and Human Services
9000 Rockville Pike
Bethesda, Maryland 20892
DIETARY SUPPLEMENT RESEARCH CENTERS: BOTANICALS RELEASE DATE: December 22, 2003 RFA Number: RFA-OD-04-002 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/NewPages/text-com.htm. 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.
Return to NIH Guide Main Index
|
|
Department of Health and Human Services |
|
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |