Conflicts of Interest at the NIH — Resolving the Problem
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《新英格兰医药杂志》
Since December 2003, the National Institutes of Health (NIH) has been battered by accounts of the outside financial arrangements between some of its employees and pharmaceutical companies — and hence by concerns that the NIH ethics program is not working.1,2 Having "reached the conclusion that drastic changes are needed," Dr. Elias Zerhouni, the NIH director, plans to implement prohibitions and restrictions on many of these payments and new requirements for public disclosure of those that are still allowed. Zerhouni is "working to strike a careful balance."3 He does not plan to ban all drug-industry payments to institute scientists. A ban has been criticized as a draconian measure that would discourage intellectual curiosity, interfere with the recruitment and retention of talented researchers, and prevent collaborations that benefit the nation's health and economy. However, some have advocated a ban as a more appropriate, simpler, and easier-to-implement remedy. Although many of the details have yet to be finalized, the NIH aims to implement its permanent new rules and a better internal ethics-oversight system by early 2005. Some of the changes will require new federal regulations.
A report last December in the Los Angeles Times examined consulting payments from pharmaceutical companies to high-ranking NIH officials1 — including the directors of the NIH Clinical Center and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, whose payments were subsequently stopped. The ethics program has since been intensively reviewed by the NIH Blue Ribbon Panel on Conflict of Interest Policies, which Zerhouni established4; by the Office of Government Ethics5; and by the Subcommittee on Oversight and Investigations of the House Committee on Energy and Commerce, among others.
The NIH has 27 institutes and centers and an annual budget of about $28 billion (see Figure). The controversy involves the 18,000 people who are direct NIH employees, not external researchers who are funded by the institutes. In January 2004, the NIH knew of 228 employees who had a total of 365 approved outside consulting agreements. As of June, the NIH knew of 118 employees who had a total of 196 approved agreements. The cumulative number of employees who have entered into consulting agreements since 1999 and the total number of agreements they have had — including some that were not approved — are still not known.
Figure. Change in NIH Appropriations, 1994–2005.
After the controversy arose, Dr. Raynard Kington, the deputy director of the NIH, was appointed the deputy ethics counselor for the agency and was placed in charge of the ethics program. In an interview in August, Kington said, "Employees know that there has been harm to the agency because of the questions about our integrity [and] compromises of our integrity which may have occurred as a result of outside activities." There has been no evidence that patients were harmed or that decisions made at the institutes were influenced by the outside financial activities of employees. However, according to Zerhouni's testimony at a House hearing in June, "The NIH and its employees were operating within rules that allowed or did not specifically address many of the arrangements that the Subcommittee has questioned, including lecture awards and consulting with industry. In retrospect, there was not a sufficient safeguard against the perception of conflict of interest."3
In one instance in 2002, a pathologist at the National Cancer Institute (NCI) and a microbiologist at the Food and Drug Administration were assigned, as part of their official duties, to lead a cooperative research and development effort with a Maryland company to develop a test for ovarian cancer. They subsequently received approval to serve as paid consultants to another firm that was a potential competitor — an arrangement that continued until congressional investigators uncovered it earlier this year. In another instance, Dr. Richard Klausner, the former director of the NCI, was allowed to accept a $40,000 prize from the University of Pittsburgh in 1997. At the time, the university was a major recipient of funding from the NCI, with which it had an ongoing contract dispute. It had also recently settled a lawsuit, brought by Dr. Bernard Fisher, a well-known cancer researcher at the university, in which the university, the NCI, and others were codefendants. Klausner was said to have orally approved the use of $300,000 in government funds as part of the $2.7 million settlement.
These situations have particularly troubled Representative James Greenwood (R-Pa.). Greenwood chaired the House subcommittee and spearheaded its probe until July, when he unexpectedly announced that he would leave Congress to become president of the Biotechnology Industry Council. He therefore recused himself from all duties that might conflict with his future job, including the NIH inquiry.
There have also been instances in which employees apparently did not disclose their outside consulting arrangements to the NIH, as has always been required. Of 155 outside activities reviewed by the Office of Government Ethics, 74 had not been approved in advance. Late approvals were found for 39 of the 74; no approvals were found for the other 35.5 House subcommittee staff members discovered many discrepancies when they requested information from drug companies and tried to match the consulting agreements to those provided by the NIH. For example, apparently unbeknownst to the NIH, a researcher at the National Institute of Mental Health was paid more than $517,000 in fees, honoraria, and expense reimbursements over a five-year period, according to Greenwood. The institutes are still investigating many cases, and "will probably have some examples of individuals who did not disclose their activities to the agency," according to Kington.
