Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title
Proteogenomic Translational Research Centers (PTRCs) for Clinical Proteomic Tumor Analysis Consortium (U01 Clinical Trial Not Allowed)
Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type
Reissue of RFA-CA-15-022
Related Notices

  • April 23, 2021 - Pre-Application Webinar for the Clinical Proteomic Tumor Analysis Consortium (CPTAC): RFA-CA-21-023 (U24), RFA-CA-21-024 (U24), and RFA-CA-21-025 (U01). See Notice NOT-CA-21-072.

Funding Opportunity Announcement (FOA) Number
RFA-CA-21-025
Companion Funding Opportunity
RFA-CA-21-023 , U24 Resource-Related Research Project (Cooperative Agreements)
RFA-CA-21-024 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.394, 93.395
Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) supports the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) managed by the Office of Cancer Clinical Proteomics Research (OCCPR). CPTAC leverages recent advancements in cancer proteomics and genomics to better understand the complexity between the proteome and the genome in cancer and accelerate research in these areas by disseminating resources for the scientific community. The program will continue to 1) support an increased understanding of cancer through comprehensive proteogenomic approaches, 2) expand support for the development of novel cancer diagnostics and therapeutics by implementing proteogenomic strategies to understand drug response and development of resistance in the context of a clinical trial, and 3) accelerate its translation through public resources (such as data, assays, images and reagents) that catalyze hypothesis-driven science.

This FOA solicits applications for multidisciplinary Proteogenomic Translational Research Centers (PTRCs). PTRCs are intended to function as an interactive group focused on applying standardized state-of-the-art proteomic and genomic approaches to understand tumor biology in clinically relevant research projects related to treatment response. Projects should focus on the proteogenomic aspects of understanding drug response and resistance by generating and testing hypothesis using preclinical cancer models and/or human cancer samples, followed by validation using human biospecimens from clinical trials. Proposed projects are expected to be conducted in collaboration with clinical researchers, including molecular oncologists. It is envisioned that these projects will facilitate a rational approach to target cancer-related pathways and improve outcomes for patients with cancer.

PTRCs will interact with additional CPTAC Centers that include:

  • Proteogenomic Data Analysis Centers (PGDACs, to be supported by RFA-CA-21-024; U24) that will conduct integrative analyses of data across the entire proteomes and genomes of human tumors to elucidate how distinct changes at the proteome level are related to abnormalities in cancer genomes and/or changes at the functional level; and
  • Proteome Characterization Centers (PCCs, to be supported by RFA-CA-21-023; U24) that will use various standardized proteomic analysis technologies for the systematic and comprehensive proteome-wide characterization of defined sets of genomically characterized samples. These samples (human biospecimens and preclinical models) will be provided by the NCI.

Key Dates

Posted Date
April 5, 2021
Open Date (Earliest Submission Date)
June 30, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date.

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
July 30, 2021 Not Applicable Not Applicable November 2021 January 2022 April 2022

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this FOA.

Expiration Date
July 31, 2021
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in 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 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.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA) supports the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) managed by the Office of Cancer Clinical Proteomics Research (OCCPR). This reissuance of the CPTAC program seeks to expand the current achievements in clinical cancer proteogenomic discoveries and infrastructure to accelerate molecularly oriented cancer research toward basic discovery and clinical impact. The program will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes. The potential of proteomic and proteo-genomic approaches will also be explored in translational research focused on clinically relevant questions, such as the ability to predict which treatment options are most effective for a patient's tumor.

This FOA solicits applications for multidisciplinary Proteogenomic Translational Research Centers (PTRCs). PTRCs are intended to function as an interactive group focused on applying standardized state-of-the-art proteomic and genomic approaches to understand tumor biology in clinically relevant research projects related to specific treatment(s). The projects should focus on the proteogenomic aspects in understanding drug responses and resistance to therapies in a clinical context. The proposed projects are expected to be conducted in collaboration with clinical researchers and acquire human biospecimens from NCI-supported clinical trials for the Clinical Research Arm. Other human biospecimens from non-NCI-supported clinical trials may be used in an auxiliary role. The Preclinical Research Arm should use relevant preclinical models of cancer or human cancer samples with clinical outcomes to address the proposed clinical question. Proposed preclinical projects are expected to integrate comprehensive proteomics data with genomics data. It is envisioned that these projects will facilitate a rational approach to target cancer related pathways and improve outcomes for patients with cancer. In addition to preclinical research and clinical research, PTRCs are expected to interact with Division of Cancer Treatment & Diagnosis (DCTD) to develop OCCPR/DCTD collaborative projects that address specific needs in clinical trials beyond those proposed by the PTRC. These OCCPR/DCTD collaborative projects will support partnerships within the scientific scope of the parent grant and/or cooperative agreement award(s), and are anticipated to involve clinical trial samples from DCTD-supported Networks/Consortia (such as NCTN, ETCTN, CITN, PBTC, and ABTC) and from NCI-supported clinical trials that occur outside the established Networks/Consortia (such as R01, P01, P30 Cancer Centers, P50 SPOREs). As such, PTRCs will be sought that focus on specific cancer types or treatment approaches to ensure that specialized teams of researchers and physicians are created that work together in defined areas of cancer diagnostics and therapeutics. A Notice of Special Interest (NOSI) is anticipated to be released in Year 1 of the CPTAC PTRC awards to form OCCPR/DCTD collaborative projects. In addition, PTRCs are to incorporate pilot studies that include efforts to advance the identification and quantification of proteins in clinical trial biopsy specimens, especially in small sample size, and/or CPTAC-wide translational studies. These pilot studies and partnerships are expected to accelerate collaboration towards a clearer path for improved patient management.

PTRCs will interact with additional CPTAC Centers that include:

  • Proteogenomic Data Analysis Centers (PGDACs, to be supported by RFA-CA-21-024; U24) that will conduct integrative analyses of data across the entire proteomes and genomes of human tumors to elucidate how distinct changes at the proteome level are related to abnormalities in cancer genomes and/or changes at the functional level; and
  • Proteome Characterization Centers (PCCs, to be supported by RFA-CA-21-023; U24) that will use various standardized proteomic analysis technologies for the systematic and comprehensive proteome-wide characterization of defined sets of genomically characterized samples. These samples (human biospecimens and preclinical models) will be provided by the NCI.

This FOA is open to all qualified applicants regardless of whether they participated in the previous issuance of the program.

