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August 1, 2008
Psychiatric Times. Vol. 25 No. 9
News
Conflicts Grow Over Conflicts-of-Interest Policies and Practices
Arline Kaplan
Debates over conflicts of interest
(COIs) in medical research and practice are intensifying with recent
proposals to ban industry funding of medical education, to better
“manage” industry-physician relationships, and to mandate public
disclosure of industry payments to physicians and medical institutions.
Caught in the cross fire are prominent psychiatrists accused of
underreporting payments received from pharmaceutical companies. |
Harvard is among the medical schools re-evaluating its current policies and considering improvements. One catalyst for the review is Sen Charles Grassley (R, Iowa), who accused 3 psychiatrists at Massachusetts General Hospital (MGH), an affiliate of Harvard Medical School (HMS), of violating federal and university research COI policies.
In the June 4 Congressional Record, Grassley claimed that Joseph Biederman, MD, Thomas J. Spencer, MD, and Timothy E. Wilens, MD, of MGH failed to report the full amount they earned from drug companies over a 7-year period. Only after Harvard and MGH asked the psychiatrists to take a second look at the money they had reported receiving, Grassley said, did Biederman admit “to over $1.6 million from the drug companies,” while Spencer admitted to “over $1 million,” and Wilens reported “over $1.6 million.”
Grassley charged that Biederman and Wilens were awarded grants from the NIH to study atomoxetine (Strattera) and “if a researcher is taking money from a drug company while also receiving federal dollars to research that company’s product, then there is a conflict of interest.”
Grassley’s accusations against the psychiatrists were covered in the media, including The New York Times (June 8, 10). Grassley also sent letters to NIH Health Director Elias Zerhouni, Harvard President Drew Faust, and MGH President Peter Slavin requesting further detailed information about the grants and COI procedures by mid-June.
Both institutions are cooperating with Grassley’s investigation, said HMS spokesperson David Cameron, “but we are not releasing our correspondence to the senator in deference to his process.”
According to current policies, HMS faculty members cannot participate in clinical research on a company’s technology (eg, compound, drug, or medical device) and receive consulting fees of more than $20,000 from that company.
HMS Office of the Dean has referred the cases of the 3 psychiatrists to the Standing Committee on Conflicts of Interest and Commitment for review. Its findings and recommendations will be forwarded to the dean for further action. Sanctions can include formal admonition, ineligibility for grant applications, and dismissal from the faculty.
Meanwhile, HMS Dean Jeffrey Flier, MD, announced a new cycle of mandatory COI disclosures for all HMS and School of Dental Medicine faculty, specifically reminding them to include CME speaking engagements and outside activities that relate to their roles as a faculty member regardless of the amount of financial interest involved.
HMS also is evaluating its efforts to educate faculty members about COI rules, reviewing the disclosure forms and re-examining its COI policies as they relate to the institution, individuals, and special issues presented by clinical research.
This fall, Harvard is planning a university-wide review of its policies on COI. At MGH, Slavin with David Torchiana, MD, chairman and chief executive officer of the Physicians Organization, in a joint letter said that MGH is undertaking a “thorough internal review of all the issues” raised by Grassley. Also, MGH leadership, they said, is participating in a taskforce initiated by Partners HealthCare, the hospital’s parent organization. The taskforce will examine and, if necessary, revise MGH’s policies relating to its interactions with industry.
In their own defense, the 3 psychiatrists have issued public statements. “I have devoted my entire career to scientific research that benefits the sick and suffering. My interests are solely in the advancement of medical treatment through rigorous and objective study,” said Biederman. “I have cooperated fully with all requests for information from Senator Grassley, as communicated through the institutions that employ me. Through my full and complete disclosure of the requested information, I hope that Senator Grassley will recognize my long-term intention to comply fully with and adhere to the conflicts of interest policies of those institutions. I have always taken those policies very seriously and will continue to do so for the rest of my career.”
Wilens noted, “Speaking to colleagues at conferences and other gatherings is one of the best ways to discuss developments and share ideas in the treatment of children with ADHD and other similar disorders. In accepting these invitations to speak, and in what I reported on my disclosure forms, I have always believed that I was acting within the applicable relevant guidelines and rules.”
