Part I Overview Information

Department of Health and Human Services

Participating Organization
National Institutes of Health (NIH) (http://www.nih.gov/)

Component of Participating Organization
National Cancer Institute (NCI) (http://cancer.gov/)

Title: Community Clinical Oncology Program (U10)

Announcement Type

This Funding Opportunity Announcement (FOA) is a reissuance of RFA-CA-05-014, which was previously released April 23, 2004.

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

• May 25, 2007 (RFA-CA-07-048) - This RFA has been reissued as RFA-CA-07-048.

• The Division of Cancer Prevention of the National Cancer Institute (NCI) established the Community Clinical Oncology Program (CCOP) in 1983 to develop and conduct state-of-the-art cancer prevention clinical trials and control and treatment clinical trials with significant involvement of community oncologists and populations they serve. The mission of the CCOP includes: (1) increasing the participation of oncologists and other community specialists in NCI-approved clinical 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 NCI-funded 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 Clinical Cooperative Group or at an NCI-designated Cancer Center.
• This Funding Opportunity Announcement (FOA) solicits U10 cooperative agreement applications from new and currently funded CCOP groups and CCOP Research Bases.
• The NCI intends to commit approximately $32 million in total costs in FY 2007 to fund approximately 17 CCOP group and 11 Research Base awards. In addition, it is anticipated that approximately $28 million in total costs will be committed to support several ongoing and/or approved large-scale cancer prevention trials, such as those that are conducted by some of the currently funded CCOP Research Bases.
• For CCOP groups, the total project periods may not exceed 3 years for new applications, and no more than 5 years for renewal applications. For CCOP Research Bases, the total project period may not exceed 5 years for new as well as renewal applications.
• A CCOP group may be formed by oncologists from one or more eligible institutions, who collectively must be capable of achieving specific goals for annual accrual to treatment clinical trials and to prevention/control clinical trials.
• The following categories of institutions/organizations (here forth referred to as community institutions ) are eligible to apply for CCOP group awards: hospitals; clinics; groups of practicing physicians; health maintenance organizations (HMOs); and consortia of hospitals and/or clinics and/or physicians and/or HMOs that agree to work together with a principal investigator (PI) and a single administrative operation center.
• A university, Veterans Administration (VA) hospital, or military treatment facility (MTF) may be included in a CCOP group application as a member of a consortium led by a community institution, but may not be the applicant organization or the major contributor to participants/patient accrual. A non-university clinical trials cooperative group member that is not currently funded by NCI is eligible to apply. 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.
• Potential applicants for CCOP group award from community institutions serving primarily minority populations should consider the companion funding opportunity for the Minority-Based Community Clinical Oncology Program (MBCCOP) (for details, see RFA-CA-07-026, http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-07-026.html).
• Institutions NOT ELIGIBLE to apply as the CCOP group applicant organization 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, NCI.
• Only NCI-funded Clinical Trials Cooperative Oncology Groups (Cooperative Groups) and NCI-designated Cancer Centers are eligible to apply for CCOP Research Base awards. An NCI Clinical Cooperative Group applying to become a CCOP Research Base must propose to develop and implement clinical trials in cancer prevention and control as well as in cancer treatment. An NCI-designated Cancer Center applying to become a CCOP Research Base must propose to develop and implement only cancer prevention and control clinical trials, but may, in addition, propose to develop and implement cancer treatment clinical trials as well.
• Eligible Principal Investigators (PIs) with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institutions to develop an application for support. Individuals from under-represented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.
• Each applicant may submit only one application.
• Applications must be prepared using the PHS398 research grant application and forms. Application materials are available from the NIH Office of Extramural Research (OER) at http://grants.nih.gov/grants/oer.htm.
• See Section IV.1 for application materials.
• Telecommunications for the hearing impaired is available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt and Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Sharing Research Data
D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

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

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose:

The overall objective of this Request for Applications (RFA) is to develop and conduct state-of-the-art cancer prevention clinical trials and control and treatment clinical trials with a 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 participate in 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 RFA solicits 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 who accrue patient/participants to clinical trials designed and conducted by the CCOP Research Bases. Each CCOP group must be capable of accruing annually at least 50 patients to treatment clinical trials and at least 50 participants to prevention and control clinical 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 chemopreventive 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. These clinical trials include those designed to evaluate: chemoprevention and the clinical validation of biomarkers; screening and early detection; symptom management; and quality of life, pain control, and continuing care interventions.

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 2005, the CCOP network consisted of 50 CCOP groups, located in 30 states and comprising more than 395 hospitals and more than 3,325 physicians. The CCOPs enrolled approximately 8,300 patients to treatment trials and 5,250 participants/patients to prevention and control trials. The network also included 14 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 CCOP group award from community institutions serving primarily minority populations should consider a companion funding opportunity for Minority Based-CCOP (for details, see RFA-CA-07-026, http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-07-026.html).

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

Section II. Award Information

1. Mechanism(s) of Support

This FOA will use the NIH U10 cooperative agreement award mechanism.

This funding opportunity uses the just-in-time concepts. It also uses the non-modular budget format described in the PHS398 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 U10 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 NIH staff being substantially involved as a partner with the PI, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award."

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 RFA is a one-time issuance, it is expected that a CCOP RFA will be published in the NIH Guide for Grants and Contracts on an annual basis, provided that funds are available.

