission that proof of the dangers of generics is lacking, saying that no definitive study randomizing patients to brand name vs. generic has been done. But in fact, at least two randomized studies have been done. In one, patients randomized to generic carbamazepine had no more breakthrough seizures than patients randomized to a brand-name version. In another, patients on generic Dilantin actually had somewhat higher serum levels than brand name.

But these are all scientific quibbles, and they can reasonably argued in various ways. The most glaring problem is that there is no information about Dr. Wilner's numerous conflicts of interest. Instead, the article is said to be "independently developed by Mcmahon Publishing."

Discovering Dr. Wilner's industry ties is as easy as entering the terms "Wilner and disclosures" in Google. As it turns out, Dr. Wilner has received grants from several makers of anti-epileptic medications, including Shire (maker of Carbatrol), UCB (Keppra), and Novartis (maker of Trileptal). In fact, the first anti-generic survey study reviewed in the article was funded by Shire, and was conducted by none other than....Dr. Wilner!

I was astonished when I discovered this undisclosed conflict, and I wrote Dr. Wilner and the publisher this letter seeking a response. The first response was from the publisher, Donald Pizzi, who said that he had paid Dr. Wilner directly to write the article and that no industry money was involved. Pizzi said that historically, no disclosures are made in his journal, but "eventually" he will add them.

A bit later, Dr. Wilner sent me this letter. He parses the data a bit, engages in what I would consider some artful tweaking, but you can judge it for yourself if you choose to read it. I found it especially interesting that he defends his lack of disclosure by saying: "Regarding disclosures, while I have received grants and honoraria from the pharmaceutical industry in the past, I currently have nothing to disclose." I guess it depends, in the words of a former president, on what "is" is. In December of 2005, Dr. Wilner was funded by UCB pharmaceuticals, and in April of 2006 he helped write this article for a group of industry-funded neurologists, though it's unclear exactly who paid him. Other instances of his pharma funding can be found here and here and here.

Timing aside, the key issue is that Dr. Wilner's article appears to be biased in favor of brand medications, and he has been recently paid by precisely those companies whose profits are threatened by generics. He and the publisher should have disclosed this. If they had, readers would have given little credence to the article. But that would not have made the CNS News drug company advertisers very happy.

By the way, for a more balanced view of generics, visit this post on the Prescription Project's blog, Postscript.

Payback Time: A Counter-Detailing We Will Go

I received many helpful suggestions for how to part with my "dirty thirty." I've decided that the most logical solution is to donate time to "counter-detailing," which is essentially the opposite of giving drug talks. Pioneered as "academic detailing" by Jerry Avorn at Harvard Medical School, counter-detailing involves visiting doctor's offices and teaching about evidence-based medicine. The emphasis is on confronting the latest marketing claims of more expensive me-too medications and alerting doctors to the subtle statistical deceptions so common in pharmaceutical advertising.

Reviewing my Wyeth pay stubs, I can replicate my 2002 March of Shame through local doctor's offices and counter-detail them on my own dime. Anyone who wants a free talk for their organization can contact me at drcarlat@comcast.net. I'll do these until my 30K runs out.

By the way, several physicians at the National Physician's Alliance (NPA) are available for free talks on pharmaceutical industry influence, and they span the specialties, offering counter-detailing on treatments in internal medicine, cardiology, pediatrics, etc.... And join NPA while you're on their site. Unlike the AMA, they will never sell your name to drug companies.

"Return the 30K, You Cheap Thief"

Or so opines one of the commenters on the WSJ Health Blog, where you will find many angry folks calling me a "hypocrite," a "pathetic liar," etc....

I'd be curious to hear opinions about: A. Whether I should return the dirty money; and B. Where it should go if I can bear to part with it?

Other comments that I've received about Dr. Drug Rep:

--"Don't blame Wyeth, blame yourself. Nobody was holding a gun to your head--you chose to take the money." Can't argue with this. The article was, in fact, a long confessional about a series of unethical choices I made every step of the way. I don't blame Wyeth, nor do I blame the pharmaceutical industry in general. I blame the doctors who allow themselves to be complicit and corrupted by the allure of money. And yes, I was there with the worst of them!

--At his excellent blog, Hooked, Howard Brody raises the interesting possibility that Wyeth paid me the 30K as a bribe to get me to prescribe more Effexor in my practice. I'm sure that was one of the motivations, and I received letters from some drug reps indicating that this is standard operating procedure in the industry.

--I've received many letters from people who either are taking Effexor now or had difficulties coming off the drug in the past. While my article may have seemed an indictment of Effexor, it was not meant that way. Effexor is a very effective antidepressant, and I continue to prescribe it in my practice, usually as a second-tier agent. But the hypertension and drug withdrawal risks are real. For a very interesting article profiling one man's struggle with Effexor withdrawal, see Bruce Stutz's article, "Self Nonmedication," also published in the New York Times Magazine.

