Clinical Research
NIH Has Implemented Key Provisions of the Clinical Research Enhancement Act Gao ID: GAO-02-965 September 18, 2002Clinical research is critical for the development of strategies for the prevention, diagnosis, prognosis, treatment, and cure of diseases. Clinical research has been defined as patient-oriented research, epidemiologic and behavioral studies, and outcomes research and health services research. The National Institutes of Health (NIH) is the principal federal agency that funds clinical research supporting individual clinical investigators, clinical trials, general and specialized clinical research centers, and clinical research training. For many years, there have been concerns that clinical research proposals are viewed less favorably than basic research during the peer review process at NIH and that clinical research has not received its fair share of NIH funding. In November 2000, the Clinical Research Enhancement Act was enacted to address some of these concerns. NIH reports that it has increased its financial support of clinical research and that spending on clinical research has kept pace with total NIH research spending. NIH has taken some steps to improve its peer review of clinical research applications. The Center for Scientific Review recently added two new peer review study sections for the review of clinical research applications--one for clinical cardiovascular science and other for clinical oncology. NIH has increased its support of general clinical research centers, as required by the act, although the program has grown more slowly than NIH's overall estimated expenditures on clinical research. NIH has established the four clinical research career enhancement award programs mandated by the act. Three of these programs have been implemented, and they support new and midcareer clinical investigators and institutional clinical research teaching programs. The fourth program is designed to support graduate training in clinical investigation. NIH has initiated a new extramural loan repayment program specifically for clinical investigators as required by the act. This program was launched in December 2001. NIH received 456 applications by the February 2002 deadline. Twenty-one of NIH's institutes plan to fund 396 loan repayment contracts, for a total of $20.2 million, by the end of fiscal year 2002.
RecommendationsOur recommendations from this work are listed below with a Contact for more information. Status will change from "In process" to "Open," "Closed - implemented," or "Closed - not implemented" based on our follow up work.
Director: Team: Phone:GAO-02-965, Clinical Research: NIH Has Implemented Key Provisions of the Clinical Research Enhancement Act
This is the accessible text file for GAO report number GAO-02-965
entitled 'Clinical Research: NIH Has Implemented Key Provisions of the
Clinical Research Enhancement Act' which was released on September 18,
2002.
This text file was formatted by the U.S. General Accounting Office
(GAO) to be accessible to users with visual impairments, as part of a
longer term project to improve GAO products' accessibility. Every
attempt has been made to maintain the structural and data integrity of
the original printed product. Accessibility features, such as text
descriptions of tables, consecutively numbered footnotes placed at the
end of the file, and the text of agency comment letters, are provided
but may not exactly duplicate the presentation or format of the printed
version. The portable document format (PDF) file is an exact electronic
replica of the printed version. We welcome your feedback. Please E-mail
your comments regarding the contents or accessibility features of this
document to Webmaster@gao.gov.
This is a work of the U.S. government and is not subject to copyright
protection in the United States. It may be reproduced and distributed
in its entirety without further permission from GAO. Because this work
may contain copyrighted images or other material, permission from the
copyright holder may be necessary if you wish to reproduce this
material separately.
United States General Accounting Office:
GAO:
Report to Congressional Committees:
September 2002:
Clinical Research:
NIH Has Implemented Key Provisions of the Clinical Research Enhancement
Act:
GAO-02-965:
Contents:
Letter:
Results in Brief:
Background:
Growth in NIH‘s Spending on Clinical Research Has Kept Pace with Total
Spending:
NIH Has Taken Steps to Improve Its Peer Review of Clinical Research:
NIH Has Increased Its Support and Scope of GCRCs:
NIH Has Increased Its Support of Clinical Research Career Development
and Training:
NIH Has Established an Extramural Loan Repayment Program for Clinical
Investigators:
Conclusion:
Recommendation for Executive Action:
Agency Comments:
Appendix I: NIH‘s Estimated Expenditures for Extramural and Intramural
Clinical Research, by IC, Fiscal Years 1997 - 2001:
Appendix II NIH‘s Extramural Clinical Research Loan Repayment Contracts
by IC, Fiscal Year 2002:
Appendix III Comments from the National Institutes of Health:
Tables:
Table 1: Extramural and Intramural Total and Clinical Research
Expenditures in Fiscal Year 2001:
Table 2: Funding, Number, and Activities of GCRCs Have Increased from
Fiscal Year 1997 to Fiscal Year 2001:
Table 3: Clinical Research Career Development Award Programs
Established by NIH since Fiscal Year 1999:
Figures:
Figure 1: Percentage of NIH Extramural Clinical Research Expenditures
by Funding Mechanism in Fiscal Year 2001:
Figure 2: NIH‘s New Clinical Research Career Development Awards
Relative to All NIH Career Development Awards in Fiscal Year 2001:
Abbreviations:
AAMC: Association of American Medical Colleges:
AMA: American Medical Association:
CREA: Clinical Research Enhancement Act:
CSR: Center for Scientific Review:
GCRC: general clinical research center:
ICs: institutes and centers:
IOM: Institute of Medicine:
NCI: National Cancer Institute:
NCRR: National Center for Research Resources:
NHLBI: National Heart, Lung, and Blood Institute:
NIAID: National Institute of Allergy and Infectious Diseases:
NIH: National Institutes of Health:
NIMH: National Institute of Mental Health:
OER: Office of Extramural Research:
OMB: Office of Management and Budget:
[End of section]
United States General Accounting Office:
Washington, DC 20548:
September 18, 2002:
The Honorable Edward M. Kennedy:
Chairman:
The Honorable Judd Gregg:
Ranking Minority Member:
Committee on Health, Education, Labor, and Pensions:
United States Senate:
The Honorable W.J. ’Billy“ Tauzin:
Chairman:
The Honorable John D. Dingell:
Ranking Minority Member:
Committee on Energy and Commerce:
House of Representatives:
Clinical research is critical for the development of strategies for the
prevention, diagnosis, prognosis, treatment, and cure of diseases.
Clinical research has been defined as patient-oriented research,
[Footnote 1] epidemiologic and behavioral studies, and outcomes
research and health services research.[Footnote 2, Footnote 3] In
contrast, basic biomedical research involves fundamental investigations
that do not focus directly on patients or their diseases. [Footnote 4]
The National Institutes of Health (NIH) is the principal federal agency
that funds clinical research, supporting individual clinical
investigators, clinical trials, general and specialized clinical
research centers, and clinical research training. NIH‘s total budget
grew dramatically from about $12.8 billion in fiscal year 1997 to an
estimated $23.6 billion in fiscal year 2002. NIH‘s 27 institutes and
centers (ICs) each receive separate appropriations and accomplish their
missions through intramural research (government scientists conducting
research at NIH‘s own laboratories and clinics) and, to a greater
extent, through extramural research (scientists conducting research at
institutions outside of NIH). Scientists compete for funding from NIH,
and research proposals are evaluated for their eligibility for funding
by peer review study sections of primarily nonfederal scientists.
As NIH‘s overall budget has grown, more attention has focused on its
support of clinical research. For many years there have been concerns
that clinical research proposals are viewed less favorably than basic
research during the peer review process at NIH and that clinical
research has not received its fair share of NIH funding. Also at issue
have been the declining numbers of physician-investigators and the
challenges they face, such as inadequate clinical research training and
high debt from educational loans. In November 2000 the Clinical
Research Enhancement Act (CREA) was enacted to address some of these
concerns. [Footnote 5] The act directed NIH to consider recommendations
from earlier studies for enhancing clinical research and to support and
expand its resources for clinical research in general and in specific
ways. [Footnote 6] The act also mandated that we evaluate NIH‘s
implementation of its provisions. To that end, we determined whether
and how NIH has (1) increased its funding of clinical research and
expanded its clinical research activities, (2) improved its review of
clinical research proposals, (3) supported general clinical research
centers GCRC) [Footnote 7] and expanded their activities, (4)
established new clinical research career development and training
programs, and (5) implemented a loan repayment program for extramural
clinical investigators.
