The Science Board Subcommittee on FDA Research was established in March of 1996 by Michael A. Friedman, M.D., Deputy Commissioner for Operations, to provide preliminary recommendations to the parent advisory committee, the Science Board to the Food and Drug Administration, on appropriate criteria for determining the quality and mission relevance of FDA-sponsored laboratory investigation. The roster of the Subcommittee can be found in Appendix A and the full charge from Dr. Friedman to the Subcommittee, in Appendix B.
In essence, Dr. Friedman asked the subcommittee to consider the fundamental issue of how the FDA should best position itself to ensure that the agency's regulatory review and decision-making processes would continue, in an era of extraordinarily rapid scientific advancements, to be informed by the very best and most current scientific information available. To guide the subcommittee's deliberations, Dr. Friedman posed four basic questions about the organization and operation of the Agency's intramural research programs and their interactions with the extramural scientific community:
The subcommittee met and conducted its deliberations over the course of ten months. Given the breadth and time frame of its assignment, the Subcommittee recognized at the outset that it would not be feasible to attempt to visit individual Centers and laboratories, or to conduct specific evaluations of individual scientists, laboratories or programs. Rather, it chose to undertake a high-level review of the state of intramural science in the FDA and focus its attention on the organization of the scientific programs, their interactions with the extramural scientific community, and the policies, procedures and standards that governed their conduct. Accordingly, the subcommittee emphasizes that in communicating its findings and conclusions in general terms, it recognizes that there may well be specific exceptions and mitigating circumstances among the diverse Center/ORA programs with respect to details. The subcommittee report is the result of interviews of FDA management and scientists, written descriptions of organization, regulatory responsibilities and research activities from each of the Centers, and letters from FDA staff.
The subcommittee unanimously and emphatically affirms that the presence in the FDA of a vigorous, high quality intramural program of scientific research provides the essential foundation of sound regulatory policy and performance, and ensures that the FDA is, and will continue to be, best positioned to carry out its statutory responsibilities to protect, promote and enhance the health of the American people.
The subcommittee finds that the FDA presently lacks a culture of science and scientific communication that is essential for the nurture of high quality science. The intramural science program is uneven in quality, mission-relevance and efficiency. The current organizational structure and function of the agency significantly impede the creation of the flexible, responsive, high quality and cost-effective research establishment that the agency requires to accomplish its public health mission. This need is especially acute in an era in which extraordinary advancements in the foundational sciences will yield a profusion of entirely new biologicals, drugs and devices.
The remedial approach chosen by the subcommittee calls for the establishment of a "virtual" Science Center, to be headed by a newly appointed "Chief Scientist of the Food and Drug Administration," and to be responsible for the oversight, management and coordination of all scientific research activities of the agency. The subcommittee believes that this approach can effectuate the desired changes in the scientific climate and create a new scientific ethos by establishing a community of scientists and scientific resources across the agency, which, although transparent to Center barriers, will be accessible to all Centers in support of their regulatory responsibilities. Moreover, the approach avoids the need for disruptive and costly relocations of existing personnel and is considerate of the agency's present financial constraints.
The subcommittee recommends the creation of a new and empowered position of Chief Scientist of the FDA to share the "Office of the Deputy Commissioner for Operations" (the office occupied by the Deputy Commissioner for Operations of the FDA is officially designated in agency parlance as the "Office of Operations, Immediate Office"). The Chief Scientist shall be the advocate for science at the highest level within the FDA and shall have delegated responsibility, authority and accountability for all aspects of the agency's scientific research activities, including personnel, programs, finances and space.
The subcommittee further recommends that under the leadership of the Chief Scientist there shall be developed agency-wide policies, procedures and standards, including rigorous, periodic peer review of personnel and programs, to ensure the uniformly high quality, responsiveness and mission-relevance of the intramural research program in support of the FDA's responsibility to protect and promote the public health.
