Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	National Cancer Institute (NCI)
Funding Opportunity Title	AIDS and Cancer Specimen Resource (ACSR) (UM1)
Activity Code	UM1 Multi-Component Research Project Cooperative Agreements
Announcement Type	Reissue of RFA-CA-08-501
Related Notices	August 09, 2018 - This RFA has been reissued as RFA-CA-18-012.
Funding Opportunity Announcement (FOA) Number	RFA-CA-13-005
Companion Funding Opportunity	None
Number of Applications	Only one application per institution is allowed, as defined in Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.393, 93.394, 93.395, 93.396, 93.399
Funding Opportunity Purpose	In this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) is seeking applications for the AIDS and Cancer Specimen Resource (ACSR). The primary objective of the ACSR will be to acquire, store and equitably distribute tumor tissues, biological fluids and associated demographic data from patients with HIV-associated malignancies. In addition, the ACSR will serve and support biorepository banking activities for the AIDS Malignancy Clinical Trials Consortium (AMC). The AMC is an NCI funded, multicenter clinical trials group that performs clinical trials research in the treatment and prevention of HIV-associated malignancies. Due to the changing HIV epidemic and recent estimates of the associated malignancy trends, applicants are encouraged to focus their efforts in acquiring high priority collections that would include: 1) biospecimens with associated clinical, pathological, diagnostic, and demographic data; 2) fresh frozen biospecimens that are suitable for comprehensive molecular and genomic analyses; 3) biospecimens collected with informed consent acceptable for high level future use for deep sequencing and genome wide association studies; 4) biospecimens representing non-AIDS defining cancers (NADCs); and 5) biospecimens from the developing world, especially Sub-Saharan Africa.

Posted Date	December 12, 2012
Letter of Intent Due Date(s)	January 14, 2013
Application Due Date(s)	February 14, 2013
AIDS Application Due Date(s)	Not Applicable)
Scientific Merit Review	May/June, 2013
Advisory Council Review	August, 2013
Earliest Start Date	September, 2013
Expiration Date	February 15, 2013
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

In this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) is seeking applications for the AIDS and Cancer Specimen Resource (ACSR). The primary objective of the ACSR will be to acquire, store and equitably distribute tumor tissues, biological fluids, and associated demographic data from patients with HIV-associated malignancies. In addition, the ACSR will serve and support biorepository banking activities for the AIDS Malignancy Clinical Trials Consortium (AMC). The AMC is an NCI funded, multicenter clinical trials group that performs clinical trials research in the treatment and prevention of HIV-associated malignancies. Due to the changing HIV epidemic and recent estimates of the associated malignancy trends, applicants are encouraged to focus their efforts in acquiring high priority collections that would include: 1) biospecimens with associated clinical, pathological, diagnostic, and demographic data; 2) fresh frozen biospecimens that are suitable for comprehensive molecular and genomic analyses; 3) biospecimens collected with informed consent acceptable for high level future use for deep sequencing and genome wide association studies; 4) biospecimens representing non-AIDS defining cancers (NADCs); and 5) biospecimens from the developing world, especially Sub-Saharan Africa.

There are an estimated 34 million people living with HIV/AIDS (PLWHA) in the world. Cancer continues to be a leading cause of morbidity and mortality in those infected with HIV. In the United States (U.S.), widespread use of highly active antiretroviral therapy (HAART) has led to a decrease in some AIDS-defining tumors (Kaposi sarcoma [KS] and non-Hodgkin lymphoma [NHL]). However, the incidence of non-AIDS defining cancers (NADCs) has increased in a 'surviving' and aging HIV-positive population. Approximately 70% of the PLWHA live in resource-poor Sub-Saharan Africa, which also has a high prevalence of viruses that cause HIV-associated tumors, such as KS and Burkitt lymphoma.

In the early 1990s, advisory boards to the NCI assessed that research in HIV-associated malignancies was being hindered by the difficulty in accessing patient samples. It was believed that collections of biospecimens from people in the U.S. and across the globe, that represent various populations, treatment regimens, and eras of the HIV epidemic, would facilitate research directed towards identifying potential genetic, viral, and environmental cofactors contributing to the development of malignancies in the context of HIV-infected persons.

The ACSR has been supported since 1994 through a number of independent cooperative agreements representing a series of four initiatives (RFA-CA-94-03; RFA-CA-97-021; RFA-CA-02-001; RFA-CA-08-501) sponsored by the NCI. The ACSR is primarily a repository of human biospecimens that reflects changes in the HIV/AIDS epidemic, domestically and internationally, over time. Over nearly 20 years, the ACSR has established itself as a unique resource for the collection, storage, and provision of biospecimens with associated clinical, pathological, diagnostic, and demographic data. Biospecimens and associated data have been made available to the research community-at-large at no cost. The ACSR has served investigators from more than 50 institutions, including 11 foreign institutions. In 2010, the ACSR assumed the activities of the AIDS Malignancy Clinical Trials Consortium (AMC) Biorepository. The ACSR has also served a supportive biorepository role for a number of NCI funded investigators and other NCI initiatives.

The current structure of the ACSR consists of three independently funded Regional Biospecimen Repositories (RBRs) and an independently funded Central Operations and Data Coordinating Center (CODCC) that are governed and coordinated through an Executive Committee. The RBRs and their member institutions contribute biospecimens to the ACSR, and the RBR coordinates the biospecimen procurement/distribution activities and data management of that regional group. The CODCC is the administrative unit that coordinates the ACSR's activities.

The current ACSR awardees have established a strong infrastructure and a large collection of HIV-associated malignancy biospecimens. Nonetheless, the NCI Leadership and Advisory Committees believe that the ACSR will benefit from a re-organization and a reinvigoration of its membership via an open competition. It is expected that the new structure will enable the ACSR awardee to address the changing needs of the AIDS-malignancy basic and clinical research community in a more coordinated and efficient way.

This FOA is designed to fund the ACSR as a single, consolidated, UM1 award for all of the functional components of the ACSR. These changes were instituted to encourage centralized leadership, administration, and oversight of the ACSR activities. It is anticipated that these changes will enhance the accountability, efficiency, productivity, and communication of the ACSR.

The primary goal of the ACSR is to meet the biospecimen needs of clinician and basic researchers in HIV-associated malignancies by acquiring, storing, and equitably distributing tumor tissues and biological fluids from patients with HIV-associated malignancies. It is expected that the ACSR will interact and collaborate with the AMC and maintain its role in serving as the AMC Biorepository. Additionally, the ACSR may establish collaborations and agreements with other NCI or NIH-funded initiatives/investigators in HIV/AIDS and/or cancer related research in order to provide biospecimen/biorepository support and/or improve the research community's access to biospecimens. It is expected that the ACSR awardees will consult with the NCI and seek its approval for such additional collaborations.

