Uh Oh! Thomas Insel gets pulled into Nemeroff's World

One truism of professional life is that some favors, no matter how alluring, should be politely turned down. The trick is predicting which bestowers of favors spell D-A-N-G-E-R, and which do not. Unfortunately, it looks like Dr. Tom Insel, the director of the National Institute of Mental Health, made the mistake of accepting multiple favors from Charles Nemeroff, and he is now paying the price.

Several media outlets have covered this developing saga, or scandal, or Greek tragedy (following the analogy of the Trojan horse, the most famous examples of bad judgment in gift-accepting). The best and most thorough coverage is in this article in The Chronicle of Higher Education, which broke the story. Also, see today's coverage in the Washington Post, and ongoing coverage in Health Care Renewal.

Here's the digest of key events. Charles Nemeroff is a psychiatrist and researcher who makes friends easily, gives great talks, and exudes charisma and power. He's probably a genius and has an encyclopedic knowledge of neuroscience. Unfortunately, he has shown repeatedly that he is willing to bend institutional rules and play loose with the truth in order to accomplish his various financial and professional objectives. His self-imposed trials and tribulations are well known to readers of this blog.

The Low Points:

--2002: Nemeroff co-authored a review article saying wonderful things about an investigational antidepressant, mifepristone, without disclosing that he had a significant financial stake in the product. Nemeroff said that he would have disclosed the conflict of interest if the journal had only asked him to: "If there is a fault here, it is with the journal's policy." (see this coverage in the New York Times).

--2006: Nemeroff co-authored a positive review article about vagus nerve stimulation. The Wall Street Journal soon reported that Nemeroff neglected to disclose his significant financial relationships with Cyberonics (the maker of VNS), and that the article itself was possibly ghost-written by a medical writer hired by Cyberonics. This time, Nemeroff could not convincingly blame the journal, because he was the journal's editor-in-chief! He was soon forced to quit the post. (See my article covering the debacle here).

--2007: Nemeroff co-authored an industry-funded CME supplement to the journal CNS Spectrums which his "co-author" Linsey Devane called "ridiculous" and "inaccurate," and he claimed that Nemeroff had encouraged him to be involved "for the sake of selling CME time." (See my coverage here). Eventually, the ACCME determined that the article violated its Standards for Commercial Support because it was biased in favor of the Bristol-Myers Squibb's drug EMSAM.

--2008: Both the New York Times and the Wall Street Journal simultaneously broke the story that Nemeroff had consistently failed to disclose payments from GlaxoSmithKline for promotional talks, even while he was in charge of an NIH grant studying the company's drugs. This led to Nemeroff's resigning his chairmanship of the Emory University Department of Psychiatry.

Given Nemeroff's track record, I am surprised that Tom Insel agreed to endorse his standing with the NIH to Dr. Goldschmidt, the dean of University of Miami's medical school. The proper thing would have been for Insel to politely decline to discuss Nemeroff at all. In today's Washington Post, Insel is backtracking, saying that "I didn't recommend him" for the Florida job. But Goldschmidt's recollection of the phone conversation was that Dr. Insel "confirmed to me that Charlie was absolutely in fine standing" with the NIH, according to the Chronicle for Higher Education.

What a mess for Insel, for the University of Miami, for the NIH, and once again, for Charles Nemeroff. Now Senator Grassley is involved and is requesting all relevant information concerning the relationship between Insel and Nemeroff. Presumably, Insel's lapse of judgment in this matter was a result of his long-time friend "Charley" calling in favors--but exactly what those favors are will be determined once the documents are released.

File this under: "To be continued...."

Team Grassley, a Lawyer's Eye View

You might love him or you might hate him (I'm obviously one of his fans), but either way Senator Charles Grassley and his passionate staff have shaken up the world of medicine and have made "conflict of interest" a household term.

Recently, I read this article published on the website LawyersandSettlements.com that provides a succinct rundown of Team Grassley's accomplishments. Lawyers, of course, are particularly big Grassley fans because each one of his investigations creates instant jobs for dozens of attorneys on various sides of the issue. Thus, you can count on them to be particularly vigilant and accurate monitors of the COI body count as it rises. For the confused, the overwhelmed, or the plain curious, this article makes for a nice fact sheet.

Med Page Today Interviews Dr. Paul Appelbaum and Me on Industry Relationships

Yesterday, John Gever of Med Page Today interviewed me and Dr. Paul Appelbaum on various topics about the relationship between the pharmaceutical industry and psychiatry, which I have posted above for your viewing pleasure. Dr. Appelbaum is a former president of the APA and is the chairman of the "Ad Hoc Work Group on Relationships Between Psychiatrists and Medical Industries." He and the members of this group have drafted a report with recommendations for how we can clean up our act. While the report has not yet been formally approved by the Board of Trustees and is therefore not public, I can tell you that it contains many of the same elements as the recent Institute of Medicine report, which I described here. Appelbaum's report was discussed in the APA Assembly on Sunday and the review was frankly somewhat mixed. What will happen next is that the Board of Trustees will continue to elicit feedback from the APA membership and will eventually vote on whether to adopt some version of the current report. My prediction is that the current version will be adopted with very few changes, but that's only a prediction (I'm not a member of the Board, just the Assembly).

There have been a number of excellent symposia over the last few days on how to set the right distance between doctors and commercial interests and I'm coming away from this meeting with high optimism that we are really turning a corner in our profession.

Disclosure Wars: The Case of Goozner vs. Pies

Transparency has become all the rage in medical publishing these days, which is a good thing. A recent battle between the Integrity in Science Project website and the journal Psychiatric Times is a great illustration of some of the more complicated issues involved.

What makes this case especially interesting is that there is no “good versus evil” dynamic here. One on side of the ring is Merrill Goozner, a former business journalist who is the director of the Integrity in Science Project, part of the nonprofit organization Center for Science in the Public Interest. I know Merrill personally and can vouch for his ethics and passion for honesty in science.

Standing in the other corner is Ron Pies, M.D., a psychiatrist and editor-in-chief of Psychiatric Times. Ron and I are friends and colleagues, and he is one of the most thoughtful people I have met on issues of ethics. In fact, he invited to write this two part article on conflicts of interest in psychiatry, which he published in Psychiatric Times two years ago, in November of 2006.

We have two fine individuals scrimmaging over an issue they both care deeply about. So what happened?

Here’s the sequence of events.

First, on August 1, Dr. Pies wrote this editorial in which he discussed Senator Grassley’s investigation of conflicts of interest, and announced that his journal would henceforth begin posting the financial disclosures of its entire editorial board.

Then, on September 2, Merrill Goozner posted this short piece on his Integrity in Science Watch in which he acknowledged Psych Times’ efforts at transparency but nonetheless added a little jab by claiming that Dr. Pies personally has industry ties, which is at odds with the recommendations of The International Committee of Medical Journal Editors' “Uniform Requirements for Manuscripts Submitted to Biomedical Journals,” which declares that “editors who make final decisions about manuscripts should have no personal financial involvement in any of the issues they might judge.”

In response to Goozner’s backhanded complement, in the current issue of Psychiatric Times there is an unusual commentary entitled “Setting the Record Straight.” It is unusual in that it is written by both Susan Kweskin, the journal’s editorial director, and by Dr. Pies, who is the editor-in-chief.

The gist of this article is that, in fact, Dr. Pies has accepted no money from drug companies since becoming editor in January 2007. When Dr. Pies wrote to Goozner to correct the error, Goozner’s response was that “We use a 5-year-look-back period for conflicts of interest. This is the same look-back period used by the Journal of the American Medical Association.”

Fair enough, responded Dr. Pies, but it seemed to him that Goozner has chosen JAMA’s particularly long look-back period to “single out specific editors-in-chief and their publications” for subtle accusations that they are allowing conflicts of interest to bias the content. Furthermore, Dr. Pies scolded Goozner for failing to contact him directly to find out if he, indeed, had conflicts of interest that would continue to be relevant to his current responsibilities.

Goozner has yet to respond to this latest installment of the drama.

So who’s right and who’s wrong? Both.

Goozner is right to be concerned about editors who have had recent financial relationships with companies related to their editorial work. While there is nothing magic about a five year vs. a one year look-back, it is probably true that editors who have received money relatively recently from a company are more likely to have their judgment affected than those who left the entanglements behind many years ago.

However, in his zeal to root out the rascals, Goozner went overboard and skipped some of his due diligence. Dr. Pies in particular was not the person to go after, and Goozner could have learned about his reputation for honesty by asking anybody in the field. Furthermore, Goozner claimed that Robert Freedman, editor in chief of the American Journal of Psychiatry, also has drug company ties, but in his slap-dash web search he linked to the wrong person: a “Robert R. Freedman, PhD,” who is a professor of psychiatry and obstetrics and gynecology at Wayne State University School of Medicine, and who has no connection to the Psychiatry Journal’s Robert Freedman. As it turns out, the “real” Dr. Freedman indeed has had some connections to pharma, but it’s not clear what they are, or whether they are ongoing—this was a confusing issue that I once tried to clarify in correspondence with Dr. Freedman, described in this blog entry.