The subcommittee recognizes the challenge that faces the FDA in allocating very limited resources to meet a steadily expanding burden of increasingly complex regulatory responsibilities, and acknowledges that the successful implementation of the steps herein recommended will require incremental resources over time. Moreover, the subcommittee is aware from its review of four decades of agency history that many past efforts to accomplish objectives quite similar to those recommended here have foundered on the shoals of inadequate resources. Accordingly, the subcommittee affirms in the strongest possible terms that sound public policy demands that the resource needs of a first-rate, cutting-edge program of intramural scientific research be strongly advocated both within the councils of the FDA and the Department of HHS, and beyond that, in the highest levels of the Congress and the Administration.
The Science Board Subcommittee on FDA Research was established in March of 1996 by Michael A. Friedman, M.D., Deputy Commissioner for Operations, to provide preliminary recommendations to the parent advisory committee, the Science Board to the Food and Drug Administration, on appropriate criteria for determining the quality and mission relevance of FDA-sponsored laboratory investigation. The roster of the Subcommittee is presented in Appendix A and the full charge from Dr. Friedman to the Subcommittee, in Appendix B.
In essence, Dr. Friedman asked the subcommittee to consider the fundamental issue of how the FDA should best position itself to ensure that the agency's regulatory review and decision-making processes would continue to be informed, in an era of extraordinarily rapid scientific advancements, by the very best and most up-to-date scientific information available. To guide the subcommittee's deliberations, Dr. Friedman posed four basic questions about the organization and operation of the Agency's intramural research programs and their interactions with the extramural scientific community:
This report describes the procedures the subcommittee used to study the issues raised, the findings, recommended solutions, and an outline for implementation of those solutions.
The subcommittee, in considering its charge from Deputy Commissioner
Friedman, elected to focus its attention on that component of the FDA's
activities that met the subcommittee's definition of "scientific research" and
not to embrace the entire panoply of "science" and "scientific
activities" that take place on a regular, day-to-day basis in the conduct of the
agency's diverse statutory responsibilities. (A fuller discussion of these
definitional issues can be found in Appendix C).
The subcommittee met and conducted its deliberations over the course of ten months. During the meetings, the subcommittee met with agency-level management, including the Deputy Commissioner for Operations, the Senior Advisor for Science, the Associate Commissioner for Science, the Office of Science, the Office of Financial Management, Center Directors and the Associate Commissioner for Regulatory Affairs, members of the Senior Science Council and the Committee for the Advancement of FDA Science (CAFDAS), and representatives of the Offices of Management of the Centers and the Office of Regulatory Affairs (ORA). The subcommittee was provided with voluminous documents describing the organization, responsibilities and functions of the Centers and ORA. In response to an invitation pledging confidentiality to all FDA staff who wished to submit their views on the issues posed in Dr. Friedman's charge, the subcommittee received and carefully reviewed nearly 100 letters from staff in all components of the agency. The letters were thoughtful and demonstrated their authors' deep commitment and concern for the agency; the subcommittee found the letters informative and paid them close heed.
At the inaugural meeting, subcommittee members were provided overviews from each Center and ORA on their laboratory research programs, including information on their respective research resource bases, research program areas, guidelines for peer review of personnel and research programs, and continuing education/staff development. The Centers and ORA discussed the criteria used for selection of research programs and the processes by which decisions are made for funding specific research programs and projects.
At a subsequent meeting, the Office of Financial Management and the Office of Science presented an overview of the agency's budget formulation and execution processes, and provided detailed information representing each Center's and ORA's best estimates of their absolute and relative expenditure of resources on research and laboratory testing, including budget and personnel (the costs of space used in scientific research could not be clearly identified).
Representatives of the Committee for Advancement of FDA Science (CAFDAS) met with the subcommittee on three separate occasions to present their views on the importance of intramural research to the effective functioning of the agency. CAFDAS members discussed such topics as the justification for performance of relevant intramural research, the need for priority-setting to guide resource allocation for laboratory activities, and the necessity of FDA-wide peer review to ensure excellence of FDA science. CAFDAS also addressed the need to enhance inter- and intra-Center communication, improve the research support infrastructure and increase collaborations within the FDA and with the external scientific community.
The subcommittee studied the organizational structure of research operations within each Center and ORA, the research budget process, methods and outcomes of research peer and program review, and programs for continuing education and training of scientific personnel.
Finally, the subcommittee reviewed the most recent external reviews of Center and ORA research programs for those Centers in which such reviews had been conducted.