To assess NIH‘s progress in complying with the requirements of CREA, we
reviewed NIH documents and data on clinical research expenditures, peer
review of clinical research, clinical research training and career
development award programs, and the clinical research loan repayment
program. We also interviewed officials at several offices and institutes
within NIH, including the Office of the Director, the Center for
Scientific Review (CSR), the National Center for Research Resources
(NCRR), and other institutes. Finally, we interviewed and consulted
with key stakeholders, including the Association of American Medical
Colleges (AAMC), the Institute of Medicine‘s (IOM) Clinical Research
Roundtable, and other clinical research experts. The scope of our
report was restricted to NIH‘s implementation of CREA, and we did not
evaluate the effectiveness of NIH‘s actions in promoting clinical
research. NIH took some actions required by CREA prior to its passage.
For this reason, we looked at all relevant actions taken by NIH, not
just those initiated since November 2000. We conducted our work from
December 2001 through August 2002 in accordance with generally accepted
government auditing standards.
Results in Brief:
In general, NIH reports it has increased its financial support of
clinical research and that spending on clinical research has kept pace
with total NIH research spending. In fiscal year 2001, NIH reported
that overall it spent approximately $6.4 billion on clinical research,
or about 32 percent of its total research dollars. Total clinical
research expenditures increased by 44 percent (adjusted for inflation)
from fiscal year 1997 to fiscal year 2001, while the proportion of
NIH‘s total research dollars spent on clinical research remained
constant during the same time. NIH‘s reports of clinical research
expenditures represent the best available indications of financial
trends over time, but they are not precise figures because the process
of counting clinical research dollars varies widely across ICs. NIH
officials told us that they are working on ways to make their counting
of clinical research dollars more uniform across the ICs. In response
to CREA, some institutes have developed new clinical research
initiatives, including funding new clinical research centers for a
variety of diseases and conditions.
NIH has taken some steps to improve its peer review of clinical research
applications. CSR, the center that reviews most research grant
applications submitted to NIH, recently added two new peer review study
sections for the review of clinical research applications, one for
clinical cardiovascular science and the other for clinical oncology.
For other clinical research applications, CSR officials said it is
their general goal to review them in study sections in which at least
30 percent of the applications involve clinical research and in which
at least 30 percent of reviewers are themselves clinical investigators.
However, they stated that this goal cannot always be achieved if the
number of clinical research applications in a specific scientific area
is small, because reviewing applications in a study section that
provides the appropriate scientific context is given priority over
quantitative targets for grouping. NIH has also established peer review
mechanisms at the ICs for the review of the career development and
training awards established under CREA.
NIH has increased its support of GCRCs, as required by CREA, although
the program has grown more slowly than NIH‘s overall estimated
expenditures on clinical research. Funding for the GCRCs increased by 24
percent (adjusted for inflation) from $153,521,000 in fiscal year 1997
to $220,824,000 in fiscal year 2001, while the number of GCRCs grew
from 74 to 79. NIH officials told us that the mission of the GCRCs has
remained the same, but their scope of activities has increased in
response to CREA. For example, most GCRCs have hired research subject
advocates to strengthen the protection of human research subjects in
GCRC studies, an area of heightened concern in clinical research, and
some GCRCs have begun to participate in bioinformatics networks to
facilitate the sharing of data and information about clinical trials
and biomedical research.
NIH has established the four clinical research career enhancement award
programs mandated by CREA. Three of these programs have been
implemented and support new and midcareer clinical investigators and
institutional clinical research teaching programs. The fourth program,
which is just beginning, is designed to support graduate training in
clinical investigation. NIH has also established extramural and
intramural clinical research training programs for medical and dental
students and clinical research continuing education programs mandated
by CREA.
NIH has initiated a new extramural loan repayment program specifically
for clinical investigators as required by CREA. This program was
launched on December 28, 2001, and by the February 28, 2002, deadline,
NIH had received 456 applications. Twenty-one of NIH‘s institutes plan
to fund 396 loan repayment contracts, for a total of $20.2 million, by
the end of fiscal year 2002. Currently, a clinical investigator is
eligible for the loan repayment program only if engaged in NIH-
supported clinical research. However, NIH officials told us they have
plans to broaden eligibility for the loan repayment program in fiscal
year 2003 to clinical investigators who receive funding from other
sources, such as other federal agencies and nonprofit foundations.
We are recommending that NIH develop a consistent, accurate, and
practical way to count intramural and extramural clinical research
expenditures. Having an accurate and consistent system for tracking and
reporting expenditures is key to monitoring NIH‘s support of clinical
research in the future. In its comments on a draft of this report, NIH
concurred with our recommendation.
Background:
In the 1990s, a number of influential studies sponsored by NIH, IOM, and
AAMC and the American Medical Association (AMA) identified some
major problems in clinical research and highlighted NIH‘s role in
addressing some of these problems. [Footnote 8] First, there was a
general concern that clinical research was receiving substantially less
support than basic research at NIH, yet there was little systematic
data to document how much, in fact, NIH was spending on clinical
research. In an analysis of NIH investigator-initiated extramural
grants active in 1991, an IOM committee found that 16 percent involved
human research. [Footnote 9] A few years later, a panel appointed by
the NIH director known as the ’Nathan Panel,“ developed a broad
definition of clinical research (the definition NIH now uses) and,
applying this definition to all NIH competing extramural research
grants in fiscal year 1996, found that 27 percent of grants and 38
percent of dollars were devoted to clinical research. [Footnote 10] The
Nathan Panel believed that this fraction of the extramural budget
devoted to clinical research was reasonable and should remain about the
same, as efforts to increase the NIH budget as a whole were pursued.
The studies sponsored by NIH, IOM, and AAMC/AMA recommended that NIH
monitor and track its expenditures on clinical research.
A second concern was that clinical research proposals, especially those
from individual investigators, did not fare as well as basic research
proposals in peer review at NIH. Grant applications for clinical trials,
clinical research centers, and clinical research training are typically
reviewed by the sponsoring institute; however, the peer review of
individual investigator grant applications usually takes place
centrally, within CSR. CSR has approximately 65 study sections that
review research. A study section is a panel of experts established
according to scientific disciplines or research areas for the purpose
of evaluating the scientific and technical merit of grant applications.
In 1994 an NIH-commissioned study reported that patient-oriented
research applications were less likely to receive favorable reviews in
CSR than laboratory-oriented research applications when reviewed in
study sections with less than 30 percent patient-oriented research
applications. [Footnote 11] However when patient-oriented research
applications were grouped in study sections with greater than 50
percent patient-oriented research, they fared as well as laboratory-
oriented research applications. Consequently, this report recommended
that study sections reviewing patient-oriented research should have at
least 50 percent of such applications and that a means should be
developed and implemented to collect and track data prospectively on
research applications that are predominantly patient-oriented,
laboratory-oriented, mixed, or clinical epidemiology and behavioral
research. Similarly, the Nathan Panel recommended that panels that
review clinical research must include experienced clinical
investigators and that at least 30 to 50 percent of the applications
reviewed by these panels must be for clinical research. The IOM
committee also recommended more oversight of study section composition,
functions, and outcomes pertaining to human research.
A third problem identified in these studies was the adequacy of support
for the infrastructure (that is, facilities, equipment, data systems,
and research personnel) for the conduct of clinical research. Since the
late 1950s, NIH has funded GCRCs across the U.S to provide clinical
research infrastructure”facilities, equipment, and personnel”for NIH-
funded investigators as well as non-federally funded investigators
conducting patient-oriented research. Interdisciplinary and
collaborative research is encouraged at these centers. The Nathan
Panel, the IOM committee, and others recommended increasing financial
support for GCRCs and broadening their leadership role in clinical
research and research training.
A fourth concern was the decline in the number of physicians conducting
clinical research. According to data collected by the AMA, the number of
physicians reporting research as their primary career activity fell by 6
percent from 1980 to 1997 (from 15,377 to 14,434), while the number
reporting patient care as their primary career activity almost doubled
(376,512 to 620,472). [Footnote 12] Observers identified a variety of
challenges in pursuing a career as a clinical investigator, including
the indebtedness of medical students, the length of time a clinical
scientist must train, the culture of academic medicine, as well as the
competition from other career options. For many years NIH has supported
the training of investigators through extramural and intramural
predoctoral, postdoctoral training and career development awards.
