and Human Services (HHS)
EXPIRED
Department of Health and Human Services
Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov/)
Components of Participating Organizations
National Center for Complementary and Alternative Medicine (NCCAM), (http://nccam.nih.gov)
Office of Dietary Supplements (ODS), (http://dietary-supplements.info.nih.gov)
Title: Probiotics for Pediatric Illnesses
Announcement Type
Update: The following updates relating to this announcement have been issued:
Program Announcement (PA) Number: PA-05-035
Catalog of Federal Domestic Assistance Number(s)
93.213
Key Dates
Release Date: December 28, 2004
Application Receipt Dates(s): Standard dates apply, please see http://grants.nih.gov/grants funding/submissionschedule.htm for details.
Peer Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants funding/submissionschedule.htm for details.
Council Review Date(s): Standard dates apply, please see http://grants.nih.gov/grants funding/submissionschedule.htm for details.
Earliest Anticipated Start Date: Standard dates apply, please see http://grants.nih.gov/grants funding/submissionschedule.htm for details.
Additional Information To Be Available Date (Url Activation Date): Not applicable.
EXPIRATION DATE for R21 Non-AIDS Applications: March 2, 2006
EXPIRATION DATE for R21 AIDS and AIDS-Related Applications: May 2, 2006
EXPIRATION DATE for All R01 Applications: May 19, 2006
Due Dates for E.O. 12372
Not Applicable
Additional Overview Content
Executive Summary
The purpose of this PA is to provide support for pilot research on mechanism(s) of action, safety and efficacy of probiotics, as well as for more robust intervention studies for the prevention and treatment of pediatric illnesses for which more convincing preliminary data are available. 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. The total amount awarded and the number of awards will depend upon the mechanisms, numbers, quality, duration, and costs of the applications received. This funding opportunity will use the R01 and R21 award mechanisms. You may submit (an) application(s) if your organization has any of the following characteristics: for-profit or non-profit; public or private institutions; units of State and local governments; eligible agencies of the Federal government; foreign or domestic institutions; or faith-based or community-based organizations. 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. There is no limitation on the number of different applications an institution or individual may submit. The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html. Telecommunications for the hearing impaired is available at: TTY 301-451-5936.
Table of Contents
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement1. Research Objectives
The purpose of this PA is to provide support for pilot research on mechanism(s) of action, safety and efficacy of probiotics, as well as for more robust probiotic intervention studies for the prevention and treatment of pediatric illnesses for which more convincing preliminary data are available.
The NIH defines children as individuals under the age of 21. While the intent of this PA is to focus on conditions unique to or prevalent in children, studies of individuals aged 21 or over may be justified as a precursor to studies in children.
Probiotics are defined as microorganisms that when administered in sufficient quantities may improve health. Prebiotics (nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of bacterial species already established in the colon) and synbiotics (mixtures of pro- and prebiotics) are distinct from probiotics and not the focus of this PA. However, their inclusion in studies focused on probiotics is acceptable.
Background
Use and Efficacy:
Probiotics have traditionally been thought to be useful in the treatment of various gastrointestinal diseases. One of the primary areas of research in children has been in the treatment and prevention of diarrhea, e.g., antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, rota-viral diarrhea, and traveler's diarrhea). Some studies in adults show a reduction of symptoms associated with irritable bowel syndrome. Newer areas of research include systemic immune responses (including atopic eczema) that accompany food-related allergies in children. In addition, there is some evidence that probiotics enhance antibody response to vaccines, and decrease occurrence of respiratory and ear infections. Other potential indications for use in children include the treatment of inflammatory bowel disease, necrotizing enterocolitis, small bowel bacterial overgrowth, juvenile rheumatoid arthritis, and vaginitis, as well as the prevention of mother-baby transmission of HIV, recurrent urinary tract infections and tumors preceding the development of cancer.
Common side effects of oral antibiotics relate to the intestinal tract and include nausea, abdominal cramps, diarrhea, and loose stools. Published studies of children receiving probiotics concurrent with antibiotics report reduction of the intestinal side effects. The effects of probiotics in minimizing the nutritional and intestinal side effects of antibiotics used in treating or preventing infections, including ones associated with bioterrorism, are not known.