This unique combination of coordinating research approaches, sharing of research data, and combining proteomic with genomic analysis, should allow the CPTAC program to produce a more unified understanding of cancer biology with translational potential. In addition, data and resources (assays and antibodies) are to be made publicly available to the research community through CPTAC's Data Warehouse -- Proteomics data in CPTAC’s Data Coordinating Center (DCC) and NCI’s Proteomic Data Commons (PDC), assays in CPTAC’s Assay Portal, antibodies in CPTAC’s Antibody Portal, and coordinated with the Center for Cancer Genomics and the Cancer Imaging Program, genomics data in the Genomic Data Commons (GDC) and medical images in The Cancer Imaging Archive (TCIA) and NCI’s Imaging Data Commons (IDC), and other pertinent portals to maximize utility and public benefit. These open community resources and knowledge are expected to lead to novel translational approaches and, ultimately, to accelerate the development of new cancer diagnostic, prevention, and treatment strategies.

Key Definitions:

The following key terms are used in the FOA as defined below.

  • "Cancer proteomics" refers to the comprehensive characterizations and analyses of proteins and their derivatives translated from a cancer genome using human cancer samples or a preclinical cancer model (such as patient-derived xenografts or organoids). The term "discovery proteomics" refers to the "untargeted and unbiased" identification and quantification of a maximal number of proteins in a biological or clinical sample. The term “targeted proteomics” refers to the quantitative measurements focused on a defined subset of total proteins in a biological or clinical sample.
  • "Cancer proteogenomics" denotes the integration of cancer proteomics and genomics and, specifically, understanding how various distinct changes at the proteome level are related to abnormalities in cancer genomes and/or changes at the functional level (i.e., in gene expression), while protein information helps improve and refine cancer genome annotation. In the context of this FOA, particularly important is the potential of proteogenomic approaches to better explain cancer complexities than genomics or proteomics alone.
  • For the CPTAC program, the term "proteomic data generation" means the identification and quantitation of either proteome-wide data (comprehensive) or specific proteins of interest (targeted) using human cancer samples/preclinical cancer model samples. The term "proteomic/proteogenomic data analysis" refers to the use of bioinformatic approaches and computational tools to analyze the primary data in various ways and in conjunction with other available complementary data, aiming to achieve higher levels of data/pathways/concepts integration. Three levels of data analysis are envisioned below:
  • Level 1 (required under this FOA): Discovery Proteomics Research - Analysis of raw experimental data to generate results on peptide/protein identification and quantitation, post-translational modifications (PTMs) identification, site localization and quantitation using a reference genome; and Targeted Proteomics Research - Analysis of raw experimental data to generate quantitative results on peptide/protein concentrations.
  • Level 2 (required under this FOA): Integration of genome-proteome data at the linear sequence level (DNA, RNA, peptides/proteins with relative quantitation obtained from Discovery Proteomics Research and/or Targeted Proteomics Research using personalized genomic data).
  • Level 3 (required under this FOA): Integration, visualization and analysis of omics data mapped onto networks and pathways obtained from Discovery Proteomics Research and /or Targeted Proteomics Research.
  • Applicants seeking PTRC awards should focus on proteogenomic research projects covering a “Preclinical Research Arm” and Clinical Research Arm of any cancer type with unmet translational needs and/or clinical question(s). Preclinical Research Arm” refers to studies that include (a) comprehensive characterization of proteins and their additional forms (e.g., variants and/or PTMs) along with genomic characterization in a preclinical cancer model or human cancer samples with clinical outcome; (b) development and application of quantitative proteomics/proteogenomics approach to selected, cancer-relevant protein targets identified and prioritized using human cancer samples with clinical outcome. (see [a] above). “Preclinical cancer model” refers to a model that mimics a human cancer condition such as patient-derived xenografts, organoids, and models must be well defined and have corresponding genomic characterization which meets TCGA or equivalent platform and data quality standards. “Human cancer sample” refers to archived biopsy or surgical tissue from cancer patients with clinical data including clinical outcome. Clinical Research Arm refers primarily to the application of quantitative proteomics/proteogenomics approaches to selected, cancer-relevant protein targets (identified through Preclinical Research Arm or preliminary data submitted at the time of the application) in individual patient's tumors from clinical trials using analytically validated targeted proteomic technologies and platforms.

Background

Despite significant progress in understanding cancer at the molecular level, the complexity that comprises this disease remains a daunting barrier to developing interventions that are needed to diagnose, treat, and prevent cancer in the era of precision medicine. Vital to the progress in these areas are the discovery and understanding of cancer-specific aberrations at various molecular and cellular levels. Although proteins reflecting the genomic changes in cancer have the potential to become clinically meaningful molecular markers, their discovery and confirmation for clinical use have proven to be extremely challenging. In the past decade, cancer researchers have made significant progress in identifying a new molecular taxonomy of cancer through the use of genomics. This FOA aims to leverage the investments in cancer genomics by building on the achievements in cancer proteomics in order to accelerate molecularly oriented cancer research toward discovery and translational research, and clinical impact.

The CPTAC program (RFA-CA-07-012) was launched in 2006 as a part of the Clinical Proteomic Technologies for Cancer initiative at the NCI. The purpose of CPTAC was to develop standardized proteomic workflows to ensure analytical rigor and reproducibility of proteomic measurements. Highlights include the standardization of mass spectrometry (MS) methodologies for comprehensive proteomics (discovery proteomics), standardization of MS methodologies for targeted proteomics (such as multiple reaction monitoring [MRM]), adoption of a MRM assay for thyroglobulin by clinical reference laboratories, development of an open-source computational tool (Skyline) for designing assays (such as MRM) that is supported by major MS instrument vendors, the development of mock 510(k) device clearance documents for regulatory approval of fit-for-purpose targeted proteomic assays in collaboration with the Food and Drug Administration (FDA) and the American Association for Clinical Chemistry (AACC), and the development of open data sharing policies in proteomics that are supported by peer-reviewed journals.

The second iteration of CPTAC began in 2011 (RFA-CA-10-016) and applied these new standardized and harmonized proteomic workflows to genomically characterized tumors (such as those from The Cancer Genome Atlas (TCGA) and others). The goals were to comprehensively characterize the relationships between proteins derived from altered genes and related biological processes to determine if the additional layer of protein biology would further enhance the molecular understanding of cancer in ways not possible through genomics alone. The major insights gained from these studies were that genomic changes often do not result in predictable effects at the protein level, and that post-translational modifications (PTMs) such as protein phosphorylation provide critical data on functional regulations that genomics alone does not resolve. Thus, integrating comprehensive proteomic characterization with comprehensive genomic characterization can provide more information and insight into cancer development and growth. All data and analytical tools were made broadly available to the research community through public databases (CPTAC's Research Resources: Data Portal, https://proteomics.cancer.gov/data-portal; Assay Portal, https://assays.cancer.gov; Antibody Portal, https://antibodies.cancer.gov), in order to democratize proteomics science.