Applicants responding to this FOA must propose scientifically appropriate and rigorous approaches to accruing, curating, and storing biospecimens and data. These approaches and activities must address all the specific key elements defining the scope of ACSR that are identified below but are also expected to reflect the creativity and distinct capabilities of the applicant team. However, these approaches must conform to best practices in biospecimen sciences (as defined by the NCI and/or the International Society for Biological and Environmental Repositories [ISBER]) and the laws of the countries from which biospecimens are procured.

Priorities for Biospecimen Collection

In developing this funding initiative, NCI leadership and advisors defined pressing needs for the scientific research community in HIV-associated malignancies. The defined areas of priority are listed below. Applicants responding to this FOA are expected to address these priorities.

1) Collection of biospecimens with associated clinical, pathological, diagnostic, and demographic data, if available;

2) Collection of fresh frozen biospecimens with matching non-tumor germline samples for comprehensive molecular and genomic analysis;

3) Collection of biospecimens from the developing world, especially Sub-Saharan Africa;

4) Collection of biospecimens representing non-AIDS-defining cancers (NADCs); and

5) Biospecimens with high level informed consent that allows for genomics research.

While this list defines priority collections, biospecimen collections for the ACSR should be broad in scope and not be limited to these priority areas.

General Requirements and Capabilities

Applicants responding to this FOA must address the following specific challenges, requirements, and capabilities.

• Evolving Nature of the Epidemic. It is essential to ensure that the ACSR collection reflects the evolution of the HIV epidemic over the past 30 years and changes that may occur during the funding period. This would include collection of biospecimens that represent patients from both pre- and post HAART eras. For example, in the U.S., with extensive use of HAART, the types of HIV-associated malignancies have changed. Some AIDS-defining malignancies (KS and NHL) have appeared to decrease in frequency, whereas NADCs (such as lung, liver and anal cancer) are increasing in frequency. The applicants' plans for ACSR biospecimen collections must appropriately reflect these changes.
• Need to Curate Diverse Collections. The applicants must be able to curate a collection representing a wide variety of rare tumor types (KS, NHL, cervical cancer) and a number of biospecimen processing types (frozen, formalin fixed paraffin embedded [FFPE], plasma, serum, saliva, urine). These types may include non-tumor biospecimens of patients who have developed tumors; control specimens from patients without tumors; and specimens from cohorts followed before the development of tumors. ACSR collections will primarily represent tumors occurring in the context of HIV infection, but applicants should also demonstrate that, whenever possible, they are capable of procuring control biospecimens that represent these same, or similar, rare tumors occurring in HIV-negative individuals.
• Value of Biospecimen Sets to the Community. The focus of the resource is expected to be on acquiring specimens of particular value to the research community with appropriate adjustments in response to changing needs. Acquisition of biospecimen sets representing cohort collections that have followed participants over long periods, and include associated demographic and treatment data are important for the AIDS-associated malignancy research community. Applicants should define how decisions for acquisition of special collections will be made, and describe the processes they will use to incorporate large collections of biospecimens and data into the ACSR. Applicants may provide examples of relevant experience with the transfer of large biospecimen and data sets.
• Applicants Expertise and Background. ACSR investigators will be expected to stay current in their knowledge and implementation of the most recent best practices in biospecimen science and have appropriate, up-to-date, expertise in technological advancements in clinical and basic research. Applicants must be experienced in developing and carrying out team approaches to acquiring, storing, and distributing biospecimens to the research community. Applicants must demonstrate their capabilities in these areas.
• Global Nature of the Collection. Investigators must be able to meet the challenge of the global nature of the HIV epidemic, and have a broad based understanding of how the HIV epidemic is being addressed throughout the world, in both resource rich and resource poor countries. They must be aware of the limitations and constraints in procuring biospecimens and data that are of sufficient quality to be used in basic and/or clinical research. They must also be capable of developing a global collection of biospecimens that respects the cultures and laws of many different nations. Applicants should describe their capabilities and experience in obtaining biospecimens that represent a global epidemic.
• Equitable Biospecimen Distribution. It is expected that the awardee team will be committed to equitably distributing biospecimens to funded investigators engaged in research on HIV/AIDS and its associated malignancies. Applicants must provide specific plans to meet this requirement and, if possible, provide examples of their willingness to share resources with the scientific community at large.
• Outreach Efforts. Applicants are expected to propose an efficient outreach program that informs investigators about the ACSR and encourages them to use the ACSR's biospecimens in their research. Applicants should propose activities that coordinate with other NCI initiatives in order to improve and increase the use of the ACSR. Applicants are encouraged to suggest ways to actively engage the research community in guiding the resource. For example, the actual and potential users of the resource may advise the group regarding the inclusion of specific technological tools (such as tissue microarrays [TMAs], whole genome amplified [WGA] DNA), biospecimen types, tumor types, and processing types that would be most valuable for their research.
• Bioinformatics Development and Maintenance. Applicants are also expected to provide plans for development and/or improvement of bioinformatics tools to audit the collections, and to monitor and track the inventory use in order to better guide collections and serve the science being supported by the ACSR.

For optimal functioning, the proposed ACSR must include components with the following characteristics:

1. ACSR Chairperson's Administrative Office to coordinate ACSR governance and evaluation of its components

2. Central Operations and Data Coordinating Center (CODCC) with Bioinformatics Core and Administrative Core

3. Regional Biospecimen Repositories (four to six core facilities)

4. AMC Biorepository

5. Working Groups to coordinate key activities for the ACSR

Specific requirements and expectations for these characteristics are outlined below.

ACSR Chairperson's Administrative Office

The Program Director/Principal Investigator (PD/PI) of the awardee institution is expected to provide centralized leadership (as ACSR Chairperson) to ensure that the ACSR's major structural components are capable of carrying out their respective responsibilities and operate in a well-coordinated fashion. The ACSR Chairperson will be responsible for the scientific and technical integrity, productivity, governance, and fiscal decisions of the group. The ACSR Chairperson's Administrative Office is expected to support these activities as well as performance evaluation for the ACSR components.

