Standards of Ethics at the National Institutes of Health
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《新英格兰医药杂志》
As of early February, the federal government has banned payments by drug companies to any employee of the National Institutes of Health (NIH) and has implemented broad restrictions on employees' outside activities and financial arrangements, including the holding of stock in biotechnology and pharmaceutical companies and the acceptance of prizes (see box).1 In addition, the NIH is reviewing its conflict-of-interest rules for the thousands of outside experts who provide advice to the agency each year — for example, through service on advisory committees, data and safety monitoring boards for clinical trials, and consensus-development panels. And Dr. Elias Zerhouni, the director of the NIH, has called for an ethics summit later this year at which leaders in government, academia, and industry would address conflicts of interest throughout biomedical research and clinical trials.
New Regulations Regarding the Outside Activities of NIH Employees.
"It became quite apparent that we have a systemic issue that we needed to deal with," Zerhouni said in an interview. "It is important that we address this issue. It is undermining in a profound way — more profound than I personally realized at the beginning of the process — the integrity of our research and our ability to maintain public trust in our research."
Zerhouni had initially rejected as too draconian a complete ban on drug-company payments to NIH employees.2 His subsequent decision to seek such a ban followed more than a year of internal review, embarrassing revelations about lucrative financial deals between industry and some leading scientists at the institutes, and congressional pressure. The revelations in the media and congressional hearings "appalled" government officials and outside scientists and damaged the reputation of the agency, Zerhouni said at an "all hands" meeting with employees in February. As the NIH director learned more about the facts, he became convinced that the institutes' existing policies "were not on solid ground" and that the ethics controversy was "standing between the prestigious history of NIH and its future."
The NIH includes 27 institutes and centers, has an annual budget of about $28 billion, and is widely regarded as the world's premier biomedical research institution. The new ethics standards are even more stringent than the restrictive policies that were in place before 1995.3 In that year, NIH director Harold Varmus relaxed the rules as part of his effort to recruit and retain high-level scientists. The policy he implemented placed no dollar limit, for example, on the amount of money employees could earn from outside activities, and they were permitted to accept stock and stock options as well as money for their services. Because these 1995 regulations have remained in effect, Zerhouni said the agency required new regulations to provide it with the legal authority to stop employees from engaging in activities it now deems inappropriate. "We needed to have a clean break," he said.
Under the new standards, the 18,000 people who are direct employees of the NIH, including about 5000 scientists, are subject to rules similar to those covering employees of a regulatory agency, such as the Food and Drug Administration or the Securities and Exchange Commission. One specific impetus for this shift was the outside activities of several dozen scientists. Some had not even disclosed their consulting arrangements to the NIH, as has always been required. Some of their activities "really were purely and simply what you would call product-endorsement activities, speaking for a company on behalf of a product to entice physicians to prescribe that product at greater levels," Zerhouni said at the agency meeting. "Is this really what NIH stands for? My response was no." The more general reasons for the change were the increased complexity of the relationships between the NIH and industry and the increasingly powerful influence that decisions at the agency can have on financial markets. "The fundamental explanation is that the world changed," said Dr. Raynard Kington, deputy director of the NIH, who is in charge of the institutes' ethics program. "That did not mean that we should go ahead and exempt and allow conflicts."
The regulations are known in administrative parlance as an "interim final rule." This means that although they went into effect as soon as they were published, the Department of Health and Human Services will consider comments received by April 4, 2005, before issuing the final regulations. In general, employees who are engaged in an activity that has been prohibited will have 30 to 90 days to stop; those who must sell stock will have 150 days to do so. About 6000 employees are prohibited from holding stock in biotechnology or pharmaceutical companies. The NIH will evaluate the effect of the regulations on the recruitment and retention of researchers, the financial situation of employees, and other areas and says that it will make adjustments as needed. A group of the agency's scientists, including some who have had financial relationships with industry,4 say the new rules "substantially overreach" their objectives and "will severely and irreparably compromise the NIH's mission."5 They have proposed alternative rules that are less strict.
The rules apply to employees' outside activities, not to work performed in collaboration with industry or research institutions that is part of their official duties. For example, cooperative research and development agreements with industry are not affected. These public–private partnerships facilitate the commercialization of scientific knowledge and technology developed in federal laboratories. Indeed, the agency's goal is to make it easier for employees to interact with the scientific world and participate on an official basis in activities that are no longer allowed as outside activities, such as serving as an officer of a professional association. An employee serving in such a capacity as part of his or her job at NIH could be reimbursed for travel expenses but could not receive additional compensation. "We are reviewing our official-duty policy and expect to amend it so that more activities are permitted," Holli Beckerman Jaffe, the director of the NIH Ethics Office, explained. In all instances, such activities would require prior approval.
