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: Innovations in Cancer Sample Preparation (R21, R33, R21/R33)

Announcement Type
This is a reissue of RFA-CA-06-004.

Request for Applications (RFA) Number: RFA-CA-07-003

Catalog of Federal Domestic Assistance Numbers
93.392, 93.393, 93.394, 93.395, 93.396

Key Dates 
Release Date: December 8, 2005
Letters of Intent Receipt Dates: January 23, 2006; April 26, 2006
Application Receipt Dates: February 22, 2006; May 26, 2006
Peer Review Dates: June/July 2006; October/November 2006
Council Review Dates: September/October 2006; January/February 2007
Additional Information To Be Available Date (URL Activation Date): Not Applicable.
Earliest Anticipated Start Dates: September 2006; February 2007
Expiration Date: May 27, 2006

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
    2. Research Topics

  Section II. Award Information
    1. Mechanism(s) of Support
    2. Funds Available

  Section III. Eligibility Information
    1. Eligible Applicants
      A. Eligible Institutions
      B. Eligible Individuals
    2. Cost Sharing
    3. Other - Special Eligibility Criteria

  Section IV. Application and Submission Information
    1. Address to Request Application Information
    2. Content and Form of Application Submission
    3. Submission Dates
      A. Receipt and Review and Anticipated Start Dates
        1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
    4. Intergovernmental Review
    5. Funding Restrictions
    6. Other Submission Requirements

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
    3. Merit Review Criteria
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative 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

Purpose

The National Cancer Institute (NCI) invites applications for research projects involving the development and significant enhancement or adaptation of sample preparation methodologies and technologies, the development of assays to assess sample quality, and studies designed to elucidate the criteria by which to judge sample quality. The outcome will be products and methods designed to optimize sample utility. Samples may originate from residual material not necessary for patient care or from cell lines, model organisms, or other sources relevant to cancer research.

The development of new and/or improved cancer sample preparation methodologies and technologies, the development of assays to assess sample quality, and studies to elucidate the criteria needed to judge sample quality covers a wide range of project sizes and innovation levels. This funding opportunity will allow the submission of applications involving the R21, R33, and (combined/phased) R21/R33 grant mechanisms. R21 applicants may propose small, highly innovative feasibility studies or small, short-term exploratory studies to meet one of the goals of this funding opportunity. R21/R33 applicants should propose projects that require a small feasibility study followed by a well-defined development plan. Successful completion of the R21 feasibility study and the resulting transition to the R33 phase will be judged by NCI staff per NCI R21/R33 policy. Projects for which feasibility has already been established may be proposed as R33 applications. Feasibility means that some preliminary experiments have been performed and that there is sufficient technical data to support proof-of-principle of the technology/hypothesis.

This funding opportunity is part of a broader technology development program within the NCI. That program underscores the desire of NCI to develop and integrate novel technologies focused on the molecular analysis of cancers and their micro-environment in support of cancer research, diagnosis, and treatment. In the research continuum of discovery, development, and delivery, this program thus emphasizes the link between development and delivery. This specific initiative aims to foster the development of sample preparation techniques and methodologies that are essential for effective research, technology development, and validation that will eventually lead to clinical applications.

This funding opportunity capitalizes on both the success and intent of the original NCI sponsored Innovative Molecular Analysis Technologies (IMAT) program in bringing together a multi-disciplinary group of scientists and engineers to work on cancer and the expansion of interest in technology development across the NCI and other NIH institutes. This continuation of the IMAT program consists of the following three initiatives: Innovative Technologies for the Molecular Analysis of Cancer; Innovations in Cancer Sample Preparation; and Application of Emerging Technologies for Cancer Research. This funding opportunity is designed to support research focused on sample preparation methods. Applicants may submit more than one application in response to this RFA, provided that they are scientifically distinct. Projects focused on the development of novel technologies may be most suitable for RFA-CA-07-001, Innovative Technologies for the Molecular Analysis of Cancer. Projects focused on evaluating emerging technologies that are ready for initial clinical or biological application in cancer research may be most suitable for RFA-CA-07-002, Application of Emerging Technologies for Cancer Research. Applicants from small businesses are encouraged to submit applications to the parallel RFAs for this IMAT initiative that will utilize the SBIR (R43, R44) and STTR (R41, R42) grant mechanisms (RFA-CA-07-010 and RFA-CA-07-011, respectively).