--Many physicians wrote their own mini-confessionals about giving drug talks. One doctor, also a reformed Effexor speaker, described a teleconference in which Norm Sussman minimized withdrawal problems with Effexor. In response, the doctor had an "ethical lapse" and couldn't help mentioning to the audience that Lexapro might be an easier drug for primary care doctors to prescribe, much to Sussman's annoyance. The writer eventually quit speaking for Wyeth.

--I've also received some shocking marketing stories from drug reps and former drug reps, some of which I'll be sharing in the future as I get permission to do so from the parties involved.

Dr. Drug Rep

To see how I made an extra $30,000 in 2002, click here. The article is published in this Sunday's New York Times Magazine. By the way, the Wyeth-sponsored "Faculty Development Programs" are still being held; a friend tells me he just went to one in Florida.

Antipsychotics for the Masses?

When it comes to antipsychotic medication, it appears that psychiatry has come full circle. The very first antipsychotic, Thorazine, was introduced in 1952, and had originally been considered to be an antihistamine, a bit like Benadryl. Eventually, we understood that it had extraordinary effects on the delusions and hallucinations of schizophrenia.

Over the years, many other antipsychotics have been introduced, and they are all effective at reducing psychotic symptoms, as their name implies. But over the past decade, they have also won FDA approval for treating bipolar disorder. Now, the companies marketing these drugs have their eyes on depression, which represents a far larger potential market than either schizophrenia or bipolar disorder. On November 21, Abilify received FDA approval as an add-on treatment for major depression (see the news item here). This follows closely on the heels of a study published a couple of weeks ago in the Annals of Internal Medicine showing that Risperdal was effective as an adjunctive depression treatment.

How effective are these drugs for depression? Not terribly. The Abilify data, for example, shows a remission rate of 26% vs. 16% for placebo augmentation, meaning that 1 out 10 patients would be expected to respond to an Abilify-induced boosting of their current antidepressant. The design of this study was somewhat manipulated in order to make sure Abilify beat placebo, a fact brought to my attention by this excellent post in Cl Psych. Nonetheless, the Risperdal data are very similar, and I'm convinced that atypicals provide a small antidepressant effect. Enough of an effect to overcome the potential side effects? That's unclear.

What is abundantly clear is that drug companies are going to be pushing both psychiatrists and primary care doctors to think of "antipsychotics" as "antidepressants." Look closely at the data before you buy the message!

Luvox CR: Let the Marketing Battles Begin

My Luvox CR posting from this past Monday somehow made its way quickly to the upper echelons of Jazz Pharmaceuticals. Lloyd Davies, the Director of Finance of the company (at least that's his title in this recent industry training event), responded to my early review of Jazz's new product with the following email:

(November 21, 2007)
"I just read your blog. There are a few factual inaccuracies that you might want to correct. 1) It's Luvox CR not SR; 2) The product has not actually been approved yet - presumably why the adverts do not mention the product; 3) Luvox CR is a once a day formulation as opposed to the old product which was twice a day. Therefore the half life might be different right? 4) I am guessing that it is "comorbid" not "comorbic" which is not a word that exists.If you want people to pay attention to what you say you should at least get your facts straight. Perhaps quality would be better than quantity. Lloyd"

I think that my response was civil, but you can be the judge:

November 21, 2007
"Mr. Davies,
Thank you for your corrections, which I have already fixed. However, regarding the half life, my understanding is that CR formulations do not change the actual half-life of the molecules upon with they are based. The major relevant example would be Effexor vs. Effexor XR. The sustained release version is advantageous because it produces fewer GI side effects, but there is no evidence that I am aware of that XR causes fewer discontinuation side effects. Regarding the relationship between half lives and once a day vs. twice daily dosing, this is a non-issue for most psychiatrists. Both Cymbalta and nefazodone are short half life antidepressants that are typically dosed once-daily with no evidence of therapeutic disadvantages. Perhaps Jazz has conducted head to head studies of Luvox vs. Luvox CR--if so, the results would be informative.
Best, Danny Carlat"

I haven't heard back yet from Mr. Davies. I'm guessing that some folks higher up in the company are mulling over the best response, from a marketing perspective. I'd also hazard a guess that the CEO is none-too-pleased with Mr. Davies' e-mail to me. Somehow, I doubt that his message was vetted through media relations at Jazz. But I could be wrong!

Nature Journal Publishes Major Article on Biased Medical Education

A few months ago, Jim Giles, a science writer for the New Scientist and Nature, called me out of the blue to ask about my opinions on drug industry-funded CME. I gave him my usual earful, and mentioned a preliminary study on CME bias that I presented at the American Psychiatric Association meeting two years ago. He asked to see the raw data, meaning the ghost-written CME articles, and it impressed me that he took this level of interest. The result is this article published in this week's issue of Nature.

