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: Advanced Proteomic Platforms and Computational Sciences for the NCI Clinical Proteomic Technologies Initiative (R01, R21, R21/R33)

Announcement Type
New

Request For Applications (RFA) Number: RFA-CA-07-005

Catalog of Federal Domestic Assistance Number(s)
93.392, 93.393, 93.394, 93.395, 93.396

Key Dates
Release Date: December 8, 2005
Letters of Intent Receipt Date(s): March 11, 2006
Application Receipt Dates(s): April 11, 2006
Peer Review Date(s): June/July 2006
Council Review Date(s): September/October 2006
Earliest Anticipated Start Date: September 26, 2006
Additional Information To-Be-Available Date (URL Activation Date): Not applicable.
Expiration Date: April 12, 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

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 or Matching
  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 and Times
    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
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
  3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
  1. Award Notices
  2. Administrative and National Policy Requirements
  3. Reporting

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose. The NCI invites applications for research project grants to support innovative research and development in critical areas of proteomic technology to be applied for the measurement of proteins and peptides of interest in clinical cancer studies  This funding opportunity sets out to establish the Advanced Platforms, Data Analysis Methods, and Computational Sciences components of the NCI Clinical Proteomic Technologies Initiative for Cancer This funding opportunity supports two focus areas for protein measurement technology and application in cancer research. The first area encompasses the development of innovative technology for protein and peptide detection, recognition, measurement, and characterization in biological fluids that will overcome current barriers in protein/peptide feature detection, identification, quantification, and validation. A major technical barrier of interest to be addressed by research supported through this solicitation is the enhancement of throughput rates for measurement and data analysis. The second focus area supports computational, statistical, and mathematical approaches for the analysis, processing, and facile exchange of large proteomic data sets.  Advancing the technological and analytical capabilities in proteomic research will allow the research community to better characterize and understand the differences between the normal and diseased human proteome and to develop diagnostic and treatment procedures based on these distinctions.

Background.  The NCI recognizes the significant challenges in protein and peptide discovery and analysis and has committed approximately $10 million in FY 2006 to address several of these challenges through this announcement. Current proteomic technology approaches are insufficient to reliably and reproducibly discover, identify, and quantify peptides and proteins of clinical significance for cancer from complex mixtures such as tissues, urine, sputa, plasma, sera, or other blood products. Despite advances in protein and peptide labeling, separation, detection, measurement, and characterization, many challenges remain in applying these platforms to clinical applications.

Technology platforms such as mass spectrometry and protein microarrays have shown potential to interrogate the proteome and identify unique and clinically relevant proteins/peptides in complex biological mixtures such as tissues or plasma. However, deployment of these platforms and others to translational research and clinical application has been hampered by limitations including the difficulties in isolating and identifying low abundance or low molecular weight peptides/proteins. In addition, application of these technologies to measure proteins and peptides in biological samples yields large datasets that are not readily comparable across laboratories and platforms and often lack the methodological and statistical rigor needed for assessing reproducibility and comparability of data between laboratories. Furthermore, the lack of standardization in sample preparation, statistical analysis, and data processing limits comparisons of data.

The challenges of proteomic technology design and application stem from the complexity of protein dynamics and the vast amount of information required for characterizing the proteome. Innovative design and engineering strategies will be needed to overcome the current challenges facing proteomic research. Advanced technology improvements and developments can be made in sample preparation and storage, sample fractionation, automation, microfluidics, mass spectrometry, informatics  as well as in affinity capture methods, including antibodies, aptamers, and protein arrays. Advanced data analysis methodologies and informatics algorithms are needed to address data preprocessing and management, peptide/protein identification, relative and direct quantification, elution time normalization and peak alignment, signal processing, the extraction of diagnostic “molecular fingerprints,” and peptide/protein sequencing within and among large data sets. This will require well developed and characterized ontologies and bioinformatic annotations for use across the scientific community.

Advanced computational tools, data mining algorithms, and emerging data exchange format standards will facilitate the management, archiving, and electronic exchange and analysis of spectral data. Several proteomic data formats are currently used for data exchange and data representation, including mzXML (XML format for MS) and the Human Proteome Organization (HUPO) data standards, such as mzData (XML format for MS), mzIdent (XML format for identification), and the Minimum Information About Proteomics Experiment (MIAPE). Standardized proteomics formats and algorithms can be incorporated into the software and this would allow scientists to easily obtain and analyze proteomic data across various data repositories.

