[Congressional Record (Bound Edition), Volume 154 (2008), Part 13] [Senate] [Pages 17671-17674] [From the U.S. Government Publishing Office, www.gpo.gov]PAYMENTS TO PHYSICIANS Mr. GRASSLEY. Mr. President, I have been examining several doctors at universities across the country to see if they are complying with the financial disclosure policies of the National Institutes of Health. I ask unanimous consent to have my latest letters to Stanford University and to the National Institutes of Health printed in the Record. I yield the floor. There being no objection, the material was ordered to be printed in the Record, as follows: U.S. Senate, Committee on Finance, Washington, DC, July 30, 2008. Dr. John L. Hennessy, President, Stanford University, Office of the President, Stanford, CA. Dear Dr. Hennessy: First, I would like to thank you for your prompt attention to the matter involving payments made by pharmaceutical companies to Dr. Alan Schatzberg, Chairman of the Department of Psychiatry at Stanford University (Stanford/University). Investigators with the Senate Finance Committee (Committee) believe that the following chart provides a better representation of Dr. Schatzberg's disclosures to Stanford and company reports to the Committee. Committee investigators understand that differences in reporting requirements and accounting methods may result in differences between Dr. Schatzberg's reports and reports from companies that can only be explained in writing. The Committee understands that Stanford will provide a comprehensive response to the initial letter sometime soon, which will include these details. Stanford has notified the Committee that any discrepancies in the chart are most likely due to differences in accounting between Stanford and the various companies contacted by the Committee. As Stanford pointed out in a public statement, there was an error in the chart that the Committee sent to you regarding payments from Eli Lilly to Dr. Schatzberg in 2007. That chart stated that Dr. Schatzberg had ``not reported'' this money when in fact he had. Therefore, this letter is being placed in the congressional record to correct the official record. Stanford also noted that Dr. Schatzberg's reports on payments from Eli Lilly in 2004 include compensation of less than $10,000 for advisory board activities and $10,000 to $50,000 for honoraria for papers, lectures and consulting. This also matches the footnote in the Committee's chart and appears to capture all the monies reported by Eli Lilly ($52,134) for that year. However, Committee investigators still have concerns regarding Johnson & Johnson's report of paying Dr. Schatzberg $22,000 [[Page 17672]] in 2002. According to Stanford's statement, ``Dr. Schatzberg did disclose this payment to the university and also reported it to the Committee. He disclosed the $22,000 payment from Jannsen, the wholly-owned subsidiary of Johnson & Johnson that made the payment.'' The reason that we continue to be concerned is because Dr. Schatzberg reported less than $10,000 from Jannsen for academic year 2002 (September 2, 2001 through August 31, 2002) and less than $10,000 for academic year 2003 (September 1, 2002 through August 31, 2003). Johnson & Johnson did not delineate payments from subsidiaries such as Jannsen when it reported the information to the Committee. Johnson & Johnson reported a payment of ``fee for services'' of $22,000 to Dr. Schatzberg on August 19, 2002. Even noting differences in accounting methods, Dr. Schatzberg's reports on Jannsen do not appear to fully explain the discrepancy. Inconsistencies also appear among the payments reported to us by Eli Lilly in 2002. Eli Lilly reported paying Dr. Schatzberg $19,788 that calendar year. However, Dr. Schatzberg reported that he received less than $10,000 from Eli Lilly for academic year 2002 (September 2, 2001 through August 31, 2002) and more than $10,000 for academic year 2003 (September 1, 2002 through August 31, 2003). Noting possible differences in accounting methods, Dr. Schatzberg's reports on Eli Lilly may explain the discrepancy, but only if one combined the 2002 and 2003 academic years. Further, based on documents in our possession, it appears that Wyeth paid Dr. Schatzberg for testifying as an expert witness in 2006. This work was in response to lawsuits brought against Wyeth regarding its antidepressant, Effexor. As Dr. Schatzberg wrote in an undated expert report on behalf of Wyeth, ``My hourly rate for review of materials or for testimony is $500.'' Dr. Schatzberg was apparently an expert witness in at least two cases for Wyeth, but payments for this work cannot be found in his reports of outside income to Stanford. Therefore, I would appreciate your clarification of Dr. Schatzberg's expert witness fees and how they are recorded on Stanford's