Key Opinion Leader With A Very Short Fuse

Psychiatrist Joe "Short Fuse" Biederman of Harvard University is really in hot water now. The sordid details can be seen in a fantastic article by Gardiner Harris of the New York Times. Here's just one snippet:

In a November 1999 e-mail message, John Bruins, a Johnson & Johnson marketing executive, begs his supervisors to approve a $3,000 check to Dr. Biederman as payment for a lecture he gave at the University of Connecticut. “Dr. Biederman is not someone to jerk around,” Mr. Bruins wrote. “He is a very proud national figure in child psych and has a very short fuse.” Mr. Bruins wrote that Dr. Biederman was furious after Johnson & Johnson rejected a request that Dr. Biederman had made for a $280,000 research grant. “I have never seen someone so angry,” Mr. Bruins wrote. “Since that time, our business became non-existant (sic) within his area of control.”

Mr. Bruins concluded that unless Dr. Biederman received a check soon, “I am truly afraid of the consequences.”

A series of documents described the goals behind establishing the Johnson & Johnson Center for the study of pediatric psychopathology, where Dr. Biederman serves as chief. A 2002 annual report for the center said its research must satisfy three criteria: improve psychiatric care for children, have high standards and “move forward the commercial goals of J.& J.,” court documents said.

And from Bloomberg,

Biederman “approached Janssen multiple times to propose the creation of a Janssen-MGH center,” according to an e-mail from a J&J executive. The center would “generate and disseminate data supporting the use” of Risperdal in children, the e-mail said. Pediatric use was approved by U.S. regulators in August 2007.

Wow. And the plot sickens, er, thickens from there. Normally, being caught with one's hands this deep into the cookie jar would lead me to write a much more blistering piece, but the day job shows no signs of abating in its workload. Fortunately, Philip Dawdy is rolling with the story at Furious Seasons (1, 2).

Let's see if Biederman's defenders can defend him in another op-ed as they did a few months ago. Or maybe we can leave Joe to defend himself. Here's what he said a few months ago when facing criticism:

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.

Nope, most of his critics cannot match his credentials of apparently shaking down hundreds of thousands of dollars from Johnson & Johnson. But maybe I just like brownies and he likes hot dogs. Another key opinion leader whose reputation is deservedly shot to shreds. Nemeroff, Biederman, and the list goes on.

Investigative Journalism Par Excellence

I am a little late in reporting this story, but there is a must-read post from Jonathan Leo over at Chemical Imbalance that I must bring to your attention. Many bloggers have chimed in about the radio program The Infinite Mind broadcast about SSRIs. Most writers have focused, understandably, on the myriad unreported conflicts of interest of the guests on the show. But the conflicts of interest are not the most important part of this saga -- the terribly misleading information on the program, which aired on National Public Radio outlets, is the main problem.

Leo compares the data on SSRIs and suicide to the blatantly false statements made by the The Infinite Mind commentators. He notes, for example, that it is utter BS to state that nobody committed suicide in antidepressant trials submitted to the FDA -- in children there were no suicides, but among adults there certainly were. And kids who dropped out of the studies due to poor response or side effects, well, who knows what happened to them?

Leo also notes that the commentators were dead wrong about their alleged evidence linking decreased prescriptions of SSRIs to an increase in suicides. I also noted the same problem. He then proceeds to make point after point about the commentators overstating the efficacy of antidepressants.

As I've written before, conflicts of interest are important. But rather than just noting that people have conflicts, it is important to show the data -- are people with conflicts of interest misstating the evidence in a manner that reflects the conflict of interest? In the case of The Infinite Mind, the answer is a clear yes. Leo's post is quite lengthy, but well worth the time.

Update (08-31-08): My mistake. I had earlier called the program All in The Mind, which is vastly incorrect. The program was The Infinite Mind (as has been corrected above). This post has absolutely nothing to do with All in The Mind, which is a program which airs on Australia's Radio National. In fact, I've listened to a couple of All in the Mind broadcasts previously and found them to be well-done. Thanks to a commenter for catching my error.

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.  

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?

