WALK THE WALK

WALK THE WALK

For some time a jeremiad theme has been dominant in the psychiatric sector of the academic-industrial complex. Blockbuster psychiatric medications are going off patent, the pipeline is viewed as alarmingly empty, and several corporations are scaling back or even abandoning their research programs in this area. Analyses of the reasons range from the enlightened to the pragmatic to the pedantic to the foolish. Everyone predicts that things will turn bleak in academic clinical research if the corporate spigot is turned off.

Lost in the wailing is a clear understanding that the defecting corporations are acting out of their own enlightened self interest. For 50 years, no fundamentally incisive innovations have occurred, so the defectors are telling the academics to get their act together in respect of better understanding disease mechanisms. Trouble is, too many academic clinical investigators have devolved into key opinion leaders promoting corporate marketing messages at the expense of generating original clinical science. Now they are squawking about being caught with their pants down.

The latest academic psychiatrist to opine about this issue is Steven Hyman at Harvard Medical School. In a new commentary that has just appeared, Dr. Hyman talks up his favorite theme of translational medicine, which sounds lovely until you perceive that he has no contemporary examples of same in psychopharmacology. It’s all airy rhetoric. Dr. Hyman is not just a Harvard professor – he is a former Director of the National Institute of Mental Health (NIMH). Then he was Provost at Harvard under President Larry Summers. Now he is Director of a psychiatric research center at Harvard.

Someone else who noticed Dr. Hyman’s new commentary is our fellow blogger Dr. John M. (Mickey) Nardo across at 1Boringoldman.com. His take on the Hyman piece is right on target. Basically, the Hyman commentary is a hortatory fantasy that we can all do better by buying in to his vision of interdisciplinary research, pooling the efforts of academia, industry, and government. Problem is, his vision hasn't worked so far. Here is an example.

   

Towards the end of his term as NIMH Director, Dr. Hyman set the ball rolling for new centers cast in his mold of translational research. Dr. Nardo mentioned “… a bunch of centers that haven’t produced very much.” The model of such failed centers is the one that existed at Emory University under the direction of Charles Nemeroff. It was called the Emory-GlaxoSmithKline-NIMH Collaborative Mood Disorders Initiative 5U19MH069056 (Principal Investigator Charles Nemeroff). It was conceived with all the right buzzwords about innovative models of drug discovery and translational benefit for patients through partnerships of academic centers with commercial drug makers (the Request for Applications (RFA) actually used this language). From the start, the Initiative was poorly managed and it never lived up to its billing. 

Annual Progress Reports from the Initiative to NIMH, obtained through a FOIA request, reveal unacceptably low scientific productivity, and lack of leadership to promote the intended scientific synergies among laboratories. When I assessed the overall productivity of this project four years after the end of the first 5-year funding period, it was apparent that the U.S. taxpayer received little value for the $5.3 million investment by NIMH. Only 7 original scientific publications could be attributed to the federal support (that count excludes a host of potboiler review articles and other academic padding). Five of these 7 originated from a single participating laboratory at Emory. The NIMH component, under Dennis Charney, also was a serious underperformer.

The collaborating drug company GlaxoSmithKline obtained valuable preclinical information from the Emory laboratories, much of which has never been published even though federal funding supported the work. If the data are being treated as confidential proprietary information by GSK, then that posture would be contrary to the spirit of the original RFA. Maybe GSK just decided it was worthless data. In addition, GSK benefited from the conduct of a Phase II clinical trial of one of their candidate drugs in posttraumatic stress disorder (PTSD), even though this study returned a negative result. Even worse, the trial did not meet the stated criteria of the RFA. It was not based on any well founded theory of PTSD. Instead, it was a routine, exploratory study of a new compound. Because the study design did not permit strong inference, nothing substantive was learned from the negative result. This Phase II trial could have been performed better and less expensively by GSK itself as a normal business activity. GSK certainly did not need scarce NIMH dollars for this routine, early Phase II trial. The Emory-GSK-NIMH Initiative added no scientific value.

Notwithstanding the clear evidence of under-productivity, NIMH under Director Thomas Insel, MD, continued the Initiative for all 5 years of the original funding period, and then renewed the Initiative for a second 5 year period at an increased funding level under a new P.I., Helen Mayberg, M.D. Dr. Mayberg is a respected clinical scientist, but she is not a psychiatrist, she is not a psychopharmacologist, and she has no track record of research in the priorities announced by the RFA. What actually is going on? Did NIMH just hand a favor to Dr. Insel’s former employer, Emory University, to the tune of another $6 million?

One lesson of this episode is that the chatter by federal scientific administrators (Hyman, Insel) about translational research strategies and innovative models of drug discovery is mostly vacuous rhetoric. The RFA was an imprudent conceit to begin with, having no base in solid clinical science, and this expensive Initiative failed catastrophically to meet its grandiose objectives. It is ironic that Dr. Hyman presumes to scold and sermonize to the field yet again about translational research, as it was he who set the ball rolling in the first place for the disastrous Emory-GlaxoSmithKline-NIMH Collaborative Mood Disorders Initiative. Last time I looked, nobody has been held accountable for the failure of the Initiative. Where is NIMH Director Thomas Insel when we need him to set standards of accountability and ethics?

So, the next time you hear academic psychiatrists lamenting how bad it is, remind them about this scandalous example of waste and mismanagement of federal research funding. Cleaning up cesspools like this would be a step to unblocking the drug development pipeline. And we need leaders who walk the walk, not just talk the talk.

