Part I Overview Information

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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: NCI Limited Competition: Cooperative Human Tissue Network-CHTN (U01)

Announcement Type
This funding opportunity announcement (FOA) is a reissue of RFA-CA-01-009, which was previously released March 23,2000.

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

• February 21, 2013 - This RFA has been reissued as RFA-CA-13-007.

Request For Applications (RFA) Number: RFA-CA-08-503

Catalog of Federal Domestic Assistance Number(s)
93.394

Key Dates
Release Date: September 18, 2007
Letters of Intent Receipt Date: September 30, 2007
Application Receipt Date: October 30, 2007
Peer Review Date: December 2007
Council Review Date: May 2008
Earliest Anticipated Start Date: July 2008
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: October 31, 2007

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• The Division of Cancer Treatment and Diagnosis of the National Cancer Institute (NCI) invites competing renewal applications from the current Cooperative Human Tissue Network (CHTN) awardees to collect and distribute high quality human tissue specimens to facilitate basic and developmental cancer research. This Funding Opportunity Announcement (FOA) is designed to continue the mission of CHTN to: (1) prospectively collect and distribute high quality tissue specimens to investigators throughout North America and elsewhere; (2) assist individual investigators with regard to specific needs of their research; (3) assist in developing and disseminating knowledge on high quality practices for successfully operating a biospecimen repository; and (4) educate the community about the importance of the availability of high quality human tissue specimens to medical research.
• This FOA solicits U01 cooperative agreement applications from the six currently funded CHTN awardees (these awards include: 5U01CA091664; 5U01CA091654; 5U01CA054021; 5U01CA044974; 5U01CA044971; and 5U01CA044968).
• The NCI intends to commit $5.8 million per year in fiscal years 2008-2012, for a total allocation of $29 million over the indicated 5 years.
• Eligible organizations include: non-profit organizations and public or private institutions, such as universities, colleges, hospitals, and laboratories but only the awardee organizations representing the current six CHTN divisions are eligible to apply: University of Pennsylvania; University of Virginia; The Ohio State University; University of Alabama at Birmingham; Vanderbilt University; and Children’s Hospital at Columbus, Ohio.
• Eligible principal investigators (PIs) must be the current PI and/or any other individual(s) designated/approved by the current CHTN awardee institution with the skills, knowledge, and resources necessary to carry out the proposed research. The PI of each application must be an experienced surgical and/or anatomical pathologist.
• Each eligible CHTN institution may submit only one application in response to this FOA.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

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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

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Section I. Funding Opportunity Description

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1. Research Objectives

PURPOSE

The Cancer Diagnosis Program of the National Cancer Institute (NCI) invites competing continuation applications for cooperative agreement awards from current awardees of the NCI-supported Cooperative Human Tissue Network (CHTN).

CHTN (also referred to as Network ) with all individual CHTN awardees (referred to as CHTN Divisions ) collectively form the CHTN national resource. Presently, the organizational structure of the Network comprises six Divisions (i.e., six individual CHTN awardees).

The purpose of this existing CHTN resource is to collect and distribute benign, pre-cancerous, and cancerous human tissue biospecimens for basic and developmental studies in cancer research. The Network was established to facilitate research by providing human tissue specimens to the general scientific community. Since its establishment by the NCI in 1987, the CHTN has provided more than 720,000 malignant, benign, diseased, and uninvolved (normal adjacent) high quality human tissue specimens from a wide variety of organ sites to over two thousand investigators. The objective of this Funding Opportunity Announcement (FOA) is to continue support for CHTN to ensure that biospecimens critical to progress in cancer research are available to the scientific community.

