DIETARY SUPPLEMENT RESEARCH CENTERS: BOTANICALS

RELEASE DATE:  December 22, 2003

RFA Number:  RFA-OD-04-002 (This RFA has been reissued, see RFA-OD-06-001)

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov)

COMPONENTS OF PARTICIPATING ORGANIZATION:
Office of Dietary Supplements (ODS)
 (http://ods.od.nih.gov)
National Center for Complementary and Alternative Medicine (NCCAM)
 (http://nccam.nih.gov)
National Institute of Environmental Health Sciences (NIEHS)
 (http://www.niehs.nih.gov) 

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S)  93.213 93.113 

LETTER OF INTENT RECEIPT DATE:  May 18, 2004
APPLICATION RECEIPT DATE:  June 15, 2004

THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION

o  Purpose of this RFA
o  Research Objectives
o  Mechanism of Support 
o  Funds Available
o  Eligible Institutions
o  Individuals Eligible to Become Principal Investigators
o  Special Requirements 
o  Where to Send Inquiries
o  Letter of Intent
o  Submitting an Application
o  Supplementary Instructions  
o  Peer Review Process
o  Review Criteria  
o  Receipt and Review Schedule
o  Award Criteria
o  Required Federal Citations

PURPOSE OF THIS RFA

NIH currently supports six Dietary Supplement Research Centers focused 
on botanicals, collectively referred to as the Botanical Research 
Centers (BRC) Program.  Grants for the centers were awarded in response 
to RFA solicitations in 1999 and 2000.  In 2003, the three major NIH 
co-sponsors (i.e., ODS, NCCAM, NIEHS) convened an expert panel to 
assess the status of the BRC Program.  This RFA is based on 
recommendations provided by the panel 
http://nccam.nih.gov/training/centers/bot-research-index.htm as well as 
the research priorities of NIH co-sponsors.

The ODS, NCCAM, and NIEHS invite applications to support research 
centers of excellence which will (1) promote interdisciplinary 
collaborative study of botanicals, particularly those that are found as 
ingredients in dietary supplements and (2) conduct research of high 
potential for being translated into practical benefits for human 
health.  This initiative is intended to advance the spectrum of 
botanical research activities (e.g., plant identification, chemical 
characterization, bioavailability studies, assessment of bioactivity 
and mechanism(s) of action, early phase clinical studies). Preclinical 
research, however, is encouraged as the primary focus. This RFA 
supports the enhancement of existing research infrastructure to 
increase interactions among scientists from a variety of disciplines 
and to provide outstanding training and research environments for 
future leaders in botanical dietary supplement research. 

This RFA will use a P50 award mechanism to provide support for a broad 
interdisciplinary research program consisting of highly integrated 
research activities and associated research infrastructure. Taken as a 
whole, a BRC funded under a P50 mechanism is expected to reach a level 
of achievement exceeding that expected on the basis of the sum of its 
parts.

For the purpose of this RFA, “botanical” is defined as plants, plant 
parts (e.g., bark, leaves, stems, roots, flowers, fruits, seeds, 
berries), plant exudates, algae, and macroscopic fungus. Bacterial or 
yeast fermentation products are not included. The definition of 
“botanical” is further extended to include botanical extracts and 
isolated bioactive constituents other than essential nutrients. 
Synthetic compounds derived from botanical sources are not encouraged 
as test materials for research conducted under this initiative.  If the 
applicant proposes to study synthetic compounds, their use must be 
scientifically justified.  This RFA is not supportive of applications 
aimed at new drug discovery.

RESEARCH OBJECTIVES

Background

National surveys indicate that more than half of adults in the U.S. 
take some form of dietary supplement; botanicals comprise about 25 
percent of the supplement market. These products are used by consumers 
to promote health and wellness, prevent and treat disease. 

Botanical ingredients in dietary supplements are derived from two 
primary sources: traditional herbal medicines (e.g., St. John’s wort, 
valerian, ginkgo, chamomile) and foods (e.g., soy, cranberry, broccoli, 
garlic).  Both of these contain bioactive constituents with potential 
health promoting properties. Despite widespread use of dietary 
supplements with botanical ingredients and promising science, 
biomedical research in this area has been relatively limited and 
unfocused. As a consequence, efficacy and safety of many widely used 
botanical ingredients have not been adequately evaluated.  Before these 
issues can be addressed, high quality basic and mechanistic research 
and early phase clinical studies are needed.  

Botanicals of Interest 

For the purpose of the RFA, botanicals of particular interest include 
plants commonly referred to as traditional herbal medicines or 
phytomedicines, many of which are widely available in the U.S. as 
dietary supplements. The National Toxicology Program (NTP) has an 
ongoing effort in the area of Herbal Medicines 
http://ntp-server.niehs.nih.gov/htdocs/liason/factsheets/HerbMedFacts.pdf.  
NIEHS encourages applications to study botanicals which are undergoing 
evaluation as part of the NTP.  This RFA also supports research on foods 
of plant origin which by virtue of biologically active components may 
provide health benefits beyond basic nutrition; these bioactive 
constituents are appearing with increasing frequency as ingredients in 
dietary supplements. Botanicals as dietary supplements are intended to 
be ingested. Other intended routes of administration (e.g., topical) are 
not within the scope of this RFA.

Botanical test materials ranging from whole fresh plants to isolated 
bioactive constituents are appropriate test materials for the proposed 
research. However, botanicals should not be thought of simply as sources 
of isolated phytochemicals to be studied.  A broader perspective is 
needed.  For example, applicants proposing to study isolated 
constituents from plants are advised to consider the potential effects 
of removing bioactive constituents from their original matrix and the 
potential difference in biological effects and clinical response as one 
moves from a relatively complex extract to an isolated bioactive 
constituent.

Objectives of the Research Program 

The purpose of this program is to support research centers of 
excellence to promote collaborative interdisciplinary study of 
botanicals with high potential for being translated into practical 
benefits for human health. While this initiative is intended to 
emphasize basic and preclinical research, clinical studies are not 
excluded. The goals of the BRC Program are to:

1. Build collaborative research teams that will advance the basic 
science to inform clinical studies; the following activities are 
emphasized 

o Characterize the chemical composition of botanicals and study their 
biological effects to provide better predictions of safety and efficacy 
in humans  
o Expand the research base via development and improvement of 
preclinical model systems (e.g. in vitro and in vivo) that will inform 
clinical studies 
2. Cultivate the use of contemporary technologies and innovative 
approaches (e.g., mass spectrometry, bioimaging, genomics, proteomics, 
metabolomics, bioinformatics, systems biology) in botanical research
3. Conduct clinical studies such as PhaseI/II trials (Optional)

BRC Themes

Each BRC will be structured around a central scientific theme. Themes 
provide a focus for center activities. 

An overarching research theme can be developed in a number of ways. For 
example, the proposed research may be conducted under the umbrella of a 
traditional medical system (e.g., Ayurveda); health issues of an under-
studied population group (e.g., children); a biological process with 
multiple clinical endpoints (e.g., inflammation); potential beneficial 
effects on an organ system (e.g., digestive); biological effects of a 
class of bioactive compounds (e.g., flavonoids, saponins, sterols, 
alkaloids, glucosinolates, terpenes) derived from botanicals with 
purported health promoting properties or as modifiers of the risk of 
disease (e.g., cancer, cardiovascular disease, diabetes).