Quis Custodiet Ipsos Custodes? Redux

Revised HHS Rules for Conflict of Interest Fall Short

This morning NIH Director Dr. Francis Collins announced revisions to the existing 1995 regulations on objectivity in research that is funded by the Public Health Service. The focus is on significant financial interests (SFI) and on financial conflicts of interest (FCOI). The regulations illustrate the 3-way dance involving academic institutions (the grantees), NIH (the grantor) and academic scientists (the investigators). Thanks to Senator Grassley (R-Iowa) and his investigator Paul Thacker, headlined revelations in recent years about unacceptable management of FCOI at places like Stanford (Alan Schatzberg), Emory (Charles Nemeroff) and Harvard (Joseph Biederman) forced these revisions of the NIH regulations.

The general initial reaction to the new rules has been critical – here and here, for instance. Many stakeholders had urged the NIH to require that institutions make the disclosed FCOI of their investigators available on a public website. Dr. Collins had intimated that we could expect to see this change, so there is consternation that it somehow became derailed by institutional lobbying in recent months. The stated concern was that institutions would feel burdened by the need to maintain these data bases. Instead, if citizens wish to inquire about FCOI involving PHS-derived research funding, they will need to write to the institution, which is obliged to respond within 5 days. That’s not exactly user friendly. POGO today made the smart suggestion that the data could easily be attached to information about awarded funds on the NIH RePORTER website, that already exists.

A second failing is that the revised regulations do not close the regulatory loophole through which Charles Nemeroff strolled when he moved from Emory to the University of Miami. We covered that incident several times on this blog last year. Though Nemeroff was under a 2-year sanction and banned from participating in NIH-funded research at Emory, his friend Thomas Insel, Director of NIMH, assured the dean of the medical school at Miami that Nemeroff was in good standing to apply for NIH funding when he moved from Emory. To underline the point, Insel displayed the bad judgment of appointing Nemeroff to 2 new NIMH review committees.

Do today’s revised regulations prevent a repeat of this administrative travesty? No, they don’t. There is some mention of ensuring oversight if a sanctioned investigator wishes to transfer a grant to a new institution, but nothing to prevent the Nemeroff-Insel dance from being repeated. Here is the relevant section of today’s announcement (page 89):

We did, however, agree with one respondent that it would be helpful to clarify, in the grants context in particular, that institutional sanctions against an Investigator can travel with the Investigator upon his or her transfer to another Institution. Specifically, we have revised 42 CFR 50.606, paragraph (a), as follows: “If the failure of an Investigator to comply with an Institution’s financial conflicts of interest policy or a financial conflict of interest management plan appears to have biased the design, conduct, or reporting of the PHS-funded research, the Institution shall promptly notify the PHS Awarding Component of the corrective action taken or to be taken. The PHS Awarding Component will consider the situation and, as necessary, take appropriate action, or refer the matter to the Institution for further action, which may include directions to the Institution on how to maintain appropriate objectivity in the PHS-funded research project. The PHS may, for example, require Institutions employing such an Investigator to enforce any applicable corrective actions prior to a PHS award or when the transfer of a PHS grant(s) involves such an Investigator.”

This revision is intended to reference the range of options for the PHS Awarding Component to consider, depending on the specific circumstances at issue. For example, PHS may decide to initiate government-wide suspension or debarment of the Investigator under 2 CFR Part 376; or to use enforcement measures under 45 CFR 74.62, e.g., perhaps to make the approval of a transfer contingent upon the former Institution’s disclosure of the corrective action- including the specific sanctions against the Investigator- to the new Institution; and/or to use special award conditions under 45 CFR 74.14, e.g., perhaps to make the new Institution agree to take the same or similar action against that Investigator or explain to the PHS Awarding Component in writing why such action was not taken and what alternative measures will be used to ensure compliance.

What’s wrong here? Everything is optional; everything is discretionary; everything is contextual – that is a formula for NIH and the academic institutions to just look the other way. And if a Nemeroff decides just to relocate without transferring a grant then he is free to start reapplying again right away. Miami would not be required to continue applying the Emory sanction banning him for 2 years from involvement in federal grants. The PHS Awarding Component (NIMH in this case) may or may not get involved, or it may pass the buck to the new institution. So what has changed? If it is left up to compromised federal bureaucrats like Thomas Insel, and institutional administrators like Pascal Goldschmidt at Miami, then nothing has changed. It's business as usual, folks.

Dr. Collins, you have not done what you set out to do. Too bad.

IMPEACHMENT: IT’S ABOUT THE INSTITUTION, NOT THE PERSON

IMPEACHMENT: IT’S ABOUT THE INSTITUTION, NOT THE PERSON

The impeachment trial of Judge G. Thomas Porteous of Louisiana this week was a lesson in civic ethics. The lessons of the Porteous trial apply to academic medical centers, professional medical societies, medical journals, and granting agencies like NIH.

The Porteous trial is a straightforward case of bribes, kickbacks and corruption involving a Federal judge. The most enlightening arguments came from prosecutor Rep. Adam Schiff, D-California, laying out the case for impeachment in the Senate. He gave a lucid presentation of the logic and the historical origins of the impeachment process. The key points are these: impeachment serves to protect the dignity, honor, and credibility of the office more than to punish the wayward office holder; and impeachment is a constitutionally sanctioned way to clean the Augean stables without necessarily having to prove criminal liability. It is sufficient to demonstrate that the bad actors have brought disgrace on their offices.

What this means for us in medicine is that legalistic charges and defenses are not the right way to go in exposing and ejecting bad actors from our field. In the highly publicized cases of ethical compromise over the past few years, our group disapproval, when there was any at all, generally has run on two parallel tracks. The first is legalistic, and it favors the bad actors, who flaunt their constitutional protections with the taunt, prove it. The second ground of disapproval is esthetic, based on the tackiness of the bad actors’ behaviors – regardless of technical legalities, what they do is an affront and an insult to professional standards and mores. When we look at how recent incidents in medicine actually played out, however, we see a disconnect. The bad actors have narrowed the debate to the first ground of disapproval, while forcing the second off limits. In this strategy, they have received conscious or unconscious assistance from the professional establishment. The focus has been on legal technicalities involving the bad actors rather on preserving the dignity and credibility of high offices in academic medicine.