With the success of the prior issuance on proteomic measurements adding an additional dimension to tumor biology, in 2016 NCI expanded CPTAC’s infrastructure to include prospective tissue collection, genomic and proteomic characterization and analysis (global and phospho proteomics), and resource dissemination. The overarching goals of the third iteration were (i) to increase our understanding of cancer by comprehensively characterizing tumors (proteomically and genomically), (ii) to continue to produce public resources (data, assays, images, reagents) that catalyze hypothesis-driven science, and (iii) to support clinical research projects [using both sets of omics] that address mechanisms of treatment response, resistance, or toxicity. To achieve these goals, CPTAC evolved into two united and coordinated sub-programs: The Tumor Characterization Program and the Translational Research Program, whose activities are performed by Proteome Characterization Centers (PCCs, supported by RFA-CA-15-021), Proteogenomic Data Analysis Centers (PGDACs, supported by RFA-CA-15-023) and Proteogenomic Translational Research Centers (PTRCs, supported by RFA-CA-15-022). Such an approach to precision oncology has been highly successful in proving the scientific benefits of integrating proteomic analysis with genomics to produce a more unified understanding of cancer, while creating open community resources across several collaborating entities that are widely used by the global cancer community.

Overall CPTAC Structure and Functions

CPTAC has two united and coordinated sub-programs, whose activities are carried out through three types of cooperative centers. The united and coordinated sub-programs are:

  • Tumor Characterization Program. Its goal is to apply deep comprehensive proteogenomic characterization to new cancer types (tumors and normal adjacent tissues) and preclinical models using standardized protocols, when possible, optimized for proteomic and genomic analyses, and to publicly release all available corresponding data (DNA, RNA, protein, and medical images), assays and reagents. Proteome Characterization Centers (PCCs) and Proteogenomic Data Analysis Centers (PGDACs) are integral partners in the tumor characterization program. See below for roles of each center. Note: metastatic and recurring cancers as well as human cancer samples with patient outcome will also be explored.
  • Translational Research Program. Its goal is to support clinically relevant research projects in collaboration with clinical researchers and the use of human biospecimens from clinical trials to facilitate a rational approach to target cancer related pathways and improve outcomes for patients with cancer. Proteogenomic Translational Research Centers (PTRCs) and Proteogenomic Data Analysis Centers (PGDACs) are integral partners in the translational research program. See below for roles of each center.

The cooperative centers are:

  • Proteome Characterization Centers (PCCs; RFA-CA-21-023, U24). To improve the molecular understanding of cancer, PCC awardees will comprehensively characterize the proteomic composition of human biospecimens and preclinical models (to be provided by the NCI). PCC teams will provide experimental raw data and metadata to the Data Coordinating Center (see below), and coordinate data analysis activities with PGDACs.
  • Proteogenomic Translational Research Centers (PTRCs, covered by this FOA). To complement the comprehensive approaches of the PCCs, PTRC awardees will address clinical questions of drug response/toxicity prediction and resistance. PTRCs will include well-conceived translational and/or clinical questions, access to appropriate clinical trial biospecimens (tumors), state-of-the-art proteomic capabilities, and a proteogenomic-based research approach. PTRCs will provide experimental raw data, metadata and preliminary analysis results to the Data Coordinating Center, and coordinate data analysis activities with PGDACs.
  • Proteogenomic Data Analysis Centers (PGDACs; RFA-CA-21-024, U24). In collaboration with the PCCs and the PTRCs, PGDAC awards will support innovative bioinformatics development and application to integrate data analyses across the entire proteome and genome, and in conjunction with any complementary data to achieve higher levels of data/pathway/concepts integration. PGDACs are to assist researchers (PCCs, and PTRCs accordingly) to integrate, visualize and analyze the data at linear sequence, network and pathway level, including PTMs of proteins and protein-protein interactions.

Additional resources supported by the NCI:

  • NCI-supported Biospecimen Resources (Note: only PCC awardees will receive NCI-collected specimens):
  • Tissue Source Sites (TSS), which collect human biospecimens and clinical data.
  • Biospecimen Core Resource (BCR) that serves as a centralized laboratory(ies) that receives, processes, qualifies, and distributes treatment-naïve tumor and matched normal control human biospecimens to the PCCs. In addition, the BCR may also distribute other tissue types, such as retrospective samples. The BCR serves as the interface between the CPTAC program and the TSSs collecting, ensuring and verifying that CPTAC human subjects protections and guidelines are adhered to and that all regulations are followed at each TSS, including use of language consistent with the CPTAC informed consent documents.
  • Genomic Characterization Center (GCC) that will genomically characterize the same biospecimens provided by CPTAC to PCCs for proteomic characterization.
  • Clinical Data Resource (CDR) that will receive, qualify, store, and distribute clinical data.
  • Data Coordinating Center (DCC): All CPTAC awardees will use DCC as the repository for their data, protocols, tools, etc. DCC serves as the hub and central repository of all data, and facilitates the transfer of data between the Centers. The DCC will also implement the CPTAC common data analysis pipeline, consisting of quality control metrics applied to proteomic data and peptide/protein identification and quantification for proteomic data.
  • CPTAC Research Resources. The CPTAC program currently has several dedicated public resources for disseminating its research findings. Applicants are encouraged to use the resources within these portals, as appropriate. These include:
  • Data Portals
    • Proteomics Data:
      • CPTAC Data Portal (https://proteomics.cancer.gov/data-portal), which serves as a centralized repository for the dissemination of proteomic data collected by the CPTAC program to be used among the Centers.
      • Proteomic Data Commons (https://pdc.cancer.gov), which serves as a centralized repository for the dissemination of proteomic data collected by the CPTAC program to be shared with the public.
    • Genomic Data:
      • Genomic Data Commons (https://portal.gdc.cancer.gov), which serves as a centralized repository for the dissemination of genomic data collected by the CPTAC program to be used by the Centers and shared with the public.
    • Imaging Data:
  • Antibody Portal (https://antibodies.cancer.gov), which serves as a community resource of well characterized fit for purpose renewable antibodies (monoclonal) with all associated SOPs and characterization data made publicly available to the research community.

Research Objectives and Main Requirements for this FOA

The overarching research objective for PTRCs is to apply proteogenomics to better understand drug response and resistance in pre-clinical research models and/or human cancer samples to generate and test hypothesis, followed by validation using human biospecimens from clinical trials.

To be responsive, applications must cover BOTH preclinical studies (using cancer model systems or human cancer samples with clinical outcome) and studies with clinical trial biospecimens. Accordingly, each PTRC should focus on a Preclinical Research Arm and a Clinical Research Arm.

