WALK THE WALK
Saturday, April 06, 2013
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.