However, there was concern that these awards were being directed toward
basic research and were not sufficiently supporting the training and
development of clinical investigators. The IOM committee, the Nathan
Panel, and the AAMC/AMA reports recommended that NIH provide
substantial new support for clinical research training, career
development, and debt relief.
Growth in NIH‘s Spending on Clinical Research Has Kept Pace with Total
Spending:
NIH reports that it increased its funding of clinical research and
expanded its clinical research activities in response to CREA. NIH
estimates that it spent about one-third of its budget, or approximately
$6.4 billion, on clinical research in fiscal year 2001. Based on these
estimates, the proportion of the NIH budget spent on clinical research
has remained fairly constant since fiscal year 1997. NIH‘s estimates of
clinical research expenditures represent the best available indications
of financial trends over time, but they are not precise figures because
the process of counting clinical research dollars varies widely across
ICs. Finally, in response to CREA, some NIH ICs have developed specific
clinical research initiatives.
NIH Estimates That It Spends about One-Third of Its Budget on Clinical
Research:
In fiscal year 2001, NIH estimated that it spent approximately $6.4
billion on clinical research, which represented about 32 percent of
total research spending (see table 1). The institutes that spent the
most on clinical research in fiscal year 2001 were the National Cancer
Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI);
and the National Institute of Mental Health (NIMH) (see app. I). NIH‘s
estimated expenditures on clinical research have kept pace with the
overall growth in NIH‘s budget. As NIH‘s reported clinical research
expenditures increased by 44 percent (adjusted for inflation) from
fiscal year 1997 to fiscal year 2001, the proportion of research
dollars spent on clinical research remained constant, at 32 percent,
each year. [Footnote 13]
Table 1: Extramural and Intramural Total and Clinical Research
Expenditures in Fiscal Year 2001 (Dollars in millions):
Extramural:
Total expenditures: $17,061.2;
Clinical research expenditures: $5,904.2;
Clinical research expenditures as percentage of total: 35%.
Intramural:
Total expenditures: $1,952.3;
Clinical research expenditures: $529.0;
Clinical research expenditures as percentage of total: 27%.
Other[A]:
Total expenditures: $1,293.8;
Clinical research expenditures: [Empty];
Clinical research expenditures as percentage of total: [Empty].
Total:
Total expenditures: $20,307.3;
Clinical research expenditures: $6,433.3;
Clinical research expenditures as percentage of total: 32%.
Note: Numbers may not add to total because of rounding.
[A] Other includes expenditures for Research Management and Support,
Office of the Director, National Library of Medicine, and in-house
cancer control activities.
Source: NIH Office of Budget.
[End of table]
NIH estimates that in fiscal year 2001, it spent approximately $5.9
billion on extramural clinical research, about 35 percent of its total
extramural research expenditures. NIH‘s extramural clinical research
dollars were spent through a variety of funding mechanisms in fiscal
year 2001. About 40 percent of the awarded dollars were grants to
individual investigators, followed by other funding mechanisms, center
grants, cooperative agreements, research program projects, and research
and development contracts (see fig. 1). [Footnote 14] Of NIH‘s total
extramural research expenditures for cooperative agreements and center
grants, the majority of dollars were spent on clinical research in
fiscal year 2001.
Figure 1: Percentage of NIH Extramural Clinical Research Expenditures
by Funding Mechanism in Fiscal Year 2001:
[See PDF for image]
This figure is a pie-chart, depicting the following data:
Research grants to individual investigators[A]: 40%;
Other mechanisms: 17%;
Center grants[B]: 15%;
Cooperative agreements[C]: 12%;
Research program projects[D]: 10%;
Research and development contracts[E]: 6%.
[A] A discrete, defined project performed by a designated investigator.
[B] Supports shared resources and facilities for categorical research
by a number of investigators.
[C] Typically, organized efforts of large groups of investigators and
projects aimed at a specific objective.
[D] Often a long-term, broad-based research program with a specific
objective.
[E] Used to develop and/or apply new knowledge or to test, screen, or
evaluate a product, material, device, or component.
Source: NIH Office of Extramural Research data.
[End of figure]
In fiscal year 2001, NIH estimated that it spent about $529 million, or
27 percent of its intramural research expenditures, on clinical
research. NIH‘s intramural clinical research activities include
research at the Clinical Center on NIH‘s Bethesda, Maryland, campus, as
well as research by individual institutes. The Clinical Center‘s budget
represents more than half of the intramural clinical research
expenditures. The budget of the Clinical Center increased from
approximately $204 million in fiscal year 1997 to an estimated $303
million in fiscal year 2002. This budget increase supported an increase
in admissions, inpatient days, and outpatient visits.
Flaws Exist in NIH‘s Process of Counting Clinical Research
Expenditures:
NIH‘s reports of clinical research expenditures represent the best
available indications of financial trends, but are not precise figures.
The methods NIH uses to count clinical research dollars are
inconsistent across ICs, potentially underestimating or overestimating
its actual clinical research expenditures. Since fiscal year 1997, the
Office of Budget, within the Office of the Director, has collected
information from each IC on its extramural and intramural clinical
research expenditures. The ICs use the NIH definition of clinical
research (described earlier), but they count the dollars in very
different ways. The 20 ICs that fund clinical research reported three
different ways of counting clinical research dollars. First, 12 ICs
count 100 percent of the grant dollars of research projects that
include any clinical research. Second, one institute, NCI, codes a
research project‘s ’percent relevance“ to clinical research. Projects
are coded as 100 percent, major, minor, or 0 percent clinical research.
If they are classified as ’major,“ they are assigned a percentage
relevancy of 50 percent, and 50 percent of the dollars are counted. If
they are classified as ’minor,“ they are assigned a percentage
relevancy of 5 percent, and 5 percent of the dollars are counted.
Third, 7 ICs either attempt to estimate the dollars of a research
project spent on clinical research or the percentage of a project that
is clinical research and apply that percentage to the total grant
dollars.
These different methods of counting clinical research dollars can
produce very different results. For example, given a hypothetical grant
to an investigator of $300,000 for which an IC has estimated that
$50,000 of the budget would be spent on clinical research, some ICs
would report that $300,000 was spent on clinical research; NCI could
conclude that this grant has only minor relevance to clinical research
and therefore would count 5 percent, or $15,000, as clinical research
dollars; the rest of the ICs would estimate that this project is about
17 percent clinical research and therefore count $50,000 of the grant
as clinical research dollars.
The Office of Budget said that the reason the ICs count clinical
research dollars differently is that each developed its own methods
over time, and for historical consistency, they are reluctant to
change. One IC director, who heads an NIH Director‘s committee
concerned with clinical research spending told us that NIH is working
on ways to make its process of tracking and reporting clinical research
dollars more consistent and accurate.
NIH Institutes Have Developed New Clinical Research Initiatives:
In response to CREA, some institutes have developed new clinical
research initiatives. For example, since the passage of CREA, NCI has
funded two new clinical cancer centers and funded 22 new Specialized
Programs of Research Excellence for different types of cancer, all of
which involved early phase clinical trials. NHLBI is establishing new
clinical research centers to study ways to reduce racial and economic
disparities in asthma prevalence, treatment, and mortality and is
funding trials to assess innovative strategies to improve the
implementation of clinical practice guidelines for heart, lung, and
blood diseases. The National Institute of Arthritis and Musculoskeletal
Diseases has a new osteoarthritis initiative; funds multidisciplinary
clinical research centers in arthritis, musculoskeletal, and skin
diseases; and plans to enhance its translational research projects in
children‘s diseases. The National Institute of Allergy and Infectious
Diseases (NIAID) has continued to fund large clinical trial networks
such as the AIDS Clinical Trials Group, a $120 million per year
initiative that involves research on pediatric and adult AIDS.
NIH Has Taken Steps to Improve Its Peer Review of Clinical Research:
Since passage of CREA, NIH has acted to strengthen its peer review of
clinical research applications. CSR established two new study sections
in the areas of clinical oncology and clinical cardiovascular sciences.
In study sections with a mix of clinical and basic proposals, CSR tries
to group clinical research applications and reviewers, but officials
could not provide data to determine how successful it has been in
achieving this goal. NIH has established peer review mechanisms at the
institutes for the review of career development and training awards
established under CREA.
