It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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. 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.

Part 1. Overview Information
Part 2. Full Text of the 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

The purpose of this limited competition Funding Opportunity Announcement (FOA) is to support the biobanking infrastructure and operations for the Experimental Therapeutics Clinical Trials Network (ETCTN) and other NCI-supported early and experimental trials.

The goals of this FOA are:

• To ensure the collection, processing, storage, and distribution of quality human biospecimens procured from cancer patients participating in ETCTN early (0, 1, or 2) phase and pilot clinical trials for investigational drug agents, and in other NCI-supported early phase and experimental therapeutic clinical trials.
• To ensure that biospecimens collected in the course of the NCI-supported ETCTN and other early phase and experimental cancer clinical trials are available for distribution to qualified investigators at NCI-approved reference research laboratories and institutions, for correlative laboratory studies and early clinical evaluation of innovative cancer therapies.

Currently, this biobanking infrastructure supporting NCI early experimental clinical trials is part of a biobank serving primarily another NCI program, the National Clinical Trials Network (NCTN). Through a separate U24 award under this FOA, the NCI aims to separate the existing ETCTN-serving biobanking infrastructure and operation from the current NCTN Biobank. This separated entity will be termed: Early-Phase and Experimental Clinical Trials Biospecimen Bank (also referred to as EET Biobank). Although the EET Biobank and the "parent" NCTN Biobank may be hosted in the same institution, they are expected to become independent operations with separate leaderships.

EET Biobank will be responsible for collecting, processing and storing a variety of human specimens from patients with cancer who are participating in NCI-funded ETCTN and other NCI-supported early and experimental clinical trials. The responsibilities of EET Biobank will also include up-to-date maintenance of specimen inventory and distribution of specimens to qualified NCI-approved investigators and research laboratories.

Key Terms for This FOA

NCI Biobank: A biospecimen bank (biobank) refers to an infrastructure designed to store human biospecimens collected during NCI-supported clinical trials as well as distributing these biospecimens to investigators. An institution hosting a given biobank is referred to as Biobank-hosting institution. An institution may host one or more biobanks.

Experimental Therapeutics Early Clinical Trial Network: ETCTN is a network of clinical trial sites and infrastructure that is devoted to the early clinical development of anticancer drugs. ETCTN clinical trials are supported by integrated centralized clinical and administrative services sponsored by NCI. The coordination of the ETCTN efforts and oversight of this program is provided by the NCI Investigational Drug Branch (IDB), which is part of the Cancer Therapy Evaluation Program (CTEP).

Current Situation and Reorganization of Biobanking Support for NCI Early Phase and Experimental Clinical Trials.

For years, the NCI has been supporting a standing clinical trials infrastructure to facilitate the early stages of development and evaluation of anti-cancer therapeutic agents in partnership with industry and academia. This infrastructure, the Experimental Therapeutics Clinical Trials Network (ETCTN), is currently funded through several UM1 Cooperative Agreement awards under RFA-CA-19-007. Presently, the biobanking needs of ETCTN are served by a biobank, which is a sub-operation (through restricted funds) to a "parent" U24 "SWOG Biospecimen Bank", awarded under RFA-CA-14-501, that serves NCTN clinical trials.

Because of the distinct nature of the biobanking needs for the early-phase and experimental versus NCTN clinical trials, the NCI has decided to separate these two biobanking infrastructures and operations. Accordingly, reorganization under this FOA is expected to transition the ETCTN-serving infrastructure to a separate U24 EET-biobank award. (SWOG Biospecimen Bank is expected to continue serving NCTN through a separate FOA, RFA-CA-20-002).

Characteristics of Biobanking Support for NCI Early Phase and Experimental Clinical Trials.

The ETCTN biobank collects, processes and stores high-quality human biospecimens from cancer patients, who participate in NCI Phase 0, I, and Phase II, and other experimental therapeutic cancer trials. Specimen collections from such patients offer several advantages such as: (a) uniform information on medical history and treatment details; (b) biospecimen quality assurance/quality control (QA/QC); and (c) reasonable costs compared to other sources. These specimen collections are associated with comprehensive clinical data, including a detailed drug information, treatment histories/outcomes, and cancer recurrence data.