Central Operations and Data Coordinating Center (CODCC)

The CODCC is intended to serve as the coordinating and administrative body of the ACSR. Applicants may structure this 'body' in a way they envision best serves the needs of the ACSR. However, at a minimum, CODCC is expected to provide the following functions:

1) centralized administrative coordination, communications, logistical support, and reporting; and 2) bioinformatics, biostatistical, and information technology support (including database development, and maintenance).

Regional Biospecimen Repositories (RBRs)

Applicants may propose no less than four and no more than six RBRs. These 'Core' repositories are expected to provide the infrastructure to acquire, store and distribute biospecimens and data for the ACSR enterprise. Each RBR proposed must have both clinical laboratory and pathology components, as well as appropriate administrative component (Regional Operations Office).

AMC Biorepository

The ACSR awardee is expected to perform AMC Biorepository activities. These activities are expected to adhere to established Standard Operating Procedures, protocols and collaborative agreements between the ACSR and the AMC.

Working Groups

A series of Working Groups will address key administrative, policy, scientific and technical issues of the ACSR and contribute to the ongoing revision and refinement of activities addressing these issues. The proposed Working Groups must address, at a minimum, the following required areas:

a) Scientific and technological strategic planning; assessment of trends in the HIV epidemic, research or technology; promotion of new techniques; identification of current trends in technology or the HIV epidemic; and identification of new scientific or technical opportunities;

b) Bioinformatics - addressing the practical user issues and communication efforts regarding the bioinformatics systems and upgrades;

c) Tracking the use of the ACSR, the inquiries, Letters of Intent (LOIs), research results, and other metrics;

d) Quality management of ACSR biospecimens, data and controls; creation and/or maintenance of checklists, assessment tools and surveys; and

e) Outreach and promotion of the ACSR to both the research and patient communities.

Governing Committee: The ACSR (with the participation of the NCI) is expected to form a self-governing body for the resource the Governing Committee (GC). The GC will be responsible for ensuring that the ACSR's major structural components are capable of carrying out their respective responsibilities and operating in a well-coordinated fashion. GC is also expected to provide final approval for LOIs and administrative oversight for the ACSR enterprise. GC will provide recommendations regarding support for RBRs and initiatives based upon the results of evaluation procedures adopted by the ACSR. The GC may form sub-committees as needed, including an Advisory Sub-Committee".

An Advisory Sub-Committee: This sub-committee would act as a 'think tank' for the ACSR awardee. This committee would provide input regarding the scientific and outreach direction of the ACSR enterprise.

Review and Evaluation Decision Panel (REDP): All research proposing to use biospecimens and data from the ACSR will be subject to evaluation by a panel of external experts, the Review and Evaluation Decision Panel (REDP).The REDP's decisions will be made independently from the ACSR or its Governing Committee. The NCI will coordinate the logistics for the REDP. ACSR applicants must agree (and plan accordingly) that all standard LOIs will be evaluated by the REDP according to evaluation and review criteria established by ACSR's Governing Committee.

For details on the composition and functions of the Governing and Advisory bodies, see Section VI.2. Cooperative Agreement Terms and Conditions of Award in this FOA.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS 398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NCI intends to fund one award, for a total cost of $3.9 million in fiscal year 2013. The financial plans of the NCI provide support for this initiative through 5 years. Award pursuant to this funding opportunity is contingent upon the availability of funds.
Award Budget	Application budgets are limited as follows, but need to reflect actual needs of the proposed project. Proposed budgets for years 1 and 2 must not exceed $3,900,000, each year (in total costs). Proposed budgets for years 3, 4, and 5 must not exceed $4,400,000, each year (in total costs). The budgetary increases in years 3, 4, and 5 are specifically designed to support the Sub-Saharan Africa Regional Biospecimen Repository.
Award Project Period	Applicants must request a project period of 5 years.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• System for Award Management (SAM) must maintain an active entity registration (formerly CCR registration), to be renewed at least annually. Use the Sam.gov Manage Entity function to manage your entity registrations. See the Grants Registration User Guide at SAM.gov for additional information.
• eRA Commons

All Program Directors/Principal Investigators (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS 398 Application Guide.

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

Only one application per institution is allowed.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Rebecca Liddell Huppi, PhD
Office of HIV and AIDS Malignancy
National Cancer Institute
31 Center Drive, Suite 3A33, MSC 2440
Bethesda, MD 20892-2440 (for US Postal Service regular or express mail)
Bethesda, MD 20892 (for non-USPS delivery)
Telephone: 301-496-4995
Email: [email protected]

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

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

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Referral Officer
Division of Extramural Activities
National Cancer Institute (NCI)
6116 Executive Blvd, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for US Postal Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements for the Research Strategy subsections listed below:

A. ACSR Overview: 12 pages

B. ACSR Chairperson's Administrative Office:6 pages

C. Central Operations and Data Coordinating Center: 6 pages

D. Working Groups and Research Agenda: 6 pages

E. ACSR Proposed Regional Biospecimen Repositories (RBRs): 12 pages

F. ACSR Associated Programs: 6 pages

The following sections supplement the instructions found in the PHS 398 Application Guide.

The grant application should be assembled and paginated as one complete document in the following order:

Face Page

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells

Detailed Budget for Initial Budget Period

Budget for Entire Proposed Period of Support

Budgets Pertaining to Consortium/Contractual Arrangements

Biographical Sketches

Resources

Research Plan

Specific Aims

Research Strategy

• A. ACSR Overview
• B. ACSR Chairperson's Administrative Office
• C. Central Operations and Data Coordinating Center
• D. Working Groups and Research Agenda
• E. ACSR Proposed Regional Biospecimen Repositories (RBRs)
• F. ACSR Associated Programs

Bibliography and References Cited

Protection of Human Subjects

Inclusion of Women and Minorities

Targeted/Planned Enrollment Table

Inclusion of Children

Vertebrate Animals

Select Agent Research

Multiple PD/PI Leadership Plan

Consortium/Contractual Arrangements

Letters of Support (e.g., Consultants)

Resource Sharing Plan

Appendix

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions for the application parts listed below.

Modify Form Page 3 of the PHS 398 to replace standard sub-sections of "Research Strategy" with the following new sub-sections:

A. ACSR Overview

B. ACSR Chairperson's Administrative Office

C. Central Operations and Data Coordinating Center

• i. Administrative
• ii. Bioinformatics

D. Working Groups and Research Agenda

E. ACSR Proposed Regional Biospecimen Repositories (RBRs)

F. ACSR Associated Programs

• i. AMC Biorepository
• ii. Sub-Saharan Africa Regional Biospecimen Repository

Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5).