financial disclosure forms. Thank you again for your continued cooperation and assistance in this matter. I look forward to a complete response to outstanding questions in the near future. If you have any questions, please do not hesitate to contact Paul Thacker at (202) 224-4515. Sincerely, Charles E. Grassley, Ranking Member. Attachment. SELECTED DISCLOSURES BY DR. SCHATZBERG AND RELATED INFORMATION REPORTED BY PHARMACEUTICAL COMPANIES AND DEVICE MANUFACTURERS ------------------------------------------------------------------------ Amount Disclosure filed company Year Company with institution reported (academic year) (calendar year) ------------------------------------------------------------------------ 2000 Bristol Myers Squibb. No amount provided.. $1,000 Eli Lilly............ No amount provided.. $10,070 2001 Bristol Myers Squibb. No amount provided.. $4,147 Corcept Therapeutics. >$10,000<$50,000 \1\ n/a Eli Lilly............ <$10,000 \2\........ $10,788 2002 Bristol-Myers Squibb. No amount provided.. $2,134 Corcept Therapeutics. >$100,000 \3\....... n/a Corcept Therapeutics. <$10,000 \1\........ n/a Corcept Therapeutics. <$10,000 \4\........ n/a Eli Lilly............ <$10,000............ $19,788 Johnson & Johnson <$20,000 \5\........ $22,000 (Jannsen). 2003 Bristol-Myers Squibb. No amount provided.. $4,000 Corcept <$10,000 \4\......... n/a................. Therapeutics Corcept Therapeutics. >$10,000<$50,000 \1\ n/a Corcept Therapeutics. >$100,000 \3\....... n/a Eli Lilly............ >$10,000............ $18,157 2004 Bristol-Myers Squibb. <$10,000............ $0 Corcept Therapeutics. >$10,000<$50,000 \1\ n/a Corcept Therapeutics. $100,000 \3\........ n/a Eli Lilly............ <$110,000........... $52,134 Pfizer............... Not reported........ $2,500 ------------------------------------------------------------------------ Reporting by Calendar Year ------------------------------------------------------------------------ 2005 Bristol-Myers Squibb. <$10,000............ $0 Corcept Therapeutics. >$10,000<$50,000 \1\ n/a Corcept Therapeutics. >$100,000 \3\....... n/a Eli Lilly............ >$10,000<$50,000.... $9,500 Pfizer............... No amount provided.. $2,000 2006 Bristol-Myers Squibb. Not reported........ \6\ $6,000 Corcept Therapeutics. <$10,000 \4\........ n/a Corcept Therapeutics. >$10,000<$50,000 \1\ n/a Corcept Therapeutics. >$100,000 \3\....... n/a Eli Lilly............ >$10,000<$50,000.... $20,500 Pfizer............... Not reported........ $300 2007 Eli Lilly............ <$60,000............ $10,063 ------------------------------------------------------------------------ \1\ Physician disclosed payment for a variety services including Advisory Board Membership, Board of Directors, and consulting. \2\ Physician disclosed <$10,000 for academic year 2001. No amount provided for prior academic year. \3\ Physician disclosed equity value. \4\ Physician disclosed payment for royalties from Stanford's licensing agreement with Corcept Therapeutics. \5\ This sum combines two academic years. \6\ Bristol-Myers Squibb stated that Stanford intended to pay Dr. Schatzberg $6,000 for conducting an annual course for which the company provides a grant. Note 1: When a Physician named a company in a disclosure but did not provide an amount, the text reads ``no amount reported.'' Stanford has noted that amounts were not required in each specific case. When a Physician did not list the company in the disclosure, the column reads ``not reported.'' The Committee contacted several companies for payment information and the notation n/a (not available) reflects that a company was not contacted. Note 2: The Committee was not able to estimate the total amount of payments disclosed by Dr. Schatzberg during the period January 2000 through June 2007 due to the fact that some amounts were not provided and in other instances ranges were used. Information reported by the pharmaceutical companies indicate that their reports do not match Dr. Schatzberg's disclosures. ____ U.S. Senate, Committee on Finance, Washington, DC, July 31, 2008. Dr. John L. Hennessy, President, Stanford University, Office of the President, Stanford, CA. Dear Dr. Hennessy: The Senate Finance Committee (Committee) recently sent you a letter attempting to clarify discrepancies in a chart comparing reports of payments made by several pharmaceutical companies against disclosures of outside income filed by Dr. Alan Schatzberg, a psychiatrist at Stanford (Stanford/University). As Committee investigators explained to Stanford officials, we have further questions regarding Dr. Schatzberg's grants from the National Institutes of Health and his relationship with Corcept Therapeutics (Corcept/Company). Corcept was founded in part by Dr. Schatzberg, who has several million dollars of equity in that company. In addition, I am interested in understanding Stanford's involvement with Dr. Schatzberg and Corcept. Dr. Schatzberg received grants from the National Institutes of Health (NIH) to study mifepristone and major depression. At the same time, Dr. Schatzberg received compensation from Corcept and had a large equity interest in the Company. This equity could grow dramatically if the results of Dr. Schatzberg's government sponsored research find that mifepristone could be used to treat psychotic major depression. I have come to understand, based on documents provided to me by Stanford, that your institution had and may still have a financial relationship with Corcept. This agreement has resulted in Stanford paying Dr. Schatzberg royalties. For instance, Dr. Schatzberg reported in his Stanford disclosures that he received payments of less than $10,000 for royalties from Stanford's licensing agreement with Corcept Therapeutics. These payments were made in 2002, 2003, and 2006. As is well established, the NIH relies on universities to manage the conflicts that exist between a grantee and any outside financial interests. However, not only does Dr. Schatzberg have a financial interest in Corcept, but Stanford also had a relationship with Corcept and may still at this time. These facts raise multiple questions and concerns. For example, how can Stanford manage Dr. Schatzberg's conflicts of interest with Corcept, when Stanford apparently has a similar conflict of interest? Furthermore, when did Stanford notify the NIH of this conflict? Additionally, I have many questions and concerns about Stanford's recent press statement regarding how it managed Dr. Schatzberg's conflicts of interest with Corcept. In that statement, Stanford claimed that steps to manage this conflict ``included his not participating in any human subjects research involving mifepristone. . . .'' However, based upon a search of published literature, Dr. Schatzberg's name appears as the author of several published studies involving human subjects research and mifepristone. Most of these studies were funded by NIH although one study was funded by Corcept and another one was funded by both the NIH and Corcept. These studies include: 2002--Dr. Schatzberg was the final author on a paper in Biological Psychiatry that reported on a trial to study mifepristone to treat psychotic major depression in 30 patients. The study listed support by Corcept along with two grants from the National Institute of Mental Health (MH50604 and T-32MH19983), which is one of the NIH's institutes. Dr. Schatzberg is the primary investigator for grant MH50604. 2006--Dr. Schatzberg published a study involving human subjects treated with mifepristone for psychotic major depression. This study was supported by several NIH grants. Dr. Schatzberg is the primary investigator for three of these grants (R01 MH50604, R01 MH47573, T32 MH019938). In the acknowledgements section of the paper, Dr. Schatzberg disclosed that he had a financial interest in Corcept which has a licensing agreement for mifepristone. Dr. Schatzberg also disclosed that he ``played no direct role in the recruitment, assessment, or follow-up of subjects enrolled in this study,'' and ``was not directly involved in the analysis of data stemming from this research.'' (emphasis added) I am not in a position to interpret the disclosures and apparent recusals from research involvement made by Dr. Schatzberg in the 2006 study, however, I am seeking guidance from Stanford regarding its duties to ``manage'' conflicts in light of a possible contradiction. According to the ``NIH Grants Policy Statement,'' the primary investigator of an NIH grant is ``responsible for the scientific or technical aspects of the grant and for day-to-day management of the project or program.'' So, the question arises: how could Dr. Schatzberg monitor the research funded with his NIH grants if he was not involved closely in the study? I also would appreciate your guidance on how Dr. Schatzberg could have been recused from involvement in research when he is listed as the primary investigator for several trials. For instance, Stanford's website has a clinical trials directory, which lists Dr. [[Page 17673]] Schatzberg as a co-investigator for a trial seeking to enroll 20 patients in a study using mifepristone to treat patients with psychotic major depression. The anticipated start of the trial was January 1, 2003 and the listed collaborator for the trial is the NIH. Dr. Schatzberg is also listed as the primary investigator on ClinicalTrials.gov for another study that began in 2005 to treat depressed patients with mifepristone. This NIH funded trial is listed as active, but not recruiting patients. The estimated enrollment was 100 patients in this randomized, double-blind, placebo-controlled study. In