RFA-CA-08-015: Community Clinical Oncology Program (U10)

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://cancer.gov)

Title: Community Clinical Oncology Program (U10)

Announcement Type
This funding opportunity announcement (FOA) is a re-issuance of RFA-CA-07-048.

Request For Applications (RFA) Number: RFA-CA-08-015

Catalog of Federal Domestic Assistance Number(s)
93.399

Key Dates
Release Date: April 29, 2008
Letters of Intent Receipt Date: June 10, 2008
Application Receipt Date: July 10, 2008
Peer Review Date: November 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: June 1, 2009
Additional Information To Be Available Date (URL Activation Date): Not Applicable
Expiration Date: July 11, 2008

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This funding opportunity announcement (FOA) solicits applications from institutions/organizations that propose to contribute to the mission of the NCI-supported Community Clinical Oncology Program (CCOP) Network, which was established in 1983 to develop and conduct state-of-the-art cancer prevention, control, and treatment clinical trials with significant involvement of community oncologists and populations they serve. The CCOP Network mission includes: (1) accelerating development of interventions to prevent and treat cancer and its symptoms by increasing accrual to trials; (2) fostering quality care in the community through adoption of results from clinical trials; and (3) increasing the involvement of minority and underserved patient/participant populations in cancer clinical trials and associated research. The CCOP Network consists of two types of components, CCOP Groups (also referred to as CCOPs) and CCOP Research Bases. A CCOP Group encompasses community oncologists who accrue patients/participants to NCI-approved clinical trials. These trials are designed and conducted by the CCOP Research Bases, which also manage and analyze the data, and report the results. CCOP Research Bases must be located either at an NCI-supported Clinical Cooperative Group or at an NCI-designated Cancer Center.
Mechanism of Support. This FOA utilizes the NIH U10 cooperative agreement award mechanism.
Funds Available and Anticipated Number of Awards. The NCI intends to commit up to $8.2 million in total costs in FY 2009 to fund approximately ten CCOP Group and/or Research Base awards.
Budget and Project Period. For CCOP Groups, the total project periods may not exceed 3 years for new applications and 5 years for renewal applications. For CCOP Research Bases, the total project period may not exceed 5 years for new and renewal applications. The expected direct cost for individual awards will vary due to differences in the nature and scope of the proposed research among the CCOP Groups and CCOP Research Bases.
Application Research Plan Component Length: The U10 application Research Plan component of the PHS398 may not exceed 50 pages, including tables, graphs, figures, diagrams, and charts. See Section IV.2
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization 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.
Resubmissions. Resubmission applications are permitted in response to this FOA; however, any such application must include an Introduction addressing the previous peer review critique (Summary Statement).
Renewals. Renewal applications are permitted in response to this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
Application Materials. See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-0088.

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, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
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 overall objective of this Funding Opportunity Announcement (FOA) is to develop and conduct state-of-the-art cancer prevention clinical trials and control and treatment clinical trials with prominent involvement of the community oncologists and populations that they serve. To accomplish this overall goal, the Division of Cancer Prevention, National Cancer Institute (NCI), established in 1983 the Community Clinical Oncology Program (CCOP), which is a community-based clinical trials network that links community physicians, who accrue participants/patients to cancer clinical trials as part of their overall practice, with NCI Cooperative Groups and Cancer Centers that serve as their “CCOP Research Bases.”

The CCOP Network is designed to: (1) increase the involvement of community oncologists, other specialists (e.g., surgeons, family practitioners, gastroenterologists, urologists, gynecologists), and their patients in clinical trials designed by NCI Cooperative Groups and Cancer Centers; (2) involve a wider segment of the community in cancer clinical trials, including minorities, women, and other underserved (e.g., rural) populations; and (3) accelerate the transfer of knowledge gained from clinical trials to community oncology practices.

This FOA elicits two types of applications for the components of the CCOP Network, as follows: (1) new and currently funded (renewal) CCOP Groups (also referred to as CCOPs); and (2) new and currently funded (renewal) CCOP Research Bases.

A CCOP Group consists of community oncologists from one or more interacting community institutions that accrue patient/participants to clinical trials designed and conducted by the CCOP Research Bases. Each CCOP Group must accrue annually at least 50 patients to treatment clinical trials and at least 50 participants to prevention and control clinical trials. Equally important to accrual, CCOPs also assure the quality of the data collected and the safety of the participants/patients entered on trials.

A CCOP Research Base designs clinical trials for use in the CCOP Network. It also conducts the trials, manages and analyses the data, and reports the results. CCOP Research Bases must either be NCI Clinical Cooperative Groups or NCI-designated Cancer Centers.

Cancer prevention/control clinical trials include clinical evaluations of: the effectiveness of chemo-preventive agents; methods for early detection of cancer and precancerous lesions; interventions to improve patients’ quality of life or to treat symptoms arising from cancer or cancer therapy; and ways to improve continuing, palliative, and end-of-life care.

Background

The CCOP Network was initiated in 1983 as a mechanism for including community oncologists and their patients in treatment clinical trials designed by NCI Cooperative Groups and Cancer Centers. In 1986, the Network’s focus expanded to include cancer prevention/control clinical trials research aimed at reducing cancer incidence, morbidity, and mortality through the evaluation of interventions in controlled clinical trials. Prevention and control research in the CCOP Network has increased steadily since funding began in 1987.

The CCOP Network is a vital resource for conducting NCI cancer prevention/control clinical trials because the Network provides access to: (1) large national cancer prevention trials; (2) large populations of cancer patients for symptom management, supportive care, and quality-of-life interventions; (3) large populations of former cancer patients and survivors who may benefit through participation in chemoprevention clinical trials; (4) cancer patients' family members and other classes of individuals who may be at increased risk of developing cancer and thus be candidates for cancer prevention and/or detection studies; and (5) geographic areas inhabited by diverse populations not always available in university or urban settings. Several large chemo-prevention trials have been implemented through the CCOP Network, among them the prostate cancer prevention trial with finasteride (PCPT), the study of tamoxifen and raloxifene in the prevention of breast cancer (STAR), and the selenium and vitamin E trial in the prevention of prostate cancer (SELECT).

In 2007, the CCOP Network consisted of 49 CCOP Groups, located in 29 states and comprising more than 370 hospitals and more than 3,050 physicians. The CCOPs enrolled approximately 5,350 patients to treatment trials and 5,500 participants/patients to prevention and control trials. The Network also included 13 CCOP Research Bases, which conducted several hundred treatment/prevention/control trials.