The specimens collected are to be used for:

• Development of validated integral and integrated biomarker assays that can be incorporated as endpoints into ETCTN studies;
• Demonstration of drug target engagement, mechanism of action, mechanisms of resistance, or to enhance patient selection in subsequent studies;
• Achievement of a long-term goal to accelerate the development of NCI-IND agents to improve the outcome of cancer therapy; and
• Assessment of pharmacokinetic (PK) and pharmacodynamic (PD) of the studied experimental therapeutic agents.

The goal of this Limited Competition FOA is to ensure the continuity of operation of the ETCTN-supporting biobank that already exists and operates under one of the NCTN biobanking awards. A separate U24 award for this existing bank will allow for expansion of the operations to include other NCI-supported early phase and experimental trial networks/investigators. This reorganization is also expected to facilitate enhancements and/or administrative improvements that applicant team may need to expand and optimize their operation.

General Expectations:

The EET Biobank proposed must have the following capabilities and characteristics:

• Providing consistent, integrated and well-coordinated infrastructure for specimens from the ETCTN clinical trials;
• Expanding operation to include, as needed, the specimens from other (non-ETCTN) NCI-supported early phase and experimental clinical trials;
• Harmonizing biobanking operating procedures for all clinical trial networks/investigators to be served;
• Scientific leadership with extensive hands-on expertise in biobanking operations for complex NCI clinical trial networks.

Specific Responsibilities of the EET Biobank Regarding ETCTN:

• Collecting, processing, storing and distributing specimens from ETCTN;
• Collaborating on the aspects relevant to the biobanking operation with ETCTN Lead Academic Organizations (LAOs)/ Lead Protocol Organizations (LPOs), and the NCI;
• Distributing banked specimens for downstream analysis to the NCI-approved ETCTN investigators and the appropriate laboratories as specified in the protocol or after appropriate review of the proposed research studies by CTEP.
• Providing biobanking operations for specimens collected on the ETCTN clinical trials that require distribution to CIMACs (CIMAC) for downstream analysis, and collaborating with ETCTN and CIMACs on processing, storage, and distribution of such specimens.

Specific Responsibilities Regarding Other NCI Early and Experimental Trials:

The EET Biobank will be responsible for biobanking of specimens that will be collected during other NCI early and experimental clinical trials, such as cancer immunotherapy trials.

In this context, the EET Biobank will have the following specific obligations:

• Receiving specimens from approved early phase and experimental trials (as per respective clinical trial protocols);
• Storing and processing formalin-fixed paraffin-embedded (FFPE) blocks and histological slides from diagnostic and research biopsies;
• Storing and processing frozen tissue specimens and nucleic acids may also be collected and prepared; and
• Storing other specimens including but not limited to serum, plasma, whole blood, white blood cells, bone marrow, urine, skin, and sputum/buccal samples (per trial protocol).

Required Capacities for Specimen Collections

The specimens from collection sites will be sent to the EET Biobank.

EET Biobank must be prepared for and capable of the following activities:

• Receiving, processing, storing and distributing ETCTN and other early phase and experimental clinical trial specimens for development and validation of (integral and integrated) markers (as defined in the trial protocol). The specimens will encompass adult and pediatric solid malignant tumors (e.g., tumors of the brain, breast, gastrointestinal tract, genitourinary tract, gynecologic/reproductive system, head and neck, skin, liver, lung, soft tissue, and thyroid gland) and hematologic malignancies (leukemia, lymphoma, and multiple myeloma)
• Handling formalin-fixed, paraffin-embedded (FFPE) blocks and histological slides from diagnostic biopsies and surgical resections from patients with cancer, fresh and frozen specimens, serum, plasma, whole blood, white blood cells, biomolecules (such as nucleic acids), circulating tumor DNA (ctDNA), bone marrow, urine, skin, stool and sputum/buccal and other samples as defined in the trial protocol.
• Developing and following standard operating procedures (SOPs) as needed.
• Building special collection kits as defined in the trial protocol and distributing them to the collection sites.
• Scanning and storing digital tissue whole slide images.
• Implementing specialized processing procedures for specimens from the Cancer Immunotherapy trials and distributing such specimens to CIMACs.