Use Additional Form Pages 4 and 5 to provide detailed separate budget information (first year and cumulative budgets for the entire project period) for the following individual application components:

• ACSR Chairperson's Administrative Office
• Central Operations and Data Coordinating Center
• AMC Biorepository
• Independent Biospecimen Procurement Initiatives
• Sub-Saharan Africa RBR

The following information is meant to serve as budgetary guidance. Note that dollar figures for individual components are suggestions for an overall balanced budget but are NOT mandatory caps. Applicants may adjust the budgets for individual components if desired but a clear and specific justification is expected for deviations from the guidelines.

ACSR Chairperson’s Administrative Office (up to approximately $250,000): Allowable costs that may be budgeted under this component should support the oversight of all ACSR activities, and support the internal auditing and site visit processes. Costs may include travel for the Chairperson and site-visit teams. Allowable costs may include appropriate and justified levels of FTE support for the ACSR Chairperson and other staff positions essential for this office, including CODCC Operations Director, Administrative Assistant, and Database Technician.

Central Operations and Data Coordinating Center (up to approximately $750,000): Allowable costs that may be budgeted under this component may be used for database development and data management, information technology support and statistical support. In addition, costs may include support for all coordinating activities of the CODCC, which would include meeting support, telecommunications, marketing materials and attending meetings/conferences for marketing purposes, travel, progress reports, ACSR programmatic tracking activities and other administrative activities. It will include FTE positions such as: bioinformatics leadership and staff, biostatistics leadership, and operations leadership and staff.

Basic Regional Biospecimen Repository Support (up to approximately $2,100,000): Allowable costs for this component are meant to provide infrastructure support for no less than four and no greater than six RBRs (excluding the African RBR) with a range of $150,000 to $500,000 available per RBR site. Allocation of these funds will be highly dependent on the activity, holdings, and sustained productivity of the RBR (based upon criteria established by the ACSR Governing Committee), and the number of RBRs brought into the group. Staff and effort will vary between RBRs. Additionally, these funds may be used for equipment, maintenance contracts, pathology reagents and antibodies, nucleic acid extraction, laboratory supplies, storage (liquid nitrogen), shipping, and travel.

AMC Biorepository Costs (up to approximately $300,000): Allowable costs under this component may include the laboratory costs for biospecimen processing, storage, protocol specific distribution of biospecimens to central laboratories, and bioinformatics system development specifically for AMC biospecimens. In addition, costs may include maintenance of biospecimen inventories for future correlative science and personnel costs of technical staff time.

Independent biospecimen procurement fund ($400,000 suggested): Allowable costs for this component may include procurement of biospecimens from independent sites or investigators that will not receive infrastructure funds. Allowable costs may include services such as Autopsy Programs, collaborative projects, international collections, and/or to bring special collections to the ACSR. The GC, with NCI concurrence, will authorize the use of these funds

Discretionary Fund ($100,000 suggested): The allowable costs for this component may be used for unforeseen events and piloting emerging scientific opportunities. This component is meant to provide flexible infrastructure support to investigators or repositories in order to maintain collections for use by the scientific community. These funds may be used to immediately respond if a natural disaster threatens existing resources. These funds may be used for beta-testing new technologies, equipment, and/or other opportunities that become available for biospecimen repositories. The use of these Discretionary Funds will require concurrence of the Governing Committee and final authorization by NCI Program Staff.

Sub-Saharan Africa RBR (recommended $500,000; years 3-5): The allowable costs for this component may be used to provide infrastructure support for the continued development and maintenance of an African RBR, including support for the development of the RBR, domestically. Costs may cover staff and effort as is appropriate for any RBR. Costs may include funds for equipment, maintenance contracts, pathology reagents and antibodies, nucleic acid extraction, laboratory supplies, storage (liquid nitrogen), shipping and travel. Appropriate funds may be allocated for the effort and travel of the U.S. Liaison. Additionally, the applicants may allocate funds for regional meetings, training, monitoring, bioinformatics development, and costs incurred by the CODCC in oversight and coordination of the RBR.

Budgets for individual ACSR Proposed Regional Biospecimen Repositories must be provided as individual subcontractual budget pages following the PHS 398 instructions.

In addition to standard content of this section, applicants are encouraged to include appropriate detailed summary tables, lists, and other relevant detailed information documenting their capabilities and accomplishments in biospecimen collection.

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Research Strategy

Standard sub-sections of the Research Strategy of the PHS 398 Research Plan are replaced by the new sub-sections A-F detailed below. Please refer to the Page Limitations section above for information on the page limits for each of these sub-sections.

A. ACSR Overview Following the NCI guidance in Section I. Funding Opportunity Description, describe the proposed structure for the ACSR. Briefly outline the vision and proposed goals for the ACSR, its organization and governing structure. Define lines of authority and decision-making processes. Describe how the ACSR components will interact to address key administrative, policy, scientific and technical issues of the ACSR. Provide an organizational chart showing the place of each component in the overall scheme. Summarize major strengths and critical experience and accomplishments of the team relevant to the proposed ACSR structure (including key scientific as well as administrative personnel). Summarize special features in the environment and resources that reflect unique strengths of the proposed components and participants in the ACSR.

• Background and Infrastructure: Applicants should discuss previous biorepository activities and experience that demonstrate their ability to perform resource functions. The applicants should discuss existing resources, capability, infrastructure, relevant collaborations, and other related initiatives that demonstrate a ready platform for establishing the resource. Identify available bioinformatics expertise and systems that will enable a rapid assumption of biorepository activities.
• Applicants representing current ACSR awardee team: cover in this narrative your role in the current ACSR infrastructure and accomplishments.
• Applicants previously unaffiliated with ACSR: describe experiences, accomplishments, infrastructure, capabilities, etc. relevant to the ACSR objectives defined in this FOA.

Information on background and existing resources may include the scale of conducted biospecimen collection, tumor types/tissue types, other special collections as well as other relevant activities, collaborations, publications, etc. Applicants who have participated in acquiring/storing/distributing biospecimens may include information regarding the scale of biospecimen requests processed (requests vetted, requests approved, and biospecimens distributed).

Note: In addition to the narrative in this section, applicants may provide detailed summary tables, lists for the relevant information under the "Resources" section of the application.

