The 83rd meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December 6, 2001. Dr. Ruth Kirschstein, Acting Director, NIH, began by introducing several new committee members and reviewing recent personnel changes at NIH. Since October 1, 2001, the beginning of fiscal year (FY) 2002, NIH has been operating under a continuing resolution at FY 2001 levels. However, the final FY 2002 appropriation for NIH is expected to provide an increase for the fourth consecutive year of a series of increases that will double the NIH budget within a five-year period. Dr. Kirschstein also described recent visits by HHS Secretary Tommy Thompson to NIH, major awards to NIH grantees, and continuing deliberations over several sets of guidelines for dealing with conflict-of-interest issues.
Dr. Wendy Baldwin, Deputy Director for Extramural Research, NIH, reviewed the findings in a report that was presented to Senator Ron Wyden (D-OR), who sought information in regard to the return on investment for NIH following cooperative research and development agreements (CRADAs) between NIH and commercial establishments. The report focuses on blockbuster drugs, namely those that earn more than $500 million in annual sales, for which there was early NIH support, and identifies four such drugs. To improve the current process, NIH is asking grantee institutions to include reports on marketed drugs in the Federal electronic invention reporting system, which tracks information about inventions from Federally-sponsored research programs. This change will provide additional data to help in monitoring the return on investment of NIH programs.
Ms. Robin Kawazoe, Director of the NIH Office of Science Policy and Planning, and Dr. Myron Weisfeldt of Johns Hopkins University School of Medicine summarized the recently completed annual Government Performance and Results Act (GPRA) assessment of NIH. Dr. Weisfeldt said that he and Dr. Richard Lifton from Yale University, who co-chaired the GPRA Assessment Working Group, along with other members of that group concluded that NIH made significant advances in research across a broad range of biomedical fields, meeting and frequently surpassing designated goals.
Dr. Kirschstein reminded ACD members that President Bush announced on August 9, 2001, that Federal funding would be allowed for use on those human embryonic stem cell lines that existed prior to that date and which met several additional criteria. To facilitate such research, NIH established a Website-based registry for cells meeting these criteria, and is taking additional steps to implement the new system. Dr. Baldwin said that many issues related to intellectual property rights will need to be resolved in regard to the use of these different lines of stem cells.
Dr. Kirschstein said that, during 2001, NIH responded to two exceptional circumstances, one arising from severe damage caused by Tropical Storm Allison to research institutions in Houston and the other following the September 11 attacks in New York City and at the Pentagon. Dr. Baldwin said that appointing a case manager is an essential component of the NIH approach to dealing with the damage caused by disasters such as the one that occurred in Houston, and she noted that institutions should put in place good back-up systems and records because they are of great value in assessing damage and recovering from such events.
Dr. Kirschstein said that, following the September 11 events, security is being significantly enhanced on the NIH campus, where 16,000 employees work and another 5,000 individuals visit each day. NIH is working closely with other Federal agencies in regard to bioterrorist counter-measures as well as a specific response to the deliberately inflicted anthrax cases that resulted in several deaths during the latter months of 2001.
Dr. Larry Smarr, who serves on the President's Information Technology Advisory Council (PITAC), summarized key findings from a PITAC report, "Transforming Health Care Through Information Technology," that was completed early in 2001. Dr. Smarr said that NIH and HHS should take a leadership role in sponsoring information technology (IT) research, its application to biomedical and clinical research, and its eventual role in health care delivery. He also urged NIH to work closely with other Federal agencies and departments to further these goals.
Dr. William Brody reviewed the three principal recommendations of a report on meeting research facilities construction needs. The recommendations call for direct support for construction through NIH grants and similar awards, a new program of Federal loan guarantees, and changes in facilities and administrative (F&A) rates to enable institutions to capture some construction costs. Members of the ACD endorsed the report, and encouraged NIH to develop ways for implementing its recommendations.
The 83rd meeting of the Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) was held on December 6, 2001. Dr. Ruth Kirschstein, Acting Director, NIH, began by thanking the members of the committee for their service, noting that Dr. Christine Cassel, who could not attend, recently was appointed Dean of the Oregon Health Sciences University Medical School, and that Dr. Larry Smarr was reappointed to a four-year term on ACD. Dr. Kirschstein also introduced Dr. Thomas Ansfield from the University of Wisconsin, Dr. David Korn of the Association of American Medical Colleges (AAMC), Dr. James Martin of the Carolinas HealthCare System, and Dr. Steven Paul of Eli Lilly Research Laboratories who was not able to attend the meeting.
Dr. Kirschstein reviewed several matters concerning personnel at NIH, noting the resignations of Dr. Richard Klausner, Director of the NIH National Cancer Institute (NCI), who became the President of the newly founded Case Institute of Medical Research on October 1; Dr. Alan Leshner, Director of the National Institute on Drug Abuse (NIDA), who is now the Executive Director of the American Association for the Advancement of Science; Dr. Steven Hyman, Director of the National Institute of Mental Health (NIMH), who will serve as the Provost of Harvard University; and Dr. Enoch Gordis, Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), who is retiring. Several search committees to identify replacements for those positions have been established.
Dr. Kirschstein also noted that Dr. Maria Freire, who was Director of the Office of Technology Transfer (OTT), left NIH to join the Global Alliance for Tuberculosis Drug Development. Dr. Mark Rohrbaugh has been appointed Acting Director of OTT. Meanwhile, Mr. Larry Self was appointed Director of the NIH Office of Equal Opportunity; he comes to NIH from the Commerce Department.
Dr. Kirschstein said that, since October 1 and the beginning of fiscal year (FY) 2002, NIH has been spending funds on the basis of a continuing resolution at FY 2001 levels. She reminded ACD members that the President's proposed FY 2002 budget for NIH calls for $23 billion, which continues, for the fourth year, a series of increases that will lead to a doubling of the NIH budget over a five-year period. She said that, in keeping with the President's budget proposal, the House version of the FY 2002 appropriation for NIH would add more than $2.6 billion to the previous appropriation, whereas the Senate version calls for a larger increase of $3.4 billion. An agreement is being worked out to reconcile the differences. In general, this delay of the final appropriations bill is not significantly affecting the NIH grant awards process, according to Dr. Kirschstein. Training stipends will be raised by 10 percent during FY 2002, and postdoctoral stipends will also be increasing.