Background:

High quality sample preparations are the foundation for effective technology validation as well as for meaningful biological and clinical research. Sample preparation covers the spectrum from preparation of molecules to cells to tissues. Preparation of the highest quality samples can be hampered by technical issues, lack of standards by which to judge quality, and lack of standard practices. Sample preparation methods vary. Researchers often develop sample preparation methodologies in an ad hoc fashion as part of other projects. This lack of information and standardization affects the quality and comparability of data across all fields of cancer research and across all technological platforms.

Objectives and Scope:

Sample preparation methods and technologies may be developed for sample collection, processing, isolation, storage, purification, preservation, and, in the case of stored tissues, reversal of adverse events resulting from storage and preservation. Methods may be for preparation of molecules, fluids, tissues, or any other samples necessary for cancer research. Researchers may propose to develop methods to isolate cells or sub-cellular components, such as classes of molecules, organelles, or sub-cellular structures. They may propose to isolate specific classes of molecules, such as membrane-bound proteins. They may also propose studies to determine the effects of collecting, processing, and storage on molecular components of interest in stored specimens. The goal is to develop products and methodologies that maximize the quality and utility of samples for research and, in the case of human specimens, maximize the quality of the samples for research and clinical needs without compromising patient care. Methods and technologies for measuring and monitoring changes in biomolecule expression in response to specimen handling variables are encouraged.

Sample preparation methods may impact the results or interpretation of biological studies. Investigators may apply different methods of sample preparation using the same measurement technology. In many cases of measuring biological response, no “gold standard” exists by which to compare research results obtained from the different sample preparation methods. There is a need for methods to assess the quality of samples prepared using different methodologies. This funding opportunity will support methods to assess sample quality and studies that elucidate the criteria needed to judge sample quality under different conditions. This funding opportunity will also support the development of technologies to make these assessments, such as the development of sample reference materials that can be used to calibrate the effectiveness of new fixatives or new detection methodologies.

It is expected that many investigators who developed successful cancer sample preparation techniques under previous IMAT initiatives (i.e., with R21, but not R33, grant award funds from RFA-CA-06-002, RFA-CA-06-003, RFA-CA-06-004, RFA-CA-05-002, RFA-CA-05-003, and/or RFA-CA-05-004) will propose projects for this funding opportunity. However, this funding opportunity is not limited to techniques developed under the IMAT program. Investigators are encouraged to use any sample preparation methodologies or techniques relevant to cancer.

For all projects proposed, it will be important to substantiate the ultimate value of the innovation for analyzing samples, optimizing analysis, and/or evaluating sample quality for the purpose of research and eventually clinical applications. Also of importance is the potential for ultimately transferring knowledge, technologies, and/or methodologies to other laboratories or the clinic. In the case of technologies intended for use on clinical specimens or in patients, applications from or collaborations with investigators involved in the clinical research of cancer are encouraged.

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

Section II. Award Information

1. Mechanisms of Support

Support for this program will be through the National Institutes of Health (NIH) Exploratory/Developmental Research Grant (R21), the Exploratory/Developmental Research Grant Phase 2 (R33), and the Phased Innovation Award (R21/R33) mechanisms. Except as otherwise stated in this funding opportunity, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement, March 2001, available at http://grants.nih.gov/grants/ policy /nihgps_2003/NIHGPS_Part2.htm. Hard copies are not available. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant.

The total project period for an application submitted in response to this funding opportunity may not exceed the following durations: R21, 2 years; R33, 3 years; combined R21/R33 application, 4 years. In the combined application, the R21 phase cannot extend beyond 2 years.