CSR Has Established Two New Clinically Focused Study Sections for Peer
Review:
In response to concerns that clinical research proposals are not fairly
reviewed in its study sections, CSR has established two new clinically
oriented study sections, Clinical Oncology and Clinical Cardiovascular
Sciences. In these scientific areas, CSR found that there were a
sufficient number of clinical research applications to justify separate
study sections. Although the two new clinical research study sections
have been welcomed by the research community, some concerns remain among
clinical investigators about the fairness of the review of clinical
research by other study sections that have a mix of clinical and basic
research. In these study sections, CSR officials told us they try to
group clinical research applications and clinical research reviewers.
CSR officials told us that it is their general goal to review clinical
research applications in study sections in which at least 30 percent of
the applications involve clinical research and in which at least 30
percent of the reviewers are themselves clinical investigators. CSR
officials also explained that this goal cannot always be achieved
because if the number of clinical research applications in a specific
scientific area is small, it may not be possible to group the
applications to 30 percent and still review them in a study section that
provides the appropriate scientific context for review. They emphasized
that reviewing applications in the appropriate scientific context is
given priority over quantitative targets for grouping. CSR officials
could not provide data on the extent to which they have been able to
group clinical research applications and have very limited data on
which reviewers are clinical investigators. The officials told us that,
to date, they do not have reliable and accurate methods for identifying
and tracking clinical applications or clinical reviewers.
CSR officials told us they are in the process of a broader review and
restructuring of their peer review system, with input from the
scientific community, to account for new developments in science.
[Footnote 15] According to CSR, one of the goals of this reorganization
is grouping applications and reviewers at 30 percent so that there is a
’density of expertise“ in review sections. In addition, CSR has
recently appointed a special advisor on clinical research review to
serve as a liaison with the clinical research communities.
Clinical Research Career Development and Training Applications Are
Reviewed by ICs:
To determine NIH‘s response to CREA‘s requirement that NIH establish
appropriate mechanisms for the peer review of clinical research career
development and training applications, we surveyed nine ICs that
sponsored the highest number of clinical research career development
awards in fiscal year 2001. We found that three ICs used a Special
Emphasis Panel, [Footnote 16] while the six others used established
committees or subcommittees to review clinical research career
development and training applications. In addition, the ICs reported
that most of the reviewers of these applications have clinical research
experience, and some are involved in clinical research training. One
institute brings in temporary reviewers to augment its committee if
special expertise is needed. NCRR uses CSR for peer review of some
career development applications that require very specific scientific
expertise and therefore require review by the discipline-specific study
sections of CSR.
NIH Has Increased Its Support and Scope of GCRCs:
NIH has increased its support of GCRCs and GCRCs‘ scope of work, as
required by CREA. The GCRC budget has grown over time, although more
slowly than NIH‘s estimates of clinical research spending. Adjusted for
inflation, the funding for GCRCs increased by 24 percent from fiscal
year 1997 to fiscal year 2001, compared to a 44 percent estimated
increase in clinical research spending at NIH during that same period.
Although NIH has stopped funding some GCRCs, there has been a gradual
increase in the number of GCRCs over time, from 74 in fiscal year 1997
to 79 in fiscal year 2001. There has also been an increase in the
activities of GCRCs and some expansion in their scope since passage of
CREA.
Funding, Number, and Activities of GCRCs Have Increased:
NIH has increased funding for the GCRC program, although funding for
the GCRCs has grown more slowly than NIH‘s estimate of overall
expenditures on clinical research. From fiscal year 1997 through fiscal
year 2001, funding for the GCRCs increased from $153,521,000 to
$220,824,000 (see table 2). Adjusted for inflation, this represents an
increase of 24 percent, compared to the 44 percent estimated growth in
total clinical research expenditures during this period. [Footnote 17]
The number of GCRCs gradually increased during this period, from 74 to
79. [Footnote 18] Funding levels for individual GCRCs in fiscal year
2001 ranged from $712,339 to $6.2 million, with an average funding
level of about $2.8 million. NIH officials told us that in fiscal year
2002, they are opening two new GCRCs, one at the University of Maryland
and one at the University of Miami. Establishing a new GCRC costs about
$2.5 million and requires a certain threshold of investigators. Once a
GCRC is set up, attracting additional investigators and research
activities is easier, according to NIH officials.
Table 2: Funding, Number, and Activities of GCRCs Have Increased from
Fiscal Year 1997 to Fiscal Year 2001:
Fiscal year: 1997;
Number of GCRCs: 74;
Amount awarded (in millions): $153.5;
Protocols[A]: 5,844;
Investigators[B]: 8,588;
Publications[C]: 4,547;
Inpatient days[D]: 70,814;
Outpatient visits[E]: 282,125.
Fiscal year: 1998;
Number of GCRCs: 75;
Amount awarded (in millions): $165.4;
Protocols[A]: 6,072;
Investigators[B]: 9,083;
Publications[C]: 4,385;
Inpatient days[D]: 71,309;
Outpatient visits[E]: 313,100.
Fiscal year: 1999;
Number of GCRCs: 77;
Amount awarded (in millions): $195.7;
Protocols[A]: 6,410;
Investigators[B]: 8,570;
Publications[C]: 4,412;
Inpatient days[D]: 70,100;
Outpatient visits[E]: 313,579.
Fiscal year: 2000;
Number of GCRCs: 78;
Amount awarded (in millions): $198.6;
Protocols[A]: 6,785;
Investigators[B]: 9,195;
Publications[C]: 5,448;
Inpatient days[D]: 65,211;
Outpatient visits[E]: 328,889.
Fiscal year: 2001;
Number of GCRCs: 79;
Amount awarded (in millions): $220.8;
Protocols[A]: 7,020;
Investigators[B]: 9,572;
Publications[C]: 5,381;
Inpatient days[D]: 62,769;
Outpatient visits[E]: 334,828.
[A] Number of research studies conducted at a GCRC.
[B] Number of individuals engaged in research at a GCRC. Investigators
may be supported by NIH, other federal agencies, state and local
entities, or the private sector.
[C] Number of research articles published in peer review journals that
used GCRC resources.
[D] Number of days human research subjects are used in research
conducted at a GCRC, using GCRC facilities such as research beds and
rooms.
[E] Number of visits by human research subjects who used GCRC
facilities but were not hospitalized at midnight. These visits may be
as short as a few minutes or as long as almost 24 hours.
Source: NIH‘s NCRR.
[End of table]
Also shown in table 2, some activities of GCRCs have increased in recent
years. For example, the number of research protocols and investigators
supported by GCRCs increased from fiscal year 1997 through fiscal year
2001. While the number of inpatient days funded by GCRCs declined from
70,814 in fiscal year 1997 to 62,769 in fiscal year 2001, the number of
outpatient visits increased from 282,125 to 334,828 during the same
period.
Scope of GCRC Activities, Including Telecommunications, Has Expanded:
Since passage of CREA, NIH officials told us there has not been a change
in the mission of GCRCs, but there has been an increase in the scope of
GCRC activities. For example, in fiscal year 2002, 27 GCRCs have funded
Clinical Research Feasibility pilot projects to support the research of
beginning investigators. In addition, 76 GCRCs now each have a Research
Subject Advocate who helps ensure that GCRC research is conducted
safely and protects human research subjects.
CREA required that NIH expand the activities of the GCRCs through
increased use of telecommunications and telemedicine initiatives. In
response, NIH officials told us they increased their support of
specialized bioinformatics networks that electronically link research
data across GCRCs. Specifically, NCRR established a Biomedical
Informatics Research Network, a computerized network that allows
investigators affiliated with GCRCs to share high-resolution images of
human brains and large volumes of complex data and conduct remote
analysis of the data. In fiscal year 2001, NCRR funded five
bioinformatics centers at $2.1 million, and a coordinating center at
$1.6 million, spending a total of $3.7 million on this initiative. In
fiscal year 2002, $6 million has been set aside to extend this network.