BACKGROUND

The CHTN (http://www-chtn.ims.nci.nih.gov) was established to address the increasing demand by the scientific community for access to high quality human tissue specimens (biospecimens) for cancer research. Often, researchers are unable to establish the necessary clinical collaborations for access to the biospecimens they need. This cooperative network of tissue collection laboratories was established to make high quality human tissue specimens available to the general scientific community for basic and developmental cancer research. The CHTN currently consists of a network of six institutions, each of which is referred to as a CHTN Division, that collect specimens prospectively to meet researchers requests. Normal, benign, pre-cancerous, and cancerous human tissue specimens with associated histopathologic and demographic data are provided to researchers throughout North America and elsewhere. The CHTN does not generally serve as a tissue bank, but it does store limited numbers of specialized tumor types, such as rare pediatric tumors, to ensure their availability. Five Divisions of the CHTN provide tissues from adults and each is assigned a geographic area of the United States from which requests from researchers are received. A sixth Division, the Pediatric Division, provides rare pediatric tumor specimens nationwide. In order to serve investigators as rapidly as possible, biospecimen requests that cannot be filled within a few weeks by the assigned division are "networked" to all Divisions. The existing Network has demonstrated the feasibility of a network approach for responding to requests for biospecimens. Systems have been developed to facilitate efficient communication among laboratories and to share tissue requests and determine biospecimen availability. Since 1987, the CHTN has become a vital resource for the cancer research community. The CHTN has continued to increase its capacity, providing more than 70,000 biospecimens in 2006. Efforts to define the molecular signatures of cancer cells and the continued emphasis on the application of molecular and other emerging technologies to human specimens is expected to significantly increase the demand for specimens. Services, such as tissue microarrays, microdissections, and RNA/DNA preparations, may also be needed. Through this FOA, the NCI requests applications to continue the Network in order to ensure that the necessary resources are available to the scientific community. The Network is expected to facilitate basic discovery in cancer research as well as the development and application of new technologies to clinical specimens.

OBJECTIVES and SCOPE

This limited competition RFA requests applications for cooperative agreements from the six existing organizations participating in the CHTN. The major focus of this cooperative biospecimen collection and distribution network will be to continue and improve access to high quality human tumor tissue with associated histopathologic and demographic data. The NCI will fund the six institutions to work together as a network to prospectively collect and distribute high quality tissue specimens to investigators throughout North America and elsewhere. The Network will provide large numbers of tumor specimens from a wide variety of cancers and it will also provide researchers with access to biospecimens of rare tumor types. Normal, malignant, and benign human tissue specimens will be collected and prepared to meet researcher requests. Biopecimens will be excess materials collected during the course of routine medical care or at autopsy. The Network does not generally function as a tumor bank, but it may store biopecimens pending the completion of shipments and may bank rare tumors that would not otherwise be available. Pre-malignant lesions, when available, can also be stored for future distribution to facilitate early detection research. The Network is intended to provide biospecimens for basic and developmental studies. Therefore, data routinely provided with the biospecimens will generally be limited to histopathologic and demographic information, such as that related to diagnosis, sex, age, and race.

Members of the Network will be expected to collaboratively establish and implement appropriate procedures to collect, process, and handle biospecimens to assure that they are of the highest quality and suitable for a wide variety of studies and technologies. In order to ensure the availability of suitable biospecimens for patient diagnosis and quality control of research specimens, the Principal Investigator (PI) of each participating group must be an experienced surgical or anatomical pathologist, actively involved in the operation of a pathology laboratory that has demonstrated access to human cancer tissues. Applicant institutions with the necessary expertise will provide additional services such as RNA/ DNA preparations, tissue microarrays, macrodissections, and/or laser capture microdissections; these services should be carefully described and justified. Although separate awards will be made to a number of institutions, awardees will be required to work collaboratively with other Network members. Requests for biospecimens will be shared by network participants so that requests can be filled more rapidly. The awardees will use a common informatics system to share requests for biospecimens.

General operating policies for the Network will be established by a Coordinating Committee that will consist of the Principal Investigators (PIs), a second representative from each participating institution (the coordinator) and a representative from the NCI (i.e., the Program Official serving as Project Scientist). The Coordinating Committee will establish standards for quality control, define equitable policies for distributing specimens, set processing and handling fees, develop biohazard procedures, and establish policies to address the legal, ethical, and human subjects issues related to the use of human specimens for research.

Awardees must agree to provide biospecimens to the scientific community without any requirement for collaboration. The costs of processing and handling, shipping and other appropriate costs may be charged to researchers, in accordance with policies established by the Coordinating Committee and consistent with NIH regulations.

The awardees will work, as much as possible, to adopt the recommendations by NCI Best Practices for Biospecimens Resources (http://biospecimens.cancer.gov/practices/).

Individual awardees and the entire CHTN Network will be expected to address compatibility with the Cancer Biomedical Informatics Grid (caBIG) program (https://cabig.nci.nih.gov).

The Network is expected to remain responsive to changes in the science. The Coordinating Committee will establish mechanisms to assess the changing specimen needs of the scientific community and make operational changes or modifications of CHTN services as needed to rapidly respond to those needs.

