Conflicts Grow Over Conflicts-of-Interest Policies and Practices

Arline Kaplan;

Publication

Article

August 1, 2008

Psychiatric Times

Psychiatric Times Vol 25 No 9

Volume25

Issue 9

Conflicts Grow Over Conflicts-of-Interest Policies and Practices

Author(s):

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.

At its June annual meeting, the AMA’s Council on Ethical and Judicial Affairs (CEJA) contended that existing mechanisms to manage potential COIs were “insufficient” and recommended that physicians and institutions of medicine, including medical specialty societies, not accept industry funding to support professional education activities, such as live or Web-based CME programs. It also asked medical schools to limit industry marketing on their campuses and urged health professionals to seek noncommercial funding of professional education activities.¹

CEJA’s report warned that commercial support of providers accredited by the Accreditation Council for Continuing Medical Education (ACCME) keeps rising, reaching $1.2 billion in 2006, and that academic medicine–industry relationships are entangled. To support its point, CEJA cited a 2006 national sur-vey of department chairs at US medical schools and teaching hospitals.² The survey showed that nearly two-thirds (60%) of the responding department chairs had some form of personal relationship with industry-including serving as a paid consultant (27%), a member of a scientific advisory board (27%), a paid speaker (14%), an officer or executive of a company (7%), a founder of a company (9%), or a member of the board of directors (11%). Two-thirds (67%) of departments as administrative units had relationships with industry (eg, 65% of clinical departments received industry funds for CME and 37% for residency training).

“The full CEJA report was presented to the House of Delegates, and some people were shocked by it,” said Mark Levine, MD, former CEJA chair and associate clinical professor at the University of Colorado’s School of Medicine. Other AMA members, he said, worried that the report called for immediate implementation (it does not) and some protested that it did not distinguish between certified CME and promotional activities.

On the recommendation of the reference committee, the AMA’s House of Delegates decided to refer it back to CEJA for possible changes and presentation at a subsequent AMA meeting, Levine added.

Alan A. Stone, MD, Touroff-Glueck Professor of Law and Psychiatry at Harvard University, warned that the economic entanglements between medicine and the pharmaceutical and medical device industry as well as other parts of corporate America “go much deeper than the general public and many doctors appreciate.”

These entanglements have occurred, in part, he said, because doctors have had to find other ways to make money, now that their income is limited by managed care.

“It is . . . going to be a very difficult task at this point to extract everyone in academia and in research from these economic connections,” Stone told Psychiatric Times. “For example, there are all sorts of distinguished professors who not only take money from drug companies but sit on their boards, and there are medical schools and drug companies in joint ventures. So the idea that we are going to find some simple way to extract ourselves from this set of problems I don’t think is going to happen.”

Policy Restrictions

Still, attempts are being made. As part of a 2-year project, the Institute of Medicine’s Committee on Conflict of Interest in Medical Research, Education, and Practice is sponsoring 6 hearings before creating a consensus report.³ The task of managing COIs, the committee said, has become more challenging since industry is now the leading funder of medical research and is involved in funding the development of evidence reviews and practice guidelines. At the committee’s March 13 meeting, Carolyn Robinowitz, MD, then American Psychiatric Association (APA) president, described APA’s COI procedures for meetings, publications, and DSM-V committees.

The consensus report, due before July 31, 2009, will examine COIs in research, practice guideline development, and other areas and will propose principles and policies to identify and manage COI “without damaging constructive collaboration with industry.”

In June, the Association of American Medical Colleges (AAMC) urged all medical schools and teaching hospitals to adopt policies that prohibit drug industry gifts and services to physicians, faculty, residents, and students and to limit industry support of CME activities. The recommendations were part of a new AAMC taskforce report, “Industry Funding of Medical Education,” that was unanimously approved by the association’s Executive Council. In adopting the report, the AAMC’s leadership urged all association members to implement policies and procedures, consistent with the report’s guidelines, by July 1, 2009.⁴

Among its recommendations, AAMC proposed that academic medical centers establish a central CME office to receive and coordinate the distribution of industry support for CME activities and strongly discourage participation by faculty in industry-sponsored speakers’ bureaus.

Other attempts to help prevent COI have involved determining which medical schools have already adopted both institutional and individual COI policies and practices and how comprehensive they are. Ehringhaus and others,⁵ for example, published a survey of deans in 125 medical schools to collect data on the existence and nature of policies for addressing potential institutional COI.

The American Medical Students Association (AMSA) also surveyed 150 academic medical centers to obtain their COI policies regarding industry interaction with medical school faculty and trainees to create a comparative scorecard and promote stronger policies. Each responding school’s policies were rated according to 11 potential areas of conflict, such as restrictions on gifts. Schools received A to F grades. Only 7 of the 150 medical schools included in the rankings received a grade of A on the AMSA PharmFree Scorecard 2008 (http://amsascorecard.org) posted in June. Sixty schools got a failing grade because of weak policies or failure to respond. Some 28 schools, or nearly 1 in 5, were in the midst of revising their COI policies.

Psychiatrists Accused

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.”