Safety:
Some microorganisms have a long history of use as probiotics without established risk to humans. Nevertheless, probiotics may theoretically be responsible for: (1) systemic infections; (2) deleterious metabolic activities; (3) excessive immune stimulation in susceptible individuals; or (4) gene transfer. Probiotic organisms may be inherently resistant to antibiotics, and the concern has been raised that probiotics might transfer drug-resistance genes to pathogenic microbes.
Administration:
Careful consideration should be given to the matrix in which probiotics are administered, whether one provides viable or inactivated organisms, and the dosage and schedule of administration, as these may impact critically on efficacy and/or safety. Probiotics can be administered orally as dietary supplements and in yogurt, fermented and unfermented milk, infant formula, bacterial lyophilizates, juices, and even candy. They may be applied topically and as suppositories. Probiotics in dietary supplements or foods may be live, heat treated, irradiated, spray dried, or freeze dried. Inactivated probiotics may be as effective as live probiotics in certain conditions and may be favorable because of lower risks (especially in infants whose gut defense barrier is immature). The best possible way to administer probiotics and the appropriate dose for each probiotic organism for its intended use are understudied. For example, some areas of controversy and lack of data include: (1) the impact of administration in different parts of the life-cycle or in infants vs. mothers late in pregnancy; (2) the impact of administration in food vs. as a dietary supplement; and 3) the effect of continuous (every day for a defined period of time) vs. pulsed (few days on, few days off, few days on, etc.) dosing.
Product Quality:
The quality of probiotics has received little attention. Quality issues for probiotic supplements can include the following: (1) the types of microorganism in the product; (2) the viability of microorganisms in the product; (3) stability of different strains under different storage conditions and in different product formats; and (4) enteric protection of the product. Viability of live organisms is an important factor, the importance of which may be different in different situations. In vitro test protocols can be readily adopted to examine the maintenance of a strain's ability to tolerate acidic conditions, survive and grow in the presence of bile, and metabolize selective substrates (e.g., carbohydrate and protein utilization patterns). Molecular techniques are also available to examine strain identity and stability.
Mechanisms of Action:
Human studies have been undertaken with probiotic strains without an understanding of mechanism of action related to the specific strain and the mode of administration. Different strains of probiotic bacteria may work by distinctly different mechanisms. In some cases, animal models exist to provide substantiation of in vitro effects and determination of probiotic mechanism.
Previous research into the mechanisms associated with probiotics focused on the bacteriology of the gut and concentrated on intestinal colonization and probiotic-induced suppression of pathogen growth and/or invasion. This may be accomplished by probiotic secretion or production of acids, hydrogen peroxide, antimicrobial substances, and/or bacteriocins (proteins elaborated by probiotic organisms that have specific antimicrobial effects against sensitive species) antagonistic to pathogen growth; competition for nutrients required for growth of pathogens; or competitive inhibition of adhesion of pathogens. In addition, some strains may coaggregate, persist and multiply forming normal, balanced flora. Whether colonization is critical for probiotics to have their effect remains unresolved.
More recent research has turned toward understanding the role of probiotics and their secreted products in enhancing and modulating innate and adaptive immune responses in the host by other mechanisms. They may interact with epithelial and immune cells and alter signal transduction pathways in the presence or absence of pathogenic bacteria and cytokines. Oral administration of probiotics has been shown to result in altered immunity at distant mucosal sites, including the female genital tract, the respiratory tract, the skin, and the nasal passages.
Gastrointestinal Bacteriology:
The precise qualitative and quantitative monitoring of enteric population changes has not been well addressed but seems to be a central requirement for the study of gut flora manipulation. Accurate methods for monitoring bacterial changes are absolutely essential. The simple absence or presence of probiotic strains in vivo is not sufficient to demonstrate their roles. Current genetic techniques and molecular methods may discriminate closely related bacteria and determine the constituents of complex microbiota.