Spencer talked of his deep commitment “to helping children with ADHD and other similar disorders find treatments that can help improve their lives. Presenting the findings of our clinical trials to other doctors in this field at conferences helps to keep them up to date on the latest developments and generate new ideas. It was my sincere belief that I was at all times complying with the relevant policies and procedures as to outside income.”
“Sweeping changes are under way at Harvard Medical School,” observed Stone.
“It seems clear to me that the most important issue for psychiatrists and their patients is the scientific rigor and validity of the published research itself. I have good reason to believe that the economic influences cited by Senator Grassley did not bias this important clinical research, but such assurances need to come from those who are more qualified to speak.”
Less confident in the research is E. Fuller Torrey, MD, executive director of the Stanley Medical Research Institute, a nonprofit organization supporting research for schizophrenia and bipolar disorder.
“There is no question that industry sponsorship affects the results of drug trials, and this has been well documented,” he said, noting that “tainted research” is of “limited usefulness.”
“Insofar as psychiatrists are known to be taking gifts and favors from drug companies,” he added, “it seriously undermines patient trust in their psychiatrist.”
Continuing Investigation
More accusations and revelations about the drug industry’s influence on research are under way. In the June 23 Congressional Record, Sen Grassley said that he has sent letters to almost 2 dozen research universities across the United States asking questions about the COI disclosure forms signed by some of their faculty.
At the same time, he raised questions about Alan Schatzberg, MD, Psychiatric Times’s editorial board member and APA’s president-elect. Grassley contended that there was a “lack of consistency” between what was reported in financial disclosures to Stanford University, where Schatzberg is professor and chair of the department of psychiatry and behavioral sciences, and what the drug companies said he was paid. The discrepancies total about $70,000. Stanford immediately responded that there was no reporting error by Dr Schatzberg. The university said that Schatzberg—contrary to Sen Grassley’s claim—did disclose to the university a $22,000 payment from Johnson & Johnson in 2002. The payment came from Janssen—the wholly owned subsidiary of Johnson & Johnson.
In addition, Sen Grassley claimed that in 2004, Schatzberg reported to Stanford that he received between $10,000 and $50,000 from Eli Lilly, but Eli Lilly’s reports showed $52,000. Stanford responded that Schatzberg disclosed 3 different sources of compensation from Lilly: less than $10,000 for being on the advisory board, $10,000 to $50,000 for consultation, and $10,000 to $50,000 for honoraria; “together, this disclosure fully accounts for the 2004 payments from Lilly.”
Other discrepancies cited by Sen Grassley most likely resulted from differences in record-keeping and fiscal years, Stanford said.
The ranking Republican on the Senate Finance Committee also questioned the thoroughness of Stanford’s COI guidelines.
Stanford responded in a June 25 press statement: “Based on our
extensive investigation to date, we believe Schatzberg has fully
complied with the University’s rigorous conflict of interest policy.”
As described in the statement, Schatzberg was the original principal
investigator on a NIMH grant exploring the biology of psychotic
depression in the 1990s. That work led to Stanford’s receiving a patent
for certain uses of the drug mifepristone (known as Corlux). When
Stanford received the patent, it licensed it to Corcept Therapeutics, a
company engaged in developing medications for treating severe
psychiatric and metabolic diseases. Mifepristone is in Phase 3 trials
for psychotic depression and has received the FDA’s fast-track status.
Stanford received a small amount of equity in Corcept under a
technology license but later divested the stock in order to adhere to
its policy on institutional COI.
Schatzberg, a cofounder of Corcept Therapeutics in 1998, served as a
member of its board of directors through 2007, and now chairs its
scientific advisory board.
“Before the patent was issued, Dr Schatzberg did not have any financial
interest in this drug. Once he was aware he was going to have a
financial interest in mifepristone, he disclosed it, and Stanford
University managed the conflict of interest,” Stanford responded.