B. ACSR Chairperson's Administrative Office

The applicant will name the individual(s) who will assume leadership of proposed governance, advisory and performance evaluation bodies. It is expected that the PD/PI of the awardee institution will serve as the ACSR Chairperson. It is also expected that the ACSR Chairperson will act as the Chairperson of the Governing Committee. ACSR Chairperson and its Administrative Office must establish a system to perform RBR evaluation and evaluation of major ACSR sanctioned initiatives. Resulting evaluation information will be presented to the GC, which will make recommendations regarding continued support for underperforming RBRs and initiatives.

In this section, list qualities and experience in those proposed individuals that support appointment to a leadership role. Describe the structure, general participant make-up (no specific participant names are needed), and roles of the governance, advisory and performance evaluation bodies. Describe how the RBRs, the CODCC, and new programs/collaborations will be evaluated for effectiveness and establish a plan outlining the decision-making processes for initiation, continuation, or discontinuation of focused initiatives. "Focused initiatives" may include special programs or collaborations for tissue procurement, derivative development, or technological improvements to the ACSR. Funds for these focused initiatives may be derived from the Independent biospecimen procurement fund or the Discretionary fund described in the Budgetary Guidance notes above. Describe the infrastructure to support the required administrative activities of the ACSR Chairperson, including, but not limited to, logistics and organization of meetings, site visits and preparation of required reports associated with performance evaluation. NOTE: Administrative and logistical tasks for the remaining ACSR activities (governance, advisory, Working Groups, etc.) are expected to be performed by the CODCC (see below).

C. Central Operations and Data Coordinating Center

The CODCC must have components that address the following: 1) Bioinformatics and database management, development, and maintenance; 2) Day-to-day, centralized administrative coordination and communications; 3) ACSR biostatistical support and leadership; 4) Meeting (both face-to-face and telecommunication) logistical support; 5) Programmatic tracking activities and progress reports; and 6) Information technology support.

Describe the proposed leadership and structure of the CODCC, including both the administrative and bioinformatics functions. The description should include lines of authority, decision-making processes, key personnel, policies, and procedures for ACSR communication, committee support, and administrative duties (maintenance of documentation, preparing reports, assuring compliance to NCI Best Practices). Describe relevant experience and proposed strategies/plans for the public interface, and/or publicizing of the ACSR. A key role for the CODCC is its coordination of the ACSR's bioinformatics systems. Describe plans for maintenance, revision, updates, and continued compliance to best practices for the bioinformatics systems of the ACSR. In addition, address issues regarding the structural changes of the ACSR, including plans for expansion to accommodate more/new RBRs, an RBR in resource poor Sub-Saharan Africa, and the AMC Biorepository.

D. Working Groups and Research Agenda

Appropriate Working Groups need to be proposed to address scientific and technological challenges of the ACSR. The proposed Working Groups must address, at a minimum, the following required areas:

a) Scientific and technological strategic planning; assessment of trends in the HIV epidemic, research or technology; promotion of new techniques; identification of current trends in technology or the HIV epidemic; and identification of new scientific or technical opportunities;

b) Bioinformatics - addressing the practical user issues and communication efforts regarding the bioinformatics systems and upgrades;

c) Tracking the use of the ACSR, the inquiries, Letters of Intent (LOIs), research results, and other metrics;

d) Quality management of ACSR biospecimens, data and controls; creation and/or maintenance of checklists, assessment tools and surveys; and

e) Outreach and promotion of the ACSR to both the research and patient communities.

Other Working Groups, and the specific structure and functions of all Working Groups are to be defined by the applicants.

Outline the proposed Working Groups and describe their leadership, membership, intended activities, and future directions. Outline how these Working Groups will contribute to the ongoing refinement and revision of the ACSR goals, objectives, and research agenda.

Any given Working Group may include, as members, investigators of appropriate profile from several RBRs and other collaborators or investigator-users of the ACSR with relevant experience. List qualities and experience of key leaders and members of Working Groups that make them uniquely qualified to contribute to the Working Group.

The applicants should describe how, through these Working Groups or other initiatives, they will enrich procurement of high priority biospecimen collections defined in this FOA. Address "Challenges, Requirements and Capabilities" listed above. The applicants should describe how they will focus on acquiring specimens of particular value to the research community and how they will address changing research needs during the funding period (and make adjustments in response to changing needs). The description may include new or established programs and collaborations with appropriate rationale and a brief discussion of how proposed/established programs contribute to the ACSR goals. Working Groups may propose special programs or collaborations for tissue procurement, derivative development, or technological improvements to the ACSR. Funds for these initiatives may be derived from the Independent biospecimen procurement fund or the Discretionary fund described in the Budgetary Guidance notes above.

E. ACSR Proposed Regional Biospecimen Repositories (RBRs)

Applicants may propose no less than four and no more than six RBRs. In addition to providing infrastructure to acquire, store and distribute biospecimens and data for the ACSR, each RBR proposed must have both clinical laboratory and pathology components. Each RBR must include a pathologist as part of the key personnel. Each RBR must also include a Regional Operations Office to perform RBR administrative duties and to manage clinical data and tissue and biological fluids related repository data. The Regional Operations Office will supply biospecimen data update information to the ACSR's central bioinformatics systems. Additionally, the Regional Operations Office will perform the RBR's self-auditing and reporting processes, and other administrative activities of the RBR. An important role of the RBR Operations Office is to facilitate communication between the RBR and the CODCC.

Each proposed RBR must be able to effectively obtain, curate, and distribute biospecimens and data. Describe these capabilities of the proposed RBRs. Include in the description their ability to communicate with the ACSR CODCC and contribute to the ACSR's overall research and technical program. Outline their ability to meet requirements and best practices for running a biorepository, and expressed commitment to follow ACSR Standard Operating Procedures (SOPs) and the Manual of Operations (MOOs), or get approved variations in these procedures and policies through the ACSR GC. For each proposed RBR, include the description (diagrams are preferred) of the RBR structure and organization, management and communications, levels of authority and objectives. Note that each RBR must have a Regional Operations Office and defined anatomic and/or clinical pathology expertise. Describe the expertise of RBR leadership and key staff, and how the RBR can uniquely add value to the ACSR's overall program. The applicants should note any previous experience with and contributions to the ACSR enterprise of the proposed RBR. It is intended and expected that the RBRs will solely handle the storage/distribution of ACSR biospecimens and communication of associated data to the CODCC. Exceptions to this rule might be possible if approved by the ACSR Governing Committee, but such exceptions are expected to be very few, if any. The applicant must describe minimal requirements for becoming an RBR, a plan of continuing review and assessment of the RBRs' productivity, and a general plan for the development of metrics and milestones for each RBR.