In addition to CCOP, a related funding initiative, the Minority-Based Community Clinical Oncology Program (Minority Based-CCOP) has similar goals, but is distinctly focused on community institutions and oncologists serving primarily minority populations. Potential applicants for support as CCOP Groups who are working at community institutions serving primarily minority populations should consider a companion funding opportunity for Minority Based-CCOP (for details, see RFA-CA-08-016)

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

Section II. Award Information

1. Mechanism of Support

This funding opportunity uses the NIH U10 cooperative agreement award mechanism.
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/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 Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

NCI has determined that there is a continuing need for community participation in cancer clinical trials that cover both cancer prevention/control and treatment. While this FOA is a one-time issuance, it is expected that a CCOP FOA will be published in the NIH Guide for Grants and Contracts on an annual basis using the U10 cooperative agreement award mechanism, provided that funds are available.

2. Funds Available

The estimated amount of funds available for approximately 10 CCOP Group and/or Research Base awards as a result of this announcement is $8.2 million for fiscal year 2009. Future year amounts will depend on annual appropriations.

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 NIH IC(s) 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.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

1. A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institutions of Higher Education;
Private Institutions of Higher Education;
Hispanic-serving Institutions;
Historically Black Colleges and Universities (HBCUs);
Tribally Controlled Colleges and Universities (TCCUs);
Alaska Native and Native Hawaiian Serving Institutions;
Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education);
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education);
For-Profit Organizations (Other than Small Businesses);
Indian/Native American Tribal Governments (Federally Recognized);
Indian/Native American Tribally Designated Organizations;
Eligible Agencies of the Federal Government;
Faith-based or Community-based Organizations; and
U.S. Territory or Possession.

1. B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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

This program does not require cost sharing as defined in the current NIH Grants Policy Statement.

3. Other-Special Eligibility Criteria

For new and renewal CCOP Group applications, the following provisos apply:

An application may be submitted by a community institution defined as a hospital, a clinic, a group of practicing physicians, a health maintenance organization (HMO), or a consortium of hospitals and/or clinics and/or physicians and/or HMOs that agree to work together with a PI and a single administrative focus;
A university, Veterans Administration (VA) hospital, or military treatment facility (MTF) may be included in an application as a member of a consortium led by a community institution, but may not be the applicant organization or the major contributor to patient accrual;
A non-university clinical trials cooperative group member that is not currently funded by NCI is eligible to apply; and
Funded cooperative group affiliate programs are eligible to apply, but should state in the application that support through this mechanism will be relinquished if a CCOP award is received.

Institutions not eligible to apply for the CCOP Group awards include:

An NCI-funded Cancer Center;
A university hospital that is the major teaching institution for that university; and
A university hospital clinical trials cooperative group member funded by the Division of Cancer Treatment and Diagnosis (DCTD), NCI.

For new and renewal Research Base applications, the following provisos apply:

An application must be submitted by an NCI-funded Clinical Trials Cooperative Oncology Group (Cooperative Group); an NCI-funded Cancer Center; or an existing CCOP Research Base;
Cooperative Groups as CCOP Research Bases must propose to design and conduct both cancer treatment and prevention/control clinical trials; and
Cancer Centers as CCOP Research Bases must propose to design and conduct only cancer prevention/control clinical trials.

Applicants may submit a resubmission application; however, such an application must include an Introduction addressing issues raised in the previous critiques (i.e., Summary Statements).

Renewal applications will be permitted for this FOA.

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 (Revision 11/2007). Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

A suggested application format is available at http://prevention.cancer.gov/programs-resources/programs/ccop/apply. Applicants are encouraged to use the suggested format instructions for organizing the specific information concerning the FOA programmatic requirements in the PHS 398. Tables should be part of the body of the application and counted toward the page limitation if included in appropriate sections of the Research Plan. Some tables may also be included as part of the Resources, Progress Report, and/or Human Subjects Research sections, as appropriate. Do not include the tables in the appendix.

Note: A part of the standard PHS 398 Research Plan (Items 2-5 as per Revision 11/07 of the PHS 398 Table of Content, previously known as “Sections A-D”) is substituted with Sections 1-7 with altered page limits as indicated below. Other items of the PHS 398 Research Plan remain unmodified.

A. Form and Content of Application for CCOP Group Award

For CCOP Group applications submitted in response to this FOA, the standard PHS 398 "Research Plan" (Items 2-5) is altered as follows:

The number of pages has been increased from 25 to 50 pages (applicants are encouraged to use the minimum number of pages necessary to clearly and succinctly describe the research plan); and
The 50 pages (or fewer if possible) should be apportioned as desired by the applicant to cover Sections 1-7, as outlined below.

Research Plan for all CCOP Group Applications must contain the following Sections:

Section 1: Progress Report. An application from a currently funded CCOP Group (a renewal application) must include a progress report. NOTE: new CCOP Group applicants should insert “Not applicable” in this section. The progress report should at a minimum, consist of:

A summary of CCOP Group activities and accomplishments, including annual accrual over the funding period;
A plan for continuing to meet prevention and control accrual requirements including plans for follow-up of participants from the large prevention trials;
An evaluation of CCOP Group performance by affiliated CCOP Research Base(s); and
A complete description of how the applicant has met the special cooperative agreement terms and conditions of the award [see Section VI. 2.A. Cooperative Agreement Terms and Conditions of Award; 1.Part A. CCOP Awardee Responsibilities (including PI Responsibilities)].

Section 2: Catchment Area. Each application must delineate its catchment area. A map of the service area, designating counties or zip codes from which approximately 80 percent of the patients will be drawn, should be provided. A description of other cancer care resources in the catchment area (i.e., hospitals, clinics, physicians, cancer centers) that are not part of the application should be included. A description of the study population in the application’s catchment area, with a breakdown by percentage of the gender and minority composition, should be provided.

Section 3: Accrual Requirements. Each application must include plans for maintaining or increasing accrual to cancer prevention/control trials and treatment trials. Plans must list estimated accrual to specified NCI-approved trials. Strategies for implementing the trials and facilitating accrual should also be described. In addition, plans for recruiting women and minority populations must be described. Applications must include evidence that the CCOP Group can meet or exceed the requirement to accrue 50 new participants/patients to cancer prevention/control trials and 50 new participants/patients to cancer treatment trials, annually (with exceptions noted below). For renewal CCOP Groups, the best evidence is prior accrual and trends in accrual. Exceptions and additional considerations are as follows:

The above requirement quotas for cancer prevention/control and treatment may be waived for applicants whose specialty is pediatrics and who are able to enroll a majority of their eligible patients on cancer prevention/control and treatment clinical trials.
The requirement quota of 50 new treatment accruals may be waived for a CCOP Group with an outstanding record of accrual to cancer prevention/control trials.
The quotas of newly accrued participants/patients to cancer prevention /control trials may , in part, be fulfilled by listing active follow-up of participants previously accrued to multi-year chemoprevention trials. For purposes of meeting accrual targets, however, ten participants in active follow-up are needed to substitute for three participants enrolled in cancer prevention/control trials.