  • Preclinical Research Arm includes (1) comprehensive characterizations of proteins and their additional forms (e.g., variants and/or PTMs) along with genomic characterization in a preclinical cancer model or human cancer samples with clinical outcome to generate hypothesis; and (2) quantitative proteomics/proteogenomics approaches to selected, cancer-relevant protein targets identified and prioritized from the hypothesis. These studies are to use analytically validated discovery and targeted proteomic technologies and platforms that meet the criteria described in Section IV.2. These types of molecular characterizations should be conducted in a high-throughput manner and be deployable at the start of the project. If applicant(s) believes that they have satisfied the requirements of the Preclinical Research Arm, then this application should include research findings that support the applicant (if awarded) to start with the Clinical Research Arm as described in Section IV.2.
  • Clinical Research Arm focus is the application of quantitative proteomics/proteogenomics approaches to cancer-relevant protein targets (identified through Preclinical Research Arm or preliminary data submitted at the time of the application) in individual patient's tumors from clinical trials using analytically validated proteomic technologies and platforms, preferably in a targeted manner, that meet the criteria described in Section IV.2. These specimens must have well-annotated clinical data and appropriate genomic characterization. These types of targeted measurements should be conducted in a high-throughput manner using a detailed analytical method appropriate for the clinical question and clinical trial requirements. If applicant(s) believes that they have satisfied the requirements of the Preclinical Research Arm to start with the Clinical Research Arm as described in Section IV.2, the PTRC awardees should be capable to develop the assay in timely manner to deploy the measurement at the start of the project.

Note: All preclinical cancer model and human cancer samples for Preclinical Research Arm and Clinical Research Arm are to be provided by each applicant.

Preclinical cancer models and/or Human cancer samples with clinical outcome. PTRCs are expected to comprehensively characterize preclinical cancer models (such as patient-derived xenografts or organoids) and/or human cancer samples with clinical outcome in the Preclinical Research Arm. Preclinical cancer models must be well defined (i.e, must represent the relevant features of the cancer under study) and well characterized (i.e, models must have corresponding genomic characterization which meets TCGA or equivalent platform and data quality standards [analyses such as: whole exome sequencing; RNA sequencing; genotyping and DNA copy number as appropriate]). Well-justified novel mouse model systems of human cancers, e.g., for the high-risk, poor prognosis cancer subtypes generated through rapid, non-traditional approaches, may also be considered. Established cancer cell lines may be proposed only if there is sufficient information documenting that these cell lines maintain phenotypic attributes of a given cancer and their signature of molecular abnormalities (at the genetic and other levels) matches respective cancer signatures established for biospecimens from patients. In addition, in the context of this FOA, human cancer samples with clinical outcome may be used in lieu of preclinical cancer models, or in conjunction. These specimens must be a homogeneous cohort in terms of cancer types, treatment, cancer stage but with different clinical outcome (such as progression-free survival and overall survival) to correlate molecular biology of each samples to the clinical outcome.

Clinical trial biospecimens. In the context of this FOA, clinical trial biospecimens refer to individual patient's tumors to be analyzed in the Clinical Research Arm. These specimens must be accompanied with detailed medical and genomics data as described above in Preclinical cancer models and/or Human cancer samples with clinical outcome. At the time of application submission, research projects must have access to NCI-supported clinical trials (written support) to characterize such specimens. Samples can be retrospective from a completed or open (ongoing) trial, prospective from an open trial, or a combination of retrospective with prospective samples (see Section IV. Research Strategy: Sub-section C). Wherever feasible, prospective samples should be collected using proteomics- SOPs (e.g., CPTAC's collection protocols, available upon request) in order to minimize pre-analytical variables such as ischemia. Other types of human biospecimens from non-NCI-supported clinical trials may be used in an auxiliary role.

Main Capabilities. Each PTRC applicant must have appropriate capabilities described below:

  • Scientific capabilities, infrastructure, instrumentation, quality assurance processes, etc., to conduct all the required proteomic/proteogenomic analyses as well as statistical analysis must be in place from the start of the project period;
  • Applicants are expected to have extensive expertise in the standardization of proposed proteomic platforms for both discovery and targeted proteomics approaches, including:
    • Ability to ensure rigor and reproducibility in all types of analyses;
    • Ability to use a comprehensive proteogenomics-based approach to prioritize proteins/peptides for targeted assay development for validation in additional samples;
    • Expertise in computational proteomic and proteogenomic analysis methods for Levels 1-3;
    • Ability to perform complex bioinformatic analyses and interpretation of omics data in conjunction with clinical data;
  • Operate as an interactive group that leverages the data and knowledge from other CPTAC Centers. Use of information from comprehensive characterization datasets such as The Cancer Genome Atlas (TCGA; https://cancergenome.nih.gov) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC; https://proteomics.cancer.gov) are highly encouraged; and
  • Applicants are expected to access and obtain samples which would be used in the proposed research (Preclinical Research Arm and Clinical Research Arm) that were described in Part 2, Section I.

Effort Coordination

Each PTRC must have appropriate logistical support for the expected administrative, communication, and coordination needs.

Coordination with PGDACs. Bioinformatics teams in the PTRCs are required to conduct proteogenomic data analyses and contribute to the overall interpretation of the results. It is required that the characterization data produced by the PTRCs be shared with the PGDACs. Since levels 2-3 analysis are also to be performed by PGDACs with possible different computational omics, joint analyses are to be coordinated between PTRC and PGDAC. Therefore, PTRCs will provide all data and analysis results to the CPTAC DCC where quality control and assurance of the data will be performed prior to distributing the data to the PGDACs for integrative analyses, target prioritization, and releasing the data to the public as appropriate (see Section IV).

Governance of the NCI Clinical Proteomic Tumor Analysis Consortium

The CPTAC program will be governed by a CPTAC Steering Committee (SC). The SC will oversee and coordinate the activities of all PCCs, PTRCs, and PGDACs. Details on the composition and functions of the SC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, “Areas of Joint Responsibility.”

Evaluation of the Program

PTRCs will be required to participate in an external evaluation process of the CPTAC program coordinated by NCI Program Staff. The purpose of the evaluation process is to monitor and assess the performance of the PTRCs in achieving the goals of this FOA. Criteria for the evaluation part will be developed by NCI Program Staff in partnership with the CPTAC External Scientific Evaluation Panel (ESEP) (as described in Section VI).

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

Section II. Award Information

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 scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NCI intends to commit $4,600,000 in FY 2022 to fund 4 awards.

Future year amounts are anticipated to be at the same levels but will ultimately depend on annual appropriations.