The bottom line is that in 14/15 articles I reviewed, the sponsored drug received the highest number of favorable mentions. That may not be terribly surprising, but it is evidence of commercial bias, which is not allowed by ACCME standards of commercial support.

Giles is right that the instrument I used, called the Commercial Bias Inventory (CBI), has not been tested for reliability, but I'm now working with two psychiatrist colleagues, Ingrid Li at Tufts and Robert Kelley at Cornell, to validate the CBI. Once it's validated, we're going to blindly rate a number of CME articles and report our findings. If anyone else out there is interested in collaborating with us in this research, let me know (drcarlat@comcast.net).

Luvox CR and All That (Yawn) Jazz

Jazz Pharmaceuticals is running two-page spreads in the psychiatric journals advertising...well, it's hard to figure out what. The headline reads: "Anxiety disorders often present first, before other comorbid conditions." Then there are two blurbs, one about social anxiety disorder (SAD), and the other about obsessive compulsive disorder (OCD). No drug is mentioned.

So you have to google Jazz Pharmaceuticals and social anxiety disorder to find out that Jazz bought the rights from Solvay to market a "new" product, Luvox CR. According to press releases, it is close to FDA-approval for both SAD and OCD and will be released sometime in the first quarter of 2008. What a bummer--not that we have to wait, but that it is being foisted on us at all.

Luvox is another SSRI, and actually the first ever used by psychiatrists, having been approved in 1984 for the treatment of OCD. It has very little going for it. Its half-life is about 15 hours, and it causes more drug-drug interactions than any other SSRI. Before, Luvox was a pretty useless drug; come next year, we'll have a pretty useless drug that lasts even longer than the original.

Jazz Pharmaceutical's advertising slogan is "Innovation that performs." With Luvox CR, there's precious little innovation, and the only performance is a level of marketing chutzpah that is guaranteed to turn off prescribers.

Some Great Blogs to Peruse

Nice to have some good news to report--namely, that I've added three great blogs to my blogroll.

1. The Psych Central Blog by John Grohol. John is a great psychologist and web expert who I know personally. While I've known about his famous Psych Central website for a long time, I only just started reading his blog. He's been posting at a furious pace (unlike me) and everything he writes is interesting and fresh. I'm not really sure how he does it, I just know I'm jealous.

2. PostScript, the new blog by Kate Peterson and The Prescription Project. These are more or less weekly postings covering the world of excessive drug industry influence in medicine. They are thorough, informative, and beautifully written. These are not rants pounded out in the middle of the night, unlike some blogs I know!

3. Hooked: Ethics, Medicine, and Pharma, by Howard Brody. Dr. Brody is an ethics expert and author of the book Hooked, which argues eloquently that we physicians need to reclaim our integrity. Don't blame Pharma, people, it's up to us!

How Money Doth Breed CME Niches!

First, my apologies for the sparsity of posts lately--I ran behind on some newsletter work and I have to keep my subscribers happy.

I just received a flyer from an outfit called "CME Peer Review" (look them up on the web here), a new company which has wormed its way into a brand new niche in the commercial CME world--"independent content validation."

This is NOT their marketing copy, but it might as well be:

THE PROBLEM: OK, you're making money hand over fist by providing drug company-sponsored "medical education" (nudge-nudge, wink-wink). It's a sweet gig, getting million-dollar grants to hire medical writers to scribble out pseudo-newsletters. Donald-me-no-Trumps, these are FAT profit margins...and all yours! So what's the problem? A new "regulatory environment," that's what. Suddenly, everyone from the New England Journal of Medicine to the Senate Finance Committee is whining about "conflict of interest" and "commercial bias." Haven't they read Nietzche?! You are beyond such fairy tales as truth and morality, but in order to maintain your uber status, you must play the game.

THE SOLUTION: At CME Peer-and Jeer Review, our "turn-key system helps you ensure your CE activities are valid, aligned with the public interest and compliant with regulatory guidance and accreditation standards" (that's lifted verbatim from their actual marketing copy!). Got an article sponsored by Pfizer pushing more docs to prescribe Geodon? Choose from our "ever-expanding independent network of reviewers" to find just the shill to give your article the seal of approval. Don't worry, we have a patented system of laundering our reviewers--they're spic and spam and ready to deploy our CME SCRUB DOWN (TM) process for your CME activity.

CLIENT TESTIMONIALS:

"We encountered a difficult situation in which management had already spent the sponsor's grant on a $100,000 rehab of his office shower. Then, at the last minute, we found out the activity was hopelessly biased. We called CME Peer-and-Jeer Review and our problems were solved--what a quick turn-around! Thanks, guys!"

"Your team found an issue in one of our activities--it was subtly promoting a competitor's drug! By helping to bring the activity back in line with the sponsor's agenda, you helped us secure double our original grant for next year. We feel so much more confident about our income stream, thanks to you."

CME Peer-and-Jeer Review: Your CME SCRUB DOWN specialists!