Part I Overview Information


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 (R21)

Announcement Type
This is a reissue of PA-05-035 which was previously released December 28, 2004.

Update: The following update relating to this announcement has been issued:

NOTICE: Applications submitted in response to this FOA for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least 4 weeks prior to the grant submission date. See Section IV.

Two steps are required for on time submission:

1) The application must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the submission date (see “Key Dates” below).

2) Applicants must complete a verification step in the eRA Commons within 2 business days of notification from NIH. Note: Since e-mail can be unreliable, it is the responsibility of the applicant to periodically check on their application status in the Commons.

Program Announcement (PA) Number: PA-06-316

Catalog of Federal Domestic Assistance Number(s)
93.213

Key Dates
Release/Posted Date: April 5, 2006
Opening Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov).
Application Submission Date(s): See http://grants.nih.gov/grants funding/submissionschedule.htm
Peer Review Date(s): See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s):See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward  
Earliest Anticipated Start Date(s):See http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward   
Additional Information To Be Available Date (Url Activation Date): Not applicable
Expiration Date:  November 2, 2007 (now January 8, 2008 per NOT-OD-07-093)

Due Dates for E.O. 12372
Not applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism 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. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, 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
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 Announcement


Section I. Funding Opportunity Description


1. Research Objectives

The purpose of this Funding Opportunity Announcement (FOA) 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 FOA 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 FOA. 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 FOA

Research responsive to this FOA may include, but is not limited to, the following objectives:

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This funding opportunity will use the NCCAM R21 (Exploratory/Developmental Project) award mechanisms.  

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 (http://nccam.nih.gov/research/instructions/r21/index.htm) are available:  (1) Basic and Preclinical Research on Complementary and Alternative Medicine and (2) NCCAM Exploratory/Developmental Grant for Clinical Studies.  Applicants are advised to check the website for the most current (or succeeding) NCCAM R21 announcements and to abide by the application guidance and allowable project period length and direct cost limits.

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.

This FOA uses just-in-time concepts. It also uses the modular budget formats (see the “Modular Applications and Awards” section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide).

2. Funds Available

The total amount awarded and the number of awards will depend upon the numbers, quality, duration, and costs of the applications received. This funding opportunity will use the NCCAM R21 award mechanisms. The NCCAM R21 award 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 (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, which was published in the NIH Guide.

Section III. Eligibility Information


1. 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 support.

2. Cost Sharing or Matching

Not applicable. This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

Applicants may submit more than one application, provided each application is scientifically distinct.  However, NCCAM R21 grants may not be renewed.  Competing continuation of projected developed under this grant mechanism should be submitted through the R01 grant mechanism.

Section IV. Application and Submission Information


Registration and Instructions for Submission via Grants.gov


To download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started.

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take 4 weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.


For further assistance, contact GrantsInfo; Telephone: 301-435-0714, E-mail: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R &R) application forms and in accordance with the SF424 (R&R) Application Guide (MS Word or PDF).

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Tips and Tools for Navigating Electronic Submission” on the front page of “Electronic Submission of Grant Applications.”

The SF424 (R &R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information

Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget

Optional Components:
PHS398 Cover Letter File
R&R Subaward Budget Attachment(s) Form

Note: While both budget components are included in the SF424 (R&R) forms package, the NIH R21 uses ONLY the PHS 398 Modular Budget. (Do not use the detailed Research & Related Budget.)

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Proposed research should provide a unique research opportunity not available in the U.S.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review and Anticipated Start Dates
Opening Date: May 2, 2006 (earliest date an application may be submitted to Grants.gov).
Letter of Intent Receipt Date:
Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Council Review Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
Earliest Anticipated Start Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm

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

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically
PAPER APPLICATIONS WILL NOT BE ACCEPTED.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A.  for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Upon receipt, applications will be transferred from Grants.gov to the NIH Electronic Research Administration process for validation. Both the PD/PI and the SO for the organization must verify the submission via Commons within 2 business days of notification of the NIH validation.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit 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 an application already reviewed with substantial changes, but such application must include an “Introduction” addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 the NIH Grants Policy Statement.

6. Other Submission Requirements

Investigators 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 (http://nccam.nih.gov/research/instructions/r21/index.htm): (1) NCCAM Exploratory/Developmental Grant for Clinical Studies and (2) Basic and Preclinical Research on Complementary and Alternative Medicine. The application instructions differ between the two NCCAM R21 funding mechanisms. Applicants are advised to check the website for the most current (or succeeding) NCCAM R21 announcements.

The applicant must follow the NCCAM Interim Applicant Guidance:  Product Quality:  Biologically Active Agents Used in Complementary and Alternative Medicine and Placebo Materials:  http://grants.nih.gov/grants/guide/notice-files/NOT-AT-05-004.html.  Instructions are provided on the type of information that should be included in the application, as well as the type of information that NCCAM may request after review but before grant award.

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 FOA, 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 direct costs in each year of $250,000 or less (excluding consortium F&A costs), must be submitted in a modular budget format using the Modular Budget Component provided in the SF424 (R&R) Application Package and Instructions Guide (see specifically Section 5.4). 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.

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 (see the NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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). See Section VI.3., “Reporting.”

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete will be evaluated for scientific and technical merit by an appropriate review group convened by NCCAM in accordance with the review criteria stated below.

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.

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?

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?

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?

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)?

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 item 6 of the Research Plan component of the SF424 (R&R).

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 item 7 of the Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. Is the effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

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. NCCAM does not require a data sharing plan for applications requesting less than $500,000.

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 at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.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.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

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), See Section VI.3., “Reporting.”


3. Anticipated Announcement and Award Dates
Standard review and start dates apply.  

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons.

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/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA 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.

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 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/archive/grants/policy/nihgps_2003/index.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/archive/grants/policy/nihgps_2003/index.htm).

3. Reporting

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 Contacts


We 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: kleinm@mail.nih.gov

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: CostellB@od.nih.gov

Direct questions about IND applications to the FDA:

Jennifer Ross,  PhD
Food and Drug Administration
Center for Biologics Evaluation and Research
Office of Vaccines Research and Review
Division of Vaccines and Related Products Applications
Phone: 301-827-3070
Fax: 301-827-3532
E mail: Jennifer.Ross@fda.gov

2. Peer Review Contacts:

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: mg85x@nih.gov

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: gt35v@nih.gov

Section VIII. Other Information


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 scientific merit or the priority score.

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 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 funding opportunity 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.

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/archive/archive/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 SF424 (R&R); 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.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://PublicAccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_manual.htm).

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.health.gov/healthypeople.

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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