Award Budget

Application budgets for each Center may not exceed $750,000 in direct costs per year and need to reflect the actual needs of the proposed project.

Award Project Period

Applicants may request up to 5 years of support.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

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)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

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 allowed. 

Required Registrations

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.
  • 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.

Eligible Individuals (Program Director/Principal Investigator)

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 a PD/PI on a PGDAC application in response to RFA-CA-21-024 (U24), cannot be designated as a PD/PI under this FOA. However, these individuals can serve as key personnel within a PTRC application.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

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)

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in 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.

Letter of Intent

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:

Henry Rodriguez, M.S., Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-781-3370
Email: rodriguezh@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

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.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

Facilities and Other Resources: In addition to standard items, applicants must describe the following:

  • The specialized or unique PTRC exclusive facilities, core resources, and services that each team member will provide towards achieving the objectives of the proposed studies. List PTRC exclusive proteomic platforms/technologies/tools, access to instruments necessary to accomplish required throughput, capabilities of institutional information technology systems in terms of handling massive flows of data that are to be expected, etc. If resources listed are shared (i.e., not exclusive to the proposed PTRC, such as instruments, institutional information technology systems, shared resources cores, etc.), specify and document arrangements through which priority and sufficient access will be granted for the purposes of the project.
  • The expert technical or advisory personnel and information of other components of the supporting infrastructure pertinent to the application.
  • Any relevant ongoing institutional, and/or private sector support and resources that augment or complement resources for which funding from this FOA is sought.
  • Available laboratory information management system, proteomics analysis tools, data storage, security, archiving, and retrieval systems. Applicants must also describe standardized formats for data reporting and the validation process for data prior to submission to the CPTAC DCC for data evaluation and data mining across the CPTAC program, and public access.

Other Attachments: Upload the items indicated as a single attachment using file name "SOPs" for instruments and data analyses QA/QC with appropriate performance metrics (this file name will become a bookmark in the application). If SOPs to be used have been previously developed by the CPTAC, list those SOPs but do not attach their full text. Upload software documentation for research software expected to be used. Upload the items indicated as a single attachment using file name "Software Documentation" (this file name will become bookmark in the application). If software to be used has been previously developed by CPTAC, list but do not attach its full text.

SF424(R&R) Senior/Key Person Profile

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

In addition, the following specific requirements must be addressed:

  • Each team must have expertise in proteomics and clinical research. A PTRC application must designate at least two PDs/PIs (a clinician familiar with unmet clinical needs, clinical trials, with access to trial samples; and a proteomics researcher).
  • Each team should also have expertise in other disciplines, such as genomics, cancer biology, molecular oncology, clinical oncology, biostatistics, experimental design, bioinformatics, and clinical laboratory science/clinical chemistry.
  • Given the need for integration of multidisciplinary efforts in each PTRC, the scientific leadership and other senior members of the team are expected to have considerable experience in collaborative, multidisciplinary research and development.

R&RBudget

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

Additional guidance applies, as specified below:

Total Costs for Samples Characterization and Specimens. Applicants should budget for genomic characterization, discovery and targeted proteomic characterization to be developed and applied in Preclinical Research Arm and/or Clinical Research Arms (e.g., total cost of a quantitative proteomics/proteogenomics approaches per sample, number of targets per sample if performed in multiplexed fashion). In addition, the budget for tumor procurement from clinical trials (excluding the costs for clinical trials) should be included whenever applicable.

Restricted Funds for Pilot Studies and OCCPR/DCTD collaborative projects. The budget requested must include $100,000 in direct costs per year to be allocated by each PTRC specifically for pilot studies and OCCPR/DCTD collaborative projects. The release of these restricted funds will be approved for pilot studies by the CPTAC Steering Committee and/or through NOSI for the OCCPR/DCTD collaborative projects.

Site visits. Because of the complexity of the PTRCs, NIH/NCI Program Staff members will conduct annual administrative site visits. PTRC applicants should be prepared for annual visits and should budget appropriately (including travel for collaborators and other necessary costs).

Costs of participating in CPTAC meetings. Applicants should budget for the PDs/PIs and/or alternative designated representatives (in aggregate, up to 4 members of each PTRC) to attend semi-annual face-to-face CPTAC investigator meetings.

Note: Capital equipment requests (for equipment over $5,000) are not allowed under this FOA.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Specific Aims: Describe the specific aims for the PTRC to address clinical questions of drug response/toxicity prediction and resistance, including major milestones. In addition to a brief description of the specific aims and approach(es) to be employed, applicants must outline the scope of the proposed research and its relevance to a specific unmet clinical need in order to improve the outcome of a treatment.

NOTE: At least one of the Specific Aims should describe the Preclinical Research Arm with preclinical cancer models and/or human cancer samples with clinical outcome and at least one of the Specific Aims should describe the Clinical Research Arm using human tumor biospecimens from an NCI-supported clinical trial. Other types of human biospecimens from non-NCI-supported clinical trials may be used in an auxiliary role.

Research Strategy: Instead of the standard sub-sections defined in the Application Guide, Research Strategy must consist of sub-sections as defined below.

Sub-Section A. Significance and Innovation

Present the overall vision for the proposed PTRC including the following items:

  • Outline the overarching aims for the PTRC to address protein identification, prioritization and target confirmation in both Preclinical Research Arm and Clinical Research Arm.
  • Describe the rationale of how the proposed quantitative proteomics/proteogenomics-based research approach will address clinical questions of drug response and resistance.
  • Describe the integration of the two PTRC Research Arms and how such integration will enhance the understanding of proteogenomic aspects in drug responses and resistance.
  • Group Capabilities.
  • Provide details on collective aspects of the team expertise and capabilities (that are not covered and cannot be covered by individual biosketches). For example, outline how each member of the Team (including proteomics, clinical trials, translational activities, genomics, cancer biology, clinical oncology, biostatistics, experimental design, bioinformatics, and clinical laboratory science/clinical chemistry experts) contributes to achieving the objectives of the proposed studies. Highlight how the diverse expertise of the Team members may: stimulate innovation in research proposed, the ability to anticipate new directions, and the flexibility to redirect research when warranted. Provide evidence of previous successful collaborations among members of the applicant team if applicable.
  • Without repeating information from individual biosketches, summarize the group’s collective proficiencies and capabilities in using the proposed proteomic technologies, understanding the strengths and weaknesses of the measurements (including quality control and assurance), and understanding how the characteristics and shortcomings of the collected data affect the interpretation of the results.
  • Without repeating information from individual biosketches, summarize the group’s collective proficiencies, ability and experience involved in clinical trials research. Describe relevant basic and clinical research activities related to drug response or resistance. Applicants representing current awardees in NCI's programs such as NCTN or ETCTN should narrate their role and accomplishments under the current or past award(s). Demonstrate the ability of the investigators (documented by past performance) to collect sufficient number of biospecimens for clinical trials, if applicable.
  • Applicants should briefly describe existing and planned partnerships with other organizations or state “Not Applicable” if there are no such collaborations. The role of such partners should be clearly delineated
  • Innovation. Pilot studies are to enhance efforts to address clinical questions and to identify and quantify proteins in specimens, especially limited input material. No specific pilot studies are to be described in the application.
  • Preliminary Data. Preliminary data relevant to the PTRC research objectives, proposed methods and/or technologies and platforms should be included in this sub-section. These data should demonstrate applicants' proposed research in meeting the specific aims and capability to meet the scientific requirements stated. Preliminary data included should also serve as evidence for the quality of the data that may be anticipated from the proposed technology platforms utilized by the applicants. For example, if proteogenomics-based research has been completed by the applicants prior to applying, a detailed description of the results and scientific justification for selected targets to be tested must be provided. In some cases, additional discovery and targeted proteomics research may be required to help refine the protein targets selected. Similarly, if quantitative proteomics/proteogenomics approaches are being or have been developed at the time of this application, describe the current state of development and use (such as the analytical rigor and the function of the assay in a complex sample matrix, including the current reagents and technologies and types of specimens that the assay will use on (e.g., fresh or FFPE tissue), and sample requirements). If study(ies) that satisfy the Preclinical Research Arm were already performed and the hypothesis is already tested using human cancer samples, then the applicant should provide the statistical analysis plan that addresses the clinical question(s) and supports moving directly to the Clinical Research Arm. The statistical analysis plan should include a detailed information including hypothesis/study objective, method, sample size, analysis, and summary of the performed study(ies). For these quantitative proteomics/proteogenomics approaches, the applicant should describe the method including target analytes, technical platform, analytical performance of the assay, quantitative scoring system, sample requirement, etc.

Sub-Section B. Approach for Preclinical Research Arm

Studies proposed under Approaches for Preclinical Research Arm are expected to build foundation for and drive the design of studies with clinical trial biospecimens. As appropriate, these studies using preclinical cancer models should examine responses to therapeutic agents of interest at the proteomic and genomic levels by comparing samples before and after exposure to such agents, and studies using human cancer samples should examine responses to therapeutic agents of interest at the proteomic and genomic levels by comparing molecular profiling of patient’s tumors and their clinical outcome. Applicants should plan to accomplish respective preclinical goals early enough (within first 2-3 years at time of award) to allow for sufficient time for the conduct of the clinical studies based on those preclinical findings.

All studies proposed for the Preclinical Research Arm must adhere to all the requirements listed below.

a) Proteomic technology(ies)/platform(s). A technology/platform must be reproducible, quantitative and sensitive for both comprehensive proteomic characterizations (discovery) and targeted proteomic characterization. For the purpose of this FOA, a comprehensive (untargeted and unbiased) technology/platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed and validated in at least one other laboratory; 2) is capable of generating reproducible results within and across laboratories using standards and metrics in high-throughput, large-scale proteomic research studies; and 3) has been previously published in a peer-reviewed journal. Similarly, a technology/platform for targeted proteomic characterization is expected to be a reproducible, quantitative and multiplexed targeted methodology that has been analytically validated. A technology/platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed in at least one other laboratory (preferably published in a peer-reviewed journal); 2) involves high-throughput targeted assays capable of sampling the depth of proteomes studied and spanning a wide dynamic range, specifically being able to measure protein/peptide concentrations in the range of low femtomole/microgram to low femtomole/milligram (proteins); 3) demonstrates the analytical rigor of quantitative data obtained from within and across laboratories using standards and metrics. For example, Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), one of the quantitative technology platforms standardized by the CPTAC program, will be used as a reference point for criteria such as throughput, sensitivity, specificity, multiplexing capability, reproducibility, and portability (https://assays.cancer.gov). Other technologies/platforms are highly encouraged provided that they meet the specified analytical requirements. A minimum of a Tier 2 analytical characterization for mass spectrometry (https://proteomics.cancer.gov/assay-portal/about/assay-characterization-guidance-documents) or an equivalent of such criteria for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place) is expected. Describe the plan for the proposed proteogenomic characterizations of preclinical cancer models or human cancer samples for the therapeutic agents of interest to be studied, including any analysis of proteins, PTMs and genetic aberrations. At a minimum, include experimental study design, throughput and enumeration of characterization capacity per year, efficiency, sensitivity, number of proteins and/or PTMs identified and quantitated per characterization/analysis, error rate of identification, repeatability and reproducibility of targeted assays, and expertise (personnel) involved in the process. The plan must address the amount of sample materials needed to perform the proposed characterizations (e.g., wet tissue weight of patient-derived xenografts, total weight of human tumor tissue, or total number of cells for cell culture).

b) Genomic characterization (data). Describe a plan to obtain or access genomic data on preclinical cancer models or human cancer samples to be analyzed proteomically, or to perform certain types of genomic characterizations on such samples, adherent to TCGA or similar platform and data standards.

c) Analytical capacity. Describe the capability to meet throughput requirements, including identifying maximal capability and potential for increasing throughput during Years 2–5. It is expected that each PTRC should identify and quantify a sufficiently large number of unique proteins as appropriate for the sample under study. PTRCs should describe a minimum number of unique proteins identified and quantified for the technology/platform proposed, database and algorithm used, control process for typical error rates for the proposed technology platforms. Applicants need to define timelines and milestones specific to the technology platforms and describe the acceleration of sample throughput rates throughout the course of the project. Automated solutions for increased analysis throughput are highly encouraged. All capital equipment instruments must be operational and available at the proposed start of the project period.

d) Process for assay development. Describe the process for targeted assay development. Attributes to be included are throughput (assay development capacity and application per year, lead time needed), quality control, reagents needed, timeline, and expertise (personnel) involved in the process.

e) Quality Assurance/Quality Control criteria for technology(ies)/platform(s). Describe a strategy to monitor and ensure the quality of instrument performance and data generated. Include plans to ensure implementation of metrics for instrument quality control and SOPs for sample storage/processing/analyses. Where applicable, use metrics and SOPs previously developed by the CPTAC. Examples of such metrics that provide evidence of adequate instrument performance may include (but are not limited to): reference materials, limits of detection, limits of quantitation, total number of unique protein identification and quantitation, and signal-to-noise ratio.

f) Data analysis. Three levels of proteomic data analysis were developed in the CPTAC program (see Section I). In the context of this FOA, PTRCs are required to perform Level 1-3 analysis for understanding the molecular mechanisms of drug response and resistance that lead to relevant protein candidate selection and prioritization. Since Levels 2-3 analyses are also to be performed by the PGDACs (RFA-CA-21-024) for the entire CPTAC program possibly with different computation -omics tools, joint analysis activities are to be coordinated between PTRCs and PGDACs.