The Network must meet the requirements of the Federal Human Subjects Regulations 45CFR46 (i.e., the Common Rule; http://grants.nih.gov/grants/oprr/humansubjects/45cfr46.htm). Federal requirements to protect human subjects apply to a much broader range of research than many investigators realize, including research that uses biospecimens (e.g., cells, blood, urine, and saliva), residual diagnostic biospecimens, and medical information. Information on Office for Human Research Protections (OHRP) Policy on Coded Specimens and Data can be found at http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf.

The Network is expected to address the evolving legal, ethical, and human subjects policy issues related to the use of human biospecimens for research purposes. These issues addressed in the NCI Best Practices for Biospecimen Resources and the OHRP website (http://www.hhs.gov/ohrp/).

A consensus is emerging that informed consent beyond that provided in the surgical consent form is desirable for research use of identifiable specimens collected during routine medical care. Applications submitted in response to this FOA must include plans to obtain consent for future research use of specimens collected during this project or to sever any link between the specimen to be distributed to the researcher and the identity of the patient.

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

Section II. Award Information

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1. Mechanism(s) of Support

This FOA will use the NIH U01 cooperative agreement award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This FOA 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 PI retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NCI staff member(s) 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."

2. Funds Available

• The NCI intends to commit approximately $5.8 Million dollars in FY 2008 for renewal of cooperative agreements resulting from this FOA. Depending on the merit of the competing continuation (renewal) applications, up to six CHTN divisions are anticipated to be funded. An applicant may request a project period of up to 5 years.
• The expected amount for individual awards (direct costs) is up to $833,000 dollars per year.
• The amount of funding per award, on average, for last year was approximately $590,000 in direct costs.
• The anticipated start dates for new awards are in July 2008.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size 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

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1. Eligible Applicants

1.A. Eligible Institutions

Eligible organizations include: non-profit organizations and public or private institutions, such as universities, colleges, hospitals, and laboratories. However, as this FOA is a limited competition opportunity soliciting competing continuation applications, only the six current CHTN U01 awardees (University of Pennsylvania; University of Virginia; The Ohio State University; University of Alabama at Birmingham; Vanderbilt University; and Children’s Hospital at Columbus, Ohio) are eligible to submit applications.

1.B. Eligible Individuals

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

The PI of each participating group must be an experienced surgical and/or anatomical pathologist, who is actively involved in the operation of a pathology laboratory that has demonstrated access to human cancer tissues. Either the PI on a current CHTN award or another qualified individual designated by the current CHTN awardee institution may serve as the PI on the application in response to this FOA.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing.

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

3.A. Special Requirements and Provisions

Effort Commitment of Principal Investigator. The PI is expected to contribute at least 20% of his/her time to the network effort. A strong rationale must be provided (in budget justification) for commitment of less than 20%.

Budgetary Requirements

1) Travel Funds. Funds for travel of two people to attend each of the two Coordinating Committee meetings per year should be included as a budget line item. Travel to national meetings to take part in exhibits to market the CHTN should also be included. Travel for other purposes may be proposed with appropriate justification. Justified situation includes, but is not limited to, travel for Coordinating Committee subcommittee meetings and/or other appropriate meeting travel.

2) Shared Network Services. Budget items may be proposed, with appropriate justification, for expenses to be shared by all network members. These expenses include, but are not limited to, shared costs for administrative activities, database development, publication and impact analysis, and maintenance and marketing activities. A detailed budget justification should be provided for each shared budget item requested.

3) CHTN Informatics and Other Budget Items. Budget items in support of the CHTN informatics activities may be proposed with appropriate justification, for expenses by individual division. Budgets may include, but are not limited to, expenses associated with computer hardware, software, development, and support that are needed at each site. Budgets may include expenses for key personnel (PIs and the coordinators) at each site to attend meetings related to biospecimen resources and development of biospecimen informatics resources which impact the CHTN, such as caBIG. A detailed budget justification should be provided for these items.

Acceptance of the Terms and Conditions of Award. Successful applications for each Network component will be awarded as separate cooperative agreements to the sponsoring institutions and will include the Terms and Conditions of Award specified in this RFA. In the Research Plan (Section 3), applicants must state their willingness to accept the Terms and Conditions of Award.

Section IV. Application and Submission Information

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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) 710-0267; Email: [email protected].

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 (http://grants.nih.gov/grants/funding/phs398/phs398.html) unless specific exceptions are indicated below.

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/.

Key Personnel (Form Page 2): It is imperative that all applicants list all key personnel individuals and their institutions, including those with no requested salary support.