Key Opinion Leaders, Osteoporosis, Vioxx, Psychiatry, Science, and Patients

Remember Richard Eastell? To summarize briefly, he is a professor at Sheffield University who was lead author on a publication that showed positive results for the osteoporosis drug Actonel. One problem: the data did not actually provide good news for Actonel. In a key graph in the published paper, 40% of patient data was missing. Now that's an interesting form of science: Just eliminate the pesky 40% of the data that don't go along with your hypothesis and POOF!, you get exactly the results you are looking for. An excellent writeup of the situation can be seen in Jennifer Washburn's excellent piece in Slate. Making the plot more interesting, Eastell did not have the raw data; Procter & Gamble's (Actonel's sponsor) statisticians were in charge of the analysis. Hence the missing 40% of the data, which helped to cast Actonel in a more positive light. Read more on the topic here. When all data are included, the analysis does not support Actonel's marketing points. Eastell signed off on the original (misleading) paper saying that he had seen all of the data, which was, of course not true.

I noted in October 2006 that Eastell was chairing a session on osteoporosis, one that charged a hefty registration fee. The website promoting the session at the time mentioned: "This course is suitable for pharmaceutical industry personnel from clinical through to marketing disciplines." I suppose that Eastell is a key opinion leader in his field. Being willing to put one's name on a paper where the key graph knocks out 40% of the data is a good step toward becoming an influential academic these days. I suppose Eastell could at least claim ignorance, since he was unfamiliar with the underlying data.

In psychiatry, Charles Nemeroff, a key opinion leader, put his name on a continuing medical education presentation in which the data don't match with the published article that was based on the same data set. In the CME presentation, the medication (risperidone) outperformed placebo, although the published report indicated that risperidone did not beat a placebo, and in the CME presentation, risperidone was claimed to improve sexual functioning, which was never mentioned in the published article.

Eastell and a colleague recently received a roughly $7.5 million grant. Good for them. I've got nothing against the guy personally; I just find it interesting that he is getting rewarded nicely despite the whole Actonel fiasco. And I've only described a wee bit of that strange saga. The Scientific Misconduct Blog has much, much more. Like the part where he told Blumsohn to stop bothering Procter & Gamble about the data because P & G was a good source of income for the university. I've got no problem with excellence being rewarded. Perhaps Eastell has done many excellent things. However, during the P &G/Actonel fiasco, Eastell was willing to let the sponsors push him around, even if science was being bastardized in the process. Their money meant more than good science. And if patients took Actonel thinking that it was more effective than it actually was, who cares -- they're not the ones providing the research funding, right?

Think about this for a second. Many people have been up in arms about the recently unveiled Vioxx ghostwriting scandal. For a fantastic take on the scandal, see Health Care Renewal or Hooked. Briefly, Merck and its associated medical writers wrote manuscripts that said nice things about Vioxx. Then academic authors/key opinion leaders were found to review the papers and stick their names on as lead authors. Mind you, "reviewing" the papers often meant simply meant making minimal edits, if even putting in that much effort. Did they see the data? They saw tables and figures provided by Merck, but did they see the raw data? In most cases, apparently not. Doesn't that make them information launderers? They take industry data, and clean it up with their academic reputation. Oh, Dr. So-and-So is at Sheffield or Emory or Harvard... -- he must have made sure that the sponsoring drug company is portraying the data accurately. A veneer of credibility. And an extra publication for the key opinion leader, which makes the KOL that much more important in the academic world where publication envy runs rampant.

This system is not exactly set up to benefit patient outcomes, is it?

Key Opinion Leader Is Unfairly Disparaged

Or so she said. I've written about key opinion leader, University of Cincinnati child psychiatrist Melissa DelBello a few times (here, here, and here). One key point was she was quoted as saying "Trust me. I don't make much" in regards to income received from AstraZeneca for giving favorable talks for its antipsychotic drug Seroquel. I had missed that in 2007, she claimed she was misquoted in an interesting piece on Inside Higher Ed:

[University of Cincinnati spokesperspon] Puff said that DelBello’s comment in May that she did not “make much” money from drug companies had actually come in response to the reporter’s question “about how much money she was given for making a single, individual presentation. Her comment was misrepresented and then repeated by Sen. Grassley.” Added DelBello: “I was and have been misquoted by the NYT.” (The Times reporter, Gardiner Harris, could not be reached Sunday to respond to the suggestion that he had misrepresented DelBello’s comment.)

Puff also said that “the implication of what Sen. Grassley said was that she was disingenuous in what she was paid. She has been completely open in disclosing her payments. She’s made complete disclosures to the university and its IRB. Furthermore, she’s made full disclosure to the Senate Finance Committee.... Additionally, Dr. DelBello has disclosed her funding at all speaking engagements and she’s disclosed in the patient consents of her studies.”

I wonder if she has made disclosures about her company (MSZ Associates) that Senator's Grassley's investigation claims was set up for "personal financial reasons"and well-funded by AstraZeneca. Also, does the above mean that DelBello disclosed that she has personally received hundreds of thousands of dollars from AstraZeneca and other sources in the consent forms for her studies? I have to admit I'm pretty skeptical about that, but I could be wrong. As far as full disclosure to the Senate, Grassley's most recent findings seem to contradict this claim. Hey, maybe Grassley is just making things up, so either DelBello is being unfairly persecuted or her story is simply not adding up.

Why am I making such a big deal about this? Well, such a gigantic hidden conflict of interest doesn't exactly engender my faith, and DelBello is a person who can take at least responsibility for the widespread treatment of children with antipsychotic medications. Due to her research findings that some claim support the use of antipsychotics in kids and her many marketing speeches for AstraZeneca and others, the landscape for badly behaving children is changing, and likely not for the better (1, 2, 3).

Pharmalot reports that the University of Cincinnati is unresponsive to his requests for comment. Perhaps they're going for the time-honored tradition of remaining in silence under the belief that this publicity cannot possibly last much longer.

Zyprexa and Key Opinion Leaders

Since the Zyprexa trial is ongoing in Alaska, I thought I should return to the wonderful world of Zyprexa. I encourage readers to follow the Zyprexa coverage at Furious Seasons, Pharmalot, and PharmaGossip. Today, I will discuss the link between key opinion leaders and the marketing of Zyprexa. To preface, a coveted Golden Goblet Nomination could be handed out to several individuals based on their involvement in Zyprexa marketing...

In March 2000, Zyprexa received FDA approval for treatment of manic episodes. One document laid out the multipronged marketing maneuvers that Lilly utilized to move Zyprexa shortly after its approval. Some of the details of this document have been well-covered in a terrific piece of investigative journalism at Furious Seasons. This post will provide some coverage of the link between Zyprexa and the key opinion leaders who helped popularize the drug across the nation.

Once approved for bipolar disorder, Lilly utilized several tactics to market Zyprexa for bipolar disorder, including a satellite conference beamed to about 6000 physicians, and 8000 treatment team members in 1000 facilities. The faculty providing this educational service included many of the big names in academic psychiatry, including Paul Keck, Jan Fawcett, Hagop Akiskal, and Alan Schatzberg.

Alan Schatzberg, you say? Yes, the same Alan Schatzberg who is set to become president of the American Psychiatric Association. Some have been less than pleased with his election as APA president, considering his background as a physician-marketer, a key opinion leader with large conflicts of interest. The same Alan Schatzberg who has been involved in marketing passing itself off as continuing medical education.

Lilly also bankrolled dinner meetings, anticipated to draw 150-400 physicians per sitting. Dr. Schatzberg was also listed as a speaker for such dinners. One mental health service provider was impressed enough with receiving such excellent medical education that you can find it on his CV.

In the document outlining Zypexa's big marketing launch, Paul Keck's name appears in the following contexts:

• Satellite symposium provider
• Trainer of "local speakers." I believe this means he would train local physicians in various markets to then discuss Zyprexa with their colleagues.
• Faculty for bipolar weekend symposia
• Faculty for audio conferences
  
• Faculty for a satellite CME workshop
• Faculty for "dissemination of Bipolar information to 30,000 customers"
• Faculty on a "closed symposium" resulting in a CME newsletter and a CME audiotape, both of which were mailed to 30,000 individuals
• Author of two journal supplement articles

Paul Keck was also a member of a task force chartered by the American Psychiatric Association that served to revise the organization's guidelines to provide a more favorable view of atypical antipsychotics (including Zyprexa) in the treatment of bipolar disorder. No conflict of interest there, eh?

Keck said in a 2002 interview that:

"Often," Keck said, "patients with bipolar disorder require complex treatment regimens to manage all phases of their illness, creating a compliance challenge for patients and a management challenge for clinicians. These studies suggest that physicians may be able to use olanzapine as a foundation to simplify patients’ treatment regimens, and the combination of olanzapine and fluoxetine could be an effective treatment choice

It is likely that Keck was not performing all of his "educational" functions for Lilly in exchange for lollipops. He was likely receiving a healthy dose of cold, hard cash. Yet in the article, nothing is written about his financial links to Lilly. Keck has also appeared in press releases saying nice things about Symbyax (fluoxetine/olanzapine combination).

