Grohol Slaps TAC Senselessly Silly

The Treatment Advocacy Center (TAC) recently posted that people with schizophrenia are 10 times more likely to be violent as compared to persons not suffering from schizophrenia. I quickly said "WHA?" That seemed so far detached from reality that I didn't even know where to start. So Marissa Miller had a nice analysis of their figures that pointed out a number of flaws in the analysis. Nice job, Marissa.

Then John Grohol stepped in and (BAM) slapped the TAC analysis silly. Absolutely senselessly silly. I won't even try to steal his thunder. Just go to Psych Central and you'll come away saying, "Those *@!@ at TAC!" Nice job slicing and dicing, Dr. Grohol! I'm always proud when a fellow psychologist throws the BS flag when needed.

Lilly and Cash

Pharmalot has a very interesting post regarding how Lilly disseminates cash to various organizations. The largest recent recipient was Massachusetts General Hospital, which by sheer coincidence (?), is where Mauricio Tohen, the lead scientist on the Zyprexa team happens to hang his hat (See update below!). In the first quarter of this year, Lilly doled out over a half million dollars to the National Alliance for the Mentally Ill. This should come as no surprise, given that a few years ago, the head of NAMI was a Lilly executive "on loan" from Lilly. So it comes as no surprise that NAMI often finds itself issuing talking points that coincide nicely with Lilly's goals, such as lobbying against restricting Zyprexa usage. Much more over at Pharmalot and the Wall Street Journal (registration required).

UPDATE: I made an error. I thought that Dr. Tohen held an academic appointment at Mass General -- I was mistaken -- he holds no such appointment. I sincerely apologize for the mistake. Mea culpa. Rather than delete the offending text and leave the impression I am trying to cover my mistake, I will leave it above so that my error can be recognized publicly.

Cyberonics Says Ouch

A CEO switch and a 15% cut in workforce, for starters. Things are not swinging so well at Cyberonics, manufacturer of the vagus nerve stimulator, used to treat severe depression. Concern regarding its efficacy has made VNS use quite infrequent. Cyberonics made my sights due to some clever (and ethically dubious) marketing on behalf of one of its associated academics, Charles Nemeroff. Background here and here.

I've had readers provide numerous comments and send emails on VNS. Suffice to say, it is pretty controversial and there are some who swear by VNS and some who swear at it. The efficacy trials do not paint a generally favorable picture.

Hat Tip: Pharmalot.

Reconciling with Spot

Apparently drug marketers are making drug names to appeal directly to humans (duh), but in a manner that is more direct. Think about drugs for humans, like Prozac -- well, Pro is good, but what the hell is Zac? But new doggie drug names like Reconclie (doggie Prozac), Slentrol (for fat pooches), and Serenia (to prevent dogs from puking) -- pretty straightforward. After all, it's easier to be serene when one's dog is not yakking all over the floor. Slentrol (uh, slender-control), and Reconcile (no, you're a GOOD doggie parent -- reconcile with your sad dog with dog-Zac) are likewise easy to figure out.

Hat tip to Pharmalot and Name Development.

Lilly Plays The Heavy

Lilly has apparently threatened to sue the pants off an individual who disseminated some of its documents regarding the Zyprexa debacle. Health Care Renewal indicated (via a Nature article unavailable to most) that David Egilman, who played a role in getting the infamous documents disseminated may face severe legal sanctions. The kind that cost a lot of money.

The irony is that Lilly claims that the documents which paint a rather awful picture of its off-label marketing (here, here, here, and here) are taken out of context, yet they refuse to make any additional information available. If the documents are out of context, why don't you provide some context? Indeed, they are suing those who tried to disseminate information pertaining to the drug. And let's also not forget about the email exchange where a Lilly employee discussed ways in which a study casting dispersions on the "safety" of Zyprexa could get deep-sixed through nefarious means.

And The Blogosphere Wept

Very sad news to report. Pharma Giles, easily the most entertaining pharma-related blog, has decided to call it quits. I wish he were just pulling a Peter Rost and retiring for a week, then coming back, but Giles strikes me as pretty serious. That being said...

PLEASE DON'T GO!!! PharmaGossip and Peter Rost agree with me, as I'm sure do others. You can't possibly leave. Who will fill your shoes?

Don't Diss Berenson

Drug Wonks has a post saying that Alex Berenson's latest reporting on the Zyprexa scandal is likely erroneous because he is pulling information from just a few Lilly documents. Indeed, it is stated...

Once again, Berenson uses the "one paper out of several thousands of documents" approach to depict Lilly as a criminal corporation.

Further, it is added

On the heels of intense criticism of the NYT coverage of the Duke rape case and the paper's falling earnings, the Berenson reporting is another example of the Times decline.

OK. Here's my challenge. I'd like Drug Wonks or, well, anyone to read the following posts. Read the Lilly documents that are freely available and are linked within said posts. Then talk about how Lilly is a good corporate citizen, and did not promote Zyprexa off-label. Here you go...

• Demented Marketing of Zyprexa?
• Marketing Zyprexa as the New Mood Stabilizer...
• Zyprexa Off-Label Promotion (?)
• Zyprexa Off-Label Marketing (?): Part 2

As for the "well, we haven't seen every single document" argument, please see my earlier post for why I think that argument is weak.

Paxil and Pimping

A preliminary ruling has indicated that GlaxoSmithKline should pay out $63.8 million to make amends for making misleading claims about its antidepressant Paxil (Seroxat) in kids. Of course, the company admits no wrongdoing.

I wonder if the authors who stamped their names on the the main ghostwritten "scientific" publication for Paxil in kids should also be shelling out some cash. After all, it was the paper (chock full of HUGE misinterpretations of the study data) with their names on it that was doubtlessly used as part of the Paxil in kids marketing campaign. Were these "independent" academics innocent parties who were misled by the corporate meanies at GSK? Or, conversely, were these academics an integral part of the marketing team and should they also be held accountable for making false claims? Like these claims made in the infamous GSK study 329 (from an earlier post)...

Article: Paroxetine is generally well-tolerated and effective for major depression in adolescents (p. 762).

Data on effectiveness: On the primary outcome variables (Hamilton Rating Scale for Depression [HAM-D] mean change and HAM-D final score < 8 and/or improved by 50% or more), paroxetine was not statistically superior to placebo. On four of eight measures, paroxetine was superior to placebo. Note, however, that its superiority was always by a small to moderate (at best) margin. On the whole, the most accurate take is that paroxetine was either no better or slightly better than a placebo.

Data on safety: Emotional lability occurred in 6 of 93 participants on paroxetine compared to 1 of 87 on placebo. Hostility occurred in 7 of 93 patients on paroxetine compared to 0 of 87 on placebo. In fact, on paroxetine, 7 patients were hospitalized due to adverse events, including 2 from emotional lability, 2 due to aggression, 2 with worsening depression, and 1 with manic-like symptoms. This compares to 1 patient who had lability in the placebo group, but apparently not to the point that it required hospitalization. A total of 10 people had serious psychiatric adverse events on paroxetine compared to one on placebo.

What exactly were emotional lability and hostility? To quote James McCafferty, a GSK employee who helped work on Study 329, “the term emotional lability was catch all term for ‘suicidal ideation and gestures’. The hostility term captures behavioral problems, most related to parental and school confrontations.” According to Dr. David Healy, who certainly has much inside knowledge of raw data and company documents (background here), hostility counted for “homicidal acts, homicidal ideation and aggressive events.”

Suicidality is now lability and overt aggression is now hostility. Sounds much nicer that way.

What counts as safe and effective on Planet Paxil passes as ineffective and dangerous to us Earthlings. So while I'm glad to see that it appears GSK will be shelling out some dough to compensate its , consumers, the systemic problems of ghosted science and outright lying are not addressed. What is $64 million to GSK? Roughly a drop in the bucket. And the "key opinion leaders" who pimped Paxil escape unscathed.

Please read the fine post at Health Care Renewal about how academics might be brought to think twice before becoming drug pimps. I also think that giving out sarcastic awards to academics who participate in ghosted science is a good idea, so here goes...