2. Funds Available

The NCI intends to commit approximately $32 million dollars in FY2007 to fund approximately 28 new and/or renewal CCOP and Research Base cooperative agreement awards in response to this RFA. Approximately seventeen CCOP group and eleven Research Base awards are anticipated. In addition, approximately $28 million dollars will be committed to support several ongoing and/or approved large-scale cancer prevention trials conducted by one or another of the renewal Research Base applications. A CCOP group application may request a project period of up to 3 years in a new application and up to 5 years in renewal application. A Research Base application may request up to 5 years for a new or a renewal application. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the NCI provide support for this program, awards pursuant to this FOA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. The anticipated start date for the application(s) selected for funding is June 2007.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

With the additional restrictions outlined below, you may submit (an) application(s) for a CCOP group or CCOP Research Base award if your organization has any of the following characteristics:

• For-profit organizations;
• Non-profit organizations;
• Public or private institutions, such as universities, colleges, hospitals, and laboratories;
• Domestic Institutions; and
• Faith-based or community-based organizations.

Foreign institutions and organizations are ineligible to apply for either a CCOP group or CCOP Research Base award.

Additional conditions of eligibility:

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) or an NCI-funded Cancer Center;
• 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 may propose to design and conduct only cancer prevention/control clinical trials or can proposed to develop and conduct treatment trials as well.

1. B. Eligible Individuals

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

2. Cost Sharing or Matching

Cost sharing is not required for this FOA.

3. Other Special Eligibility Criteria

Not applicable.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS398 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 forms. For further assistance, contact GrantsInfo; Telephone: (301) 710-0267, E-mail: [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 PHS398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

A suggested format ( Suggestions for Organizing Information for a CCOP group or CCOP Research Base Application, ) is available at http://cancer.gov/prevention/ccop/. All applications are encouraged to use the suggested format instructions for organizing the specific information concerning the RFA programmatic requirements in the PHS398. 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 PHS398 Research Plan (Sections A-D) is substituted with new sections with altered page limits as indicated below.

A. Form and Content of Application for CCOP Group Award

For CCOP group applications submitted in response to this RFA, the standard PHS398 "Research Plan" (Sections A-D) 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);
• The 50 pages (or fewer if possible) should be apportioned as desired by the applicant to cover new Sections 1-7, as outlined below; and
• Other sections of the PHS398 Research Plan (Sections E-L) remain unmodified.

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, which at a minimum consists 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.

NOTE: new CCOP group applicants should insert Not applicable in this section.

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. Plans must list estimated accrual to specified NCI-approved trials. Strategy 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 annually (with exceptions noted below).

• This requirement quota 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 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.

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 chemopreventive 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 item g below).

Section 4: Team Organization and Qualifications. A designated PI is required. An Associate PI should be named to assure continuity in the event of resignation of the PI. The qualifications and experience of both must be described, specifically documenting their ability 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 must be described.

The application should include a description of planned organizational structure and procedures for implementing the CCOP group workflow. 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 and exceed accrual goals. Such 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 approximately 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 with the CCOP group application. 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://cancer.gov/prevention/ccop 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. 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 RFA, the standard PHS398 Research Plan (Sections A-D) 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).
• The 50 pages (or fewer if possible) should be apportioned as desired by the applicant to cover new 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).
• Other sections of the PHS398 Research Plan (Sections E-L) remain unmodified.

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 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, which at a minimum consists of:

• A summary of CCOP Research Base activities and accomplishments pertinent to the development and conduct of the CCOP Research Base’s cancer prevention/control clinical trials research program, including a discussion of how clinical trials build on and/or complement subsequent trials to further the group’s targeted clinical 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.

NOTE: new CCOP Research base applicants should insert Not applicable in this section.

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

• Each application must demonstrate the ability 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.
• In addition, CCOP Research Base applications from Cancer Centers proposing the participation in treatment clinical trials must demonstrate the ability to design and implement multi-institutional cancer treatment clinical trials. A list of treatment clinical trials available for CCOP participation must be provided.
• 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 treatment clinical trials (if applicable) and prevention/control clinical trials of high scientific merit. The portfolio of active and accruing trials, the clinical 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 exceed the stated minimal number of accruals.
• 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 treatment (if applicable) and/or 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-Bases 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 cancer prevention clinical research agenda of the institution applying for the Research Base award. The experience and pertinent contributions of the member/affiliate institution(s) designated Prevention Member should be described, including how the designee will further the cancer prevention research agenda 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 large-scale 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 ability of the team to manage 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. Statistical infrastructure must exist 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 review of other Research Base member/affiliates institutions participating in cancer prevention/control clinical trials must be described, as well.
• Plan 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 N/A.

3.A. Receipt, Review, and Anticipated Start Dates
Letters of Intent Receipt Date(s): July 28, 2006
Application Receipt Date(s): August 28, 2006
Peer Review Date(s): November 2006
Council Review Date(s): January 2007
Earliest Anticipated Start Date: June 2007

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 PI;
• 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 NCI staff to estimate the potential review workload and plan the review.

