Expired PA-06-398: Novel Technologies For In Vivo Imaging (R21/R33)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

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)

Title: Novel Technologies For In Vivo Imaging (R21/R33)

Announcement Type
This is a reissue of PA-04-095, which was previously released May 5, 2004, and is now divided into separate FOAs for R21/R33 and R33 funding mechanisms.

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.

Program Announcement (PA) Number: PA-06-398

Catalog of Federal Domestic Assistance Number(s)
93.394

Key Dates
Release/Posted Date: May 9, 2006
Opening Date: May 9, 2006 (earliest date an application may be submitted to Grants.gov).
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of applicant institution/organization).
Letters of Intent Receipt Date(s): Not applicable.
Application Submission Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
AIDS Application Receipt Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS.
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Council Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward.
Additional Information To Be Available Date (URL Activation Date): Not applicable.
Expiration Date: November 2, 2006 (unless reissued).

Due Dates for E.O. 12372
Not Applicable.

Additional Overview Content

Executive Summary

Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) solicits Phased Innovation (R21/R33) grant applications from applicant organizations that propose the development and delivery of novel image acquisition or enhancement technologies and methods for biomedical imaging and image-guided interventions and therapy, and which may incorporate limited pilot or clinical feasibility evaluations using either pre-clinical models or clinical studies. This FOA is primarily intended to facilitate the proof-of-feasibility, development, and delivery of novel imaging technologies for early detection, screening, diagnosis, image-guided interventions, and treatment of various diseases, and, secondarily, to facilitate limited evaluation studies to show proof-of-concept and functionality.

Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.
The anticipated number of awards is not known.
This FOA will utilize the NIH Phased Innovation (R21 [Phase I]/R33 [Phase II]) grant mechanism and runs in parallel with a FOA of identical scientific scope, PA-06-399, that solicits applications using the R33 grant mechanism. The Phased Innovation (R21/R33) mechanism provides support for a first phase (R21) for technical development and proof-of-principle, and a second phase (R33) for technology application and evaluation of clinical utility. The first phase should produce data to demonstrate the feasibility of the technology or technologies proposed for the second phase, and the second phase should be designed to test whether application of the strategy will provide clinical benefit to a defined set of cancer patients.
For combined R21/R33 applications, the applicant may request an R21 budget period of up to 2 years, with a combined budget guideline for direct costs of up to $275,000 for the maximum 2-year period of the Phase I study. The amount of funds requested and their distribution between the years of the Phase I study should be tailored to the needs of the project, with no more than $200,000 in direct costs allowed in any single year. Although the R33 application has no official budgetary limit, applications requesting $500,000 or more in direct costs in any single year of the grant period require prior approval from the NIH 6 weeks before submission. The total project period for an R21/R33 application submitted in response to this FOA may not exceed 4 years and the R21 phase may not exceed 2 years.
Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.
Eligible organizations: For-profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals and laboratories; units of State governments; units of local governments; eligible institutions of the Federal government; domestic institutions; foreign institutions; faith-based or community-based organizations; Indian/Native American Tribal Governments (Federally Recognized); Indian/Native American Tribal Governments (Other than Federally Recognized); and Indian/Native American Tribally Designated Organizations.
Eligible Project Directors/Principal Investigators (PDs/PIs): Any individual with the skills, knowledge, and resources necessary to carry out the proposed research; any eligible PD/PI is invited to work with his/her 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.
Applicants may submit more than one application, provided each application is scientifically distinct.
See Section IV.1 for application materials. The SF424 (R&R) Application Guide for this FOA is located at these web sites:
- http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General.doc (MS Word); and
- http://grants1.nih.gov/grants/funding/424/SF424_RR_Guide_General.pdf (PDF).
For general information on SF424 (R&R) Application and Electronic Submission, see the following web sites:

SF424 (R&R) Application and Electronic Submission Information at http://grants.nih.gov/grants/funding/424/index.htm; and
General information on Electronic Submission of Grant Applications at http://era.nih.gov/ElectronicReceipt/.

For the R21/R33 Phased Innovation Award application, the initial review group will evaluate the specific goals for each phase and the feasibility milestones that would justify expansion to the R33 phase. A single priority score will be assigned to each scored application.
Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

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

Background

The National Cancer Institute (NCI) invites applications for the development and delivery of novel image acquisition or enhancement technologies and methods for biomedical imaging and image-guided interventions and therapy, and which may incorporate limited pilot or clinical feasibility evaluations using either pre-clinical models or clinical studies. This FOA is primarily intended to facilitate the proof-of-feasibility, development, and delivery of novel imaging technologies for early detection, screening, diagnosis, image-guided interventions, and treatment of various diseases, and, secondarily, to facilitate limited evaluation studies to show proof-of-concept and functionality.

The interests of NCI focus on imaging in vivo for cancer pre-conditions, cancer screening, diagnosis, progression, treatment monitoring, recurrence, and image-based surrogate end points. NCI’s interests include development and delivery of imaging technologies that are cancer-specific, and optimization and validation of imaging technologies for cancer applications. The scope includes system integration, contrast agents, pre- and post-processing algorithms and software for imaging, image understanding, and related informatics that are cancer-specific.

This FOA is directed toward the development, optimization, and delivery of innovative image acquisition and enhancement methods, including high-risk/high-gain research on technologies, such as: (a) novel single and multimodality molecular imaging systems, methods, agents, and related software and informatics, including the integration of these technologies with emerging biomedical imaging methods for more effective health care delivery for cancer and other diseases; and (b) novel single and multimodality anatomical and functional imaging systems, methods, agents, and related software and informatics for more effective health care delivery for cancer and other diseases. In addition, research partnerships among investigators in both academia and device and drug industries are encouraged to more rapidly translate and deliver completed imaging system developments.

This solicitation utilizes the NIH Phased Innovation (R21 [Phase I, Exploratory]/R33 [Phase II, Developmental]) grant mechanism, and runs in parallel with another FOA of nearly identical scope and intent, PA-06-399 that utilizes the separate R33 (Phase II, Developmental) grant mechanism.

Phased Innovation Awards benefit from expedited evaluation of progress following the Phase 1 exploratory/feasibility study for expedited decision on transition to Phase 2 funding for expanded developmental work.

Research Objectives

The overarching Research Objectives of this FOA are to stimulate development, optimization, and delivery of novel imaging technologies and methods to capture, process, validate, present, interpret, and/or understand in vivo imaging data that support the mission of the NCI.

Significant advances in medical imaging technologies have been made over the past 25 years in such areas as magnetic resonance imaging (MRI), computed tomography (CT), nuclear medicine, ultrasound, and optical imaging. These advances largely focused on structural or anatomical imaging at the organ or tissue level. Now there is an opportunity to stimulate the development and integration of novel imaging technologies that exploit our current knowledge of the genetic and molecular bases of various diseases. Molecular biological discoveries have great implications for prevention, detection, and targeted therapy. Imaging technologies able to provide similar kinds of cellular and molecular information (i.e., in vivo molecular imaging) similar to that currently available from histological or micro-array techniques used for in vitro studies would be very useful.

The advances in molecular methods pose new requirements for the performance of conventional biomedical imaging systems. For example, molecular imaging systems may need to be optimized for a molecular probe or probes as well as anatomical imaging. The integration of molecular imaging methods into multi-modality systems will affect data acquisition, processing, reduction, display, and archiving. Therefore, there is a need to support advances in methods for both molecular and conventional anatomical and functional imaging.

The need to encourage and support biomedical imaging and imaging technology development by academic and industrial researchers was stressed by participants at several NIH- and NCI-supported forums over the past few years. The needs include: (a) promoting the development of novel, high-risk, high-gain technologies; (b) supporting those technologies to maturation, dissemination, and full exploitation; (c) integrating new technologies into commercially available imaging systems for targeted applications; (d) harmonizing imaging methods across versions of a single platform or across multiple platforms to permit similar image-based surrogate outcome metrics as required for multi-site pre-clinical and clinical investigations; (e) funding a small number of copies of integrated system prototypes for placement, as required, for off-site research and clinical feasibility studies; and (f) improving technology transfer, delivery, and dissemination by promoting early-stage partnerships between academia and industry to encourage sharing of research resources and validation studies necessary to meet Federal regulatory requirements. Therefore, the aims of this initiative and the support mechanism (Phased Innovation R21/R33 Awards) are also directed at encouraging the development and delivery of imaging "tools" and related resources to support biomedical imaging in general for applications in oncology and other diseases.

Developments of novel imaging technologies usually require multidisciplinary approaches and teams with broad expertise in a variety of research areas. Such varied expertise might include imaging physics, chemistry, molecular and cellular biology, signal and image processing, computer vision, informatics and biostatistics, and clinical sciences. The coordination and collaboration of investigators with the necessary variety of disciplines to demonstrate the utility and applicability of new imaging methods is encouraged.

The purpose of this initiative is to facilitate the development of novel imaging technologies for risk assessment, early detection, screening, diagnosis, or image-guided treatment of cancer and other diseases and to facilitate clinical evaluations and optimization studies that are specifically limited to proof of concept and pilot data on clinical functionality of the development. Clinical trials for clinical validation of emerging imaging technologies are beyond the scope and are not responsive to this FOA.

Studies with pre-clinical models and clinical studies to demonstrate the feasibility of developments are encouraged, including multi-site evaluations, where appropriate. Methods that establish "ground truth" are required at appropriate levels of resolution to validate these emerging imaging methods, e.g., imaging excised tissue using protocols similar to those used in vivo, or correlation of molecular imaging results with micro-array library analyses. Developments of molecular probes or targeted contrast agents are considered important approaches to detection of molecular changes in vivo to take better advantage of many technologies with potential for molecular imaging.

The following topics would make appropriate proposed projects. This list is not meant to be all-inclusive.

Early Disease Detection: Developments may address innovative high-resolution imaging methods, with a particular intent to identify and characterize abnormalities or other early changes, including molecular events on the path to disease. Novel solutions for in vivo microscopic imaging systems, or microscopic implanted devices with high-spatial and/or temporal resolution, that may use either intrinsic or exogenous contrast agents represent possible topics.
Disease Screening: These methods may include, but are not limited to, the development and optimization of efficient imaging systems for screening, with the intent of achieving improved sensitivity and specificity for disease detection. Applications could address innovative improvements to current imaging methods, including hardware and/or software upgrades, or emerging imaging sensors and methods. Research topics of interest include means to significantly reduce imaging time or effects of motion, use of novel contrast agents or imaging probes, and use of technologies that reduce or do not involve the use of ionizing radiation or novel contrast agents and imaging probes. System integration and software methods could include a variety of image processing and data reduction techniques including temporal analysis of serial studies, close to real-time image processing, novel image display methods, and related imaging informatics for more cost-effective solutions for screening.
Imaging for Diagnosis, Staging, or Monitoring the Effects of Therapy: This FOA encourages, but is not limited to, the development of novel imaging methods, such as functional or molecular imaging or spectroscopy methods that would significantly improve the specificity of diagnosis of cancer and other diseases, allow deterministic methods or patient-specific staging, or measure early effects of therapy. Examples of system integration would include multi-modality imaging, image fusion or registration of the different modalities employed, development of software methods that would estimate the probability of malignancy or other specific disease identification, quantitative information for monitoring the effects of therapy, and close to real-time image analysis.
Image-Guided Biopsy (IGB), Image-Guided Therapy (IGT), and Image-Guided Interventional (IGI) Procedures: This FOA encourages novel approaches using imaging technologies needed to significantly improve specificity, to identify lesion extent and microscopic involvement, and to minimize tissue damage accompanying biopsy and therapy. Of particular interest are innovative approaches to IGB, IGT, or interventional methods that include novel imaging systems that provide molecular target information or information at the cellular or molecular level sufficient for image guidance and treatment. Examples of system integration that are of interest include, but are not limited to, multi-modality imaging, navigational systems, registration methods, real-time feedback mechanisms for controlling therapy (including radiation therapy) or the use of methods that are adaptive or allow patient-specific optimization of treatment, and computer-assisted surgery.
Copies of Prototype Imaging Systems: Support may be requested to make one or more copies of the prototype for placement in collaborating facilities for research purposes, namely pre-clinical or clinical feasibility investigations, including harmonization across versions of a single platform or across multiple platforms to enable multi-center comparison studies. Investigators anticipating need for funds to build system copies, harmonize imaging methods or collaborate with NCI-funded centers are advised to contact the NIH program staff listed in the section of this document that is entitled Where to Send Inquiries.
Research Resources: Developments of publicly accessible research resources that facilitate a consensus process for optimization and validation of emerging imaging technologies are encouraged. Examples include the development of open source software, image processing software and related informatics that can be ported onto different platforms, methods and image databases required for validation of software performance, and other hardware or informatics methods that assist in more efficient delivery of imaging technologies for screening, diagnosis and treatment for cancer and other diseases. Investigators interested in development of research resources and related research are advised to contact NIH program staff.

Use of the NIH Phased Innovation (R21/R33) Grant Award

The NIH Phased Innovation (R21/R33) grant award, introduced by the NCI initially to support technology development, provides an appropriate mechanism to support the development of new prognostic and predictive markers. The R21/R33 award permits an investigator to perform initial developmental work in the R21 phase (i.e., Phase I), to demonstrate feasibility by meeting a set of quantitative, peer-reviewed milestones, and then to move directly into the clinical study in the R33 phase (i.e., Phase II).

The combined R21/R33 Phased Innovation Award application offers the following two advantages over the regular application process:

Single submission and peer review of both the R21 and R33 Phases in one application; and
Minimal or no funding gap between, the R21 and R33 phases. The award of R33 funds will be based on program priorities, on the availability of funds and on successful completion of Phase 1 aims, including negotiated Objective Performance Targets (Milestones), as determined by NCI staff in the context of peer review recommendations.

To be eligible for the Phased Innovation Award, the R21 phase must include well-defined objective; preferably quantifiable performance targets (Milestones) useful for judging the success of the proposed research, as well as a credible plan for development of technology in the R33 phase. The Phased Innovation Award must have a section labeled Milestones at the end of the R21 section of the Research Plan. This section must include well-defined, objective (quantitative if possible) performance targets (Milestones) for completion of the R21 Phase part of the application, a discussion of the suitability of the proposed Milestones for assessing success of the R21 phase work, and a discussion of the implications of successful completion of these Milestones for the proposed R33 study.

This FOA uses just-in-time concepts. It also uses the non-modular budgeting formats. Full budget presentations and justifications are required. Follow the

instructions for non-modular budget research grant applications. This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part2.htm.

Investigators may not apply for a separate R21 or R33 grant/award under this FOA; however, investigators who are ready to conduct qualified Phase II research should see the partner FOA for R33 applications, PA-06-399.

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

Section II. Award Information

1. Mechanism of Support

This FOA will use the combined NIH Phased Innovation R21 [Phase I]/R33 [Phase II] award mechanisms. Transition of the R21 to the R33 phase will be expedited and is dependent on the completion of negotiated milestones. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses just-in-time concepts. It does not use the modular budget formats.

Competing renewal (formerly competing continuation ) applications will be accepted.

Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted. See NOT-OD-03-041, May 7, 2003.

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 NIH 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.

For combined R21/R33 applications, the applicant may request an R21 (Phase I) budget period of up to 2 years, with a combined budget guideline for direct costs of up to $275,000 for the maximum 2-year period. The amount of funds requested and their distribution between years in the Phase I portion should be tailored to the needs of the project, with no more than $200,000 in direct costs allowed in any single year. Although the R33 application has no official budgetary limit, applications requesting $500,000 or more in direct costs in any single year of the grant period require prior approval from the NIH 6 weeks before submission (see Section IV.3.A.2 below). The total project period for an R21/R33 grant application/award submitted in response to this FOA may not exceed 4 years and the R21 phase may not exceed 2 years.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

The award of R33 funds will be based on program priorities, on the availability of funds, and on successful completion of negotiated scientific milestones as determined by NIH staff in the context of peer review recommendations.

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.

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:

For-profit organizations;
Non-profit organizations;
Public or private institutions, such as universities, colleges, hospitals, and laboratories;
Units of State governments;
Units of local governments;
Eligible agencies of the Federal government;
Foreign institutions;
Domestic institutions; and
Faith-based or community-based organizations;
Indian/Native American Tribal Governments (Federally Recognized);
Indian/Native American Tribal Governments (Other than Federally Recognized); and
Indian/Native American Tribally Designated Organizations.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (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.

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.

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/Apply/ and follow the directions provided on that web site.

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

Grants.gov (http://www.grants.gov/GetStarted); and
eRA Commons (http://era.nih.gov/ElectronicReceipt/preparing.htm).

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

Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants.gov registration process.
If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.
The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business days.
Direct questions regarding Grants.gov registration to:
Grants.gov Customer Support
Contact Center Phone: 800-518-4726
Business Hours: M-F 7:00 a.m. - 9:00 p.m. Eastern Time
Email support@grants.gov

2) Organizational/Institutional Registration in the eRA Commons

To find out if an organization is already Commons-registered, see the "List of Grantee Organizations Registered in NIH eRA Commons.
Direct questions regarding the Commons registration to:
eRA Commons Help Desk
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Business hours M-F 7:00 a.m. 8:00 p.m. Eastern Time
Email commons@od.nih.gov

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

The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons. It is not necessary for PDs/PIs to register with Grants.gov.
The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.
This registration/affiliation must be done by the Authorized Organization Representative/Signing Official (AOR/SO) or their designee who is already registered in the Commons.
Both the PD/PI 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 4 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 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: 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
Research & Related Budget
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

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

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

Charge back of customs and import fees is not allowed.
Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5 x 11 within each PDF.
Funds for up to 8% administrative costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.
Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., Administrative and National Security Requirements.
For additional information, see the NIH Grants Policy Statement regarding foreign grants: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

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.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: May 9, 2006 (earliest date an application may be submitted to Grants.gov).

Application Submission Date(s): http://grants.nih.gov/grants/funding/submissionschedule.htm
AIDS Application Submission Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#AIDS
Peer Review Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Council Review Date(s) http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward
Earliest Anticipated Start Date(s): http://grants1.nih.gov/grants/funding/submissionschedule.htm#reviewandaward

3.A.1. Letter of Intent

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

3.A.2. Specific Instructions for Applications Requesting $500,000 or More per Year:

Applications requesting $500,000 or more in direct costs for any year must include a PHS398 Cover Letter File identifying the NIH staff member (within one of the NIH Institutes or Centers [ICs]) who has agreed to accept assignment of the application.

Applicants requesting more than $500,000 must carry out the following steps:

Contact the NIH IC program staff at least 6 weeks before submitting the application, i.e., as you are developing plans for the study;
Obtain agreement from the IC staff that the IC will accept your application for consideration for an award; and
Identify, in the PHS398 Cover Letter File included with the application, the staff member and IC that agreed to accept assignment of the application.

This policy applies to all investigator-initiated new (type 1), competing continuation (type 2), competing supplement, or any amended or revised version of these grant application types. Additional information on this policy is available in the NIH Guide for Grants and Contracts, October 19, 2001, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-004.html.

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.

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.

If everything is acceptable, no further action is necessary. The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days.
Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed. Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.
If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants.gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process). The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov system issue.
If the AOR/SO chooses to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants.gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.
Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days.

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.

Prior to funding an application, the NCI Program Director will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel as indicated in the Summary Statement. The Program Director and the applicant will negotiate and agree on a final set of milestones. These will be the basis for judging the success of the R21 work. At least one interim progress report will be required during the R21 phase.

For funded applications, completion of the R21 milestones will elicit an expedited review by the NCI that will determine whether or not the R33 grant should be awarded. The release of R33 funds will be based on successful completion of negotiated scientific milestones, program priorities, and on the availability of funds. The expedited transitional review may result in additional negotiations of award.

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 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 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

The NIH requires the PD/PI 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. 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 Tips and Tools for Navigating Electronic Submission on the front page of Electronic Submission of Grant Applications.

Renewal (formerly competing continuation or Type 2 ) applications are permitted.

All application instructions outlined in the SF424 (R&R) application are to be followed, with the following requirements for R21/R33 applications:

R21/R33 applications will use the "Just-in-Time" concept.
The R21 phase may be either one or two years in duration. Total direct costs for the R21 phase are limited to $275,000 over a 2-year period. No more than $200,000 in direct costs will be allowed in any single year of the R21 phase.
The modular budget concept will not be used. Even though the budget for the R21 phase is limited, use the detailed SF424 RR Budget forms for all years. Indicate in the budget justification whether the budget year is for the R21 or the R33 phase. The SF424 RR cannot be accepted with a modular budget for the R21 phase and a detailed budget for the R33 phase.
Although preliminary data are not required for an R21/R33 application, they may be included.
Items 2-5 of the Research Plan of the R21 application may not exceed 25 pages, including tables, graphs, figures, diagrams, and charts.
Introduction (required for a resubmission application) is limited to 3 pages.
There should be a single Research Plan. Within the individual sections, describe the both the R21 and R33 phases as appropriate. Item 2 (Specific Aims) must provide separate sets of aims for the R21 and R33 phases. Item 5 (Research Design and Methods) must provide separate descriptions for the R21 and R33 phases, but it is not necessary to repeat background information or details of methods in the R33 section that were provided in the R21.
Milestones for the R21 phase MUST be included, and should be placed at the end of the R21 Research Design and Methods section. This section must propose milestones for completion of the R21 part of the application, a discussion of the suitability of the proposed milestones for assessing success in the R21 phase, and a discussion of the implications of successful completion of these milestones for the proposed R33 study. Milestones should be specific, quantifiable and scientifically justified; they should not be simply a restatement of the R21 specific aims.
For the R33 phase, Item 5 of the Research Plan should include a statistical section that discusses the choice of the study design and laboratory methods. Sample sizes must be clearly stated and justified with power calculations. The statistician involved with the project should be identified and a letter of support included if no effort is requested in the budget. Plans for data management and verification of clinical research data should also be described. Collaborative arrangements should be clearly documented, and where collaborations involve NCI-sponsored clinical trials the protocol numbers should be provided. Letters of support should be included in the application to substantiate plans for collection of follow-up information beyond the period of award. Where appropriate, applicants are strongly encouraged to include a copy of the complete clinical protocol in the Appendix.
Specific Aims: The applicant must present specific aims that are scientifically appropriate for each of the two phases of the project. Clearly state the clinical questions to be addressed. Identify the patient population(s) to be studied and the technology or technologies to be employed.
Background and Significance: The applicant should clarify how the prognostic or predictive strategy proposed for evaluation in this project is a significant addition to existing approaches. Explain the potential of the proposed strategy for a broad impact on patient care and improvement in patient outcomes. If preliminary data from the applicant’s own laboratory are not available, this section of the application must provide current evidence from the literature or from other investigators to substantiate the potential clinical utility of the proposed strategy.
Preliminary Data: The R21 component of an R21/R33 application will be considered exploratory, so that extensive preliminary data from the applicant’s own laboratory are not required. However, the project must be based on a strong rationale, and the applicant should provide evidence that the initial clinical evaluation of the proposed technology is promising. The R21 phase provides time for necessary preliminary work such as, for example, the substantial modification of a technology. An application may use results obtained during a previous R21 award to support a proposal in response to this FOA.
Applicants are encouraged to include all information required for adequate evaluation for reviewers. However, in the event that a technology is not yet patent protected and the applicant does not wish to include complete details, the application should at a minimum provide a demonstration of the capabilities of the proposed approach.
Applicants for R21/R33 projects need to provide information in the application or to propose milestones that will demonstrate the feasibility of the R33 phase. Milestones must be designed to permit a straightforward decision as to whether or not the applicant is ready to initiate the R33 phase of the project.
The R33 phase of the study must be described in sufficient detail to permit reviewers to assess the significance and innovation of the proposed work and the strength of the experimental design.

Note: While each section of the Research Plan needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan 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.

Up to ten publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to this project. Do not include manuscripts submitted for publication.

Publications in press: Include only a publication list with a link to the publicly available on-line journal article or the PubMed Central (PMC) submission identification number. Do not include the entire article.
Manuscripts accepted for publication but not yet published: The entire article may be submitted electronically as a PDF attachment.
Manuscripts published, but an online journal link is not available (in such cases, the entire article may be submitted electronically as a PDF attachment).

Surveys, questionnaires, data collection instruments, clinical protocols, and informed consent documents.
Graphic images of gels, micrographs, etc., provided that the image (may be reduced in size) is also included within the 15-page limit of Items 2-5 of the Research Plan. No images may be included in the Appendix that are not also represented within the Research Plan.
Do not use the Appendix to circumvent the page limitations of the Research Plan. An application that does not observe these limitations may be delayed in the review process.

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.

Plan for 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/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

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 U.S. Public Health Service (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:

Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score;
Receive a written critique; and
Receive a second level of review by the appropriate national advisory council or board.

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:

Scientific merit of the proposed project as determined by peer review;
Availability of funds; and
Relevance to program priorities.

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.

Significance
Approach
Innovation
Investigator
Environment
Additional Review Criteria

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 PD/PI 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.

Milestones: How appropriate are the proposed milestones to judge the success of the proposed R21 project and to determine whether the R33 grant should be awarded? Do they set forth specific criteria, in sufficient detail, that will permit a straightforward decision about whether or not they have been accomplished? Do the milestones establish feasibility for all aspects of the proposed R33 work?

For the R21/R33 Phased Innovation Award Application, the initial review group will evaluate the specific goals for each phase and the feasibility milestones that would justify expansion to the R33 phase. A single priority score will be assigned to each scored application. As with any grant application, the initial review group has the option of recommending support for a shorter duration than that requested by the applicant and basing the final merit rating on the recommended portion of the application. For the R21/R33 application, this may result in a recommendation that only the R21 phase be supported, based on concerns related to the application's specific goals and the feasibility milestones justifying expansion to the R33 phase. Deletion of the R33 phase by the review panel or presentation of inadequate milestones in the application may affect the merit rating of the application.

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 percent 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

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). NIH program staff will be responsible for administrative review of the plan for sharing research data.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement 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. For the R21 mechanism, the presence or adequacy of a plan should not enter into the scoring of the application.

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.

Prior to funding an application the NCI program director will contact the PD/PI to discuss the proposed milestones and any changes suggested by the review panel as indicated in the Summary Statement. The program director and the applicant will negotiate and agree on a final set of milestones, which will be the basis for judging the success of the R21 work. The final milestones will be included in the Notice of Award as one of the terms of the award.

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

At least one interim progress report will be required before a request for transition from the R21 to the R33 phase can be considered. If the R21 phase is one year in duration, this report will normally be due 6 months after the beginning date of the award.

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.

The NCI is developing a policy that will require Clinical Terms of Awards for clinical studies and trials when they are a component of the proposed research. The policy will require that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. The new policy will be posted in the NIH Guide within a few weeks. All funded applicants will be expected to adhere to the new policy.

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:

Guoying Liu, Ph.D., Keyvan Farahani, Ph.D., James A. Deye, Ph.D., or Houston Baker, Ph.D.
National Cancer Institute
6130 Executive Plaza, EPN Room 6000
Bethesda, MD 20892-7412 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: 301-496-9531 for GL, KF, HB; 301-496-6111 for JAD
Fax: 301-480-3507
E-mails: guoyingl@mail.nih.gov, farahank@mail.nih.gov, deyej@mail.nih.gov, bakerhou@mail.nih.gov

2. Peer Review Contacts:
Not applicable.

3. Financial or Grants Management Contacts:

Shane Woodward
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 service)
Telephone: 301-846-1017
Fax: 301-846-5720
E-mail: woodwars@mail.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of U.S. Public Health Service (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.

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.

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 (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 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.