For instance, when Charles Nemeroff was exposed by Senator Grassley for conflict of interest in his NIH grants, he came up with the contrived legalistic defense that his unreported payments from GlaxoSmithKline were for ‘CME-like’ presentations, and thus somehow exempt from disclosure. Nemeroff’s obfuscations finally collapsed of their own weight and Emory University took decisive action against him, even though they had sufficient evidence dating back at least 4-5 years. In the end, Emory had to go through the wringer to discipline Nemeroff, and the institution suffered grave damage to its reputation for a number of years as the price of delay.

For instance, when Thomas Insel, the Director of NIMH, assured Pascal Goldschmidt, Dean of the School of Medicine at the University of Miami, that Nemeroff was absolutely in good standing for applying for new NIH grants if he left Emory for Miami, despite a 2-year ban at Emory, he hewed to the letter of the law while disregarding its spirit in order to help his friend. Moreover, when Insel appointed Nemeroff to two new NIH Research Review Committees, he established beyond any doubt that he was intent on trying to help Nemeroff get back into circulation, and that he failed to grasp the gravity of the dishonor that Nemeroff inflicted on the field. This obtuseness on Insel’s part damaged the credibility and reputation of NIMH. To his credit, NIH director Francis Collins finally ‘got it’ and forced a review of the NIH ethics rules that had been entrusted to Insel.

For instance, when Pascal Goldschmidt, Dean of the School of Medicine at the University of Miami, claimed he had done due diligence in his recruitment of Nemeroff as chair of his psychiatry department in 2009, he focused on the legalistic aspects of Emory’s review of Nemeroff, while failing to understand the degree of negative publicity associated with Nemeroff’s name. He ended up hiring someone who is an object of ridicule, and he in turn is ridiculed by association.

For instance, when Stanford University learned of Alan Schatzberg’s boundary violations vis a vis his NIH-funded projects and his personal corporation, they first pushed back on legalistic technical grounds. Only later did the Stanford administration get the message by removing Schatzberg from his Principal Investigator role with NIH grants, and eventually appointing a new chair of psychiatry. Meanwhile, the public image of Stanford suffered.

For instance, when the American Psychiatric Association was warned that Alan Schatzberg was a problematic candidate for election as President of the association on account of his history of ethical compromise, they went ahead anyway and they have since had opportunity to regret that decision. Here again, the professional society appears to have lost sight of the ethical forest for the legal trees. The credibility and reputation of the APA have suffered because of the taint associated with Schatzberg’s presidency.

For instance, when the New York Times recently exposed the ghostwriting associated with the 1999 textbook of Charles Nemeroff and Alan Schatzberg, the so-called authors responded with typical legalistic defenses. They and the University of Miami and the American Psychiatric Association Press (the publisher) again lost sight of the ethical forest for the legal trees. This stereotyped, public relations driven response ignores the visceral and esthetic distaste most observers felt on learning about the collusion between the ‘authors,’ the professional writing company and the sponsoring pharmaceutical corporation. Even the defense that it occurred a long time ago fails. In the Porteous trial, the prosecution established that dishonorable events in an officer’s past are grounds for impeachment, whether or not they also occurred during the person’s time in office.

For instance, when Harvard Medical School planned a new CME program on psychopharmacology in mid-2011, they engaged a number of compromised academic speakers, including Nemeroff and Schatzberg. What the hell was Harvard thinking? I told the Course Director, Carl Salzman, that this amounts to pandering. He replied defensively that Nemeroff and Schatzberg are well regarded speakers and that he would ensure that they gave unbiased presentations. That’s not the point. The point is that they have done serious damage to our field, and for Harvard Medical School to give them top billing amounts to denial of the elephant in the living room. It’s collusion in service of their public rehabilitation. I told Dr. Salzman that his logic amounts to compartmentalized thinking. I might have added that Adolf Hitler gave a lot of great speeches that received rave reviews and that compartmentalized thinking was widespread in the nation of Germany between 1928 and 1945. Meanwhile, Harvard Medical School gets a black eye through its association with these compromised individuals. So do the other speakers who will be on the panel. Who needs this kind of taint? Dr. Salzman can defend Nemeroff and Schatzberg all he wants on specious legalistic grounds, but who cares? Harvard Medical School could use some moral clarity.

So, we come back to the impeachment trial of Judge Porteous. Impeachment protects the institution. When sleazebags get into positions of authority and trust they need to be dumped, and our professional and academic institutions need to have enough spine to dump them. At the very least, we don’t need to tolerate institutions like Harvard Medical School pandering to compromised academic bad actors. For shame.

Nemeroff, Seroquel, and ACCME

Nemeroff, Seroquel, and ACCME

Roy Poses has discussed the atypical antipsychotic drug Seroquel (quetiapine) several times on this site, pointing out manipulation of clinical research results to enhance the appearance of efficacy, and suppression of studies with unfavorable results. I call this augmenting the marketed profile of the drug. Daniel Carlat has commented on published Seroquel data here and ClinPsych here.

AstraZeneca, the marketer of Seroquel, has also been busy with continuing medical education (CME) programs that augment Seroquel’s profile. Last December 8, one such program went on line, aired by the provider CME Outfitters. The program’s title was “Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough.” The corporate logo for CME Outfitters is Education with Integrity. I will allow readers to decide if the company is meeting its mission statement in this respect.