In October, the National Institute of Neurological Disorders and Stroke (NINDS) and the NIMH convened a joint symposium and marked other events to celebrate their 50th anniversaries, according to Dr. Kirschstein. Several other Institutes also are involved in neurosciences and related research at NIH, and the Smithsonian has mounted an exhibit on this subject that will run through January 2002. Dr. Kirschstein said that Mr. Tommy Thompson, Secretary of Health and Human Services (HHS) established a task force to look at transmissible spongiform encephalopathies, a group of serious neurodegenerative diseases. She said that Dr. Richard Johnson of Johns Hopkins University is serving as a consultant to NIH on this subject, for which additional resources are being made available through NINDS, the National Institute on Aging (NIA), the National Institute of Allergy and Infectious Diseases (NIAID), and the Director's discretionary fund.
NIH-supported researchers recently were chosen for major awards, including Dr. Mario Capecchi of Albert Einstein School of Medicine and Dr. Oliver Smithies of the University of North Carolina for the 2001 Lasker Award for Basic Medical Research. In addition, Dr. Barry Sharpless of the Scripps Institute was a recipient of the 2001 Nobel Prize in Chemistry, while Dr. Leland Hartwell of the Fred Hutchinson Research Center was a recipient of the Nobel Prize in Medicine or Physiology. She and Dr. Tom Cech described a recent White House celebration for the recipients of these prizes. In addition, Dr. Cech provided details about forthcoming ceremonies in Sweden to commemorate the 100th anniversary of the Nobel Prizes.
Officials at NIH and elsewhere within HHS, along with representatives from non-government organizations, are considering issues related to conflict of interest as they involve Federally-supported investigators and institutions in dealing with human subjects in clinical research projects. Dr. David Korn said that an AAMC task force is completing its first report on this topic and plans to disseminate it soon. Because reports from other groups are also nearing completion, Dr. Kirschstein deferred further discussion of this topic.
Dr. Kirschstein said that, during August, HHS Secretary Thompson spent almost a week in residence at NIH, during which he visited many sites on campus, reviewed many NIH programs and office activities, and spent time in laboratories and at the Clinical Center.
Dr. Kirschstein introduced Dr. Wendy Baldwin, Deputy Director for Extramural Research, NIH, to review the findings in a report that had been requested by Senator Ron Wyden (D-OR), who was seeking information about the return on investment following cooperative research and development agreements (CRADAs) between NIH and commercial establishments. The report was presented to Sen. Wyden during a meeting that included representatives from organizations representing academic researchers as well as the pharmaceutical and biotechnology industries.
Dr. Baldwin said that the report focuses on blockbuster drugs, namely those that earn more than $500 million in annual sales, for which there was early NIH support. The report identifies four such drugs, one with input from the intramural program and the others from the extramural program. To improve this tracking process, NIH is asking grantee institutions to provide reports on marketed drugs for the Federal electronic invention reporting system (Edison), which tracks information about inventions from Federally-sponsored research programs but had not previously included actually marketed products. Although there are no plans to track royalty payments on such inventions, these other changes will help in monitoring the return on investment of NIH programs, according to Dr. Baldwin. This change in Edison's data gathering procedures, which Sen. Wyden endorsed, is scheduled to begin in January 2002.
Ms. Rebecca Eisenberg, who asked for a more detailed description of what was being monitored and reported to Sen. Wyden, was skeptical that NIH funding led to only four blockbuster drugs but also noted that any system for monitoring the NIH return on investment could be a double-edged sword. In response, Dr. Baldwin said it is broadly recognized that the NIH investment in research leads to many broad and basic discoveries that bring multiple benefits throughout science. In addition, NIH can try to follow more specifically the trail in cases where NIH investments led to patented inventions that generated commercial products. Although it is not practical to calculate return on investment for the former, more general discoveries, it did prove possible to track at least a portion of that return on investment in cases where royalties are being generated from patented products.
Ms. Eisenberg said that merely tracing inventions through patent claims might not be relevant and could be misleading. In response, Dr. Baldwin said that although this issue is open to discussion, it made sense to confine it to the available data. She also said that there are no plans to have anyone report on actual royalty figures. Instead, the Edison system will be modified, enabling it to link with other information systems that track marketed products, such as drugs, that generate income.
Dr. Rohrbaugh said that, when the report was being planned, Sen. Wyden agreed that NIH should restrict its review to commercialized inventions whose early development could be tightly linked to NIH support. He also noted that many other studies attempt to describe the broader return on investment from NIH support for basic research.
In response to another question from Ms. Eisenberg, Dr. Rohrbaugh said that NIH would look beyond blockbuster drugs to consider more modestly profitable commercial products in its follow-up monitoring through the modified Edison system. For example, a forthcoming review will include 15 or more vaccines, drugs, and other commercialized products that were developed initially in the NIH Intramural Program.
In response to a question from Dr. Kirschstein, Dr. Baldwin said that the efforts that went into preparing the report for Sen. Wyden aim primarily at refining the information available for describing how NIH investments contribute to certain commercialized products. Dr. Rohrbaugh agreed, saying that before the report was done, no one had a clear idea what the available data for NIH-supported, commercialized products signified. The report and other changes being instituted will help to clarify what those data mean. For instance, there is a broad economic impact in terms of jobs and other benefits, while royalties to NIH and universities represent only a small fraction of the overall return on investment.
Mr. Arthur Ullian said that a private group tracks patents. He also said that Mr. Peter Lynch told his group that 70 to 80 percent of patented inventions in development stem from Federally-funded research. n response, Dr. Baldwin said that such information provides a general picture of return on investment but that the recent effort was more narrowly focused.