A polyphasic strategy may be necessary to achieve an accurate interpretation of the gastrointestinal tract bacteriology and to understand the impact of probiotics. Approaches are needed to identify and monitor specific pathogenic or etiological agents, to study the effects of dietary intervention on bacterial populations, to demonstrate diversity, to quantify the population(s), to examine the complexity and dynamics of diverse microbiota, and to discriminate probiotic strains from commensal organisms. In addition, approaches are needed to address probiotic colonization and survival in the gastrointestinal tract after termination of exogenous supplementation.
Objectives of this PA
Research responsive to this PA may include, but is not limited to, the following objectives:
Phase I/II clinical studies to assess dose range effects, pharmacology, feasibility, safety, and biological efficacy of probiotic products to justify subsequent, more definitive trials of their safety and efficacy are acceptable. A Phase II study may be of modest size (about 40-160 participants), provided it explores a range of dosages or doses and is adequately powered to detect a meaningful difference between groups or validate surrogate markers of disease or clinical endpoints. For clinical trials, preference will be given to those that also test mechanistic hypotheses. Phase III studies will not be considered responsive to this PA.
See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.
Section II. Award Information1. Mechanism(s) of Support
This funding opportunity will use the R01and R21 award mechanisms. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. Applicants are encouraged to direct inquiries regarding the appropriate mechanisms to use to scientific and research staff listed in the Section VII.1. Scientific/Research Contacts.
The R21 awards are exploratory/developmental research grants for support of pilot and feasibility research designed to provide investigators with an opportunity to produce preliminary data in support of a larger project that may be submitted in the future as a research project (R01)grant application. Two NCCAM R21 funding mechanisms are available. The R21 for basic and preclinical research (http://nccam.nih.gov/research/instructions/r21/supplement.htm) allows a maximum duration of 2 years and maximum direct cost per year of $125,000. The clinical R21 (http://grants.nih.gov/grants/guide/pa-files/PAR-03-153.html) allows applicants to request a project period of up to three years with a combined budget for direct costs of up $400,000 for the three-year period. However, no more than $250,000 direct costs may be requested in any single year. Both the basic and preclinical R21 and the clinical R21 program announcements expire during the life of this program announcement. They expire July 2005 and July 2006, respectively. Applicants are advised to check the websites for the most current (or succeeding) NCCAM R21 announcements.
This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise follow the instructions for non-modular research grant applications.
2. Funds Available
The total amount awarded and the number of awards will depend upon the mechanisms, numbers, quality, duration, and costs of the applications received. This funding opportunity will use the R01 and R21 award mechanisms. The R21award mechanisms limit the amount of funds that can be requested.
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 funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.
Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-004.html.
Section III. Eligibility Information1. Eligible Applicants
1.A. Eligible Institutions
You may submit (an) application(s) if your organization has any of the following characteristics:
1.B. Eligible Individuals
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.
2. Cost Sharing or Matching
Cost sharing, matching, or cost participation is not required.
The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.
3. Other-Special Eligibility Criteria
Not applicable.
1. Address to Request Application Information
The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.
The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.
3. Submission Dates and Times
Applications must be mailed on or before the receipt date described below (Section IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Application Receipt Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Peer Review Date: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Council Review Date: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
Earliest Anticipated Start Date: Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm for details.
3.A.1. Letter of Intent
A letter of intent is not required for the funding opportunity.
3.B. Sending an Application to the NIH
Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and five 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
For R21 applications, which are reviewed by NCCAM, send two copies of the application to NCCAM. Send the original application plus three copies to Center for Scientific Review.
Martin Goldrosen, PhD
Office of Scientific Review
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-2014
FAX: (301) 480-2419
Email: [email protected]
3.C. Application Processing
Applications must be submitted on or before the application receipt dates described above (Section IV.3.A.) and at http://grants.nih.gov/grants/dates.htm. Upon receipt, applications will be evaluated for completeness by CSR.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such application must include an Introduction addressing the previous critique.
Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.
4. Intergovernmental Review
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).
Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.
The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.