Table of Content (Form Page 3): Modify the standard PHS 398 Table of Contents to account for the modified sections of the Research Plan (see below).

RESEARCH PLAN: The standard PHS 398 instructions (http://grants.nih.gov/grants/funding/phs398/phs398.html) are modified as follows:

Standard Sections A-D of the PHS 398 Research Plan are replaced by the following new Sections 1-9 (specified below). A new page limit of up to 50 pages total applies to these new sections (although the application should be as concise as possible to facilitate a thorough review). Other sections of the standard PHS 398 Research Plan (Sections E-L) remain unchanged and must be completed following the PHS 398 instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

Section 1: Progress Report (up to 10 pages suggested). The applicants should discuss the progress made during the current funding period by their individual CHTN Division and the specific contributions of their Division to the Network as a whole. This section should provide a summary of the progress to date by the applicants Division of the Network. At a minimum, this report should summarize the progress in the following aspects for the applicant’s institution/Division:

a) Role and contribution of the applicant’s Division to the productivity of the entire Network;

b) Participation in the development and execution of the overall Network resource plan;

c) Implementation of Quality Control/Quality Assurance Program;

d) Procurement, processing, storage, and distribution of biospecimens;

e) Tracking of Investigators served; and

f) Describe the efforts to assist/advise resource users (investigators, who are tissue recipients) and provide measures of their satisfaction with the services.

Section 2: Organizational structure and network operation (up to 5-6 pages suggested).

a) Describe formal organizational structure of the Division, including lines of authority and responsibility, with particular attention to the relationship of the organizational structure to the Network's major objectives.

b) Outline your vision how the operation of the Network as a whole might be improved and how the activities of your Division will integrate with those of the other Divisions of the Network. This outline should address the needs of the scientific community and explain how the applicants will facilitate research progress.

c) Describe the services that your Division intends to provide and how those services will address the needs of the scientific community. Describe access of your Division to human specimens for cancer research, including the number and types of specimens with associated histopathologic and demographic data that could be made available.

d) Applicants should propose methods by which their Division will contribute to marketing the resource to the scientific community and include appropriate costs in the budget.

Section 3: Leadership Plan and Network Interactions (up to 5 pages suggested). Avoiding repetition with the form pages, describe succinctly the qualifications and responsibilities of PI and other individuals listed as Key Personal. This description should emphasize:

(a) the scientific and administrative experience of the PIs and other key personnel in the collection, processing, quality control, and distribution of specimens for research; and

(b) past (if applicable) and/or planned mutual interactions of the participating investigators as well as integration of their efforts within the entire Network.

Roles of all key personnel individuals must appropriately match their effort commitment. The PI is expected to contribute at least 20% of his/her time in the network effort. A strong rationale must be provided for any commitment of less than 20%.

The applicants should also describe the strengths their group would bring to collaborative network activities such as updating CHTN policies and priorities, improving quality of shared network services, marketing the resource, improving information systems to manage the resource, monitoring progress, developing new strategies, as needed to ensure that the resource remains responsive to researcher’s needs, and working with CaBIG to harmonize informatics of tissue resources.

In this section, the applicants should also state their willingness to accept the Terms and Conditions of Award, specifically including the willingness to:

• Collaborate with the other awardees and integrate new aspects and ideas to improve the Division’s and Network’s operations;
• Serve on the Coordinating Committee and be bound by its decisions; and
• Accept the role of the NCI representative in the Network as defined in the Terms and Conditions of Award.

Section 4: Standard Operation Procedures (SOPs) & Manual of Operation (MOO) (up to 7 pages suggested). Describe progress toward standardization and harmonization of Standard Operating Procedures (SOPs) with the Network and the efforts to ensure the adherence to the NCI Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/NCI_Best_Practices_040507.pdf ). Describe the procedures for collecting, processing, and distributing specimens (provide an overview, not entire SOPs). In particular, the applicant(s) should:

a) Document the quality control procedures in place at each collecting site and the link between the local SOPs and the CHTN MOO;

b) Propose a system to prioritize access to specimens;

c) Describe how requests for specimens will be received and shared with other Network Divisions; and

d) Describe existing or proposed information systems to manage the resource and how they would facilitate the operation of the Network.

Section 5: Quality Management System (QMS) (up to 5 pages suggested). Describe procedures to demonstrate that adequate quality control (QC) and quality assurance (QA) measures are in place to ensure the quality of the biospecimens. Describe procedures to establish and implement individually and Network-wide QMS with adherence to the Network Manual of Operation (MOO) and NCI Best Practices for Biospecimen Resources.