The new standards do not apply to the 212,000 extramural researchers who are not employed by the federal government but are recipients of NIH grants and contracts or to outside experts who advise the institutes. The agency's 145 chartered advisory committees include review groups that initially evaluate applications for research grants or contracts; program advisory committees; boards of scientific counselors, which review NIH laboratories; and national advisory councils, which perform the second level of peer review for research grants and advise the institutes broadly about policies and programs. Members of advisory committees are subject to conflict-of-interest rules, and people may be disqualified from participating in such committees on the basis of such rules. The rules, however, are more lenient than those that apply to full-time employees.
Zerhouni said that the problem of bias in research was not "inherent or intrinsic to NIH." Nonetheless, the agency cannot apply the same standards to outside advisors as it does to its full-time employees. This is because it lacks the authority to do so and because it differs from universities and companies, where its outside advisors may work. The agency is, however, actively reviewing its policies as they apply to the members of its advisory committees and others who participate in "internal processes that are under the responsibility of NIH," and it is prepared to make changes. "Rather than assume that there is no bias and then be surprised that on a particular committee 80 percent of the members have some relationship [with industry], let's assume there is bias and let's manage it transparently and forthrightly," Zerhouni said. "It is probably time to have a frank and open review of our internal processes."
At the moment, Zerhouni's call for an ethics summit is a concept rather than a specific proposal for an event with a defined structure and goals. Nonetheless, by setting a new ethics standard for the institutes and focusing attention on the issue, Zerhouni has advanced the cause of tougher national conflict-of-interest standards. Addressing the integrity of the entire biomedical research enterprise, however, is likely to be considerably more daunting than restoring the integrity of the NIH.
Source Information
Dr. Steinbrook is a national correspondent for the Journal.
References
Department of Health and Human Services. Supplemental standards of ethical conduct and financial disclosure requirements for employees of the Department of Health and Human Services: interim final rule with request for comments. Fed Regist 2005;70:5543-5565.
Steinbrook R. Conflicts of interest at the NIH -- resolving the problem. N Engl J Med 2004;351:955-957.
Steinbrook R. Financial conflicts of interest and the NIH. N Engl J Med 2004;350:327-330.
Williman D. New rules will cost dissidents at NIH. Los Angeles Times. March 3, 2005.
NIH Assembly of Scientists' response to supplemental standards of ethical conduct and financial disclosure requirements for employees of the Department of Health and Human Services. March 2005. (Accessed March 11, 2005, at http://homepage.mac.com/assemblyofscientists/FileSharing20.html).(Robert Steinbrook, M.D.)
New Regulations Regarding the Outside Activities of NIH Employees.
"It became quite apparent that we have a systemic issue that we needed to deal with," Zerhouni said in an interview. "It is important that we address this issue. It is undermining in a profound way — more profound than I personally realized at the beginning of the process — the integrity of our research and our ability to maintain public trust in our research."
Zerhouni had initially rejected as too draconian a complete ban on drug-company payments to NIH employees.2 His subsequent decision to seek such a ban followed more than a year of internal review, embarrassing revelations about lucrative financial deals between industry and some leading scientists at the institutes, and congressional pressure. The revelations in the media and congressional hearings "appalled" government officials and outside scientists and damaged the reputation of the agency, Zerhouni said at an "all hands" meeting with employees in February. As the NIH director learned more about the facts, he became convinced that the institutes' existing policies "were not on solid ground" and that the ethics controversy was "standing between the prestigious history of NIH and its future."
The NIH includes 27 institutes and centers, has an annual budget of about $28 billion, and is widely regarded as the world's premier biomedical research institution. The new ethics standards are even more stringent than the restrictive policies that were in place before 1995.3 In that year, NIH director Harold Varmus relaxed the rules as part of his effort to recruit and retain high-level scientists. The policy he implemented placed no dollar limit, for example, on the amount of money employees could earn from outside activities, and they were permitted to accept stock and stock options as well as money for their services. Because these 1995 regulations have remained in effect, Zerhouni said the agency required new regulations to provide it with the legal authority to stop employees from engaging in activities it now deems inappropriate. "We needed to have a clean break," he said.
Under the new standards, the 18,000 people who are direct employees of the NIH, including about 5000 scientists, are subject to rules similar to those covering employees of a regulatory agency, such as the Food and Drug Administration or the Securities and Exchange Commission. One specific impetus for this shift was the outside activities of several dozen scientists. Some had not even disclosed their consulting arrangements to the NIH, as has always been required. Some of their activities "really were purely and simply what you would call product-endorsement activities, speaking for a company on behalf of a product to entice physicians to prescribe that product at greater levels," Zerhouni said at the agency meeting. "Is this really what NIH stands for? My response was no." The more general reasons for the change were the increased complexity of the relationships between the NIH and industry and the increasingly powerful influence that decisions at the agency can have on financial markets. "The fundamental explanation is that the world changed," said Dr. Raynard Kington, deputy director of the NIH, who is in charge of the institutes' ethics program. "That did not mean that we should go ahead and exempt and allow conflicts."
The regulations are known in administrative parlance as an "interim final rule." This means that although they went into effect as soon as they were published, the Department of Health and Human Services will consider comments received by April 4, 2005, before issuing the final regulations. In general, employees who are engaged in an activity that has been prohibited will have 30 to 90 days to stop; those who must sell stock will have 150 days to do so. About 6000 employees are prohibited from holding stock in biotechnology or pharmaceutical companies. The NIH will evaluate the effect of the regulations on the recruitment and retention of researchers, the financial situation of employees, and other areas and says that it will make adjustments as needed. A group of the agency's scientists, including some who have had financial relationships with industry,4 say the new rules "substantially overreach" their objectives and "will severely and irreparably compromise the NIH's mission."5 They have proposed alternative rules that are less strict.
The rules apply to employees' outside activities, not to work performed in collaboration with industry or research institutions that is part of their official duties. For example, cooperative research and development agreements with industry are not affected. These public–private partnerships facilitate the commercialization of scientific knowledge and technology developed in federal laboratories. Indeed, the agency's goal is to make it easier for employees to interact with the scientific world and participate on an official basis in activities that are no longer allowed as outside activities, such as serving as an officer of a professional association. An employee serving in such a capacity as part of his or her job at NIH could be reimbursed for travel expenses but could not receive additional compensation. "We are reviewing our official-duty policy and expect to amend it so that more activities are permitted," Holli Beckerman Jaffe, the director of the NIH Ethics Office, explained. In all instances, such activities would require prior approval.
The new standards do not apply to the 212,000 extramural researchers who are not employed by the federal government but are recipients of NIH grants and contracts or to outside experts who advise the institutes. The agency's 145 chartered advisory committees include review groups that initially evaluate applications for research grants or contracts; program advisory committees; boards of scientific counselors, which review NIH laboratories; and national advisory councils, which perform the second level of peer review for research grants and advise the institutes broadly about policies and programs. Members of advisory committees are subject to conflict-of-interest rules, and people may be disqualified from participating in such committees on the basis of such rules. The rules, however, are more lenient than those that apply to full-time employees.
Zerhouni said that the problem of bias in research was not "inherent or intrinsic to NIH." Nonetheless, the agency cannot apply the same standards to outside advisors as it does to its full-time employees. This is because it lacks the authority to do so and because it differs from universities and companies, where its outside advisors may work. The agency is, however, actively reviewing its policies as they apply to the members of its advisory committees and others who participate in "internal processes that are under the responsibility of NIH," and it is prepared to make changes. "Rather than assume that there is no bias and then be surprised that on a particular committee 80 percent of the members have some relationship [with industry], let's assume there is bias and let's manage it transparently and forthrightly," Zerhouni said. "It is probably time to have a frank and open review of our internal processes."
At the moment, Zerhouni's call for an ethics summit is a concept rather than a specific proposal for an event with a defined structure and goals. Nonetheless, by setting a new ethics standard for the institutes and focusing attention on the issue, Zerhouni has advanced the cause of tougher national conflict-of-interest standards. Addressing the integrity of the entire biomedical research enterprise, however, is likely to be considerably more daunting than restoring the integrity of the NIH.
Source Information
Dr. Steinbrook is a national correspondent for the Journal.
References
Department of Health and Human Services. Supplemental standards of ethical conduct and financial disclosure requirements for employees of the Department of Health and Human Services: interim final rule with request for comments. Fed Regist 2005;70:5543-5565.
Steinbrook R. Conflicts of interest at the NIH -- resolving the problem. N Engl J Med 2004;351:955-957.
Steinbrook R. Financial conflicts of interest and the NIH. N Engl J Med 2004;350:327-330.
Williman D. New rules will cost dissidents at NIH. Los Angeles Times. March 3, 2005.
NIH Assembly of Scientists' response to supplemental standards of ethical conduct and financial disclosure requirements for employees of the Department of Health and Human Services. March 2005. (Accessed March 11, 2005, at http://homepage.mac.com/assemblyofscientists/FileSharing20.html).(Robert Steinbrook, M.D.)