Requirements Regarding Specimen Access and Distribution:

• The proposed EET Biobank will be responsible for ensuring that the biospecimen needs of the qualified clinical trial investigators are met.
• EET Biobank must follow defined biospecimen access processes approved by NCI/CTEP.
• EET Biobank must have an established local Informatics system that will support the Biobank and integrate with the NCI Specimen Tracking system managed by Theradex Oncology (http://www.theradex.com/clinicalTechnologies/?National-Cancer-Institute-NCI-11) and will also connect the Biobank with the NCI Medidata Rave system.

Program Evaluation

As the efficiency of the funded research is an important priority for NCI, the EET Biobank awardee will be expected to participate in an external evaluation process coordinated by NCI program staff (see Section VI: Terms and Conditions of Cooperative Agreement).

See Section VIII. Other Information for award authorities and regulations.

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

Eligibility is limited to the institution that is currently hosting the existing ETCTN biobank infrastructure and operation supported by dedicated "Restricted Funds" under current 5U24CA196175 award for "SWOG Biospecimen Bank". (Note that application to this FOA should NOT be construed as a renewal of 5U24CA196175 award).

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 SF424 (R&R) Application Guide.

An individual designated as contact PD/PI can be either a pathologist (with an M.D. degree) or a laboratory scientist (with M.D or Ph.D. degree) and must have an expertise relevant to biospecimen science and a leadership experience in biospecimen banking for cancer clinical trials.

In addition, an individual designated as contact PD/PI must not be designated as a contact PD/PI on any application for NCTN Biobanks under RFA-CA-20-002.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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 activity
• 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:

Irina A. Lubensky, MD
Pathology Investigation &Resources Branch
Cancer Diagnosis Program
Division of Cancer Treatment and Diagnosis,
National Cancer Institute (NCI)
Shady Grove Campus
9609 Medical Center Drive, Rm 4W452
Rockville, MD 20850
Telephone: 240-276-5902
Fax: 301-276-7889
Email: lubenskyI@mail.nih.gov

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed with the following modification: The page limit for Research Strategy for this FOA is 30 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. Additional instructions are provided below:

Other Attachments:

Applicants must provide the following additional materials in support of their application. Each attachment should be uploaded as a separate PDF file using the indicated filenames (which will serve as application bookmarks).

Attachment 1: Operational Capability (use filename "Scale of Operation"). Provide documentation for current and future (maximal) scale of operations.

Attachment 2: Standard Operating Procedures (use filename "SOPs").

List (with synopses):

• Selected Local Standard Operating Procedures;
• Documents and procedures as adopted and implemented by your Biobank as part of the ETCTN biobanking operation;
• Key procedures related to informatics capabilities.

All instructions in the SF424 (R&R) Application Guide must be followed. Additional guidance applies:

Biosketches: For the individual designated as the contact PD/PI, document that such individual (who must be either a pathologist with M.D. degree or a Laboratory Scientist with M.D. or Ph.D. degree) is actively involved in the operation of a pathology laboratory that has demonstrated access to human cancer tissues from clinical trials.

List the accomplishments of the proposed PD(s)/PI(s) and the extent of their hands-on leadership experience in clinical trial biobanking.

All instructions in the SF424 (R&R) Application Guide must be followed. The following additional guidance applies:

PDs/PIs Effort: All PDs/PIs are expected to contribute substantially to the activities on EET Biobank awards throughout the entire project period. Effort level of at least 2 person-months is required for the contact PD/PI and 1 person-month for other PDs/PIs, if proposed. These commitments cannot be reduced in later years of the award.

Budget Justification:

Roles of all key personnel (must appropriately match their effort commitment) and planned mutual interactions within the Biobank.