Dr. Pickett said that creating such metrics for evaluating research is difficult and also encourages expectations that cannot be met. Dr. James Martin added that a better measure for Congress to consider would be the full set of new devices and drugs that NIH research helps in developing by supporting basic research. Mr. Phillip Williams agreed, saying that NIH should try to explain to Congress that extrapolating from such reviews can be misleading. Dr. Barrie Carter agreed with Dr. Martin, saying that NIH should take broad credit for commercially important products. He also said it would be misleading to try to set values for royalty streams that might be due back to NIH.
Ms. Eisenberg said that NIH should consider collecting data that could unbundle the value of NIH-sponsored research from revenues derived from specific, commercial, medical interventions. She also said that an attempt by NIH to "tax" those interventions through royalties would likely discourage their development. Dr. Baldwin said that those royalties tend to go back to investigators, who often invest them in their laboratories and into further research.
Dr. David Korn said that Sen. Wyden's principal concern is with the high cost of pharmaceutical products, and he thus is interested in seeing some of that money come back to recoup the original investment of public funds through NIH into biomedical research.
REPORT ON THE GOVERNMENT PERFORMANCE AND RESULTS ACT ASSESSMENT
Dr. Kirschstein said that the Government Performance and Results Act (GPRA) mandates an annual assessment of NIH activities. She introduced Ms. Robin Kawazoe, Director of the NIH Office of Science Policy and Planning, and Dr. Myron Weisfeldt of Johns Hopkins University School of Medicine, to summarize the recent NIH GPRA assessment.
Ms. Kawazoe said that GPRA was enacted in 1993, providing a means for Federal agencies to improve the effectiveness of their programs through increased accountability. The law mandates strategic planning, goal setting, and annual performance and reporting. NIH and other science-sponsoring agencies were faced with a formidable challenge to develop means for complying with GPRA requirements, and NIH consulted extensively with advisory boards to develop a suitable approach for conducting its assessments.
One important step involved aggregating a large number of NIH programs into relatively few categories that include research, research training and career development, and research facilities. Another step entailed identifying quantitative goals and objectives for these categories, according to Ms. Kawazoe. In addition, officials at the Office of Management and Budget (OMB) agreed to allow NIH to follow the "alternative form," which means that NIH may meet GPRA requirements, in part, by developing descriptive goals and qualitative measures, provided that it arranges an independent assessment of that set of goals. Under NIH research and research support programs, there are both quantitative and qualitative goals, which include communications, technology transfer, priority setting, and peer review systems. Quantitative goals include progress toward developing an AIDS vaccine by 2007 and the development of resources for genomics research. Other categories also have both kinds of goals, including quantitative measurements for research training and career development, for implementing an electronic system for administering grants, and for modernizing both intramural and extramural research facilities.
Dr. Weisfeldt said that he and Dr. Richard Lifton from Yale University co-chaired the GPRA Assessment Working Group. Other members of the group were drawn from ACD, the NIH Council of Public Representatives, and from other Councils of the NIH Institutes and Centers. To begin, NIH staff briefed working group members on recent NIH-sponsored scientific accomplishments, which were reviewed first by members of the working group, jointly by Dr. Weisfeldt and Dr. Lifton, and ultimately by subgroups.
Dr. Weisfeldt said that this working group identified exciting advances, including stem cell plasticity, advances in the Human Genome Project, identification of several genes related to diseases, development of more complex mouse models of human disease, crystallization of the RNA polymerase-2 protein, studies showing a decrease in disability due to aging, and knowledge about brain chemistry through magnetic resonance and positron emission tomography studies.
Several subgroups also identified additional important advances, according to Dr. Weisfeldt. The subgroup addressing the area of instrumentation and technology concluded that NIH substantially exceeded its goals and pointed to DNA microarrays, protein and modified protein arrays, DNA sequence databases and software systems, and the beginning application of DNA identifiers to humans diseases such as Alzheimer's disease and other specific conditions, such as heart failure. Other major advances include the use of computerized tomographic scanning to do virtual colonoscopies, advances in laser capture and micro-dissection techniques, an experimental proof of concept that injecting a viral vector containing the endostatin gene can successfully block neovascularization, which is a cause of blindness in diabetics and in animals whose eyes are injured.
Another subgroup considering NIH support of research that helps to prevent diseases also marked significant advances, according to Dr. Weisfeldt. For instance, there is new information indicating that exercise and diet help to prevent Type II diabetes. Another study indicates that polybrominated biphenyls can delay sexual maturation of girls when they are exposed in utero to such chemicals. Other disease prevention research efforts involve broader applications of new vaccine technologies, particularly those that use recombinant, naked DNA molecules that can be injected directly into skeletal muscles. Other studies focused on, or will further study, stroke biology and metabolism, the use of anti-inflammatory agents to prevent Alzheimer's disease, and uses of estrogens as preventive agents among post-menopausal women.
The group also concluded that NIH exceeded its goals with respect to research into disease diagnosis, according to Dr. Weisfeldt. Examples include advances in genetics and molecular analysis, the early diagnosis of Alzheimer's disease through imaging technologies, use of single-fiber optics to diagnose several conditions in the gastro-intestinal tract, early diagnosis of kidney-transplant rejection by measuring constituents in urine, and saliva-based measurements of HIV variants during the course of antiviral treatments.
In terms of goals related to research into disease treatments, the group concluded that NIH is making important advance in several areas, including studies of complementary agents such as St. John's wort to treat depression and also in finding that this agent can affect HIV protease inhibitors, according to Dr. Weisfeldt. Also important are NIH-sponsored studies in regard to the use of beta-blocker drugs to control heart failure, indicating that mortality rates from this condition have declined dramatically from about 25 to 5 percent.