To be fair, Keck has also stumped for Pfizer's Geodon in press releases. Oh, and he also said nice things about Abilify in a press release. I suppose that if one is going to be a true key opinion leader, a real mover and shaker, one should be prepared to say nice things about whatever new drug is released, since each new drug naturally represents an "important" treatment option. Keck, like Alan Schatzberg and Charles Nemeroff, is also currently listed as a member of the clinical advisory board for Neuroscience CME, a for-profit entity awash in drug industry money. Dr. Daniel Carlat has previously written that the "educational" content produced by this organization is biased, and I find that easy to believe. It's not hard to find examples of poorly done industry-funded CME. In fact, you might be interested in reading about a CME activity in which Nemeroff seems to have pulled data out of thin air.

In sum, the usual fun and games were in play when Zyprexa was initially being pushed for bipolar disorder. Some of the biggest names in psychiatry left their fingerprints all over the marketing of Zyprexa and one of these key opinion leaders recently won the presidential election for the American Psychiatric Association. I suppose, then, that American psychiatrists are generally either unaware of conflicts of interest or don't care about them.

The beautiful thing about being a key opinion leader is that one's name recognition is huge. Among psychiatrists, I bet that Schatzberg's name is better known than that of Bill Clinton, since Schatzberg's byline appears on journal supplements and CME so frequently. That can't hurt when running for president of the national professional organization. I will be very interested to see how Schatzberg handles questions about conflicts of interest and drug industry influence on his profession. Don't be expecting any major efforts at reform in the near future.

Zetia, Paxil, Medical Journals, Fraud, Etc,

I've been busy wiping up tears after the Frontline episode on medicating children with a wide variety of psychiatric medicines. Well worth watching. There are many thoughtful comments over at Furious Seasons. Feel free to add your voice. I may post on some of the highlights and lowlights of the Frontline piece later. Suffice for now to say that it sure is depressing that the media keeps up the dunce journalism of linking decreased SSRI prescriptions to an increase in suicide as if this was some sort of reliable finding. Please read my earlier posts (1, 2) for details on this constantly repeated yet incorrect interpretation of events.

Here are a few other posts worth reading:

• Is "symptom remission" a realistic or even desirable goal when treating depression? A very interesting battle of letters in the American Journal of Psychiatry receives excellent coverage at Furious Seasons.
  
• Roy Poses at Health Care Renewal demolishes an op-ed piece by Robert Goldberg (from the infamous Drug Wonks site). Also check out an incredible tale of kickbacks to a physician from multiple companies. If your hunger for bizarre tales in healthcare is not yet satiated, read about CellCyte, a company whose main product is apparently fraud.
• Are medical journals asleep at the wheel regarding problems with Zetia? Aubrey Blumsohn seems to think so, and I think he might have a point. It would not be the first time that a medical journal dropped the ball.
  
• Paxil for life. Go ahead, try to quit. What, you can't quit? A large group of individuals suing GlaxoSmithKline believe they've had difficulties quitting Paxil without significant problems. Worry not, friends, GSK said: "We believe there is no merit in this litigation... Seroxat has benefited millions of people worldwide who have suffered from depression.'' Read more about Paxil/Seroxat's special benefits. H/T: PharmaGossip.
  
• While you can catch up on the national presidential derby from many sources, there is little coverage of the race for American Psychiatric Association president. Daniel Carlat (who is popping up everywhere these days, which is a good thing) provides his take on the upcoming APA election. To nobody's surprise, some have noted an issue with one candidate's potential conflicts of interest.
  
• Pfizer = McDonald's + Estee Lauder?
  

Uh-Oh Chuck, What About the Disclosure? OR Go Team MAOI!

Introduction: As longtime readers can surmise from the headline, this post is about Dr. Charles Nemeroff. And the Dalai Lama. Let's start from the beginning. Nemeroff was featured in a CME activity on Medscape. To view it, you'll need to complete a free registration at Medscape. For those new to the wonderful world of CME, note that while CME stands for continuing medical education, it is more accurate to refer to it as commercial medical education -- it's paid advertising, dare I say cheerleading. It is rather disheartening that physicians who wish to keep their licenses must sit through a bunch of advertisements as opposed to less biased, more educational forms of training. For more on CME in general, read my earlier posts here and here, or check out Daniel Carlat's excellent work (1, 2, 3, 4, 5 ).

The Present Story: Nemeroff, in the aforementioned CME activity, discusses the transdermal patch for selegiline, a monoamine oxidase inhibitor (MAOI) and how it may serve as a good treatment option for people with depression. Here are a couple of quotes from Nemeroff:

The limited use of oral monoamine oxidase inhibitors (MAOIs) over the past decade or so has been driven largely by physicians' concerns that they might potentiate hypertensive reactions when they interact with tyramine in foods. A new transdermal system is currently available that enables the MAOI to avoid first-pass metabolism by bypassing the gut, thereby reducing the chance of hypertensive reactions caused by tyramine.

The Pande study, which I believe was done when Pande was at Lilly, compared 20 patients with atypical depression treated with fluoxetine and 20 treated with the nonselective irreversible MAOI, phenelzine. Efficacy was about equal. Certainly other data and my own experience would suggest that MAOIs are superior to SSRIs and TCAs [for atypical depression].

A case that is treated successfully (of course) with transdermal selegiline is discussed during the activity in some depth. All's well that ends well. Clearly, the CME activity backs the use of transdermal selegiline. While it discusses some of the risks associated with MAOI treatment, the program states that the transdermal system avoids many of these issues.

Chuck's Conflicts: Nemeroff lists the following disclosures in the CME activity:

Reunette W. Harris Professor and Chairman, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

Disclosure: Grants: AstraZeneca Pharmaceuticals, LP, Bristol-Myers Squibb Company, Forest Laboratories, Janssen Pharmaceutica, National Institute for Mental Health, Pfizer Inc, Wyeth-Ayerst Laboratories, Consultant: Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb Company, Concept Pharmaceuticals, Ltd, Cypress Bioscience, Inc, Cyberonics, Inc, Eli Lilly and Company, Entrepreneur Fund Inc, Forest Laboratories, GlaxoSmithKline, H. Lundbeck A/S, Ingenix i3 DLN, Janssen Pharmaceutica, Otsuka America Pharmaceutical, Inc, Pfizer Inc, Quintiles Transnational Corporation, UCB Pharma, Wyeth-Ayerst Laboratories; Speaker: Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc.; Stockholder—Acadia Pharmaceuticals; Corcept Therapeutics, Inc; Cypress Biosciences; NovaDel Pharma Inc.; Board of Directors: American Psychiatric Institute for Research and Education, NovaDel Pharma Inc, National Foundation for Mental Health

As you can gather, Nemeroff is a busy guy! According to the above, he is a consultant for 18 drug companies and a speaker for four companies. The plot is about to thicken (or, perhaps, sicken) notably...

The Missing Disclosure: Remember how the above CME was all about pushing a newer, safer MAOI drug for depression? Well, it just so happens that Nemeroff is the co-chair of the Scientific Advisory Board for CeNeRx, a company that is developing a (you guessed it) newer, safer MAOI drug for depression! Note that Nemeroff did not mention his position with CeNeRx in his disclosure for the Medscape CME activity. Here's what the CEO of CeNeRx had to say about the MAOI they are testing:

In contrast to other MAO inhibitors, our third generation RIMA series is designed to bind selectively and reversibly, with the goal of significantly reducing the cardiovascular risks and other side effects typically associated with the MAOI class. These safety results, along with the high plasma levels and favorable pharmacokinetics demonstrated in the study, support advancing Tyrima into a multiple dose safety study in late spring.

Note the similarity to what was being said about the MAOI patch in the Medscape CME. Let me put this plainly: Nemeroff stumps for an MAOI in a CME activity, yet does not disclose that he is being paid by a company which also manufactures an MAOI. Can you say "hiding a blatant conflict of interest?"

The Dalai Lama: Nemeroff is appearing with His Holiness the Dalai Lama for a presentation on depression at Emory University. Thankfully, Nemeroff is not scheduled to speak about MAOI's. He is actually scheduled to speak about the relationship between early life experience and depression, about which the research is quite interesting and important. However, given the history of Nemeroff's scientifically questionable behavior (read a summary here, which has links to more detailed stories), it strikes me as strange that he'll be presenting alongside the Dalai Lama.