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

Lori Minasian, M.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 2017, MSC 7340
Bethesda, MD 20892-7340 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery; non-USPS service)
Telephone: (301) 496-8541
Fax: (301) 496-8667
E-mail: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (for U.S. Postal Service express or regular mail)
Bethesda, MD 20817 (for express/courier delivery; non-USPS service)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and the appendix materials in pdf format must be sent to:

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

As described in NIH Guide Notice NOT-OD-06-051 and clarified in Notice NOT-OD-06-053, effective for applications for submission/receipt dates of May 10, 2006 and beyond, the instructions for including appendix material have changed. The Appendix may include publications, manuscripts (accepted for publication), abstracts, patents, or other printed materials directly relevant to the proposed project. The Appendix may not include manuscripts submitted for publication.

The new process is:

• Publications in press: Include only a publication list with a link to the publicly available on-line journal article or the NIH PubMed Central (PMC) submission identification number. Do not include the entire article.
• Manuscripts accepted for publication but not yet published: The entire article should be submitted.
• Manuscripts published but an online journal link is not available: The entire article should be submitted.

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3. C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the NCI. Incomplete and non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm).

Pre-Award Costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or competing continuation award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or competing continuation award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee’s ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

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

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 associate PI, 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

Plan for Sharing Research Data

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants 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.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

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

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

Clinical Terms of Awards

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

Section V. Application Review Information

1. Criteria

T he following will be considered in making funding decisions:

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

2. Review and Selection Process

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

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 will be discussed and assigned a priority score;
• Receive a written critique; and
• Receive a second level of review by the National Cancer Advisory Board.

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

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

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

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

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

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

In additional to the standard NIH review criteria identified above, reviewers will be asked to comment on the following criteria in order to judge the likelihood that the proposed research program will be successful in the pursuit of the goals of CCOP or Research Bases. 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 deserve a high priority score.

A. Review Criteria for CCOP Application

1. Progress Report (for renewal applications only).

Does the CCOP group demonstrate adequate progress as reflected by its accrual to cancer prevention/control/treatment clinical trials?

Are the activities and accomplishments clearly and adequately summarized, including the clear data on annual accruals?

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 the CCOP group by the affiliated Research Bases?

2. Catchment Area.

Does the application describe its catchment area adequately and provide a map of the service area?

Are other cancer care resources in the service area, that are not a part of the application, described?

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 to successfully meet or exceed the minimum accrual goals?

In addition, for new CCOP group applications:

Does the application demonstrate a plan to consistently meet or exceed the minimum (i.e., 50 participants) accrual goal to NCI-approved treatment clinical trials and prevention/control clinical trials?

Does the application already demonstrate a level of accrual to NCI-approved treatment and prevention/control clinical trials that provides evidence that it will meet or exceed minimal accrual goals?

Does the application adequately describe plans for implementing at least two NCI approved cancer prevention/control clinical trials?

In addition, for renewal CCOP applications:

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

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/associate PI 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?

Are the training and experience of physicians who are accruing patients/participants appropriate?

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?

Are the training and experience of the clinical research staff adequate and appropriate?

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 quota?

Are the proper affiliation agreements provided in the application?

Does the application include the appropriate CCOP Research Base evaluations?

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

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

Does the application demonstrate, through audit reports and otherwise [e.g., by providing CCOP Research Base evaluation(s)], appropriate and adequate procedures for investigational drug monitoring and data management and identification of false or otherwise unreliable data?

If data irregularities have occurred, has the application demonstrated appropriate and adequate resolutions of the issues and put appropriate corrective action in place?

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).

Does the application adequately describe the progress in implementing a prevention/control clinical trials program including the development and conduct of cancer prevention/control trials, accrual, data management, evaluation of performance sites?

Does the application reflect adequate progress as determined by the current status of each trial in its stage of development and progress towards meeting planned accrual goals?

Are the prior activities adequately summarized, including a clear presentation of annual accrual data, completion of clinical 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 CCOP Research Base?

2. Clinical Trials Design and Implementation

Does the application demonstrate 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)?

Does the application demonstrate the adequate procedures to collect, monitor, and analyze the data and assure the safety of patients/participants?

Does the application demonstrate the development of high quality prevention/control clinical trials that can be implemented in the community and/or among the other member and affiliate institutions of the CCOP Research Bases?

Does the application describe appropriate long-term plans for the recruitment and retention of participants/patients?

Does the application describe the evaluation process for the Research Base’s programs to recruit and retain of minorities?

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?

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

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

Has the application provided a detailed description of at least two actual or planned cancer prevention/control clinical trials?

For those Research Base applications that propose to develop and conduct treatment clinical trials, does the application demonstrate the potential to develop a selection of appropriate treatment trials to meet the minimum of 50 patient accrual quota from affiliated CCOP/MBCCOP groups?

3. Accrual Requirements

For renewal applications:

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

Has the Research Base exceeded the minimum requirements?

For new applications:

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

4. Team Organization and Qualifications

Does the application describe the appropriate qualifications and adequate experience for the PI and the individual directly responsible for the cancer prevention/control clinical trial activity?

Are there sufficient and appropriately experienced multidisciplinary health professionals and allied professionals with the skills needed to develop, utilize, and analyze treatment and prevention/control clinical trials to be evaluated?

Does the application demonstrate an organizational structure 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 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 priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by NCI Program staff through an administrative review of the plan. Reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy (see http://grants.nih.gov/grants/policy/data_sharing).

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (see the NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and at http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

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

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

3. Anticipated Announcement and Award Dates

Applicants will be notified about the disposition of their applications once the National Cancer Advisory Board completes its second level of review of the applications. Applicants can expect notification in March of 2007.

Section VI. Award Administration Information

1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 of 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 PI as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, 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 (U10), 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. 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 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.

• 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);
• 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://www.cancer.gov/prevention/ccop/resources.html
• Submits annual Progress Report PHS2590 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 P.I.

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.

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 to meet and exceed the minimum accrual goals.

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: 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.

Initial affiliations should be maintained for the duration of the funding cycle. When circumstances require changes in Research Base affiliations, prior written approval from the DCP Program Director is required. The Guidelines for Obtaining Approval of CCOP Organizational Changes is available at http://cancer.gov/prevention/ccop/guidelines.html.

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, three participants in active follow-up are needed to substitute for one participant enrolled in 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 at least 10 percent of their eligible participants/patients on trial.
• 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 DCP/NCI 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 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, 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
• 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 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 prevention and control trials), an affiliate, a component, or a Research Base affiliation. The Guidelines for Obtaining Approval of CCOP Organizational Changes is available at the URL address: http://cancer.gov/prevention/ccop/guidelines.html.

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
• 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, http://publicaccess.nih.gov/ and http://publicaccess.nih.gov/publicaccess_Manual.htm);
• 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.

The following 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.

• 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);
• Intellectual Property Option to Collaborator (http://cancer.gov/industry/ipo.html).

It is the responsibility of the Research Base in accordance with its constitution, bylaws, policies, and procedures to develop the details of the research design, including definition of objectives and approaches, planning, implementation, analysis, and publication of results, interpretations and conclusions of the trials. The Research Base shall designate Research Base investigators to serve as Study Chairpersons for each proposed clinical trial. All clinical trials will be developed in accordance with the instructions in the INVESTIGATOR'S HANDBOOK.

Specific Responsibilities of the CCOP Research Base PI

• Oversees the development of the Clinical Trials by the CCOP Research Base.
• Responsible for the content and direction of the CCOP Research Base’s cancer prevention and control research program.
• Prioritizes the plans and clinical trials in the context of the CCOP Research Base s overall scientific objectives.
• Assures that all Human Subjects Requirements are met by all accruing physicians.
• Ensures that appropriate Quality Assurance/Quality Control mechanisms are in place for complete and accurate data collection.
• Submits annual Progress Report PHS2590 to the NCI Program Official.
• Attends periodic NCI strategy meetings.
• Reports any findings of suspicious or suggestions of intentional misrepresentations of data to the NCI Program official.

Clinical Trials Development by a CCOP Research Base

The awarded CCOP Research Base is responsible for the development and conduct of high quality cancer prevention/ control clinical trials and treatment trials, if applicable, and for evaluation of the results of such clinical trials. The document that describes the clinical trial (referred to as a protocol) must be reviewed and approved by the Protocol Review Committee for either DCP, NCI or DCTD, NCI, prior to implementation.

The process for submission includes:

• Submission of all prevention/control trials to the DCP Protocol Information Office (PIO), NCI (http://cancer.gov/prevention/pio).
• An initial concept document is submitted for review.
• If the concept is approved, the protocol document with an informed consent is submitted.
• Submission of all treatment trials to CTEP Protocol Information Office (PIO), DCTD, NCI (http://cancer.gov/about/pio.html
• Appropriate and adequate response to all concerns raised in the review of the documents.
• A complete description of the submission and review process may be found at: http://www.cancer.gov/prevention/ccop/protodev.html

Accrual Requirements for a CCOP Research Base

A CCOP Research Base must meet the following minimal requirements for accrual to clinical trials which a given Research Base has designed and developed:

• For prevention/control clinical trials, at least 50 participants per year from CCOP and Minority-Based CCOP awardees, and from other member institutions.
• For treatment clinical trials, at least 50 participants/patients per year from CCOP and Minority-Based CCOP awardees.

Data Management and Analysis by CCOP Research Base

The awarded CCOP Research Base shall establish and implement mechanisms for data management and analysis that ensure:

• Adequate procedures for quality control and analysis;
• Sufficient simplicity to encourage maximum participation of physicians entering participants/patients and to avoid unnecessary expense.

Data generated are the property of the awardee; however, the CCOP Research Base must provide DCP/DCTD with access to all data generated under this award. In addition, the Research Bases must have a data-sharing plan as required by the extension of NIH policy regarding sharing research resources (See NIH Grants Policy, Part II Subpart A, Availability of Research Results). See also the Suggestions for Organizing Information for a CCOP Research Base Application, for guidance on the application of this policy to Research Base cooperative agreements at http://cancer.gov/prevention/ccop.

Data must also be available for external monitoring if required by NCI's agreement with other Federal agencies, such as the FDA and by NCI's agreements with pharmaceutical companies for the co-development of investigational agents.

Quality Control by CCOP Research Base

Each awarded CCOP Research Base must follow all the policies and procedures for quality control established by NCI.

The CCOP Research Base is responsible for monitoring the progress of each clinical trial following good clinical practices through:

• Tracking and reporting of participant/patient accrual and adherence to defined accrual goals;
• Conducting ongoing assessment of case eligibility and evaluability;
• Timely medical review and assessment of participant/patient data;
• Assuring that medical records used in support of NCI multi-institutional trials conform to usual standard for the maintenance of clear, accurate, and unambiguous medical records,
• Reporting of all adverse events that are intervention-related and communicating this information to all parties;
• Rapid reporting of all serious adverse events in compliance with DCP and DCTD policies
• Interim evaluation and consideration of measures of outcome as consistent with participant/patient safety and good clinical trials practice;
• Timely communication of results of clinical trials supported under this award
• An on-site monitoring program.