Section 6: Data Management and Informatics (up to 5 pages suggested). Describe efforts toward use of common informatics system and the improvements in information systems to manage the resource, monitor the progress, and develop the strategies to ensure that the resource remains responsive to researchers needs. Describe effort to integrate the Network’s informatics system into the CaBIG effort to harmonize the informatics of tissue resources.

Section 7: Legal, ethical, and human subjects Issues (up to 4 pages suggested). The application should address the legal, ethical, and human subjects policies issues related to the use of biospecimens for research. It must include a proposal for obtaining consent for future research use of tissue or a plan to sever the link between the specimens to be provided to the researcher and the identities of the patients. Informed consent should address the following issues as recommended by the NCI Best Practices for Biospecimens Resources: description of how Informed consent is obtained; potential use of biospecimens by profit companies; whether research results will be returned to participants or their physicians; and sharing of biospecimens with researchers outside of the institute where the biospecimens were collected.

Section 8: CHTN shared services (up to 6 pages suggested). This section should be identical for all the applications. All the applicants collectively should outline the functioning (and any proposed improvements ) in shared services of the Network s . Describe in details the purpose of each of these services and the duties of the persons in charge. Provide an estimated total cost (for the entire Network) of each of these services:

• CHTN central coordination;
• CHTN informatics services; and
• Publications resulting from CHTN services (as well as publications by CHTN researchers) and analysis of their scientific impact.

Section 9: Participation of Patient Advocates (up to 2 pages suggested). Describe the involvement of patient advocates with the applicant CHTN Division. Explain how their activities contribute to increasing the public’s awareness and understanding of the importance of biospecimens for cancer research as well as of the CHTN itself.

Appendix Materials

All the applicant CHTN Divisions should work together to prepare one set of appendix material (identical for each application) that is pertinent to common, CHTN-wide information, shared services, and progress of the entire CHTN Network.

NIH has published new limitations on grant application appendix materials to encourage applications to be as concise as possible while containing the information needed for expert scientific review. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

For details on what items are generally allowed as Appendix materials, see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html

Do not attach Appendix materials to the application. These materials must be submitted directly to the NCI, see Section IV. 3.B. Sending an Application to the NIH).

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: September 30, 2007
Application Receipt Date: October 30, 2007
Peer Review Date: December 2007
Council Review Date: May 2008
Earliest Anticipated Start Date: July 2008

3.A.1. Letter of Intent

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

• Descriptive title of proposed research;
• Name, address, and telephone number(s) of the PI;
• Names of other key personnel;
• Participating institutions; and
• Number and title of this FOA.

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 NCI staff persons to estimate the potential review workload and plan the review.

The letter of intent should be sent to:

Yaffa Rubinstein, Ph.D.
Resources Development Branch
Cancer Diagnosis Program
Division of Cancer Diagnosis and Treatment
National Cancer Institute
6130 Executive Boulevard, EPN Room 6028A, MSC 7420
Bethesda MD 20892-7240 (for U.S. Postal Service express or regular mail)
Rockville, MD 20850 (for non-USPS delivery)
Telephone: (301) 496-7147
FAX: (301) 402-7819
Email: [email protected]

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 non-USPS delivery)

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 paper copies of the application and one copy of the appendix material in paper or pdf format must be sent to the address below ( NCI encourages submission of Appendix materials in pdf format on a CD):

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041
Bethesda, MD 20892-8239 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
FAX: 301-402-0275
Email: [email protected]

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 for responsiveness by the National Cancer Institute. Incomplete and non-responsive applications will not be reviewed.

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.

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

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.

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.

In addition, data sharing plans should be consistent with the following provisions:

• CHTN Network. CHTN awardees retain custody and primary rights to data developed under these awards, subject to government (e.g., NCI, NIH, U.S. Public Health Service [PHS], and U.S. Department of Health and Human Services [DHHS]) rights of access, consistent with current NIH, PHS, and DHHS policies.
• Users of the Network resources. Any intellectual property generated by an investigator using biospecimens from the Network resource remain the property and in custody of the biospecimens user. Published data using the Network resources must include citation(s) for the source(s) of the biospecimens.

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 expects 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 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

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1. Criteria

Only the review criteria described below will be considered in the review process.
The following will be considered in making funding decisions:

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

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:

• Undergo a selection process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed and assigned a priority score;
• Receive a written critique; and
• Receive a second level of review by National Cancer Advisory Board.