6. Other Submission Requirements
Instructions for R21 applications differ from those (as described in the PHS 398 research grant application instructions) for R01 applications. Investigators intending to use the R21 funding mechanism are advised to consult the URL (http://nccam.nih.gov/research/instructions/r21/index.htm) for specific requirements and restrictions on appendices, as well as additional information. NCCAM supports two types of R21 funding mechanisms: (1) NCCAM Exploratory/Developmental Grant for Clinical studies (http://grants.nih.gov/grants/guide/pa-files/PAR-03-153.html) and (2) Basic and Preclinical Research on Complementary and Alternative Medicine (http://nccam.nih.gov/research/instructions/r21/supplement.htm). The application instructions differ between the two NCCAM R21 funding mechanisms. Both the basic and preclinical R21 and the clinical R21 program announcements expire during the life of this program announcement. They expire July 2005 and July 2006, respectively. Applicants are advised to check the websites for the most current (or succeeding) NCCAM R21 announcements.
The applicant is responsible for documenting in the application the quality of the probiotic product under investigation. This documentation may include: (1) Identification of the study agent using the scientific taxonomic nomenclature (e.g., genus, species, strain); (2) The name of the study agent supplier. If the supplier is a middle man, the provider of the source material to the supplier; (3) A letter from the supplier stating commitment to provide product and cooperate with the IND application process, if required; (4) Information on the formulation of the product (e.g., ingredients); (5) Information on enteric protection; (6) Information on the analysis of the product for contaminants, such as pesticide residues, heavy metals, toxic elements, mycotoxins, microorganisms, and adulterants; (7) The Certificate of Analysis from the supplier/manufacturer or other supporting manufacturer information; (8) Description of bioavailability, dissolution, disintegration and release if the information is appropriate and available; (9); Information on short- and long-term viability (of live microorganisms) or potency (inactivated microorganisms); (10) Information on the storage conditions appropriate for assuring viability or potency during the life of the study and how you plan to store the test agent; (11) If more than one batch will be used for the project, information on batch-to-batch reproducibility; (12) Plans to reserve and analyze product samples from all batches used during the course of the study. Plans should include how and when the samples are selected, how many samples, how the samples are stored, what analyses are conducted, the methods used, and how frequently and by whom the analyses are done. Plans should include tolerances for variability and what will be done if variability exceeds those limits.
Applicants are encouraged to address safety characteristics of the investigational products in their applications, as appropriate. For safety, probiotics may be characterized (for example) with: (1) a determination of antibiotic resistance patterns and transmission of genetic elements to other intestinal and/or food borne microorganisms; (2) an assessment for possibly deleterious metabolic activities; (3) an assessment of side effects during human studies; (4) a test for toxin production (if the strain belongs to a species known to be a mammalian toxin producer); (5) a determination of hemolytic activity (if the strain belongs to a species with known hemolytic potential).
Federal regulations attempt to achieve a balance of the protection of individual children with the importance of allowing research needed to improve pediatric medicine by empowering institutional review boards to approve pediatric research: http://www.hhs.gov/ohrp/irb/irb_chapter6.htm#g4. Investigators studying children are strongly encouraged to consult their local Institutional Review Board regarding ethical guidelines for pediatric research and how it applies the federal risk and benefit categories. Applicants are encouraged to address benefit and risk in their application.
Although Phase III studies will not be considered in response to this PA, modest-sized (about 40-160 participants) Phase II studies are allowed. Dose-ranging studies may be a component of or need to precede the Phase II studies. Applicants intending to conduct clinical trials should be aware of NCCAM's guidance on determining dose ranges: http://nccam.nih.gov/research/policies/guideonct.htm. Applicants are encouraged to provide justification for dose and dosage in their application.
NCCAM requires all clinical projects undergo review by the Office of Clinical and Regulatory Affairs (OCRA) for conformity with the NCCAM Terms of Awards for Clinical Trials: http://nccam.nih.gov/research/policies/terms-of-awards.htm. For additional points to consider when submitting a clinical study to NCCAM, the applicant is directed to: http://nccam.nih.gov/research/instructions/poc.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 Investigational New Drug (IND) applications should be addressed to the FDA. (For FDA contact, see Section VII. 1. Scientific/Research Contacts). 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.