For R21 and R21/R33 applications, the R21 phase may not exceed $275,000 direct costs for 2 years. R21 budgets can exceed this cap to accommodate indirect costs to subcontracts to the project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budgeting formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting an application with direct costs in each year of $250,000 or less, use the modular budget format described in the PHS 398 application instructions. Otherwise, follow the instructions for non-modular research grant applications.

This funding opportunity will run in parallel with two other funding opportunities of identical scientific scope, one that will utilize the Small Business Innovation Research (SBIR) R43 and R44 grant mechanisms (RFA-CA-07-010) and another that will utilize the Small Business Technology Transfer (STTR) R41 and R42 grant mechanisms (RFA-CA-07-011).

2. Funds Available

NCI intends to commit approximately $1,000,000 in FY 2006 to fund four to eight new and/or competitive continuation grants in response to this funding opportunity. An applicant may request a project period of up to 2 years for an R21, up to 3 years for an R33, and up to 4 years for a combined R21/R33 of which the R21 portion may be no more than 2 years. An applicant may request a budget for direct costs of up to $275,000 for 2 years for R21 and the R21 portion of R21/R33 applications. Budgets for R33 and the R33 portion of R21/R33 grant applications should be appropriate for the science proposed.

For the R21 award mechanism, the applicant may request a project period of up to 2 years with a combined budget for direct costs of up $275,000 for the 2-year period. For example, the applicant may request $100,000 in the 1st year and $175,000 in the 2nd year. Normally, no more than $200,000 may be requested in any single year. The request should be tailored to the needs of the project. See the link at http://grants.nih.gov/grants/funding/r21.htm.

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 NCI provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-04-040.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

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

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria
Not applicable

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants should use the currently approved version of the PHS 398. For further assistance, contact GrantsInfo, Telephone: (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements “see http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-03-055.html”. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

1. Face Page of the application:

Item 2. The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked. Also indicate if the application is an R21 only, a combined R21/R33, or an R33.

Item 7a: Direct Costs Requested for Initial Period of Support:

For the R21 or the R21 phase of the combined R21/R33 application, direct costs are limited to a maximum of $275,000 for a maximum of 2 years and the award may not be used to supplement an ongoing project. The requested budgets can exceed this cap to accommodate indirect costs to subcontracts to the project. Insert the first year of R21 support in item 7a.

Item 8a: Direct Costs Requested for Proposed Period of Support:

For the R21 phase, direct costs requested for the proposed period may not exceed $275,000 for 2 years of support. The statement in item 7a above pertaining to subcontract costs also applies here. Insert sum of all years of requested support, both R21 and R33 years, in item 8a.

2. Page 2 - Description:

As part of the description, identify concisely and completely the technology or methodology to be applied, its innovative nature, its relationship to presently available capabilities, and its expected impact on the molecular analysis of cancer, as well as the study in which the technology will be applied.

3. Budget: The application should contain a modular budget for the Initial Budget Period (form page 4), for each of the initial years of the R21 and R33 phases (or a detailed budget for R33 years that exceed $250,000 direct costs), as well as a budget for the entire proposed period of support (form page 5). Form pages should indicate which years are R21 and R33. All budgets should include a written justification.

Please note that the budget of the application should contain a request for travel funds to support the attendance of the principal investigator and one additional senior investigator at an annual meeting of all investigators funded through this program; this meeting will be held so that awardees and associated investigators can share progress and research insights that may lead to further progress in the program.

4. Research Plan:

Item a: Specific Aims

The applicant must present specific aims that the applicant considers to be scientifically appropriate for the relevant phases of the project.