F. ACSR Associated Programs

• i. AMC Biorepository. The applicants may structure the AMC Biorepository in a way they believe best serves the needs of the AMC. However, the proposed solutions should adhere to established Standard Operating Procedures, protocols and collaborative agreements between the ACSR and the AMC. If there are proposed changes in the AMC Biorepository activities, leadership, or institutional location of biospecimens, every effort MUST be made to limit disruption to the AMC's clinical trial activities. Proposed changes must be accompanied by a plan to facilitate these changes in a seamless manner for the AMC. Describe the institutional location, leadership, and structure of proposed for the AMC Biorepository. Describe the experience of the proposed leader of the AMC Biorepository and any past cooperative group clinical trials biorepository experience and existing infrastructure. Describe processes and procedures in place that will facilitate this site acting as the AMC Biorepository. If this is a newly proposed site, the applicant must propose a plan for transitioning the AMC Biorepository to a new facility. The applicant must describe why the newly proposed site is better suited to fulfill the AMC Biorepository needs.
• ii. Sub-Saharan Africa Regional Biospecimen Repository. The ACSR awardee will be required to work with and incorporate an African RBR that is currently being developed in association with the AMC. The applicants must describe their plans to fully and efficiently incorporate the African RBR into the proposed resource (beginning from the third year of the project period). This requirement applies to all applicants responding to this FOA even though they may not be involved in the early stages of the development of this African RBR. The applicants are also expected to identify a U.S.-based individual, who will serve as ACSR liaison and assist the African RBR leadership in adopting ACSR SOPs, MOO, policies and procedures, or adapting those processes to accommodate local and regional policies and laws. Describe the plans for involving the foreign investigators in ACSR activities, especially in continued training and capacity building activities that may serve to improve the African site.

Letters of Support

The applicants must provide appropriate letters of collaboration from the Institutions that will be housing the RBR in order to demonstrate institutional support for participation in the ACSR enterprise.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

Foreign (non-U.S.) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS 398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the NCI. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the resource as proposed to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the resource as proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a resource that by its nature is not innovative may be essential to advance a field.

Significance

Does the resource as proposed address an important problem or a critical barrier to progress in the field? If the aims of the proposed resource are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the proposed resource? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the resource is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Are the qualifications and expertise of the proposed ACSR Leaders, RBR Leaders, other investigators, collaborators, and participants adequate to meet the unique goals and objectives of the ACSR? How well does the entire team represent the multidisciplinary expertise that would be required for clinical, scientific, and technical advancement of the ACSR? Have team members demonstrated their ability to effectively contribute to team science efforts in the past, through NCI or NIH initiatives?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the proposed resource? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific for this FOA:

Proposed Overall ACSR Structure:

How well does the plan address the key reasons for restructuring the ACSR enterprise? Specifically, does the plan ensure sufficiently centralized, effective leadership, administration, and oversight of the ACSR activities? How well does the proposed structure address issues regarding the accountability, efficiency, productivity, and communication for all the ACSR components? Are the overall plans for the organization and functioning of the resource sufficient? Are the proposed governance elements, including advisory and evaluation panels/committees structured optimally and described in sufficient detail? Are the profiles, composition, and expertise of the proposed Working Groups optimal for the entire ACSR?

ACSR Functioning:

Are the plans for the collection, storage, and distribution of quality biospecimens and associated clinical data adequate and appropriate? Specifically, what is the likelihood that the applicants will be able to increase biospecimen donations to the ACSR in a manner that would properly reflect changing patterns of the cancer burden among HIV-infected individuals? Is the proposed accrual of new, rare, or difficult to obtain biospecimens (and associated data) sufficient and realistic? How adequate are the proposed systems for quality control and quality assurance?

Outreach:

To what degree can the ACSR, as proposed, fulfill the goal of providing unique resources and/or services otherwise not available to the HIV/AIDS malignancy research community? How adequate are plans for equitable biospecimen distribution? How sufficient are the proposed efforts for continuous adjustments to resource functioning to meet the changing needs of external HIV/AIDS researchers?

Associated Programs of the ACSR:

Are the proposed setup and procedures for serving the AIDS Malignancy Clinical Trials Consortium (AMC) biobanking activities appropriate and adequate? Are the ACSR plans in that regard optimal and sufficient for both domestic and international settings? Based on the plans described, what is the likelihood that the African RBR will be efficiently and optimally incorporated into the ACSR?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific for this FOA: What is the likelihood that all of the proposed ACSR components will integrate into a cohesive environment? How sufficient is the evidence of commitment of the individual participating institutions in the activities of the ACSR?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Central Operations and Data Coordinating Center (CODCC)

How well will the proposed CODCC Component serve its intended role of providing a strong leadership to facilitate the coordination of ACSR activities? Is the role of CODCC in enforcing the protection of human subjects and patient confidentiality adequately planned? Are the plans for the development and/or improvement of the bioinformatics systems appropriate and sufficient? Are the proposed plans for outreach to both the scientific and patient communities appropriate? Are proposed plans for publicizing the resource to the scientific community appropriate?

Regional Biospecimen Repositories (RBRs)

Are all the proposed RBRs capable of effectively obtaining, curating, and distributing biospecimens and associated data as needed for the ACSR? Are there sufficient documentation and evidence that the proposed RBRs have the ability and commitment to follow NCI Best Practices in Biospecimen Resources and other ACSR required standard procedures? Are the experience, expertise, and organizational structures of each of the proposed RBRs appropriate? Are the plans for continuing review and ensuring performance and productivity of RBRs well thought out? Is the plan for the development of metrics and milestones for each RBR well serving the goals of the resource?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Cancer Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted response to this FOA.

Applications will be assigned to the NCI and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

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

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

Throughout these Terms and Conditions of Award, "ACSR" or "Resource" refers to the organizational structure, which is composed of the ACSR Chairperson and other key personnel, the Central Operations and Data Coordinating Center, the Regional Biospecimen Repositories, Working Groups and Member Institutions ( i.e. institutions housing any of the components of the ACSR), all of whom agree to collaborate on research goals of the AIDS and Cancer Specimen Resource.