Selection of a theme and associated research projects may be guided by 
a number of additional considerations, including but not limited to: 
(1) potential to translate proposed research to human health benefits, 
(2) state of the science related to the theme and proposed research 
topics, and (3) potential for integrating research activities and 
simultaneously maintaining thematic focus. 

The rationale for selection of specific botanicals for study should be 
clearly described and could include but is not limited to the 
following: history of use, prevalence of use, indications for use, 
existing preclinical science base, results of clinical or observational 
studies, and availability and effectiveness of conventional treatments.

Applicants need to consider the quality of botanicals used as research 
material and are directed for general guidance to a document regarding 
NCCAM Policy on the Quality of Natural Products Research 
http://nccam.nih.gov/research/policies/naturalproducts.htm. 

Experimental Approaches

The increased need for collaborative and integrated research approaches 
of multiple disciplines stems, in large part, from the rapid progress 
in developing new research tools for understanding biology both at a 
molecular and systems level. Research founded on and connected to 
aspects of human biology may encompass any form of cellular, molecular, 
structural, biochemical, genetic or other appropriate experimental 
approach.

Potential research directions might include but are not limited to the 
following:

o  Standardize test materials to improve prospects for reproducibility 
of biological effects and clinical response 

o  Develop new methods to rapidly screen for bioactive constituents 

o  Identify bioactive constituent(s)

o  Identify factors that influence the concentration of bioactive 
constituents (e.g., growing conditions, harvesting)

o  Identify targets (e.g., molecular, cellular, organ) of botanical 
test materials 

o  Identify and measure the concentration of bioactive constituents (or 
their active metabolites) at target sites 

o  Determine mechanism(s) of action of bioactive constituents

o  Assess synergy and/or antagonism among bioactive constituents 

o  Compare the bioactivity of an isolated active constituent(s) to that 
of a less refined test material (e.g., crude extract) from which it was 
derived

o  Identify interactions between individual constituents in complex 
natural product extracts and mixtures of botanicals as encountered in 
the traditional practice of herbal medicine or common use of dietary 
supplements

o  Examine biological effects of removing bioactive constituents from 
the original plant matrix

o  Conduct pharmacokinetic/pharmacodynamic studies of botanical test 
materials

o  Identify and validate biomarkers of botanical intake and/or 
biological effects 

o  Study the role of botanicals as regulators of genetic pathways or  
epigenetic events associated with disease risk 

o  Develop safety testing protocols for botanical dietary supplement 
ingredients, particularly those with a history of human use

o  Optimize the therapeutic index (i.e., margin of safety) of botanical 
test materials

o  Study botanical interactions and/or interactions of botanicals with 
prescription drugs or foods; for example, study the effects of 
botanicals on the pharmacokinetics and metabolism of drugs 

Structure and Organization of a BRC

A BRC should be an identifiable organizational unit formed by a single 
institution or a consortium of cooperating institutions. A BRC must 
minimally consist of: (1) one Administrative Core; (2) a Pilot Research 
Program; (3) at least one Research Resource Core; (4) three to four R01 
level Research Projects. 

Structure and Organization of a BRC is briefly described below.  (See 
details provided in the section on Special Requirements).

1.  Administrative Core

Leadership: The Center Director is the head of the Administrative Core.  
The Director is responsible for the organization, scientific and 
administrative leadership of the BRC and expected to devote substantial 
effort (25 percent minimum) to the Center.

Advisory Groups: The Administrative Core includes two advisory groups. 
A BRC External Advisory Committee (EAC) will provide oversight and 
assist the Center Director in making scientific and administrative 
decisions. An Internal Steering Committee (ISC) comprised of the 
Research Project and Core Leaders will meet regularly with the Center 
Director to discuss research progress.  

2.  Pilot Research Program

Pilot/feasibility research of the BRC must be relevant to the Center 
theme and research goals.  The primary purpose of this support is to 
attract promising investigators to centers and provide an opportunity 
for them to generate sufficient preliminary data to permit the 
submission of new applications for peer-reviewed research. 

3.  Research Resource Core(s)

The Center Director will identify research cores that will support the 
work of the research projects. The cores are intended to provide 
infrastructure and result in increased productivity contributing to 
synergy of the research effort as a whole. Examples of research 
resource cores include but are not limited to the following: botany or 
plant science facilities, analytical chemistry laboratories, animal 
facilities, clinical and biostatistical units.

4.  Research Projects

The research projects are equivalent to R01s in size and complexity. 
The collection of research projects must show evidence of 
interdisciplinary collaborative efforts and be consistent with the 
thematic focus of the BRC. 

Projects can be basic research or clinical studies. Center grant 
applications comprised solely of basic/preclinical research projects 
should describe the relevance of the proposed research to human health 
and the potential for translation to human health applications. 
Applicants with strengths in clinical research may propose one clinical 
research project. Phase I/II clinical studies to assess feasibility, 
dose range effects, pharmacology, safety, and biological efficacy are 
acceptable. A Phase II study may be of modest size, provided it has 
adequate statistical power to estimate or determine with some degree of 
certainty the effect of a given intervention. Phase III studies will be 
considered non-responsive to this RFA.

MECHANISM OF SUPPORT  

This RFA will use the NIH P50 (Specialized Center) grant award 
mechanism. As an applicant you will be solely responsible for planning, 
directing, and executing the proposed project. This RFA is a one-time 
solicitation.  The anticipated award date is February 2005. 

This RFA uses just-in-time concepts. Although not discouraged, this 
program does not require cost sharing as defined in the current NIH 
Grants Policy Statement at 
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.

FUNDS AVAILABLE

The participating ICs intend to commit approximately $6.5 million in FY 
2005 to fund up to five Center grants in response to this RFA. An 
applicant may request a project period of up to five years and a budget 
for total costs (direct plus facilities and administrative (F&A) costs) 
of up to $1.5 million per year. Because the nature and scope of the 
proposed research will vary from application to application, it is 
anticipated that the size and duration of each award will also vary. 
Although the financial plans of the IC(s) provide support for this 
program, awards pursuant to this RFA are contingent upon the 
availability of funds and the receipt of a sufficient number of 
meritorious applications.  

ELIGIBLE INSTITUTIONS

You may submit an application if your institution has any of the 
following characteristics: 

o  For-profit or non-profit organizations 
o  Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o  Units of State and local governments
o  Eligible agencies of the Federal government  
o  Domestic institutions/organizations

Foreign institutions are not eligible to apply. However, a subcontract 
with a foreign institution(s) is allowed if the collaboration is needed 
to accomplish the research objectives of the applicant institution.  
See details included in the Special Requirements section below.

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support. Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.

SPECIAL REQUIREMENTS

This section provides detailed descriptions of required elements of the 
grant application and post-award conditions. Applications that fail to 
meet required elements of the grant application will be considered non-
responsive to the RFA and will not be reviewed.  Non-responsive 
applications would include but are not limited to the following 
examples: research projects focused on the isolation of single chemical 
constituents for the purpose of drug discovery; epidemiologic studies 
or surveys of dietary supplement use. Applicants with concerns about 
being responsive to the RFA are encouraged to contact NIH program staff 
early in the grant preparation process.