addition, Dr. Schatzberg is listed on ClinicalTrials.gov as the ``study director'' for a phase III clinical trial to ``evaluate the effectiveness of mifepristone to treat adults with psychotic major depression.'' This trial is also funded by the NIH and is now actively recruiting patients. Further, Stanford acknowledges in its press statement that it ``received a small amount of equity in Corcept under a technology license.'' However, Stanford did not explain when this relationship began or ended. And according to Dr. Schatzberg's 2006 study, Stanford's Institutional Review Board (IRB), which is responsible for approving study protocols, approved his research plan. This raises even more questions regarding how Stanford's IRB could remain independent, especially since Stanford had a financial stake in ensuring that the study protocol was approved. I seek your thoughts on this issue as well. Finally, last February the Association of American Medical Colleges (AAMC) released guidelines governing conflicts of interest. The AAMC advised that institutions report conflicts of interest ``in any substantive public communication of the research results.'' However, when Stanford issued a press release regarding the results of Dr. Schatzberg's research on mifepristone, the statement did not note if Dr. Schatzberg and/or Stanford had a financial interests in the research findings. Stanford missed another opportunity to disclose financial interests in a story that ran in the Stanford Report which reported on Dr. Schatzberg's mifepristone research. I would also like to better understand Stanford's current and past financial relationship with Corcept. Accordingly, please respond to the following questions and requests for information. The time span for this request covers 1995 to the present. For each response, please repeat the enumerated request and follow with the appropriate answer. (1) Please explain Stanford's previous and current financial relationship with Corcept Therapeutics. This response should include the date when Stanford first established a relationship with Corcept Therapeutics, the nature of that relationship, and the date when Stanford divested itself of any financial relationship(s) with Corcept. Also, detail any financial transactions between Stanford and Corcept Therapeutics (i.e. has Stanford invested in Corcept or has Corcept paid a licensing fee to Stanford). (2) Please provide a list of all patents and licenses held by Dr. Schatzberg. For each patent and/or license, please provide the following: (a) Provide a summary of the patent/license. (b) When was the patent/license first issued? (c) For each patent/license, please list any companies that have a financial interest in the success of that patent/ license. (d) Please provide an accounting of any compensation paid to Dr. Schatzberg for any patent/license, detailed by dollar amount and year. (3) Please provide a list of all studies published by Dr. Schatzberg that involve mifepristone or major depression. For each study, please provide the following: (a) Please list the grant(s) which funded each study, in whole or in part. (b) If an author listed on the study was at Stanford, please list their department, supervisor, and financial support, at that time. (4) For each study identified above, please provide the name of each member of the Institutional Review Board (IRB) that approved the study protocol. For each IRB, please provide the following information: (a) Please provide minutes of the IRB meeting when that study was discussed. (b) Please explain if the IRB considered financial interests of study investigators and/or Stanford in approving the study protocols. (c) Please explain if the IRB required reporting of conflicts of interests to human subjects participating in the study. (d) Please provide a point of contact for the IRB. (5) According to federal regulations, ``prior to the Institution's expenditure of any funds under the award, the Institution will report to the [Public Health Service] Awarding Component the existence of a conflicting interest (but not the nature of the interest or other details) found by the institution and assure that the interest has been managed, reduced or eliminated.'' Please provide the date and supporting documents that show when Stanford determined that Dr. Schatzberg had a conflict of interest regarding his federal funding of mifespristone research. (6) Please provide the date and supporting documents that show when Stanford reported this conflict to the NIH. (7) Please provide the following information on Corcept: (a) When did Dr. Schatzberg create Corcept? (b) When did Corcept apply to the FDA for approval of mifepristone to treat psychotic major depression? (c) When did Dr. Schatzberg first become vested in the company? (8) Please explain how