The PD(s)/PI(s) will have the primary responsibility for:

• The Program Director/Principal Investigator (PD/PI) (or multiple PDs/PIs, if applicable) will have the primary responsibility for defining objectives and approaches for acquiring, storing, and equitably distributing tumor tissues and biological fluids from patients with HIV-associated malignancies.
• The PD/PI representing the application-submitting institution is expected to serve as the Chairperson of the ACSR.
• The PD(s)/PI(s) will assume primary responsibility for the ACSR serving as the AIDS Malignancy Clinical Trials Consortium's (AMC) biorepository.
• The ACSR Chairperson, with assistance from the NCI Project Scientist, will oversee the development and implementation of the new ACSR structure. With guidelines from this FOA and plans presented in the application, the Chairperson along with the proposed Governing Committee and will develop and maintain an organizational structure for the ACSR. The organizational structure should include the RBRs, Working Groups, and other components of the ACSR that the Resource needs to support its research objectives.
• The Chairperson will oversee the preparation, implementation, and maintenance of SOPs, MOO, and other policies and procedures that cover all aspects of ACSR activities.
• The ACSR Chairperson and the Governing Committee will develop evaluation criteria and processes for RBRs, the AMC Biorepository, the CODCC/Administrative and Bioinformatics Cores and other ACSR programs and initiatives.
• The ACSR Chairperson, upon consultation with the Governing Committee and an 'evaluation committee', will have the right to propose to the NCI modifications or cancellations of any sub-contractual arrangements under the ACSR award. In addition, the ACSR Chairperson, in conjunction with the NCI Project Scientist and the Governing Committee, will have the right to make other changes to enhance the performance of the ACSR or address problems of performance.
• The ACSR Chairperson and other PDs/PIs (if applicable) will ensure that all RBRs and ACSR Collaborators receiving award funds for the acquisition, storage or distribution of biospecimens and data will continue to work towards compliance with NCI's Best Practices for Biospecimen Resources (http://biospecimens.cancer.gov/practices/2011bp.asp) and the International Society for Biological and Environmental Repositories Best Practices (http://www.isber.org/bp/). With rare, Governing Committee granted exception, RBRs will solely handle the storage/distribution of ACSR biospecimens and communication of associated data to the CODCC.
• The ACSR Chairperson and representatives of the participating institutions will work together, through the Governing Committee, to establish uniform collection methods and policies, and to assure quality control of biospecimens and data. All representatives of the participating institutions will be required to accept and implement the common policies and procedures approved by the Governing Committee. All representatives of the participating institutions will work together to ensure that a database of biospecimen information is kept current, using the software tools provided by the CODCC's bioinformatics component.
• The ACSR Chairperson will ensure that all ACSR components will undergo periodic evaluations that are commensurate with their roles in the ACSR. For example, RBRs are expected to undergo yearly self evaluations, periodic site visits, and internal evaluations to assure that their site is in compliance with ACSR policies.
• The ACSR Chairperson, with the Governing Committee and the NCI Project Scientist, will oversee the development of an efficient, equitable, and effective process to field inquiries, accept requests for access to biospecimens and associated data, review Letters of Intent (LOIs), and distribute biospecimens. ACSR Participants must agree to provide access to biospecimens and associated data to investigators based on the prioritization of research proposals set by the REDP and final approval by the Governing Committee. ACSR Participants must agree to abide by the decisions of the Governing Committee based on recommendations from the REDP.
• The ACSR Chairperson, with the Governing Committee, will be expected to develop an efficient and effective process to identify emerging scientific and technical opportunities to improve the ACSR, evaluate these opportunities, and select the most promising opportunities for implementation.
• The ACSR Chairperson is expected to serve as the Chairperson of the Governing Committee (see below).
• The ACSR Chairperson is responsible for convening appropriate ACSR Working Groups and overseeing their activities. Each Working Group will be expected to include, as members, investigators of appropriate profile from several RBRs and other collaborators or investigator users of the ACSR with relevant experience. The ACSR Chairperson, in coordination with the Governing Committee, will periodically review the activities and accomplishments of these Working Groups. The ACSR Chairperson will adjust goals, objectives, leadership, membership and other activities of these Working Groups as needed.
• The ACSR Chairperson will be responsible for providing the NCI Project Scientist a twice-yearly progress report indicating site/initiative/program specific contributions to tissue acquisitions and tissue distribution in response to approved Letters of Intent.
• The ACSR Chairperson will oversee the compliance of the ACSR with all the applicable regulations related to the protection of human subjects. The PDs/PIs or other senior representatives from all participating institutions must cooperate with the ACSR Chairperson to ensure that all participating institutions have an approved assurance of compliance for the protection of human subjects on file with the Office of Human Research Protection and that necessary IRB reviews are conducted by the IRBs of the appropriate institutions in accordance with 45 CFR part 46 prior to the involvement of human subjects.
• The ACSR Chairperson will be responsible for ensuring that all publications and oral presentations resulting from the ACSR award properly acknowledge the NCI support.
• The ACSR Chairperson, other PDs/PIs, and other senior representatives of the participating institutions will be expected to cooperate with the NCI in facilitating the conduct of the external evaluation of the ACSR program (to be coordinated by the NCI).
• The awardee 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.

Responsibilities of Central Operations and Data Coordinating Center (CODCCC)

• The CODCC will perform the coordinating activities of the ACSR's components. They will provide logistical support for the conduct of meetings, telecommunications, the development of marketing materials and support for attendance at meetings/conferences for marketing purposes, travel, progress reports, ACSR programmatic tracking activities and other activities of the ACSR.
• The CODCC will provide support for the ACSR Chairperson in the preparation and maintenance of SOPs, MOO, and other policies and procedures documents that cover all aspects of ACSR activities.
• The CODCC will coordinate the activities of fielding inquiries, accepting requests for access to biospecimens and associated data, management of Letters of Intent (LOIs) and the coordination and communications regarding the distribution of biospecimens. The CODCC will be responsible for communications with the Executive Secretary of the REDP and the Governing Committee regarding LOI reviews and prioritization.
• The CODCC's bioinformatics component will maintain the database of available biospecimens and clinical data.
• The CODCC's bioinformatics component will be responsible for developing and instituting training programs for implementation and use of the ACSR's software tools.
• The CODCC will be responsible for collecting site-specific tissue acquisition and distribution information, and tracking information such as inquiries, LOI, acquisition and distribution information.