A new CCOP Group application must provide implementation plans for at least two NCI-approved cancer prevention/control clinical trials that use an intervention, such as a trial of a chemo-preventive agent or a trial to study an intervention/agent for the treatment of a cancer symptom. The application should include specifics on patient/participant recruitment, compliance and follow-up. The clinical trials selected must come from CCOP Research Bases with which the applicants propose to affiliate (see Section 5 below). In addition, a new CCOP Group must describe a plan demonstrating the likelihood of accruing the 50 new participants/patients to cancer prevention/control and 50 new participants/patients treatment trials, annually.

Section 4: Team Organization and Qualifications. A designated PI is required. Command structure should identify a potential replacement for the PI to assure continuity in the event of resignation of the PI. The qualifications and experience of both persons (the PI and the replacement candidate) must be described, specifically documenting their respective abilities to organize and manage a community oncology program that includes cancer prevention/control/ treatment clinical trials and related activities, as well as experience in accruing patients/participants to clinical trials.

Each application should propose a committed multidisciplinary professional group appropriate for its expected clinical trial participation. This team should include medical oncologists, surgeons, radiation oncologists, pathologists, oncology nurses, data managers, health educators, and other disciplines (e.g., gynecology, urology, gastroenterology, pediatrics, internal medicine, family practice), as appropriate. The training and experience of participating physicians who are in the top 25 percent of the CCOP Group’s highest accruing physicians must be described.

The application should include a description of planned organizational structure and procedures for implementing the workflow necessary for choosing trials to open, accruing and following participants/patients, and data management. Details should also be provided on any prior experience of working together as a group, particularly in implementing cancer prevention/control/treatment clinical trials and related activities. An organizational chart showing how the group will function must also be included. The qualifications, experience, and proposed duties of all proposed support personnel should be described.

Section 5: Affiliations with Research Bases. Each CCOP Group application must demonstrate access to an adequate selection of cancer prevention/control/treatment clinical trials so that the CCOP Group can meet or exceed accrual goals, and provide appropriate trials to the participants/patients in the CCOP Group’s catchment area. Trial access must be documented through formal affiliations with Research Bases. Multiple Research Base affiliations are permitted, in the following configuration:

only one NCI-approved multi-specialty cooperative group (except for CCOPs participating in NCI “pilot” project); and
as many other CCOP Research Bases (excluding the multi-specialty groups) as the CCOP Group deems appropriate.

Typically, an established CCOP Group affiliates with about four to six CCOP Research Bases, in addition to the mandatory affiliation with multi-specialty cooperative group. Existing or planned affiliations with each specific CCOP Research Base must be justified in terms of the scope and breadth of research that the applicants anticipate undertaking. The conditions of affiliation must be provided in the CCOP Research Base affiliation agreement(s). Copies of these agreements should be included under the Resources section and referenced in the Research plan under Section 5. Initial affiliations should be maintained during the funding cycle. If applicable, the contributions of CCOP Group investigators and their key personnel to the infrastructure of the affiliated CCOP Research Bases may be described. Such contributions may involve, for example, participation/membership in CCOP Research Base committees, serving as chair(s) of cancer clinical trials, and authorship of joint publications.

Note: A list of currently eligible CCOP Research Bases may be obtained at http://prevention.cancer.gov/programs-resources/programs/ccop/rbccop or from the Community Oncology and Prevention Trials Research Group, DCP, NCI, at (301) 496-8541.

Section 6: Quality Assurance and Investigational Drug Management. Quality control procedures must be described in detail. Assurance of quality is the joint responsibility of the CCOP Group and its affiliated Research Bases. Quality control procedures of the CCOP Research Base will be applied to the CCOP Groups and should be specified in the CCOP Research Base affiliation agreement. In addition, procedures for investigational drug monitoring and data management must also be described in the applications.

Section 7: Facilities and Institutional Commitment. The availability of facilities, including laboratories, inpatient and outpatient resources, cancer registries, etc., must be described. A statement of commitment from each participating institution or organization and/or documentation of consortium arrangements must be provided (include in the Resources section). In addition, each application must have a defined space for administrative activities and administrative personnel that will serve as a focus for data management, quality control, and communication. The description of this space may be included under the Resources section or in the Research Plan.

B. Form and Content of Application for CCOP Research Base Award

For CCOP Research Base applications submitted in response to this FOA, the standard PHS 398 Research Plan (Items 2-5) is substituted with Sections 1- 6 with altered page limits as indicated below. Other items of the PHS 398 Research Plan remain unmodified.

The number of pages has been increased from 25 to 50 pages (applicants are encouraged to use the minimum number of pages necessary to clearly and succinctly describe the research plan).
The 50 pages (or fewer if possible) should be apportioned as desired by the applicant to cover Sections 1- 6, as outlined below.
In addition, a CCOP Research Base application that includes large-scale cancer prevention clinical trial(s) and/or “Prevention Member(s)” proposals may use up to an additional 25 pages (maximum of 75 pages total) to describe these elements of the application (see definition of “Prevention Members” below under Section 5).

The prevention/control clinical trials research agenda of a CCOP Research Base should be compatible with the scientific interest(s) and the expertise of the individual Cooperative Group or Cancer Center. In addition, the portfolio of clinical trials, including completed, ongoing, and proposed trials, should reflect the breadth and scope of research focus for the CCOP Research Base.

Research Plan for CCOP Research Base Applications must contain the following Sections:

Section 1: Progress Report. An application from a currently funded CCOP Research Base (a renewal application) must include a progress report. NOTE: new CCOP Research base applicants should insert “Not applicable” in this section. The progress report should consist, at a minimum, the following:

A summary of CCOP Research Base activities and accomplishments focusing on annual number of prevention/control trials opened and annual accrual to these trials during the funding period (this information should be supported by a discussion of trials in development and anticipated dates for opening);
A discussion of how clinical trials build on and/or complement subsequent trials to further the group’s targeted prevention/control trials research agenda;
Status of active, closed, and completed prevention/control clinical trials over the funding period;
Status of prevention/control clinical trials under development;
The process and organizational structure for the development of clinical trials and for their implementation, selection, and evaluation (auditing) of performance sites, data management, quality control, statistical analysis, and study safety monitoring;
Annual accrual to each NCI-approved prevention/control clinical trial for interacting CCOP(s), and for Research Base members and affiliates;
Annual accrual to each NCI-approved treatment clinical trial for CCOP(s);
A description of the gender and minority population(s) and subpopulation(s) served must be provided, as well as an outreach plan;
Annual accrual to cancer prevention/control clinical trials and treatment clinical trials (if applicable) by gender and ethnicity/race composition; and
A description of how the application has met the special cooperative agreement terms and conditions of the award [see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award; subsection on Research Base Awardee Responsibilities (including PI Responsibilities)].

