Will the Antipsychotic Coverup Continue?

At this point, there are a slew of lawsuits facing manufacturers of atypical antipsychotics, from individual suits ranging to suits brought by state governments. Allegations of fraudulent marketing, kickbacks, and hiding research results are among the claims made in such suits. For example, Arkansas recently filed a lawsuit. Read it here and read my take here.

The most important thing that could come from these suits in the long run is not the money that various drug companies may have to shell out in fines. No, the important piece is the information, the internal documents that I am nearly certain document numerous instances demonstrating bad science, covering up negative data, and detailing ludicrous marketing campaigns. Check out the documents on Zyprexa over at Furious Seasons and you'll get a taste for what I mean. I've written about them on a few occasions (1, 2, 3) as have others, with one monster post from Furious Seasons serving as an excellent example. If such documents from all companies who have engaged in such ethically dubious practices were to become public information, the PR hit would be enormous. Hell, the media may even wake up and run numerous stories on this issue. Imagine: 60 Minutes, Panorama, NPR, Frontline, Now, and other news programs hitting this one hard on multiple occasions. And the complicity of academic psychiatry makes the story yet more fascinating.

As I mentioned recently:

Without academics pimping these treatments well beyond what was scientifically justifiable, these medications would never have achieved such huge success, but now this rather dangerous group of medicines is used for virtually every psychiatric disorder under the sun. These uses include "bipolar disorder" in infants, ADHD, and dementia. Let's put the most vulnerable individuals on the riskiest treatments despite no clear evidence that they work particularly well. There is indeed some evidence for the efficacy of these medications in the short-term treatment of schizophrenia and bipolar disorder, and in a small number of trials, even some long-term evidence of efficacy. But their indiscriminant use across the board for virtually every condition brings great shame upon psychiatry as a profession, on Big Pharma for its slick marketing strategies (1, 2), and most especially upon academic psychiatry for its morally bankrupt role as a group of salespeople who have misrepresented scientific findings to help promote drugs (1, 2, 3, 4, 5, 6, 7, 8).

But such hopes may well be fleeting. The various offending companies may just decide to settle these cases, which nearly always means that they get to keep their dirty laundry private. Here is a sad possibility mentioned by Furious Seasons:

Risperdal goes off patent in about one month--except for some extra and short-lived pediatric indications--so I'm not sure that Janssen/J&J has a huge incentive to fight Arkansas and the other states that are suing it in order to protect what is soon to be a generic product. It's likely much cheaper for the companies to settle the case (liability insurance will cover much of the cost), write an agreement in which they admit no fault and manage to deep six any documents and other evidence of bad behavior, and move onto Invega.

Zyprexa goes off-patent in 2011 and Seroquel is off-patent the same year as well (not sure about patents on Seroquel XR), so one wonders how much incentive those companies have to fight the state suits, or whether they will just settle the cases and move onto whatever is next for them.

Maybe I am a bit too cynical, but it wouldn't shock me if that's how things played out. After all, Lilly has already settled about $1.3 billion in lawsuits over Zyprexa. Why stop now?

Unfortunately, his prognostication is likely correct. Of course, if some insider at AstraZeneca, Janssen, Bristol-Myers Squibb, or Lilly (or Pfizer --though it seems Geodon has not received much legal attention) decides to leak aforementioned documents, then we're on to something. Consider this an open call to the insiders at said companies. Email me or Peter Rost or Philip Dawdy or Ed Silverman or Jack Friday (Pharmagossip). We're all currently accepting insider documents regarding such matters...

Bristol-Myers Squibb Children's Hospital

There really is a hospital named after a drug company. I'd write more, but Roy Poses at Health Care Renewal has it covered. Are you kidding me?

Abilify: It's Tricky to Rock the FDA

In the "you're kidding me" category, we have a report from Forbes that Abilify (aripiprazole) is going to be going up for FDA priority review as a depression treatment. I was able to track down exactly one placebo-controlled study using this drug as an antidepressant. Participants who did not show satisfactory response to an antidepressant trial were assigned to receive either Abilify or a placebo in addition to their antidepressant. As you'll see, this was a study worthy of close examination.

Study Results. I read the study results and was underwhelmed. The authors (via their ghostwriter(s) to some unknown extent) reported that the difference between those receiving add-on Abilify vs. add-on placebo was three points on the Montgomery-Asberg Depression Rating Scale (MADRS). For perspective, the MADRS has 10 questions, each rated from zero to six. So suppose three of those ten questions show an improvement of one point each. Whoopee. But keep reading -- it becomes bizarre.

Study Design. Patients were initially assigned to receive an antidepressant plus a placebo for eight weeks. Those who failed to respond to treatment were assigned to Abilify + antidepressant or placebo + antidepressant. Those who responded during the initial 8 weeks were then eliminated from the study. So we've already established that antidepressant + placebo didn't work for these people -- yet they were then assigned to treatment for 6 weeks with the same treatment (!) and compared to those who were assigned antidepressant + Abilify. So the antidepressant + placebo group started at a huge disadvantage because it was already established that they did not respond well to such a treatment regimen. No wonder Abilify came out on top (albeit by a modest margin).

Here's an analogy. A group of 100 students is assigned to be tutored by Tutor A regarding math. The students are all tutored for 8 weeks. The 50 students whose math skills improve are sent on their merry way. That leaves 50 students who did not improve under Tutor A's tutelage. So Tutor B comes along to tutor 25 of these students, while Tutor A sticks with 25 of them. Tutor B's students do somewhat better than Tutor A's students on a math test 6 weeks later. Is Tutor B better than tutor A? Not really a fair comparison between Tutor A and Tutor B, is it?

Ghostwriter Watch: Yep, the study acknowledged "Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld Medical Education; funding was provided by Bristol-Myers Squibb Co." Of the study authors, all but one were employees of BMS or Otsuka (which is also involved in marketing Abilify).

Unless BMS is hiding data somewhere, this is hardly the stuff breakthrough treatments are made of. Not that the FDA has a history for expecting much in terms of efficacy, but seriously -- can we have a study without a ridiculously biased design before we jump on the Abilify for depression bandwagon?

Oh, the wonders of "evidence based medicine." This one reminds me of the ARISE-RD study for Risperdal as a depression treatment.

Update: I forgot to mention that this is not the first time I've been puzzled by Abilify's claims. For information on how Abilify is supposedly a great long-term treatment for bipolar disorder, you really have to get the story from Furious Seasons, who had a great post on the topic in December 2006. Get ready for more flimsy evidence from BMS.