NCRR also funded a collaborative pilot project between the Cystic
Fibrosis Foundation and several GCRCs, called CFnet, to assess whether
clinical trials could be facilitated across GCRC sites with Web-based
data handling. Based on the success of this pilot, NCRR plans to extend
CFnet to 20 GCRCs and also establish a comparable network among the
eight U.S. medical schools that have a high proportion of minority
students to facilitate the schools‘ participation in clinical trials
that relate to health disparities.
NIH Has Increased Its Support of Clinical Research Career Development
and Training:
NIH has established the four new career development award programs
required by CREA. Three of these have been implemented, and the fourth
is just beginning. NIH has also established intramural and extramural
clinical research training programs for medical and dental students and
clinical research continuing education programs as required by CREA.
NIH Has Implemented Three Award Programs for Career Development of
Clinical Investigators:
NIH recently established three new clinical research career development
award programs for individuals and institutions outside government that
are designed to increase the supply and expertise of clinical
investigators (see table 3). NIH used its K award mechanism, its usual
method for providing support for career development of investigators,
to establish these programs. In fiscal year 1999, NIH implemented the
Mentored Patient-Oriented Research Career Development Award (K23) to
support investigators who are committed to conducting patient-oriented
research for 3 to 5 years. In the same year, NIH implemented the Mid-
Career Investigator Award in Patient-Oriented Research (K24) to provide
support for more senior clinicians to relieve them of patient-care
duties and administrative responsibilities so that they can conduct
patient-oriented research and serve as mentors for beginning clinical
investigators. The Clinical Research Curriculum Award (K30), also
implemented in fiscal year 1999, supports the development and expansion
of clinical research teaching programs at institutions. [Footnote 19]
About half of the K30 programs offer graduate degrees in clinical
research (for example, masters or doctorate).
Table 3: Clinical Research Career Development Award Programs
Established by NIH since Fiscal Year 1999:
Career development award program (K award mechanism): Mentored Patient-
Oriented Research Career Development Award (K23);
Purpose: This 3-5 year nonrenewable award supports the career
development of investigators who are focused on performing patient-
oriented research under the supervision of a mentor. Most awards
provide candidates with a salary of up to $75,000. In terms of research
support, candidates receive $25,000 to $50,0000 per year and must give
75% minimum effort toward research career development and clinical
research.
Year implemented: FY 1999;
Initial projected annual number of awards: 80;
Cumulative number of awards: 496;
Funding level (FY 2001): $64.8 million.
Career development award program (K award mechanism): Mid-Career
Investigator Award in Patient-Oriented Research (K24);
Purpose: This 3-5 year renewable award supports clinicians in affording
them the ability to devote time to clinical research and to act as
mentors for beginning clinical investigators. Mentors receive up to 50%
of the NIH salary cap in addition to fringe benefits. They also receive
$25,000 per year for research support and must give from a minimum of
25% to a maximum of 50% effort toward mentoring and clinical research.
Year implemented: FY 1999;
Initial projected annual number of awards: 60-80;
Cumulative number of awards: 215;
Funding level (FY 2001): $23.4 million.
Career development award program (K award mechanism): Clinical Research
Curriculum Award (K30);
Purpose: This 5-year renewable award supports the administrative
infrastructure for graduate training and expansion of clinical research
teaching programs at institutions.
Year implemented: FY 1999;
Initial projected annual number of awards: 20;
Cumulative number of awards: 57;
Funding level (FY 2001): $11.5 million.
Career development award program (K award mechanism): Mentored Clinical
Research Scholar Program Award (K12);
Purpose: This 5-year award supports an institutional career development
program for physicians and dentists to acquire the skills to become
independent patient-oriented clinical investigators. Candidates are
provided a maximum of $90,000 for salary support for each year
commensurate with the applicant institution‘s salary structure for
persons of equivalent qualifications, experience, and rank. This award
is a one-time offering, but may be expanded.
Year implemented: FY2002;
Initial projected annual number of awards: Program begins in FY 2002
with 10 projected awards;
Cumulative number of awards: Not applicable;
Funding level (FY 2001): $6.2 million (FY 2002 estimate).
Sources: NIH Office of Extramural Programs; NIH Office of Reports and
Analysis; and Request for Applications and Program Announcement
Documents.
[End of table]
The response to these new award programs was substantial, and NIH
funded more awards than originally planned. NCRR and the largest
institutes (for example, NCI, NHLBI, and NIMH) sponsored the highest
number of the new K23 and K24 awards. NHLBI is administering the
majority of the K30 awards. Although NIH has received applications for
K23 and K24 awards from a variety of clinical investigators, most
applicants and awardees are physicians. The K30 awards have primarily
gone to academic medical centers. The new awards combined represent
25 percent of expenditures NIH allotted for all K awards under its
Career Development Program in fiscal year 2001 (see fig. 2).
Figure 2: NIH‘s New Clinical Research Career Development Awards
Relative to All NIH Career Development Awards in Fiscal Year 2001
(dollars in millions):
[See PDF for image]
This figure is a pie-chart that depicts the following data:
K30: $11.5;
K24: $23.4;
K23: $64.8;
Other career development awards: $301.8.
Source: NIH Office of Reports and Analysis data.
[End of figure]
NIH officials told us that they are initiating plans to evaluate the new
clinical research career development awards and track career outcomes.
The design of this assessment will be based on previous studies of
training award recipients, specifically NIH‘s study of the outcomes of
the National Research Service Awards (NRSA) [Footnote 20] and will rely
on NIH‘s new electronic grant application.
Size and Scope of New Award Program for Graduate Training in Clinical
Research Is Limited:
In 2001 NIH announced a fourth new clinical research career development
award, the Mentored Clinical Research Scholar Program (K12). This award
program, sponsored by NCRR and linked to the GCRCs, is NIH‘s response
to CREA‘s directive to support graduate training in clinical research.
NCRR decided to start the K12 program as a small pilot project and then
expand it later if successful. [Footnote 21] In fiscal year 2002, NCRR
received 43 applications for this award and expects to fund 10 of
these. In the first year of the program, each funded award may enroll
three clinical research scholars, for a total of 30 scholars. NIH
projects that the number of scholars could grow to 120 in 5 years.
We interviewed several K30 program directors who indicated that
obtaining graduate tuition and stipend support for their students and
prospective students was a major constraint. The K30 award, which has
been well received in the research community, funds curriculum, staff,
as well as tuition and other costs in special circumstances, but
generally does not directly support students. Instead, students must
seek funding from other NIH, federal, or private sources. An NIH
official estimated that the number of formal trainees in individual K30
programs ranges from several to three dozen. This official was not able
to provide data on whether these students had tuition support and what
kind of support. However, the K30 program directors we talked to said
some of their students had tuition support from other NIH funding
mechanisms; others had support from their university. Although the new
K12 program is consistent with the requirements of CREA, some K30
program directors and other experts believe the size and scope of the
program will be too small to meet the need for graduate training
support for clinical investigators.
Other NIH Clinical Research Training Programs Targeted toward Medical
and Dental Students:
In terms of fellowships for clinical research training, in fiscal year
2001, NCRR announced a new mentored medical student clinical research
program that will support a small number of medical and dental students
at GCRCs. This program provides supplemental grants to GCRCs to offer 1
year of support for medical and dental students, usually from their
third through fourth year of school, in the form of salary, supplies,
and tuition assistance. A total of five students may eventually be
supported at each GCRC site annually, although NCRR plans to provide
support for only one medical student per GCRC in fiscal year 2002.
Since 1997, NIH has also trained medical and dental students at its
campus in the area of clinical research. In this program, partially
supported by a pharmaceutical company, 15 to 20 students are selected
each year and are each paired with a mentor for a year of academic
study and clinical research experience. [Footnote 22]
NIH Has Established an Extramural Loan Repayment Program for Clinical
Investigators:
NIH has launched an extramural loan repayment program for clinical
investigators as required by CREA, and most of NIH‘s ICs participate in
the program. In the first year of implementation, eligibility for the
loan repayment program was tied to receipt of NIH funding. However, in
fiscal year 2003, NIH plans to extend eligibility to allow clinical
investigators who receive funding from other sources, such as other
federal agencies and nonprofit foundations, to apply.