Mr. Phillip Williams and Dr. Victor Dzau praised the GPRA report and recommended that it be widely disseminated. In response to a question from Dr. Dzau about evaluating relative expectations, Dr. Weisfeldt said that the usual criterion for determining whether research far exceeded expectations was based on it having a direct impact on human disease. Exceptions were made, for example, in the case of RNA polymerase-2 because information about it, although not of direct health benefit, could lead to discoveries of benefit in treating human diseases.
Dr. Barrie Carter praised the staff for completing a superbly written report.
Dr. Kirschstein said that NIH has worked with OMB to develop an approach for GPRA that avoids repeating certain evaluation procedures every year and also for conducting five-year assessments. Thus, the NIH GPRA report is likely to have a different appearance in years to come.
Dr. Larry Smarr said that for the information technology industry in almost every case, major industrial developments could be traced to Federal investments in research 10 to 15 years earlier, according to a report prepared for the National Research Council (NRC). He suggested preparing a similar report for NIH to document its contributions to industry and said that such a report could complement the findings in the GPRA report.
IMPLEMENTATION OF THE POLICY FOR USE OF HUMAN EMBRYONIC PLURIPOTENT STEM CELLS
Dr. Kirschstein reminded ACD members that President Bush issued his policy decision on Federal support for research using human embryonic stem cells in August. She also said that each ACD member had been provided with a report on this subject that was prepared by Dr. Lana Skirboll and her staff and published in July. President Bush announced that Federal funding would be allowed for use on those human embryonic stem cells that existed before August 9, 2001, and that met several criteria, including that they were derived from an embryo that was created for reproductive purposes, the embryo was no longer needed, informed consent was obtained for donating that material, and no financial inducements were provided for that donation. To facilitate such research, NIH established a Website registry for cells meeting these criteria.
Dr. Baldwin described additional steps that NIH is taking to implement this new registry-based system. For example, NIH sought written assurances from stem cell providers that their cell lines meet the President's criteria, and has also set up tracking procedures for investigators who seek to obtain and use those cells for NIH-sponsored projects. She demonstrated how the special NIH Website looks and the types of information that are available on its different pages. The Website soon will include a section of frequently asked questions and answers, and it will be updated on a weekly basis. She said that many intellectual property rights questions will need to be worked out between investigators and providers of different lines of stem cells.
Dr. Baldwin said that NIH is encouraging investigators who plan to use such cells to make arrangements through specific NIH-support programs, but also is trying to develop NIH-wide responses to issues that arise. To accommodate researchers who are seeking NIH support in the first round of review, Dr. Baldwin relaxed application deadlines from October 1 to November 27, 2001, during which about a half-dozen investigators submitted proposals; more are expected during the next round.
In response to a question related to repositories from Dr. Bettie Sue Masters, Dr. Baldwin said that establishing a repository would entail resolving other issues that still need to be addressed. However, the program announcement of November 29, 2001, offers an infrastructure award that would help stem cell providers in responding to requests for cells from scientists. She also said that these issues and concerns will likely change over the next 12 to 18 months as more research is done using such cells.
In response to a question from Ms. Rebecca Eisenberg on intellectual property issues, Dr. Baldwin said that the initial agreement between WiCell and NIH, which covered the NIH Intramural Program, was being extended to cover extramural investigators, who will merely need to sign a memorandum of understanding that was developed by NIH and which covers basic research uses of such cells. Dr. Rohrbaugh said that NIH-supported work on nonhuman primate stem cells led to a patent broadly claiming all primate embryonic stem cells that is controlled by WiCell through the University of Wisconsin and the Wisconsin Alumni Research Fund. He said that NIH is negotiating with additional providers of human embryonic stem cells that meet President Bush's criteria.
In response to another question from Ms. Eisenberg about researchers using stem cells from WiCell and from other providers, Dr. Rohrbaugh said that WiCell agreed to permit anyone with NIH funding also to use stem cells from third parties as long as those agreements do not grant commercial rights. He said that WiCell's dominant patent would allow it to assert rights for forthcoming commercial applications. Dr. Rohrbaugh said that he was not aware of additional agreements being worked out between WiCell and other stem cell providers.
Mr. Phillip Williams asked whether the President's criteria seem to set limitations but might also establish certain advantages on research with such stem cells. He also asked what other countries are doing to regulate such stem cell research. In response, Dr. Kirschstein said that Dr. Baldwin recently attended a meeting of the heads of national research organizations that was held in Strasbourg, who also are trying to develop procedures for using such cells in research. Dr. Baldwin said that, by June 2002, some European countries will likely have developed such procedures and suggested that it would be useful to revisit this topic at the next ACD meeting. She said that progress in dealing with these issues slowed following the September 11 attacks.
Dr. Kirschstein pointed out that some of the eligible stem cell lines are maintained in India. She also said that procedures for handling such stem cells and possibly establishing a repository that were being worked out in England are not moving forward so rapidly as they once were because of issues being raised in Parliament. She said that there are many technical problems to address in terms of growing and studying such cells.
Mr. Williams further suggested that the issue of therapeutic versus reproductive cloning be considered at a forthcoming meeting of ACD. In response, Dr. Kirschstein said that NIH would continue to separate these two issues, Federal funds are not permitted for reproductive cloning research, and hearings are scheduled in Congress to address bills that would make it a criminal offense to do such research even with private funding. In response to a question from Ms. Eisenberg, Dr. Kirschstein said that NIH would not be testifying at Congressional hearings looking into human cloning-related issues because President Bush has said that there will be no Federal support for such research.
In response to a question from Dr. Thomas Cech on the actual availability of stem cell lines that are listed on the NIH registry, Dr. Baldwin said that some, such as those from WiCell, are available, whereas others are not. She expects this situation to be fluid and fast-changing, and she commended the NIH National Center for Research Resources (NCRR) and several Institutes for putting together the infrastructure announcement and taking other steps to move matters forward.
In response to a question from Dr. Victor Dzau about NIH developing a special program through a request for applications on such stem cell research, Dr. Kirschstein said that many Institutes are considering this possibility. Dr. Marvin Cassman, Director of the National Institute of General Medical Sciences (NIGMS), said that a meeting is being planned for the spring of 2002 to discuss research needed to understand the fundamental biology of stem cells.
