Monday, June 30, 2008

Cymbalta: Good For Whatever Ails You

I don't have time to write much on the topic, suffice to say that John Russell of the Indianapolis Star raises some good questions about Cymbalta, Eli Lilly's antidepressant/antianxiety/analgesic/good for whatever ails you pill.  He calls it a Swiss Army Knife, which is ironic given that Lilly gave out Swiss Army Knives as part of its Viva Zyprexa campaign, likely as a reminder that Zyprexa (much like Cymbalta) was a broad spectrum psychotropic that could be used to treat, um, a lot of things.  Despite Cymbalta being touted as a cure for both depression and all sorts of different types of physical pain, once again it appears that the science has failed to live up to the marketing, at least for treating pain in depressed patients. Russell's article asks whether it is reasonable to expect that one drug could really work for so many different conditions.  It's well worth a read.

Hat Tip: Furious Seasons and an anonymous reader.

Conflicts, Bad Science, and Corlux: Part Two

The blogosphere has been abuzz with discussion of psychiatrist Alan Schatzberg's dual roles as a tycoon and an allegedly "objective scientist."  But wait... there's more.  Schatzberg is deeply involved with Corcept Therapeutics, a company that has repeatedly found that mifepristone (Corlux/RU-486) is a dud for psychotic depression.  Yet Corcept has continually attempted to spin the results as positive, in a manner that should be obvious to anyone who passed an introductory research methods or statistics course.  Schatzberg has millions of dollars in Corcept shares and should Corcept actually turn out to possess even minimal efficacy for psychotic depression, Schatzberg stands to profit quite handsomely.  

Bernard Carroll has the next chapter in this interesting saga, dealing particularly with Stanford University's claim that Schatzberg was not involved in "managing or conducting any human subjects research" using Corlux.  Such a claim is essentially saying that because of his financial connections with Corcept, Schatzberg avoided tight involvement with the studies of the drug so that he could avoid a conflict of interest.  Dr. Carroll, however, notes that it seems very likely Schatzberg was indeed involved in Corlux research.

There is reason to believe that Dr. Schatzberg had a key role in Stanford’s clinical trials of Corcept’s drug reported in 2001, 2002, and 2006. He was a co-author on all three publications, and there was no disclaimer about his role until 2006. This disclaimer is hardly credible. As Principal Investigator on the NIH grants, Dr. Schatzberg was expected to supervise the junior faculty and research staff at Stanford who recruited, assessed, and treated patients in the studies of RU 486. He was responsible for the choice of outcome measures, about which questions have been raised. He was responsible for the quality of the reported data analyses, which were, frankly, inexpert, when they were provided at all. Above all, he was responsible for the tone of the NIH-supported Stanford publications that claimed Corcept’s drug is effective.

That's just a tidbit -- there is much more to the story, and it should be read immediately at Health Care Renewal.  Keep in mind that Schatzberg is the president of the American Psychiatric Association.  You may then choose to giggle or cry -- your choice.  

Thursday, June 26, 2008

Conflicts, Bad Science, and Corlux

Recently, the watchful eyes of Charles Grassley have been peering into the bank accounts of big name psychiatrists. Melissa DelBello and Joe Biederman (1, 2) from the Wonderful World of Child Bipolar were first, and now Alan Schatzberg has been hit. Schatzberg is the Chair of Psychiatry at Stanford University. He is also the President of the American Psychiatric Association. In other words, he's kind of a big deal.

Pharmalot hits the details, but the gist is that Schatzberg is deeply involved at Corcept Therapeutics, a company for which he is chair of the scientific advisory board and holds a large amount of stock. According to Grassley, he did not disclose some of his stock sale profits or the magnitude of his multimillion dollar stock holdings in the company. Additionally, Schatzberg allegedly underreported income received from other drug companies. It appears that Schatzberg was not really required to disclose some of this information, so according to my brief review of the information, it is quite possible that he has broken no rules. Now, whether the rules need to be changed is a different story. No offense to Grassley, but I was well ahead of him on part of this story, noting in April 2007 that Schatzberg had a mega-conflict of interest going with Corcept. I also noted previously that Schatzberg was on the Zyprexa bandwagon, helping to "educate" fellow physicians about the Lilly wonder drug.

The Real Problem: But amidst all this discussion of conflicts of interest, I am afraid that we are getting a bit diverted from the main problem, that of shoddy science. It is admittedly interesting noting that Schatzberg is somehow supposed to be an independent, disinterested scientist while standing to make an absolute truckload of money if his sponsored product succeeds. But it runs deeper. While Schatzberg is a bigwig at Corcept, let's review how Corcept's main product mifepristone (RU-486; yes, the abortion pill) has done.

Mifepristone (aka Corlux) is intended to work as a treatment for psychotic depression. One main problem: It doesn't relieve depressive symptoms. In multiple trials, it has failed to demonstrate antidepressant properties. The CEO of Corcept and another member of their scientific advisory board have previously tried to spin away such inconvenient data by painting negative results as positive. To give Corcept credit, their scientists are consistent spinmeisters, seemingly always able to dredge a positive from obviously negative findings. Schatzberg has been an author on a couple Corlux-related papers that were shredded by independent analysts, who found statistical problems and overly optimistic interpretations of the study results. As the senior member of the Scientific Advisory Board, I assume that Schatzberg had some input on the other study reports that also overstated the efficacy of Corlux.