While acknowledging that Schatzberg “appropriately disclosed to
Stanford that his [Corcept] stock shares were valued at over $100,000,”
Sen Grassley complained that amount did not capture the stock’s true
value—some $6 million for the 2,738,749 shares Schatzberg beneficially
owned as of January 31. Sen Grassley expressed concern about Stanford’s
ability to adequately monitor Schatzberg’s COI with its current
disclosure policies and called for a re-examination of them.
Stanford University responded that it was “fully aware” of the extent
of Schatzberg’s stake in Corcept Therapeutics and managed the COI to
ensure it did not influence the research he was conducting. According
to the university, Schatzberg consistently discloses that his ownership
of equity in Corcept is in excess of $100,000 (the highest dollar
category on the university’s COI form), and that he further disclosed
in writing his ownership of the Corcept stock and its actual value
during reviews conducted by the Conflict of Interests Committee at the
School of Medicine as well as the Institutional Review Board.
Stanford’s statement went on to emphasize that “Schatzberg has not been
involved in managing or conducting any human subjects research
involving mifepristone” and that “Stanford and Dr Schatzberg disclosed
this conflict and the fact that Stanford was managing the conflict to
NIH.”
Sen Grassley’s concerns about Schatzberg’s disclosures of drug company
payments were also addressed in Stanford’s response.
NIH
Grants
Each year, the NIH distributes an estimated $24 billion in extramural
funds. In fiscal year 2007, HMS received $172 million in grants from
the NIH and MGH received $300 million. NIH investigators must disclose
to their institution any “significant financial interest” that may
appear to affect the results of a study. Significant interest is
defined as $10,000 in value or 5% ownership in a single entity.
In his Congressional Record statement, Grassley
criticized the NIH’s oversight of the extramural program as being “lax”
with nobody ensuring that COIs are being monitored.
In response, an NIH spokesman told the press that if violations of NIH
policy have occurred and research integrity is compromised, “we will
take all the appropriate action within our power to hold those
responsible accountable.”
Asked how the government and public could ensure that the results of
clinical trials are unbiased, Torrey responded that clinical trials
should be supported by NIMH with its $1.4 billion budget and not by the
pharmaceutical industry.
“NIMH was a leader in supporting drug trials in the 1970s but then got
out of the business in the 1980s and ceded it to drug companies,” said
Torrey, who used to work at NIMH. In addition, NIMH should require its
grant applicants to submit full disclosure of all funds being received
from pharmaceutical companies. For clinical trials, he said, the review
committee should consider COI as part of the criteria in its
deliberations.
Grassley, along with Sen Herb Kohl (D, Wis), is offering another
approach—the Physician Payments Sunshine Act (S. 2029)—that would
require drug and medical device manufacturers with revenues of more
than $100 million to report publicly any payments that they make to
physicians within certain parameters.
As of 2007, 5 states and the District of Columbia have laws mandating
state disclosure of payments made to physicians by pharmaceutical
companies.6 Other states are considering similar proposals,
but Grassley favors a national law.
Torrey said he supports Grassley’s efforts and mandatory disclosure,
and Robert Hendren, DO, and Larry Greenhill, MD, president and
president-elect of the American Academy of Child and Adolescent
Psychiatry (AACAP), respectively, recently submitted a letter to The
New York Times.
“Researchers in all areas and specialties of medicine need to be
forthright about their funding sources,” they said. “This congressional
bill, along with educational efforts under way at AACAP, will go far in
reinforcing the trust families have in our profession.”
1. American Medical Association, Council on Ethical and Judicial Affairs. Industry support of professional education in medicine. Report 1 A-08. http:// www.ama-assn.org/ama1/pub/ upload/mm/471/ceja1-2.doc. Accessed June 17, 2008.
2. Campbell EG, Weissman JS, Ehringhaus S, et al. Institutional academic industry relationships. JAMA. 2007;298:1779-1786.
3. Institute of Medicine. Conflict of interest in medical research, education, and practice. http://www.iom. edu/CMS/3740/47464.aspx. Accessed June 18, 2008.
4. Association of American Medical Colleges. AAMC calls for strict limits on industry support of medical education [press release]. http://www.aamc.org/newsroom/pressrel/2008/080619. Accessed June 19, 2008.