Awards? I'd like to nominate Dr. Karen Wagner for a Golden Goblet, or perhaps a Krusty the Klown award for her pimping of Paxil as well as her stalwart work on the "SSRIs are great for kids" report authored on behalf of the American College of Neuropsychopharmacology. Her reports of clinical trials that overstated the efficacy and hid serious side effects of Zoloft also merit special mention. Overstating the efficacy of citalopram in kids was also nice work. While she was co-authoring the report saying that SSRIs are great for kids, she was also busy conducting trials of SSRIs for kids. Sound like a conflict of interest? Worry not, because she was also sitting on the conflict of interest committee at her own university!

Please feel free to add your nominations.

Oh, and as for the latest version of SSRIs are great for kids report (in JAMA). I'll hopefully get on that sometime in the near future. Suffice to say that it is highly misleading for now.

Data Massaging at Lilly?

From the New York Times:

The FDA has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug.

That document was not submitted to the agency. But a few months later, Lilly provided data to the FDA that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.

But worry not, Lilly is claiming the above was just an honest mistake. Kind of a large mistake, eh? After the data were analyzed accurately, then Zyprexa did not appear nearly as risky. Of course, we can be sure Lilly is being honest, just like when they said that they never marketed Zyprexa as a treatment for dementia. Or the time they said that Zyprexa does not cause diabetes. Or maybe when Lilly decided to sell Zyprexa as a "safe, gentle psychotropic." I think you get the point... It is indeed possible that Lilly is being truthful, but I personally doubt it.

On a side note, good to see that Alex Berenson is back to writing about Zyprexa.

Lunesta Stomped

Health Care Renewal posted an interesting piece about the misleading ads for Lunesta, which was largely based on an NPR clip. Yeah, the sleeping pill with the butterfly ads, which raked in $567 million for Sepracor in 2006. Essentially, research on the drug has actually found that actual amount of sleep changes by somewhere in the range of 37 minutes compared to placebo, with people falling asleep, at best, 10-15 minutes faster while taking the drug compared to placebo. Another interesting dissection of Lunesta advertising is up on the Consumer Reports website.

Oh, and another study found that using behavioral sleep management techniques resulted in higher quality sleep than did taking Lunesta. So keep that butterfly out of my bedroom!

With that, I close. I'll be away for a few days. Enjoy your weekend.

Peter Rost is ON FIRE!

I bow down to Peter Rost. Why? Let's see... He broke the latest AstraZeneca Arimidex off-label marketing scandal. Rather than being a one-time story, it has continued to unfold, looking worse and worse for AZ. Rost continues to serve up hot AZ insider information, as the scandal grows wider in scope. He has also backed up his brand of investigative journalism with evidence (here and here) that points quite directly at AZ marketing their product in an off-label fashion. And the plot continues to thicken, as you can see here.

Keep up the good work Peter!

Gee, Thanks Graham!

Read the following abstract from Graham Emslie and company. I went ahead and highlighted the points of interest.

OBJECTIVE: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. METHOD: Participants received venlafaxine ER (flexible dose, based on body weight; intent to treat, n = 169) or placebo (intent to treat, n = 165) for up to 8 weeks. The primary efficacy variable was the change from baseline in the Children's Depression Rating Scale-Revised score at week 8. RESULTS: There were no statistically significant differences between venlafaxine ER and placebo on the Children's Depression Rating Scale-Revised in either study. A post hoc age subgroup analysis of the pooled data showed greater improvement on the Children's Depression Rating Scale-Revised with venlafaxine ER than with placebo (-24.4 versus -19.9; p = .022) among adolescents (ages 12-17), but not among children (ages 7-11). The most common adverse events were anorexia and abdominal pain. Hostility and suicide-related events were more common in venlafaxine ER-treated participants than in placebo-treated participants. There were no completed suicides. CONCLUSIONS: Venlafaxine ER may be effective in depressed adolescents. However, its safety and efficacy in pediatric patients has not been established. Prescribers should monitor for signs of suicidal ideation and hostility in pediatric patients taking venlafaxine ER.

Here are my gripes...

• OK, so the studies were conducted in 1997 and 2001. And they're just getting published NOW? How's that for delaying the bad news? Were the studies positive in their findings, they would have been published years ago.
  
• Suicidal ideation/suicidal attempt/suicide preparation: 8 of 182 taking venlafaxine, 0 of 179 taking placebo (these numbers come from the latest JAMA analysis, table 3).
• Grasping at straws: One analysis finds that adolescents do a bit better on the drug, and you decide to run with it? Was this finding consistent across various rating scales or was it just one one scale? My initial guess is that the difference was also of a rather small magnitude.