The key opinion leader engaged by CME Outfitters to discuss Seroquel and other atypical antipsychotic drugs was Charles Nemeroff of Emory University. He was joined by 2 KOLs-in-training, whom I will not name. The corporate sponsor that paid CME Outfitters and, indirectly, these presenters was AstraZeneca. I do not need to rehearse here the ethical issues that have surrounded Dr. Nemeroff for the past several years. Suffice it to say that, as a result of those issues, Dr. Nemeroff is no longer chair of the department of psychiatry at Emory University, he is no longer editor-in-chief of the ACNP journal Neuropsychopharmacology, he was removed from involvement with ongoing federally funded research grants at Emory University, and he was put on a short leash by the Emory administration.

On December 23, 2008 I filed a formal complaint about Dr. Nemeroff’s program with ACCME. My bill of particulars was lengthy, detailed, and backed up by extensive
materials. In due course, ACCME investigated the complaint and found that the program did violate ACCME standards. With respect to content, ACCME determined that Dr. Nemeroff’s program lacked sufficient information about possible adverse effects of treatment with atypical antipsychotic drugs; and failed to emphasize sufficiently the efficacy of alternative treatments. With respect to commercial bias, ACCME determined that bias existed as a result of the absence of contrasting therapy data, and through downplaying the drawbacks related to treatment with atypical antipsychotic drugs in depressed patients.

Following these findings by ACCME, the provider was notified of the violations in early September 2009, and the program was removed from the provider’s website. The sanitized statement of violations determined by ACCME does not capture the nuances of deceit, ineptitude, and deficient educational content in Dr. Nemeroff’s program. One remarkable example was Dr. Nemeroff’s citation of data, from one of his own publications, that were previously retracted. Did he think no one would notice?

A second example involved biased presentation of the sponsor’s data for Seroquel. Two doses of Seroquel (150 mg and 300 mg) were tested. Only the results for the 300 mg dose were statistically significant. Nevertheless, in the video presentation one of the junior presenters stated very clearly that there was “significant improvement in both response and remission with both doses” of Seroquel. That is a falsification of the scientific record. That falsification does not meet ACCME requirements for fair, balanced, truthful, and honest teaching. As moderator, Dr. Nemeroff was required to correct this false statement made by his junior assistant, but Dr. Nemeroff failed to do so.

The negative findings and sanction by ACCME against Dr. Nemeroff’s program are welcome, though I have to say it took ACCME an inordinately long time to complete their work. I also presented ACCME with several follow-on questions, which the Council is now considering. These are:

• Did ACCME notify the presenters that their program violated ACCME policies? If not, why not?

• Will CME credits be clawed back from physicians and other professionals who obtained credits through the noncompliant program? If not, why not? I believe this would be an effective form of negative feedback to the provider and the presenters.

• Does ACCME have a process to require the provider and presenters to ascertain whether any patients were injured as a result of the violations that created biased and deficient information in this program? If not, why not?

• Does ACCME require the provider to notify physicians and other professionals who completed the noncompliant program that the provider was sanctioned for violation of ACCME standards? If not, why not?

• Does ACCME require the provider to furnish corrective materials to such professionals in order to remedy the bias and incompetence to which they were subjected through violation of ACCME standards, and thereby to remove potential danger to future patients? If not, why not?

• Why did ACCME allow the noncompliant program to remain available long after the complaint was filed? I suggest that ACCME needs to place a hold on programs that are subject to active complaint. Had such a policy been in effect in December 2008, the violating program would not have been re-aired by the provider in early 2009, it would not have remained on-line for 9 months, and the damage to the continuing education community would have been contained.

• Will ACCME issue a public listing of sanctions it has enforced against providers and presenters? If not, why not? State medical boards do exactly that in relation to physicians and other professionals who violate standards of practice.

• Finally, I reminded ACCME that its primary constituents are patients, physicians and other professionals, not commercial or academic CME providers. It seems to me that ACCME was altogether too laissez-faire and dilatory in the way it handled this matter. At the time of my initial complaint last December, I requested expedited review precisely because additional airings of this violating program were scheduled.

The good news is that ACCME seems to have got the message that things need to change. As one of their officers wrote to me recently, “We sincerely appreciate the time and effort you have put into participating in our complaints and inquiries process. You have raised important issues that the ACCME will review and address.” I await their next communications on the remaining questions.

As for Dr. Nemeroff, he is yesterday’s news. The adverse findings by ACCME about his program serve as a reminder to corporate sponsors and CME companies that Dr. Nemeroff is so compromised by now that he has lost effectiveness as a front man for Pharma. Indeed, he is so toxic that he now glows in the dark.

A Blogger That Dares Not Speak His University's Name

Dr Douglas Bremner is a Professor of Psychiatry and Radiology at Emory University, and Director of the University's Clinical Neuroscience Research Unit. He has also written a book critical of the pharmaceutical industry (Before You Take That Pill), and writes a blog (also called Before You Take That Pill) that is also skeptical about certain aspects of current psychiatric dogma. Inside Higher Education reported that Emory University can apparently no longer bear to have its name mentioned in Dr Bremner's blog:

Emory University has been accused repeatedly over the last year of looking the other way while one of its prominent physicians built extremely close ties to the pharmaceutical industry and -- critics charge -- failed to adequately report those ties as required by university and federal regulations.

But what if you are an Emory professor who happens to differ with the pharmaceutical industry? Then, it appears, Emory watches you closely -- and if you are a blogger, the university can tell you that you must remove the Emory name from your Web site. That's why a recent post on the J. Douglas Bremner's blog Before You Take That Pill is called 'I Am Removing the Name of My University From This Blog.'

In the post, he notes that he was recently ordered to remove the Emory name both by the interim chair of psychiatry and behavioral sciences, and by the medical school's executive associate dean for faculty affairs. In the letters, which he provided to Inside Higher Ed, they tell Bremner to remove Emory's name, logo and letterhead from his blog because none of them can be used for 'non-Emory business.' He was also told to report on when he had removed Emory from his blog.