5. Ehringhaus SH, Weissman JS, Sears JL, et al. Responses of medical schools to institutional conflicts of interest. JAMA. 2008;299:665-671.
6. Ross JS, Lackner JE, Lurie P, et al. Pharmaceutical company payments to physicians: early experiences with disclosure laws in Vermont and Minnesota. JAMA. 2007;297:1216-1223.
Psychiatric Times. Vol. 25 No. 9
The Age of Conflicts—of Interest
"Careers, money, and fame are at stake." J. Willwerth1
Long before he became a saint, Augustine of Hippo (354-430 AD) knew
something about temptation. “. . . when [Augustine] reached Carthage,
towards the end of the year 370, every circumstance tended to draw him
from his true course: the many seductions of the great city that was
still half pagan, the licentiousness of other students, the theatres,
the intoxication of his literary success, and a proud desire always to
be first, even in evil.”2
Although Augustine was eventually to overcome such temptations—becoming
Bishop of Hippo at age 42—I will always identify with the poignant plea
of Augustine’s wilder days:
“Lord, grant me chastity and continence, but not yet.”
In our own time, many so-called conflicts of interest (COI) boil
down to temptation, as James DuBois,3
professor and department chair of health care ethics at Saint Louis
University, notes in his excellent chapter on this subject. A
physician-researcher is tempted to slant the results of his or her
study in order to maintain funding from a medical technology company. A
psychiatrist is tempted to write a glowing opinion piece on a new
antipsychotic in order to remain on the pharmaceutical company’s
“speaker’s bureau.” A cardiologist is tempted to order coronary CT
angiography on all his patients with angina in order to pay off the
cost of the expensive new equipment—despite the unclear benefits of
this technology.
But the words “in order to” are a bit misleading. For in each instance,
the physician or researcher may not even be aware of his real
motivation. We are all quite capable of rationalizing our own
self-interest in the name of “the patient’s well-being,” “the need for
the latest technology,” and so on.
As DuBois puts it, “One reason that COI can be so insidious is that
individuals are often unaware of their biases and the ways their biases
influence their behavior, often in self-serving manners.”3,4
Indeed, the opprobrium we may reflexively attach to the term “conflict
of interest” is unjustified. The term means simply, “a situation in
which financial or other personal considerations have the potential to
compromise or bias professional judgment and objectivity.”5
As DuBois points out, a conflict of interest “does not imply that a
professional intends to put his or her personal interests first; it
does not in itself imply any wrong-doing.”3
Why, then, has the issue of COI stirred up so much emotion and
consternation in recent months, particularly in the field of
psychiatry? It probably doesn’t help that Sen Charles E. Grassley (R,
Iowa) has been holding hearings looking into possible COI in the
psychiatry departments of Harvard and Stanford medical schools.6,7
The details of the allegations—involving underreporting of consulting
fees in the Harvard case and underreporting of stock ownership in the
Stanford case—are still unfolding. It is clear, however, that the
public trust has been damaged by these reports, particularly since the
integrity and validity of some research done at Massachusetts General
Hospital (on pediatric bipolar disorder) has now been called into
question.6 And when physicians lose the trust of the general
public, they have begun to lose the soul of their profession.
Psychiatric Times is not in a position to investigate
or judge the psychiatrists involved in Senator Grassley’s hearings or
to gauge the integrity of the research in question. Until all the facts
are known, I am inclined to give these psychiatrists the benefit of the
doubt. But I am also aware of my own conflicted feelings in this
matter: my instinct is to rally behind those I regard as friends and
colleagues. Thus, the need for a rigorous, independent investigation is
clear. It will not be enough for an internal committee at Massachusetts
General Hospital or at Stanford University to render a verdict.
Objective reviewers from outside these institutions must be a part of
any credible investigation.
For now, we at Psychiatric Times must ensure
that our own house is in order. This begins with our editorial
board—which includes some of the most respected names in the field of
psychiatry. With the exception of the editor-in-chief, who receives a
monthly stipend, members of the board are not paid for their editorial
work with Psychiatric Times, nor do they make executive
decisions regarding what we do or do not publish. They serve as unpaid
advisors and consultants to the editor-in-chief and the editor.