The CCOP Research Base is responsible for ensuring that all performance sites have routine audits that are reported to the NCI in accordance with the NCI/CTMB 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). In the event that the NCI determines that the awardee failed to comply with these guidelines, the accrual of new patients/participants to the Research Base's clinical trials at the affected performance site shall be suspended immediately upon notice from the NCI. The suspension will remain in effect until the awardee conducts the required audit and the audit report is accepted by the NCI.

The CCOP Research Base will be responsible for notifying any affected performance site of the suspension. During the suspension period, no funds from this award may be provided to the performance site for new accruals, and no changes to the award for new accruals will be permitted. The NCI will also notify an institution that is the direct recipient of a cooperative agreement from the NCI if it is necessary to suspend accrual at that institution.

Quality Assurance of Data Guidelines for CCOP Research Base

The CCOP Research Base must develop and follow procedures for the assurance of data quality in accordance with Research Base guidelines and NCI policies. The CCOP Research Base must follow NCI-approved procedures for the prevention and/or identification of false or otherwise unreliable data and for quality assurance of data collected. The CCOP Research Base must develop and implement NCI-approved policies for auditing the accuracy of scientific data submitted to them.

Any data irregularities identified through quality control procedures or through the audit program that raise any suspicion of intentional misrepresentation of data must be immediately reported to CTMB/CTEP/NCI. The CTMB must be notified immediately by telephone [301-496-0510] of any findings suspicious and/or suggestive of intentional misrepresentation of data and or disregard for regulatory safeguards for any of the three (regulatory, pharmacy, and patient care) components of an audit. Similarly, any data irregularities identified through other quality control procedures suspicious and/or suggestive of intentional misrepresentation of data must be immediately reported to CTMB. It is the responsibility of the CCOP Research Base to immediately notify CTMB when they learn of any significant irregularities or allegations related to scientific misconduct by a staff member or institution participating in their research program. It should be emphasized that the irregularity/misrepresentation does not need to be proven, a reasonable level of suspicion suffices for CTMB/CTEP notification. It is also essential that involved individual(s) and/or institutions follow their own institutional misconduct procedures in these matters.

In the event that there is a finding through the quality assurance and/or quality control programs of any indication of a pattern of non-compliance with protocol or regulatory requirements or a finding of possible alteration of data, these findings must be reported in accordance with the NCI-CTMB 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).

Monitoring Plan and Data Safety and Monitoring Boards for CCOP Research Base

NIH policy requires that all clinical trials require data and safety monitoring, with the method and degree of monitoring being commensurate with the risks (NIH Policy for Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 1998 (http://nih.gov/grants/guide/notice-files/not98-084.html).

The CCOP Research Base must establish and maintain Data and Safety Monitoring Committees (DSMCs) for all Phase III clinical trials in accordance with the NCI’s policy for Data Safety and Monitoring of Clinical Trials at http://nih.gov/grantspolicies/datasafety.htm. The CCOP Research Base must comply with the approved policies and procedures of the DSMB. Further, the CCOP Research Base must establish data safety and monitoring plans for all phase I and II clinical trials in accordance with NIH policies at http://nih.gov/grants/guide/notice-files/NOT-OD-00-038.html. A CCOP Research Base may develop standard monitoring plans for Phase I and II trials however; these plans should be evaluated for appropriateness to each particular clinical trial. Information concerning essential elements of data safety monitoring plans for clinical trials funded by the NCI is available at http://cancer.gov/clinical_trials. These monitoring activities are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).

Clinical Trial Closure by CCOP Research Base

The CCOP Research Base shall establish a mechanism for interim monitoring of progress and results of the clinical trials. If the CCOP Research Base wishes to close accrual to a study prior to meeting the initially established accrual goal, the interim results and other documentation should be made available to NCI staff for review and concurrence prior to closure. It is recommended that statistical guidelines for early closure be presented as explicitly as possible in the clinical trial document in order to facilitate these decisions. In the event that the DSMC has recommended early closure, DSMC procedures regarding notification of DCP must be followed.

Performance Review by CCOP Research Base

The CCOP Research Base shall establish policies and procedures for credentialing participating CCOP awardees and Minority Based-CCOP awardees and conducting periodic review of the performance and membership status of each performance site conducting prevention/control clinical trials. This review should examine scientific contributions, participant/patient accrual, data accuracy and timeliness, protocol compliance, and audit results.

In addition, procedures for selecting institutions as Prevention Members of the CCOP Research Base should be established, if applicable, as well as evaluation criteria for these members progress.

Access to CCOP Research Base Data Files by NCI

Upon the request of the Grants Management Officer, NCI, copies of data files and supporting documentation for all NCI-supported protocols that have a major impact on patterns of care, as determined by the NCI, shall be made available to the NCI in a timely manner.

Investigational Drug Management by CCOP Research Base

Investigators performing trials under cooperative agreements will be expected, in cooperation with DCP/DCTD, to comply with all FDA distribution, monitoring, and reporting requirements for investigational agents.