Dr. Kirschstein said that NIH responds to natural disasters, such as floods and earthquakes, by helping local grantee institutions cope with lost equipment and research-related materials. In 2001, NIH faced two exceptional circumstances, one arising from damage caused by Tropical Storm Allison that affected several institutions in Houston and the other following the September 11 attacks in New York City and at the Pentagon.
June 2001 Tropical Storm Allison in Houston, Texas
Dr. Baldwin said that intense rains from Tropical Storm Allison overwhelmed the local storm drainage systems in Houston, leading to major water damage at several research institutions, particularly the Texas Medical Center. Dr. Baldwin, Ms. Carol Alderson, and other NIH staff members, HHS Secretary Tommy Thompson, and officials from the Federal Emergency Management Administration (FEMA) were among those who visited damaged biomedical research sites in that area, provided assistance, and developed guidance documents for coping with the damage. Dr. Baldwin said that appointing a case manager is an essential component of the NIH approach to dealing with such matters because such an individual can provide researchers and administrators at affected institutions with a single point of contact with NIH. The individual can help affected researchers in their dealings with other Federal agencies, such as FEMA, and in contacting appropriate Institutes, Centers, and offices within NIH, particularly as researchers attempt to repair or replace major pieces of shared instruments, lost materials, and other damaged items.
An important lesson is that research institutions should have good systems and good records in place because they are of great value in assessing damage from such events, according to Dr. Baldwin. Also, researchers need to store valuable data sets at separate locations and, where possible, valuable specimens, including cell lines, animals, and other materials that would be especially difficult to replace. Dr. Baldwin said that NIH will prepare a guidance document based on lessons learned from the experience in Houston.
September 11, 2001 Attacks in New York City and Washington, D.C., and Events Thereafter
Dr. Kirschstein said that circumstances at NIH changed dramatically after the September 11 attacks on the World Trade Center in New York and the Pentagon. For example, security is being enhanced on the NIH campus, where 16,000 employees work and another 5,000 individuals visit each day.
Some NIH-sponsored research programs were affected directly by the attacks. For instance, the social sciences research that was being conducted at the World Trade Center was damaged or lost, although those working on the project are safe, according to Dr. Kirschstein. NIH-sponsored research at City University of New York also was affected because its administrative offices had to relocate, delaying 19 grants, and the Alan Guttmacher Institute similarly lost access to its offices, leading NIH to agree to allow delays in application deadlines, and to assign a case manager to deal with additional problems.
Shortly after the attacks, several NIH staff members were deployed to New York as part of an HHS disaster medical assistance team, along with other NIH staff members who are commissioned officers. The Surgeon General froze all commissioned officers in position, postponing retirements and resignations. In addition, the NIH blood bank stepped up its blood collection efforts, and provisions were made to use facilities at the Clinical Center at NIH and similar facilities at neighboring Federal hospitals. The National Institute of Environmental Health Sciences (NIEHS), which supports three centers in New York, provided advice to address local environmental concerns.
While NIH was working with the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) on plans for bioterrorist-defense vaccination programs, the first anthrax case came to light, leading to a second phase of the emergency response, according to Dr. Kirschstein. As part of the response to bioterrorism threats, Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), Dr. John LaMontagne, the NIAID Deputy Director, and other staff are working intensively with HHS Secretary Tommy Thompson on such matters, along with Dr. D. A. Henderson and others, including Dr. Joshua Lederberg, according to Dr. Kirschstein. Dr. Deborah Wilson, Director of the NIH Occupational Health and Safety Branch, is testing suspicious mail and other items for evidence of bioterrorist-related contaminants, while the clinical laboratory at the NIH Clinical Center is also involved in such testing.
Dr. Kirschstein said that NIAID is taking the lead in basic research on agents of potential use for bioterrorism, and those efforts include determining the genomic sequence of some of those organisms, such as the Bacillus anthracis Ames strain that was used in the deliberately inflicted cases of anthrax. Because supplies of the vaccine that protects against smallpox are low, some first responders have been vaccinated as a precaution, and NIAID is conducting a study with volunteers to determine whether that vaccine retains efficacy if administered in diluted form. Other efforts include projects to develop new and alternative vaccines as well as safe and effective antiviral agents to use against these and other disease agents that might be used in bioterrorist attacks.
Dr. Bettie Sue Masters said that researchers in Texas, including an assistant professor who lost a valuable nuclear magnetic resonance instrument, are very grateful for the assistance NIH has provided.
Dr. Thomas Cech asked several questions about NIH contingency plans if the campus were forced to close for an extended period. For example, how would NIH maintain continuity of its grant programs? In response, Dr. Baldwin said that NIH operations were closed several years ago for more than one month when the Federal government was shut down because of a budget dispute. She also said that extramural programs are now being managed by means of an electronic data system with extensive back-up features. Of course, any major disruption has multiple effects, and the September 11 events forced the temporary closure of Reagan National Airport, which led NIH to cancel many meetings. She said that NIH has met these contingencies with a willingness to accommodate reviewers, would-be meeting attendees, and others in as flexible a manner as possible.
In response to another question from Dr. Cech about possible lost access to NIH offices, Dr. Baldwin said that many staff members have access to NIH data from computers at home but arranging for them to work together at an alternate site would be a challenge. Dr. Kirschstein said that there are plans for dealing with some, but not all, contingencies. Dr. Cech said that the Howard Hughes Medical Institute (HHMI) is trying to develop its own set of contingency plans, including plans to provide offsite servers that would enable staff members to access databases from home or from emergency centers. Also, HHMI will set up a special facility in Virginia for use in emergencies. Dr. Baldwin said that NIH staff members will need to learn more about backing up materials onto networks that are themselves backed up.
In response to questions from Dr. Larry Smarr, Dr. Kirschstein said that efforts are under way to develop better diagnostic and detection methods for bioterrorist agents. She also said that the experience of coping with recent anthrax attacks indicates how unfamiliar physicians and microbiologists are with this disease and also that available information is out-of-date and inadequate for dealing with this disease, particularly when the pathogen is deliberately disseminated as very small, specially prepared particles.
In response to a question from Dr. Masters about distributing vaccines, Dr. Kirschstein said that Secretary Thompson is meeting with vaccine manufacturers to develop such plans. She also said that vaccines often produce side effects, and there is a Federal indemnification program to handle such problems. She said that a great deal of education is needed at the professional level to deal with these issues.
Dr. Thomas Ansfield said that the University of Wisconsin as well as local companies are developing varied disaster response programs, but he questions how much of this planning is practical.
In response to a question from Mr. Arthur Ullian about risks to foods, Dr. Kirschstein said that foodborne illnesses represent a continuing risk to the public, and also that FDA is developing food safety plans for dealing with bioterrorist threats.
Dr. Smarr said that improvements in information technology could help in bioterrorist surveillance efforts, including at emergency rooms where data describing potential victims could be aggregated and automatically analyzed to detect outbreaks that appear suspicious and might be due to a bioterrorist attack. In response, Dr. Kirschstein said that CDC has revitalized the Epidemic Intelligence Service and is strengthening state and local health departments that monitor infectious diseases.
Dr. Donald Wilson said that it is important to realize how costly such efforts are, particularly as they extend to the level of emergency rooms. In response to comments from Ms. Rebecca Eisenberg that data collected by health insurance companies or by pharmacies might be useful for monitoring outbreaks, Dr. Wilson said that reliance on such systems would not work because their response times are too slow. Dr. Smarr said that the health care system is regressive in terms of harnessing modern information technologies.
Dr. Kirschstein said that there will be a follow-up discussion of these issues at the June 2002 ACD meeting.
PRESENTATION ON PRESIDENT'S INFORMATION TECHNOLOGY ADVISORY COUNCIL
Dr. Yvonne Maddox, NIH Acting Deputy Director, chaired the remainder of the ACD meeting due to Secretary Thompson's request that Dr. Kirschstein attend a meeting at the White House. Dr. Maddox introduced Dr. Larry Smarr, who serves on the President's Information Technology Advisory Council (PITAC).
Dr. Smarr began serving on PITAC when it was founded about five years ago by Congress and the White House. The members of PITAC, who are drawn from leaders in the information technology (IT) field from universities and industry, delivered their first report in February 1999, and it focused on four areas, namely software, scalable information infrastructure, high-end computing, and the socioeconomic impact of information technology. It was followed by a series of reports, and they have had an impact across agencies of the Federal government, including many that support research.
Dr. Smarr focused on one of those reports, "Transforming Health Care Through Information Technology," which was made public in February 2001. It was developed through a committee, co-chaired by Dr. Edward Shortliffe of Columbia University College of Physicians and Surgeons and by Dr. Sherrilynne Fuller of the University of Washington School of Medicine, and whose other members were (IT) professionals. The committee members learned a great deal about exciting areas where IT and biology research are coming together, such as genomics and clinical medicine.
Dr. Smarr said that, despite many isolated examples of applying IT, U.S. biological researchers do not share a common vision of how IT will transform health care and biomedical research, and that some current policies are blocking developments that would lead to wide adoption of IT among such researchers. Although NIH has an important role to play in promoting IT, there are not enough appropriately trained professionals by one or two orders of magnitude to achieve that goal, which will require a long-term commitment.
Dr. Smarr said that NIH needs to take a leadership role in IT research, rather than depending on the efforts of other Federal agencies such as the National Science Foundation (NSF) or the Defense Advanced Research Projects Agency (DARPA). Instead, NIH has said that it does not fund computer science research, meaning that the needs for IT in studying complex biological problems are not being taken into account or helping to drive computer science research. He said that an exception is the National Library of Medicine (NLM), which has been at the forefront of IT applications to biomedical research.
Dr. Smarr said that much in that February 2001 report deals with clinical issues outside the sphere of NIH research, including information-based decision-making systems in hospitals. For example, information about best clinical practices is, in many cases, sequestered in private records kept by individual physicians. Dr. Smarr said that if such information were incorporated into information technology systems, it could become part of an artificial intelligence base from which useful and important conclusions could be drawn that would benefit medical practice. He said that the report focuses on the health care industry and is broadly critical of the Department of Health and Human Services for not fostering the development of IT expertise in its staff and for not developing policies that would speed the adoption of IT throughout the health care system.
Dr. Smarr said that some recommendations in the February 2001 PITAC report overlap with those in the NIH Biomedical Information Science and Technology Initiative (BISTI) report, which was developed by a committee that he co-chaired with Dr. David Botstein of Stanford University. For example, both reports recommend supporting technology centers where biomedical practitioners and IT specialists work together. The BISTI report emphasizes computational biology and biological databases, whereas the February 2001 PITAC report emphasizes use of IT in clinical trials and for health care delivery and practice.
Further, the BISTI report recommends that NIH partner with other agencies, such as NSF and DARPA, to design and deploy a scalable national computing and information system to support biomedical research, according to Dr. Smarr. He said that the PITAC report acknowledges and emphasizes the need for designing IT systems for use in health care that ensure privacy. The report also recommends increasing the number of people who are trained both in health care specialties and in IT, that HHS take a leadership role in determining how IT can improve health care and that the department support research that will address such issues, that agencies within HHS invest in computer science research, and that HHS appoint someone at the Secretary's level to lead these IT efforts.
Dr. Smarr said that a recent $20 million award from the NIH National Center for Research Resources to support a multi-institutional Brain Imaging Research Network (BIRN) is an important early step to support broad-based IT efforts. This project will entail software architecture development as well as a networking effort. Early plans also call for moving to a wireless system that can be accessed by physicians and researchers at a variety of institutions and locations. Eventually, the system will move beyond its initial focus on the brain to encompass other organ systems.
