Stanford, Schatzberg, and Corcept Therapeutics
The case
of
chairman of Stanford’s department of psychiatry, has been in the news
for a week. Senator Grassley raised concerns
about conflicts of interest, reporting of same, and Stanford’s policies. In
play are a company called Corcept Therapeutics that
Dr. Schatzberg founded, and a drug called Mifepristone or RU 486 that is in clinical trials for a
severe form of depression. Interest in this case is especially high because Dr.
Schatzberg is the president-elect of the American Psychiatric
Association. Daniel
Carlat, Clin Psych, and University Diaries have had
cogent commentaries on the wider implications of this breaking issue.
The University issued a statement
in response to Sen. Grassley. This statement asserted that Dr. Schatzberg has fully complied with the University’s
rigorous conflict of interest policy and that Dr. Schatzberg
“has not been involved in managing or conducting any human subjects
research involving Mifepristone, a pharmaceutical
that Corcept licenses for the treatment of psychotic
major depression.”
Stanford’s account of Dr. Schatzberg’s arm’s-length
role in Stanford’s NIH-supported studies of RU 486 (mifepristone)
for depression is questionable, if not disingenuous. Dr. Schatzberg’s
patent application filing for use of RU 486 in depression occurred in 1997, and
he founded the corporation Corcept Therapeutics in
1998. He was a member of the board of directors from 1998 to 2007. He has chaired
the corporation’s scientific advisory board since 1998.
There is reason to believe that Dr. Schatzberg had a
key role in Stanford’s clinical trials of Corcept’s
drug reported in 2001, 2002, and 2006. He was a co-author on all three
publications, and there was no disclaimer about his role until 2006. This
disclaimer is hardly credible. As Principal Investigator on the NIH grants, Dr.
Schatzberg was expected to supervise the junior
faculty and research staff at Stanford who recruited, assessed, and treated
patients in the studies of RU 486. He was responsible for the choice of outcome
measures, about which questions have been raised. He was responsible for the
quality of the reported data analyses, which were, frankly, inexpert, when they
were provided at all. Above all, he was responsible for the tone of the
NIH-supported Stanford publications that claimed Corcept’s
drug is effective.
If there were any doubt that Dr. Schatzberg’s hands
were all over these Stanford studies, one only has to see the record of his
leading role in responding to scientific critiques of their design, execution,
analysis, and interpretation. He was clearly the manager.
Moreover, the record is clear that Corcept relied on
the NIH-supported Stanford publications for positive claims to enable the
corporation to raise capital (well over $100 million by now, with nothing to
show for it). Corcept’s own Phase III clinical trials
have been uniformly negative. For this strategy to succeed, the Stanford trials
had to be portrayed as positive. As Paul Jacobs detailed in the San Jose
Mercury News in 2006, using independent statistical experts, Dr. Schatzberg and his Stanford/Corcept
colleagues made seriously exaggerated claims for the drug’s efficacy in their
2001 and 2002 publications. These exaggerated claims have been assiduously
repeated by Dr. Schatzberg, by Stanford faculty
members answerable to him, and by academic members of Corcept’s
scientific advisory board in many scientific journals and textbooks. All these
testimonials are compromised. The effect of these repeated, unjustified, claims
is to raise the profile of the corporation and of the drug. It amounts to
public relations and branding through academic outlets. Roy Poses on this site
has dissected
the scientific credibility of claims for the utility of RU 486 in depression.
Far from being removed from the scientific debate about Corcept’s
drug, Dr. Schatzberg has had the leading role in “selling”
the story to the scientific community, in “defending the brand” against
scientific criticisms, and in providing his corporation a plausible story line
to attract new capital. It was Dr. Schatzberg who
talked about how the drug “may be the equivalent of shock treatments in a pill”
in a 2002 Stanford press release. There is no clear boundary between Dr. Schatzberg’s NIH-supported academic roles and his service
to the corporation he founded. As for not being involved in the management of
the Stanford projects, Dr. Schatzberg acknowledged to
Paul Jacobs of the San Jose Mercury News “that he has considerable influence
over the junior faculty members doing the studies. As chairman of psychiatry,
he helps set their salaries and can affect their career advancement. And he
continues as a co-author of the resulting papers.”
I have already commented
on Dr. Schatzberg’s efforts
to sell large parcels of Corcept stock during the
company’s IPO attempts. Had these efforts been successful, Dr. Schatzberg would have benefited by $7-11 million, while
still retaining over 2 million shares of Corcept
stock. This aspect of the issue troubles many people. In our capitalist system,
considered so necessary for developing innovative drugs, nobody complains when
an entrepreneur makes a fortune inventing a useful product. Dr. Schatzberg’s apparent intent, however, was to reach for the
reward before contributing any product of redeeming social value. The prospects
of RU 486 succeeding as a useful treatment of psychotic depression are close to
zero. People view such behavior as gaming the system.
Moreover, under Stanford’s existing rules, these projected stock sales might
never have been reported.
Are these significant conflicts of interest? Yes. Have they “influence(d)
the conduct of medical research” at Stanford (quoting now from Stanford’s June
24 statement)?
Yes. Dr. Schatzberg’s NIH grants dovetail with the
efforts of his corporation, and the corporation used data from the
NIH-grant-supported projects for commercial promotion. Had the corporation not
existed, these particular grants likely would not have been initiated or would
have had different scientific emphases. Has Dr. Schatzberg’s
research “been compromised by his financial stake”? Yes. His academic
publications on depression and RU 486 are compromised by exaggerated and
self-serving claims for his corporation’s drug. Senator Grassley is right: it
is time for Stanford to get real about corporate-academic boundaries.
This column was written by Dr.
its original version here.
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