Dr. Pies is right to be peeved about Goozner’s “broad brush approach to disclosure,” as he put it. I have certainly been guilty of this practice as well. The fact is that those of us involved in blogging and the media feel a constant pressure to publish something, and we really need to be more cautious about the claims we make.

On the other hand, Dr. Pies has chosen to edit a journal more dependent on drug company funding than most. Unlike JAMA and the American Journal of Psychiatry, Psych Times is a “controlled circulation” journal. This means that doctors don’t have to subscribe to get it. In fact, every month it is sent for free to over 40,000 psychiatrists. Just about every last dime of the journal's income comes directly from the pharmaceutical industry. Companies pay extremely high prices for their ads (here is the journal's rate card) precisely because the journal can guarantee that ads will be viewed by 40,000 sets of prescribing eyes. Furthermore, the parent company, CMP Medica, presides over a veritable industry CME empire, including the U.S. Psychiatric Congress, and produces industry supplements packaged with Psychiatric Times. (Dr. Pies has no editorial control over these supplements.) I reviewed one of these supplements last year, and found it to be a subtle advertisement for Bifeprunox, an antipsychotic made by the supplement’s corporate sponsors, Wyeth and Solvay.

This is not to impugn Dr. Pies’ reputation, but rather to point out that he has an exceedingly challenging job of ensuring unbiased reporting in a journal that must, to a greater degree than many others, keep the drug companies happy to survive.

Bottom line: Watchdogs like Merrill Goozner (and myself) are crucial during a time when medicine is finally taking a close look at its relationships with drug companies. But we need to be careful not to take an indiscriminate shotgun approach in our investigations. On the other hand, there are some ethical editors like Dr. Pies who have decided to work within an industry-supported environment, but who are trying to keep their journals’ noses clean. May the Force be with us all!

New York Times' Judith Warner on Nemeroff

When Judith Warner, a major columnist for the New York Times, writes a piece focusing on American psychiatrists, and entitles it "Diagnosis: Greed," you know the profession is in serious trouble.

Bringing a fresh perspective to an issue that readers of this blog may be seeing as a dead horse, Warner points out that the astonishing revelations of psychiatrists earning millions from drug companies is part and parcel of the broader financial ruination that we are witnessing daily. Just as lack of government regulation and oversight allowed our economy to collapse because of the rise of subprime mortgage-backed securities, the lack of regulation of the physician/pharmaceutical relationship has led to a medical culture of greed and the collapse of confidence in our profession.

To quote Warner:

Nemeroff didn’t bring down any banks, didn’t freeze the American credit markets, hasn’t plunged the world economy into recession. But his extensive, excessive and untransparent ties to the pharmaceutical industry are all too common, unfortunately, among his cohort of “thought leaders” in psychiatry and other medical specialties. And these relationships have led to a dangerous crisis of confidence in the basic integrity and validity of America’s medical research.

The APA and other medical organizations are beginning the process of reforming themselves. I think we need to speed things up. There isn't a moment to lose.

Full Disclosure = MORE Bias?

I've lagged in posting lately in order to take my recertification exam in psychiatry. I hope I passed. For some reason, there were a lot of questions about physostigmine, a medication the Board seems to believe is crucial for psychiatric practice. I guess they got bored writing questions about SSRIs.

Lacking any urgent CME news, I caught up on some reading and came across this interesting article on the perverse negative effects of full disclosure. Usually, we think that disclosure minimizes the biasing effects of conflict of interest (COI). Accordingly, the ACCME's standards for commercial support are based primarily on an elaborate series of guidelines about how to disclose COI in educational activities. But a funny thing happens on the way to CME programs: even with full disclosure, they continue to be commercially biased. Why is that? Why doesn't disclosure solve the problem?

Business school researchers at Carnegie Mellon University conducted two experiments to answer these questions. Undergraduates from the university were asked to estimate the number of coins in a glass jar. Some were assigned the "estimator" role and others, the "advisor" role. In the CME world, the advisors correspond to hired gun speakers, and the estimators are physicians in the audience.