Could his millions of dollars in Corcept holdings bias Schatzberg, either subconsciously or overtly? You be the judge. But remember that this is not just about conflicts of interest -- this is about science. There is hard evidence that the research on Corlux, which is tightly linked to Schatzberg, has been misinterpreted for the sake of marketing. Conflicts of interest sometimes lead to bad science, but rather than focus just on conflicts of interest, we need to dig a layer deeper and see the poor science -- the shoddy evidence that is used as the foundation for "evidence based medicine" in many cases.

Note also that David Healy has written an interesting piece on the topic of conflicts of interest and bad science, pointing out that a larger problem is lack of access to company-owned data. Think Paxil and suicide. He concludes:
If I were employed in a company marketing department I would much prefer to have the field think that all that is wrong is that a few corrupt academics fail to declare competing interests than to have the field think that company practices that restrict access to data while still claiming the moral high ground of science are the real source of the problem.
I'd love to know what American Psychiatric Association members think about this. The news had already broken about Schatzberg overstating the efficacy of Corlux before he was elected APA president. Do APA members not care that their president has a documented record of putting product promotion before scientific evidence?

Friday, June 13, 2008

More Than Filling My Shoes

I'll be on hiatus for a while. Too many things to do in too little time. Fortunately, material that is right in the sweet spot for readers of this site can be found at:
  • Carlat Psychiatry Blog. His takedown of Medscape is much needed, as is further digging into ye olde coverup of industry cash by child psychiatry key opinion leaders.
  • PsychCentral. Who cares about St. John's Wort for ADHD? JAMA seriously published a small trial of SJW versus placebo. I thought JAMA was for higher importance issues -- and so did John Grohol at Psych Central.
  • Furious Seasons. Overdiagnosis of ADHD? Not a new complaint, but interesting perspective is provided by a Canadian psychologist who thinks the ADHD label is being passed about unnecessarily in Canada.
I hope to return soon.

Monday, June 09, 2008

Say It Ain't So Joe

It appears that Joe Biederman, King of Child Bipolar, has been caught with his hands in the cookie jar. More specifically, the New York Times and Bloomberg have noted that Biederman has received a great deal of pharma cash (like at least $1.6 million dollars from 2000-2007) and has not been very forthcoming about such funds. How was such undercover money revealed? Courtesy of Charles Grassley, the Iowa Republican Senator whose prior investigation unearthed a similar situation impacting another Bipolar Child Key Opinion Leader, Melissa DelBello from the University of Cincinnati.

Here's one example, from Gardiner Harris and Benedict Carey at the New York Times:
In one example, Dr. Biederman reported no income from Johnson & Johnson for 2001 in a disclosure report filed with the university. When asked to check again, he said he received $3,500. But Johnson & Johnson told Mr. Grassley that it paid him $58,169 in 2001, Mr. Grassley found.
So Biederman is supposed to report outside income to the university, but he didn't. Then, his amended reports were in some instances a wild underestimate of his outside income. So how well is the "honor system" working out for conflicts of interest, anyway? To be fair, Biederman is not alone -- two other Harvard psychiatrists (Timothy Wilens and Thomas Spencer) had similar reporting problems. Indeed, there is nothing to say that Biederman's conflicts of interest are any more noteworthy than those of other "stars" in the academic psychiatry universe.

Worry not, Biederman is still interested in saving lives. He is recruiting 4 to 6 year olds with "bipolar disorder" for a Seroquel trial.

For some reason, I thought Biederman's prior comments were worth repeating here. From the Boston Globe:
Biederman dismisses most critics, saying that they cannot match his scientific credentials as co author of 30 scientific papers a year and director of a major research program at the psychiatry department that is top-ranked in the "US News & World Report" ratings.

"The critics 'are not on the same level. We are not debating as to whether [a critic] likes brownies and I like hot dogs. In medicine and science, not all opinions are created equal,' said Biederman, a native of Czechoslovakia who came to Mass. General in 1979 after medical training in Argentina and Israel. He now lives in Brookline.

You tell 'em, Joe! I suppose those who dare critique his conflicts of interest are "not on the same level" as him. Some say that we shouldn't be concerned about conflicts of interest, that we should just look at the quality of a person's work, regardless of financial conflicts. Well, Biederman is the undisputed King of Bipolar in kids, and I'm still awaiting any impressive outcome dataon the "bipolar" kids being treated with antipsychotics. Especially the young kids. 4 year olds on Seroquel -- I'm glad I'm not on Joe's level. Are we better off now that the diagnosis of bipolar has run rampant in kids?

Also see and Furious Seasons and Pharmalot.

Update: Also read the Carlat Psychiatry Blog post on the topic.

Wednesday, June 04, 2008

Antipsychotics: Global Buckets of Money

Antipsychotics were the sixth best selling class of medications globally in 2007, according to IMS Health. They raked in a cool $20.7 billion, an increase of 10.7% from 2006. Thank God we are doing a better job of overrecognizing, er, appropriately treating bipolar disorder. Antidepressants were #7, at $19.7 billion, down nearly seven percent. This does not appear to be due to declining prescriptions. Blame generics, not decreased prescriptions for the lower numbers. With Cymbalta, Lilly has shown that new antidepressants don't have to be anything special, so it would behoove other companies to release other run of the mill antidepressants, attach a comical, er, highly educational marketing campaign such as Depression Hurts, then watch the money roll in. Just some free advice.

How about the top 10 drugs? Three of them were antipsychotics. No, I'm not kidding. Most surprisingly, Zyprexa had the best figures worldwide, which was interesting given the flat U.S. sales in 2007. Seroquel outsold Zyprexa in the U.S., but Zyprexa had a better run globally. Who knows what tricks are being used to sell Zyprexa internationally? Never mind, it's not like Lilly would do anything sly to market Zyprexa.

The new era of antipsychotics for everything appears to be in full swing.