Section 2: Clinical Trials Design and Implementation. The following elements must be described:

Each application must demonstrate the ability of the investigators to design and implement multi-institutional cancer prevention/control clinical trials that are appropriate for the participation of CCOPs. A list of the CCOP Research Base’s cancer prevention/control clinical trials available for CCOP Groups and Research Base member/affiliate institution participation must be provided. For renewal CCOP Research Base applications, the best evidence is the record of opened trials and demonstrated accrual to those trials.
Each application must describe long-term plans for the recruitment and retention of participants/patients to cancer clinical trials, including programs for recruitment and retention of minorities. Procedures and time frame to evaluate the effectiveness of such programs should be described.
Each application must demonstrate the ability to provide to CCOP Groups a selection of approved and active prevention/control clinical trials of high scientific merit. The accrual to these trials, the trials submitted to NCI for review, and trials in earlier phases of development will serve as a measure of such ability.
A new CCOP Research Base application must provide at least two examples of active or proposed cancer prevention/control clinical trials and describe plans for study design, intervention(s), and statistical considerations; access to potential study patients/participants; and procedures for data management, quality control, and follow-up. The availability of the appropriate expertise to design, implement, and analyze the results of the proposed clinical trials must be documented.

Section 3: Accrual Requirements. The following elements of patients/participants recruitment must be described (if applicable):

Each application must demonstrate that the proposed Research Base can accrue at least 50 participants annually from CCOP and/or member/affiliate institutions to NCI-approved prevention/control clinical trials designed by the CCOP Research Base. An established Research Base is expected to have exceeded the stated minimal number of accruals and have a credible plan for maintaining or increasing accrual throughout the funding period.
For treatment clinical trials (if applicable), the application must demonstrate that the proposed Research Base can accrue at least 50 patients from CCOPs annually to the NCI-approved treatment clinical trials designed by the CCOP Research Base. An established Research Base, participating in treatment clinical trials, is expected to achieve a higher number of accruals annually.
A new application must demonstrate that the proposed Research Base can develop a selection of treatment clinical trials (if applicable) and cancer prevention/control clinical trials to meet the accrual minimums by the end of the first competing project period.

Section 4: Team Organization and Qualifications.

A designated PI is required and his/her qualifications and experience must be described. An individual designated to coordinate cancer prevention and control research must be qualified in the field of cancer prevention/control and have experience within the Research Base. His/her qualifications and experience within the Research Base structure must be described. Each application must also demonstrate the availability of professionals with the appropriate expertise to design and implement the proposed treatment and/or cancer prevention/control clinical trials. Medical, surgical, radiation, and other oncology specialists, nurse oncologists, epidemiologists, health educators, and/or other public health professionals and basic scientists may be included.

Each application must have an organizational structure that involves the appropriate personnel to assure the timely development, conduct, analysis, and reporting of cancer prevention/control clinical trials. An organizational chart and a description of the Research Base operations showing the relationship(s) between the scientific and administrative units of Research Base organization in conducting clinical trials must be provided.

The organization applying for Research Base award must describe the scope of its cancer prevention/control clinical trials research. A description of the prevention and/or control committee(s) (or equivalents) and their activities must be provided. In addition, their relationship to other clinical trial committees must be described.

Section 5: Membership.

Collaboration with affiliated CCOPs and/or Minority-Based CCOPs in treatment clinical trials (if applicable) and cancer prevention/control clinical trials is required. The application must describe the ability of the organization applying for Research Base award to involve community physicians and administrators in designing cancer clinical trials that are appropriate for use in community research organizations, such as CCOP Groups. Details should be provided on the ways to involve affiliated CCOPs and/or Minority-Based CCOPs in the organizational structure of the Research Base (e.g., committee memberships, clinical trial chair positions, training programs, authorship on publications, etc.). Research Base affiliation agreements with CCOPs and/or Minority-Based CCOPs must be included in the application.

Prevention Members: The application may designate selected Research Base member/affiliate institutions as “Prevention Members,” provided these institutions have already contributed, or are expected to contribute, in a significant way to the proposed Research Base’s cancer prevention clinical research. The experience and pertinent contributions of the member/affiliate institution(s) designated “Prevention Member” should be described, including how the designee will contribute to cancer prevention research and the overall goal(s) of the proposed Research Base. Examples of significant contributions might include:

Outreach to establish community networks of non-oncology medical specialties that participate in Research Base cancer prevention protocols;
Member institutions that accrue large numbers of participants to the Research Base’s large-scale prevention trials and/or support disease-specific multidisciplinary prevention working group(s) that develop the relevant research agenda(s);
Conducting pilot and/or early phase I/II trials pertinent to chemo-preventive agent(s) development;
Research focused on the mechanism(s) of action of chemo-preventive agents;
Correlative studies addressing specific questions that emerge from the conduct of prevention trials; and/or
Research pertinent to recruitment and retention strategies relevant to prevention trials.

Section 6: Quality Assurance and Data Management. Each application must describe the following elements:

The process and procedures for managing the data from multi-institutional treatment (if applicable) and/or cancer prevention/control clinical trials. Data management includes development of data collection forms, procedures for data transmittal, data entry, data editing, compilation, analysis, quality control and verification of submitted data. Standards should exist for determining eligibility and evaluability of patients/participants entered on clinical trials. Describe the infrastructure that exists to develop the statistical parameters for clinical trial, analyze the data, and report results.
Data-sharing plan. See Section IV. 6. Other Submission Requirements. Include the procedures that will be used and a timeline for making the data available. In addition, discuss how the rights and confidentiality of participants are protected.
Ability to train and maintain the proficiency of personnel from affiliated CCOP and/or Minority-Based CCOP Groups on research techniques required in the successful management of treatment (if applicable) and cancer prevention/control clinical trials. Training activities should include data managers/nurses and any other individuals responsible for data collection, monitoring, or carrying out the intervention(s).
Ability to conduct periodic performance review(s) of affiliated CCOP and/or Minority-Based CCOP Groups, including on-site monitoring (auditing) and written procedures and criteria for continued affiliations. Periodic reviews of other Research Base member/affiliates institutions participating in cancer prevention/control clinical trials must be described, as well.
Plans for independent data and safety monitoring for all prevention/ control clinical trials implemented by the Research Base.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times: Not applicable.