Statement of Institutional Commitment

An institution considering applying for a BRC should demonstrate a 
commitment to the BRC stability and success by incorporating the BRC 
high within its institutional priorities. The applicant must provide a 
statement of commitment that includes a plan addressing how the 
institutional commitment will be established and sustained, how the 
institution will maintain accountability for promoting scientific 
excellence, and how the BRC research effort will be given a high 
priority within the institution relative to other research efforts. The 
institutional commitment may be in the form of support for recruitment 
of scientific talent, faculty appointments for BRC investigators, 
provision of discretionary resources to the BRC Director, assignment of 
specialized research space, cost sharing for resources, or other ways 
proposed by the applicant institution. A letter from the Dean or 
individual of similar rank should be attached confirming this 
commitment. If the grant application includes research activities that 
involve institutions other than the applicant organization, the 
proposed BRC is a consortium effort. In the case of a BRC that involves 
a consortium arrangement between two or more institutions, the 
institution that submits the P50 application must include in the 
application a formal written agreement(s) from the other participant 
organization(s).

Administrative Core

The organization of the Administrative Core should encompass a support 
structure sufficient to ensure accomplishment of the following: 
coordinating and integrating the Center activities; developing a plan 
for evaluation of scientific progress; formation and interaction with 
the two advisory groups (EAC and ISC); regular evaluation of scientific 
progress; overseeing the solicitation, review and selection of pilot 
research studies; overseeing training and career development efforts; 
and working with the applicant institution to enhance the visibility 
and effectiveness of the center as a focus for botanical research.
 
The Center Director is the leader of the Administrative Core. While the 
final administrative structure of the Center will be left to the 
discretion of the Director, experience demonstrates that effective 
development of a Center program requires interaction among the 
Director, Research Project Leaders, Research Core Leaders, advisory 
groups (EAG and ISC), appropriate institutional administrative 
personnel, and the staff of NIH. In addition, it is important that a 
person with institutional management expertise and experience be 
involved directly with the fiscal aspects of the application and grant.

The applicant has the option to include a Project Manger in the 
Administrative Core.  The position should be described and justified. 
In addition to the Center Director and Project Manager, additional 
administrative support personnel may be budgeted at one full time 
equivalent (FTE) which may be divided among one or more positions. This 
FTE should be fully justified. The Administrative Core may include 
limited funds for program enrichment activities such as seminars and 
research workshops. Funds from the center grant cannot be allocated for 
website development or maintenance, newsletters, consumer information 
or outreach activities.

Applications should include yearly travel expenses in the 
Administrative Core to pay for the Center Director and at least two 
Research Project Leaders to attend one two-day meeting of the Center 
Directors.

Center Director

Each applicant institution shall name a Center Director as the 
Principal Investigator (PI) who will be the key figure in the 
administration and management of the Center grant. The Center Director 
must be an experienced scientist with leadership and administrative  
skills commensurate with those required for a P50 or similar award 
mechanism. The Center Director will be responsible for the organization 
and operation of the Center and for communications with NIH. The 
Director is also required to be a Project Leader of one of the R01 
level research projects within the Center. The Director’s 25 percent 
effort (minimum requirement) should be allocated as follows: Leader of 
the Administrative Core (10 percent) and Leader of a Research Project 
(15 percent). 

The applicant may elect to provide a plan for assignment of 
administrative responsibilities if the Center Director is on prolonged 
leave from the institution or otherwise unavailable for administration 
and/or decision making. The plan could include the appointment of a co-
Director of the BRC at the applicant institution.  

The Center Director is the only PI for this grant application. The 
research projects will be headed by Research Project Leaders.  A 
Research Project Leader is equivalent to a PI on a standard NIH R01 
grant application.  Research cores will be headed by Research Core 
Leaders.

Annual Meeting of Center Directors

The Center Directors and at least two selected Research Project Leaders 
shall participate in one meeting per year, alternating between the 
Washington DC metropolitan area or another site agreed to by the Center 
Directors and the NIH. Funds should be included in the proposed budgets 
to support attendance at this annual meeting. The purpose of the 
meeting is to meet with NIH staff to share scientific information, 
assess scientific progress, discuss problems, identify new research 
opportunities, discuss potential collaborations, and review research 
priorities.

External Advisory Committee (EAC)

The Center shall establish an EAC to provide oversight and assist the 
Center Director in making scientific and administrative decisions. The 
EAC will have oversight authority for the research projects submitted 
in the grant application but will not have the authority to review and 
modify projects already approved by NIH. In addition to evaluating 
scientific progress of the Center, the EAC should periodically review 
Center operations to ensure that resources, especially core resources 
are used for the most scientifically worthy projects. The EAC is 
expected to participate in the review of pilot project applications and 
may perform other duties deemed appropriate by the applicant.  For 
example, termination of research projects should be discussed with the 
EAC.

The EAC members and the committee chair will be appointed by the Center 
Director; members serve on a rotating basis. The Center Director will 
serve on the EAC in an ex-officio capacity only. The EAC should consist 
of at least six members in addition to the Center Director. Over the 
anticipated five year award period, the Center Director is urged to 
appoint to the EAC a pharmacognosist or ethnobotanist, toxicologist, 
research clinician, biostatistician, and other individuals with 
scientific expertise specific to the BRC (e.g., health outcome(s) under 
investigation, relevant technologies). EAC members may be employees of 
the grantee institution, participating institutions, or from outside 
institutions, but they cannot participate directly in the research of 
the BRC. If an EAC member becomes directly involved in the research of 
the Center, the resulting committee vacancy must be reported to NIH 
program staff and a replacement sought in a timely manner.

Please note that APPLICANTS SHOULD NOT IDENTIFY POTENTIAL EAC MEMBERS 
IN THEIR APPLICATION. However, the process by which members will be 
chosen must be specified.

The EAC should be established within nine months of the start of first 
budget period and meet once before the end of that period. Thereafter, 
the EAC shall meet at least twice a year. Minutes of all (i.e., 
scheduled and ad hoc) EAC meetings must be kept. Minutes of regularly 
scheduled meetings shall be sent to NIH staff within 60 days and also 
be included in the annual Progress Report. At least one of the semi-
annual meetings must take place in person; other meetings may be 
conducted by video- or teleconference. Support for the EAC must be 
explicitly budgeted in the Administrative Core. If the EAC committee 
will include individuals who require travel expenses, these costs 
should be reflected in the administrative budget.

Internal Steering Committee (ISC)

The ISC will meet regularly to discuss research progress and problems, 
utilization of core resources, new research opportunities, and program 
development. Regular meetings of the ISC are intended to facilitate 
internal communication, cooperation, and collaboration among BRC 
investigators. The applicant should provide a plan for ISC meetings.

Pilot Research Program

The Center must request funds to support pilot projects.  The 
application must describe the process for soliciting, reviewing, 
selecting and monitoring the pilot projects. The EAC must be involved 
in the review process for selection of pilot awards, either directly as 
reviewers or indirectly as part of EAC oversight responsibilities.  

Pilot research studies are typically limited to a period of one to two 
years.  No more than $100,000 (direct costs) per year may be devoted to 
pilot research projects.  This is not a per project maximum, but rather 
an aggregated maximum of all pilot research projects. The first pilot 
studies should be awarded during the first budget year and new awards 
are expected in subsequent budget years.
 