New Extramural Loan Repayment Program Established by NIH:
In response to CREA, NIH established an extramural Clinical Research
Loan Repayment Program. This new loan repayment program joins four
other extramural loan repayment programs [Footnote 23] and four
intramural loan repayment programs [Footnote 24] that are administered
by NIH‘s Office of Loan Repayment and Scholarship. The new extramural
Clinical Research Loan Repayment Program was implemented on December
28, 2001, and a total of 456 applications were received by February 28,
2002. NIH plans to fund 396 loan repayment contracts for a total of
$20.2 million by the end of fiscal year 2002. [Footnote 25] The program
provides for the repayment of up to $35,000 per year of the principal
and interest of an individual‘s educational loans for each year of
obligated service. [Footnote 26] These individuals are obligated to
engage in clinical research for at least 2 years. The clinical research
loan repayment program represents a sizeable proportion (almost two-
thirds) of the total extramural loan repayment program budget.
To be eligible for the clinical research loan repayment program, a
clinical investigator must have received an NIH research service award,
training grant, career development award, or other NIH grant as a first-
time principal investigator or a first-time director of a subproject on
a grant or cooperative agreement. In fiscal year 2003, the Director of
the Office of Loan Repayment and Scholarship told us that NIH plans to
remove the NIH-funding restriction and allow clinical investigators who
receive funding from other sources, such as other federal agencies and
nonprofit foundations, to apply for the loan repayment program.
[Footnote 27] In addition, NIH expects to almost double the size of the
extramural Clinical Research Loan Repayment Program in fiscal year
2003.
Twenty-one of NIH‘s ICs Participate in the Loan Repayment Program:
Although NIH has a central office that administers all the loan
repayment programs, funding for the clinical research loan repayment
program was distributed to the ICs, based on reported clinical research
expenditures in fiscal year 1999. Thus 21 of NIH‘s 27 ICs plan to
participate in the program by reviewing applications and awarding loan
repayment contracts (see app. II). The ICs sponsoring the highest
number of contracts are NCI, NHLBI, and NIMH. NCRR also plans to
sponsor a significant number of loan repayment contracts. As with most
of the training and career development awards, an NIH official told us
that the ICs were in the best position to assess applications and the
clinical research career potential of awardees.
Conclusion:
In general, NIH has complied with the key provisions in CREA. It has
increased its financial support of clinical research, expanded its
clinical research activities, made improvements in its review of
clinical research proposals, expanded its support of GCRCs, established
new clinical research career development and training programs, and
begun to implement a new extramural clinical research loan repayment
program. Some of NIH‘s actions were taken prior to CREA‘s passage and
some are still being implemented. However, we identified some
inconsistencies with the way that NIH counts clinical research
expenditures. These inconsistencies limit the precision of NIH‘s
reports of clinical research expenditures and its ability to monitor
the support of clinical research.
Recommendation for Executive Action:
To strengthen the tracking and reporting of intramural and extramural
expenditures for clinical research, we recommend that the Director of
NIH develop and implement a consistent, accurate, and practical way for
all ICs to count intramural and extramural clinical research
expenditures.
Agency Comments:
NIH reviewed a draft of this report and provided comments, which are
included as appendix III. NIH concurred with our recommendation and
reported that it is taking steps to implement a better, more unified
system for tracking and reporting clinical research expenditures across
the ICs. According to NIH, this new system will be implemented in
fiscal year 2003. NIH also provided technical comments, which we
incorporated as appropriate. In particular, NIH clarified its response
to our questions about the peer review of clinical research. NIH
emphasized that it recognizes the importance of collecting data on the
grouping of clinical research applications and reviewers. Toward that
end, NIH stated that one of the responsibilities of CSR‘s newly
appointed Special Advisor on Clinical Research Review will be to
investigate new methods to reliably identify and track clinical
research applications and clinical research reviewers.
We will send copies to the Secretary of Health and Human Services, the
Director of NIH, appropriate congressional committees, and others who
are interested. We will also make copies available to others on
request. In addition, the report will be available at no charge on
GAO‘s Web site at [hyperlink, http://www.gao.gov].
If you or your staffs have any questions, please contact me at (202)
512-7119 or Martin T. Gahart at (202) 512-3596. Key contributors to
this assignment were Anne Dievler, Cedric Burton, and Elizabeth
Morrison.
Signed by:
Janet Heinrich:
Director, Health Care”Public Health Issues:
[End of section]
Appendix I: NIH‘s Estimated Expenditures for Extramural and Intramural
Clinical Research, by IC, Fiscal Years 1997 - 2001 (dollars in
millions):
Institutes and centers: National Cancer Institute;
FY 1997: $740.0;
FY 1998: $750.0;
FY 1999: $818.4;
FY 2000: $941.2;
FY 2001: $1,045.3.
Institutes and centers: National Heart, Lung, and Blood Institute;
FY 1997: $524.0;
FY 1998: $550.0;
FY 1999: $621.1;
FY 2000: $785.3;
FY 2001: $848.5.
Institutes and centers: National Institute of Mental Health; 474.0
FY 1997: $474.0;
FY 1998: $498.1;
FY 1999: $493.6;
FY 2000: $549.4;
FY 2001: $729.7.
Institutes and centers: National Institute of Allergy and Infectious
Diseases;
FY 1997: $444.4;
FY 1998: $452.9;
FY 1999: $553.3;
FY 2000: $639.6;
FY 2001: $693.4.
Institutes and centers: National Institute of Child Health and Human
Development;
FY 1997: $340.4;
FY 1998: $364.5;
FY 1999: $414.8;
FY 2000: $495.5;
FY 2001: $553.8.
Institutes and centers: National Institute on Drug Abuse;
FY 1997: $274.1;
FY 1998: $295.0;
FY 1999: $340.5;
FY 2000: $390.9;
FY 2001: $446.7.
Institutes and centers: National Institute of Diabetes and Digestive
and Kidney Diseases;
FY 1997: $220.0;
FY 1998: $238.9;
FY 1999: $272.3;
FY 2000: $312.0;
FY 2001: #357.0.
Institutes and centers: National Institute on Aging;
FY 1997: $201.2;
FY 1998: $182.1;
FY 1999: $247.8;
FY 2000: $287.8;
FY 2001: $337.2.
Institutes and centers: National Institute of Neurological Disorders
and Stroke;
FY 1997: $232.5;
FY 1998: $218.5;
FY 1999: $259.2;
FY 2000: $286.0;
FY 2001: $259.6.
Institutes and centers: National Center for Research Resources;
FY 1997: $162.0;
FY 1998: $175.2;
FY 1999: $210.0;
FY 2000: $217.6;
FY 2001: $251.1.
Institutes and centers: National Eye Institute;
FY 1997: $58.7;
FY 1998: $147.0;
FY 1999: $165.9;
FY 2000: $196.0;
FY 2001: $213.5.
Institutes and centers: National Institute on Alcohol Abuse and
Alcoholism;
FY 1997: 0;
FY 1998: $117.5;
FY 1999: $142.7;
FY 2000: $158.7;
FY 2001: $171.2.
Institutes and centers: National Institute on Deafness and Other
Communication Disorders;
FY 1997: $84.7;
FY 1998: $91.0;
FY 1999: $103.1;
FY 2000: $114.4;
FY 2001: $107.9.
Institutes and centers: National Institute of Arthritis and
Musculoskeletal and Skin Diseases;
FY 1997: $77.7;
FY 1998: $70.6;
FY 1999: $72.5;
FY 2000: $94.8;
FY 2001: $97.9.
Institutes and centers: National Institute of Nursing Research;
FY 1997: $46.4;
FY 1998: $46.4;
FY 1999: $57.7;
FY 2000: $76.5;
FY 2001: $90.5.
Institutes and centers: National Institute of Dental and Craniofacial
Research;
FY 1997: $63.1;
FY 1998: $62.0;
FY 1999: $66.7;
FY 2000: $74.6;
FY 2001: $78.6.
Institutes and centers: National Center for Complementary and
Alternative Medicine;
FY 1997: 0;
FY 1998: 0;
FY 1999: 0;
FY 2000: $32.6;
FY 2001: $60.8.
Institutes and centers: National Institute of Environmental Health
Sciences;
FY 1997: $35.8;
FY 1998: $39.4;
FY 1999: $44.5;
FY 2000: $50.0;
FY 2001: $55.3.