The goal of NIH-supported human specimen resources is to facilitate research that advances the understanding of biological systems, improves the control of disease, and enhances health. In the written comments, reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed resource would 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.

Progress of the Applicant CHTN Division (Specific to this CHTN RFA):

• Has the applicant CHTN Division shown adequate progress during the current funding period in developing comprehensive standard operation procedures (SOPs) for procurement processing, storage, and distribution of biospecimens?
• Has the applicant CHTN Division contributed to the development of the Network manual of operation? How effective was the individual CHTN applicant Division in enhancing collaboration with the other participating CHTN Divisions?
• How successful has been the applicant CHTN Division with efforts toward harmonizing the information system of the entire CHTN Network?
• Has the applicant CHTN Division developed adequate procedures for quality control and quality assurance procedures compliant with the Network MOO?
• Have the applicant CHTN Division made sufficient efforts to provide satisfactory services and assistance to resource users?

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?

Specific for this CHTN RFA:

• Will the CHTN Division, as proposed by the applicant, help to fulfill the needs of the cancer research community? Does this CHTN Division, as proposed by the applicant, provide access to unique resources or provide services to the general cancer research community which would otherwise not be available?
• To what extent will the proposed CHTN Division benefit the cancer research community? Will the proposed CHTN Division have significant contribution to the goals of the CHTN as national Resource and impact on progress in cancer research?
• What are the chances for the resource to make any significant scientific impact in the field? Will the resource have inspiring effect on young investigators research?
• How is this resource unique and different from other biospecimens resources?

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? For applications designating multiple PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PIs?

Specific for this CHTN RFA:

• What is the merit of the proposed plans for the collection and distribution of specimens? Are these plans realistic and properly addressing the overall goals of the Network?
• Are there appropriate plans to assure the collection of large numbers of high quality specimens with associated demographic and histopathologic data or rare specimens which would otherwise not be available?
• Are there appropriate plans proposed to improve quality control of specimens and/or services?
• Are the proposed procedures for the protection of human subjects and patient confidentiality appropriate?
• Are the proposed procedures for the evaluation of requests for specimens and other services reasonable and equitable?
• Are the plans for cooperation and coordination with other participating CHTN awardees (i.e., other CHTN Divisions) and the NCI well-described? Are they likely to be effective?
• Are the current and proposed actions properly and sufficiently addressing the issue of caBIG compatibility and harmonization of informatics of tissue resources?

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?

Specific for this CHTN RFA:

• Do the applicants propose creative or improved methods, such as more efficient and effective means of collecting high quality specimens, new approaches for obtaining informed consent from human subjects and maintaining confidentiality, more efficient and effective methods of sharing specimen requests, improved information systems to support resources or more effective marketing techniques or strategies to utilize the resource?
• What steps are proposed to improve and increase awareness of the applicant CHTN Division and the entire Network in the scientific community?
• Are there any innovative attempts proposed to involve patient advocates in formulating the goals and specific efforts of the applicant CHTN Division?

Investigators: Are the PI and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator(s) and other researchers? Do the PI and investigative team bring complementary and integrated expertise to the project (if applicable)?

Specific for this CHTN RFA:

• Is the PI of each participating group, an experienced anatomic and/or surgical pathologist with access to specimens?
• Are the qualifications, experience and proposed responsibilities of the PI and other key personnel well suited to organize and maintain the CHTN Division, maintain quality control and equitable access, and manage record keeping?
• Is the proposed effort of the PI and key personnel sufficient to ensure (i) proper overseeing of all operations and management; (ii) integration with the other participating groups; and (iii) a high quality of biospecimens?

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?

Specific for this CHTN RFA:

• Are the facilities and equipment for the resource adequate?
• Is there an adequately supportive environment to facilitate collegial interactions within the applicant’s Division and collaborations with other Divisions.

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). (See also the criteria included in the section on Federal Citations, below.)

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from 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). (See criteria included in the section on Federal Citations, below).
.
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 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 expects 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 athttp://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

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1. Award Notices

After the peer review of the application is completed, the 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 email notification from the awarding component to the grantee business official (designated in Item 12 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 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 Principal Investigator 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 U.S. Office of Management and Budget (OMB) administrative guidelines, HHS 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 NIH, PHS, and DHHS 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 below.

