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.cancer.gov)

Title: Alliance of Glycobiologists for Detection of Cancer and Cancer Risk (U01)

Announcement Type
New

Update:

Request For Applications (RFA) Number: RFA-CA-07-020

Catalog of Federal Domestic Assistance Number(s)
93.394

Key Dates
Release Date:  June 16, 2006
Letters of Intent Receipt Date(s):  July 23, 2006
Application Receipt Date(s): August 23, 2006
Peer Review Date(s): September/October 2006
Council Review Date(s): February 2007
Earliest Anticipated Start Date: March 2007
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: August 24, 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
    A. Cooperative Agreement Terms and Conditions of Award
       1. Principal Investigator Rights and Responsibilities
       2. NIH Responsibilities
       3. Collaborative Responsibilities
       4. Arbitration Process
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 solicits applications for cooperative agreements supporting innovative research in the discovery and development of diagnostic cancer biomarkers based specifically on complex carbohydrate structures.  This funding opportunity will establish one component of a new trans-NIH consortium entitled the Alliance of Glycobiologists for Detection of Cancer and Cancer Risk. Several Tumor Glycome Laboratories  funded through this initiative represent the key component of the Alliance. The intended roles of the Tumor Glycome Laboratories are: (a) to identify glycan-based cancer-related abnormalities with the potential to serve as cancer biomarkers; (b) to evaluate the performance of such biomarker candidates in case versus control clinical specimens in terms of sensitivity and specificity; and (c) to ultimately lead the translational efforts to test the most promising biomarker candidates in clinical validation studies. The research needs of Tumor Glycome Laboratories will be supported by additional components of the Alliance (which comprise specialized consortia described in the next paragraph). The translational emphasis of this biomarker research effort is a high priority of the Alliance and the multidisciplinary support provided through the different Alliance components is designed to facilitate maturation of glycan cancer biomarkers for clinical testing. By reaching into the underexplored field of glycomics, this FOA complements the other major NCI-funded efforts aimed at cancer biomarker discovery that are based on the cancer-specific genomic, transcriptomic, and proteomic aberrations.

Interactive Structure of the Alliance

The Alliance of Glycobiologists for Detection of Cancer and Cancer Risk will be comprised of several components. The laboratories funded in response to this RFA will constitute glycan biomarker discovery/development laboratories termed Tumor Glycome Laboratories. The unique needs of Tumor Glycome Laboratories for technologies embracing carbohydrate chemistry will likely necessitate access to special reagents or analytical services available from partnering laboratories in this Alliance. The Consortium for Functional Glycomics (CFG) (http://www.functionalglycomics.org) funded by the National Institute of General Medical Sciences (NIGMS) and several Glycomics and Glycotechnology Resource Centers (http://www.ncrr.nih.gov/Glycomics) supported by the National Center for Research Resources (NCRR) are available to participate as partners in this Alliance. Tumor Glycome Laboratories may request support from these resources to facilitate their own research activities. Examples include obtaining technical assistance with analyzing glycan profiles, requiring access to and assistance with glycan arrays or glyco-gene arrays, or obtaining specific glycomic reagents and products. All applicants are encouraged to consider the resource capabilities of the CFG and NCRR glycomic centers in planning their research proposals.

The Early Detection Research Network (EDRN)(http://edrn.nci.nih.gov/) funded by NCI is a consortium to promote clinical validation of cancer biomarkers for diagnosis, early detection, and cancer risk or recurrence. As the development of promising glycan biomarkers by Tumor Glycome Laboratories matures, they will be considered for clinical validation studies. The EDRN will function in the Alliance to facilitate validation of glycomic cancer biomarkers in several ways. Assistance with study design and statistical analysis is provided by the EDRN Data Management and Coordinating Center. Clinical Epidemiology and Validation Centers may assist with patient accrual and collection of clinical specimens for validation studies. These centers may also offer certain Tumor Glycome Laboratories limited access to clinical specimens during their discovery/developmental phases of biomarker investigation. Biomarker Reference Laboratories can participate in the development and standardization of specific tests and offer cross-laboratory confirmation of test results.