From its very beginnings (see Appendix D), the FDA has supported intramural programs of scientific research in manifestation of its commitment to the principle of science-based regulation. The agency dates its origin to the establishment of the Bureau of Chemistry in the Department of Agriculture in 1906. One of that Bureau's earliest actions was to set up a dedicated Food Research Laboratory; and from its inception the Bureau encouraged its field laboratories to mount research programs in analytical methodologies and publish their findings, so as to enhance the quality of their regulatory activities and advance the state of knowledge of their discipline. The legislative history of the FDA reveals the explicit conferral of authority on the Secretary to conduct research and testing ("examinations and investigations") for the purposes of the Act, beginning with the Federal Food, Drug and Cosmetic Act of 1938. The Food and Drug Administration Act of 1988, which transferred the agency into the DHHS, empowered the Secretary through the Commissioner, FDA to conduct research relating to foods, drugs, cosmetics, and devices in carrying out the statute.
The subcommittee unanimously and emphatically affirms that robust, high-quality programs of intramural research are essential components of the FDA's science base and are critical for supporting, in a scientifically sound and rigorous fashion, the review and regulatory decisions made by the agency in discharging its mission to promote and protect the public health. The intimate proximity and interaction of cutting-edge scientific research with review and regulatory activities is more important today than ever before given the extraordinarily rapid pace of advancements in such foundational scientific disciplines as biomedicine, materials science, micro-electronics, information technology, and others. Moreover, scientific advancement is more intimately coupled than ever before with equally rapid translation into new and complex materials and technologies for diagnosing, treating and preventing human (and animal) diseases and promoting health.
A strong and well-managed intramural research program provides the foundation for creating a climate of science and scientific communication within the FDA that enhances the ability of the agency to recruit and retain high quality scientific staff; to address existing regulatory issues and anticipate future problems; to keep pace with rapidly emerging and complex cutting-edge technology and respond timely, flexibly and competently to new scientific and technological initiatives and regulatory needs; and to identify the appropriate expertise, either internal or external, to recognize specific problems and explore specific questions.
Research-based internal expertise enhances the agency's ability to seek out and critically evaluate external scientific input, and it creates a platform from which agency staff can productively interact with external scientific expertise, especially from within the regulated industry, as respected, knowledgeable and impartial colleagues.
A high quality intramural research program enhances the ability of the FDA to collaborate with sister agencies, academia and industry to marshall resources effectively and efficiently to address issues of current and emerging public health importance.
The majority of the subcommittee rejected as specious the arguments that most (or all) of the scientific research needs of the FDA can be obtained from extramural sources in a more cost-effective manner that would meet criteria of timeliness, competence and freedom from conflict of interest. Likewise, the subcommittee rejected the notion that a strong program of intramural scientific research is not necessary for the recruitment and retention of high quality scientific staff, or the creation within the agency of a platform of sound, up-to-date scientific knowledge and expertise to inform regulatory review and decision-making.
The FDA presently lacks a "culture of science" and "culture of communication," that is, an environment which promotes scientific discourse and interchange and makes scientists feel that they are integral and respected members of the agency staff. Such a culture is essential for nurturing high quality cutting-edge science.
The existing intramural scientific research programs across the Centers are inconsistent in quality and mission-relevance, and science management practices are generally poor.
The quality of electronic information technology in the FDA is uneven. Autonomous Center decisions have led to investments in systems that are incompatible between Centers, which significantly compromises the capacity, and blunts incentive, for internal and external scientific communication. Poor connectivity only exacerbates the lack of intra-agency communication created by the agency's organizational structure and the pervasive disinclination among Centers to share data and expertise.
Scientific communication and the sharing of data and human and physical resources within and between Centers, and with extramural scientists in other government agencies, academia and industry, are generally inadequate. This leads to the inefficient use of resources, duplication of efforts and expertise, and a general sense of frustration and demoralization among the scientists, and especially, and most ominously, among the cohort of younger scientists. The generally low morale found within the research cadre is worrisome.
The excessive compartmentalization of the agency as it is presently structured, with Centers operating relatively autonomously, is antithetical to first-class science and impedes the creation of a sound environment for science by fostering bureaucracy, internal politics, and duplication of effort, and obstructing communication and the efficient use and sharing of resources.