Zerhouni intends "to prohibit senior NIH employees, as well as all employees involved in extramural funding decisions, from consulting with industry for compensation or any other form of remuneration"3 (see Table). This includes senior staff in the office of the director; directors and deputy, clinical, and scientific directors at the institutes and centers; and members of the extramural staff. Some scientists — which ones and how many have not been determined — would be allowed to engage in outside consulting. They would be subject to a stricter internal approval process and new limits, such as a proposed maximum of 400 hours of outside consulting per year and a proposed compensation cap of 25 percent of their base salary. Zerhouni also intends "to prohibit the holding of stock in individual biotechnology and pharmaceutical companies as is done at the Food and Drug Administration." He will increase "the number of senior managers who must publicly disclose their compensated activities and the amounts received."3 The number of employees who would be subject to these rules has not been determined.
Table. Changes and Proposed Changes in NIH Policies Regarding the Outside Activities of Employees.
Some are urging tougher standards that would ban or nearly ban drug-industry payments to all NIH employees. In a report issued in July, Marilyn Glynn, the acting director of the Office of Government Ethics, discussed a "permissive culture" that has existed at the NIH and noted that "expanded disclosure is not a substitute for appropriate substantive standards of ethical conduct." Without broader restrictions than those currently contemplated, the institutes "could give the appearance that some level of misuse of office is tolerable." There are ongoing investigations by the Office of Inspector General of the Department of Health and Human Services and the Government Accountability Office, and there may be more congressional hearings after Labor Day.
The NIH seeks to eliminate the possibility that the activities of its employees could harm its public health mission because of real or perceived conflicts of interest. "The biggest challenge for all of us is the uncertainty," Kington said. "We are in the midst of drafting the final proposed regulations. We are in the midst of completing some of the investigations that are under way. I am optimistic that once we finalize what the rules will be, this will be behind us." For the moment, however, it is still unclear how restrictive the new rules will be and how many employees will be affected. The NIH has made progress, but its conflict-of-interest problem has yet to be resolved.
References
Willman D. Stealth merger: drug companies and government medical research. Los Angeles Times. December 7, 2003:A1.
Steinbrook R. Financial conflicts of interest and the NIH. N Engl J Med 2004;350:327-330.
Zerhouni EA. Testimony before the House Energy and Commerce Oversight Investigations Subcommittee, June 22, 2004. (Accessed August 13, 2004, athttp://olpa.od.nih.gov/hearings/108/session2/testimonies/conflictc.asp.)
Report of the National Institutes of Health Blue Ribbon Panel on Conflict of Interest Policies: a working group of the Advisory Committee to the Director National Institutes of Health, June 22, 2004. (Accessed August 13, 2004, at http://www.nih.gov/about/ethics_COI_panelreport.pdf.)
Willman D. NIH is pressured to bar drug industry stipends. Los Angeles Times. August 6, 2004:A1.(Robert Steinbrook, M.D.)
A report last December in the Los Angeles Times examined consulting payments from pharmaceutical companies to high-ranking NIH officials1 — including the directors of the NIH Clinical Center and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, whose payments were subsequently stopped. The ethics program has since been intensively reviewed by the NIH Blue Ribbon Panel on Conflict of Interest Policies, which Zerhouni established4; by the Office of Government Ethics5; and by the Subcommittee on Oversight and Investigations of the House Committee on Energy and Commerce, among others.
The NIH has 27 institutes and centers and an annual budget of about $28 billion (see Figure). The controversy involves the 18,000 people who are direct NIH employees, not external researchers who are funded by the institutes. In January 2004, the NIH knew of 228 employees who had a total of 365 approved outside consulting agreements. As of June, the NIH knew of 118 employees who had a total of 196 approved agreements. The cumulative number of employees who have entered into consulting agreements since 1999 and the total number of agreements they have had — including some that were not approved — are still not known.
Figure. Change in NIH Appropriations, 1994–2005.
After the controversy arose, Dr. Raynard Kington, the deputy director of the NIH, was appointed the deputy ethics counselor for the agency and was placed in charge of the ethics program. In an interview in August, Kington said, "Employees know that there has been harm to the agency because of the questions about our integrity [and] compromises of our integrity which may have occurred as a result of outside activities." There has been no evidence that patients were harmed or that decisions made at the institutes were influenced by the outside financial activities of employees. However, according to Zerhouni's testimony at a House hearing in June, "The NIH and its employees were operating within rules that allowed or did not specifically address many of the arrangements that the Subcommittee has questioned, including lecture awards and consulting with industry. In retrospect, there was not a sufficient safeguard against the perception of conflict of interest."3
In one instance in 2002, a pathologist at the National Cancer Institute (NCI) and a microbiologist at the Food and Drug Administration were assigned, as part of their official duties, to lead a cooperative research and development effort with a Maryland company to develop a test for ovarian cancer. They subsequently received approval to serve as paid consultants to another firm that was a potential competitor — an arrangement that continued until congressional investigators uncovered it earlier this year. In another instance, Dr. Richard Klausner, the former director of the NCI, was allowed to accept a $40,000 prize from the University of Pittsburgh in 1997. At the time, the university was a major recipient of funding from the NCI, with which it had an ongoing contract dispute. It had also recently settled a lawsuit, brought by Dr. Bernard Fisher, a well-known cancer researcher at the university, in which the university, the NCI, and others were codefendants. Klausner was said to have orally approved the use of $300,000 in government funds as part of the $2.7 million settlement.