Throughout these Terms and Conditions of Award, Cooperative Human Tissue Network (CHTN or Network ) refers to all individual CHTN awardees forming together the CHTN resource. The Network and its Divisions (i.e., each individual CHTN awardee) comprise the organizational structure which is composed of the awardee institution(s), principal investigators (PIs) and other key personnel, all of whom agree to collaborate on research goals of the CHTN resource.

2.A.1. Awardees and Principal Investigators Rights and Responsibilities

• The PI of a Cooperative Human Tissue Network award must be an experienced surgical and/or anatomic pathologist with demonstrated access to a wide range of human cancer tissues. The PI retains primary responsibility for the performance of activities supported by each award.
• Two members of each awarded research group (one of whom must be the Principal Investigator) are required to serve as members of the CHTN Coordinating Committee (as stipulated below) to help formulate and implement CHTN operating policies.
• Awardees are required to have access to appropriate cancerous and normal human tissue specimens and to make them available to the research community according to the policies established by the CHTN Coordinating Committee.
• Awardees must agree to implement procedures to obtain consent for future research use of specimens or to sever the link between the specimens to be distributed to researchers and patient identities according to the policies and time frames established by the Coordinating Committee.
• Each awardee is required to submit reports summarizing their individual activities to the Coordinating Committee, according to the formats, frequencies, and time frames established by the Committee.
• Awardees retain custody and primary rights to data developed under these awards, subject to government (e.g., NCI, NIH, or PHS) rights of access, consistent with current NIH, PHS, and DHHS policies.
• In case the PI of any of the participating groups cannot continue serving, the designated replacement PI must be approved by the NCI. The replacement PI must also be an experienced anatomic and/or surgical pathologist with access to human tissue specimens.
• Awardees must agree that each awarded CHTN Division and the entire Network will be subject to continued evaluation by the NCI of the overall performance and adequacy of the financial and scientific aspects of the resource. This evaluation will include (but not be limited to) human subject issues, procurement and distribution, quality assurance and quality control, informatics system(s), and involvement of patient advocates.
• Awardees must agree to provide biospecimens to the scientific community without requiring any collaborative arrangements. The costs of processing and handling, shipping and other appropriate costs may be charged to researchers, in accordance with policies established by the Coordinating Committee and consistent with NIH regulations.

2.A.2. NIH Rights and Responsibilities

The NCI will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The Cancer Diagnosis Program of the NCI’s Division of Cancer Treatment and Diagnosis will designate an NCI Program Director to serve as a Project Scientist. The role of the Project Scientist will be to advise, assist and facilitate, but not to direct the activities of the Network. Specifically, the CHTN Project Scientist will:

• Monitor the operation of the Network and participate in the decisions of the Network by serving as a voting member on the Coordinating Committee (with only one vote in total for the NCI) and participating (as a voting member) in each subcommittee formed by the Coordinating Committee;
• Coordinate and facilitate the complex interactions and information sharing among multiple participating institutions and serve as liaison between the Coordinating Committee and the participating groups;
• Assist the Coordinating Committee in developing operating policies and procedures and assure that those policies are (a) acceptable to the NCI and (b) consistent with NIH policies and federal regulations;
• Assist ongoing CHTN harmonization and standardization efforts to adhere to NCI Best Practices for Biospecimen Resources;
• Coordinate the development of a centralized database and the informatics system which can best meet the needs of the individual Network institutions as well as the needs of the CHTN to be consistent with NCI Best Practices for Biospecimen Resources;
• Provide close communication with the NCI Tissue Expediter (http://www.cancerdiagnosis.nci.nih.gov/specimens/finding.html#expediter) to ensure referral of requests to the most appropriate resource and identify needs which are not currently being met;
• Review the operations of individual laboratories for compliance with quality control standards and with operating policies developed by the Coordinating Committee.

Project Scientist will monitor the operation of the Network and may request the Coordinating Committee to consider modification of operating policies, as required to maintain quality control or to serve new research needs of the scientific community.

Project Scientist may review the operations of individual laboratories for compliance with quality control standards and with operating policies developed by the Coordinating Committee.

Project Scientist may recommend withholding of support and/or suspending or terminating an award for failure to adhere to policies established by the Coordinating Committee.

Additionally, an NCI Program Official will be responsible for the normal scientific and programmatic stewardship of the award. The NCI Project Scientist and the NCI Program Official may be the same person. In that case, Program Official/Project Scientist will seek NCI waiver according to the NCI procedures for management of conflict of interest to enable her/him to attend peer review meetings of renewal (competing continuation) and/or supplemental applications when necessary.