Specific Instructions for Modular Grant applications
Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.
Specific Instructions for Applications Requesting $500,000 (direct costs) or More per Year.
Applicants requesting $500,000 or more in direct costs for any year must carry out the following steps:
1) Contact the IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study;
2) Obtain agreement from the IC staff that the IC will accept your application for consideration for award; and,
3) Include a cover letter with the application that identifies the staff member and IC who agreed to accept assignment of the application.
This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.
Plan for Sharing Research Data
The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.
Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).
The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.
Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.
The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.
Section V. Application Review Information1. Criteria
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications submitted for this funding opportunity will be assigned to the ICs on the basis of established PHS referral guidelines.
Appropriate scientific review groups convened in accordance with the standard NIH peer review procedures (http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific and technical merit.
As part of the initial merit review, all applications will:
The following will be considered in making funding decisions:
Additional considerations for award will include portfolio balance, diversity among institutions and individuals within institutions, product quality, and geographic diversity.
The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority 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.
1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
2. Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?
3. Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?
4. Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?
5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?
2.A. Additional Review Criteria:
In addition to the above criteria, the following items will continue to 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 the Research Plan, Section E on Human Subjects in the PHS Form 398).
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 will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).
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 Form 398 research grant application instructions will be assessed.
2.B. Additional Review Considerations
Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.
2.C. Sharing Research Data
Data Sharing Plan : The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing. Program staff will be responsible for the administrative review of the plan for sharing research data.
2.D. Sharing Research Resources
NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible. Program staff will be responsible for the administrative review of the plan for sharing research resources.
The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.
3. Anticipated Announcement and Award Dates
Not applicable.
Section VI. Award Administration Information1. Award Notices
After the peer review of the application is completed, the Principal Investigator will also receive a written critique called a Summary Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).
A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.
Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.
NCCAM will send or email the Principal Investigator notification of intent to grant award.
2. Administrative and National Policy Requirements
In addition to the Terms and Conditions listed below related to clinical research, applicants submitting clinical trial applications in response to this announcement should also follow the NCCAM Policy on Terms of Award for Clinical Trials: http://nccam.nih.gov/research/policies/terms-of-awards.htm.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.
2.A. Cooperative Agreement Terms and Conditions of Award
Not applicable.
Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.
Section VII. Agency ContactsWe encourage your inquiries concerning this funding opportunity 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:
1. Scientific/Research Contacts:
Marguerite Klein
Division of Extramural Research, Training and Review
National Center for Complementary and Alternative Medicine
National Institutes of Health
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 402-5860
FAX: (301) 480-3621
Email: [email protected]
Rebecca B. Costello, Ph.D., F.A.C.N.
Office of Dietary Supplements
National Institutes of Health
6100 Executive Blvd., Room 3B01, MSC 7517
Bethesda, Maryland 20892-7517
Telephone: (301) 435-2920
FAX: (301) 480-1845
Email: [email protected]
Direct questions about IND applications to the FDA:
Julienne Vaillancourt, MPH, R.Ph.
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Vaccines Research and Review
Division of Vaccines and Related Products Applications
Bacterial Vaccines Branch
Phone: 301-827-3070
Fax: 301-827-3532
E mail: [email protected]
2. Peer Review Contacts:
Not applicable for R01 applications. For R21 applications:
Martin Goldrosen, PhD
Office of Scientific Review
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-2014
FAX: (301) 480-2419
Email: [email protected]
3. Financial or Grants Management Contacts:
George Tucker, MBA
Grants Management Office
National Center for Complementary and Alternative Medicine
6707 Democracy Boulevard, Suite 401
Bethesda, MD 20892-5475
Telephone: (301) 594-8853
FAX: (301) 480-2419
Email: [email protected]
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
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). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
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 and 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.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.
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 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is 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 Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
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 (http://grants.nih.gov/grants/funding/children/children.htm).
Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available 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 (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).
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 PA 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.
Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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