Pilot project funds cannot be awarded to the Center Director, co-
Director, Research Project Leaders or Core Leaders. Otherwise, both 
junior and established investigators from the applicant institution 
and/or a consortium are eligible to apply for funding. The research 
must be related to the Center theme and research objectives. Pilot 
studies may include clinical research. Pilot or other Center funds 
cannot be used to assess the variability of botanical ingredients in 
products available to consumers; this activity is not likely to lead to 
the submission of grant applications for additional research.

NIH program staff must be notified before funds can be expended to 
initiate pilot projects, to verify (1) EAC approval and (2) approval of 
animal care and use and human subject assurances.  The notification 
should include the proposal and specific research aims, the pilot 
research budget, and a biosketch of the pilot study investigator.

Career Development and Training

The establishment of a BRC is expected to provide a rich environment 
for training and career development. The applicant should include plans 
for obtaining funds to provide training and career development 
opportunities. Supplemental funding for training and career development 
could be sought from NIH Ruth L. Kirschstein National Research Service 
Awards, institutional training grants (T32), individual fellowships 
(F31, F32), mentored career development awards (K01, K08) and other 
sources including, but not limited to, the parent institution and 
private foundations.

Centers are encouraged to provide interdisciplinary research training 
and career development opportunities to graduate students, postdoctoral 
fellows, and physician-investigators and fully integrate the training 
and career development activities into the research of the BRC. 

Research Resource Cores 

A research core is defined as a resource that enhances research 
productivity or in other ways benefits investigators working to 
accomplish the common research goals of the Center. A Center must 
establish at least one Research Resource Core. Each core must be 
utilized by at least two research projects.  Applicants should provide 
a core utilization table showing an estimate of percent effort devoted 
to each proposed research project in the first year of the grant. (See 
details included in the section Special Instructions for Preparing a 
Competing BRC Grant Application below.) Core resources should not 
duplicate resources already available to Center investigators. However, 
fee-for-service core components (i.e., Center use of existing 
facilities) are acceptable with adequate justification.

While the research core should function primarily as a service entity, 
core scientists can also be involved in conducting original research. 
Chemistry cores, for example, may need to develop new methods of 
analysis.

Research Projects

The research projects are individual research studies funded through 
the Center. Each of the R01 level research projects must request at 
least three, but not more than five, years of support. The research 
projects should be of a scope similar to the traditional NIH R01 
research grant; inclusion of preliminary data is required. The 
applicant should list grant support of each Research Project Leader in 
the Biosketch section of the application. (See details included in the 
Supplementary Instructions section below.) Applicants with questions 
regarding eligibility of project leaders are encouraged to contact NIH 
program staff.

Research projects in the application may be simultaneously submitted to 
the CSR as investigator-initiated applications (e.g., NIH R01). The 
dual submission must be clearly documented in the Center application 
under “pending” support. If, following review, both the Center 
application and the R01 application are found to be in the fundable 
range, the research project investigator must relinquish the R01 and 
will not have the option to withdraw from the Center grant.  This is an 
NIH policy intended to preserve the scientific integrity of a multi-
project grant, which may be seriously compromised if a strong component 
project is removed from the program.  Investigators wishing to 
participate in a multi-project grant must be aware of this policy 
before making commitments to the Center Director and applicant 
institution.

Applications must include at least three, but no more than four,   
research projects. Collectively, the research projects must show 
evidence of interdisciplinary collaboration among scientists across the 
Center. At least three of the submitted projects, must be judged 
meritorious by the peer-review panel for the application to meet the 
minimal requirements of a P50 Center. Failure to meet this requirement 
will remove the application from funding consideration.

At least three R01 level research projects must be active throughout 
the period of grant support. If this requirement is not met, the grant 
mechanism may be changed. An exception to this requirement may be made 
if the applicant submits only three R01 level research projects and one 
is a clinical study which cannot be implemented prior to obtaining 
results from related preclinical research projects included in the 
application.

Not more than one of the research projects may be a clinical study. 
Early (Phase I and Phase II) clinical trials can be proposed as part of 
the application.  Epidemiologic and behavioral studies, population 
surveys and health services research are NOT permissible as clinical 
studies and cannot be proposed either as primary research projects or 
submitted for consideration for pilot funding.

NCCAM requires all clinical projects to undergo review by the Office of 
Clinical and Regulatory Affairs (OCRA). Those grants supported by NCCAM 
and which contain a clinical component will be required to obtain NCCAM 
approval. Grants supported by another Institute/Center may be subject 
to a similar review. Applicants are directed to the NCCAM guidance 
document for clinical studies 
http://nccam.nih.gov/research/policies/clinical-considerations.htm 

It is the sole responsibility of the applicant to obtain all necessary   
clearances from the Food and Drug Administration (FDA) as required. 
Questions regarding IND applications should be addressed to the FDA. 
(For FDA contact, see Where To Send Inquiries section below).

Applicants are strongly encouraged to consult their local Institutional 
Review Boards (IRB) regarding IND applications. The applicant should 
present a plan for IND submission, evidence that an IND application is 
in process or that the FDA has allowed an exemption.

Intellectual Property Rights

The institution should provide written assurance that it will protect 
the intellectual property rights of the BRC investigators and their 
collaborators and under no circumstances engage in formal/legal 
agreements with commercial sources (e.g., pharmaceutical companies, 
dietary supplement ingredient suppliers or manufacturers) that would 
compromise the ability of BRC investigators to have unhampered access 
to institutional resources in BRC-related research or participate fully 
in collaborations with any other researchers. The statement of 
commitment should also include a written assurance that in its 
interactions with commercial entities under sponsored research 
agreements, the BRC will comply with the requirements of the Bayh-Dole 
Act and NIH funding agreements while upholding basic principles of 
academic freedom. Sponsored research agreements with commercial 
entities should be entered into by a BRC only upon due consideration of 
the points outlined in "Developing Sponsored Research Agreements: 
Considerations for Recipients of NIH Research Grants and Contracts 
(Federal Register, Vol. 59, No. 215, Tuesday, November 8, 1994, pp. 
55674-55679)", a copy of which can be viewed at: 
http://ott.od.nih.gov/spons_research.html. The statement of 
commitment should also include a written assurance that the BRC will 
manage its interactions with third parties so that they do not restrict 
the ability of a BRC to receive and disseminate biomedical research 
materials from and to the scientific community. Likewise, letters 
should be supplied by any relevant third parties confirming their 
adherence to these policies.  Third party agreements should be 
identified at the time of grant submission. If third party agreements 
with commercial sources are established after application submission: 
(1) but prior to review, contact NCCAM (Dr. Goldrosen); (2) and after 
review but prior to award, contact ODS (Dr. Swanson).

Foreign Collaborations

This RFA is not intended to support international studies or build 
research infrastructure in foreign institutions. Funding support for 
such activities may be available from other initiatives at the NIH.   
Foreign collaborations are appropriate if they are needed to achieve 
the research objectives of the applicant institution. Applicants should 
describe the nature of the collaboration, plans to formalize a 
relationship, obtain necessary permits, and establish contract 
elements.  At a minimum, applicants are advised to consider the 
following issues: intellectual property rights, particularly as they 
pertain to traditional healing practices; regulations for collection of 
botanical material from foreign countries; and rights and 
responsibilities of both parties if any patents are developed from the 
proposed research.  Relevant host country, governmental, non-
governmental and community organizations should be consulted early in 
the grant planning stage to ensure that research plans are compatible 
with national and local policies and to identify potential barriers to 
collaboration.  

WHERE TO SEND INQUIRIES

We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

o  Direct questions about scientific/research issues to:

Christine A. Swanson,Ph.D.
Director, Botanical Research Centers Program
Office of Dietary Supplements
Office of Disease Prevention, Office of the Director
6100 Executive Blvd. Room 3B01, MSC 7517
Bethesda, MD  20892-7517
Telephone:  (301) 435-2920
FAX: (301) 480-1845
Email: swansonc@od.nih.gov 

o  Direct questions about specific scientific/research interests of 
participating ICs to:

Qi-Ying Liu, M.D., M.Sci.
Program Officer
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Blvd.
Democracy 2, Suite 401
Bethesda, MD  20892-5475
Phone:  (301) 402-5867
Fax:  (301) 480-3621
Email: liuqiy@mail.nih.gov

Elizabeth A. Maull, Ph.D.
Program Administrator
Susceptibility and Population Health Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233 (MD EC-21)
Research Triangle Park, NC 27709
Phone:  (919) 316-4668
Fax: (919) 316-4606
Email:  maull@niehs.nih.gov

o  Direct your questions about peer review issues to:

Martin Goldrosen,Ph.D. 
Director, Office of Scientific Review
National Center for Complementary and Alternative Medicine
6707 Democracy Blvd., Suite 401, MSC 5475
Bethesda, MD  20817-5475
Telephone:  (301)594-2014
FAX:  (301)480-2419
Email: goldrosm@mail.nih.gov

o  Direct your questions about financial or grants management matters 
to:

George Tucker, M.B.A.
Deputy Chief Grants Management Officer
Division of Extramural Activities 
NIDDK
II Democracy Plaza, Room 718
Bethesda, MD  20892
Telephone:  (301) 594-8853
FAX:  (301) 480-3504
Email: tucker@extra.niddk.nih.gov 

o  Direct your questions about IND applications to:

Shaw T. Chen, M.D., Ph.D.
Associate Director, ODE-V
HFD-105, CDER, FDA
9210 Corporate Blvd., S-103
Rockville, MD 20850
Telephone (301) 827-2601
FAX:      (301) 827-2317
Email: chens@cder.fda.gov

Applicant Information Meeting:

In order to improve the quality of applications submitted in response 
to this RFA, as well as give potential applicants an opportunity to 
clarify any issues or questions concerning the RFA, an Applicant 
Information Meeting (AIM) will be held.  

The meeting will be held at or in close proximity to the NIH campus 
approximately one month after the RFA is issued. There is no 
registration fee, but attendee travel to the meeting and all other 
travel costs are the responsibility of the attendee.  For additional 
information regarding the AIM as well as registration instructions, 
please visit the ODS web site http://ods.od.nih.gov or call 301 435-
2920.  A summary of the presentations and issues discussed at the 
meeting will be made available through the ODS web site within two 
weeks of the AIM meeting.  

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o  Descriptive title of the proposed research
o  Title of research projects
o  Name, address, and telephone number of the Principal Investigator
o  Names of other key personnel 
o  Participating institutions
o  Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows IC staff to estimate the potential review 
workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to:

Christine A. Swanson, Ph.D.
Director, Botanical Research Centers Program
Office of Dietary Supplements
Office of Disease Prevention, Office of the Director
6100 Executive Blvd. Room 3B01
Bethesda, MD  20892
Telephone:  (301) 435-2920
FAX: (30) 480-1845
Email: swansonc@od.nih.gov

SUBMITTING AN APPLICATION 

Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/. The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

SUPPLEMENTARY INSTRUCTIONS  

Special Instructions for Preparing a Competing BRC Grant Application    

A. General Information 

General instructions for the preparation of NIH grant applications are 
contained in the standard NIH grant application kit (PHS Form 398, 
revised May 2001). Even though the PHS 398 is intended primarily for a 
single research project grant (i.e. R01), many of the general 
instructions and forms also apply to BRC grant applications.  
Exceptions are due unique requirements of BRCs and corresponding 
modifications of review criteria. Accordingly, the special instructions 
in this document were prepared for use along with the PHS Form 398 
grant application kit. Unless otherwise specified, PHS 398 instructions 
apply. 

B. Detailed Instructions 

1. Face Page (Page 1)
The face page is the same as the face page (form page 1) in the PHS 398 
kit. In item 1, enter the title of the Center. The title should be 
descriptive and reflect the thematic focus of the Center. In item 2, 
insert the RFA number, and enter the title “Dietary Supplement Research 
Centers: Botanicals”. In item 3, indicate the name, degree, and 
position (or equivalent) title of the BRC Principal Investigator. 

2. Description, Performance Sites, and Key Personnel (Page 2) 
Page 2 is the same as form page 2 in the PHS 398 application kit. 
Provide a brief description of the BRC in the space provided, 
specifically addressing each project and proposed resource core. Fill 
in all the performance sites and all key professional personnel 
including all Research Project and Core Leaders and key personnel of 
the Pilot Research Program and Career Development effort, using 
continuation pages as required.

3. Table of Contents (Page 3)
Instead of using form page 3 in the PHS 398 application kit, prepare a 
Table of Contents that identifies by page number all major parts of the 
BRC application so that each can be readily located. When listing 
individual projects and core components, identify each by a project or 
core number, title and responsible investigator (i.e., Research Project 
or Core Leader) in the order in which they appear in the application.

For the Table of Contents it is recommended that applicants follow a 
format similar to that outlined below using continuation pages as 
needed:

I. Face Page 

II. Description, Performance Sites, Key Personnel   

III. Table of Contents of Center Grant Application  

IV. Initial Program Budget (see Detailed Instruction #4 below)

V. Summary Program Budget (see Detailed Instruction #5 below)

VI. Biographical Sketches (see Detailed Instruction #6 below)

VII. Institutional Commitment (see Detailed Instruction #7 below)  

VIII. Center Description (see Detailed Instruction #8 below)  

o Title Page with Principal Investigator

o Center Overview 

o Center Theme and Botanicals to be Studied 

o Center Organizational Structure 

o Scientific Integration – Interactions and Collaborations

o Center Director

o Institutional Resources (unique facilities at applicant institution 
plus those of other participating institutions, if applicable)

o Research Plan: including Summary of Research Projects and Cores  

o Literature Cited

IX. Research Projects (see Detailed Description #9 below) 

Project 1 

o Title Page with Project Leader

o Abstract Page 

o Budget/Budget Justification Pages

o Resources

o Research Plan 

Project 2 (same format as above) etc, for additional projects

X. Core Resources (see Detailed Instruction #10 below) 

Core 1 Administrative Core (required)

o Title Page with Core Leader/Center Director

o Abstract

o Budget/Budget Justifications

o Resources

o Plan/Interactions/Progress (for competing renewals)

Core 2 (at least one Research Resource Core required)

o Title Page with Core Leader

o Abstract Page

o Budget/Budget Justifications

o Resources

o Resource Plan 

o Human Subjects or Vertebrate Animals or “Assurances”

o Literature Cited

Core 3 (follow format for Core 2) etc., for additional cores 

XI. Pilot Research Program (see Detailed Instruction #11 below)

o Title Page with Pilot Program Leader

o Program Plan

XII. Training and Career Development (see Detailed Instruction #12 
below)

o Title Page 

o Program Plan

XIII. Checklist

XIV. Appendix

4. Summary Program Budget for the Initial Budget Period 
Use PHS 398 form page 4 to present the summary budget for the first 
year. For each category, show separately the total amounts requested 
for each research project and core. Applicants may request up to $1.5 
million in the total costs (direct plus facilities and administrative 
(F & A) cost) for the first year. 