I'll be able to address some of these issues as soon as I get my hands on the article. Our library subscribes to this journal online, but the April issue has somehow not yet arrived. More to come.

Going to the Dogs

One blogger (Pharmalyst) has estimated that Lilly's new doggie Prozac could bring in $270 million annually in US sales. Sounds over the top, but maybe it could happen. I looked for the clinical trials, because I really want to know how one measures canine depression, but I couldn't find any information.

Son of Effexor: Good News

According to Reuters:

Wyeth on Thursday said low doses of its experimental drug Pristiq were effective against both depression and hot flashes and caused less nausea than seen in prior studies of higher doses, boosting prospects for the company's most important experimental drug.

Well, good. With antidepressants, we all know by now that "effective" means "slightly better than placebo" on average. Pristiq, a knock-off of Effexor, is hoping to nab FDA approval early in 2008. Can't wait to see the ad campaign. Depression Hurts is already taken, so with the depression/hot flash combo, I have the following idea:

Does Depression Make You Hot? Let Pristiq Cool You Down.

You like?

Hat tip: Pharmalot

DSM System is WHA?

The DSM system of diagnosing mental disorders is dehumanizing. Not my words (though I think it's largely true), but the words of Nancy Andreasen, a rather big-name psychiatry researcher at the University of Iowa. Here's a quote [emphases added]...

The DSM has had a dehumanizing impact on the practice of psychiatry. History taking—the central evaluation tool in psychiatry—has frequently been reduced to the use of DSM checklists. DSM discourages clinicians from getting to know the patient as an individual person because of its dryly empirical approach. Third, validity has been sacrificed to achieve reliability. DSM diagnoses have given researchers a common nomenclature—but probably the wrong one. Although creating standardized diagnoses that would facilitate research was a major goal, DSM diagnoses are not useful for research because of their lack of validity.

Ouch. Training in psychiatry programs as well as (sigh) some psychology programs has often been reduced to memorizing symptoms and asking yes-no questions from a checklist. See what diagnosis a person has by asking a bunch of structured questions then whip out a prescription pad. Talk with the patients about their problems, develop a relationship? Nah, we never learned about that in our graduate/medical training.

Hat tip: AHRP.

Imus and His Ilk

Pick up some lowlights from the following video to remind yourself that Imus was just one in a long lineup of folks who drone on and on with racist/sexist/gay-bashing banter... Hat tip: Supergirlest

Lexapro is Waaaaaay Better than Celexa (?)

...according to Forest Labs. Dr. Roy Poses at Health Care Renewal received a letter telling him about the dangers of using citalopram versus using Lexapro. As you may recall, Lexapro (escitalopram) is essentially a one-off copycat of Celexa (citalopram). An urgent letter was recently sent out from a marketing firm (which was hired by Forest) to inform doctors that evil managed care firms may attempt to switch their patients from Lexapro to generic citalopram. Now, I'll agree that if someone seems to be doing well on a medication, it would seem odd to change their medication. I don't think there is any firm evidence on what would happen if you switch someone from a drug A to drug B, which is nearly identical to drug A (i.e., escitalopram to citalopram), but one could certainly wonder about the merits of drug switching.

In any case, the letter then goes on to make some astounding claims, including [bold font in original letter]

The clinical profile of Lexapro and citalopram are distinct, as illustrated by the following:

- Lexapro is effective in the treatment of major depressive disorder (MD) and generalized anxiety disorder (GAD). In contrast, citalopram is not indicated for GAD, or for any other anxiety disorder. [citations were to the respective drug labels.]

- There is clinical evidence for the greater efficacy of Lexapro vs. Celexa

...among others. For a very nice analysis of why these claims are misleading, please read the full post at Health Care Renewal. My two cents on why the claims are misleading is as follows:

• Since its patent was running out, Forest opted to not seek FDA approval for any anxiety disorders. No study has ever compared the two compounds in treating anxiety. While true that citalopram is not FDA-indicated, this should not be taken as a sign that it would perform worse than escitalopram in anxiety. Indeed, across the class, SSRIs are efficacious (in the short-term, and not a lot better than placebo) for anxiety.
• The evidence cited to support the greater efficacy of escitalopram over citalopram is very weak. It comes from looking only at the few instances where escitalopram showed a very small advantage over citalopram and ignoring the great majority of the evidence that suggests equivalent efficacy of the two compounds. An excellent article by Svensson and Mansfield laid this issue to rest years ago. Here's what they said regarding Forest's prior advertising claims that Lexapro is more effective than Celexa:

"The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices."

My thought is that the letter may have something to do with managed care policies, but it is also a stealth advertisement for Lexapro as being the most efficacious SSRI. After all, if it is "better" than Celexa, then maybe it is "better" than other SSRIs. Of course, this would not be the first time that something Lexapro-related was looking at the scientific evidence through rose colored glasses.

Lilly Posts 1Q Earnings

And they're pretty good. Of psych note, Zyprexa sales were up 10% compared to the 1st quarter of '06; Cymbalta sales up 89% from 1Q '06, and Strattera sales down 8% from 1Q '06. Overall, sales were up 14%. Source.

According to Bloomberg, Lilly is planning to ramp up marketing of Cymbalta and Zyprexa. Can you say Viva Zyprexa Strikes Back? How about Anxiety Hurts (1, 2)? I wonder to whom Lilly will market Zyprexa? Seriously -- they've tried primary care, psychiatrists, and likely the geriatric market, so who's next? How about pediatricians? Tantrum = Zyprexa?

AZ: The Plot Thickens

The gang of seven concerned employees as AstraZeneca march forward with more details concerning their allegations of off-label marketing. This one could really blow up into something large, if the facts are straight. Check out the latest from Brandweek NRX and Peter Rost.

Lest you forget, AZ also makes Seroquel, and the lawsuits have already begun about the, um, liberal, marketing of that product. More on Seroquel's ever-expanding market here and here.

Links Of The Week

Some good stuff you should all be aware of as you head into the weekend...

• AHRP notes that the FDA review panel which will examine the risks associated with Merck's new COX-2 inhibitor, etoricoxib (Arcoxia), is stacked to find that the drug is safe. How? Well, as AHRP said:
  

  The arthritis specialists who voted to keep the COX-2 inhibitors on the market were reappointed. But the four most vocal critics of the COX-2 pain killers were NOT to reappointed. FDA apparently wants to avoid a full examination of the safety issues when considering approval of Merck's Vioxx replacement drug.

• But the good news is that with the exception of one member (and who the hell was that one member?), Arcoxia got voted down by a 20-1 margin. GoozNews has a great post that mentions how the advisory committee decided getting fooled twice was not an option. David Graham, unsurprisingly stepped up the the plate yet again. Incredibly, Merck decided to compare Arcoxia to another drug that has an elevated risk of causing heart problems. And the IRB that approved that study was...? By comparing it to a risky drug, Merck could attempt to claim that Arcoxia didn't increase cardiovascular risk. That's like comparing a drug to getting hit by a sledgehammer. "Well, the drug was actually less risky than being brained with a large blunt object; therefore, it is clearly safe." Nice to see that the FDA didn't fall for it this time.
  
• Pharmalot also has a nice summary of the Arcoxia debacle.
  
• No surprise here -- Pharma Giles is guilty of causing me to nearly suffer the same fate as those who took the ill-fated drug Uleak due to my Def Comedy Jam type laughter at two of his recent posts. Here's the one on Uleak and here's one thinly disguised parody of the latest developments at AstraZeneca.
• Peter Rost received some information, allegedly from an Astra Zeneca insider, stating that they were tired of AZ's unethical practices, specifically referencing the marketing of Arimidex (anastrozole). Can Seroquel be far behind?
• I also give Dr. Rost credit for applying for positions in the drug industry. Read his hilarious (and accurate) cover letter.
• Philip Dawdy notes that yet another class action lawsuit has been filed against Lilly for its heavy pimping of Zyprexa.
  
• Seroxat Secrets points out another example of patient advocacy groups carrying Big Pharma's water. In this case, it appears that the Depression Alliance is participating in the marketing of Cymbalta. The Cymbalta Pimp-A-Thon continues.