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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 Cancer Institute (NCI) (http://www.nci.nih.gov)
National Heart, Lung and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov)
National Institute on Aging (NIA) (http://www.nia.nih.gov)
National Institute of Dental and Craniofacial Research (NIDCR) (http://www.nidcr.nih.gov)
National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) (http://www.niddk.nih.gov)
National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov)
National Institute of Environmental Health Sciences (NIEHS) (http://www.niehs.nih.gov)
National Institute of General Medical Sciences (NIGMS) (http://www.nigms.nih.gov)
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov)
National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov)

Title: Application of Metabolomics for Translational and Biological Research (R01)

Announcement Type:
New

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

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (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.

Program Announcement (PA) Number: PA-07-301

Catalog of Federal Domestic Assistance Number(s)
93.393, 93.394, 93.395, 93.396, 93.837, 93.839, 93.866, 93.279, 93.121, 93.847, 93.848 .

Key Dates
Release/Posted Date: January 17, 2007
Opening Date: January 17, 2007 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Not Applicable
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).
Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Additional Information To Be Available Date (URL Activation Date): Not Applicable.
Expiration Date: January 3, 2010 (now January 8, 2010 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. Submitting an Application Electronically 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 Contacts
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

Purpose

The purpose of this Funding Opportunity Announcement (FOA), sponsored by multiple NIH Institutes/Centers (ICs), is to promote the use of metabolomic technologies in translational research in human health and disease for the purposes of enabling and improving disease detection, diagnosis, risk assessment, prognosis, and prediction of therapeutic responses. In addition to this overall goal, specific scopes and objectives of the participating ICs are presented below. Using the NIH Research Project Grant (R01) funding mechanism, this FOA focuses on well developed projects supported by preliminary data.

Related Funding Opportunity: Investigators proposing early phase, pilot/exploratory projects should submit applications in response to the partner FOA of identical scientific scope (PA-07-302), which uses the R21 grant mechanism.

Background

Metabolomics deals with a global analysis of small molecule metabolites and metabolic patterns. Metabonomics, another term used in relation to metabolic profiling, refers specifically to metabolic measurements in organisms in response to external stimuli or genetic modifications. In the post genomic era, metabolomics has emerged as a field of great significance for both translational and basic biological research. Unlike approaches in which biomolecules/metabolites are selected and analyzed one (or few) at a time, metabolomics focuses on broad identification and analysis of multiple metabolites simultaneously. The state of the metabolome cumulatively reflects the states of gene expression, protein expression, and the cellular environment as well as multidirectional interactions among these elements. The metabolomic information can provide important insights into physiological and disease states and facilitate in depth understanding of underlying biochemical pathways. Metabolomics has the potential to provide valuable information on various patho-physiological conditions such as cancer, Alzheimer’s and cardiovascular diseases.

Recent technological advances in NMR spectroscopy, mass spectrometry, and separation techniques enable direct evaluation of multiple metabolic components and analyses of metabolic fluxes. Metabolomic information is complementary, yet distinct, from that generated by genomic and proteomic approaches. Metabolomic information enables a deeper understanding of biological processes, in particular by facilitating information integration into a larger context of systems biology. Metabolomic analyses allow for comprehensive monitoring of functional and physiological changes associated with environmental factors such as diet and drugs that influence disease process. Thus, applications of metabolomics may be useful for such aspects as; (1) diagnosis; (2) assessing the progress of therapeutic interventions; (3) detecting sub-clinical toxic effects of novel therapies; and (4) evaluating the metabolic changes involved in disease processes. While the field of metabolomics holds great promise for translational and biological research, metabolomic technologies are just beginning to mature into a stage conductive for the development of reliable translational applications.

Metabolomics research has been supported by several trans-NIH funding opportunities under the NIH Roadmap Initiative (http://nihroadmap.nih.gov/). These efforts have resulted in significant progress in technology and resource development and have established a collaborative platform for the advancement of the study of metabolomics. Despite these advances, the potential of metabolomics is only beginning to be fully realized. For example, it remains to be established whether the metabolic changes that distinguish normal from malignant tissue are reflected (and measurable) in easily obtainable bodily fluids such as blood, plasma, saliva, urine, and stool. It is also important to characterize the metabolome (and various specific biochemical pathways) of tissue subtypes, including disease-related metabolome changes. If metabolomic approaches are adapted and implemented in the clinic, such information may, for example, offer a basis for novel diagnostic and therapeutic strategies, and/or enable improvements in the existing strategies.

Various factors, such as patient heterogeneity, environmental agents, diet, toxic exposures, and drugs, may influence the state of the metabolome on a transient or permanent basis. Metabolomic investigations must take into account all these influences. There is also a need for improved analytical methods to process and interpret the vast amounts of data generated by high throughput metabolomics platforms in the context of pathological conditions (e.g., cancer or Alzheimer’s disease). Further efforts in these directions are necessary to promote the application of metabolomic technologies in the study of patho-physiological conditions as well as for the purpose of the diagnosis, prognosis, and treatment monitoring.

Overarching Research Goals

The ultimate goal of this FOA is to generate a comprehensive understanding of how metabolic signatures are affected in various patho-physiological conditions and employ such knowledge to translational research.

To address this goal, research projects prompted by this FOA are expected to advance such areas as:

  1. Identification and quantification of cellular metabolites and their fluxes at high anatomical, spatial and temporal resolution and characterization of these metabolic profiles in biological fluids and tissues in various patho-physiological conditions;
  2. Development of mathematical models and algorithms to facilitate the application of metabolomic information for translational research;
  3. Development of approaches to the integration of metabolomic information in the context of systems biology in health and disease; and
  4. Application of metabolomic information to clinical context (e.g., metabolomic biomarkers in disease detection, diagnosis, prognosis, and prediction) of therapeutic responses of the various human diseases and conditions of interest specified in this funding opportunity.

Scope of Interest of the Sponsoring NIH Institutes

Scientific interests of each of the sponsoring NIH Institutes in the context of this FOA are described as follows.

1) National Cancer Institute: The carcinogenic process involves many cellular changes including alterations in metabolic profiles. However, the ability of cancer biologists to understand the roles of metabolites in the development and treatment of cancer is limited by a lack of detailed information about the metabolome. The NCI is interested in characterizing the tumor cell metabolome and determining how it differs from the normal cell metabolome. Application of this knowledge holds promise for cancer detection and diagnosis and may improve therapeutic strategies. The NCI is also interested in determining whether tissue metabolic profiles are reflected in body fluids to enable robust and inexpensive means for cancer detection and monitoring responses to therapy. Note: Head and neck cancers, including oral and pharyngeal cancers, may also be within the scope of interest of the National Institute of Dental and Craniofacial Research, and brain tumors may also be within the scope of interest of the National Institute of Neurological Disorders and Stroke (see below).

2) National Heart, Lung and Blood Institute: The NHLBI is interested in applying innovative metabolomic technologies and methods to study the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep disorders. Examples of research include global approaches to identify and characterize metabolites that could serve as new tools to monitor the state of health or disease and to understand the underlying mechanisms of disease processes. The NHLBI is particularly interested in tools that allow earlier detection of disease and a more precise monitoring of disease during its progression with and without treatment.

3) National Institute on Aging: NIA is interested in applying metabolomic technologies to the quantitative analysis and potential treatment of aging and age-related diseases. The Institute is interested in systems biology approaches to determine global and specific changes in the metabolome due to aging in humans, which would include the metabolomic analysis of serum, lymph, spinal fluid, and urine, as well as the metabolomes of organs, tissues, and cells. The NIA is interested in identifying changes in these metabolomes during natural aging, under caloric restriction, or as a result of age-related diseases such as Alzheimer’s disease, sarcopenia, cardiovascular diseases, and kidney failure. It is expected that these efforts will lead to mathematical models that will be useful for monitoring the progression of age-related metabolic disorders and predicting chances for successful treatment. The NIA is also interested in applications of metabolic profiling to assess stress, allostatic load, and sense of wellbeing in humans, as well as the effects of prescription and over-the-counter drug use in population studies.

Of particular interest is the development of metabolomic technologies that would address how the metabolic complement of the brain changes during normal aging and during pathological brain aging characteristic of Alzheimer’s dementia. The NIA is interested in exploring the usefulness of different metabolomic platforms towards the identification of systemic metabolic profiles characteristic of age-related cognitive decline, mild cognitive impairment, and different stages of Alzheimer’s dementia. These efforts may aid the identification of early diagnostic markers for Alzheimer’s disease and reliable biochemical measures of disease progression during clinical trials for the prevention and treatment of Alzheimer disease.

4) National Institute of Dental and Craniofacial Research: The NIDCR is interested in applying metabolomic technology to a number of oral and craniofacial diseases and disorders. Of particular interest are investigations on an inventory of the salivary metabolome as it relates to affecting and predicting oral and craniofacial health status. Metabolomic technology can be applied to the study of the following disease areas: (1) head and neck cancers, including oral and pharyngeal cancers; (2) host response to oral infection, inflammation, head and neck tumors or chronic autoimmune and complex disorders such as Sjogren s syndrome; (3) chronic orofacial pain conditions including temporomandibular joint and muscle disorders. The NIDCR will also welcome research proposals that are designed to apply metabolomic approaches to examine the effects of drugs used in the treatment of oral and craniofacial diseases. Examples include the use of pilocarpine for xerostomia and drugs that present oral complications such as bisphosphonates-associated osteonecrosis of the jaw. It is anticipated that application of metabolomics technologies to oral and craniofacial disorders will aid diagnosis and predicting the onset and risk for developing conditions that compromise the oral and craniofacial health status.

5) National Institute of Diabetes and Digestive and Kidney Disease: The NIDDK is interested in applying metabolomic technologies to the study of metabolism in diabetes, and diabetes-related complications and other metabolic disorders, insulin resistance, energy balance, kidney and urologic diseases, hematologic diseases, digestive diseases, liver diseases and nutrition. The scope of interest includes the following areas: (1) whole body metabolomic analyses and cellular intermediate metabolism, e.g., the regulation of gluconeogenesis and glucose disposal, protein turnover rate and regulation, cellular and whole body lipid fluxes, interaction between carbohydrate and lipid metabolism, rate of tricarboxylic acid cycle flux and energy production in the cell, and the effect of nutrient co-factors on the regulation of these processes; (2) identification and characterization of metabolic phenotypes of rare metabolic diseases and identifying more common metabolic factors relating to predisposition to obesity and insulin resistance and metabolic alterations in diabetes and its complications that may improve treatment strategies; (3) global metabolomic studies of ion movement and fluid electrolyte dynamics as they relate to kidney function; (4) energy balance and nutrition, including the understanding of normal and abnormal absorption, digestion and excretion of macro- and micro-nutrients, their physiologic function, and mechanism of action/interaction within the body, nutrient influence on gene regulation; endocrine functions relating to feeding behavior; the role of nutrient antioxidants, and the general improvement in assessing complex nutritional status in health and disease.

6) National Institute on Drug Abuse: The NIDA is interested in promoting research applying metabolomic technologies to enhance the understanding of the mechanisms of drug addiction, and discovery of biomarkers for potential drug development by studying the biological pathways and network regulation both in normal and addictive states. Once administered, drugs interact with cells and tissues and disturb the ratios, concentrations, and fluxes of endogenous biochemicals in key intermediary cellular metabolic pathways and manifest their effects. Interaction of recreational drugs with cellular metabolic pathways in the central nervous system may alter the normal metabolic pathways of various neuro-chemicals, and/or produce substance(s) that may result in addiction of recreational drugs. Thus, metabolic profiling of individuals under the influence of drugs of abuse may provide biomarkers for understanding the mechanisms of drug addiction and subsequently a novel target for therapeutic drug development.

7) National institute of Environmental health Sciences: The NIEHS mission is to prevent disease and improve human health by using environmental sciences to understand human biology and disease. The NIEHS promotes the application of global technologies, including metabolomics, to understanding the mechanisms by which environmental factors influence disease course and in translating these findings from basic, mechanistic research into improved public health and clinical practices. In the context of this FOA, the NIEHS is interested in applications that use metabolomic approaches within the following broadly defined areas: (1) identifying the mechanisms of environmentally influenced diseases, (2) probing the pathways of responses to exposures and how these pathways affect individual susceptibility to exposures, and (3) identifying and validating biomarkers of biological responses to exposure including compensatory responses and early indicators of disease. It is expected that, ultimately, these studies will improve the understanding of disease etiology and prognosis and will improve diagnosis and treatment on an individual level.

8) National Institute of General Medical Sciences: The NIGMS is interested in promoting research projects that discover, develop, utilize, and/or apply metabolomic techniques in the study of drug action as well as in the study of the pathophysiology of injury, burns, and wounds. Of particular interest would be research projects proposing metabolomic approaches to the following areas; (1) drug absorption, metabolism, distribution, transport, and excretion; (2) mechanisms of drug toxicity and predictive drug toxicology; and (3) determining phenotypes more precisely for pharmacogenomic studies. The NIGMS is also interested in fostering research on predicting sequelae to trauma and burn injury and on wound healing. Other areas of interest include metabolomic analyses of the components and regulation of primary and secondary metabolism, including studies that would emphasize biotechnology and metabolic engineering.

9) National Institute of Mental Health: The NIMH is interested in applying metabolomic technologies to the study of brain function in health and in neuro-psychiatric illness. Changes in brain metabolic pathways may lead to alterations in brain function that result in abnormal behavior and psychopathology. Innovative approaches in metabolomics can be used to identify and characterize metabolic changes that occur during healthy brain development and psychiatric disease progression, as well as to discover biomarkers of psychiatric disease states, treatment responses, and medication side effects. Understanding the metabolic profiles underlying psychiatric illnesses may also provide novel therapeutic targets for treatment development. Studies to determine whether brain metabolic profiles are reliably reflected in cerebrospinal fluid (CSF) and other body fluids are also of interest. Note: Brain metabolic patterns may also be within the scope of interest of the National Institute of Neurological Disorders and Stroke (see below).

10) National Institute of Neurological Disorders and Stroke: The NINDS is interested in the development and application of metabolomic technologies for detecting and characterizing the metabolic changes and profiles of normal brain function, in neurological disease, and in traumatic brain or spinal cord injuries. In addition, the NINDS is interested in the classification of patients with progressive neurological diseases into clinically relevant groups on the basis of their metabolite profiles. Of particular interest to the institute is the ability to functionalize the genotype through correlation of the genes, genetic variations; and gene/protein expression profiles with the metabolic phenotypes in these neurological conditions and in responses to insults or treatments. Studies exploring the significance of these profiles in the areas of translational research, early detection, diagnoses, prediction of clinical outcome, and development/improvement of novel therapeutic strategies are particularly encouraged.

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 Announcement (FOA) will use the NIH Research Project Grant (R01) award mechanism.

The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses Just-in-Time information 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 a U.S. organization and 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).

U.S. applicants requesting more than $250,000 in annual direct costs and all foreign applicants must complete and submit budget requests using the Research & Related (R&R) Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

2. Funds 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. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

F&A costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your institution/organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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.

Section IV. Application and Submission Information

To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/applicants/apply_for_grants.jsp 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 Registered

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.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

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 four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/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 the 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: 301-710-0267, Email: [email protected].

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 for this FOA through Grants.gov/Apply.

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 Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in 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 or Research & Related Budget, as appropriate (See Section IV.6., Special Instructions, regarding appropriate required budget component.)
Research & Related Budget (required for foreign applications)

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

Foreign Organizations (Non-Domestic [non-U.S.] Entity)

NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in Item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of PD/PI. Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the Credential field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled Multiple PD/PI Leadership Plan (Section 14 of the Research Plan Component in the SF424 (R&R) or Section I of the Research Plan in the PHS 398), must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are note required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: January 17, 2007 (Earliest date that an application may be submitted to Grants.gov)
Application Submission/Receipt Date(s): Standard dates apply, please see http://grants.nih.gov/grants/funding/submissionschedule.htm
Peer Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

A letter of intent is not required for this funding opportunity.

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp 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.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

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. The submitting AOR receives the Grants.gov acknowledgments. The AOR and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status 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.

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 renewal (formerly 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 renewal 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 the NIH Grants Policy Statement.

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI(s) to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

PHS398 Research Plan Component Sections

Items 2-5 of the PHS398 Research Plan component are limited to 25 pages. While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

Special Instructions for Modular Grant applications

R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs (excluding consortium F&A costs) must be submitted in a modular budget format. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm. When submitting a modular budget, the applicant organization will include only the PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further instructions regarding the use of the PHS398 Modular Budget component.

Foreign organizations may not submit modular budgets. See NOT-OD-06-096.

Special Instructions for Applications Requesting $500,000 (direct costs) or More Per Year

Applicants requesting $500,000 or more in direct costs for any year (excluding consortium F&A costs) 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 the PHS398 Cover Letter component with the application to identify the staff member and IC who agreed to accept assignment of the application.

This policy applies to all new applications, competing renewal (formerly competing continuation ) applications, resubmission (formerly revised/amended ) applications, and revision (formerly competing supplemental ) applications. See NOT-OD-02-004, October 16, 2001.

APPENDIX MATERIALS

Stop SignIMPORTANT NOTE: NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (see http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

Foreign Applications (Non-Domestic [non-U.S.] Entity)

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 Web site, 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 expects that grant 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/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). 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.

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 (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

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:

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

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? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs?

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 or methodologies, tools, or technologies for this area?

Investigators: Are the PD/PIs and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level(s) of the principal investigator(s) and other researchers? Do the PD/PIs and investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment: Do(es) the scientific environment(s) 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(s), 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:

Resubmission Applications (formerly revised/amended applications): Are the responses to comments from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate?

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 Human Subjects Sections of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects of 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 Human Subjects Sections of the PHS398 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 adequacy of the plans for their care and use will be assessed. See the Other Research Plan Sections of the PHS398 Research Plan component of the SF424 (R&R).

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. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

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).

2.D. Sharing Research Resources

NIH policy expects that grant 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/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). 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 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.

Model Organism Sharing Plan: Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations.

3. Anticipated Announcement and Award Dates

Not Applicable

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.

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 Section IV.5., Funding Restrictions.

2. Administrative and National Policy Requirements

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Grant Progress Report (PHS 2590) annually 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 Contact(s):

NCI contacts:

Padma Maruvada, Ph.D.
Cancer Biomarkers Research Group
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Suite 3144, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service regular or express mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-3893
Fax: (301) 402-8990
E-mail: [email protected]

Sudhir Srivastava, Ph.D., M.P.H.
Division of Cancer Prevention
National Cancer Institute
Executive Plaza North, EPN 3142, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-3983
Fax: (301) 402-8990
E-mail: [email protected]

John R Knowlton, Ph.D.
Division of Cancer Biology
National Cancer Institute
6130 Executive Boulevard, EPN Suite 5000, MSC 7385
Bethesda, MD 20892-7385 (for U.S. Postal Service regular or express mail)
Rockville, MD 20892 (for express/courier delivery)
Telephone: (301) 435-5226
Fax: (301) 480-2854
Email : [email protected]

NHLBI contact:

Deborah Applebaum-Bowden, Ph.D.
NHLBI/DCVD/AT&S
6701 Rockledge Drive, RKL2 Room 10190, MSC 7956
Bethesda, MD 20892-7956 (for U.S. Postal Service regular or express mail)
Bethesda, MD 20817 (for express/courier delivery)
Telephone: (301) 435-0513
Fax: (301) 480-2858
Email: [email protected]

NIA Contact:

Suzana Petanceska, Ph.D.
NNA/NIA
7201 Wisconsin Ave, GWY Room 350, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-9350
Email: [email protected]

NIDCR Contact:

Yasaman Shirazi, Ph.D.
CIBID/ NIDCR
45 Center Drive, 45/4AN18C
Bethesda, MD 20892-6402
Telephone: (301) 59404812 FAX: (301) 480-8318
[email protected]

NIDA Contact:

Hari Singh
DNBR/ NIDA
6001 Executive Boulevard, NSC/4261
Rockville, MD 20892-9555
Telephone: (301) 435-1310
Fax: (301) 594-6043
Email:[email protected]

NIEHS Contact

David M. Balshaw, Ph.D.
Center for Risk and Integrated Sciences
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
PO Box 12233, EC-27
79 T.W. Alexander Drive
Research Triangle Park, NC 27709
(919) 541-2448
FAX: (919) 541-4937
Email: [email protected]

NIDDK Contact:

Arthur Castle, Ph.D
DDEM
National Institute of Diabetis, Digestive and Kidney Diseases
6707 Democracy Blvd, Room 2DEM/791, MSC 5460
Bethesda, MD 20892-5460
Voice: (301) 594-7719
FAX: 301-480-0475
E-mail: [email protected]

NIGMS contact:

Michael Rogers, Ph.D
Division of Pharmacology, Physiology, and Biological Chemistry
National Institue of General Medical Sciences
45 Center Dr, Room 45/2AS49H, MSC 6200
Bethesda, MD 20892-6200
Voice: (301) 594-3827
Fax: (301) 480-2802
E-mail: [email protected]

NIMH Contact:

Laurie Nadler, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Blvd, Room 7200, MSC 9645
Bethesda, MD 20892-9645
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 443-3563
Fax: (301) 443-1731
E-mail: [email protected]

NINDS Contact:

Danilo Tagle, Ph.D
Division of Neurogenetics
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Room NSC/2133, MSC 9525
Bethesda, MD 20892-9525
Rockville, MD 20852 (for express/courier delivery)
Voice: (301) 496-5745
Fax: (301) 402-1501
E-mail: [email protected]

2. Peer Review Contact(s):

Not Applicable.

3. Financial/Grants Management Contact(s):

Lan Hoang
Grants Management Specialist
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-9048
Fax: (301) 496-8601
E-Mail: [email protected]

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 (45 CFR 46) 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); and 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 institutional review board (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.

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. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal 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) application; 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.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) 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 HHS 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. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

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 FOA 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 Part 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 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 2 years to the research. For further information, please see http://www.lrp.nih.gov/.

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