The budget request may include costs associated with:

• Materials and supplies needed for biospecimen collection/processing/storage/distribution;
• Local IT system;
• QA/QC;
• Digital whole slide images scanning and storage for defined specimen sets and for biobank QA/QC purposes;
• Specialized processing/handling/distribution of ETCTN immunotherapy trial specimens to CIMACs.

Capital Equipment. In general, capital equipment (i.e., equipment with unit cost of $5,000 or more) is not allowed. In exceptional situations, however, capital equipment may be requested if supported by a clear and strong justification (e.g., to replace an outdated or malfunctioning equipment that is essential for the biobank operation.) Each such request will be considered on a case-by-case basis.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: Outline Specific Aims for the proposed EET Bank. Ensure that these Aims properly and comprehensively address the key responsibilities defined in Section I of the FOA regarding: specimen collection/processing, QA/QC, storage, and distribution of biospecimens.

Research Strategy: Instead of the standard sub-sections, Research Strategy must consist of the following sub-sections:

Sub-section A. Biobank Overview;

Sub-section B. Leadership Structure and Interactions;

Sub-section C. Biobank Operations; and

Sub-section D. Data Management and Informatics

Specific guidelines and requirements for these Sub-sections are described below.

Sub-section A. Biobank Overview

• Provide a brief background for your current biobank (ETCTN Biobank).
• Characterize the capabilities of the biobank in terms of the current and future scale of operation.
• Summarize specific contributions of the biobank in the last five years.
• Highlight the scientific impact of the biobank that will result from the future specimen use.
• Describe organizational structure proposed for the EET Biobank and its relationship to the ETCTN and other affiliates (include organizational chart, define lines of authority and individual responsibilities).

Note: supporting documentation for this sub-section is requested under "Other Attachments" (Attachment 1&2).

Sub-section B. Biobank Leadership

Describe the responsibilities of the EET Biobank leadership and key personnel interactions with the ETCTN specimen collection sites and investigators/PI. This description should address:

• The strengths that the applicant's team would bring to collaborative network activities such as updating EET Biobank policies and priorities, improving quality of services, improving information systems to manage the resource, monitoring progress, developing new strategies, as needed to ensure that the resource remains responsive to researchers' needs.
• Your vision on how your biobank operation might be improved.

Sub-section C. Biobank Operations

This sub-section should address all essential aspects of biobank operations, including QA/QC and human biospecimen-related legal and ethical issues. Specific items to be covered include but are not limited to:

• Receipt of biospecimens from the collection sites (biospecimens include but are not limited to FFPE blocks, histological slides and frozen tissue from diagnostic biopsies and surgical resections specimens, serum, plasma, whole blood, white blood cells, bone marrow, urine, skin, stool and sputum/buccal samples per trial protocol);
• Processing and storing biospecimens at the biobank (including conducting pathology reviews and providing histology services, preparing nucleic acid extracts and ctDNA from specimens);
• Conducting QA/QC of the biospecimens before distributing them to investigators;
• Processing and sending specimens to CIMACs from cancer patients treated on ETCTN immunotherapy trials;
• Distributing biospecimens to investigators and/or laboratories;
• The ways of handling legal and ethical aspects related to human biospecimens.

Note on Innovative Aspects: In respective parts of this sub-section, highlight any proposed improved practices for specimen processing and QA/QC, specimen tracking, and/or other creative ways to increase the utilization of the resource.

Sub-section D. Data Management and Informatics

This sub-section should address not only the local IT solutions but also plans for integration with the Theradex Specimen IT Tracking System and NCI Medidata Rave system. Specific items to be covered include but are not limited to:

• The biobank’s current local IT system that tracks bank specimens, and associated data;
• A plan to facilitate data exchange, particularly between Biobank, collection site and RAVE Informatic systems.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) 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.

Appendix:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the NCI, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this announcement, note the following:

The emphasis of this FOA is on building a state-of the-art Biobanking Resource that will serve ETCTN and other NCI-supported early and experimental clinical trials. The EET Biobank is expected to ensure that biospecimens from patients participating in the NCI-supported cancer clinical trials are annotated, processed, stored and distributed to the laboratories/investigators using harmonized approach (SOPs). The responsibilities of EET Bank will also include maintenance of up-to-date specimen inventory.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project 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 project 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 project that by its nature is not innovative may be essential to advance a field.