However, we do sometimes ask board members to review submissions for
relevance and accuracy and to recommend potential topics and authors.
There is clearly room for COI. For example, a board member with
substantial stock in a pharmaceutical company might—consciously or
not—tend to favor an article that praised a drug made by that company.
Yet the job of the editor-in-chief is not to banish any
psychiatrist—however brilliant and informed—who may have a potential
COI. Rather, it is the editor-in-chief’s job to know of potential
conflicts and to make executive decisions accordingly. One very
experienced journal editor told me that in certain cases, it is useful
to have a controversial article reviewed by someone who is known to
have a strongly opposing view—maybe even an “axe to grind”—in order to
ferret out weaknesses in the article. This amounts to using someone’s
bias in service of the truth—so long as the bias is known, weighed
carefully, and not allowed to determine the article’s fate.
Accordingly, Psychiatric Times will ask all members
of our editorial board to submit a detailed disclosure form, involving
such items as:
• Membership on a pharmaceutical company speaker’s bureau.
• Major stockholdings in a drug or medical device company.
• Receipt of funding for research, or of frequent honoraria, from such
companies.
I believe that this policy will help ensure fair and accurate
reporting, as well as balanced and scientifically grounded opinion and
commentary. So far as I’m aware, Psychiatric Times
will be one of a very few psychiatric publications requiring such
disclosure by its editorial board.
But what about the readers of Psychiatric Times? Should
they have the right to know of potential COI among editorial board
members? After considerable discussion with our board members, I
believe the answer is yes. Therefore, Psychiatric Times will
make the disclosures of board members available to our readers, either
in print, online, or both—we are still working out the logistics. In
addition, we will move toward a similar policy of detailed disclosure
for the authors of our major clinical and CME pieces.
Arguably, every editor whose publication relies on advertising revenues
from major pharmaceutical companies has a potential conflict of
interest. That said, in my time as both Science Content Editor and
Editor-in-Chief, I have never once been asked to reconsider or revise
any articles, owing to concerns on the part of an advertiser or
corporate officer. Furthermore, we have at least 3 “lines of defense”
that help us keep our writing scientifically objective: our outside
peer reviewers; our Editorial Board members; and—perhaps most
important—our readers. Indeed, without the continued confidence of our
readership, there would likely be no advertisers willing to put up
money for ads.
Professor DuBois suggests—only half-facetiously, I think—that in order
to prevent COI entirely, we would need to develop a “vaccination”
against temptation. He is probably right. In the meantime, we can at
least avoid falling into the self-serving mind-set that says, “Lord,
grant me integrity and honesty—but not yet.”
"Conflicts Grow Over Conflicts-of-Interest Policies and Practices"
1. Willwerth J. How to tell if the men in white coats are lying to you (investigative journalism and research abuse). Account Res. 1997;5:51-58.
2. Herbermann CG, Pace EA, Pallen CB, eds. The Catholic Encyclopedia: An International Work of Reference on the Constitution, Doctrine, Discipline, and History of the Catholic Church. http://home.newadvent.org/cathen/02084a.htm. Published 1913. Accessed July 7, 2008.
3. DuBois JM. Ethics in Mental Health Research, Principles, Guidance and Cases. Oxford, UK: Oxford University Press; 2007.
4. Dana J, Loewenstein G. A social science perspective on gifts to physicians from industry. JAMA. 2003; 290:252-255.
5. Responsible Conduct of Research. Conflicts of interest. http://www.columbia.edu/ccnmtl/projects /rcr/ rcr_conflicts/foundation/index.html. Accessed July 7, 2008.
6. Harris G, Carey B. Researchers fail to reveal full drug pay. New York Times. June 8, 2008. http://www.nytimes.com/2008/06/08/us/08conflict.html?scp=1&sq=Researchers+fail+to+reveal+full+drug+pay&st=nyt. Accessed July 8, 2008.
7. Goldstein J. Grassley questions Stanford psychiatrist’s industry ties. Wall Street Journal. June 25, 2008. http://blogs.wsj.com/health/2008/06/25/grassley-questions-stanford-psychiatrists-industry-ties/. Accessed July 8, 2008.