The agency's organizational structure has not promoted uniformly high-quality science and impedes the implementation of agency-wide policies and procedures necessary to support a consistently high standard of mission-related scientific accomplishment. Rapidly evolving technology demands a nimble, responsive organization; the agency as presently structured does not meet this criterion.
The decreasing agency budget is of overarching concern. Although there is general appreciation of the fact that in times of constrained resources the agency must take particular care that its mandated regulatory responsibilities are competently discharged, there is a widely held perception among agency scientists that the research programs do not have strong advocacy at the highest levels of agency leadership and are front-line targets for curtailment or elimination as discretionary resources decline. The subcommittee believes strongly that starving the agency's base of intramural scientific expertise must inevitably compromise the quality of review and regulatory activities. Moreover, times of budgetary constraint demand an even higher quality of scientific management to ensure that limited resources are invested in scientific themes of the highest priority and not dribbled across Centers and programs in inadequate amounts, which leads to waste, inefficiencies and high opportunity costs.
The subcommittee recognizes that the FDA cannot possibly encompass, internally, expertise in all areas of relevant science at a time of such rapid advancements in science and technology. Moreover, it is illogical to attempt to maintain a large research organization in anticipation of all major issues that may arise. Consequently, there is a need for the agency to be creative in supplementing its intramural capabilities by expanding existing routes of access and establishing novel, alternative approaches to needed scientific information from external sources.
The FDA is not currently making the best possible use of resources in the external scientific community. This appears to be due to several factors, including agency culture and history, the deficiency of up-to-date electronic communications capabilities, and possibly, overly restrictive interpretations of conflict of interest regulations by the Department and the Congress. Effort must be made to mitigate impediments to free scientific interaction between FDA research scientists and their extramural scientific colleagues, and mechanisms must be explored to identify, evaluate, fund and monitor selected research activities and programs by non-FDA institutions.
In deliberating on different approaches to correcting the deficiencies described in the preceding section of this Report, the subcommittee was sensitive to the complexity of the FDA's organization and mission in an age of scientific and technological advancement of unprecedented rapidity. The group was also cognizant of the agency's dilemma in confronting a continually increasing burden of challenging regulatory tasks with a budget that is severely constrained and has been steadily decreasing in real terms in recent years. The subcommittee believes that the approach recommended can address the identified problems and significantly improve the environment for science with the least disruption in the agency's formal organizational structure. Although the subcommittee made no attempt to obtain a cost analysis of its proposal, the group believes that the proposed consolidation of management and upgrading of performance of the intramural science programs can lead to budget savings from improved efficiencies, as well from the elimination of existing duplicative Center functions and substandard research. Were the agency working with an adequate budget base, the subcommittee believes that its proposals could be implemented to a large extent through the reallocation of existing agency resources; given the reality of an inadequate budget base, incremental funds will likely be necessary.
The approach chosen by the subcommittee calls for the establishment of a "virtual" Science Center, to be responsible for the management, coordination and oversight of all scientific research activities of the agency. The "Center" would be headed by a newly appointed "Chief Scientist of the Food and Drug Administration," who would be situated within the office occupied by the Deputy Commissioner for Operations of the FDA. (This office is officially designated in agency parlance as the "Office of Operations, Immediate Office"). This proposal is intended to create an "Office of the Deputy Commissioner for Operations" that will be shared by the Deputy Commissioner and the Chief Scientist of the agency as collegial partners. The recommendation is deliberate and is meant to send to FDA and Departmental administration, as well as the intramural and extramural scientific communities, an unambiguous signal of the importance of this high-level administrative positioning to the subcommittee's intent.
The subcommittee believes that the implementation of a "virtual center" can effectuate the desired changes in the scientific climate and create a new scientific ethos by establishing a true community of scientists and scientific resources across the agency (a "virtual pool" of expertise), which, although transparent to Center barriers, will be accessible to all Centers in support of their regulatory responsibilities. Moreover, the "virtual center" avoids the need to consider disruptive relocations of existing personnel at great costs of time and money.
The Science "Center" should require only a modest administrative staff and budget, which might feasibly be funded to a significant degree by savings from centralizing duplicative administrative functions now dispersed among the Centers, streamlining the management and coordinating the conduct of the scientific research programs, and eliminating substandard programs of research and research support.