The technologies and methodologies developed through these advancements will be incorporated into other Clinical Proteomic Technologies Initiative for Cancer programs and will be available to the scientific community through the Cancer Biomedical Informatics Grid (caBIG) as described below.

This initiative addresses NCI’s mission to eliminate the suffering and death due to cancer by developing and disseminating the technology platforms and data analysis methodologies needed for the systematic understanding of cancer proteomics, which will thereby enable the field of proteomics to have a clinical impact in cancer diagnostics and treatment.

Objectives. This funding opportunity aims to support innovative platform technology development, as well as novel data analysis methods and computational approaches, to support the identification and measurement of peptides and proteins of relevance to cancer processes from clinical cancer specimens. This funding opportunity will not support research addressing discovery of (or mechanistic studies about) proteins and peptides (biomarker discovery), clinical correlative studies of biomarkers, hypothesis-based studies for the understanding of proteins related to biological processes of cancer, or studies focused exclusively on post-translational modification of proteins. Programs funded through this funding opportunity should be designed to overcome technological barriers integral to the measurement, analysis, and comparison of clinical proteomic data from clinical cancer specimens. While the goals of the Clinical Proteomic Technologies Initiative for Cancer focus primarily on the proteomics of readily available biological fluids in humans, such as tissues, urine, sputa, plasma, sera, or other blood products, applicants for this funding opportunity should not feel bound by these restrictions.  However, applicants should develop research plans for use on human or mouse biological samples.  Since clinical cancer samples are a highly valuable and non-renewable resource, applicants are encouraged to use mouse models of cancer if the models will be of assistance in developing protocols or pilot studies.  However, each applicant is required to have well developed plans for incorporation and application of the research technology on human clinical cancer specimens.  Due to the limitations of two-dimensional gel electrophoresis in throughput and in identifying low abundance proteins, applicants applying for the advanced proteomic platforms should avoid including two-dimensional gel electrophoresis as a component of their technology platforms and focus on developing technologies based on mass spectrometry, microarray analysis, or other higher-order technologies capable of effectively separating, resolving, and recognizing peptides/proteins of clinical significance.

The following list provides descriptive examples of technology subject areas for applicants to consider.  Applicants are encouraged to develop platforms encompassing one or more of these areas:

This announcement does not intend to be proscriptive in developing these platforms.  Instead, it intends for the applicants to design high throughput and innovative technologies and computational algorithms capable of overcoming current challenges in clinical proteomics. However, applicants should develop research plans for use on human or mouse biological samples.  Current technology platforms have various performance endpoints that can be improved, including dynamic range, mass accuracy, sample throughput, peptide/protein identification, quantification, reproducibility, and cost. Applicants should develop concepts that explore prototypes that have capabilities to increase throughput and detection capabilities by an order of magnitude relative to currently available methods and platforms.

This initiative encourages designs and algorithms that will be open source and shared within the scientific community for broad application.  To maximize the impact of this program across scientific and research organizations, applicants should intend for analytical algorithms to be integrated into a centralized pipeline hosted by the Cancer Biomedical Informatics Grid (caBIG).  As such, the format and tools for data analysis will need to be compatible through caBIG (http://cabig.nci.nih.gov) listed below.

caBIG Compatibility Requirements for datasets.  caBIG is a voluntary network or ‘grid’ of individuals and institutions that are working to create both a better environment for the sharing of cancer research data and software tools for speeding the delivery of innovative approaches for the prevention, detection, and treatment of cancer.  caBIG-compliant programs will be incorporated into a federated open source/open access network formulated to involve public observation and contribution from the participating scientific community.  Applicants are encouraged to develop the proteomic and analysis platforms to be compliant with the guidelines set forth by caBIG.  The incorporation of caBIG guidelines allows compatibility among software and analytical systems so that data may be exchanged across a network of voluntary participating scientists and institutions.  caBIG has developed four increasing levels of compliance and interoperability (i.e., Legacy, Bronze, Silver, and Gold) based on the requirements met by the analysis systems.  caBIG requirements cover four main areas for compatibility: data format and programming/messaging interfaces, common data elements, information models, and vocabularies and ontologies.  The degree of caBIG compliance for a meritorious application will be determined by NCI program staff (after peer review, but before award) through coordination and consultation with staff of the National Cancer Institute’s Center for Bioinformatics.  More information on caBIG compatibility is available at https://cabig.nci.nih.gov/guidelines_documentation/caBIGCompatGuideRev2_final.pdf.