These situations have particularly troubled Representative James Greenwood (R-Pa.). Greenwood chaired the House subcommittee and spearheaded its probe until July, when he unexpectedly announced that he would leave Congress to become president of the Biotechnology Industry Council. He therefore recused himself from all duties that might conflict with his future job, including the NIH inquiry.
There have also been instances in which employees apparently did not disclose their outside consulting arrangements to the NIH, as has always been required. Of 155 outside activities reviewed by the Office of Government Ethics, 74 had not been approved in advance. Late approvals were found for 39 of the 74; no approvals were found for the other 35.5 House subcommittee staff members discovered many discrepancies when they requested information from drug companies and tried to match the consulting agreements to those provided by the NIH. For example, apparently unbeknownst to the NIH, a researcher at the National Institute of Mental Health was paid more than $517,000 in fees, honoraria, and expense reimbursements over a five-year period, according to Greenwood. The institutes are still investigating many cases, and "will probably have some examples of individuals who did not disclose their activities to the agency," according to Kington.
Zerhouni intends "to prohibit senior NIH employees, as well as all employees involved in extramural funding decisions, from consulting with industry for compensation or any other form of remuneration"3 (see Table). This includes senior staff in the office of the director; directors and deputy, clinical, and scientific directors at the institutes and centers; and members of the extramural staff. Some scientists — which ones and how many have not been determined — would be allowed to engage in outside consulting. They would be subject to a stricter internal approval process and new limits, such as a proposed maximum of 400 hours of outside consulting per year and a proposed compensation cap of 25 percent of their base salary. Zerhouni also intends "to prohibit the holding of stock in individual biotechnology and pharmaceutical companies as is done at the Food and Drug Administration." He will increase "the number of senior managers who must publicly disclose their compensated activities and the amounts received."3 The number of employees who would be subject to these rules has not been determined.
Table. Changes and Proposed Changes in NIH Policies Regarding the Outside Activities of Employees.
Some are urging tougher standards that would ban or nearly ban drug-industry payments to all NIH employees. In a report issued in July, Marilyn Glynn, the acting director of the Office of Government Ethics, discussed a "permissive culture" that has existed at the NIH and noted that "expanded disclosure is not a substitute for appropriate substantive standards of ethical conduct." Without broader restrictions than those currently contemplated, the institutes "could give the appearance that some level of misuse of office is tolerable." There are ongoing investigations by the Office of Inspector General of the Department of Health and Human Services and the Government Accountability Office, and there may be more congressional hearings after Labor Day.
The NIH seeks to eliminate the possibility that the activities of its employees could harm its public health mission because of real or perceived conflicts of interest. "The biggest challenge for all of us is the uncertainty," Kington said. "We are in the midst of drafting the final proposed regulations. We are in the midst of completing some of the investigations that are under way. I am optimistic that once we finalize what the rules will be, this will be behind us." For the moment, however, it is still unclear how restrictive the new rules will be and how many employees will be affected. The NIH has made progress, but its conflict-of-interest problem has yet to be resolved.
References
Willman D. Stealth merger: drug companies and government medical research. Los Angeles Times. December 7, 2003:A1.
Steinbrook R. Financial conflicts of interest and the NIH. N Engl J Med 2004;350:327-330.
Zerhouni EA. Testimony before the House Energy and Commerce Oversight Investigations Subcommittee, June 22, 2004. (Accessed August 13, 2004, athttp://olpa.od.nih.gov/hearings/108/session2/testimonies/conflictc.asp.)
Report of the National Institutes of Health Blue Ribbon Panel on Conflict of Interest Policies: a working group of the Advisory Committee to the Director National Institutes of Health, June 22, 2004. (Accessed August 13, 2004, at http://www.nih.gov/about/ethics_COI_panelreport.pdf.)
Willman D. NIH is pressured to bar drug industry stipends. Los Angeles Times. August 6, 2004:A1.(Robert Steinbrook, M.D.)