Consensus of Marketing, Er, Science

Seroxat Secrets has a dynamite post on "consensus statements," in which a group of "expert" academics put a stamp of approval on how a disorder should be treated. For example, there is now a "crisis" of adult ADHD in the United Kingdom (just as there is here, though we're sometimes confused about the borderline between ADHD and bipolar disorder). And this crisis requires action. What kind of action? The kind that is mentioned in the consensus statement, of course.

I can tell you that the consensus statement has a great note at the end where it mentions that more ADHD treatment will reduce crime, smoking, and unemployment. No word yet on if hunger in Africa would also be alleviated.

Which brings me to the birth of the consensus statement. Hint: There are some conflicts of interest and perhaps stealth marketing involved... Please read the whole story at the excellent Seroxat Secrets.

It sure was nice of several drug companies who manufacture ADHD medications to sponsor the aforementioned consensus statement. And to think that the kindhearted folks at these companies would just give their money away to these dispassionate academics who make perfectly reasonable claims (like more ADHD treatment will lower unemployment). A heart-warming tale, indeed.

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?

More "Science"

During my semi-hiatus, which has been far from recreational, I have mostly kept up with my reading (but obviously not writing). Of particular note to psychiatry, marketing, and pseudoscience, check out a couple great posts from Dr. Daniel Carlat.

One is about an incredibly bogus "survey" that turns up favorable results for Abilify. Oh, how I LOVE that the "science" is stacking up behind Abilify these days.

The other is regarding the alleged (and fake) hidden epidemic of ADHD among depression patients.There are many other good posts that I've not the time to cover now.

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.

Atypical Antipsychotics Down Under

Furious Seasons has a roundup of the latest regarding atypicals in Australia. How about a substantial number of deaths related to their use? Add in a substantial number of patients complaining of other side effects and, for good measure, how about Lilly facing legal action over Zyprexa? Crikey.

JAACAP Strikes Again

Aubrey Blumsohn has detailed how the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) is standing behind its work, despite some huge questions -- See Chapter 2 below.

Chapter 1: Paxil 329. You might recall my hissy-fit over JAACAP editor in chief Mina Duncan's declaration regarding Paxil Study 329:

I don’t have any regrets about publishing [the study] at all – it generated all sorts of useful discussion which is the purpose of a scholarly journal.

This comment was especially interesting given that the published study had the following issues:

• Renamed suicidality as "lability" and overt aggression as "hostility."
• Declared superiority over placebo in treating depression when, in fact, the study data did not support such an assertion
• Determined (by magic?) that a placebo can make you suicidal while Paxil could not. The folks who became suicidal on Paxil -- it was not because of Paxil, but the one patient who became suicidal on placebo became suicidal due to the placebo. How does that work?
• Study was ghostwritten
• Lead author Marty Keller appears not to have read the study data

Read more about all of the above here. Despite the study being somewhat of a joke, which was noted to some extent by reviewers, Dr. Duncan published it anyway and said she had no regrets about it.

Chapter 2: The Gillberg Affair

To make a long story short, another study that was published in JAACAP has come under a pile of scrutiny. The study claimed that a syndrome called DAMP (Deficits in Attention, Motor control and Perception) was quite common. There was concern that the data was fraudulent, as can be seen by following this link. My point is not to discuss whether the data were or were not cooked -- I have not given this enough investigation to weigh in.

The point is that the lead researcher Christopher Gillberg refused to provide the data to defend against charges that the data were fraudulent. Mind you, no identifying information was being requested. Just the numbers. The plot thickens substantially from there, but one key point worthy of mention here is that a Swedish court insisted that the DAMP study data be provided to investigators. The data were then destroyed. That would be a no-no in science. If nobody can see the numbers, how do we know they weren't cooked?

Aubrey Blumsohn has engaged in email correspondence with JAACAP staff that I found illuminating. JAACAP's point seems to be that they don't care if the study data were destroyed -- it's not their problem.

No, journals, which serve as the official scientific record, don't need to hold study authors accountable to making sure their study data are accurate. That would be just too much to ask, apparently.

Guilt By Association

Over at Drug Wonks is a recent post by Robert Goldberg that would be funny if it weren't so insulting. I have previously discussed how Drug Wonks appears to be a part of the drug industry PR machine. The latest is at least the second swipe that the Drug Wonks have taken at Carlat. It would appear that Carlat is guilty of guilt by association according to Goldberg's reasoning. Carlat was previously guilty of the heinous sin of criticizing the drug industry.

Carlat has linked to the AHRP in his list of sites labeled "Great Pharma Information". This induced a rant from Goldberg in which he called the folks at AHRP "whack jobs." I have likewise linked the AHRP on my blogroll, so I suppose I am equally guilty. Goldberg is also hot under the collar about Carlat linking to Prescription Access Litigation. Those greedy lawyers linked to PAL are just suing drugmakers to line their own pockets, or at least that's the Goldberg argument. The problem is that it has taken litigation to unearth the infamous Zyprexa documents, which have suggested strongly that Lilly's marketing of Zyprexa was waaaaaaay out of line (1, 2, 3 ). Are the lawyers set to make out like bandits in these lawsuits? Sure. But how else are corporations to be held accountable for pushing drugs for inappropriate uses or masking side effects of their products?

And more from Goldberg...