The appointee must be an outstanding scientist of high national standing, and recruited by an open, competitive, national search that actively seeks out candidates from academe, industry and government. The success of this proposal rests squarely on the stature and credentials of the individual selected to fill this position.
The appointee must have exceptional scientific leadership abilities and demonstrated management skills, with the vision and capacity to create an intramural scientific enterprise of consistently high quality, which is respected by and interactive with the external scientific community, and is committed to providing dependable, timely and effective support of the agency's mission.
It will be the Chief Scientist's responsibility to create a nimble, responsive scientific research organization of uniformly high quality that consistently brings the best science possible to bear on regulatory review and decision-making.
The Chief Scientist will be an advocate for science and research at the highest level within the FDA, and, by delegation from the Commissioner, represent FDA in the highest councils of science in the federal government.
The Chief Scientist will be responsible for the development and implementation of policies and procedures to insure the highest quality of FDA science in support of the agency's mission by fostering the cooperative participation of research personnel with review staff in regulatory decision-making, and by integrating the agency's regulatory/review and scientific research staff and functions to the maximum extent possible.
The Chief Scientist will facilitate and foster scientific communication and cooperation at all levels within and between FDA Centers, and will make special efforts to develop and nurture improved communication and interaction with the external scientific community.
The Chief Scientist will be accountable for the consistently high quality of research across the FDA through the establishment and implementation of agency-wide standards, policies and procedures for recruitment, conversion and promotion of scientific research personnel, regular external peer review of scientists and scientific research programs, and regular assessment, by peers and intramural scientists, of the management of research in the FDA Centers.
(Note: In the following sections, the term "scientific research personnel" is meant to describe those scientists who are intended to function in the role of principal investigators in scientific research.)
The Chief Scientist will oversee recruitment of all scientific research personnel, in consultation with the Center directors. To this end, the Chief Scientist will establish agency-wide policies and procedures for recruitment of all scientific research personnel by a process that is openly advertised, nationwide in scope, and competitive for all permanent appointments. The Chief Scientist must authorize recruitment and hiring of all scientific research personnel, and ensure that commitments of time and resources made as incentives for recruitment are honored. Further, the Chief Scientist will work with the Deputy Commissioner for Operations to develop and establish a parallel mechanism for recruitment of review scientists.
The Chief Scientist will establish and monitor mechanisms to ensure that each research scientist regularly participates in reviews and/or serves as a consultant on regulatory and review issues.
The Chief Scientist will be responsible for fostering the professional development of research scientists. In doing so, he/she will oversee the establishment of programs for professional development that include opportunities and support for sabbaticals, attendance at scientific meetings and continuing education, and participation, as appropriate, in collaborative programs of education and research, including clinical investigations, with the extramural scientific community. He/she will ensure that the development opportunities are responsive to the expressed needs of scientific staff.
While recognizing that scrupulous avoidance of conflict of interest is essential to the integrity of the FDA, the subcommittee concluded that current interpretations of conflict of interest regulations and policies can impede important collaborative interactions between agency scientists and colleagues in industry and academia, to the detriment of the agency. The Chief Scientist should seek innovative ways, within the limits of statute and regulation, to foster and enhance scientific dialogue between the agency and the extramural community.
The Chief Scientist will establish, implement and approve policies and procedures for promotion of scientific research personnel, which may, in consultation with Center directors, be adapted without compromise of excellence to meet specific Center needs. The Chief Scientist will approve promotions of scientific research personnel upon recommendation of a committee of inter-Center and external scientists and endorsement by the Center Director. In addition, the Chief Scientist will work with the Deputy Commissioner for Operations to develop and establish a parallel mechanism for promotion of review scientists.
Review of Center directors
The Chief Scientist will participate in regular periodic review of Center directors, in conjunction with the Commissioner and the Deputy Commissioner for Operations. The purpose of this authority is to make clear that nurture of a climate of science that conforms to agency policies, procedures and mission is the responsibility of every Center director and will be an element in his/her performance evaluation.
The Chief Scientist, in consultation with the Deputy Commissioner for Operations and the Center directors, will develop an FDA Science and Research Plan that represents the thinking of the agency and will provide a mechanism for prioritizing and accomplishing the research needs of the FDA. The plan will provide the basis for agency-level coordination of individual Center research activities, maintenance of an agency-wide research inventory of facilities, equipment and expertise, and effective implementation of procedures for annual evaluation and prioritization of research programs based on quality and mission relevance.
The Chief Scientist, in consultation with the Center directors, is responsible for the conduct of all scientific research program reviews to ensure their conformity with agency-wide policies and procedures, as well as their quality and relatedness to agency mission. Program reviews should take place at regular intervals, and review teams should be composed of intramural researchers and reviewers, as well as extramural experts. The Chief Scientist, in consultation with the cognizant Center director, is responsible for ensuring follow-up of program review committees' recommendations.
The Chief Scientist, in consultation with the Center directors, is responsible for the initiation, continuation, termination, translocation or consolidation of all scientific research programs within and across Centers, and the outsourcing of research programs to extramural research organizations (make/buy decisions). To this end, the Chief Scientist will determine, in consultation with the Center directors, whether any proposed new scientific research program should be located intramurally or extramurally, and if intramurally, in which Center(s).
The Chief Scientist must have broad budgetary oversight authority to empower the new position and accomplish the fundamental reformation of the agency's intramural scientific research programs that the subcommittee intends. Accordingly, the subcommittee recommends that the Chief Scientist have oversight of the entire scientific research budget of the agency.
The Centers will retain primary responsibility for developing their budgets, but budget planning and development must involve active participation by working scientists, both researchers and reviewers. Prior to submitting their proposed budgets to the Commissioner, Center directors must review them with the Chief Scientist, who will have approval authority for all scientific research programs. The review will focus on quality, mission-relatedness, duplication/redundancies with other intramural programs, and whether programmatic objectives could be better met elsewhere in the agency, or extramurally.
The Chief Scientist must have an adequate budget to conduct the administrative functions of his/her office and to stimulate/implement new scientific research programs.
The subcommittee believes that the recommendations proposed herein fully address the substance of the charge presented to it by Deputy Commissioner Friedman. By focussing on the overarching issues of organization, standards and expectations of the agency's intramural programs of scientific research, and the need for distinguished scientific leadership and advocacy of those programs at the highest level of the agency's governance, the subcommittee is confidant that the more subordinate elements of the charge will be appropriately addressed and readily managed.
The subcommittee respects the complexity of the FDA and the severe difficulties it is facing at a time of increasing regulatory demand and complexity and tightly constrained budgets. In such times, it is tempting to adopt the seemingly straightforward response of putting more and more resources into review and regulatory responsibilities and progressively diminishing support for intramural scientific research. But at a time of unprecedented advancements in science and technology, and the equally unprecedented rapidity at which those advancements are being translated into new medical products that were unimaginable even a short time ago, the dependence of the FDA on the very best contemporary science to inform its regulatory activities and decisions is also without precedent. Accordingly, starvation of the base of intramural research will inevitably compromise the quality of regulatory performance. The subcommittee repeats its earlier affirmation that the presence in the agency of a robust, high quality program of scientific research provides the essential foundation for sound regulatory policy and performance, and ensures that the FDA will continue to be well-positioned to carry out its statutory responsibilities to protect, promote and enhance the health of the American people. Sound public policy demands no less.
(NOTE: This report does not address the laboratory activities of the Office of Regulatory Affairs. The subcommittee recognizes that the field laboratories must maintain an ongoing program of research and development focussed on analytical methodology, but the subcommittee did not have the time or expertise to study these operations and can offer no judgments about their quality, efficiency and cost-effectiveness. The letters received from ORA personnel were mixed in their assessments of these matters. The subcommittee recommends that the ORA program should be reviewed by a special committee with appropriate experience and expertise assembled from industry, academe and government.)
Appendix A - Science Board Subcommittee
Appendix B - Charge from Dr. Friedman to the Subcommittee
Appendix C - Definitional Issues
Appendix D - Upgrading the Quality of Science in the FDA
Hypertext created on 03/14/97 by Jonathan Boswell, OSB, Center for Devices and Radiological Health.