Through interactions with these NCI resources, as well as other Federal and private sector groups, it is expected that this program and its initiatives will catalyze targeted discovery and development efforts and spawn new partnerships with the private sector. In this regard, the NCI recognizes that significant issues exist concerning the intellectual property rights with respect to patentable inventions and algorithms developed within the program.  Within this context, however, it is the NCI’s intention that inventors will work with the NCI to exercise any intellectual property rights retained on inventions developed as part of the program in a way that will promote wide accessibility to and further development of the resources and analysis tools that are generated.

The Clinical Proteomic Technologies Initiative for Cancer.  Many technologies have been used in the field of proteomics, including mass spectrometry (MS), two-dimensional gel electrophoresis, enzyme-linked immunosorbent assay (ELISA), and protein microarray.  The NCI Clinical Proteomics Technologies Initiative is an integrated approach to develop and enhance proteomic technology measurement capabilities to support the discovery of clinically relevant peptides and proteins and measure them as reliable indicators of biological cancer processes.  The NCI recognizes that there are immense opportunities for using proteomic technologies to solve mission-critical problems in cancer research.  The approaches adopted by the Clinical Proteomic Technologies Initiative are founded on the premise that clinically relevant and cancer-specific peptides and proteins exist in readily accessible body fluids (e.g., tissues, urine, sputa, plasma, sera, or other blood products), that successful identification of individual and/or panels of such peptides and proteins will help achieve high specificity and sensitivity in early detection and diagnosis of cancer, that current technologies are capable of discovering these proteins and peptides, and that the current applications of this technology can be improved.  Factors such as the dynamics of protein concentration, protein isoforms, and post-translational modifications challenge the research community to advance the technological capabilities of current proteomic technologies and to develop clinically feasible platforms that increase the range, accuracy, specificity, and sensitivity of these platforms in a reproducible manner.

The Clinical Proteomic Technologies Initiative for Cancer will:

Program Coordination.  The Clinical Proteomics Technologies Initiative for Cancer will establish a Program Coordinating Committee composed of NCI staff and extramural scientists to oversee the development and integration of the programs.  The main activities of the Program Coordinating Committee are as follows:

Integration with NCI Resources. The Clinical Proteomic Technology Initiative for Cancer and associated programs will integrate into a network of extant NCI resources, leveraging the strengths of existing programs to develop a national proteomics research infrastructure. Examples of these resources and their specific areas of relevance include the following:

Through interactions with these NCI resources, as well as with other Federal and private sector groups, it is expected that this Initiative will catalyze targeted discovery and development efforts and spawn new partnerships with the private sector. Applicants are encouraged to collaborate with private sector technology development entities in developing approaches to overcome current barriers and facilitate technology dissemination.

Plan for Sharing Research Data.  The NCI intends that databases, proteomic standards, and reference sets developed through the Clinical Proteomic Technology Initiative be publicly available.  Through these efforts the scientific community will have open and equal access to common reagents and data to facilitate discovery and cross validation of studies.  The NCI has already funded two mouse cancer proteomic consortia that have developed and optimized processes in sample acquisition, preparation, and analysis. While the data collected must be publicly available, 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 should briefly describe 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).  Applicants are encouraged to develop publicly available data and materials in a manner compliant with caBIG.  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.

All applicants are expected to include a plan for sharing research data in their application.  The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing.  All investigators responding to this funding opportunity should include a description of how final research data will be shared and pledge to work with the caBIG community to integrate the data in a manner compliant with caBIG.

Sharing Research Resources.  NIH policy requires that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication.  See the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131. Investigators responding to this funding opportunity are expected to include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

Intellectual Property Management Plan. Guidance for Preparation of Research Tools Sharing Plan and Intellectual Property Plan.  Restricted availability of unique research resources, upon which further studies are dependent, can impede the advancement of research. The NIH is interested in ensuring that the research resources developed through this Initiative also become readily available to the broader research community in a timely manner for further research, development, and application, in the expectation that this will lead to products and knowledge of benefit to the public health.

Investigators conducting biomedical research frequently develop unique research resources. The policy of the NIH is to make available to the public the results and accomplishments of the activities that it funds. To ensure that research resources are made accessible to the broader biomedical community, NIH expects applicants who respond to this funding opportunity to submit a plan for: (1) sharing the research resources generated through any grants awarded (e.g., human biospecimens and novel cancer biomarkers); and (2) addressing how they will exercise intellectual property rights, should any be generated through an award, while making such research resources available to the broader scientific community consistent with this initiative. Therefore, such research resources sharing and intellectual property management plans would make unique research resources readily available for research purposes to qualified individuals within the scientific community in accordance with the NIH Grants Policy Statement (http://grants.nih.gov/grants/policy/) and the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources: Final Notice, December 1999 (http://ott.od.nih.gov/NewPages/64FR72090.pdf) (“NIH Research Tools Guidelines Policy”). These documents also: (1) define terms, parties, and responsibilities; (2) prescribe the order of disposition of rights and a chronology of reporting requirements; and (3) delineate the basis for and extent of government actions to retain rights. Patent rights clauses may be found at 37 CFR Part 401.14 and are accessible from the Interagency Edison web page (http://www.iedison.gov); see also 35 USC § 210(c); Executive Order 12591, 52 FR 13414 (Apr. 10, 1987); and Memorandum on Government Patent Policy (Feb. 18, 1983). If applicants plan to collaborate with third parties, the research tools sharing plan would need to address how such collaborations would not restrict their ability to share research materials produced with NIH funding. 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 broadly available on reasonable terms. In the development of any research resources sharing and intellectual property management plans, applicants should confer with their institutions' office(s) responsible for handling technology transfer-related matters and/or sponsored research. If applicants or their representatives require additional guidance in preparing such plans, they are encouraged to make further inquiries to the appropriate contacts listed above for such matters. Further, applicants may wish to independently research and review examples of approaches considered by other institutions such as those described on the NCI Technology Transfer Branch web site (http://ttc.nci.nih.gov/intellectualproperty/). The foregoing guidance is provided by way of example to assist applicants in preparing the expected research resources sharing and intellectual property management plans in a manner that encourages partnerships with industry. While these approaches will likely suit most situations, these approaches are not exclusive and applicants should feel free to submit alternative versions for consideration.

The majority of transfers to not-for-profit entities should be implemented under terms no more restrictive than the Uniform Biological Materials Transfer Agreement (UBMTA) (http://ott.od.nih.gov/NewPages/UBMTA.pdf). In particular, recipients are expected to use the Simple Letter Agreement (SLA) provided at http://ott.od.nih.gov/NewPages/SimplLtrAgr.pdf , or another document with no more restrictive terms, to readily transfer unpatented tools developed with NIH funds to other recipients for use in NIH-funded projects. If the materials are patented or licensed to an exclusive provider, other arrangements may be used, but commercialization option rights, royalty reach-through rights, or product reach-through rights back to the provider are inappropriate. Similarly, when for-profit entities are seeking access to NCI-funded tools for internal use purposes, recipients should ensure that the tools are transferred with the fewest encumbrances possible. The Simple Letter Agreement (SLA) may be expanded for use in transferring tools to for-profit entities, or simple internal use license agreements with execution or annual use fees may be appropriate.

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

Section II. Award Information

1. Mechanism(s) of Support

This funding opportunity will use the R21 Exploratory Development award, the R21/R33 Phased Innovation award, and the R01 award mechanisms.  Applications involving the R33 mechanism will not be accepted.

As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses just-in-time concepts. It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are 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.

2. Funds Available

The NCI intends to commit approximately $10 million in FY 2006 to fund approximately 10 new grants in response to this funding opportunity.

Applicants applying for advanced proteomic technology platform development will use the R21 Exploratory/ Developmental Award or the NIH R21/R33 Phased Innovation Award. For the R21 Exploratory/ Developmental Award, an applicant may request a project period of up to 2 years and a budget for direct costs of up to $275,000 in keeping with standard R21 mechanism guidelines. Applicants using the R21/R33 Phased Innovation Award may request a project period of up to 3 years for an R33 and no more than 2 years for the R21 portion, for a total of 4 years. Applications for the R33 award alone will not be accepted. Projects in technology development using the R21 or combined R21/R33 mechanism must include quantitative performance “milestones” that are directly related to the specific aims (see Section IV.2).

Applicants applying for grants that support data analysis methods and computational sciences will use the R01 award mechanism.

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-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 his/her institution to develop an application for support. Individuals from under-represented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.

2. Cost Sharing or Matching

Cost sharing is not required for eligibility.