Let Carlat ally himself with anti-science extremists and tort lawyers. In the wake of the SSRI-suicide debacle I will put my trust in the so-called pharma-academic complex any day

Oh, Goldberg is apparently in the SSRI's are never linked to suicidality camp? Not sure, but it looks that way. He may want to refresh his knowledge on such matters here or here. Oh, but I guess that actually looking at the data from clinical trials and noting that it indicates SSRIs are related to a greater incidence of suicidal acts than placebo makes me a "whack job." That's for y'all to decide, I suppose.

Catching My Eye

Yeah, I'm way behind on linking to many great posts by my fellow mental health and drug industry bloggers. In the short time that I have, here we go...

• Key Opinion Leaders as Pokemon Cards and a post on Big Pharma trying to discuss bribing doctors with booze in a politically correct manner. I'm definitely liking the new Carlat Psychiatry Report.
• How about a New Orleans psychiatrist being brought up on charges of research misconduct (involving Paxil ) and healthcare-related fraud? Check out Fiddy's site for more.
• Furious Seasons has the latest from the bipolar child battlefield. Oh boy.
  
• Peter Rost calls it exactly right regarding Bush releasing Libby from prison.
  
• Pfizer scares the bejeezus out of research sites in a move that could potentially lead to yet more scientific misconduct (via Cutting Edge)
• PharmaGossip has the quote of the week.
• Pharma Giles scores with a great parody of the latest AIDS treatment hullabaloo
  
• Health Care Renewal has a gut-churning post on how the firms that conduct research to evaluate new drugs are also (drum roll please) investing in the compounds that they are "independently" investigating. So if the drug they are "independently" evaluating works, they make more money. Just when you thought the system could not get any more corrupt...

My time's up. Apologies to the good work I did not cite here. Have a Happy 4th of July and stay away from the fireworks that double as deadly weapons.

Quellin' in the Joint

I'm never sure how Ed at Pharmalot is able to keep up on literally everything drug-industry related, such as the recent story regarding the use of psychotropic medications in Vermont prisons. The latest story that I picked up from his site included estimates of 40 and 46 percent of the Vermont prison population being on some form of psychotropic medication. If either of those are close to correct, then I'm pretty sure we have a problem. In one Vermont prison, 20% of inmates were on Seroquel.

Perhaps that is not surprising in light of earlier research that Seroquel (or "Quell" as it is known in some correctional circles) is crushed and snorted in prisons and that some folks find it quite difficult to stop taking the medication. There have been other case reports indicating difficulties in patients discontinuing the Quell (1, 2 ). It was also reported (though it is unclear to what extent this is true) that some inmates request Seroquel because it gives them "a buzz."

And I thought Seroquel was just another "safe, gentle psychotropic..."

None of Your Business

The Associated Press ran a recent story indicating that two top FDA officials who are required by law to post their appointments had not been doing so for several years. The calendars of high-ranking officials Janet Woodcock and Steven Galson were described as "virtually empty" for a period of several years. After a congressional investigation noted the blankness of their calendars, FDA officials filled in their calendars retroactively. To nobody's surprise, their calendars included many meetings with drug industry officials as well as others. Just how blank were their calendars?

There were just three listings for Woodcock between January 1999 and December 2006, even though she occupied two positions during that time that required her meetings to be listed: director of the center for drug evaluation and research and, later, deputy commissioner for operations. Investigators found no listings for Galson, who took over the drugs office from Woodcock on a full-time basis in July 2005.

Yeah, that's pretty blank. I'm not suggesting it is entirely wrong for them to have met with drug industry officials, as that is obviously part of the job. But why cover it up? At the very least, it creates an impression that there is something to hide. Worry not, the FDA has described it as "administrative oversight." Perhaps the FDA has an intern in charge of schedules who resembles the PhRMA intern of John Mack fame.

Hat Tip: AHRP

Seroquel for Everything: Off-Label Marketing?

Peter Rost has a trio of documents on his site regarding potential off-label marketing of Seroquel. As you may recall, I promised to track the Seroquel lawsuit saga that I am fairly certain will continue to unfold. Why the lawsuits? Partially due to allegations of off-label marketing. The latest chapter, from Rost's site, is that AZ appears to have sent out a letter to sales representatives asking them to inform doctors about "medical education" events. As you probably know by now, "medical education" is quite often drug company-speak for "advertising." (1, 2, 3 ).

These "medical education" events were available via VHS, DVD, or webcast for doctors to view at their convenience. One event discussed Seroquel use in the young and the elderly, while another focused on Seroquel for bipolar depression prior to Seroquel receiving FDA approval for such an indication. Is that naughty? Yes. Is it illegal off-label marketing? I'm no lawyer, but I bet not.

Why? Well, the medical education was not provided by AZ. No, it was provided through a third party (i3 CME ), which was "supported" by AZ. i3 CME then found some key opinion leaders to provide "education" to their physician peers. The marketing message is laundered through i3 CME so that AZ can say, "We weren't marketing anything off-label -- we're not responsible for what i3 CME did with the program -- i3 CME is independent!"

Yeah, right. Should i3 CME wish to stay in business, they're going to make sure to get pro-AZ speakers and design a program that paints Seroquel in a good light. My favorite part is this snippet from the letter from the AZ CME director to sales reps.

AstraZeneca supported an independent educational activity on October 8, 2006 in the areas of "psychosis and dementia."

So if AZ supported an "independent" educational activity, doesn't that make the activity, um, not independent? Give me a break. For more on the Seroquel for everything saga, please read prior posts here and here.