Golden Goblet: Does this earn Nemeroff a nomination for a Golden Goblet ? I believe so.

Selling an Organization

Bob Fiddaman has an interesting post about the Obesity Society and its ties to GlaxoSmithKline, maker of the weight loss pill Alli. Yes, the Alli of I Pooped My Pants fame.

Bob noted that, in the new video promoting Alli, it is mentioned that a portion of sales of a new book that discusses weight loss will be donated to the Obesity Society. Bob connects the dots by noting that the Obesity Society needed funding, GSK provides some funding for the Obesity Society, and that GSK was about to launch a diet pill (Alli).

I also noticed that, on the Obesity Society's website, it is stated that

On February 7th, the Food and Drug Administration approved Alli, an over-the-counter version of orlistat (trade name Xenical). Alli, manufactured by GlaxoSmithKline, will be available in June. It is a 60mg version of Xenical, which has been available as a prescription product for several years. Xenical, at 120mg, will continue to be available to patients needing a higher dose and who are under a physician's care. Prescription Xenical is made by Roche. Obesity Society President Eric Ravussin was quoted on the front page of USA Today indicating that the product was safe and effective. GlaxoSmithKline's educational efforts include a paperback book on weight loss; part of the proceeds of the book's sale will go to The Obesity Society. The society has received other support from GlaxoSmithKline.

Part of GSK’s “educational” efforts as well as part of GSK’s marketing, but the Obesity Soceity wouldn’t want to draw attention to that. You can also see what’s happening with corporate sponsorship of their meeting. Here’s a snippet…

Become a Benefactor of the Obesity Society's 2007 Annual Scientific Meeting and heighten awareness of your company and product(s) among the experts and thought leaders in the obesity field. Benefactor Sponsorship provides the most economical way to reach all of the 2,000+ Annual Meeting attendees frequently before, during, and after the meeting:

Benefits:

• Sponsorship of 3 general sessions:
• One Symposium
• One Workshop/Tutorial/Debate
• One Key Lecture
• Sponsor recognition in registration area
• Sponsor logo on Learning Center Website (your choice of ONE the four Annual Meeting Tracks) OR sponsor logo on attendee registration bags
• Sponsor recognition on meeting website
• Sponsor recognition in several issues of The Obesity Society’s electronic newsletter
• Sponsor recognition in all on-site publications
• Final Program
• Abstract Supplement
• Complimentary insert into attendee registration bag
• Complimentary use of one mailing list of:
• Pre-registered attendees ( 4 - 6 weeks prior to meeting)
• Final meeting attendee list (approx 2,300 names)

Sponsorship Fee: $50,000

It’s nice that researchers pay membership dues to join the Obesity Society, then their organization sells the names of members to corporate sponsors so that members can then receive solicitations.

I understand that the Obesity Society needs money and that obesity researchers likewise require funding for their research. I wonder, however, if this is the proper manner in which to raise funds.

This works great for the sponsors. Their products (such as Alli) are featured prominently in advertising that is received by Obesity Society members. They get to recruit “thought leaders” from the Obesity Society ranks, who will then go forth and speak on behalf of their products. The Obesity Society is by no means unique. The American Psychiatric Association, for example, has long been noted for its strong ties with corporate sponsors. Yet these organizations call themselves independent.

As a side note, how well does Alli work? According to one abstract of a trial comparing low-dose orlistat (Alli) to placebo over 16 weeks, Alli patients lost 3.05 kilograms compared to 1.90 kgs lost by those taking placebo. Pretty small difference, yet the president of the Obesity Society (quoted above) seemed impressed. I wonder why?

4.83 Million Reasons to Be Conflicted

Corcept Therapeutics just got an infusion of cash. From the press release:

Corcept Therapeutics Incorporated (NASDAQ: CORT) today announced the completion of a private placement of 9,000,000 shares of its common stock at a price of $1.00 per share, pursuant to a definitive agreement entered into today with accredited investors. The investors are led by Paperboy Ventures LLC, who is currently a significant shareholder of Corcept. Sutter Hill Ventures, Alta Partners, LLP, venture capital firms that are currently significant shareholders in Corcept, and members of the Corcept Board of Directors, Joseph C. Cook, Jr., James A. Harper, David L. Mahoney, Alan F Schatzberg, M.D. and James N. Wilson, are also investors. In addition, investors in this financing round included Black Point Group, LLP, Vaughn Bryson and Daniel Bradbury.

Already a good short-term investment, as the stock is now at $1.21 a share. If you've read my prior writings about Corcept, you can see that I'm highly skeptical about it's main product, Corlux (mifepristone/RU-486), which is aiming to treat psychotic depression. Although the company has tried to spin negative findings as actually being positive, it's hard to see how a series of studies showing poor efficacy will lead to helping patients in any meaningful fashion. Might the latest influx of cash help out the Corcept insiders who hold a major stake in the company? Sure.

Conflicts of Interest: It appears that Dr. Alan Schatzberg bought 50,000 shares in the latest round of funding. It has been reported previously that Schatzberg has written quite positive comments about Corlux in journals and some have questioned whether his financial stake in the company has skewed his judgment on the topic. I want everyone to consider the following conundrum...

Schatzberg holds about 4.83 million shares of Corcept currently. So, if Corlux bombs a clinical trial, is he going to:
A. Immediately report the negative results in a press release
B. Move publishing the negative results in a scientific journal to the top of his to-do list
C. Spin the results in a very favorable fashion (or make sure that someone who writes the press release and/or scientific paper does so)
D. Just bury it entirely (probably not an option with such a small company that likely announces most if not all of its trials beforehand)

If I was in a position where I had such a large financial stake, I'd have a hell of a time doing A. or B. When large dollar amounts are at stake, it's not easy to say, "Hey, this product doesn't seem to work" and watch your stock holdings evaporate. This is why conflicts of interest are a problem.

Some academic researchers really are just in it for the money. I think they are a very small minority. I bet that most researchers who end up with big-time conflicts of interest start off thinking, "Hey, this could be a great new form of treatment for condition X." Then, hey, why not make some money while you're doing God's work, helping to heal people. We're an entrepreneurial society, so we tend to believe that people should be rewarded for having an enterprising spirit. Now, if the product turns out to not be so effective and/or to have some unpleasant side effects, then look at the predicament... Here's the conflict -- help people with condition X or help my own cash flow?

Or say I'm a doctor who makes some good money on the side giving "educational" speeches to fellow physicians about a drug, say, Zyprexa. When I find out that said drug is linked to numerous health problems, do I bring that up in my speeches, knowing fully that such discussion is likely going to get me canned from the speaking circuit?

The list of potential examples could go on for days.

Pepsi: Good for What Ails You

Roy Poses, as usual, has a great take on a story that you just could not have made up, even if you tried your hardest.

Deborah Powell, the Dean of the University of Minnesota Medical School, has taken a board of directors position for PepsiAmericas, which is interesting considering that Pepsi consumption promotes both tooth rot and obesity. Don't get me wrong, there is such a thing as responsible Pepsi consumption, but should a Med School Dean be in the position of helping to maximize Pepsi sales? Perhaps she can also be on the Board of Philip Morris or Coors?

Read the whole story, then roll your eyes and/or bang your head, as you deem appropriate.

For-Profit Research Update

I recently wrote about a psychiatrist, Dr. Andrew Cutler, who made misleading statements regarding the BOLDER I study. I ran across a little clip that mentioned more about his research venture:

Still, some junior faculty members are now abandoning academia to get into the drug-study business. Dr. Andrew Cutler, a psychiatrist, left the faculty at the University of Chicago to join the Psychiatric Institute of Florida in Orlando, a private practice with a research business. Then last year, he formed his own company, Coordinated Research of Florida, to perform drug studies full time.

Without a patient base to draw from for studies, Cutler found other ways to recruit subjects, including serving as a nursing home consultant.

"I will strategically pick a nursing home that has a large population that meets the criteria for a study," he said. "If there is a large community practice in town, I may work out a referral arrangement, or make them a co-investigator, and the arrangement is that they would be providing the patients."

Interesting. If I understand this right (and I'm not sure that I do), then he goes to local nursing homes, chums with the people in charge, then gets them to help recruit their residents as participants in drug studies from which both he and the nursing home administrators who get listed as "investigators" stand to make some cash. This is not necessarily bad, but it shows that the reach of clinical research teams, funded solely by industry, is fairly wide. Making money from enrolling your own residents in a research trial must certainly raise some conflicts of interest for nursing home administrators and physicians.