If the grant application includes research activities that involve 
institutions other than the applicant organization, the proposed 
program represents a consortium effort. It is essential to explain the 
programmatic, fiscal, and administrative arrangements for such 
activities. These matters also should be discussed in general terms in 
the Center Description section of this application and more 
specifically within descriptions of pertinent projects. Include in the 
designated blocks on form page 4 the total cost (direct plus F & A 
cost) associated with such third party participation. 

5. Summary Program Budget for Entire Project Period
Use PHS 398 form page 5 to show the total BRC budget requested for each 
of the five years. Justifications for increases in succeeding years 
should not be included here; they should be delineated in the detailed 
budgets for individual projects and cores. Current NIH practice limits 
overall budget escalation per year to 3 percent cost-of-living. 

6. Biographical Sketches
Prepare biographical sketches as described in the PHS 398 application 
kit. Begin with the Principal Investigator/BRC Director and then 
proceed in alphabetical order. Biographical sketches are required for 
all key personnel participating in the individual BRC projects and 
cores, including consultants.

7. Institutional Commitment 
In two pages or less, describe how the institution will make the BRC an 
area of high priority. For example, describe the space, personnel and 
other resources that the institution will make available to ensure that 
the BRC exists in an appropriate environment for conducting an 
effective research program. Outline plans for the commitment of future 
resources in space and personnel to strengthen the research capability 
of the BRC. The application should describe how the institution will 
participate in overseeing research progress and generally assuming a 
high level of accountability for the success of the BRC in achieving 
research goals and objectives. 

A letter of institutional commitment from the Dean or another person of 
similar rank should be included. If the application is a consortium 
effort, similar letters of support from participating institutions 
should be included.

8. Center Description (20 page limit not including description of 
institutional resources or literature citations; additional 10 pages 
allowed for competing renewals. 

The order of the items listed in the table of contents may be changed 
in the application, but all topics should be included.

Title Page:
A title page with the name of the BRC and Center Director on a plain 
piece of paper.

Center Overview:
Provide a concise description of the BRC.

Center Theme and Botanicals to be Studied: 
Discuss the rationale for the thematic focus of the Center and for the 
selection of botanicals to be studied. Discuss the scientific 
significance of the research to be conducted as well as the potential 
for the research to be translated into practical benefits for human 
health.

Center Organizational Structure:
Discuss the overall breadth of the administrative and scientific 
capabilities of the BRC to address critical research needs related to 
botanical dietary supplement ingredients. Explain how the organization 
of the BRC will maximize the potential to achieve research objectives. 
Include an organizational chart showing the relation of key center 
components (e.g., Research Projects and Cores). Describe the role of 
the External Advisory Committee and the Internal Steering Committee. 

Scientific Integration - Interactions and Collaborations: 
Discuss how interactions will be maintained and fostered among 
researchers within the research projects and among researchers within 
the research cores (e.g., nature and frequency of project and core 
meetings). Describe how the core resources will be integrated 
effectively into the program to maximize the research capability of the 
BRC. Describe how the projects and cores will function collectively to 
produce a truly interdisciplinary collaborative program in which the 
whole is greater than the sum of its parts. If applicable, describe how 
the effects of geographic separation will be overcome to maximize 
critical scientific interactions. Include a table showing an estimate 
of the allocation of core effort (percent) for each of the proposed 
research projects. 

Center Director:
Describe the authority, scientific and administrative experience of the 
principal investigator to provide leadership and direction to the BRC. 
Describe the processes and chain of responsibility for scientific 
decision-making and day-to-day administration and management of the 
BRC. If a co-Director will be appointed at the applicant institution, 
the justification and responsibilities of the co-Director should be 
described. 

Institutional Facilities and Resources:
Describe the institutional facilities and resources available to BRC 
scientists at the applicant institution. If there are multiple 
performance sites, then resources available at each site should be 
described.  Summarize the special features of the institutional 
facilities and resources that make this application strong and/or 
unique.
 
Research Plan, including a Summary of Projects and Cores:
This important section provides the group of investigators an 
opportunity to give conceptual wholeness to the overall program by 
giving a statement of the research objectives and by laying out a broad 
strategy for addressing them. In this section, the applicant summarizes 
the overall research plan for the multi-project application.  The 
application should be viewed as a collection of complementary research 
projects, each capable of standing on its own scientific merit but 
accomplishing more as part of a center grant than as an isolated R01 
award. The aims of each project and core should be summarized along 
with a concise plan to achieve the stated objectives.
In 10 pages or less, applicants for competing renewal grants should 
address overall progress of the BRC in meeting research objectives 
during the last project period, as well as describing the evolution of 
project goals over time.  

9. Research Projects (Follow PHS 398 page limitations; five additional 
pages allowed for competing renewals, excluding literature citations.)
Page limitations specified for individual R01 grant applications in the 
PHS 398 application kit must be followed for individual research 
project plans. For each research project provide the following: 

o A title page with a project number, a title for the project, the 
Project Leader and co-investigators on a plain piece of paper.

o An abstract of the research plan. Follow PHS 398 instructions for all 
sections of this page.

o Budget Pages
The detailed budget for the first year and the overall budgets for each 
succeeding year for each research project should be presented 
separately using the PHS form pages 4 and 5. 

O Resources
Follow PHS 398 instructions for Resources. If there are multiple 
performance sites, then resources available at each site should be 
described. 

o Research Plan
Use the PHS 398 instructions for the Research Plan (Items a-i). The 
Research Plan should include sufficient information needed for 
evaluation of the project, independent of any other documentation. 
Detailed interactions between projects and cores not illustrated in the 
organizational chart under the Center Description section should be 
provided in this section. 

o For competing renewals a) describe the scientific accomplishments for 
each research project proposed in the last grant term (i.e., from date 
of original center award to present.) Do not repeat information 
included as preliminary data under the Research Plan section. Limit 
this narrative to three pages plus publication citations for each 
project. Citations are limited to published articles or those in press; 
do not include submitted articles or those in preparation.  b) If the 
applicant proposes to renew and/or expand a research project funded in 
last grant term, provide a justification (e.g., Project Leader met 
original research objectives and developed additional research aims 
and/or identified new research opportunities during the course of 
conducting proposed research).
   
10. Core Resources (allow ten pages per core excluding literature 
citations; allow three additional pages for competing renewals, 
excluding literature citations)
 
The BRC must include an Administrative Core and at least one scientific 
Research Resource Core that clearly enhance the specialized research of 
the BRC. The Administrative Core should include plans for overseeing 
the Pilot Research Program as well as training and career development 
efforts. Scientific cores must serve at least two R01 level projects.  
For each Core Resource, whether administrative or scientific, provide 
the following information:
 
o A title page with the core resource number, a title for the core, the 
names of the Core Leader and co-investigators on a plain piece of 
paper. 

o An abstract of the Core Resource, using form page 2 of the PHS 398 
application kit as described for research projects in item 9, above. 
The abstract should describe the nature and purpose of the resource. 
The bottom sections of form page 2 should include performance sites and 
all key professional personnel as instructed.

o Budget Pages 
Use same format as in item 9, above, for research projects. 

o Resources  
Use same format as in item 9, above, for research projects.

o Resource Plan (Plan/Interactions/Progress for competing renewal 
applications).  As appropriate for the proposed Core, use the plan 
format suggested for research projects in the PHS application kit 
(sections a-d). At a minimum, the application should state the specific 
aims of the core; preliminary studies should also be included if 
appropriate.   