Institutes and centers: National Center on Minority Health and Health
Disparities;
FY 1997: 0;
FY 1998: 0;
FY 1999: 0;
FY 2000: 0;
FY 2001: $20.9.
Institutes and centers: National Human Genome Research Institute;
FY 1997: $17.5;
FY 1998: $22.3;
FY 1999: $22.5;
FY 2000: $14.5;
FY 2001: $14.3.
Institutes and centers: Office of the Director;
FY 1997: 0;
FY 1998: 0;
FY 1999: $13.9;
FY 2000: 0;
FY 2001: 0.
Institutes and centers: Total;
FY 1997: $3,999.0;
FY 1998: $4,321.4;
FY 1999: $4,920.5;
FY 2000: $5,717.3;
FY 2001: $6,433.3.
Source: NIH Office of Budget.
[End of table]
[End of section]
Appendix II: NIH‘s Extramural Clinical Research Loan Repayment
Contracts by IC, Fiscal Year 2002:
Institute and centers: National Cancer Institute;
Number of contracts: 55.
Institute and centers: National Heart, Lung, and Blood Institute;
Number of contracts: 49.
Institute and centers: National Institute of Mental Health;
Number of contracts: 43.
Institute and centers: National Institute of Allergy and Infectious
Diseases;
Number of contracts: 30.
Institute and centers: National Institute on Aging;
Number of contracts: 29.
Institute and centers: National Institute on Drug Abuse;
Number of contracts: 29.
Institute and centers: National Center for Research Resources;
Number of contracts: 22.
Institute and centers: National Institute of Diabetes and Digestive and
Kidney Diseases;
Number of contracts: 22.
Institute and centers: National Institute of Child Health and Human
Development;
Number of contracts: 21.
Institute and centers: National Institute on Alcohol Abuse and
Alcoholism;
Number of contracts: 17.
Institute and centers: National Institute of Neurological Disorders and
Stroke;
Number of contracts: 17.
Institute and centers: National Institute of Arthritis and
Musculoskeletal and Skin Diseases;
Number of contracts: 16.
Institute and centers: National Eye Institute;
Number of contracts: 14.
Institute and centers: National Institute on Deafness and Other
Communication Disorders;
Number of contracts: 9.
Institute and centers: National Institute of Dental and Craniofacial
Research;
Number of contracts: 7.
Institute and centers: National Human Genome Research Institute;
Number of contracts: 4.
Institute and centers: National Institute of Environmental Health
Sciences;
Number of contracts: 3.
Institute and centers: National Institute of General Medical Sciences;
Number of contracts: 3.
Institute and centers: National Institute of Nursing Research;
Number of contracts: 3.
Institute and centers: National Center for Complementary and
Alternative Medicine;
Number of contracts: 2.
Institute and centers: John E. Fogarty International Center;
Number of contracts: 1.
Institute and centers: Total;
Number of contracts: 396.
Source: NIH Office of Loan Repayment and Scholarship.
[End of table]
[End of section]
Appendix III: Comments from the National Institutes of Health:
Department Of Health & Human Services:
Public Health Service:
National Institutes of Health:
Bethesda, Maryland 20892:
[hyperlink, http://www.nih.gov]
August 30, 2002:
Janet Heinrich, Ph.D.
Director, Health Care-Public Health Issues:
U.S. General Accounting Office:
441 G Street, NW:
Washington, D.C. 20548:
Dear Dr. Heinrich:
I enclose the comments of the National Institutes of Health (NIH) on
the General Accounting Office (GAO) draft report entitled, "Clinical
Research: NIH Has Implemented Key Provisions of the Clinical Research
Enhancement Act," GAO-02-965. This report provides a comprehensive
evaluation of our compliance with the provisions of the Clinical
Research Enhancement Act, and we are pleased that it acknowledges the
substantial efforts we have made.
We concur with the recommendation to develop and implement a better
system of counting intramural and extramural clinical research
expenditures. Our comments identify the ongoing or planned actions we
are undertaking to implement this recommendation. We also offer a
series of technical comments that we believe will improve the report's
accuracy and clarity.
Thank you for giving us the opportunity to review and comment on this
draft report.
Sincerely,
Signed by:
Elias A. Zerhouni, M.D.
Director:
Enclosure:
Comments of the National Institutes of Health (NIH):
On the U. S. General Accounting Office (GAO) Draft Report "Clinical
Research: NIH Has Implemented Key Provisions of the Clinical Research
Enhancement Act," GAO-02-965:
We appreciate the opportunity to review and provide comments on this
draft report. The report provides a comprehensive evaluation of NIH's
compliance with the provisions of the Clinical Research Enhancement Act
(CREA) and we are pleased that it acknowledges the substantial efforts
we have made.
GAO Recommendation:
To strengthen the tracking and reporting of intramural and extramural
expenditures for clinical research, we recommend that the Director of
NIH develop and implement a consistent, accurate, and practical way for
all Institutes and Centers (IC) to count intramural and extramural
clinical research expenditures.
NIH Comments:
We concur. As noted in the report, the process of counting clinical
research dollars varies widely across ICs. As a result, consolidated
NlH reports of clinical research expenditures are not precise figures.
We were aware of these issues and are working on ways to make the
process of tracking and reporting clinical research expenditures more
consistent and accurate. To begin, the NIH Director appointed a
Committee to identify the most consistent and accurate methods to
report the NIH clinical research spending. This Committee conducted an
analysis that identified the variabilities among ICs in reporting
funding for both intramural and extramural clinical research.
The Committee determined how it could best harmonize the different
reporting systems from the various ICs. Four different methods of
coding clinical portions of grants were used to assess a large and
representative sample of extramural grants. Three of these four methods
produced nearly identical results. As a consequence, the Committee
decided that all Institutes would report their clinical research for
each grant and contract and their activity on a proportional (0, 25
percent, 50 percent, 75 percent, or 100 percent) basis. These numbers
for extramural clinical research will be reported by each IC through
its own budget office to the central NIH Office of Budget.
With regard to intramural clinical research, each IC will report its
proportional allocations (excluding Clinical Center costs) through its
budget office. The total Clinical Center operational costs will be
added to these numbers to determine the total intramural clinical
research allocation. The intramural and extramural clinical research
dollar totals will then be available through the central NlH Office of
Budget. The Committee also discussed the feasibility of attributing any
other core clinical costs to the NIH clinical research allocation. The
Committee decided that almost all of these costs are already accounted
for and considerable effort would be required to capture the very small
amount of additional dollars spent. Finally, this new clinical research
tracking and reporting system will be implemented in FY 2003. We
believe that this will provide for a consistent, accurate, and
transparent way for the NIH to report its expenditures for clinical
research.
[End of section]
Footnotes:
[1] Patient-oriented research is research conducted with human subjects
or on material of human origin, such as tissues, specimens, and
cognitive phenomena. It includes research that focuses on mechanisms of
human disease, therapeutic interventions, clinical trials, and the
development of new technologies.
[2] Experts consider that clinical research also covers the area of
’translational research,“ the process by which discoveries move between
the laboratory and the patient (from bench to bedside), for example,
laboratory research on the brain that can be translated to the
treatment of addiction or strokes.
[3] This is the definition the National Institutes of Health currently
applies to its clinical research. However, there are other definitions
of clinical research that have been developed over time, and there is
still no consensus on an exact definition of clinical research. The
Clinical Research Enhancement Act of 2000 used a broad and inclusive
definition of clinical research that is similar to the one described
here.
[4] In classifying its basic research expenditures, NIH uses the Office
of Management and Budget‘s (OMB) definition: ’systematic study directed
toward fuller knowledge or understanding of the fundamental aspects of
phenomena and of observable facts without specific applications towards
processes or products in mind.“ (OMB Circular A-21, p. 279).
[5] P.L. 106-505, §§ 201-207, 114 Stat. 2314, 2325-30 (2000).