Applicants must describe how data will be analyzed at each level, including: descriptions of data processing, identification algorithms and quantitation strategies, databases used, error rate analysis for protein/peptide identification, PTM site localization and quantitation, mutational analysis, and computational tools for proteogenomic integration, and network/pathway analysis. Applicants are to clearly describe strategies for selecting targets for targeted proteomics research studies. If mass spectrometry is used for comprehensive characterizations of materials, applicant(s) is to clearly describe computational methodologies and quality control procedures for protein identification and quantitation with a desirable protein-level identification error rate at <10-15%. An equivalent of metrics should be used for Level 1-2 analysis if other platforms are proposed. In addition, PTRCs will submit their raw data, metadata and analysis results to the DCC for additional analysis by the PGDACs.

Sub-Section C. Approach for Clinical Research Arm

If study(ies) that satisfy the Preclinical Research Arm were already performed and the hypothesis is tested using human cancer samples, then the applicant should provide the preliminary findings (Sub-Section A) that verified the clinical question and support moving directly to the Clinical Research Arm. Clinical studies using human tumor biospecimens and proposed under Approaches for Clinical Research Arm should focus primarily on quantitative proteomic/proteogenomics approaches (defined in Preclinical Research Arm) for specific proteins implicated in the responses to therapeutic agents of interest. If such data are unavailable or limited, clinical studies should be preceded by appropriate characterizations under Preclinical Research Arm. Depending on the availability of the biospecimens, the types of studies that may be proposed include:

  • Correlative studies linking proteogenomic patterns in specimens collected before treatment(s) by the therapeutic agents of interest with therapeutic outcomes after such treatment(s);
  • Comparative proteogenomic analyses using specimens collected before AND after treatment by the therapeutic agents of interest (e.g., pharmacogenomic determinations to examine the effects of drug treatment on specific protein targets or pathways).

Applicants proposing to start with Clinical Research Arm should provide evidence of secured access to clinical trial samples. See ”Letters of Support” below for details.

All studies proposed for the Clinical Research Arm must address clinical questions and adhere to all the requirements listed below.

a) Proteomic technology(ies)/platform(s). A technology/platform for targeted assays is expected to be a reproducible, quantitative and multiplexed targeted methodology that has been analytically validated. A technology/platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed in at least one other laboratory (preferably published in a peer-reviewed journal); 2) involves high-throughput targeted assays capable of sampling the depth of proteomes studied and spanning a wide dynamic range. Specifically, being able to measure protein/peptide concentrations in the range of low femtomole/microgram to low femtomole/milligram (proteins); 3) demonstrates the analytical rigor of quantitative data obtained from within and across laboratories using standards and metrics. For example, Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), one of the quantitative technology/platforms standardized by the CPTAC program, will be used as a reference point for criteria such as throughput, sensitivity, specificity, multiplexing capability, reproducibility, and portability (https://assays.cancer.gov). Other technologies/platforms are highly encouraged provided that they meet the specified analytical requirements. A minimum of a Tier 2 analytical characterization for mass spectrometry (https://proteomics.cancer.gov/assay-portal/about/assay-characterization-guidance-documents) or an equivalent of such criteria for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place) is expected. Describe the plan for the proposed targeted assays development and testing in patients' tumor samples that have undergone therapeutic agent treatments to be studied, including any analysis of peptides, proteins, PTMs and variants. At a minimum, include experimental study design, throughput and enumeration of assay capacity per year, efficiency, sensitivity, number of proteins and/or PTMs to be measured per analysis, repeatability and reproducibility of the assays, and expertise (personnel) involved in the process. The plan must address the amount of clinical trial materials needed to perform the proposed analysis (wet tissue weight of a patient's tumor). Applicants will be evaluated on their capability and efficiency in using this material, throughput levels, and the capabilities for accurate and precise measurements of targets in such material.

b) Genomic characterization (data). Describe a plan to obtain access to genomic data on preclinical cancer research models to be analyzed proteomically (if available), or to perform certain types of genomic characterizations on such samples, adherent to TCGA or similar platform and data standards.

c) Quality Assurance/Quality Control criteria for proteomic technology(ies)/platform(s). Describe a strategy to monitor and ensure the quality of instrument performance and data generated. Include plans to ensure implementation of metrics for instrument quality control and SOPs for sample storage/processing/analyses. Where applicable, use metrics and SOPs previously developed by the CPTAC. Examples of such metrics that provide evidence of adequate instrument performance may include (but are not limited to): reference materials, limits of detection, limits of quantitation, total number of unique protein identification and quantitation, and signal-to-noise ratio.

d) Data analysis. Describe how raw data from targeted measurements of proteins in clinical trial samples will be analyzed in combination with genomic information from the same sample, including descriptions of data processing, error analysis, and quality control procedures of data analysis. Also describe briefly how proteomics data will be integrated with other types of data (e.g., genomics and clinical outcome data) from the clinical trials.

e) Coordination of multiple clinical trials. Depending on the sample size of clinical trial materials committed to be analyzed at the start of the program and the analytical capacities of a specific PTRC, applicants may gain access to tumor samples from more than one clinical trial relevant to the goals of the PTRCs at different times during the entire project period. If so, describe a plan to coordinate analysis activities for multiple clinical trial materials to maximize the PTRC network's throughput and the benefit of molecular knowledge.