The instructions in the PHS 398 booklet for this section of research grant applications suggest that the applicant state the hypotheses to be tested. Since the goal of this funding opportunity announcement is to support the pilot application of innovative technologies, hypothesis testing per se may not be the driving force in developing such an application and, therefore, may not be applicable. Furthermore, for R21 grant applications, preliminary data are not required, although they should be included when available. For both the R21 phase and the R33 phase, research that supports the pilot application of new technologies is likely to require the application of principles of fields such as engineering, materials science, physics, mathematics, and computer science. Clear statements of these underlying principles are essential. In particular, studies pursuing comprehensive analyses may result in hypothesis generation rather than hypothesis testing.

Item b: Background and Significance

Elaborate on the innovative nature of the proposed research. Clarify how the technology development proposed in this project is a significant improvement over existing approaches. Explain the potential of the proposed technology for having a broad impact on cancer research. Clearly identify how the project, if successful, would result in new capabilities for research, the immediacy of the opportunity and how these proposed technologies would differ from existing technologies.

Item d: Research Design and Methods

Follow the instructions in the PHS 398 booklet. In addition, for the R21 phase only, the following information must be included as a final section of Item d:

Applications must include a specific section labeled “Milestones” following the Research Design and Methods of the R21 phase (see the instructions for preparing milestones below). Milestones should be well described, quantitative, and scientifically justified and they should not be simply a restatement of the specific aims. A discussion of the milestones relative to the success of the R21 phase, as well as the implications of successful completion of the milestones for the R33 phase should be provided. The page number of the milestones section should be indicated in the Table of Contents.

Applications lacking this information, as determined by the NCI program staff, will be returned to the applicant without review. For funded applications, completion of the R21 negotiated milestones will elicit an NCI expedited review 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 milestones, program priorities, and on the availability of funds. The expedited review may result in additional negotiations of award.

Specific Instructions for Preparing the R21 Application

Please see the link for the NIH Exploratory/Developmental Research Grant Award Program at http://grants.nih.gov/grants/funding/r21.htm for instructions on submitting R21 applications.

Milestones. R21 and combined R21/R33 applications must include a specific section of no more than two pages labeled “Milestones” following the Research Design and Methods of the R21 phase. Milestones should be well described, quantitative, and scientifically justified and not be simply a restatement of the specific aims. Discuss the milestones as a means of judging the success of the R21 phase as well as providing proof of principle for a future R33 phase. The page number of the Milestones section should be indicated in the Table of Contents. The Milestones section must be clearly labeled as such and contained within the standard 15-page limit for sections a-d text for an R21 application. Specific aims may not be regarded as milestones (unless they include quantitative end points).  The specific aims describe the goals and intended path of the research. Quantitative milestones are a way of determining whether an applicant has successfully reached the specified goal.  In most cases, applicants should provide a milestone for each specific aim. Milestones should be clearly stated and presented in a quantitative manner, such as numerical specifications of sensitivity and specificity or a count of some desired kind of newly discovered molecule, etc. Quantitative milestones include, but are not limited to, the following examples:

a. Detection of one cancer cell in 106 normal blood cells;
b. Identification of 10 new cancer-associated cDNAs;
c. Detection of substance “x” at a concentration of 1 pmol/mL in serum;
d. Cost of new technology is 10 percent that of the current technology;
e. Detection of one mutated gene in the presence of 103 normal genes;
f. Demonstration that the technology gives the same result in 95 out of 100 assays; and
g. Demonstration that the technology is capable of detecting 25,000 different polypeptides from a cell or tissue type.

An application lacking quantitative milestones as determined by the NCI program staff will be returned to the applicant without review.

Please note that for items a-d, there is a strict 15-page limit for R21 applications.

Specific Instructions for Preparation of an R33 Application

Applications for R33 grants are to be submitted on the grant application form PHS 398 (rev. 9/2004) and prepared according to the instructions provided unless specified otherwise within the items below.

R33 applicants must present detailed preliminary data in support of the feasibility of the proposed technology or approach that is proposed for development. These applications will also have the added burden of demonstrating the innovation of the particular technology or approach.