[6] Specifically, CREA required NIH to support and expand the resources
available for the diverse needs of the clinical research community,
including resources for inpatient, outpatient, and critical care
clinical research; award grants for the establishment of general
clinical research centers to provide additional infrastructure for
clinical research and expand their activities through
telecommunications and telemedicine; make grants to support clinical
research career enhancement of beginning and midcareer clinical
investigators, graduate training in clinical investigation, and
programs of core curricula for training clinical investigators;
establish intramural and extramural clinical research fellowship
programs for medical and dental students and a continuing education
clinical research training program at NIH; establish mechanisms for the
review of applications for these new awards and fellowships; and
establish a loan repayment program for clinical investigators.
[7] GCRCs are NIH-funded entities located primarily at academic medical
centers that provide research infrastructure such as inpatient and
outpatient beds, laboratory services, and statistical support for
publicly and privately funded clinical investigators.
[8] NIH Clinical Research Study Group, ’An Analysis of the Review of
Patient-Oriented Research Grant Applications by the Division of
Research Grants“ (N.p., Nov. 21, 1994); IOM, Division of Health
Sciences Policy, Committee on Addressing Career Paths for Clinical
Research, Careers in Clinical Research: Obstacles and Opportunities,
eds. William N. Kelley and Mark A. Randolph (Washington, D.C.: National
Academy Press, 1994); NIH Director‘s Panel on Clinical Research,
’Report to the Advisory Committee to the NIH Director“ (N.p., December
1997); and AAMC and AMA, Report of the Graylyn Consensus Development
Conference (Washington, D.C.: AAMC, Nov. 20-22, 1998).
[9] In this analysis, the IOM committee counted as human research
studies involving human subjects, studies with both human subjects and
fundamental research, and human epidemiologic research.
[10] NIH‘s Office of Extramural Research (OER) conducted the Nathan
Panel‘s analysis. OER counted the entire study as clinical research if
any part of the study fit the Nathan Panel definition of clinical
research.
[11] In this study, the review success of individual investigator
applications from two NIH review cycles (January and October 1994
council rounds) was evaluated. The percentage of applications in the
top 20th percentile was used as an indicator of review success.
[12] See Tamara R. Zemlo and others, ’The Physician-Scientist: Career
Issues and Challenges at the Year 2000,“ The FASEB Journal 14 (February
2000): 221-30.
[13] Dollars have been adjusted to fiscal year 1997 using the Bureau of
Labor Statistics‘ Medical Consumer Price Index.
[14] NIH‘s estimate of $5.9 billion spent on extramural clinical
research was provided by the Office of Budget, which collects
information from the ICs. However, because the Office of Budget cannot
provide a breakdown of extramural research dollars by funding mechanism,
the percentage breakdown of clinical research dollars by funding
mechanism was provided by OER. OER‘s procedures overestimate clinical
research expenditures because, as stated earlier, OER counts as
clinical research spending all of the expenditures of a study if any
part of the study fits the Nathan Panel definition of clinical
research.
[15] In April 1998, CSR established the Panel on Scientific Boundaries
for Review to conduct a comprehensive examination of the organization
and function of the CSR review process. The panel consisted of research
experts from outside NIH and incorporated extensive input from the
extramural research community. Phase I of the panel, which is complete,
proposed a new organizational structure for CSR, and Phase II involves
the designation of study sections. Phase II is expected to be completed
by 2005.
[16] A Special Emphasis Panel is a group of scientists chosen as
reviewers because they are expert in the areas covered in the
applications being reviewed.
[17] Dollars have been adjusted to fiscal year 1997 using the Bureau of
Labor Statistics‘ Medical Consumer Price Index.
[18] NIH reported that in the past 15 years, it discontinued funding
eight GCRCs. In some cases, GCRCs did not reapply for NIH funding. In
other cases, they did reapply but did not reach a competitive funding
score through the peer review process.
[19] This award program supports the administrative infrastructure for
graduate training, but generally does not provide tuition/stipends to
students.
[20] NIH‘s Office of Research Training and Committee on Research
Training Assessment obtained data on students in the biomedical and
behavioral science fields who received NRSA support from 1981 through
1992. See Georgine M. Pion, The Early Career Progress of NRSA
Predoctoral Trainees and Fellows, NIH Pub. No. 00-4900 (Bethesda, Md.:
NIH, March 2001).
[21] The K12 pilot at NCRR is not the only type of K12 program being
used to support clinical research at NIH. For example, NCI created a
Clinical Oncology Career Development Program 10 years ago that is one
of the major ways it trains investigators to do translational research
as well as design and implement clinical trials.
[22] NIH also provides ongoing clinical research training for
scientists working at its Bethesda campus and other institutions.
Courses include Introduction to the Principles and Practice of Clinical
Research, Principles of Clinical Pharmacology, Ethical and Regulatory
Aspects of Human Subjects Research, and Clinical Research Training. NIH
also collaborates with Duke University and the University of Pittsburgh
to offer distance-learning programs that provide clinical research
training to physicians, dentists, Ph.D.‘s, and allied health
professionals.
[23] NIH supports four other extramural loan repayment programs: Loan
Repayment Program for Pediatric Research, Loan Repayment Program for
Minority Health Disparities Research, Loan Repayment Program for
Clinical Researchers from Disadvantaged Backgrounds, and Loan Repayment
Program for Contraception and Infertility Research.
[24] NIH‘s intramural loan repayment programs include a Clinical
Research Loan Repayment Program as well as an AIDS Research Loan
Repayment Program, a General Research Loan Repayment Program, and a
General Research Loan Repayment Program for Accreditation Council for
Graduate Medical Education Fellows.
[25] During the implementation phase of the loan repayment program,
NIH‘s ICs were instructed to assume an average cost of $100,000 for
each loan repayment contract to guide determination of how many awards
they could make. However, the level of debt among potential awardees
has been found to be less than what was originally thought, so NIH
intends to fund more repayment contracts in fiscal year 2002 than it
originally planned.
[26] The exact amount of each loan repayment contract will vary and
will depend on the total eligible debt of each awardee. Eligible
individuals must have qualifying educational debt in excess of 20
percent of their annual income or compensation at their expected date of
program eligibility. NIH will apply a portion of the budgeted $20.2
million toward federal and state taxes.
[27] Federal employees will not be eligible.
[End of section]
GAO‘s Mission:
The General Accounting Office, the investigative arm of Congress,
exists to support Congress in meeting its constitutional
responsibilities and to help improve the performance and accountability
of the federal government for the American people. GAO examines the use
of public funds; evaluates federal programs and policies; and provides
analyses, recommendations, and other assistance to help Congress make
informed oversight, policy, and funding decisions. GAO‘s commitment to
good government is reflected in its core values of accountability,
integrity, and reliability.
Obtaining Copies of GAO Reports and Testimony:
The fastest and easiest way to obtain copies of GAO documents at no
cost is through the Internet. GAO‘s Web site [hyperlink,
http://www.gao.gov] contains abstracts and fulltext files of current
reports and testimony and an expanding archive of older products. The
Web site features a search engine to help you locate documents using
key words and phrases. You can print these documents in their entirety,
including charts and other graphics.
Each day, GAO issues a list of newly released reports, testimony, and
correspondence. GAO posts this list, known as ’Today‘s Reports,“ on its
Web site daily. The list contains links to the full-text document
files. To have GAO e-mail this list to you every afternoon, go to
[hyperlink, http://www.gao.gov] and select ’Subscribe to daily E-mail
alert for newly released products“ under the GAO Reports heading.
Order by Mail or Phone:
The first copy of each printed report is free. Additional copies are $2
each. A check or money order should be made out to the Superintendent
of Documents. GAO also accepts VISA and Mastercard. Orders for 100 or
more copies mailed to a single address are discounted 25 percent.
Orders should be sent to:
U.S. General Accounting Office:
441 G Street NW, Room LM:
Washington, D.C. 20548:
To order by Phone:
Voice: (202) 512-6000:
TDD: (202) 512-2537:
Fax: (202) 512-6061:
To Report Fraud, Waste, and Abuse in Federal Programs Contact:
Web site: [hyperlink, http://www.gao.gov/fraudnet/fraudnet.htm]:
E-mail: fraudnet@gao.gov:
Automated answering system: (800) 424-5454 or (202) 512-7470:
Public Affairs:
Jeff Nelligan, managing director, NelliganJ@gao.gov:
(202) 512-4800:
U.S. General Accounting Office:
441 G Street NW, Room 7149:
Washington, D.C. 20548:
