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: Innovative Technologies for Molecular Analysis of Cancer (R21, R33)

Announcement Type
This funding opportunity announcement is a reissue of RFA-CA-06-002.

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

Request for Applications (RFA) Number: RFA-CA-07-001

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 proposing the development of highly innovative cancer-relevant molecular technologies. Technology encompasses methods and tools that enable research, including, but not limited to, instrumentation, techniques, and devices. Technology is distinct from resources such as databases, reagents, and tissue repositories. Applications for support of such resources will not be considered responsive to this funding opportunity announcement. Technologies solicited include, but are not necessarily limited to, those that are suitable for the detection of alterations and instabilities of genomic DNA; measurement of the expression of genes and gene products, including proteins; analysis and detection of gene and/or cellular products, including post-translational modification and function of proteins; identification and characterization of exogenous infectious agents in cancer; and assaying the function of major signal transduction networks involved in cancer. Developing technologies would include those that will support molecular analysis in vitro, in situ, or in vivo in discovery processes as well as in pre-clinical models and clinical research.

This funding opportunity is part of a broader technology development program within the NCI to harness technology in the fight against cancer. The NCI technology program underscores the desire of NCI to develop and integrate novel and emerging technologies in the support of cancer research, diagnosis, and treatment. In the research continuum of discovery, development, and delivery, this program accelerates development and delivery. This specific initiative will serve as the discovery tool of the larger program by soliciting and funding highly innovative, high risk and cancer-relevant technology development projects associated with the molecular analysis of cancer.

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 announcement is designed to support technology development projects. Technologies developed or adapted for sample preparation methodology may be most suitable for RFA-CA-07-003, Innovations in Cancer Sample Preparation. Research projects to evaluate 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-07-006 and RFA-CA-07-007, respectively). Researchers who emphasize the assessment of in vivo imaging technologies as the primary focus of their grant applications should contact the Cancer Imaging Program (http://www3.cancer.gov/bip/) for information on appropriate funding opportunities. Researchers focusing on applying new bioinformatics or statistical techniques as the primary focus of their applications should consider one of the (BISTI) initiatives (http://www.bisti.nih.gov/bistic_funding.cfm).

This funding opportunity employs separate discovery (R21) and development (R33) awarding mechanisms. The R21 application will emphasize the high risk, high innovation feasibility phase and potential impact. The development (R33) phase application must contain proof of feasibility of the proposed technology. In addition, the R33 application should contain an outline of a plan for further development of the technology towards its ultimate use and application.  This funding opportunity announcement does not solicit and will not accept combined R21/R33 applications. Under this funding opportunity announcement, applicants must submit either an R21 application or a fully developed R33 application, according the guidelines provided in Sections II and IVApplicants may submit more than one application, provided they are scientifically distinct.

Background

In order to meet the goal of eliminating death and suffering due to cancer, the NCI will continue to support the development of creative methods to understand, prevent, diagnose, and treat cancer. In the past several decades, basic discovery research has revealed that cancer is a complex disease involving myriad molecular and cellular processes, and that cancers arise as the result of the gradual accumulation of genetic changes in specific cells. Identifying which subset of the genes encoded within the human genome can contribute to the development of cancer remains a challenge. Even more challenging is the subsequent understanding of the proteins and other functional products encoded by these genes. The identification and characterization of these cancer genes and their associated gene products remains a high priority in cancer research. New technologies and approaches not only address specific questions in basic research and clinical practice but are also beneficial in uncovering and developing new directions and paradigms in cancer research. Taken together, these points highlight the leading and critical role that technological advances play throughout the NCI's mission.

The IMAT program was originally designed in 1999 with three objectives: to focus technology development on cancer, to solicit highly innovative technology development projects, and to accelerate the rate of maturation of meritorious technologies from feasibility through development of the technology. Through solicitation, outreach, and communication with the investigator community, the IMAT program has been successful in focusing a diverse spectrum of new and emerging technologies onto cancer applications. The program has focused on both the inception and development of cancer-related technologies. Some of the technologies originally generated with IMAT funding have gone on to support the acquisition of basic knowledge about cancer, which feeds the discovery pipeline. Other IMAT supported technologies have been applied to questions of clinical importance. Through the R21/33 Phased Innovation Award, originally invented and piloted by this program, the IMAT program has also been successful in accelerating meritorious technology development projects by minimizing the funding gap between feasibility and development phases. While the overall NCI technology program maintains these general goals, this initiative will be more focused on the R21 or high-risk portion of an investigator's scientific effort, with emphasis on the extent to which the idea is novel and innovative. Therefore, to reiterate, this funding opportunity announcement will not support the Phased Innovation Award (combined R21/R33), but only R21 alone and R33 alone applications, as outlined in Section II.1, Mechanisms of Support.

This funding opportunity is intended to support the development of molecular analysis tools that will not only allow for the more careful examination of the molecular basis and profiles of cancer, but will also provide the ability to identify the molecular characteristics of individuals that influence cancer development and prognosis. These tools will allow for an examination of genetic factors that influence an individual's risk of developing cancer or his/her ability to respond to damaging external agents such as radiation, carcinogens, and therapeutic regimes.

In order to fully understand cancer and define the molecular responses of the host to cancer, it will be critical not only to have knowledge at the DNA level, but also to have a complete understanding of the processing of genetic information in cellular function. Current discoveries indicate that alterations in many of the cellular processes, pathways, or networks may contribute to the genesis of cancer and that these alterations could be exploited for therapeutic or preventive intervention. Therefore, it is important to invoke technologies that can detect molecular changes in the cell without preconceived ideas about what changes would be the most valuable to monitor. In the discovery phase, the emphasis will be on technologies that can effectively scan, through highly multiplexed analysis, structural variations or functional changes in many or all members of the populations of DNA, RNA, or proteins present in cells. Current technologies for the multiplexed analysis of molecular species are at a stage where the greatest utility exists for the analysis of large numbers of relatively homogeneous cell populations that can be assayed in vitro. While many of the existing technologies have relatively sophisticated multiplexing capabilities in the assay format, none are comprehensive for any particular molecular species (DNA, RNA, or protein). Therefore, opportunities exist for further development to insure that the resulting technologies provide enhanced assay potential, adequate sensitivity and discrimination, robust data analysis tools, and easy adaptation to the basic, preclinical, and clinical research settings.

Objectives and Scope

The purpose of this funding opportunity announcement is to encourage applications from individuals and groups interested in developing novel technologies suitable for the molecular analysis of cancers and their host environment in support of basic, clinical, and epidemiological research. Technologies to support research in the following areas are considered to be appropriate. Examples given below are not intended to be all-inclusive, but they are illustrative of the types of capabilities that are of interest.

New tools that allow development of more complete molecular profiles of normal, pre-cancerous, and cancerous cells, as well as the process of carcinogenesis, are needed to support the basic discovery process. The same sort of technological approaches will also be needed to examine the tumor micro-environment, including stromal and vascular interactions. These tools will also allow more thorough examination of the variations that influence predisposition to cancer and individual variability in response to therapeutic and prevention agents. Of interest are technologies and data analysis tools for:

For all technologies proposed, it will be important to substantiate the ultimate value of and role for the technology in deciphering the molecular anatomy of cancer cells or analyzing the molecular profile of the individual. It is also important for applicants to discuss the ultimate potential for the transfer of ensuing technology to other laboratories or the clinic and, for more mature technologies, plans to ensure dissemination of the technology. 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). The R33 mechanism provides a second phase for the support of innovative exploratory and developmental research that may or may not have been initiated under the R21 mechanism. This funding opportunity announcement does not solicit and will not accept combined R21/R33 (phased innovation) applications. Except as otherwise stated in this funding opportunity announcement, awards will be administered under NIH grants policy as stated in the NIH Grants Policy Statement at http://grants.nih.gov/grants/ policy /nihgps_2003/NIHGPS_Part2.htm. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant.

In response to this funding opportunity, applicants may also submit an R33 application if feasibility can be documented, as described in Section IV.2, Content and Form of Application Submission. The proposed R33 project period may be up to a maximum of 3 years.

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, you should 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-07-006) and another that will utilize the Small Business Technology Transfer (STTR) R41 and R42 grant mechanisms (RFA-CA-07-007).

2. Funds Available

NCI intends to commit approximately $3,000,000 in FY 2007 to fund 10 to 15 new and/or competing continuation grants in response to this funding opportunity.

An R21 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. The request should be tailored to the needs of the project. For additional information, go to http://grants.nih.gov/grants/funding/r21.htm. An R33 applicant may request a project period of up to 3 years with a budget appropriate for the science proposed. 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, especially in the case of R33 awards, will also vary.

Although the financial plans of the NCI provide support for this program, awards pursuant to this funding opportunity announcement 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-05-004.

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/grants/policy/nihgps_2003/nihgps_Part2.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. 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:

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 or R33.

2. Description:

As part of the description, identify concisely 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 or 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). All budgets should include a written justification.  4. Research Plan:

Item a: Specific Aims

Applicants must present specific aims that are 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. For both the R21 and R33 phases, 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 within the specific aims section are essential. Studies pursuing comprehensive analysis in particular may result in hypothesis generation, rather than hypothesis testing.

Item b: Background and Significance

Elaborate on the innovative nature of the proposed research. Applicants must explain how the technology development proposed in this project is a significant improvement over existing state-of-the art 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.

Specific Instructions for Preparation of an 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 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 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. Several examples of quantitative milestones follow:

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 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.

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 application.

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

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 courier delivery)
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 dates described above (Section IV.3.A.). If an application is received after the relevant date, it will be returned to the applicant without review. Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by the NCI. Incomplete and non-responsive applications will not be reviewed.

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 this funding opportunity, it is to be prepared as a NEW application. That is, the application 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/grants/policy/nihgps_2003/NIHGPS_Part6.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 and do not need to be included 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

Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the NCI. Incomplete and/or non-responsive applications will not be reviewed.

Applications that are complete and responsive to the funding opportunity 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 items will be considered in the determination of scientific merit and the priority score:

Milestones (R21 applications only): the adequacy of the proposed quantitative milestones as described under Section IV.2. above.

Feasibility (R33 applications only): R33 applicants must present detailed preliminary data in support of the feasibility of the proposed technology or approach that is proposed for development. They will also have the added burden of demonstrating the innovation of the particular technology or approach. Feasibility means that some preliminary experiments have been performed and that sufficient technical data exist to support proof of principle of the technology/hypothesis.

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.

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

2.B. Additional Review Considerations

Budget: 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.

Multidisciplinary review: The review panel will be drawn from a wide range of expertise, so the applications should be written accordingly, with a minimum of field-specific jargon.  All important concepts should be carefully defined.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing). 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/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/grants/policy/nihgps_2003/NIHGPS_part4.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/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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 delivery)
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/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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