Network Participation of CCOP Research Bases

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

Federally Mandated Requirements as Pertinent to CCOP Research Base

Each Research Base must establish mechanisms to meet FDA regulatory requirements for clinical trials involving DCP/DCTD-sponsored investigational agents and DHHS/PHS regulations for the protection of human subjects. These regulations include, but are not limited to, Title 21 CFR 50, 56 and 312 and Title 45 CFR 46.

At a minimum, the CCOP Research Base must be able to:

• Demonstrate that each performance site has a current approved Federal Wide Assurance (FWA) on file with the Office of Human Research Protections (OHRP);
• Demonstrate that each clinical trial and informed consent is approved by the responsible Institutional Review Board (IRB) prior to participant/patient entry,
• Demonstrate that each investigator has a current FDA Form 1572 and curriculum vitae on file with the Pharmaceutical Management Branch, (PMB), CTEP, DCTD;
• Demonstrate that each participant/patient (or legal representative) gives written informed consent prior to entry on study;
• Implement the CTEP requirement for storage and accounting for investigational agents provided under DCP/DCTD sponsorship;
• Establish an on-site audit program for periodic data verification and review of regulatory responsibilities at each affiliated CCOP awardee, cooperative group member, cooperative group affiliate program, and cancer center affiliate institution;
• Provide a method, upon DCP/DCTD request, of summarizing efficacy and toxicity data to be included in DCP/DCTD's annual reports to the FDA for each investigational agent;
• Establish a method for the timely reporting of all serious and unexpected toxicities;
• Verify completion of education on the protection of human research participants for all investigators involved in the design or conduct of research involving human subjects;
• Institute data and safety monitoring plans for all phase I and II clinical trials and establish and maintain Data and Safety Monitoring Committee (DSMC) for all Phase III clinical trials in accordance with the NCI’s policy for Data Safety and Monitoring of Clinical Trials. See also Section VIII. Other Information - Required Federal Citations.

Affiliations of CCOP Research Bases with CCOP and/or Minority-Based CCOP awardees

CCOP Research Bases must establish guidelines for CCOP and MBCCOP awardees to affiliate (i.e. become members). The awarded CCOP Research Bases must fulfill their promises to affiliate made to the proposed CCOPs/Minority-Based CCOPs when these groups are actually funded.

Publications by CCOP Research Base

Timely publication of major findings is encouraged. Publication or oral presentation of work done under this agreement requires proper acknowledgment of NCI support.

Procedures in the Event of Scientific Misconduct

If a duly authorized governmental or institutional body issues a final determination that scientific misconduct has occurred or if the awardee determines that other events have occurred which have significantly affected the quality or integrity of the Group data or participant/patient safety, the awardee is responsible for notifying the Group Data and Safety Monitoring Committee (DSMC), the CTMB, the collaborating investigators, the appropriate Institutional Review Boards (IRBs), and other sponsors of the affected work.

The awardee is also responsible, if the events described above have occurred, for ensuring that submitted but unpublished abstracts and manuscripts are corrected, if possible. If publication deadlines have passed or if abstracts and/or manuscripts containing the affected data have already been published, the awardee is responsible, within 90 days after learning of the event(s) significantly affecting the quality of the Group data or participant/patient safety, for submitting to NCI a re-analysis of the results deleting the false or otherwise unreliable data, and disclosing within the text the reason(s) for the re-analysis. The awardee must submit the re-analysis for publication. The NCI may disseminate information about the re-analysis as broadly as it deems necessary.

The awardee must use its best efforts to notify all scientists, research laboratories, and other organizations to which the awardee has sent research materials affected by false or otherwise unreliable data.

True copies of data files and other supporting documentation from studies affected by scientific misconduct or other findings affecting the quality or integrity of data or participant/patient safety shall be made available to the NCI in a timely manner upon the request of the Grants Management Officer, NCI. The NCI reserves the right to re-analyze, to publish, or to distribute its analyses of these data when it is in the interest of public health. Prior to release, publication or distribution of such analyses, the NCI will provide such analyses to the awardee.

Notification of Participants/patients by the Awardee during Participants/patient s Lifetime

In order for there to be an appropriate response in the event the NCI determines, either while a clinical trial is active or (if relevant) during the lifetime of the participants following the trial s closure, that a medically important toxicity or side effect is associated with the study intervention or that the medical care of one or more participants may have been compromised by scientific misconduct or other finding affecting the integrity of the data or patient safety at the awardee institution or at a third-party institution, funded or unfunded, the awardee shall assure that the institution(s) responsible for these participant(s') accrual, whether funded or unfunded, will have procedures in place to: (a) contact each participant individually at his or her last known address on file with the institution and give each participant contacted appropriate information and the right to communicate with an appropriate institutional representative and, in the event of misconduct, to meet with a physician not connected with the clinical trial or study in which the participant has participated; and (b) encourage participants to notify the institution of any changes of address. The procedure must provide for informing the participants fully of the consequences of the toxicity or misconduct for their care and well-being, if any, and the availability of follow-up; and their opportunity to examine any portion of their medical records relevant to the potential effect of the toxicity or side effect upon them or that may be affected by scientific misconduct or other findings affecting the quality or integrity of the data or participant/patient safety.

It is understood that under regulations at 45 CFR Section 74.53, NCI has a right of access to research records pertinent to the NCI funding. In exceptional circumstances, such as a public health emergency, the institutions will be required to provide participant names and treatments to the NCI in a format that allows direct notification of the participant/patient by the NCI.