The most current Grants Policy Statement can be found 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 must 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 current PHS 398 research grant application instructions and forms. Applications must have a 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.

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.

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 successful accomplishment of the specific aims 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 items a-d text of the research plan 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 might include, but are not limited to, the following examples:

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

Specific Instructions for Preparing the Combined R21/R33 Phased Innovation and R01 Award Applications

The combined R21/R33 application offers two advantages over the regular application process, which are:

Single submission and evaluation of both the R21 and the R33 as one application; and

Minimal or no funding gap between R21 and R33.

The R21/R33 application must include 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. Milestones should be well described, quantitative, and scientifically justified (see examples in the previous section). 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. The release of R33 funds will be based on successful completion of negotiated scientific milestones, program priorities, and on the availability of funds. The expedited review may result in additional negotiations of award.

The R21/R33 Phased Innovation Award 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 PHS 398 form Table of Contents 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 composite a-d text (i.e., items a-d and milestones for the R21 and items a-d for the R33 phase must all be contained within the 25-page limit).

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, a Phased Innovation Award 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 the R21 phase are critical. The presentation of milestones that are not sufficiently scientifically rigorous to be valid for assessing progress in the R21 phase will reflect upon the scientific judgment of the applicant.

Applicants for R01 grants must present specific aims that he/she considers to be scientifically appropriate for the purposes of the project.  For R01 applications that are submitted in response to this RFA, research that develops new fundamental understanding, technologies, or tools will require the application of principles of fields such as computer science, mathematics, and bioinformatics.  Clear statements of these underlying principles within this section are essential.

1. Face Page of the application:

Item 2. Check the box marked YES and type the number and title of this request for applications. Also indicate if the application is an R21, an R21/R33, or an R01.

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

For the R21 or 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 for indirect costs to subcontracts to the project. Insert the first year of R21 Direct Costs 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 Direct Costs in item 8a.

2. Page 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 state-of-the-art in proteomics technologies 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.

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 is to support the development of advanced proteomic technologies and computational sciences, hypothesis testing per se may not be the driving force in developing such an application and, therefore, may not be applicable. Furthermore, for R21 and R21/R33 grant applications, preliminary data are not required, although they should be included when available. 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.

Preliminary data, if available, is encouraged for an R01 application.

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.  Descriptions should include the following:

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., and the adherence to this requirement will be determined by NCI program staff before peer review of the application and/or prior to any grant award.

3. Submission Dates and Times
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

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

Letters of Intent Receipt Date(s): March 11, 2006
Application Receipt Dates(s): April 11, 2006
Peer Review Date(s): June/July 2006
Council Review Date(s): September/October 2006
Earliest Anticipated Start Date: September 26, 2006

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.
Director, Office of Technology and Industrial Relations
Office of the Director
National Cancer Institute
Building 31, Room 10A-52, MSC 2580
31 Center Drive
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 research grant applications found in the PHS 398 instructions for preparing a research grant application. 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 material 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 date 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 evaluated for completeness by the CSR and responsiveness by the NCI. Incomplete and non-responsive applications will not be reviewed. If the application is not responsive to the funding opportunity, NIH staff may contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next appropriate NIH review cycle.

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.

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.

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

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, R21, R21/R33 phased innovation, and R01 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 R21, R21/R33, or R01 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

R21 and R01 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.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

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 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 continue to be considered in the determination of scientific merit and the priority score:

Milestones (R21 applications and the R21 phase of R21/R33 applications): the adequacy of the proposed quantitative milestones (as described under Section IV.2.) above as well as how those milestones provide proof-of-principle for a proposed or future R33 phase.

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.


Sharing Resources: 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.  See Section V.2.D.

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: The reasonableness of the data sharing plan or the rationale for limited sharing or not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

2.D. Sharing Research Resources

NIH policy requires that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps/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, and financial or grants management issues:

1. Scientific/Research Contacts:

Gregory J. Downing, D.O., Ph.D.
Director, Office of Technology and Industrial Relations
Office of the Director
National Cancer Institute
Building 31, Room 10A-52, MSC 2580
31 Center Drive
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:

Ms. Kathryn Dunn
Grants Management Specialist
National Cancer Institute
Grants Administration Branch
Fairview Center, Room 300
1003 West 7th Street
Frederick, MD  21701-4106
Telephone:  301-846-6829
E-mail: dunnkath@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 institutional review board (IRB) rules, as well as local, State, and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement 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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