Describe the nature of the resource and its importance to the 
specialized research of the BRC; describe the projected operation of 
the core, placing special emphasis on cost effectiveness and/or quality 
control factors; describe the qualifications of the individual(s) 
assigned to administer/operate the resource.  

For competing renewal applications, describe the past performance of 
the resource core in relation to accomplishing the original BRC 
research goals. 

o Human Subjects and Vertebrate Animals 
If applicable, provide information on human subjects and/or vertebrate 
animals (sections e-f) following instructions in the PHS 398 
application kit.
 
11. Pilot Research Program (5 pages for the program summary, plus an 
additional 5 pages for competing renewal applications)
 
The Pilot Research Program should be incorporated into the 
Administrative Core activities, but listed separately in the table of 
contents.

o Title Page with "Pilot Research Program" and the name of the program 
leader on a plain piece of paper. 

o A program plan containing the following elements: a) A description of 
the process used by the BRC to solicit, review and fund pilot studies 
within the BRC institution(s); b) A description of how the BRC will 
work with pilot study grantees to promote the submission of new 
applications for peer-reviewed research relevant to the BRC.

o For competing renewal applications, provide a summary identifying the 
achievements of all pilot projects (ongoing or terminated) supported 
during the last project term. Identify the pilot project grantee; list 
the publications and/or grant submissions resulting from the research; 
and/or describe how pilot projects improved prospects of R01 level 
projects. 

12. Training and Career Development 
 
Although the BRC does not provide special funds for a training and 
career development program, the BRC is expected to provide a rich 
environment for these activities. This section of the application 
should include: 

o A title 

o A summary of the program containing the following elements: a) List 
potential funding sources for research training and career development 
for the BRC; b) Describe plans for seeking funding; c) Provide a brief 
description of prospective mentors who will interact directly with 
candidates.

o For competing renewal applications, list all of the individuals 
supported by training and career development awards during the past 
term of the grant. The present position and recent accomplishments of 
these individuals (e.g., funded grants, publications) should also be 
described to demonstrate how the BRC has contributed to their research 
careers.

13. Checklist

Complete the checklist as required in the PHS 398 application kit.

14. Appendix Material
As an additional requirement for this RFA, provide five copies of a 
single appendix for the entire document.  Order of materials in the 
appendix should follow that of the application (Center Description, 
Research Project #1, #2, #3, Core #1, #2, etc.). Each section should be 
clearly labeled. 

Appendix materials should be limited and should not be used to 
circumvent the page limits for the research plans. Copies of appendix 
material will only be provided to the primary reviewers of the 
application and will not be reproduced for wider distribution among all 
reviewers. The following materials may be included in the appendix: 

Up to TEN publications per project or core, limited to including 
manuscripts (published or accepted for publication), abstracts, patents, 
or other printed materials directly relevant to the project.  
   
Surveys, questionnaires, and data collection instruments.  These may be 
stapled as sets.  
   
Original glossy photographs or color images of gels, micrographs, etc., 
provided that a photocopy (may be reduced in size) is also included 
within the 25-page limit of items a-d of the research plan.

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at: 
http://grants.nih.gov/grants/funding/phs398/labels.pdf.

SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten 
original of the application, including the Checklist, and three signed, 
photocopies, in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application and 
all copies of the appendix material must be sent to:

Martin Goldrosen,Ph.D. 
Director, Office of Scientific Review
National Center for Complementary and Alternative Medicine
6707 Democracy Blvd., Suite 401, MSC 5475
Bethesda, MD  20817-5475
Telephone:  (301)594-2014
FAX:  (301)480-2419
Email: (goldrosm@mail.nih.gov)

APPLICATION PROCESSING:  Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an 
application is received after that date, it will be returned to the 
applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within eight weeks.

The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

PEER REVIEW PROCESS  

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by NCCAM. Incomplete and non-responsive applications 
will be returned to the applicant without further consideration.  

Applications that are complete and responsive to the RFA will be 
evaluated for scientific and technical merit by an appropriate peer 
review group convened by NCCAM in accordance with the review criteria 
stated below. As part of the initial merit review, all applications 
will:

o  Undergo a process in which only those applications deemed to have 
the highest scientific merit, generally the top half of the 
applications under review, will be discussed and assigned a priority 
score
o  Receive a written critique
o  Receive a second level review by the NCCAM National Advisory Council 
and the National Advisory Environmental Health Sciences Council.

REVIEW CRITERIA

The following components of the BRC application will be evaluated:
A.  Individual Research Projects
B.  Cores
C.  Pilot Project Program 
D.  Principal Investigator
E.  Resources and Environment
F.  Program Synergy
G.  Overall Program

(A) Individual Research Projects

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health. 
In their written comments, reviewers will be asked to evaluate 
individual research projects. They will judge the likelihood that the 
proposed research will have a substantial impact on the pursuit of NIH 
goals. Each of the five following criteria will be addressed and 
considered by the reviewers in assigning an overall project score, 
weighting them as appropriate for each research project. The research 
project does not need to be strong in all categories to be judged likely 
to have a major scientific impact and thus deserve a high project score.  
For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 
forward. 

SIGNIFICANCE:  Does this study address an important problem? If the 
aims of the application are achieved, how will scientific knowledge be 
advanced? What will be the effect of these studies on the concepts or 
methods that drive this field? Is the research project consistent with 
the thematic focus of the BRC? For competitive renewals, completed and 
ongoing projects will be critically evaluated for their scientific 
progress and success in adhering to the original research goals.

APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the research project? Does the research project leader acknowledge 
potential problem areas and consider alternative tactics? Rationale for 
changing scientific direction and/or approach will also be evaluated 
for competitive renewals. 

INNOVATION:  Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 
technologies?

INVESTIGATOR:  Is the investigator appropriately trained and well 
suited to carry out this work? Is the work proposed appropriate to the 
experience level of the research project leader and other researchers 
(if any)? Is the research project leader, cognizant of the importance 
of characterization and quality assessment of botanical test materials?

ENVIRONMENT:  Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements? Is there 
evidence of institutional support?  

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, in 
accordance with NIH policy, all research components will also be 
reviewed with respect to the following: 

Inclusion:  The adequacy of plans to include both genders, minorities 
and their subgroups, and children as appropriate for the scientific 
goals of the research. Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria included in the 
section on Federal Citations, below).

Protections:  The adequacy of the proposed protection for humans, 
animals or the environment, to the extent they may be adversely affected 
by the project proposed in the application.

Data Sharing:  The adequacy of the proposed plan to share data.

Budget:  The reasonableness of the proposed budget and duration in 
relation to the proposed research.

Based on the evaluation described above, each project will receive a 
numerical project score from 1.0 to 5.0.

(B) Cores

In their written comments, reviewers will be asked to provide a 
qualitative assessment of individual cores using the following criteria:  

Research Resource Cores
o  Technical merit and justification of the proposed core; 
o  Adequacy of plans for use of the core by the research projects; 
o  Potential of the core to increase productivity of research projects 
contributing to synergy of the research effort as a whole

Administrative Core
o  Justification
o  Qualifications and experience of core personnel
o  Development of an organizational structure which will facilitate  
coordination, integration and evaluation of Center activities and 
progress; formation of and interaction with the two advisory groups 
(EAC,ISC); plans for development and evaluation of a pilot research 
program; oversight of training and career development efforts.

Based on the criteria described above, each core will receive a merit 
descriptor (i.e., outstanding, acceptable, unacceptable).

(C) Pilot Research Program

The evaluation of the pilot research program will be based primarily on 
the proposed plan to utilize BRC funds and resources to attract 
promising investigators to the center and provide them with an 
opportunity to generate preliminary data to submit new applications for 
peer-reviewed research. 

Each application will receive a merit descriptor for the Pilot Research 
Program (i.e., outstanding, acceptable, unacceptable) that reflects the 
following:

o  Adequacy of the proposed plan for establishing pilot research 
program.  
o  Adequacy of the proposed plan for continuously reviewing and funding 
a spectrum of pilot projects. 
o  For competitive renewals, past success in attracting promising new 
investigators and their success in generating preliminary data to submit 
new applications for peer-reviewed research.  

(D) Principal Investigator (Center Director)

The PI will be evaluated on the following criteria: 

o  Adequacy of leadership and scientific skills needed to develop and 
administer a complex program of integrated research projects and cores 
with a well-defined thematic focus; 
o  Time commitment: a minimum of 25 percent 

(E) Resources and Environment 

Each application will receive a merit descriptor for Resources and 
Environment (i.e., outstanding, acceptable, unacceptable) that reflects 
the following:

o  Institutional commitment to the program
o  Ability to build collaborative research teams to advance basic 
science to inform clinical studies
o  The potential for interdisciplinary research  
o  The intellectual resources available to BRC scientists, including the 
potential for intellectual exchange
o  Potential of the BRC to provide an outstanding training and research 
environment for future leaders in botanical dietary supplement research.
o  Adequacy of facilities and resources to support the research, 
including laboratory facilities, animal facilities, clinical facilities, 
and data management systems when needed

(F) Program Synergy

Each application will receive a merit descriptor (i.e., highly 
integrated, integrated, not integrated) that reflects the degree of 
synergy of the projects and cores within the proposed BRC. In 
particular, program synergy will be evaluated on:

o  The potential for scientific impact of the proposed BRC. The 
scientific contributions of a center should be greater than those of the 
sum of its component research projects and cores, i.e., the proposed 
components should interact to add value to the BRC as a whole.
o  Demonstration of a collaborative relationship among participating 
departments and institutions, including documentation of current 
relationships, as well as the functions, commitments and contributions 
that each collaborating entity will bring to the BRC.
o  the nature, scope, and effectiveness of the plans for communication, 
coordination, and collaboration among research project investigators.

(G) Overall Program

A single numerical priority score will be assigned to the BRC 
application as a whole. Although primary emphasis will be placed on 
scientific merit of the research projects, and past productivity (i.e., 
of competing renewals), significant consideration will also be given to 
the strength of cores, the pilot research program, leadership ability of 
the Center Director, institutional commitment, resources and 
environment, and program synergy.  In addition, reviewers will consider 
the potential for translating the proposed research into practical 
benefits for human health (e.g., safety and efficacy of dietary 
supplement ingredients) and the use of contemporary technologies. 

An application in which the reviewers consider no more than two 
component research projects to be of substantial and significant 
scientific merit will not satisfy the requirements for this P50 award, 
and therefore will be recommended for "no further consideration".

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK:  The involvement of 
human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
 
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH:  The adequacy 
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the 
sections on Federal Citations, below)

CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH:  If vertebrate animals 
are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.

ADDITIONAL REVIEW CONSIDERATIONS

Sharing Research Data:  Applicants requesting more than $500,000 in 
direct costs in any year of the proposed research must include a data 
sharing plan in their application. The reasonableness of the data 
sharing plan or the rationale for not sharing research data will be 
assessed by the reviewers. However, reviewers will not factor the 
proposed data sharing plan into the determination of scientific merit 
or priority score.

BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date: May 18, 2004
Application Receipt Date: June 15, 2004
Peer Review Date: October/November 2004
Council Review: January 2005 
Earliest Anticipated Start Date: April 2005

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o  Scientific merit (as determined by peer review)
o  Availability of funds
o  Programmatic priorities, which include building a Botanical Research 
Centers Program with a diversity of themes.
 
REQUIRED FEDERAL CITATIONS 

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm 

DATA AND SAFETY MONITORING PLAN:  Data and safety monitoring is 
required for all types of clinical trials, including physiologic, 
toxicity, and dose-finding studies (phase I); efficacy studies (phase 
II); efficacy, effectiveness and comparative trials (phase III).  The 
establishment of data and safety monitoring boards (DSMB) is required 
for multi-site clinical trials involving interventions that entail 
potential risk to the participants.  (NIH Policy for Data and Safety 
Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: 
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

SHARING RESEARCH DATA:  Starting with the October 1, 2003 receipt date, 
investigators submitting an NIH application seeking $500,000 or more in 
direct costs in any single year are expected to include a plan for data 
sharing or state why this is not possible. 
http://grants.nih.gov/grants/policy/data_sharing  Investigators should 
seek guidance from their institutions, on issues related to 
institutional policies, local IRB rules, as well as local, state and 
Federal laws and regulations, including the Privacy Rule. Reviewers 
will consider the data sharing plan but will not factor the plan into 
the determination of the scientific merit or the priority score.

INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH:  It is the 
policy of the NIH that women and members of minority groups and their 
sub-populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health of 
the subjects or the purpose of the research. This policy results from 
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a 
complete copy of the updated Guidelines are available at 
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.   
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 
differences.

INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN 
SUBJECTS: The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 
1998.

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at 
http://grants.nih.gov/grants/funding/children/children.htm

REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS:  
(if applicable) NIH policy requires education on the protection of 
human subject participants for all investigators submitting NIH 
proposals for research involving human subjects.  You will find this 
policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

HUMAN EMBRYONIC STEM CELLS (hESC):  Criteria for federal funding of 
research on hESCs can be found at http://stemcells.nih.gov/index.asp and 
at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see 
http://escr.nih.gov).   It is the responsibility of the applicant to 
provide, in the project description and elsewhere in the application as 
appropriate, the official NIH identifier(s) for the hESC line(s)to be 
used in the proposed research.  Applications that do not provide this 
information will be returned without review. 

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  
The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at 
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:  
The Department of Health and Human Services (DHHS) issued final 
modification to the “Standards for Privacy of Individually Identifiable 
Health Information”, the “Privacy Rule,” on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as “covered entities”) must do so by April 14, 2003 (with the exception 
of small health plans which have an extra year to comply).

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on “Am 
I a covered entity?”  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and 
proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, Internet 
addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the 
Internet sites.   Furthermore, we caution reviewers that their anonymity 
may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at 
http://www.healthypeople.gov/.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of 
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92. All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at http://grants.nih.gov/grants/policy/policy.htm. 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.


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NIH Funding Opportunities and Notices


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