The letters cite complaints that the university received about a blog post Bremner made in January in which he criticized the eviction of a man with bipolar disorder who was being forced out of his apartment for smoking. Bremner made his point in the form of a mock letter 'To Whom It May Concern' giving his blessing for the man to continue to smoke. According to Bremner's Emory superiors, complaints they received suggested that he was making 'clinical recommendations for a patient you do not know and have never examined,' and these postings made them feel the need to tell him to stop using the Emory name.

And even more concerning:

Sarah E. Goodwin, director of media relations for Emory Health Sciences, said that Emory's objection to the use of its name in non-official places was 'across the board' and not related to the content of Bremner's blog. When told about other blogs or Web sites where Emory professors' university affiliation was noted on non-Emory business, she said she didn't know why that was the case but insisted that the ban was 'across the board.'

She noted that Bremner has been 'blogging for some period of time,' and that 'if you read it over a long period of time, you can see comments he makes that may be of concern.' She declined to identify those comments.

So there you have it. It appears that faculty members, even senior faculty at Emory who make comments "that may be of concern" to an Assistant Vice President for Health Sciences, and Director, Media Relations, are not supposed to identify themselves as Emory faculty. This is the sort of policy one might expect from certain corporations. But Emory is a university. It proclaims it

is an inquiry-driven, ethically engaged and diverse community whose members work collaboratively for positive transformation in the world through courageous leadership in teaching, research, scholarship, health care and social action.

It proclaims its strategic plan is entitled:

Where Courageous Inquiry Leads

We can see where courageous inquiry leads at Emory. It leads to University executives attempting to censor faculty blogs when they included "concerning" remarks. As Inside Higher Education noted, Emory executives have not attempted to have other faculty bloggers remove references to the University, or to the bloggers' faculty status from their writing. Presumably, those bloggers were more politically correct.

We have often written about the suppression of medical research that is now a plague upon medicine, and the most dire threat to the evidence-based medicine approach. The research most likely to be suppressed is that which offends vested interests, particularly vested interests in selling particular health care goods or services. On the other hand, the Foundation for Individual Rights in Education (FIRE) for years has been fighting to uphold free speech and academic freedom on campus, but has mostly dealt with threats to politically or socially unpopular speech.

This case seems to blend these these different kinds of threats to free speech and academic freedom. It once again shows how elite universities increasingly are run like for-profit corporations, putting the prerogatives of managers ahead of the individual rights of faculty and students, and putting the mission of the university, to discover and disseminate the truth in the spirit of free enquiry, in the trash.

Dr Bremner's own comments in his blog are here. He concluded that Emory managers were "thinking more like a corporation than a university, where the free exchange of ideas, regardless of the perceived value or political correctness of those ideas, is held to the highest standard."

See also comments by Prof Margaret Soltan in the University Diaries.

ADDENDUM (15 July, 2009) - Emory has backed down, and will once again allow Dr Bremner to identify himself as a faculty member. See this post by Dr Bremner, and this post on The Torch (the FIRE blog).

INSTITUTE of MEDICINE REPORT on CONFLICT of INTEREST

INSTITUTE of MEDICINE REPORT on CONFLICT of INTEREST

Today we saw a new marker laid down in the arena called Conflict of Interest (COI). The Institute of Medicine of the National Academy of Sciences issued a report of its Committee on Conflict of Interest in Medical Research, Education and Practice. The report is comprehensive, even exhaustive, running to 353 pages. Gardner Harris in the New York Times today calls it “scolding,” “stinging,” and “damning.” The recommendations go well beyond any proposed in the recent past by medical schools or by other professional organizations. The NYT quoted David Rothman, president of the Institute on Medicine as a Profession at Columbia University: “With the I.O.M.’s endorsement, issues that were once controversial now are indisputable. Conflicts of interest in medicine are no longer acceptable.”

It will take some time for the field to digest the scope of the IOM recommendations. It will take even longer for the new standards to be implemented. For now, I offer just a few observations.

First, if the IOM hopes for maximum credibility then it might ought want to do some housecleaning. A few years ago I fired a shot across the bow of the IOM concerning COI. [Can the Institute of Medicine Review the FDA? Nature Medicine 11, 369 (1 April 2005) doi:10.1038/nm0405-369] Nothing much changed, and in the following years, national scandals erupted involving several of the issues I had highlighted. Prominent IOM members, who were well known to be poster boys for COI, were exposed by Senator Charles Grassley (R-Iowa). Their embarrassing behaviors included incomplete financial disclosures and noncompliance with NIH policy on financial conflict of interest. The exposés included Emory’s Charles Nemeroff and Stanford’s Alan Schatzberg. In both cases, administrative rearrangements have now been implemented. The case of Dr. Nemeroff has been referred by Senator Grassley to the Inspector General of the Department of Health and Human Services. It is perhaps no accident that Dean Claudia Adkison of Emory and Dean Philip Pizzo of Stanford were included as external reviewers of the draft IOM report. Their insights would have been invaluable.

Another ongoing embarrassment for the IOM is Lester Crawford. He was the FDA Commissioner who resigned abruptly in 2005 and later pleaded guilty to criminal conflict of interest. He had been charged with falsely reporting information about his stock holdings in companies he was in charge of regulating. He received a sentence of three years of supervised probation and a fine of about $90,000. He is now senior counsel with a health care lobbying firm in Washington, DC. The Institute of Medicine does not help its image by continuing the membership of such a compromised individual.