3.A. Receipt, Review, and Anticipated Start Dates
Letter of Intent Receipt Date: June 10, 2008
Application Receipt Date: July 10, 2008
Peer Review Date: November 2008
Council Review Date: January 2009
Earliest Anticipated Start Date: June 1, 2009

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 of the Principal Investigator;
Names of other key personnel;
Participating institutions; and
Number and title of this funding opportunity.

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

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Lori Minasian, M.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 2017, MSC 7340
Bethesda, MD 20892-7340
Telephone: (301) 496-8541
FAX: (301) 496-8667
Email: minasilo@mail.nih.gov

3. B. Sending an Application to the NIH

Applications must be prepared using the forms 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 all copies of the appendix material must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041,
Bethesda, MD 20892-8329 (for U.S. Postal Service express or regular mail)

Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX: (301) 402-0275
Email: ncirefof@dea.nci.nih.gov

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, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or 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.

Resubmission applications are permitted in response to this FOA; however, any such application must include an Introduction addressing the previous peer review critique (Summary Statement).

Renewal applications are permitted in response to this FOA. An application from a currently funded CCOP Group (a renewal application) must include a progress report.

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 NIH Grants Policy Statement.

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 renewal award if such costs: 1) are necessary to conduct the project, and 2) 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 renewal 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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm).

Restrictions for CCOP Applications:

Allocation of funds to support community costs for receipt, handling, and quality control of patient data must be specified. Allowable items in the budget are requests for full or part-time administrative personnel, clinical research associates, data managers, and study assistants; supplies and services directly related to study activities (e.g., processing and sending material for pathology review, processing and sending port films for radiation therapy quality control); and appropriate travel to meetings directly related to study activities (e.g., Research Base meetings, NCI-sponsored strategy sessions/workshops, local travel). Funding is not allowed for clinical care provided to patients (e.g., reimbursement of patient care expenses; transportation costs). Funding is not allowed for clinical support personnel (e.g. pharmacist, physicist, clinical psychologist, dosimetrist). Physician compensation is only an allowable cost for the PI and the designated PI replacement candidate, specifically for time spent on CCOP organizational/administrative tasks. Justification must be provided for personnel time, effort, and funds requested.

Restrictions for Research Base Applications:

Requests for funds must reflect operations/statistical costs for quality control and data management costs for CCOP participation in protocols. This estimate is based on the expected accruals from affiliated CCOP/Minority-Based CCOP Groups and for member/affiliate accruals in cancer prevention and control. CCOP-Research Base affiliation agreements must be included. Each application should include a budget for monitoring and auditing activities. Funding can be requested for scientific development and pilot testing of new cancer prevention and control research initiatives (including support of a cancer prevention and control committee(s) for the Research Base), and for appropriate travel to meetings directly related to study activities (such as NCI-sponsored strategy sessions/workshops).

6. Other Submission Requirements and Information

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information."

Research Plan Page Limitations

Applicants are allowed up to 50 pages for the research plan portion of the application (applicants are encouraged to use the minimum number of pages necessary to clearly and succinctly describe the research plan).

In addition, a CCOP Research Base application that includes large-scale cancer prevention clinical trial(s) and/or “Prevention Member(s)” proposals may use up to an additional 25 pages (maximum of 75 pages total) to describe these elements of the application (see definition of “Prevention Member” under IV.2.B. Form and Content of Application for CCOP Research Base Award, Section 5.

Appendix Materials

All paper PHS 398 applications submitted for May 25, 2008, and subsequent due dates must provide appendix material on CD only, and include five identical CDs in the same package with the application. Paper applications submitted for due dates prior to May 25, 2008, may voluntarily provide the appendix on five identical CDs; if submitting CDs it is not necessary to include a paper appendix (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information

1. Criteria

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

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by National Cancer Institute and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

Undergo a selection process in which only those applications deemed to have the highest scientific and technical 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 NCI’s National Cancer Advisory Board.

The following will be considered in making funding decisions:

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

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 meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

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

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

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

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

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

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the priority score.

A. Review Criteria for CCOP Application

1. Progress Report (for renewal applications only).

Does the CCOP Group meet or exceed accrual requirements for prevention/control/treatment trials, and does the trend in accrual over the funding period provide evidence for continuing accrual at these levels during the upcoming funding period?

Are plans for the follow-up of participants enrolled on the large-scale prevention trials (e.g., STAR, SELECT) described and are the plans adequate?

Does the progress report include the performance evaluations of the CCOP Group by the affiliated Research Bases?

2. Catchment Area.

Does the information on the CCOP Group’s catchment area (including geography, population, location and number of components, presence of cancer care resources that are not part of the application) demonstrate access to a patient population that will provide adequate accrual to trials and that will benefit from the CCOP Group’s portfolio of trials?

Is the study population in the application’s catchment area described, along with a breakdown by gender and minority?

3. Accrual Requirements.

For all CCOP Group applications:

Does the application demonstrate the ability of the investigators to successfully meet or exceed the minimum accrual goals (i.e., at least 50 accruals to treatment trials and 50 accruals to prevention/control trials)?

In addition, for new CCOP Group applications:

Do the applicants plan for opening clinical trials and accessing appropriate participants/patients to consistently meet or exceed NCI’s minimum accrual requirements (i.e., at least 50 accruals to treatment trials and 50 accruals to prevention/control trials)?

Does the application already provide evidence (based on a level of accrual to NCI-approved treatment and prevention/control clinical trials) that that the applicants will meet or exceed minimal accrual goals?

Do the plans for implementing at least two NCI approved cancer prevention/control trials demonstrate the CCOP Group’s ability to participate successfully in Research Base trials, as indicated by the proposed operations for identifying and accruing participants/patients in the CCOP components, and managing the data?

In addition, for renewal CCOP applications:

Does the application demonstrate a successful past history on the part of the investigators of accrual to NCI-approved treatment and prevention/control clinical trials, as demonstrated by exceeding the minimum (i.e., at least 50 accruals to treatment trials and 50 accruals to prevention/control trials)?

If the application describes participation in only pediatric oncology clinical trials, does the application show accrual of a majority of the eligible patients even if the minimum accrual requirements are not met?

Does the application demonstrate outstanding accrual to cancer prevention/control clinical trials even without meeting the minimum accrual goals for cancer treatment trials?

4. Team Organization and Qualifications

Are the qualifications, training, and experience of the PI and the designated PI replacement candidate appropriate for organizing and managing a community oncology clinical research program that includes accrual to NCI approved treatment and prevention/control clinical trials as well as related activities?

Do the applicants document availability of appropriate professional resources (e.g., radiotherapy, pediatrics, surgery, gynecology, urology, gastroenterology, pathology, internal medicine, family practice, nursing, and nutrition) for multidisciplinary clinical trials?

Is the overall structure of the organization stable? Does it demonstrate institutional support for ongoing accrual? Is there evidence of previous success in collaborating as a group?

Does the proposed organizational structure demonstrate previous success in implementing cancer treatment and prevention/control clinical research and related activities?

5. Affiliations with CCOP Research Bases

Has the applicant demonstrated affiliation of the CCOP Group with CCOP Research Bases to ensure access to an adequate selection of clinical trials needed to meet or exceed the accrual requirements and provide an appropriate menu of trials to the participants/patients in their catchment area?

Are the proper affiliation agreements and appropriate Research Base evaluations included in the application?

Has the CCOP Group demonstrated contributions by its team to the overall structure of one or more of its affiliated CCOP Research Bases, by committee participation, serving as committee chairs and/or chairs of cancer clinical trials, and by authorship in joint publications?

6. Quality Assurance and Investigational Drug Management

Have the applicants demonstrated appropriate and adequate mechanisms for quality assurance for both cancer treatment and prevention/control clinical trials?

Do the applicants demonstrate, appropriate and adequate procedures for investigational drug monitoring and data management and identification of false or otherwise unreliable data (through audit reports and otherwise, e.g., by providing CCOP Research Base evaluations)?

If data irregularities have occurred, have the applicants demonstrated their ability to resolve such issues by appropriate corrective actions?

7. Facilities and Institutional Commitment

Are the available facilities, including laboratories, in-patient and outpatient resources, cancer registries, etc., adequate to support the research activities?

Is there adequate and appropriate space for administrative activities and personnel?

B. Review Criteria for CCOP Research Base Applications

1. Progress Report (for renewal applications only).

Has the Research Base developed a portfolio of active cancer prevention/control clinical trials that are appropriate for use in CCOP Groups and member and affiliate institutions, as demonstrated by successful and timely accrual?

Is the portfolio of cancer prevention/control trials open in the Research Base large enough to make a significant contribution to the prevention/control needs of the CCOP Groups, as measured by the ability of the Research Base to meet or exceed accrual goals?

Has the Research Base demonstrated that it will maintain accrual and continue to open new prevention/control trials by having an adequate number of studies in various stages of development that are both scientifically meritorious and feasible for timely accrual in CCOP Groups and member and affiliate institutions?

Are the prior activities adequately summarized, including a clear presentation of annual accrual data, completion of prevention/control trials, interim data analyses, publication of findings or other form of dissemination of trial findings throughout the Research Base, and other milestones in successfully meeting the requirements for a Research Base?

2. Clinical Trials Design and Implementation

Has the Research Base demonstrated the ability to successfully design, develop, conduct and complete multi-institutional NCI-approved clinical trials in cancer prevention and control (i.e., those with interventions affecting quality of life, cancer and treatment-related symptoms, and early detection)?

Are adequate procedures in place to collect, monitor, and analyze the data and assure the safety of patients/participants?

Are appropriate long-term plans in place for the recruitment and retention of participants/patients?

Is the evaluation process for the Research Base’s programs to recruit and retain of minorities adequate?

In addition, for new applications:

Has the application demonstrated the potential of the team to successfully design, develop, conduct and complete multi-center clinical trials?

Is a detailed plan with adequate procedures to collect, monitor, and analyze the data and assure the safety of patients/participants provided?

Has the application demonstrated the potential of the investigators to develop a selection of cancer prevention/control clinical trial as needed to meet its minimum criteria of 50 participant accruals from affiliated CCOP/ MB-CCOP Groups and member/affiliate institutions?

Are detailed descriptions of at least two actual or planned cancer prevention/control clinical trials provided?

3. Accrual Requirements

For renewal applications:

Has the Research Base generated 50 accruals from treatment trials (if applicable) from CCOP/MBCCOP Groups and 50 accruals from prevention/control trials from CCOP/MBCCOP Groups and/or member/affiliate institutions?

Has the Research Base exceeded these minimum accrual requirements?

For first-time renewal applications:

For first-time renewal applications, where the original funding period was less than 5 years, has the Research Base developed a portfolio of active cancer prevention/control clinical trials and trials in development that support the expectation that the Research Base can meet or exceed the goal of 50 accruals to cancer prevention/control trials annually during the next funding period?

For new applications:

Does the application demonstrate the potential of the group to accrue to appropriate clinical trials the required minimum of 50 participants from affiliated CCOP/ MB-CCOP Groups and member/affiliate institutions?

4. Team Organization and Qualifications

Are the qualifications and experience of the PI and the individual directly responsible for the cancer prevention/control clinical trial activity adequate and appropriate for the individuals holding these positions within the Research Base?

Are there sufficient and appropriately experienced multidisciplinary health professionals and allied professionals with the skills needed to develop, conduct, and analyze prevention/control clinical trials and treatment (if applicable)?

Is the organizational structure staffed with sufficient and appropriately trained personnel to assure the timely development, conduct, analysis and reporting of clinical trial data? Does the application have an organizational focus for cancer prevention/control research, as demonstrated by the composition and activities of the cancer prevention/control committee(s), and its relationship to other clinical trial committees and activities?

5. Membership

Does the application demonstrate the contribution of investigators from the affiliated CCOP Group(s) in the organizational structure of the CCOP Research Base? For example, do the CCOP members (accruing physicians, nurses, and clinical research associates) participate in the full spectrum of CCOP Research Base committees or in the design and development of the clinical trials?

For new applications:

Are there sufficient numbers of affiliated CCOP and/or MB-CCOP Groups through which the CCOP Research Base can meet the minimum accrual goals?

Does the application provide the required CCOP Research Base affiliation agreements?

Has the application demonstrated the investigators’ experience in successfully working with community oncologists and orienting their clinical research staff to the study specific requirements?

For applications with designated “Prevention Members”:

Does the application demonstrate relevant accomplishments of each previously designated “Prevention Member” (e.g., protocol development, conduct of pilot or laboratory studies, and/or accrual) that have enhanced the productivity of the cancer prevention research for the Research Base?

Does the application provide evidence that the newly proposed “Prevention Member” (if applicable) will enhance the productivity of cancer prevention research in the Research Base?

6. Quality Assurance and Data Management

Does the application adequately describe appropriate quality control, quality assurance and data management procedures? Are there appropriate and adequate mechanisms for the periodic review of quality control, quality assurance, data management procedures, safety monitoring (including the procedures for the data safety and monitoring committees and on-site auditing programs)?

Does the application adequately demonstrate experience in the collection, management, and analysis of multi-institutional clinical trials? Is there adequate data management staff to perform the proposed scope of work?

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 rating:

Resubmission Applications (formerly “revised/amended” applications): Are the responses to comments from the previous scientific review group adequate? Are the improvements in the resubmission application appropriate? Remove if not applicable

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 on Human Subjects in the PHS 398 instructions).

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 on Human Subjects in the PHS 398 instructions).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five points described in the Vertebrate Animals section of the Research Plan 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. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the NIH IC will be responsible for monitoring the resource sharing.

Data Sharing Plan (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm)
Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html)
Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html)

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.

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

The administrative and funding instrument used for this program will be the cooperative agreement 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.

2. A.1. Principal Investigator Rights and Responsibilities

Separate sub-sections below outline the Rights and Responsibilities of CCOP Awardees and Research Base awardees (Part A and Part B, respectively).

2. A.1. Part A. CCOP Awardee Responsibilities (including PI Responsibilities)

Throughout these Terms and Conditions of Award, “CCOP awardee” refers to the organizational structure which is composed of the key personnel (including the designated accruing physicians) and the institutions/organizations of the performance sites, including those designated as affiliates and CCOP components, all of whom agree to collaborate on research goals of the NCI Community Clinical Oncology Program.

The following three documents (and any subsequent modification to them) are hereby incorporated by reference as terms of award. These documents describe the programmatic responsibilities for the conduct of the research supported by this cooperative agreement. The documents are as follows:

INVESTIGATOR'S HANDBOOK, a Manual for Participants in Clinical Trials of Investigational Agents Sponsored by the Division of Cancer Treatment and Diagnosis, (DCTD), National Cancer Institute (http://ctep.cancer.gov/handbook/);
GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS, CCOP RESEARCH BASES and THE CANCER TRIALS SUPPORT UNIT (CTSU) (http://cancer.gov/monitoring/guidelines.html); and
Intellectual Property Option to Collaborator (http://cancer.gov/industry/ipo.html).

Specific Responsibilities of the CCOP PI

Oversees the implementation of the Clinical Trials across the CCOP awardee.
Assures that all Human Subjects Requirements are met by all accruing physicians.
Ensures appropriate Quality Assurance/Quality Control is in place for complete and accurate data collection.
Submits quarterly accrual reports in a standard format as described at http://prevention.cancer.gov/programs-resources/programs/ccop/resource
Submits annual Progress Report PHS 2590 to the NCI Program Official.
Attends periodic NCI strategy meetings and meetings of affiliated CCOP Research Bases.
Reports any findings of suspicious or suggestions of intentional misrepresentations of data to the NCI Program official and the Research Base PI.

Clinical Trials Appropriate to Meet the CCOP Accrual Requirements

To receive credit for accruals the CCOP awardee must access NCI-approved treatment and prevention/control clinical trials through the CCOP Research Bases with which CCOP awardee has affiliation agreements. The CCOP awardee also may access treatment trials from Research Bases with which it is not affiliated through the NCI’s Cancer Trials Support Unit (CTSU). Accruals by CCOP awardees to CTSU protocols will receive credits (towards the required accrual quotas) and not per case reimbursement.

All clinical trials originating at the CCOP Research Bases must be reviewed and approved by the Protocol Review Committee of the Division of Cancer Prevention (DCP) or the Division of Cancer Treatment and Diagnosis (DCTD), NCI, prior to implementation.

Required Affiliations of CCOP Awardees with Research Bases

Each CCOP awardee must affiliate with one national multi-specialty cooperative group having a spectrum of cancer treatment and prevention/control clinical trials. As an exception, CCOP awardees may be granted permission to affiliate with more than one multi-specialty group, if the CCOP awardee participates in NCI-sponsored “pilot” projects. In addition, each CCOP awardee may affiliate with as many other Research Bases (exclusive of the multi-specialty groups) as the CCOP deems appropriate.

Typically, an established CCOP Group is expected to affiliate with approximately four to six CCOP Research Bases (in addition to its affiliation with multi-specialty cooperative group). Through these affiliations, the CCOP awardee must ensure an access to an adequate selection of clinical trials for its patient population and to meet/or exceed the minimum accrual requirements.

If participation of the CCOP awardee in the clinical trials of one CCOP Research Base competes with that of another CCOP Research Base with which the CCOP awardee is affiliated, the CCOP must prioritize the protocols to avoid bias in the allocation of participants/patients to competing protocols.

Note: A list of eligible Research Bases may be obtained from the CCOP Web pages at http://cancer.gov/prevention/ccop/rbccop.html or by contacting the Community Oncology and Prevention Trials Research Group (COPTRG), DCP, NCI, at (301) 496-8541.

When circumstances require changes in Research Base affiliations, prior written approval from the DCP Program Director is required. The Guidelines for Approval of CCOP Organizational Changes is available at http://prevention.cancer.gov/programs-resources/programs/ccop/resource

Accrual Requirements for CCOP Awardees

Each CCOP awardee must accrue a minimum of 50 participants/patients per year to cancer prevention/control clinical trials.

The quotas of newly accrued participants may be, in part, fulfilled by listing active follow-up of participants previously accrued to multi-year chemoprevention trials. For purposes of meeting accrual targets, however, ten participants in active follow-up are needed to substitute for three participants enrolled in cancer prevention/control trials.
The minimum for cancer prevention/control accruals may be waived for applicants whose specialty is pediatrics and who are able to enroll a majority of their eligible participants/ patients on cancer prevention/control trials.

Each CCOP awardee must accrue a minimum of 50 participants/patients per year to treatment clinical trials. The minimum of 50 treatment participants/patients may be waived in case of:

CCOP awardees that participate only in pediatric cancer clinical trials and able to place the majority of their eligible participants/patients on treatment trials; and/or
CCOP awardees with an outstanding record in accrual to cancer prevention/control trials.

Quality Control Guidelines for CCOP Awardees

In accordance with CCOP Research Base guidelines and NCI policies, the CCOP awardee must establish and follow procedures for the assurance of data quality and for the prevention and/or identification of false or otherwise unreliable data. The CCOP awardee must follow policies developed by the CCOP Research Bases with which they are affiliated. Any data irregularities identified through quality control procedures or through the audit program that raise the suspicion of intentional misrepresentation of data must be reported to the NCI DCP Program Director within 24 hours. COPTRG must be notified by telephone (301-496-8541) of any findings suspicious or suggestive of intentional misrepresentation of data and/or disregard of regulatory safeguards for any of the three components (regulatory, pharmacy, and patient care) within an audit. It should be emphasized that a reasonable level of suspicion is sufficient to warrant notification to NCI of irregularity and/or misrepresentation.