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project 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?

Specific to this FOA: Based on the infrastructure and scale of operations, what is the likelihood that the proposed Biobank and use of its biospecimens will contribute significantly to clinically relevant cancer research and/or influence clinical practices?

How well can the Biobank support the banking needs of the NCI early and experimental clinical trial networks?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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 project 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:

• How strong are the background and expertise in pathology and laboratory science, and hands- on leadership experience in biospecimen banking operation of the PD(s/PI(s)?
• How well are the qualifications of the Biobank leader(s) and key personnel suited to lead and operate a large-scale biospecimen banking operation, ensuring a high level of quality for specimens and records? Based on accomplishments over the last five years, how competent is the PD/PI (or PDs/PIs) in overseeing/directing biospecimen banking operation for early and experimental clinical trials?
• How committed is the leadership to optimizing the Biobank functioning, including strong leadership interactions and oversight of biobanking operation, monitoring progress, developing new strategies, and ensuring that the resource remains responsive to researcher’s needs?
• Are the interactive structures and lines of communications between the PD/PI (or PDs/PIs) of the Biobank and the ETCTN clearly defined and appropriate?
• How strong is the vision of the Biobank leadership to improve and harmonize banking operations?

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?

Specific to this FOA: Has the applicant team introduced and/or proposed any innovative, improved specimen-related practices (e.g., with regard to specimen processing, QA/QC, specimen tracking, optimized fee for service schemes) and/or other creative ways to operate the resource?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA:

Biobank Operations:

• How capable and efficient is the biobanking operation in processing, storing, and distributing different types of biospecimens including fresh-frozen tissues, FFPE blocks, histological slides, others? Are the QA/QC efforts appropriate to ensure sufficiently high quality of biospecimens and their annotated data?
• What are the necessary QA/QC steps to be completed before the distribution of biospecimens to the laboratories and investigators?
• How well thought out are the applicant's plans to address the needs of the early and experimental trial scientific community?
• Are the legal and ethical issues related to human biospecimens receiving sufficient attention? Are these issues handled competently and adequately?

Data Management and Informatics:

• How advanced is the integration of a local biobank IT system with the Theradex Specimen IT Tracking System and NCI RAVE system?
• What strategy is in place to achieve IT integration in terms of functioning of the Biobank as an integrated EET resource?
• How efficient are the interactions between the Biobank IT team and NCI Clinical Trials Management System (CTMS) personnel?

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?

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.

For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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.

Not applicable

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).

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) Genomic Data Sharing Plan (GDS).

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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 NCI, 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:

• Will receive a written critique.

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications 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 (NCAB). 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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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.

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

• Overseeing the operations of the Biobank and Biobank's Informatics System and its interactions with the Theradex Specimen IT Tracking System;
• Overseeing the interactions of the Biobank personnel with the personnel of the specimen collecting sites and laboratories where the specimens will be distributed;
• Participating in the work of EET Working Group (both directly and through designated representatives);
• Implementing (to the extent consistent with applicable grant regulations) policies and recommendations developed by the EET Working Group (in areas such as defining regulatory procedures, best practices or operating policies and procedures, education of research community, and quality assurance measures for all aspects of the operation of the EET Biobank).
• Harmonizing the operations of the Biobank to be consistent with the NCI Best Practices for Biospecimen Resources Guidelines (https://biospecimens.cancer.gov/bestpractices/index.asp ), EET Biobank Manual of Operations, and other documents prepared and/or approved by the EET Working Group; and
• Assuring that designated banked tissues are available to the trial investigators/laboratories in accordance with the access policies developed by the EET Working Group.