As the Emory-Nemeroff and Stanford-Schatzberg cases unfolded it appeared that the respective institutions had themselves contributed to the problems, either through inaction or through studiously nontransparent procedures on disclosure. Stanford, for instance, apparently did not require faculty members to report the proceeds of stock sales, and when challenged the university invoked on-line financial reporting services and SEC filings as a sufficient substitute. Not surprisingly, because Stanford didn’t know about Dr. Schatzberg’s realized gain of some $109,000 from sale of founder’s stock in his biotech start-up company, Corcept Therapeutics, this information was not reported to NIH.

Recommendation 4.1 One of the IOM’s recommendations applies particularly to the Stanford-Schatzberg case. Recommendation 4.1 addresses the boundary between academia and commerce in the case of research involving human subjects. Here is the specific language:

“Academic medical centers and other research institutions should establish a policy that individuals generally may not conduct research with human participants if they have a significant financial interest in an existing or potential product or a company that could be affected by the outcome of the research. Exceptions to the policy should be made public and should be permitted only if the conflict of interest committee (a) determines that an individual’s participation is essential for the conduct of the research and (b) establishes an effective mechanism for managing the conflict and protecting the integrity of the research…” (page S-14).

Last year I posted several times about this issue in the Stanford-Schatzberg case. It is gratifying now to see the IOM affirm the importance of the boundary. The activities declared off-limits by the IOM include not only “recruiting subjects; obtaining informed consent; assessing the clinical end points;” but also “analyzing data; or writing the results, conclusions, and abstracts for publications reporting the findings of the study.” (page 4-17). In Stanford’s earlier plan for managing the conflict and protecting the integrity of the research, Dr. Schatzberg was free to engage in the latter group of activities. Indeed, his hands were all over the project when it came to responding to scientific critiques, managing the climate of professional opinion, attacking and threatening critics, promoting his company’s interest through review articles and press releases, slipping unpublished and non-peer-reviewed commercial data into academic reviews, and generally conducting commercially slanted public relations through academic outlets.

When Stanford adopts the IOM recommendations, such activities will be blocked. As I stated last year, “Review articles that assess a field and synthesize data form a crucial part of science that has to be off-limits to Dr. Schatzberg just as much as assessing patients in one of his clinical trials would be.”

We should congratulate the IOM committee members for their work, and we hope to see the field embrace their recommendations.

Bernard Carroll.

UPDATE 04-30-2009: The link provided earlier for the IOM report document is no longer operative. Here is where to go now for a copy of the report. This time it will cost you.

http://www.nap.edu/catalog.php?record_id=12598

The Nemeroff Case vs the Anechoic Effect

The saga of Dr Charles Nemeroff was most recently discussed on Health Care Renewal here and here. We had first posted about his failure to disclose relevant conflicts of interest relating an article he wrote for a journal he also edited here. Other posts about Nemeroff's questionable behavior are here, here. Nemeroff has also starred in numerous posts on the Clinical Psychology and Psychiatry Blog, amongst others.

Now the tale of how Nemeroff raked in hundreds of thousands of dollars as a paid speaker on behalf of drug marketers, and denied these earnings while he ran a US government funded project meant to evaluate some of the products of his commercial sponsors, has splashed across major newspapers. There has been a lot of good discussion about the case in the blogsphere. (We await, of course, discussion in scholarly medical and health care journals, if it ever appears.)

I am a bit surprised that, in defiance of the anechoic effect, this case has now inspired some pithy commentary in the editorial pages of major media outlets. Particularly vigorous was Judith Warner writing admittedly for her blog, but a blog sponsored by the New York Times.

Yet the story of Nemeroff, who earned $2.8 million in fees from 2000 to 2007, and had at one point consulted for 21 drug and device companies simultaneously, wasn’t really a departure from the news of the week – or of this whole benighted era – at all.
It was, rather, yet another iteration of the ever-unfolding saga of greed and how the deregulation of absolutely everything has brought our country to this painful season of reckoning. Because Nemeroff’s story – which is hardly unique – belongs uniquely to this time in our nation’s history.

It is a product of legislative and cultural changes that have altered the practice of medicine, the work of research universities and the relationship between those universities and industry. And it is marked, like so much of what’s gone off the rails in our era, by the failure of our government to step in to protect citizens.

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.

Her discussion of the history behind the Nemeroff case is of interest,

How did all this happen?

It’s a familiar story: About three decades ago, it became possible to make serious money as a university researcher. Not that the money was so bad before, of course. It was respectable. But it wasn’t Wall Street-type money.

That changed in the early 1980s with the passage of legislation that allowed universities to patent their publicly funded research results and then grant exclusive licenses to pharmaceutical companies. The public-private wall came down. The universities received royalties on the drugs, and the royalties were split between the researchers and the departments. Start-up companies were spun off and sold. University researchers became, essentially, partners to industry.

The change wasn’t just structural, however. There was a cultural shift, a kind of boundary melt.

'Greed became respectable,' Angell, a professor of global health and social medicine at Harvard Medical School and the former editor in chief of The New England Journal of Medicine, recalled. 'There used to be a sort of tension between doing well and doing good for medical researchers. If they wanted to make a lot of money in a high-risk sort of job they could work for industry. If they wanted to do important, exciting research they stayed in academia and they had a comfortable life but not great wealth.'

'Before 1980, they were aware of this tension,' she said. 'Before 1980, those who went into industry were held in some disdain. With Reagan, all this changed. There was a strong feeling that the world divided into winners and losers. In medical research this just has had enormous implications.'

It’s had enormous implications for our world generally. On Wall Street, change had to come via catastrophe. Let’s hope it won’t take a disaster to bring sense back to medicine.

We have said similar things on Health Care Renewal.

I must add, however, that I think the cultural change went beyond just making greed respectable. It also somehow made deception respectable, even in the context of academic institutions that are supposed to be about discovering and disseminating the truth. So it not only became acceptable for top academics to earn hundreds of thousands in consulting fees and honoraria for talks. It became acceptable for those academics to give their talks and write articles while cloaked in their academic respectability, and without revealing that they were being paid extremely generously by drug marketers to help them hawk drugs. It became acceptable for these academics to let drug, biotechnology and device companies tell them how their clinical research would be designed, implemented and reported, but the academics still took credit for being pretend "principal investigators," and "first authors." It even became acceptable for academics to let these companies make the slides for their talks, and provide ghost-writers for their articles, but the academics still acted like they were speaking their own words of wisdom, rather than signing off on pitches authored by marketers.

Also, an unsigned editorial in the New York Times declared,

We’ve long feared that the integrity of medical research is being eroded by conflicts of interest and manipulation of scientific data. Still, it was disheartening to learn that one of the nation’s most prominent psychiatrists has taken large, undisclosed payments from a drug company whose products he evaluated and that another company manipulated studies to make a drug look far more beneficial than it actually is.

It also linked the Nemeroff case to the allegations that Pfizer marketers manipulated the reporting of clinical research to make it appear more favorable to their drug, Neurontin, as we discussed in this post.

In addition, an editorial in the Atlanta Journal-Constitution began to suggest solutions,

It now seems pretty clear that researchers at major universities — including the head of psychiatry at Emory University — failed to properly disclose their financial ties to drug companies. And evidence of that failure suggests academic medical centers are not capable of policing their faculty’s potential conflicts of interest.

These recent disclosures are more evidence that the requirements for reporting payments from the drug industry — in essence an honor system that relies on the researchers to tell their universities what they are earning — are simply inadequate. At a minimum, Congress should approve Grassley’s proposal requiring annual disclosures by companies of payments of $500 or more to researchers, a suggestion several pharmaceutical manufacturers have voluntarily adopted.

But much more needs to be done. The culture that has infected drug company sponsorship of academic medicine needs a thorough cleansing. Disinfecting it may result in a temporary reduction in the amount of money going into research and continuing physician education. But in the long run, the nation’s medical schools will want to enhance the reputation of faculty members who are doing quality, independent research unencumbered by questions about whether they are protecting the lives of patients or protecting their own wealth.

This was echoed by an op-ed in the same newspaper by Peter Lurie and Jonas Hines from Public Citizen,

The problem is the notion that disclosure alone is a panacea for conflict of interest. Disclosure amounts to an evasion of responsibility because the consumer of the disclosed information then becomes responsible for interpreting it. Is a talk by a presenter who has received $30,000 from a sponsor twice as tainted as one by a presenter who has accepted $15,000?

Certain relationships are so egregious that no amount of disclosure will suffice. For instance, investigators in clinical trials should have no direct financial interest in the products they are investigating.

There should also be a low ceiling on total external payments to academics. What assurance did Emory have that Nemeroff was fulfilling his responsibilities as department chair if he was continually jetting off to extol Paxil’s virtues?

Congress is considering bills that would create a database of drug and device companies’ payments to physicians. But the legislation has been watered down to garner support from drug companies and organized medicine. Meanwhile, some leading medical schools, such as the universities of Pennsylvania and Massachusetts, are taking the initiative, implementing stringent policies that restrict the relationships between physicians and industry.

But these efforts remain voluntary and compliance is likely to be spotty. To restore public trust, doctors will have to “just say no” to drug company trinkets, medical schools should keep companies out of clinics and insulate company-funded research from meddling, and government must develop policies that stamp out the worst excesses. Mere disclosure will not suffice.

On the other hand, the President of Emory University wrote,

The federal government has ... long understood the importance of well-managed collaboration between private industry and the academy. From such collaborations have come many of the biomedical discoveries that have improved human life and alleviated suffering in the past 20 years.

It is also essential, however, to manage properly any conflicts of interest that might jeopardize the scientific validity of the results of these collaborations.

As we have said before, requiring full and detailed disclosure of conflicts of interest affecting physicians, medical academics, and health care decision makers would begin to make the public and the medical profession aware of the magnitude of the conflicts of interest problem. What should be disclosed is not merely the existence of a relationship, but the size of payments and the nature of the activities that were done to earn that payment. Even for a simple talk, it is very different for someone to say, for example, "This talk was supported by GSK," than to say, "I was paid $3500 plus all expenses by the marketing department of GSK for this talk meant to help market Paxil." Given the fragmentary nature of the disclosure now usually made, it is particularly outrageous when influential figures in health care fail to provide even limited information.

That being said, I fully agree (and have said before) that even full disclosure is not a way to adequately "manage" many conflicts of interest. Disclosure does not remove the subconscious influence and confusion that conflicts may create, especially conflicts involving substantial sums of money. In fact, there is evidence that disclosure may give some of the conflicted a license to slant their speech and writing even more heavily (see this post). There is also evidence that people who receive disclosures do not know how to interpret them, and may fail to allow for the degree of influence the disclosed conflict may have on the conflicted.

So I agree that we ought to put an end to most of the financial relationships between health care academics whose teaching could sway audiences to use specific products and services, and who do research evaluating specific products and services, and the companies who supply those services and manufacture those products. Although it is true that collaboration between academics and industry can yield innovation, one can collaborate without being paid off by one's collaborators. As long as academics are paid on the side for nebulous consulting work and to give talks for "education" arranged by marketers, trust in them as finders and disseminators of truth will continue to erode. That is bad for academics, bad for health care, and very bad for patients.

Thoughts on Charles Nemeroff's Not So Excellent Adventure

The saga of Dr Charles Nemeroff was most recently discussed on Health Care Renewal here. We had first posted about his failure to disclose relevant conflicts of interest relating an article he wrote for a journal he also edited here. Other posts about Nemeroff's questionable behavior are here, here. Nemeroff has also starred in numerous posts on the Clinical Psychology and Psychiatry Blog, amongst others.