Data Management by CCOP Awardees

The CCOP awardee must provide the NCI DCP Program Director with access to all data generated under this award for periodic review of data management procedures of the CCOP. Data must also be available for external monitoring if required by NCI's agreement with other federal agencies, such as the FDA, and with NCI's agreements with pharmaceutical companies for the co-development of investigational agents. The awardees will retain custody of and primary rights to their data.

Investigational Drug Management by CCOP Awardees

Investigators performing trials under cooperative agreements will be expected, in cooperation with NCI, to comply with all FDA monitoring and reporting requirements for investigational agents. Specifically, all CCOP investigators accruing participants/patients must have an active FDA Form 1572 on file with the Pharmaceutical Management Branch, Clinical Trials Evaluation Program (CTEP), DCTD, NCI.

Monitoring of the Activities of CCOP Awardees

Each CCOP awardee must agree to periodic on-site audits by representatives of its CCOP Research Base(s), NCI, or an NCI-designee. Such on-site audits may include review of the following:

use of investigational drugs;
compliance with regulations for Institutional Review Board (IRB) approval and informed consent (compliance with 45 CFR 46);
compliance with clinical trial specifications;
quality control and accuracy of data recording; and/or
completeness of reporting adverse drug reactions.

The performance sites designated as affiliates and CCOP components and the individual accruing investigators participating or collaborating with the CCOP awardee must be in compliance with the monitoring standards established by the CCOP Research Base(s) and stated in the NCI GUIDELINES FOR ON-SITE MONITORING OF CLINICAL TRIALS FOR COOPERATIVE GROUPS, CCOP RESEARCH BASES, and THE CANCER TRIALS SUPPORT UNIT (CTSU) (http://cancer.gov/monitoring/guidelines.html). Sites found not to be in compliance with the NCI monitoring guidelines may be suspended from participating in Research Base trials until compliance can be confirmed by NCI/CTMB.

Specifically, the institutions/organizations representing performance sites must adhere to the following standards:

Medical records submitted in support of NCI multi-institutional trials must conform to usual standards for the maintenance of clear, accurate, and unambiguous medical records. White-out corrections on medical records are unacceptable;
If it is the usual and customary practice of a department, laboratory, clinic, or office to prepare or issue official reports, then only that department, laboratory, clinic, or office can change the report, and alterations of the medical record must be initialed and dated by the person making such alterations (for clinical progress notes, the change must be dated and initialed by the person making the change, and only one line should be placed through the initial entry, so that both the original entry and the change are legible);
Improper modification of important participant/patient records will result in additional investigations by the NCI DCTD Clinical Trials Monitoring Branch (CTMB) and may lead to suspension of accrual and funding.

CCOP Radiotherapy Equipment

Radiotherapy equipment must have its calibration verified according to standards set by the Radiologic Physics Center (RPC) in order for institutions to participate in clinical trials requiring radiation therapy, as required by the affiliated Research Base(s).

Organizational Changes in a CCOP

Certain organizational changes in the structure of a CCOP awardee must have the prior written approval of the DCP Program Director. These changes include the addition/deletion of a participating physician, a health professional other than a physician (who is active in enrolling participants/patients to cancer treatment, prevention and control trials), an affiliate, a component, or a Research Base affiliation. The Guidelines for Approval of CCOP Organizational Changes is available at http://prevention.cancer.gov/programs-resources/programs/ccop/resource

CCOP Network Participation

CCOPs are part of a national network for conducting cancer prevention/control and treatment clinical trials. As such, each CCOP may be asked to participate in strategy sessions or workshops and in the continuing evaluation of the program and its impact in the community.

Logging Patients/Participants by CCOP Awardees

Each CCOP awardee may be asked to maintain a new patient/participant log or minimal registry to include as applicable age, sex, race, insurance status, risk factors, primary site of cancer, stage of disease, and disposition for the potentially eligible patient/participant pool seen by the CCOP investigators.

Federally Mandated Requirements as Pertinent to CCOP Awardees

Each CCOP awardee must establish mechanisms to meet DHHS/PHS regulations for the protection of human subjects. Appropriate documentation must be available for review. At a minimum, these requirements include the following:

Current and approved Federal Wide Assurance (FWA) is on file with the Office of Human Research Protection (OHRP) for each facility in which CCOP investigators are conducting clinical trials;
Each and every clinical trial is reviewed by the responsible IRB prior to participant/patient entry;
Each and every clinical trial is reviewed annually by the IRB as long as the protocol is active;
Every participant/patient (or participants/patient's parent/legal guardian) gives fully informed written consent to participation in a clinical trial prior to the initiation of the experimental intervention;
Timely reporting of all serious and unexpected toxicities to the appropriate sponsor to include Investigational Drug Branch, CTEP, DCTD, according to DCTD guidelines and/or to DCP according to DCP guidelines;
Implementation of DCP/DCTD requirements for storage and accounting for investigational agents provided under DCP/DCTD sponsorship; and
Education on the protection of human research participants for all investigators involved in the design or conduct of research involving human subjects.

For other Federally mandated requirements see the following Federal citations:

Human Subjects Protection (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm);
Data and Safety Monitoring Plan (http://grants.nih.gov/grants/guide/notice-files/not98-084.html);
Sharing Research Data (http://grants.nih.gov/grants/policy/data_sharing);
Access to Research Data through the Freedom of Information Act (http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm;
Inclusion of Women And Minorities in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html) and http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm;
Inclusion of Children as Participants in Clinical Research http://grants.nih.gov/grants/funding/children/children.htm. ;
Required Education on the Protection of Human Subject Participants http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html;
NIH Public Access Policy http://www.nihms.nih.gov/ and http://publicaccess.nih.gov/
Standards for Privacy of Individually Identifiable Health Information http://www.hhs.gov/ocr/ and http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html
Healthy People 2010 (http://www.health.gov/healthypeople);
Authority and Regulations http://www.cfda.gov/ and http://grants.nih.gov/grants/policy/policy.htm.

Publications by CCOP awardees

Timely publication of major findings is encouraged. Publications or oral presentations of work conducted under this cooperative agreement require proper acknowledgment of NCI support.

2. A.1. Part B. Research Base Awardees Responsibilities (including PI Responsibilities)

Throughout these Terms and Conditions of Award, “CCOP Research Base” refers to the organizational structure which is composed of the key personnel (including the designated accruing physicians) and the institutions/organizations of the performance sites, which implement the clinical trials and agree to collaborate on research goals of the NCI Community Clinical Oncology Program. In addition, throughout these Terms of Conditions of Award, “Research Base,” refers to all of its members no matter how the membership is defined by a particular Research Base.