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

2 .A. 2. NIH Responsibilities

A Division of Cancer Prevention (DCP)/National Cancer Institute (NCI) Program Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Additionally, an NCI Program Director/Program Official will also be assigned for each award and named in the award notice, and will be responsible for the normal scientific and programmatic stewardship for the award. The Program Director/Program Official may serve as the designated Program Scientist.

The Program Scientist or Program Director will designate other NCI staff that will have substantial involvement as described below.

Part A. NIH Responsibilities regarding CCOP Awardees

The DCP Program Scientist or designee will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Review of Clinical Trials in CCOP Network

DCP and/or DCTD Program officials must review and approve any clinical trial for which a CCOP may claim credit.

Monitoring, Investigational Drug and Data Management

• NCI, or an NCI-designee will conduct periodic on-site audits
• A DCP and/or CTMB/CTEP official will review and advise on mechanisms for monitoring, including the on-site auditing program.
• DCP/CTEP or its designee may attend the on-site audits conducted by the Research Base
• The DCP Program Scientist will have access to all data generated under this award and will periodically review the data management procedures of the CCOP.
• RAB/PMB/CTEP/DCTD and COPTRG/CADRG/DCP, will advise investigators of specific requirements and updates in requirements about investigational drug management that the FDA and NCI may mandate.

Approval of CCOP Organizational Changes

The NCI Program Director will review organizational change request and provide a written response. Organizational changes requiring NCI approval are outlined in The Guidelines for Obtaining Approval of CCOP Organizational Changes, available at: http://cancer.gov/prevention/ccop.

Program Review and Federally Mandated Requirements

• The NCI Program Director will provide a suggested format for the CCOP’s initial and renewal application as well as the annual report (PHS 2590)
• The review of each CCOP awardee by the DCP/NCI Program Director will include the following:
• An analysis of the CCOP awardee annual report, follow up of problems noted, and recommendations for improvement;
• Periodic site visits;
• Review of CCOP Research Base evaluations;
• Adjust funding annually based on planned scope of work and availability of funding;
• The NCI Program may adjust funding, withhold support, suspend or terminate the award, if the CCOP fails to meet the performance requirements set forth in the Terms and Conditions of Award in the RFA, the level of performance changes dramatically; and
• NCI Program Director and DCTD staff members review mechanisms established by each CCOP to meet the Department of Health and Human Services (DHHS)/Public Health Service (PHS) regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents.

Par B. NIH Responsibilities regarding CCOP Research Base Awardees

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

The Program Scientist or Program Director will designate other NCI Program Officials who will have substantial involvement as described below.

Scientific Resource

DCP/NCI Program officials will:

• Set priorities for prevention/control clinical trials research based on state of the science, CCOP Research Base resources and availability of funds;
• Act as a resource for scientific information on cancer prevention/control clinical trials, study regimens and clinical trial design.
• Assist in developing information required for specific trials;
• Advise the Research Base of the nature and results of relevant trials being carried out nationally or internationally;
• Sponsor strategy sessions, when indicated, to discuss specific research initiatives; and
• Provide updated information on the efficacy, toxicity and availability of all Investigational New Drugs (IND) supplied by NCI to the Research Base.

Clinical Trial Development, Review and Closure

DCP/NCI Program officials will:

• Communicate, as appropriate, with the Research Base during all stages of clinical trial development;
• Assist the Research Base in clinical trial design to develop a mutually acceptable protocol compatible with the research interests, capabilities, and needs of the Research Base, its affiliates, and NCI
• Assist in trial design, as appropriate, by providing information and/or comment on:
• Scientific rationale, programmatic relevance, priority, design, statistical requirements, and implementation of the proposed study;
• Feasibility and appropriateness of the research for use by the CCOP and/or in a community setting;
• The existence and nature of concurrent clinical trials in the area of research,
• Relevant pharmacokinetic and pharmaco-dynamic data on investigational agents;
• Availability of investigational agents, including biologic response modifiers; and
• Research in other NCI-funded programs that may be ready for clinical trials.
• DCP/DCTD Program officials review and approve all clinical trials designed by CCOP Research Bases for use by CCOP and/or Research Base member/affiliate institutions with the major considerations being:
• Strength of the scientific rationale supporting the study;
• Importance of the question being proposed;
• Avoidance of undesirable duplication with ongoing clinical trials;
• Appropriateness and feasibility of study design;
• Appropriateness of patient/participant selection, evaluation, assessment of toxicity, response to intervention, and follow-up;
• Patient/participant safety;
• Compliance with NIH and the federal regulatory requirements;
• Satisfactory projected accrual rate and follow-up period;
• Adequacy of data management; and
• A consensus review that describes recommended modifications and other suggestions as appropriate will be communicated to the Research Base PI
• NCI Program officials will review Research Base mechanisms for interim monitoring of results and will monitor clinical trial progress.
• NCI may request that a clinical trial be closed for reasons including:
• Insufficient accrual rate;
• Accrual goal met;
• Poor protocol performance;
• Patient/participant safety;
• Already conclusive study results; and
• Emergence of new information which diminishes the scientific importance of the study question

Data Management and Analysis

• DCP/DCTD will have access to all data generated under this award.
• DCP/DCTD representative may review data management and analysis procedures of the Research Base
• DCP/DCTD Data may request data be made available for external monitoring.