Responsibilities of Regional Biorepositories (RBRs)

• Each proposed RBR is expected to provide the infrastructure to acquire, store and distribute biospecimens and data for the ACSR enterprise. It is intended and expected that the RBRs will solely handle the storage/distribution of ACSR biospecimens and communication of associated data to the CODCC.
• Each RBR proposed will have both clinical laboratory and pathology components, and must include a pathologist as part of the key personnel.
• Each RBR must also include a Regional Operations Office to perform RBR administrative duties and to manage clinical data and tissue and biological fluids related repository data.
• Regional Operations Office will supply biospecimen data update information to the ACSR's central bioinformatics systems.
• Regional Operations Office will perform the RBR's self-auditing and reporting processes, and other administrative activities of the RBR. The RBR Operations Office is to facilitate communication between the RBR and the CODCC.
• RBRs are expected to undergo yearly self-evaluations, periodic site visits, and internal evaluations to assure that their site complies with ACSR policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NCI Office of HIV and AIDS Malignancy Program Staff member will serve as the NCI Project Scientist for the ACSR. Another NCI staff member will serve as a Project Coordinator. The NCI Project Scientist and Project Coordinator will have substantial scientific -programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NCI Project Scientist/Coordinator will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications. If such participation is deemed essential, these individuals will seek NCI waiver according to the NCI procedures for management of conflict of interest.

Additionally, an NCI program director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The designated Program Official may also have substantial programmatic involvement (as Project Scientist/Coordinator). In that case, the individual involved will not attend peer review meetings of renewal (competing continuation) and/or supplemental applications or will seek NCI waiver as stated above.

The main responsibilities of substantially involved NCI staff members include the following:

• The NCI Project Scientist will serve as a voting member of the Governing Committee, the advisory sub-committee, and relevant Working Group meetings. The NCI Project Scientist will cast a single, NCI vote on the Governing Committee and advisory sub-committee.
• The NCI Project Coordinator may attend, as a non-voting member, the meetings of the Governing Committee, the advisory sub-committee, and relevant Working Group meetings.
• Additional NCI representatives may attend Governing Committee and advisory sub-committee meetings as non-voting observers and may participate in relevant Working Group meetings.
• The NCI will coordinate the logistics of the Review and Evaluation Decision Panel (REDP).
• The Project Coordinator will serve as the ex officio (non-voting) member and Executive Secretary of the REDP. In his/her role as Executive Secretary, the NCI Project Coordinator will advise the ad-hoc REDP members on the procedures for reviewing the proposals requesting biological biospecimens and clinical data.
• The NCI Project Scientist and Coordinator will provide technical assistance, advice, and coordination commensurate with their roles, to assure that the Governing Committee, advisory sub-committee, and REDP follow the NIH Guidelines on conflict of interest issues and play critical roles in promoting the availability and use of ACSR resources. The roles of the NCI Project Scientist and Coordinator are to assist and facilitate, but not to direct activities of the ACSR.
• The NCI Project Scientist and Coordinator will act as liaisons between the ACSR and other Divisions, Offices and Centers of the NCI, specifically: NCI's Biorepositories and Biospecimen Research Branch (BBRB) as the ACSR works towards compliance with NCI's Best Practices; The Center for Global Health (CGH) as the ACSR continues to focus on collections from Sub-Saharan Africa and developing an African RBR; and the NCI's Cancer Biomedical Informatics Grid (caBIG) initiative. The Project Scientist/Coordinator will act as liaisons between the ACSR and other NCI/NIH-supported groups: The AIDS Malignancy Clinical Trials Consortium (AMC); The Clinical Trials Cooperative Groups; and other NCI/NIH supported groups or individuals that could contribute to, or benefit from, the ACSR's mission.
• The NCI Project Scientist and Project Coordinator will act as observers in internal evaluations.
• The NCI staff members will coordinate external evaluations of the ACSR program.

The NCI will have access to all data collected and/or generated under this Cooperative Agreement and may periodically review the data. The NCI may also review all records related to awardees performance under the award.

The National Cancer Institute reserves the right to reduce the budget, to withhold support, and to suspend, terminate, or curtail a study or an award in the event of substantial shortfall in biospecimen accrual, data reporting, inadequate quality control in biospecimens or clinical data collection, non-adherence to biohazard precautions, refusal to carry out the recommendations of the REDP or the Governing Committee, or other substantial failure to comply with the terms of award. This right extends to the termination of specific subcontractual arrangements in case of an underperforming component.

Areas of Joint Responsibility include:

• A Governing Committee (GC): Serving as the governing body of the ACSR, the GC will assist the ACSR Chairperson in the decision-making processes that will ensure that the ACSR's major structural components are capable of carrying out their respective responsibilities and operating in a well-coordinated fashion. It is expected that the GC will provide final approval for LOIs and administrative oversight for the ACSR enterprise and provide recommendations regarding support for RBRs and initiatives based upon the results of evaluation procedures adopted by the ACSR. It is expected that the ACSR Chairperson will be the Chairperson of the GC. The NCI Project Scientist will be a voting member of the GC. The NCI Project Coordinator will be a non-voting member. Voting membership should also include RBR and Bioinformatics leadership. Additional membership may include: Biostatistical and Executive Secretary support.

The GC may form sub-committees as needed. Both the NCI Project Scientist and the Project Coordinator may be members of such sub-committees as they deem appropriate (but will not chair those sub-committees). One expected sub-committee to be formed is an Advisory Panel (see below).

• An Advisory Panel: This sub-committee of the GC is expected to function as a scientific 'think tank' for the ACSR. The Advisory Panel may include representatives from RBRs, the CODCC, Working Groups, and other components of the ACSR. It is suggested that the Advisory Panel includes members with biostatistical and bioinformatics expertise, and that one or two external research scientist(s) with expertise in the field of HIV-associated malignancy research be appointed to the sub-committee. It is expected that the advisory sub-committee will have an AMC representative. The Advisory Panel should be comprised of members that have a broad level of expertise, including expertise in HIV, HIV and cancer, epidemiology, anatomic/clinical pathology and biospecimen/biorepository sciences.

Dispute Resolution:

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 Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Governing Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

The ACSR Chairperson, with assistance from the CODCC, must provide an annual progress report in its non-competitive continuation application to the Office of HIV and AIDS Malignancy, NCI. Additionally, the report should be made openly accessible to all ACSR Governing Committee members.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

eRA Commons Help Desk (Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: [email protected]

Rebecca Liddell Huppi, PhD
National Cancer Institute (NCI)
Telephone: 301-496-4995
Email: [email protected]

Referral Officer
Division of Extramural Activities
National Cancer Institute (NCI)
6116 Executive Blvd, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for US Postal Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301- 496-3428
Fax: 301-402-0275
Email: [email protected]

Julie Peoples
National Cancer Institute (NCI)
Telephone: 301-496-7208
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

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 Part 52 and 45 CFR Parts 74 and 92.