Here are the results:

1. In the first experiment, advisors were paid to give erroneous advice about the number of coins in the jar. Specifically, they were asked to exaggerate the number of coins (bias high) or to mimimize (bias low). Crucially, the estimators were warned ahead of time that the advisors had these incentives to give bad advice. But even with these disclosures in mind, the estimators followed the biased advice.

2. In this variation, some advisors were paid to give accurate advice, and others were paid to give high advice. As expected, the advisors who had an incentive to give high advice succeeded in influencing the estimators. But here's the interesting twist. A third group of advisors was paid to give high advice, and was told that the estimators would be warned about their incentive to bias the answer upward. The result? Advisors who knew their bias was disclosed actually provided more erroneous advice than the others. In other words, disclosing the COI actually makes hired guns more likely to provide biased information.

The authors speculate that disclosure worsens bias for two reasons. First, disclosure gives the advisors "moral license" to exaggerate. To quote from the paper: "When their conflict of interest is disclosed, people feel less of an obligation to protect the advice recipient." The other issue is "proactive exaggeration." Since advisors who disclose their COI worry that their advice will be discounted by the audience, they will tend to exaggerate their advice to make up for it.

This is quite an intriguing paper, and deserves to be studied by regulating bodies in all advice-giving industries, including medicine. It may well be that disclosing COI has the unintended effect of encouraging people to give worse advice than they otherwise would.

Conflict of Interest in High Places: the American Journal of Psychiatry

It's tough being the editor of a major medical journal these days. You are under constant pressure to fill your pages with high quality research, and much of this is funded by drug companies. Company-funded research is fine, and often leads to important drug discoveries. The problem is that the editors in charge of accepting articles often have their own drug industry ties, making it hard to trust the integrity of the journal content.

The New England Journal of Medicine has been embroiled in these issues for years. The current editor, Dr. Jeffrey Drazen, initially had ties to about 20 drug companies when he took over from Marcia Angell, but he has since severed those ties, and has become an important watchdog of excessive industry influence in medicine.

Unfortunately, our major psychiatric journal, the American Journal of Psychiatry, has decided to take the low road, heading back into the land of conflict of interest. Each January, the journal publishes the financial disclosures of its main editors. You can read the latest disclosures here. The editor in chief, Robert Freedman, M.D., who disclosed no competing interests last year, now discloses that he serves as an "unpaid co-investigator ... for investigations sponsored by pharmaceutical companies that are developing new drugs for patients based on his research findings."

I nearly jumped out of my seat when I read that, because this is the same editor who took the unusual step of writing an editorial criticizing an accepted article in December 2006 issue. Freedman critiqued an article by Rosenheck that presented data showing that the old antipsychotic Trilafon was more cost-effective than newer atypicals. At the end of that editorial, Freedman said he had no competing interests. Maybe that's true--perhaps he did not begin his "unpaid" investigations with companies until after he wrote the editorial. However, it seems likely that he knew at that time that he might be entering into those relationships, because he has been conducting the research on antipsychotics for many years.

What about the "unpaid" nature of his work with companies? Does this mitigate the nature of his competing interests? Of course not; Freedman co-owns a patent for a promising molecular target of new antipsychotic drugs (see this article for background), and stands to benefit hugely, either financially, or in terms of career advancement, if this target pans out as an effective treatment for schizophrenia.

Don't get me wrong: I think it's great that Dr. Freedman is doing important research and I hope it leads to effective new treatments. But is he the right man to be at the helm of the major American psychiatric journal? Certainly not. We need an editor with no competing interests, whether those interests are related to financial incentives or career incentives.

By the way, I e-mailed Dr. Freedman about my concerns and he responded with the following explanation which I found perplexing:

"My research concerns the development of new treatments for schizophrenia, for which I am funded by NIH and VA research grants. NIH and the VA funded the development of the molecule that I currently am working on. However, in the course of developing new drugs, I may need to interact with a pharmaceutical company if it has discovered a more promising molecule for the targets that my research group has identified. Although that has not happened, I want our readers to be aware that it could possibly happen. It is a disclosure in advance of any transaction that might subsequently require disclosure, so that readers can assess the issue in prospect."

That's a mind-bender! In this month's issue of his journal, he states that he "serves" as an investigator for studies sponsored by drug companies. But in his response to my question, he retracts that disclosure, saying that, in fact, he has not worked with drug companies, and does not now, but that he might in the future.

I, for one, am confused. I look forward to what Dr. Freedman has to say in his 2009 disclosures!