Now the tale of how Nemeroff raked in hundreds of thousands of dollars as a paid speaker on behalf of drug marketers, and denied these earnings while he ran a US government funded project meant to evaluate some of the products of his commercial sponsors, has splashed across major newspapers. There has been a lot of good discussion about the case in the blogsphere. (We await, of course, discussion in scholarly medical and health care journals, if it ever appears.)

I did think it was worth weighing in again just to underline some important points about this affair.

It has become common for academic leaders to earn more hawking commercial products than from teaching, research, or patient care. The database unearthed by Senator Grassley just of the speaking fees earned by Dr Nemeroff giving speeches promoting GlaxoSmithKline products is breath-taking. As noted by the anonymous blogger on the Clinical Psychology and Psychiatry Blog, Nemeroff was earning on average more than $20K a month from GlaxoSmithKline alone. That was from only one company. As that blogger also noted, Nemeroff at one point was a consultant for 18 companies, if I counted right, and gave paid talks for 4. Here is the actual relevant part of the disclosure statement.

[Nemeroff] has been a consultant to Abbott Laboratories, Acadia Pharmaceuticals, Bristol-Myers Squibb, Corcept Therapeutics, Cypress Bioscience, Cyberonics, Eli Lilly and Co, Entrepreneur’s Fund, Forest Laboratories, Inc, GlaxoSmithKline, i3 DLN, Janssen Pharmaceutica, Lundbeck, Otsuka America Pharmaceutical, Inc, Pfizer Pharmaceuticals, Quintiles Transnational, UCB Pharma, and Wyeth-Ayerst Laboratories; has been on the speakers bureau for Abbott Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Pharmaceuticals;

At most medical schools, bringing in money is more important than academic integrity, or anything else. We have previously posted about how one medical school leader explained that faculty who are "taxpayers," that is, bringers of money, are more valued than all others.

The case of Nemeroff shows how big-time taxpayers are now above the law at medical schools. As Dr Howard Brody explained it on the Hooked: Ethics, Medicine and Pharma Blog

[Nemeroff] sent a confidential letter to the dean of the medical school at Emory in May 2000, listing the dozen corporate advisory boards in which he sat. He then ticked off the grants and endowments that those firms had paid to the Department of Psychiatry at Emory, and added, 'Part of the rationale for [the companies'] funding our faculty in such a manner would be my service on those boards.' Translation--you mess with my cozy relationships with these companies, and the industry gravy train to Emory dries up. The threat is only slightly veiled, that should Emory decide to take any serious action against Nemeroff for his unreported conflicts of interest, he could easily jump ship to a more permissive med school, taking a lot of his captive research faculty and all of his industry funding with him.

Lying is an acceptable way to maintain an academic medical leadership position. Senator Grassley's letter to Emory documented this instance:

On several occasions during the life of this grant, it appears that Dr. Nemeroff
failed to report to Emory that he was participating actively on the speaker’s bureau for GSK. For instance, in an email regarding his outside activities dated October 1, 2003, Dr. Nemeroff wrote:
'…I have to dig up the agreement and send it to you, GSK no standing
contract, I chair their ad board 2-3 times per year and I am paid per board
meeting at a standard rate of $5K per weekend.'
However, and based upon information in our possession, in 2003 GSK
paid Dr. Nemeroff about $119,000 in speaking fees and expenses.

$15,000 does not remotely equal $119,000. Stating he was paid the former when he was paid the latter goes beyond "misspeaking."

Bullying helps too. As Dr Brody put it,

Nemeroff is pleased to bear the nickname 'Boss of Bosses.' He has a reputation for wielding tremendous power in psychiatry, especially taking advantage of his leverage with the big drug firms, and is ruthless in attacking those whom he doesn't like or who threaten him. One such event is described in some detail in HOOKED, the hiring and then subsequent firing of David Healy as head of a psychiatric research institute at the University of Toronto, due to Healy saying bad things about Prozac, whose manufacturer, Eli Lilly, was at the time considering a major grant to Toronto. Healy cheerfully sued Toronto and won, meaning that all the correspondence related to the firing is now in the public domain. In HOOKED I focused on Toronto's spineless behavior, but it is also interesting to note that almost certainly, Nemeroff was in the background pulling all the strings that led to Healy's dismissal.

Not only was this a case of bullying, of course, but it was also a case of the trampling of academic freedom, in this case, apparently to support the continuing relationship between pharmaceutical companies, "key opinion leaders," and medical schools, so profitable to these parties, but so detrimental to the integrity of academic medicine and of the clinical research data base.

The case of Charles Nemeroff's not so excellent adventure illustrates the sorry current state of the leadership of academic medicine. As Dr Brody put it,

In today's world, a medical school like Emory looks at all the pluses and minuses of having a guy like Nemeroff as a powerful chair, and decides that the pluses outweigh the minuses. His publication record is stellar (mostly ghostwritten of course), he brings in huge research grants, and people in his specialty all over the world want to kiss the hem of his garments. What has to change, in the regulation and the culture of the academic medical center, so that it becomes a no-brainer that having a guy like this on your faculty is a net loser?

Without such change, the public will fairly start to judge academic medicine's integrity as only slightly better than that of the garbage hauling industry, and that may be too insulting to the garbage hauling industry. It is sad beyond words that the current leadership of these once proud institutions have lead them to this pass, just for a few dollars more.

ADDENDUM (8 October, 2008) - See also comments by Dr Daniel Carlat on the Carlat Psychiatry blog here and here, and by Alison Bass on the Alison Bass blog here.