Stanford manages a conflict of interest with NIH funded researchers if Stanford has a financial interest in the outcome of the study. (9) According to Stanford's press statement, ``In addition, NIH reviews its data through its Data Safety and Monitoring Board structures.'' Please provide documentation that a Data Safety Monitoring Board (DSMB) at the NIH has been apprised of Dr. Schatzberg's and/or Stanford's financial interests in Corcept. (10) The AAMC advises institutions to report conflicts of interest ``in any substantive public communication of the research results.'' Please explain Stanford's policies for reporting conflicts of interest in press releases and other publications controlled by Stanford. (11) Dr. Schatzberg has reported in a 2006 publication that he ``played no direct role in the recruitment, assessment, or follow-up of subjects enrolled in this study,'' and ``was not directly involved in the analysis of data stemming from this research.'' Please explain how, with such constraints, Dr. Schatzberg was able to monitor the spending of his NIH grants. Thank you again for your continued cooperation and assistance in this matter. As you know, in cooperating with the Committee's review, no documents, records, data or information related to these matters shall be destroyed, modified, removed or otherwise made inaccessible to the Committee. I look forward to hearing from you by no later than August 14, 2008. All documents responsive to this request should be sent electronically in PDF format to Brian_Downey@finance- rep.senate.gov. If you have any questions, please do not hesitate to contact Paul Thacker. Sincerely, Charles E. Grassley, Ranking Member. ____ U.S. Senate, Committee on Finance, Washington, DC, July 31, 2008. Elias A. Zerhouni, M.D., Director, National Institutes of Health, Bethesda, MD Dear Director Zerhouni: As a senior member of the United States Senate and the Ranking Member of the Committee on Finance (Committee), I have a duty under the Constitution to conduct oversight into the actions of executive branch agencies, including the activities of the National Institutes of Health (NIH/Agency). In this capacity, I must ensure that NIH properly fulfills its mission to advance the public's welfare and makes responsible use of the public funding provided for medical studies. This research often forms the basis for action taken by the Medicare and Medicaid programs. I would like to follow up with you on my concerns about the lack of oversight regarding conflicts of interest relating to the almost $24 billion in annual extramural funds that are distributed by the NIH. I appreciate the comments you made recently during the NIH appropriations hearing where you mentioned several times that we need more ``sunshine.'' I could not agree more. I recently sent several letters to Stanford University (Stanford/University) regarding Dr. Alan Schatzberg, chair of Stanford's department of psychiatry. I am attaching those letters for your review and consideration. According to information found on the NIH's CRISP database of extramural grants, Dr. Schatzberg has/had NIH grants to study mifepristone as well as major depression. At the same time it appears that he has also had an ongoing financial relationship with Corcept Therapeutics (Corcept/Company). Corcept is seeking approval from the Food and Drug Administration for mifepristone to treat psychotic major depression. Corcept was founded (in part) by Dr. Schatzberg and he has several million dollars of equity in the company. Dr. Schatzberg has also received payments over several years from Corcept and has received payments directly from Stanford because of its licensing agreement with Corcept for mifepristone. The intertwined relationship between Stanford, Dr. Schatzberg, and Corcept was first reported in 2006 in a two- part series that ran in the San Jose Mercury News. In light of this article, I am interested in understanding if the NIH investigated potential conflicts of interest after this series appeared. I would also like to know when Stanford first notified the NIH that Dr. Schatzberg had a conflict of interest regarding his large equity interest in Corcept. Stanford's attempts to manage Dr. Schatzberg's conflicts of interest and his NIH grants raise several questions. According to Stanford's recent press statement, this management ``included his not participating in any human subjects research involving mifepristone. . . .'' However, Dr. [[Page 17674]] Schatzberg's name appears as the author of several published studies involving human subjects research and mifepristone. One of these studies was funded by Corcept, some were funded by the NIH, and one was funded by both Corcept and the NIH. For instance, in 2006, Dr. Schatzberg published a study involving human subjects treated with