WHEN IS DISCLOSURE NOT DISCLOSURE?

WHEN IS DISCLOSURE NOT DISCLOSURE?

Hint: When it is made by the Chairman of the DSM-5 Task Force.

Here is a case study in conflict of interest (COI). A remarkable confession has just appeared by a group of 5 prominent academics, writing in the journal JAMA Psychiatry. Having been outed to the Editors, they now admit to concealing pertinent financial information. One of the five is David J. Kupfer, MD, chairman of the DSM-5 Task Force and past chairman of the department of psychiatry at The University of Pittsburgh. The others are from Pittsburgh, Minnesota, and Chicago.

With millions in funding from NIMH, these folks have been developing new approaches to testing for anxiety and depression. The technical details are not important for this story. What matters is that they have clearly set their sights on a large market for diagnostic screening, epidemiological research, and clinical practice. They have recently published promotional reports talking up three products and projecting major applications – but before taking care of the nuts and bolts of scale development.

Their major report in JAMA Psychiatry contained a disclosure to the effect that they might at some time in the future consider commercial development of their depression scale. This disclosure was phony. We now know that, in lieu of frankly disclosing a major COI, they opted for a disingenuous, dissembling statement that was economical with the truth.

I thought the content of their report was sub-par, and the journal published a letter from me to that effect. They responded to my criticism with hand waving, and they tried to impugn me for bias related to my own (disclosed) COI. This foolish, ad hominem tactic aimed to divert attention from the substance of my critique – for which they had no adequate response.

As I am not a person who suffers fools or insults gladly, their evasive response caused me to do some checking. I quickly learned that the gang of five are shareholders in a private corporation. Before their paper was accepted by JAMA Psychiatry, the corporation was incorporated in Delaware and soon after registered to do business in Illinois. Those facts were not disclosed in the original report or in the published letter of Reply to me. These omissions were acknowledged in the notice of Failure to Report that appeared on-line today.

It gets worse. Other things that I learned – and that I communicated to the journal – make it clear that the corporate train had left the station in advance of the letter of Reply. For instance, a professional operations and management executive (Mr. Yehuda Cohen) had joined the corporation. He had established the corporate website, where he was featured as a principal, along with the gang of five. The website also displayed a professionally crafted Privacy Policy, dated ahead of the letter of Reply. This document identified what appears to be a commercial business address for the corporation. The notice of Failure to Disclose is silent on these facts.

So, the published notice of Failure to Disclose still withholds pertinent information, which makes a mockery of the weasel words that they have not released any tests for commercial or professional use. Not yet, they haven’t. But they are under way, make no mistake. This prevarication creates the impression of a habitual lack of transparency. Considering that I gave the journal all this information, one has to be surprised that JAMA Psychiatry went along with this prevarication. Plus, would it have killed them to apologize for their foolish attempt to smear me, as I requested? In correspondence with me, the Editor in Chief of JAMA didn’t want to go there, and he refused to publish my letter that detailed the facts, citing the most specious of grounds. The Editor of JAMA Psychiatry has ducked for cover when I faulted him for publishing the ad hominem material in the first place.

This deplorable episode casts a pall on the repeated assurances by Dr. Kupfer that COI issues were under control in the DSM-5 process. If the chairman of the DSM-5 Task Force doesn’t have his own act together, then what are his assurances worth? The new instruments proposed by this corporation bear an eerie resemblance to cross-cutting dimensional measures that were promoted for DSM-5 but that didn’t make the final cut. As far as I know, Dr. Kupfer didn’t declare his interest in this corporation for scrutiny vis à vis DSM-5.

Another lesson is that even Failure to Report notices can be weasel documents. I fault the Editors of JAMA Psychiatry, Joseph Coyle, MD, and of JAMA, Howard Bauchner, MD, for the non-rigorous standard they applied to the notice of Failure to Disclose. They acquiesced in another dissembling response.

Yet another lesson is that all authors are accountable for the accuracy of disclosure statements. Some of these authors might claim they relied on the lead author and president of the corporation, Robert Gibbons, PhD, a statistician at The University of Chicago, to make sure everything was kosher. Big mistake – just like the infamous case of the Nemeroff-led Cyberonics – vagus nerve stimulation review that failed to disclose that the academic authors (ahem) were paid consultants of the corporation. When your name is on the byline, be sure you cover the bases for your own protection, and don’t squawk when you are called out.

Finally, where is NIMH in all of this? Since when are public NIMH funds to be treated as commercial seed money? Who actually owns the algorithms and data bases on which the Gibbons corporation relies for its commercial aspirations? Why are they not publicly accessible? Is Thomas Insel on top of this?

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.