For R33 applicants applying to continue research begun under R21 support, the applicant must quote the final milestones from the R21 Notice of Award (NOA) as part of the R33 application.  This section should include a discussion of the extent to which the applicant achieved the milestones.  This section should constitute no more than three pages, but is in addition to the 25-page limit for items a-d.  This section on achievement of milestones should be clearly marked and located between items a and b of the Research Plan.

Research Plan

Item c: Preliminary Studies/Progress Report

This section must document that feasibility studies have been completed, and progress achieved, equivalent to that expected through the support of an R21 project. The applicant must clearly describe how the exploratory/developmental study is ready to be scaled up to an expanded application stage. In the event that an applicant feels that the technology is too proprietary to disclose, the applicant must at a minimum provide a demonstration (results) of the capabilities of the proposed technology. Preliminary data relevant to both the technology evaluations and the pilot biological study should be presented.

R33 applications should also include milestones as described in the section above that may help justify continued support under another mechanism, such as an R01.

Please note that for items a-d, there is a strict 25-page limit for R33 applications.

Specific Instructions for Preparing the Combined R21/R33 Application

The combined R21/R33 application offers two advantages over the regular application process, as follows:

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

The R21/R33 application must include the specific aims for each phase and the quantitative feasibility milestones that would justify transition to the R33 phase. Applications must include a specific section labeled “Milestones” following the Research Plan of the R21 phase (see milestones instructions above). For funded applications, completion of the R21 negotiated milestones will elicit an NCI expedited review that will determine whether or not the R33 should be awarded. Award of the R21 phase is not a guarantee of award of the R33 phase.  Awarding of R33 funds will be based on successful completion of negotiated scientific milestones, program priorities, and on the availability of funds. The expedited review may result in additional negotiations of award.

The R21/R33 application must be submitted as a single application, with one face page. Although it is submitted as a single application, it should be clearly organized into two phases. To accomplish a clear distinction between the two phases, applicants are directed to complete items a-d of the Research Plan twice: one write-up of items a-d and milestones for the R21 phase and items a-d again for the R33 phase. The Table of Contents form page in the PHS 398 instructions should be modified to show items a-d for each phase as well as the milestones. There is a page limit of 25 pages for the combined items a-d and milestones for the R21 phase and items a-d for the R33 phase.  In preparing the R21/R33 application, investigators should consider the fact that applications will be assigned a single priority score. In addition, the initial review panel has the option of recommending only the R21 phase for support. However, an R21/R33 application with an R33 Phase that is so deficient in merit that it is not recommended for support will reflect upon the judgment of the applicant. For these reasons, the clarity and completeness of the R21/R33 application with regard to specific goals and feasibility milestones for each phase are critical. The presentation of milestones that are judged not to be sufficiently scientifically rigorous for assessing progress in the R21 phase will reflect upon the scientific judgment of the applicant.

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

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

3. Submission Dates and Times

Applications must be received on or before the receipt dates described below (Section IV.3.A).

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

Letters of Intent Receipt Dates: January 23, 2006; April 26, 2006
Application Receipt Dates: February 22, 2006; May 26, 2006
Peer Review Dates: June/July 2006; October/November 2006
Council Review Dates: September/October 2006; January/February 2007
Additional Information To Be Available Date (URL Activation Date): Not Applicable.
Earliest Anticipated Start Dates: September 2006; February 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIH staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Gregory J. Downing, D.O., Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 10A52, MSC 2580
Bethesda, MD 20892-2580
Telephone: (301) 496-1550
FAX: (301) 496-7807
Email: downingg@mail.nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all five (CD-ROM or hard) copies of the appendix materials must be sent to:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

Applicants may, if they wish, submit appendix materials on CD-ROM disks.  If appendix materials are submitted as hard (paper) copies, they should be comprised of unbound materials, with separators between documents.

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the NCI.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application (unless it is an amended/revised application submitted for this latest issuance of the same funding opportunity).

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.