mifepristone for psychotic major depression. This study was supported by several NIH grants. In the acknowledgements section of the paper, Dr. Schatzberg disclosed that he had a financial interest in Corcept Therapeutics, which has a licensing agreement for mifepristone. Dr. Schatzberg also disclosed that he ``played no direct role in the recruitment, assessment, or follow-up of subjects enrolled in this study,'' and ``was not directly involved in the analysis of data stemming from this research.'' This disclosure raises some interesting questions regarding Dr. Schatzberg's involvement in the study. Specifically, how could Dr. Schatzberg monitor the research funded with his NIH grants if he was not involved closely in the study? Dr. Schatzberg was also a lead investigator in a study on mifepristone for treating psychotic major depression back in 2002. This study was supported by a grant from Corcept along with related support from the National Institute of Mental Health (NIMH), one of the NIH's institutes. I am wondering how such grants are provided and how the possible conflict of interests are managed and by whom. Furthermore, Dr. Schatzberg is listed as the primary investigator on ClinicalTrials.gov for another study to treat patients with depression with mifepristone, which began in 2005. This NIH funded trial is listed as active but is not recruiting patients. The estimated enrollment was for 100 patients in this randomized, double-blind, placebo-controlled study. Also, Dr. Schatzberg is listed on ClinicalTrials.gov as the ``study director'' for a phase III clinical trial to ``evaluate the effectiveness of mifepristone to treat adults with psychotic major depression.'' This trial is also funded by the NIH and is now actively recruiting patients. According to the ``NIH Grants Policy Statement'' the primary investigator of an NIH grant is ``responsible for the scientific or technical aspects of the grant and for day-to- day management of the project or program.'' So the question arises: how could Dr. Schatzberg monitor the research funded with his NIH grants if he was not involved closely in the study? I also understand that Stanford had a licensing agreement with Corcept and was paying royalties to Dr. Schatzberg for several years. Again, I am wondering how Stanford could manage Dr. Schatzberg's conflicts when it also has a financial interest in the company and the research outcome. I would appreciate a greater understanding of Stanford's role in ``managing'' Dr. Schatzberg's conflicts of interest regarding his NIH grants to study mifepristone. Accordingly, please respond to the following questions and requests for information. The time span of this request covers 1995 to the present. For each response, please repeat the enumerated request and follow with the appropriate answer. 1. Following the series by the San Jose Mercury News, did the NIH examine Stanford's management of Dr. Schatzberg's conflicts of interest? If yes, please provide me with copies of all pertinent documents and communications. If not, why not? 2. According to the ``NIH Grants Policy Statement,'' Dr. Schatzberg's role as the primary investigator of his NIH grants is to be ``responsible for the scientific or technical aspects of the grant and for day-to-day management of the project or program.'' How can Dr. Schatzberg live up to these obligations when Stanford's press statement claims that he ``played no direct role in the recruitment, assessment, or follow-up of subjects enrolled in this study,'' and ``was not directly involved in the analysis of data stemming from this research''? 3. Does the NIH allow researchers to recuse themselves from involvement in the research funded by their own NIH grants? If yes, did the NIH allow Dr. Schatzberg to recuse himself from any of the grants made to him by the NIH? 4. Please provide a list of all NIH grants received by Dr. Schatzberg. For each grant, please provide the following: a. Name of grant; b. Topic of grant; and c. Amount of funding for grant. 5. Please provide a list of any other interactions that Dr. Schatzberg has had with the NIH to include membership on advisory boards, peer review on grants, or the like. The span of this request covers 1998 to the present. 6. Stanford has claimed that Dr. Schatzberg's research has been monitored by an NIH Data Safety Monitoring Board (DSMB). Does the NIH DSMB provide oversight of conflicts of interest for a study? If so, please explain. If not, why not? I look forward to hearing from you by no later than August 14, 2008. If you have any questions, please contact my Committee staff, Paul Thacker at (202) 224-4515. Any formal correspondence should be sent electronically in PDF searchable format to Brian_D[email protected]. Sincerely, Charles E. Grassley, Ranking Member. ____________________