Quality Control, Data Monitoring and Investigational Drug Management

• NCI Program officials may review quality control and monitoring procedures of the Research Base including the on-site auditing program.
• NCI Program officials (DCP and DCTD) will serve as non-voting members each DSMC.
• NCI staff will assess the Research Base compliance with NCI-established policies on Data and Safety Monitoring Plans for Phase I and II trials and Data and Safety Monitoring Committees for Phase III trials.
• NCI staff may attend on-site audits conducted by the Research Base or its NCI designee.
• NCI Program staff will advise investigators of specific requirements and changes in requirements concerning investigational drug management that the FDA may mandate.

Program Review, Strategy Sessions and Federally Mandated Requirements

• The NCI Program Director will provide a suggested format for the CCOP Research Base initial and renewal applications as well as the annual progress report (PHS 2590).
• The DCP/NCI Program Director will review each CCOP Research Base by:
• A review of the annual report;
• Periodic site visits;
• A review of progress in designing, developing, implementing and completing cancer prevention/control clinical trials;
• Quarterly accrual reports by clinical trial; and
• Adjust funding annually based on planned scope of work and availability of funds.
• The NCI Program may adjust funding, withhold support, suspend or terminate the award, if the CCOP fails to meet the performance requirements set forth in the Terms and Conditions of Award in the RFA, the level of performance changes dramatically.
• NCI Program Director or designee will sponsor strategy sessions when indicated.
• NCI Program Director and DCTD staff will review mechanisms established by each CCOP to meet the Department of Health and Human Services (DHHS)/Public Health Service (PHS) regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents.

2.A.3. Collaborative Responsibilities

Execution of this program will require collaboration among the PIs of the CCOPs and CCOP Research Bases, the DCP Program Scientists(s) and staff as well as CTEP/DCTD/NCI Program officials and staff, and/or its designees/contractors as described above.

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. The panel will be composed of: one member of the recipient group, one NCI designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

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

Reporting by CCOP group awardees

CCOP group awardees will report their cumulative accrual to NCI-approved clinical trials at 6 months, 9 months (included in the annual progress report), and 12 months for each budget period.

A suggested format for CCOP specific information relative to the progress summary section of the PHS Form 2590 will be provided. The format is available at the URL address: http://www.cancer.gov/prevention/ccop/reportreq.html .

Reporting by Research Base awardees

A suggested format for Research Base specific information relative to the progress summary section of the Form PHS 2590 will be provided. The format is available at the URL address: http://www.cancer.gov/prevention/ccop/reportreq.html An update on clinical trials, in development, and clinical trials that were approved, activated, closed and/or completed during the relevant budget period should be discussed in the progress summary. Plans pertaining to clinical trial activities for the next budget period should be addressed as well. An annual performance report on each affiliated CCOP must be included. The performance report will include, at a minimum, information on: overall case accrual; cancer prevention/control clinical trials research, existing or planned; eligibility and evaluability of patients/participants entered on study; timeliness and quality of data reporting; and results of quality control review and audits if performed during that year

A Research Base must submit a list of the participating sites as defined by the Clinical Trials Monitoring Branch, CTEP, DCTD, along with the audit schedule of these sites in the annual progress report.

Clinical Trials Reporting Requirements

Reporting requirements will be in agreement with FDA regulations and NCI procedures. Interim reports of each activated and ongoing clinical trial shall appear in the minutes of each Research Base meeting and shall include specific data on patient/participant accrual as well as, when appropriate, detailed reports of treatment-associated morbidity. Quarterly accrual reports must be provided as appropriate to CTEP for all active trials through the NCI’s Clinical Data Update System (CDUS). Instructions and Guidelines for CDUS are at http://cancer.gov/reporting/cdus.html.

Adverse Event Reporting Procedures

To be in compliance with FDA regulations, all recipients of NCI support for clinical trials, including Research Bases responsible for coordinating and monitoring such trials, must promptly report adverse events (including adverse drug reactions) to the NCI and any other trial sponsor(s) according to NCI Guidelines. For treatment trials utilizing CTEP investigational agents guidelines are listed at http://cancer.gov/reporting/adeers.html. For cancer prevention and control trials utilizing DCP investigational agents, guidelines are listed at http://cancer.gov/prevention/pio/index.html.

The awardee will notify all institutions/investigators participating in this project, funded or unfunded, about the above requirement and about the institutions'/investigators' responsibility to report adverse events as specified in the protocol.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

Lori Minasian, M.D.
Division of Cancer Prevention
National Cancer Institute
6130 Executive Boulevard, EPN Room 2017, MSC-7340
Bethesda, MD 20892-7340 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 496-8541
FAX: (301) 496-8667
Email: [email protected]

2. Peer Review Contacts:

Referral Officer
Division of Extramural Activities
National Cancer Institute
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (U.S. Postal Service Express or regular mail)
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 496-3428
FAX: ( 301) 402-0275
Email: [email protected]

3. Financial or Grants Management Contacts:

Mr. Shane Woodward
Office of Grants Administration
National Cancer Institute
1003 West 7th Street, Suite 300
Frederick, MD 21701-4106
Telephone: 301-846-1014
Fax: 301-846-5720
Email: [email protected]

Section VIII. Other Information

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); and efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA 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.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools including the Authors' Manual (http://publicaccess.nih.gov/publicaccess_Manual.htm).

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002 . The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at No.93.399 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.

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