In addition:

• Awardee will be expected to continuously address the evolving legal, ethical, and human subjects policy issues related to the use of human biospecimens for research purposes following the guidelines on these issues in the NCI Best Practices for Biospecimen Resources Guidelines (https://biospecimens.cancer.gov/bestpractices/index.asp) and the Office for Human Research Protections (OHRP) website (http://www.hhs.gov/ohrp/).
• EET Biobank awardee must meet all the applicable requirements of the Federal Human Subjects Regulations 45CFR46 (i.e., the Common Rule, for guidance, see http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf).

Awardees will retain custody 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.

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

An NCI Program staff member(s) acting as a Project Scientist(s) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Additionally, an NCI program staff member 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 main responsibilities of substantially involved NCI staff members include but are not limited to the following:

• Serving as a liaison between the EET Biobank awardee and the NCI;
• Facilitating interaction among all involved organizations including the EET Biobank, ETCTN Lead Academic Organizations (LAOs), and NCI units involved, including: Investigational Drug Branch (IDB) of the Cancer Therapy Evaluation Program (CTEP), Cancer Diagnosis Program (CDP), Cancer Immune Monitoring and Analysis Centers (CIMACs), NCI Specimen Tracking System (managed by Theradex Oncology) and NCI Medidata Rave System.
• Providing technical assistance and advice to the awardee on monitoring QC/QA, developing policies and standard operating procedure (SOP);
• Monitoring QC/QA of collected human biospecimens;
• Overseeing progress toward developing policies and milestones and adherence to the project time-lines;
• Assisting with the development of best practices for collection, processing, storage, retrieval, and shipping of specimens;
• Providing consultation and advice regarding the development of appropriate processes for assuring access to the banked specimens, legal and ethical issues such as implementation of the DHHS Health Information Portability and Accountability Act (HIPAA) Privacy Rule, the common rule (45 CFR 46) and Institutional Review Board (IRB) interactions;
• Helping with the integration of EET Biobank’s informatics system with Theradex and Medidata RAVE;
• Serving on the EET Biobanking Working Group to harmonize the operation of the Biobank;
• Participating in the EET Biobanking Working Group (bi-weekly conference calls and meetings) to discuss issues such as biobanking goals, needs, and progress;
• Monitoring progress and performance of the key components of the EET Biobank Program;
• Guiding interactions between the Biobank and the NCI Clinical Trial Management System (CTMS); and
• Evaluating the performance of the EET Biobank based on handling specimens and specimen distribution to laboratories/investigators.

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 for appropriate collection, review, and distribution of biospecimens collected in association with EET trials.

Areas of Joint Responsibility include:

The NCI will organize a panel, referred to as EET Biobanking Working Group, that will include representatives from the involved organizations. This Working Group and will discuss and coordinate the biobanking activities for ETCTN and other NCI early and experimental clinical trials.

Specifically, the Working Group will consist of the EET Biobank PD(s)/PI(s), NCI Cancer Diagnosis Program (CDP) Project Scientist(s), a CTEP/IBD representative, and, as needed, other ad hoc experts/representatives from organizations involved in the EET biobanking such as the Biobank, ETCTN Lead Academic Organizations (LAOs), Cancer Immune Monitoring and Analysis Centers (CIMACs), NCI Specimen Tracking System (managed by Theradex), and NCI Medidata Rave System. Other NCI and non-NCI experts may also be asked to attend EET Working Group meetings/conference calls if their expertise is needed.

The EET Working Group will meet bi-weekly via a conference call be and will be expected to:

• Facilitate and monitor collaboration among the organizations and NCI units involved for harmonized operation of the Biobank;
• Address progress, formulate strategies and priorities, and approaches to optimize biospecimen storage and distribution;
• Work on policies and procedures to be implemented by the EET Biobanking resource, such as best practices and operations, informatics, and other biobanking activities; and
• Address any other issues relevant to EET Biobanking.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special 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 Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

General Programmatic Information
Irina A. Lubensky, MD
National Cancer Institute (NCI)
Telephone: 240-276-5902
Email: lubenskyi@mail.nih.gov

Scientific Program and Grant-related Administrative Information
Hala R. Makhlouf, MD, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-7782
Email: hala.makhlouf@nih.gov

Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: ncirefof@dea.nci.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: Woodwars@mail.nih.gov

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 Part 75.