2.A.3. Collaborative Rights and Responsibilities:

To oversee the operation of the Network, awardees and involved NCI staff members will jointly establish the CHTN Coordinating Committee to act as the governing body of the CHTN. The Coordinating Committee will act as the governing body of the CHTN. All CHTN awardees/participants will be bound by the decisions/actions of the Coordinating Committee.

Coordinating Committee Membership. A Coordinating Committee will be established to oversee the operation of the Network. The Coordinating Committee will consist of two members from each awardee institution (one of whom must be the Principal Investigator) and one member representing the NCI (a Program Director, who will serve as the Project Scientist). Voting rights are restricted to the PIs on individual CHTN awards (or their designees, if necessary, i.e., one vote per each awardee) and one vote for the NCI represented by Project Scientist. The chairperson (who may not be an NCI employee and/or representative) and Executive Coordinator of the Coordinating Committee are elected by a majority vote of its members and serve for one calendar year. Additional members (without voting rights) may be added to the committee by majority vote of the existing committee members.

Coordinating Committee Responsibilities. The Coordinating Committee shall develop Network operating policies for the implementation, which must be implemented by the PIs at each Division of the Network;

The Coordinating Committee shall reviews the operating procedures of the CHTN Divisions to ensure that these procedures are compatible with the overall goals and policies of the Network, the NCI and the NIH. Specific responsibilities of the Coordinating Committee will include the following:

• Establish uniform standards, policies, and procedures for tissue acquisition, processing, distribution, and storage;
• Develop uniform methods of histopathological diagnosis, and assure appropriate control of tissue quality;
• Establish strategies to market the resource;
• Develop policies for addressing the legal, ethical, and human subjects issues related to the use of human specimens for research and establish biohazard procedures;
• Develop guidelines and standards for informatics and data management required for operation of the Network;
• Establish procedures for effective communications;
• Develop other Network policies as needed; and
• Establish subcommittees as necessary.

The Coordinating Committee will meet initially to plan for integration of any new cooperating institutions and/or phase out of current institutions and to review and accept or modify currently established operating procedures and policies. The Coordinating Committee will meet at least twice a year.

Subcommittees. Membership on subcommittees is not limited to voting members of the Coordinating Committee. The NCI Project Scientist will be a voting member and participant in each subcommittee. The chairperson of each subcommittee (who may not be the NCI representative) will be elected by a majority vote of the Coordinating Committee. Voting Membership on subcommittees is not limited to members of the Coordinating Committee. However, only voting members of the Coordinating Committees will have voting rights, except on the following subcommittees: strategic planning, quality control, and regulatory affairs. Other subcommittees may grant voting rights also to individuals other than voting members of the Coordinating Committee., where the voting member must be the awarded PI. The Marketing subcommittee includes (but is not limited to) the coordinators from each of the cooperating CHTN each of the cooperative institutions, who also serve as the voting members.

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, including: a designee of the Steering Committee 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.

In addition, each CHTN Division will be required to submit an interim report every 6 months. In these reports, the Network and its Divisions will be expected to provide sufficient information to facilitate the continued evaluation of the overall, scientific, and financial performance of the resource. This information should include, but not be limited to, updates on human subject issues, procurement and distribution, quality control and quality assurance, informatics system and involvement of patient advocates. In addition, the Network will be expected to provide reports on the implementation of the recommendations from the NCI/OBBR review of the CHTN program.

Section VII. Agency Contacts

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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:

Yaffa Rubinstein Ph.D.
Resources Development Branch
Cancer Diagnosis Program
National Cancer Institute
6130 Executive Boulevard, EPN Room 6028A, MSC 7420
Bethesda MD 20892-7240(for U.S. Postal Service express or regular mail)
Rockville, MD 20850 (for non-USPS delivery)
Telephone: (301) 496-7147
FAX: (301) 402-7819
Email: [email protected]

2. Peer Review Contacts:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Blvd., Room 8062, MSC-8239
Bethesda MD 20892-8329 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Bethesda MD 20892-8239
Telephone: (301) 496-3428
FAX: (301) 402-0275

3. Financial or Grants Management Contacts:

Ms. Eileen M. Natoli
Office of Grants Administration
National Cancer Institute
Executive Plaza South, Room 243, MSC 7150
Bethesda, MD 20892-7150 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-8791
Fax: (301) 496-8601
Email: [email protected]

Section VIII. Other Information

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Required Federal Citations

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.

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. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 RFA 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.