6. Other Submission Requirements

An annual meeting of all investigators funded through this program will be held to share progress and research insights that may lead to further progress in the program. Applicants should request travel funds in their budgets for the principal investigator and one additional senior investigator to attend this annual meeting.

Intellectual Property Management Plan

Certain research plans will require collaboration and coordination between investigators at different institutions, some of whom may not be NIH funding recipients and who may have pre-existing intellectual property obligations to third parties. It is anticipated that commercial embodiments of the results of such research may incorporate single inventions shared by several institutions, or multiple inventions each from a separate institution. Therefore, prior to funding, R33 grant applicants must address how they will coordinate patent prosecution and licensing activities, if necessary to enable a licensee to access the bundle of intellectual property needed to take a product to market on commercially viable terms. Suggested strategies include: (1) assigning intellectual property rights to related inventions to an invention management firm; (2) designating one organization to take the lead on patenting and licensing related inventions; and (3) agreeing in advance that if multiple parties are to independently license related inventions, the total of stacked royalties will not exceed a predetermined percentage rate.

The technology transfer/ intellectual property management/licensing officer or equivalent of the principal investigator's institution is to submit an intellectual property management plan, including at least those elements above. Alternatives to the suggested strategies, which accomplish the same goals, will be considered. Intellectual property management plans are a just-in-time requirement; it is not necessary to include the plan in the grant application but plans will be required before an R33 grant can be awarded.

The applicant's institution should avoid exclusively licensing those inventions that are research tools, unless either: (1) the field of use of the exclusive license is restricted to commercial use; or (2) the exclusive licensee will make the research tool available on reasonable terms. Applicants are directed to the NIH policy on the dissemination of biological research resources (“research tools”) at http://www.ott.nih.gov/policy/rt_guide_final.html.

Specific Instructions for Modular Grant Applications

Applications requesting up to $250,000 per year in direct costs must be submitted in a modular budget format. The modular budget format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step-by-step guidance for preparing modular budgets. Applicants must use the currently approved version of the PHS 398. Additional information on modular budgets is available at http://grants.nih.gov/grants/funding/modular/modular.htm.

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.

Section V. Application Review Information

1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities of the NCI in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The goals of NIH-supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach. Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?

Innovation. Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators. Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)?

Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following item will be considered in the determination of scientific merit and the priority score:

Milestones: In the cases of R21 alone and R21/R33 applications, are appropriate and quantitative scientific milestones included that will show, when completed by the end of the R21 period, whether or not the project has shown feasibility to pursue the R33 portion of the project?

In addition to this criterion, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data 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). (NCI program staff will be responsible for the administrative review of the plan for sharing research data.)

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and at http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates
Not applicable

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Award (NOA) will be provided to the applicant organization. The NOA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NOA will be generated via email notification from the awarding component to the grantee business official (designated in item 14 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NOA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NOA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the Notice of Award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590, annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, financial or grants management issues:

1. Scientific/Research Contacts:

Gregory J. Downing, D.O., Ph.D.
Office of Technology and Industrial Relations
National Cancer Institute
Building 31, Room 10A52, MSC 2580
Bethesda, MD 20892-2580
Telephone: (301) 496-1550
FAX: (301) 496-7807
Email: downingg@mail.nih.gov

2. Peer Review Contacts:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

3. Financial or Grants Management Contacts:

Barbara Liesenfeld
Office of Grants Administration
National Cancer Institute
6120 Executive Boulevard, EPS Room 243, MSC 7148
Bethesda, MD 20892-7148 (for U.S. Postal Service express or regular delivery)
Rockville, MD 20852 (for express/courier service)
Telephone: 301-496-3265
Fax: 301-496-8601
Email: liesenfb@mail.nih.gov

Section VIII. Other Information

Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); 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 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 at http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004, receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

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://www.nih.gov/about/publicaccess/ and view the Policy or other Resources and Tools including the Authors' Manual (http://www.nih.gov/about/publicaccess/publicaccess_Manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information," the "Privacy Rule," on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This funding opportunity is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50 percent 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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