The activities within the Alliance will be integrated by its governing body termed the Coordination Unit (CU), composed of Chairs and Co-Chairs of the EDRN and CFG Steering Committees or their designees, and the PIs from each Tumor Glycome Laboratory. Program staff from relevant NIH programs (NCI, NIGMS, and NCRR) will also serve on the CU. The roles of the CU will be to coordinate activities among all components of the Alliance, assess progress made in biomarker development in consideration for validation studies, and provide oversight and management for achieving the objectives of the Alliance. Additional details concerning the governance of the Alliance with the CU are provided under Section VI.2.A.3, Collaborative Responsibilities.

Scientific Background

Cancer is a disease characterized by the progressive accumulation of mutations and chromosomal aberrations leading to altered growth properties and oncogenic transformation of cells. Commensurate with this transformation is a marked change in gene expression. Accordingly, cancer-specific changes (aberrations) at the genomic, transcriptomic, and proteomic levels have propelled the majority of cancer biomarker studies thus far; however, there are other aspects of cellular biochemistry in which cancer cells differ from their normal counterparts. Complex carbohydrates represent one such set of molecular features that has not been rigorously explored, yet should be exploited as another class of potential diagnostic or prognostic cancer biomarkers.

The biosynthetic schemes of glycans found in glycoproteins, glycolipids, and proteoglycans are well characterized. The structures of all oligosaccharides synthesized by a cell result from the concerted action of a series of highly specific glycosyltransferases, glycosidases, and modification enzymes (sulfotransferases, acetylases, etc.) localized in the endoplasmic reticulum and the Golgi apparatus. Glycan synthesis proceeds by the sequential addition/removal of individual saccharide units. Abnormal expression of even a single enzyme participating in this process may distort the subsequent steps in this “assembly line” and give rise to aberrant oligosaccharide structures. Given the altered transcriptomic profiles of cancer cells, the glycome synthetic machinery is frequently modified by oncogenic transformation leading to the accumulation of aberrant products. One of the well-known manifestations of this phenomenon is the presence of abnormal or unusual glycan moieties in various biomolecules on the surface of tumor cells, as well as in secreted glycoproteins proteins.

Numerous studies comparing normal and tumor cells have observed that changes in glycan structures correlate with oncogenic transformation. In fact, many prominent and intensely-investigated tumor-associated antigens are glycolipids or abnormally glycosylated glycoproteins. Still, the undeniable potential of the abnormally glycosylated molecules to serve as cancer biomarkers remains unrealized. Despite the discovery (many years ago) and rather extensive characterization of important and ubiquitous tumor-associated antigens such as various Lewis structures, polysialic acid chains, and glycosphingolipids GD2, GM2 and Globo H, the practical use of such abnormalities for cancer diagnosis is woefully in its infancy.

This situation stems mainly from the technical challenges encountered in analyzing complex carbohydrate structures. In contrast to the template-driven nucleic acids and protein syntheses that result in linear polymers, the biosynthesis of glycans is a non-template process that is capable of generating very large numbers of different branched structures from the nine monosaccharides prevailing in the cell. Consequently, carbohydrate chemistry is very complex and glycomic technologies require a level of sophistication that in the past was not readily attainable. Significant advances, however, have been made in recent years to the point that effective systematic studies of glycan-based biomarkers are now feasible.

Despite the mentioned technical challenges, the field of glycomics offers several benefits as a source of potential cancer biomarkers. Whereas protein biomarkers are frequently marginal or low in abundance, distinctive cellular glycan structures are typically synthesized in fairly substantial amounts. A single glycoprotein molecule often contains multiple copies of specific glycan structures. In addition, the same glycan structures are usually present on a multitude of glycoproteins.  It is likely that the performance of glycoprotein biomarkers will be greatly improved when analysis at the protein level is combined with a comprehensive analysis of their associated glycan moieties. However, many currently used biomarkers (such as prostate specific antigen, CA125, and carcinoembryonic antigen), are monitored solely based on protein levels, with no regard for the status of the posttranslational modifications. Extracellular exposure to the immune system of aberrant glycans of tumor cells is inherent in the cell surface localization of most glycoproteins, proteoglycans, and glycolipids. Secreted glycoproteins are also usually glycosylated where these molecules might readily be identified in body fluids typically amenable for clinical testing.  This initiative will therefore seek to take advantage of these unique facets of glycobiology to develop novel diagnostic tests for cancer detection.

Research Objectives of the Alliance

The importance of early cancer detection is highlighted by the recognition that cancer patients show much improved survival and quality of life when the disease is diagnosed and treated at early stages. Accordingly, early detection, prevention and prediction of cancer are among areas of strategic focus of the NCI. The undeniable, yet underexploited, potential that glycomics offers for early cancer detection provides the scientific basis for this initiative. The chief objective of this RFA is to promote research that will bring glycan-based biomarkers to the forefront in our efforts to diagnose cancer at early stages. It is possible that the same biomarkers may serve other purposes such as being markers for cancer risk, prognosis, or monitoring of recurrence and response to therapy. While therapeutic strategies may also unfold from these investigations, the intention of the current initiative is focused specifically on cancer diagnosis and early detection. Applications focused on therapeutic aspects will not be considered responsive to this RFA.  

This FOA solicits investigations that would explore the premise that alterations in glycan profiles, which are commonly associated with neoplastic transformation, can be exploited to devise diagnostic clinical tests for cancer. Remodeling of the glycome might encompass distinct structural modifications giving rise to abnormal glycan structures and/or pronounced shifts in the relative abundances of normal glycans, thereby exhibiting an atypical glycomic signature. Since glycome profiles are tissue-specific, it is likely that different tumor types may be distinguishable by salient features of their glycan profiles. Other potential diagnostic biomarkers may be derived from certain host responses directly related to tumor glycomic alterations, such as an altered status of carbohydrate binding proteins or abnormal autoimmune responses to carbohydrate antigens.

The most important objective of this RFA is to support the discovery, development, and clinical validation of cancer biomarkers based on glycan structures. In the development and validation process, biomarkers will need to be assessed according to their performance characteristics in terms of sensitivity, specificity, and positive/negative predictive values for diagnosis or detection of cancer from clinical specimens. The clinical imperative of this translational research emphasizes the priority the NCI places on quickly bringing promising diagnostic leads to fruition for the medical community.

Scope of Applications

This initiative seeks to promote the discovery of glycan-based cancer biomarkers by supporting multiple laboratories with different approaches and technologies. The following list outlines the strategies that can be used to undertake biomarker discovery and development, but this list is by no means inclusive. All research proposals involving innovative strategies that seek to attain the primary objectives listed above are encouraged in response to this RFA. Possible research strategies to address cancer biomarkers of glycomic nature may include,but are not limited to:

General Requirement for All Studies. Projects proposed in response to this RFA must be consistent with the translational emphasis of this initiative. Therefore, experimental design must include plans to verify the utility of the proposed approach(es) for clinical testing of cancer biomarkers to allow for transition from the biomarker discovery phase to the development and validation phases. This transition requires demonstration of a significant correlation between the status of the proposed biomarker and disease status using appropriate specimens derived from cancer patients and disease-free individuals. All projects proposed under this RFA must conform to this model.

Collaborative Efforts

Research collaborations with other laboratories are encouraged. Interaction of two or more laboratories responding to this RFA may facilitate an integrated approach to specific aspects of the biomarker discovery/development process. In such a situation, projects proposed by each of the collaborating laboratories would be expected to complement those taken by partner laboratories. Still, since each such project will be individually assessed for its scientific merit and independently scored, they should use different approaches and must be independently viable and complete.

Applicants responding to this glycomics-based initiative may also benefit from inter-programmatic interaction with laboratories involved in the NCI’s Clinical Proteomics Technology Initiative (http://proteomics.cancer.gov/) .The latter program will receive its initial funding several months prior to the funding of this Alliance. We encourage investigators to keep abreast of the developments with the Clinical Proteomics Technology Initiative and seek/explore areas in which both programs can mutually benefit from a collaboration among participating laboratories. In particular, such interactions may encompass glycopeptide capture, mass spectrometric analysis of glycoproteins/glycopeptides, or capture of glycoproteins on lectin or antibody arrays.

Potential Applications of Glycomic Biomarkers for Malignancies in the Context of HIV Infection.

Beyond the scope of this RFA and depending upon the availability of funds, supplemental funding may be possible at a later date to support biomarker studies on AIDS cohorts.  The NCI AIDS Malignancy Program (http://www.cancer.gov/dctd/aids) has particular interest in investigators who might seek to complement their research on glycomic cancer biomarkers with studies on HIV-positive individuals who develop cancer. Effective therapies to treat AIDS have led to prolonged survival of HIV-infected patients. While antiretroviral therapy has diminished risk to the development of cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma, the likelihood of developing these cancers still remains higher in this population than in the non-infected population. Additionally, preliminary data suggests that this population is now exhibiting a significant risk of developing non-AIDS defining malignancies such as anal cancer, Hodgkin’s lymphoma, and lung cancer. The Office of the AIDS Malignancy Program supports the AIDS and Cancer Specimen Resource (http://acsr.ucsf.edu/) which provides AIDS malignancy biospecimens to qualified investigators. Other repositories are supported by NIH programs such as the Multicenter AIDS Cohort Study  (http://www.statepi.jhsph.edu/macs/macs.html) and Women’s Interagency HIV Study (https://statepiaps.jhsph.edu/wihs/). These programs have developed extensive repositories of prospectively and longitudinally collected patient samples. The AIDS Malignancy Program will assist interested qualified investigators in providing access to these repositories of collected specimens from HIV-positive subjects.

Applicants with an interest in extending their research projects to the AIDS area are encouraged to contact the Program Director below for additional information:

Geraldina Dominguez, Ph.D.
AIDS Malignancy Program
National Cancer Institute
6116 Executive Boulevard, Suite 505, MSC 8318
Bethesda, MD 20892-8318
Telephone: (301) 496-3204
E-mail: domingug@mail.nih.gov

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 NIH Cooperative Agreement U01 award mechanism.

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

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

The NIH U01 is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator (PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the PI, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". Plans beyond the current funding period have not been defined.

2. Funds Available

The  NCI intends to commit approximately $2.5 million dollars in Fiscal Year 2007 to fund five to six new cooperative agreements under this RFA. An applicant may request a project period of up to 5 years and a budget for direct costs up to $300,000 per year. An additional $500,000 of total costs in the first year and $700,000 annually in subsequent years will be allocated as “Collaborative Resource Funds” for special research needs of the Alliance. The intended uses of these funds are described in greater detail in Section VI. 2.A.3 under Collaborative Resource Funds. Applicants for this RFA cannot and must not apply for Collaborative Resource Funds (CR Funds) in their U01 applications.

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 (F&A) 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 support.

2. Cost Sharing or Matching

Cost sharing is not required for eligibility.

The most current NIH 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

An applicant may submit only one proposal as a PI in response to this funding opportunity.

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 301-451-0088.

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 (see http://grants1.nih.gov/grants/guide/notice-files/NOT-OD-03-055.html). The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

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.

Special Instructions for Preparation of an Application

Foreign Organizations

Several special provisions apply to applications submitted by foreign organizations:

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

3. Submission Dates and Times

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):  July 23, 2006
Application Receipt Date(s): August 23, 2006
Peer Review Date(s): September/October 2006
Council Review Date(s): February 2007
Earliest Anticipated Start Date: March 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 IC 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:

Karl E. Krueger, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Suite 3147, MSC 7362
Bethesda, MD 20892-7362
Telephone: (301) 594-1044
Fax: (301) 402-8990
E-mail: kruegerk@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 delivery; 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 a pdf version of the appendix materials must be sent to:

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

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(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated 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 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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.

The NCI reserves the right to adjust funding, withhold support, suspend, terminate, or curtail the study or an individual award in the event of a failure to comply with the Terms and Conditions of Award, data reporting, quality control, or other major breach of the protocol, or human subject ethical issues, whenever applicable.

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.

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

6. Other Submission Requirements

For this RFA, the budget instructions are modified and the organization of sections A-D in the "Research Plan" of the PHS 398 grant application format is changed.  The remainder of the PHS 398 application form remains the same.

Applicants must budget for travel and per diem expenses for the PI and a co-PI to attend one annual CU meeting and one other glycobiology- or biomarker-related meeting or workshop per year. Meetings that are particularly recommended for Alliance participants include those hosted by the EDRN (e.g., Gordon Conferences or workshops).

Sections A to D of the "Research Plan" are replaced with Sections 1-3. The limit for Sections 1-3 of up to 35 pages does not include the subsequent pages for sections E to I. Applicants may apportion the page distribution for sections 1 to 3 as they desire. Descriptions of what should be covered in each section are outlined below:

Section 1:  Tumor Glycome Laboratory Team.  Applicants should briefly describe what expertise the group encompasses, as well as specialized or unique facilities, core resources, and services that are available to support this research.  In this section, applicants should describe any ongoing grant-supported, institutional, or private sector resources that augment or complement resources for which funding from this RFA is sought.  The roles of all key personnel, collaborators, and consultants who are associated with the application should be specified here along with their capabilities as they relate to the proposal. Whereas individual laboratories may have multiple roles, each application should address all the following important aspects of a glycomic biomarker discovery program listed below (items A-D).

A.       The PI and Biomarker Discovery Component. The central component of Tumor Glycome Laboratory Team shall organize the effort in glycomic biomarker discovery and development. This component is expected to be built and led by the PI of the entire program.  In addition to glycobiologists, investigators with complementary expertise, such as proteomics or lipidomics, may serve as PIs and lead this component. If the PI has sufficient glycomic expertise, the Biomarker Discovery component may be merged (e.g., within the same laboratory) with the Carbohydrate Analytical component (item B).

B.       Carbohydrate Analytical Component. An analytical component led by a glycomic expert(s) is essential to provide the glycomic technologies needed for thorough characterization of the complex carbohydrates under investigation. As indicated above under item A, this component may coincide with the Biomarker Discovery Component, provided the PI and the members of the latter component have adequate expertise and skills in structural carbohydrate analysis. Otherwise, the PI must establish a partnership with a laboratory having adequate expertise in complex carbohydrate analysis to form a separate Carbohydrate Analytical Component.  Whereas any appropriately qualified researcher/group can serve as such partner, potential applicants should be aware that a number of scientists with a strong glycomic background are members of the Consortium for Functional Glycomics and the four glycotechnology resource centers funded by NCRR.

C.      Clinical Specimen Component – Use of sufficient numbers of clinical specimens is essential to testing the diagnostic performance of any biomarker. Each team must secure access to sufficient clinical specimens either by identifying an appropriate clinical partner who can provide specimens or by obtaining access to suitable tissue banks (see links below). Details concerning the numbers of patients (and healthy individuals) that can be accrued for sample procurement or the extent and nature of archived specimens available should be specified. Applicants can approach EDRN (in particular the Clinical Epidemiology and Validation Centers) for contacts to potential collaborations in that area. Applicants should be aware that many of the less common cancers are not currently covered by EDRN investigators.

The NCI Specimen Resource Locator (http://pluto3.nci.nih.gov/tissue/default.htm) and the NCI Tissue Expediter (http://www.cancerdiagnosis.nci.nih.gov/specimens/finding.html#expediter) can assist investigators in locating and determining appropriate human tissue resources for their research project. Applicants should remember that Federal, State, and local regulations for the protection of human research subjects apply to the use of human tissue specimens in research, and these issues must be addressed in the application. Additional information is available at http://www-cdp.ims.nci.nih.gov/brochure.html, and from the Office for Human Research Protections (http://www.hhs.gov/ohrp/). Applicants proposing clinical research with human subjects must observe NIH policies regarding the inclusion of women, minorities, and children (see below). Applicants should also refer to the information available on policies regarding the use of coded specimens (http://odoerdb2-1.od.nih.gov/oer/policies/hs/specimens.htm).

D.      Statistical Support Component – Analysis of multidimensional data from a multitude of samples requires biostatistical expertise. Every team must seek support from such experts for devising case/control study design of biomarker performance using patient samples, and to analyze the statistical significance of the results from these studies. The Data Management and Coordinating Center of EDRN can offer limited support for such services.

Letters from all collaborators on the team should be included after Section 1. These letters do not count toward the page limit.

Applicants should list and summarize their agreements with industry collaborators, if any, including a description of the materials, technologies and/or expertise to be provided by such collaborators. If an application is selected for consideration for funding, detailed documentation of license agreement(s), intellectual property arrangements, and data sharing concerning the proposed or existing collaboration with industrial partner(s) will be requested, as appropriate. If requested, such documents must be submitted by the Institutional Technology Transfer Office (or an equivalent organizational unit).

Section 2: Scope of Research.  This section is equivalent to Sections A-D of PHS form 398. Modified instructions for completing this section follow:

A.       Specific Aims or Objectives. Provide a succinct description of the goals to be achieved through the proposed research and how this work can contribute to establishing a practical clinical test for diagnosis of cancer, monitoring recurrence of cancer, or determining cancer risk.

B.       Background and Significance. Briefly highlight pertinent background information describing what is known about the specific cancer type(s) to be studied in relation to the biomarkers to be investigated. Indicate how the proposed project could impact cancer detection and diagnosis in this arena.

C.      Preliminary Data or Demonstration of Expertise. A clear description of early studies performed by the applicant’s group and results obtained relevant to the proposed project should be included in this section. Because relatively few laboratories have undertaken glycomic cancer biomarker studies, it is not mandatory that the applicants provide preliminary data directly focused on cancer biomarker discovery. In such cases, it is essential, that the applicants provide examples of related studies showing their expertise and skills in the technologies they propose to apply to glycomic biomarker discovery. This section must describe the capabilities of the team to effectively undertake the proposed studies and to achieve principal objectives pertinent to the goals of this RFA.

D.      Research Design and Methods. General guidelines for Section D in the PHS 398 instructions should be followed for this sub-section 2D to outline specific research plans. In addition, applicants should also describe their strategy to anticipate new directions in the field of glycobiology and to take advantage of emerging opportunities by adaptable channeling of resources and effort.

Section 3: Collaborative Activities.  In this section, applicants must address the following items:

A.    Required Activities within the Alliance. Applicants must describe their specific plans to comply with Cooperative Agreement Terms and Conditions of Award as stated in Section VI.2.A of this FOA.  Applicants must state their willingness to participate in several mandatory activities of the Alliance, including: (1) interaction and sharing data with the other Alliance components; (2) participation in planning Alliance-sponsored workshops and symposia and attending these events, (3) serving on the CU and adhering to its decisions and recommendations; and (4) sharing research resources with other Tumor Glycome Laboratories, the NCI, and the CFG.

B.    Relevant Collaborations and Sharing. Applicants should describe their experience in collaborative programs and activities among themselves as well as with other academic and/or industry partners that are pertinent to the application. Indicate whether any of these current or past collaborations: (i) are/were with members of the EDRN, CFG or NCRR glycomic resource centers; (ii) involve (-d) collaborative funding; (iii) involve (-d) sharing of data and resources, e.g., specimens, technology, research protocols, etc. ; and (iv) resulted in joint publications.

Additional relevant collaborations may involve:

i.      Collaborations with Other NCI-sponsored Programs. Ongoing or planned interactions with other NCI programs are not required for applicants responding to this RFA but are certainly welcomed.  Examples of other relevant programs include EDRN, the Clinical Proteomic Technologies Initiative, Specialized Programs of Research Excellence, or Cooperative Groups. Applicants can describe in this sub-section any potential collaborations they intend to engage for their studies.

ii.     Collaborations with Other Applicants to this RFA. Although not required, two or more laboratories responding to this RFA may propose to take an integrated approach to specific aspects of glycan biomarker discovery and development. Such plans should be briefly described in this section. Whereas such interactions may benefit the entire program, it is imperative that projects proposed by each of the collaborating laboratories are individually coherent and viable as self-standing projects. Each application will be individually evaluated for its scientific merit.

C.    Data and Resource Sharing Plans - Section 3 should also contain plans for sharing of: 1) data; and 2) research resources. Please see instructions below for the preparation of these plans.

Plan for Sharing Research Data

All applicants must 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, or explain why data sharing is not possible.

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 must 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.

The Data Sharing Plan must describe how that institution intends to meet the NIH policies for sharing of data or why data sharing is not possible. All investigators funded by this initiative will be required to submit any novel glycan structures elucidated under this program to the Glycan Structure Database of the Consortium for Functional Glycomics. Likewise, glycan profiles obtained from control and disease tissues, or cells, or other biospecimens will have to be deposited with the CFG’s glycoprofiling database.
 
Experimental data for sharing, their format, analytical algorithms, computational modeling and visualizations, and other bioinformatics tools resulting from this RFA must be compatible with the NIH-approved bioinformatics platforms, such as those designed and implemented by the NCI Center for Bioinformatics (http://ncicb.nci.nih.gov), ultimately including caBIG, an open source/open access information network for the sharing of cancer research data and related software tools (https://cabig.nci.nih.gov). The Consortium for Functional Glycomics (CFG) and caBIG representatives will work on implementing appropriate schemes for inclusion of data elements related to complex carbohydrate structures into caBIG. The funded Tumor Glycan Laboratories are expected to adhere to ensuing recommendations and standards for such inclusion once they become available.

The reasonableness of the data sharing plan or the rationale for not sharing research data will 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.

Investigators conducting biomedical research frequently develop unique research resources. NIH recognizes that certain research activities may result in inventions and that grantees are entitled to protect such inventions through patenting and licensing activities in accordance with the Bayh-Dole Act, 35 USC § 200 et seq. and the implementing regulations, 37 CFR Part 401 (“Bayh-Dole Act”). However, the Alliance’s core mission is based on collaborations among Alliance members and between Alliance members and industry partners. These interactions necessitate the sharing of research resources developed in Alliance-related activities. To assure that the resulting research resources are accessible to other members of the Alliance, NIH requires that applicants who respond to this RFA: (1) submit a plan for sharing the unique research resources, e.g., glycomic reagents or probes and novel cancer biomarkers, generated through the grant; and (2) address how they will exercise intellectual property rights, should any be generated through this grant.

If applicant investigators plan to collaborate with third parties owning intellectual property rights to a necessary technology, they must explain how such collaborations will be arranged so as not to restrict their ability to share research materials produced with NIH funding.

Clinical Terms of Awards

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

Section V. Application Review Information

1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by 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 address an innovative hypothesis or critical barrier to progress in the field? Does the project develop and/or employ novel concepts, approaches, methodologies, tools, and/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 experiments take advantage of unique features of the scientific environment and/or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria

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

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see 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.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will 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 presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy.

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.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

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

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (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 e-mail notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not e-mail 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 NoA. 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).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the PI as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, DHHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local governments are eligible to apply), and other DHHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined above.

The Alliance of Glycobiologists for Detection of Cancer and Cancer Risk will be comprised of several components: Tumor Glycome Laboratories(TGL); the Consortium for Functional Glycomics (CFG) funded by NIGMS; Glycomics and Glycotechnology Resource Centers funded by NCRR; and the Early Detection Research Network (EDRN) funded by NCI.   The activities within the Alliance will be integrated by its governing body, termed the Coordination Unit (CU).

2.A.1. Principal Investigator Rights and Responsibilities

The PI will have the primary responsibility for coordinating all project activities scientifically and administratively at the awardee institution and with any collaborating institutions. The PI will assume accountability to officials of the awardee organization and to the NCI for the performance and the proper conduct of the research supported by the U01 mechanism in accordance with the terms and conditions stated in the RFA. The PI will also operate in close coordination with the NCI Project Scientist and CU in integrating his/her program with the broader scope of the Alliance and be responsible for accepting and implementing the goals, priorities, procedures, and policies agreed upon by the CU.

The PI will have the primary authority and responsibility to: define objectives and approaches, including research design and study development; coordinate activities of the components of his/her team, oversee data collection and quality control; and oversee data analysis and publication of the results.

The PI will assume responsibility for managing collaborative projects approved by the CU.

The PI will serve as a voting member of the CU, will attend the annual CU meeting, and participate in regular conference calls designated for Alliance activities. In addition, the PI will attend at least one EDRN- or CFG-sponsored meeting per year. Attendance at these meetings is considered an essential part of the grant.

The PI will be responsible for collaborating on common research designs or protocols, including methods and requirements for joint participation and collaboration as directed by the CU, and handling of data, including appropriate sharing of methods and data among collaborating organizations and submission of validation study protocols to the Data Management and Coordinating Center of EDRN.

The PI will be responsible for ensuring compatibility of pertinent bioinformatics data with NIH-recommended standards, as described previously under “Plan for Sharing Research Data” of this RFA CA-07-020. The PI will also be responsible for submission of novel glycan structures and glycomic profiles to the CFG for inclusion in its databases.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Federal Government rights of access consistent with current DHHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

An NIH (NCI) Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NCI Project Scientist will have substantial scientific programmatic involvement during conduct of this activity, through technical assistance, initiation of collaborative projects, data sharing and analysis, composition of reports, and coordination with other research activities within the Alliance or EDRN.

Because of the Alliance’s diverse research agenda, and the number of tasks that have to be accomplished to achieve its goals, NIH staff members from NIGMS and NCRR will participate as needed to effectively foster necessary interactions between Tumor Glycome Laboratories and various resource components of the Alliance. A member from the Biometry Branch, Division of Cancer Prevention, NCI, will be available to assist the Alliance on issues of study design, sample size, and other statistical computations. Other NCI staff may assist and advise the Alliance on relevant programmatic and scientific issues through the NCI Project Scientist.

The Project Scientist will convene the initial meeting of the CU, and will be a voting member of the CU.

Additionally, an NCI program official (not the person who will serve as the NCI Project Scientist) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice (i.e., the NoA).

2.A.3. Collaborative Responsibilities

Coordination Unit (CU):

The CU will have major scientific management oversight and responsibility for developing collaborative research designs, protocols, facilitating the conduct and monitoring of studies, and reporting study results. All awardees will be required to accept and implement policies approved by the CU.

The CU will be composed of the following full members:

Each full member will have one vote.

The Chair will be selected by the CU from among the PIs of the Tumor Glycome Laboratories. Subcommittees or working groups will be established and maintained by the CU, as it deems appropriate; the NIH CU members will serve on subcommittees as they deem appropriate.

After all the Alliance Tumor Glycome Laboratories have been funded, the CU will convene and continue to meet on an annual basis.  Responsibilities of the CU include, but are not limited to:

The CU will promote and foster the inclusion of women and ethnic minorities in clinical validation studies and assure the completeness of informed consent.

The CU will track Alliance research progress and oversee the process of preparing the results of laboratory investigations and clinical studies for publication in peer-reviewed journals to ensure its timely manner and adherence to the publication policies of the Alliance.

The CU may also evaluate the validation data for biomarkers/reagents developed by the Alliance, and decide when a biomarker is sufficiently validated, or recommend when to stop non-productive experiments relating to biomarker validation.

Data on testing clinical specimens will be submitted centrally to the EDRN Data Management and Coordinating Center. The CU will define the rules regarding access to data and publications consistent with NCI policies.

The EDRN Data Management and Coordinating Center will manage the logistics for the annual CU meetings.

The CU, in consultation with the NCI, will determine the PI of any Alliance-wide validation study.

Collaborative Resource Funds:

After the CU is formed and elects its Chair, Collaborative Resource Funds (CR Funds) in the amount of $500,000 for the first year and $700,000 in subsequent years will be made available by the NCI Office of Grants Administration (OGA) as a separately administered item in the CU Chair’s award. The Chair’s institution will NOT receive Facilities and administrative (indirect) costs on the CR Funds.

The CR funds are reserved for post-award necessities of the Alliance as listed below:

The CU will be responsible for how CR Funds are used. Consensus of the CU for allocating CR Funds for specific purposes will be determined by a majority vote.

Supplements from the CR Funds will provide direct and appropriate facilities and administrative costs.

There is flexibility to permit investigators outside the Alliance to collaborate with a Tumor Glycome Laboratory or bring their promising discoveries or platforms for inclusion in the research activities of the Alliance. To support such efforts, the CU may allocate CR Funds to supplement the investigator’s ongoing research provided that the focus of this collaboration is to meet the objectives of the Alliance as specified in this RFA. The investigator, in turn must agree to share his/her research findings and participate in Alliance research meetings and conference calls.

Recipients of CR Funds that are outside the Alliance, such as commercial laboratories, industrial partners, and outside investigators will be subjected to the resource sharing and intellectual property requirements set forth in Section 6  of this RFA CA-07-020 under Sharing Research Resources. Awardees must advise CR Fund recipients of these requirements.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the CU chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

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.

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

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Karl E. Krueger, Ph.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Room 3147, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service or regular mail)
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 594-1044
Fax: (301) 402-8990
E-mail: kruegerk@mail.nih.gov

Sudhir Srivastava, Ph.D., MPH
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, Room 3147, MSC 7362
Bethesda, MD 20892-7362 (for U.S. Postal Service or regular mail)
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 435-1594
Fax: (301) 402-8990
E-mail: srivasts@mail.nih.gov

2. Peer Review Contacts:

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

3. Financial or Grants Management Contacts:

Mr. Shane Woodward, MBA
Office of Grants Administration
National Cancer Institute
Fairview Center Building, Suite 300
1003 West 7th Street
Frederick, MD 21701-4106
Phone:  (301) 846-5720
Fax: (301) 846-5720
E-mail:  woodwars@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); 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 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://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/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 PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 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% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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NIH Funding Opportunities and Notices

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