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.