Dr. Smarr said that, in his opinion, NIH is moving too slowly to support IT, in part, because it is not hiring highly qualified IT experts and also because it is not joining forces with other agencies and has not really been part of PITAC. However, he added, hiring Al Graeff to be the chief information officer was an important step forward.
Dr. Smarr also endorsed the use of handheld Blackberry devices by high level NIH staff as a culture changing method.
Dr. David Korn said that, whenever NIH has considered IT, its focus was on basic research, not on clinical research or patient care-related issues. In response, Dr. Smarr agreed and said that IT could make important contributions at the interface between basic research and clinical medicine. He also said that former NIH Director Dr. Harold Varmus and former NCI Director Richard Klausner convinced him to be a co-chair of BISTI in part because of their enthusiasm over the potential for bringing IT developments forward to meet various basic needs throughout genome research and for eventual use of IT in clinical trials.
Dr. Korn said that because Congress did not pass comprehensive privacy legislation, HHS developed a rule that will hamper clinical and public health research because it severely restricts access to patient records. In response, Dr. Smarr said that these matters were not addressed explicitly by the PITAC group in developing the February 2001 report, but committee members are aware of those restrictions and, in their recommendations, urge HHS to take a stronger leadership role in overcoming such obstacles. He also predicted developments in the next decade that would harness IT for use for far-reaching diagnostic breakthroughs, such as virtual colonoscopies and for tailoring drug therapies to an individual's genetic peculiarities through read-outs of the genome. However, he added, political decisions may interfere with this progress.
Dr. Victor Dzau commented on the fundamental problem of health care systems using so many different IT systems and the shortage of funding for a global IT system for health care. In response, Dr. Smarr said that the PITAC report recognizes that the health care system is a mixed public- and private-sector enterprise. However, he also noted that the movement to develop health maintenance organizations was leading to some consolidation of disparate health care organizations within the entire system, and that consolidation often consists of linking different IT systems and making them compatible with one another. Dr. Dzau said that it will be important not to generate additional independent IT systems that cannot be linked, and predicted that it will take a substantial investment and a Federal mandate to do so. Dr. Smarr agreed, citing recommendation five in the February 2001 report that calls for HHS to establish a blue ribbon panel to take a leadership role on these issues.
In response to a question from Mr. Arthur Ullian about affording health care, Dr. Smarr said that other sectors in the economy have grown rapidly during the past decade because they have invested in IT, whereas there has been little such investment by the health care sector, particularly where IT might be used by physicians in their direct dealings with patients and with their medical records. He said that this same problem permeates biology as reflected in the BISTI report, which indicates that many young scientists go into biology because they were avoiding mathematics and computer science courses.
Dr. Masters said that universities are trying to train individuals who are expert in biology and in computer science subjects, but help is needed at the basic level. In response, Dr. Smarr said that, although there were shortages of IT specialists for hire by universities a few years ago, changes in the private sector since so many "dot.com" companies failed mean that many more such specialists are available.
Dr. Donald Wilson said that hospitals might want to hire such specialists but often cannot afford to do so. However, the Veterans Administration (VA) hospitals have marked progress in digitizing radiology, setting up electronic systems for patient records, and computerizing the pharmacy system. Dr. Smarr agreed, noting that the VA hospital in San Diego has a much more sophisticated electronic system than does the hospital at the medical school of the University of California, San Diego. He also said that an important goal is to lower the costs of such systems to make them more widely available.
Dr. William Brody agreed with Dr. Wilson about the shortage of capital within the health care system, a fact that makes it difficult for hospitals, including those at universities, to invest in sophisticated IT systems, leading instead to investments seeking short-term payoffs. Although many hospitals are losing money, it is important to make such investments, he added. Dr. Dzau agreed, saying that this issue is of fundamental importance and national in scope. He further said that the Partners Healthcare system in Massachusetts has invested a great deal in its IT system but, even so, it is rudimentary in many respects. He suggested that the necessary investment could be very large and that meeting this challenge at the national level will be very difficult. In response, Dr. Smarr said again that HHS needs to take a leadership position and make this issue a national priority.
Ms. Rebecca Eisenberg asked whether there is a failure by the private sector not to meet IT needs in biomedical research and health care. In response, Dr. Brody said that IT companies see the health care system as slow to make decisions on IT purchases and also not a sufficiently lucrative market. He said that 40 percent of the hospitals in Maryland are losing money, thus exemplifying the shortage of funds for investing in IT systems.
Dr. Maddox said that NIH has supported substantial research efforts in IT in conjunction with biomedical research, particularly through extramural research programs. For example, the NIH Biomedical Research Infrastructure Network Program and a similar program are looking at medical rehabilitation networks. She said that BISTI represents another major area and that there is a need for more private-public partnerships to promote IT development.
Dr. Maddox introduced Dr. James Battey, Jr., who is chair of the NIH IT Board of Governors. He said that a new clinical research information system is being developed for the new hospital at the NIH Clinical Center that will ensure security while providing access to data for use by researchers. He estimated that the cost for this system would be $60 million over five years. Dr. Smarr said that this effort is a good example of real progress and could help the NIH Clinical Center to set standards for other institutions to meet.
Dr. Judy Vaitukaitis said that the nodes of the NIH BIRN system will be located at many dozen biotechnology research centers, clinical research centers and other sites; will include physicists and other specialists; will conduct imaging research on humans and animals; and will include hardwired and wireless connections for transmitting data among the nodes. Dr. Smarr suggested that this system be reviewed next year as part of the GPRA evaluation. He also said that NIH is making progress and is beginning to take IT seriously. Al Graeff said that IT systems in clinical centers are difficult to manage and use, that it will take a careful and organized effort to change those systems, and those changes need to be considered in light of meeting patient privacy requirements.
In response to a question from Mr. Ullian about mandating a study, Dr. Smarr said that such an undertaking is formidable and it should focus on the interface between clinical care and research, rather than on IT and basic research.
FURTHER DISCUSSION AND DECISION ON EXTRAMURAL CONSTRUCTION REPORT
Dr. Maddox said that a committee was formed in 2000 to consider research facilities construction needs and reminded ACD members that Dr. William Brody presented a preliminary report on this subject during the June 2001 meeting. She said that the three main recommendations in the report from the committee are to look at Federal grants programs for facilities renewal, to consider a Federal loan guarantee program, and to review Federal indirect cost policies to determine how they could better serve extramural research facilities construction needs.
Dr. Brody said that committee members agreed that the national research infrastructure requires a major capital investment from NIH, particularly to keep pace with recent growth in its budget. The committee recommends that NIH appropriate the full $250 million that is authorized for FY 2002 for construction grants and that it consider increasing that total to as high as $1 billion. Within that category, NIH should assign some fraction of construction funds to emerging and minority-serving institutions, allowing them to compete for such funding in a separate category.
Dr. Brody said that, although the Office of Management and Budget apparently does not favor a program of Federal loan guarantees for constructing research facilities, such a program would enable institutions to borrow at favorable rates and could save the government in terms of lowered interest payments on construction loans.
The third set of recommendations in the report addresses changing facilities and administrative (F & A) rates to capture construction costs, according to Dr. Brody. However, changes that tend to increase F & A rates are likely to prove untenable politically. He said that a policy statement indicating that the Federal government was committed to reimburse F & A costs and that the increasing facility costs to fund new construction and renovation would be reimbursed. Such a policy would encourage institutions to continue to make long-term commitments to invest in facility construction.
In response to a question from Dr. David Burgess, Dr. Brody said that there is considerable deferred maintenance among research facilities along with obsolescence because of fast-changing technologies. He said that accelerating depreciation rates would help to address some of those issues, but such a move would increase costs. He also said that 30 years ago donors were more inclined to provide funds for construction, whereas they now tend to endow programs rather than invest in facilities. Dr. David Korn agreed with Dr. Brody's description of trends among donors.
Dr. Korn also said that current depreciation schedules for research facilities are unrealistic, and thus should be revised to help institutions recover their outlays. In response, Dr. Judy Vaitukaitis said that there is greater flexibility in depreciation schedules than institutions realize and that she would provide ACD with additional information on this subject.
Dr. Bettie Sue Masters said that, during this period of generous funding by Congress, NIH should regard funds for construction as a sound investment. She also said that extramural researchers support this notion as well as the recommendation in the report calling for Federal loan guarantees for research facilities construction costs.
Dr. Maddox said that, although this recommendation for loan guarantees would likely remain difficult to implement, NIH is moving ahead to provide some funds for construction through grant mechanisms. For example, in FY 2001, NIH issued $75 million in 43 one-time awards for such purposes. Funding for this program for FY 2002 is expected to be somewhere between $97 million to $125 million. In response, Dr. Brody said that, although such funding is welcome, it falls far short of the committee's recommendation. He said that the estimated need for such construction spending is much higher, in the range of $5 billion to $15 billion.
Dr. Donald Wilson said that ACD should endorse the report and its three central recommendations. Dr. Barrie Carter agreed. In response to a question from Mr. Phillip Williams, Dr. Maddox said that NIH would respond to this endorsement by reviewing among themselves, members of HHS and OMB, and others how best to implement those recommendations. Dr. Brody said that it will be useful to look at those three sets of recommendations to determine a realistic dollar impact for implementing each of them. He volunteered to work with NIH officials to analyze and evaluate these options in terms of their quantitative impact. Dr. Maddox said that other members of ACD may be called on to participate in this effort.
The Advisory Committee to the Director (ACD) of the National Institutes of Health (NIH) met on December 6, 2001, to consider a review of overall NIH performance, progress in implementing President Bush's policy for research using human embryonic stem cells, the NIH response to exceptional events, and recommendations on information technology research and on increasing support to meet extramural research facilities construction needs.
The ACD acknowledged, commented on, and endorsed several of the recommendations in the reports. ACD members also recommended a broader dissemination of the GPRA findings and development of several alternative ways to evaluate overall NIH performance. They also advised NIH to develop ways of implementing the recommendations in the research facilities construction report.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Yvonne Maddox, Ph.D. Acting Executive Secretary Advisory Committee to the Director
Appointment of Christine K. Cassel, M.D., as Head, Oregon Health and Science University School of Medicine
September 18, 2001 article from The New York Times
October 5, 2001 article from the Oregon Health and Science University news and Information
NIH Guide: National Research Service Award (NRSA) Stipend Increase and Other Budgetary Changes Effective for Fiscal Year 2001
Implementation of the Policy for Use of Human Embryonic Pluripotent Stem Cells
NIH Human Embryonic Stem Cell Registry and Example
Implementation Issues for Human Embryonic Stem Cell Research Frequently Asked Questions
NIH Guide: Notice of Criteria for Federal Funding of Research on Existing Human Embryonic Stem Cells and Establishment of NIH Human Embryonic Stem Cell Registry, Nov. 7, 2001
NIH Guide: Notice of Extended Receipt Date and Supplemental Information Guidance for Applications Requesting Funding that Proposes Research with Human Embryonic Stem Cells, Nov. 7, 2001
Office for Human Research Protections: Guidance for Investigators and Institutional Review Boards Regarding Research Involving Embryonic Stem Cells, Germ Cells and Cell-Derived Test Articles, Nov. 16, 2001
NIH Guide: Federal Government Clearances for Receipt of International Shipment of Human Embryonic Stem Cells
NIH Guide: Notice of Withdrawal of NIH Guidelines for Research Using Pluripotent Stem Cells, Corrected Nov. 21, 2001
NIH Stem Cell Information
NIH Stem Cell Information Archives
Final Report of the NIH Working Group on Construction of Research Facilities, July 6, 2001
President's Information Technology Advisory Committee
Information Technology for the Twenty-First Century Initiative, September 8, 1999
Transforming Health Care Through Information Technology, February 2001
* Copies of these reports and articles are available upon request by calling (301) 496-0959.