Sub-Section D. Effort Coordination and Improvements of Proteomic Technologies

In this Sub-section, address the following specific elements:

  • Effort Coordination:
    • Timeline for the Specific Aims and milestones for both Research Arms.
    • Expected PTRC needs in terms of administrative support, communications, coordination within the proposed PTRC, interactions with other CPTAC Centers, awardees, Steering Committee, etc., and other similar activities. Explain how these needs will be met, such as designating a Project Manager with whom NCI Program Staff can communicate regarding various details and activities of the study.
  • Improvement of Proteomic Technologies:
    • Enhancing sample throughput capabilities and/or reducing sample quantity input requirement to quantify proteins from clinical specimens.
    • Meaningful improvements of the selected characterization methods/technology platforms in terms of such aspects as: detection sensitivity, quantitation accuracy, resolution, and proteome coverage, and/or reducing unit costs per characterization/analysis.
    • Developing strategies to take advantage of technology changes that may emerge during the project period, including a provision for a complete change in platform utilized, should it benefit the project.
  • Letters of Support: Applicants should provide Letter(s) of Support that identify clinical trials with samples that would fulfill the next step of clinical validation. If Applicant is proposing a Preclinical Research Arm, the Letter(s) should state that the proposed research questions are clinically aligned/clinically relevant to trials being conducted and for which appropriate samples (in quality and quantity) may be available. If applicants propose to start with Clinical Research Arm, they should also provide evidence of secured access to clinical trial samples. For example, if obtaining specimens via NCI Navigator from completed phase 2/3 or phase 3NCTN studies, the applicants should document a CTEP/NCI Core Correlative Science Committee-approved proposal. Use of NCTN specimens not available via Navigator will require documentation of CTEP biospecimen access proposal approval. For other NCI-supported or for non-NCI-supported clinical trials, please describe the required approval process for obtaining clinical specimens and the investigator’s commitment to fulfill these requirements at the start of the program. In addition, Letter(s) must at least specify the following parameters:

    • Expected number of such specimens and amounts that will be available to the PTRC applicants;
    • Timing of the availability (listed by relevant categories, such as tumor type, treatment type, etc.);
    • Specimen nature (including whether pre-treatment, post-treatment, or both);
    • Types of accompanying data (medical, genomic, etc.).

    Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.

  • CPTAC Intellectual Property Policy: Consistent with achieving the goals of this program and maximizing the benefit of all research funded as part of the CPTAC program for the improvement of public health through discoveries of the scientific community, CPTAC Data Sharing and Data Release policies expect a broad freedom-to-operate for all users of CPTAC data (e.g., by rapidly placing all data in the public domain). In addition, computer algorithms produced specifically to analyze CPTAC data, software source code or other resources (reagents) made possible under the auspices of CPTAC are expected to be made broadly available. It is expected that any data producer in the PTRCs will make all information available, without requirement for licensing, for applications such as, but not necessarily limited to, the use of markers in developing assays or targets for therapeutic and diagnostic purposes. All PTRC members and affiliated institutions must acknowledge agreement to the CPTAC Intellectual Property Policy. Investigators and their institutions must expressly acknowledge and agree to abide by this policy.

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.

The following modifications also apply:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
  • Data Sharing Plan should be consistent with accomplishing the goals of the CPTAC program. Specifically
    • Data Sharing Plan should acknowledge that all PTRC awardees will be required to upload all of their data to the CPTAC DCC during the five-year project period, and upon request from NCI Program Staff.
    • The plan should specify how and when data obtained throughout Preclinical Research and Clinical Research Arms, and algorithms produced will be released and shared. The timing and frequency of data sharing are expected to be consistent with achieving the goals of CPTAC (such as submitting all data to the CPTAC DCC and National Center for Biotechnology Information's The database of Genotypes and Phenotypes (dbGaP) within 30-60 days after completion of data generation and Level 1 data analysis, to become publicly available after appropriate Quality Assurance as determined by the CPTAC Steering Committee), and with NIH data sharing guidelines.
    • All PTRC awardees will be expected to adhere to the general proteomic data sharing principles established such as in the Amsterdam Principles for mass spectrometry (https://proteomics.cancer.gov/data-portal/about/data-use-agreement) or an equivalent for other technologies/platforms.
    • Similar to TCGA and other programs, CPTAC data will be subject to a period of embargo (https://proteomics.cancer.gov/data-portal/about/data-use-agreement).
    • Any data linked to clinical trials will be uploaded once the requirements of clinical trial restrictions and clauses such as de-identification of patients are satisfied.
  • Sharing Additional Resources: Consistent with achieving the goals of this program, all resources generated by the PTRCs (e.g., standards, reagents, and SOPs) will promptly become available through a CPTAC Public Resource (CPTAC Data Portal, Assay Portal and Antibody Portal; https://proteomics.cancer.gov), and NCI Proteomic Data Commons (https://pdc.cancer.gov). It is anticipated that other distribution avenues will be made available by the NCI if determined to be necessary. Resource sharing plans would be expected to describe the type(s) of resources that will become available through the proposed center.
Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
PHS Human Subjects and Clinical Trials Information

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.

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

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.

Section V. Application Review Information

1. Criteria

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 particular announcement, note the following:

In determining the merit of applications, reviewers will assess the potential of the applicants' proposed studies to improve clinical outcomes for the drug treatments, as well as the applicants' capabilities and plans in terms of the stated scientific, technological, and organizational requirements. To be viewed as meritorious, the application must be consistent with all of these requirements.

Overall Impact

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).

Scored Review Criteria

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.

Significance

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: How will the proposed research activities significantly advance the overall goals of the PTRCs, that is, understanding molecular mechanisms of drug responses and resistance to therapies in a clinical context? How extensively will the PTRCs, as proposed, be able to introduce appropriate proteogenomics-based research and analytically validated “fit-for-purpose" targeted proteomic assays into oncology clinical trials in a timely and efficient manner? How well does the application address appropriate unmet mechanisms of response or resistance against cancer therapeutic agents in clinical oncology?

Investigator(s)

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 adequate are the quality and breadth of expertise of the PD(s)/PI(s) and the entire team for the conduct of state-of-the-art proteogenomics basic and translational research, various bioinformatics analyses, and informative integration of data from various sources, including clinical data and well-matched to the project proposed? What are the leadership qualities for PDs/PIs on both the proteomic site and clinical oncology site? How well would these investigators work as a coherent research team?

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 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: How well does the preliminary data substantiate each proposed study in the Preclinical and Clinical Research Arms? If studies under Clinical Arm depend on the accomplishment of the Preclinical Arms, how are these plans (and their timing and feasibility) justified? How strong are other elements critical to accomplishing the goals (e.g., documentation of applicants' capabilities, access to biospecimens, etc.)? How appropriate and logical are the proposed plans of integrating Preclinical Research Arm with Clinical Research Arm and how well will they increase the likelihood of successfully identifying and validating protein targets involved in response to cancer therapeutic agents?

How adequate are the findings from the submitted preliminary studies in satisfying the requirements of the Preclinical Research Arm (hypothesis generated and tested using human cancer samples) in order to proceed to Clinical Research Arm? How detailed is the information on hypothesis/study objectives, method (target analytes, technical platform, analytical performance of the assay, quantitative scoring system, sample requirement), sample size, analysis, and summary of the performed study(ies) included in the statistical analysis plan?

How optimal are the proposed technologies/platforms, methodologies, procedures, etc. in terms of the ability to efficiently conduct all the expected types of analyses with the needed throughput, accuracy, sensitivity, and other applicable parameters? How sufficient are efforts to ensure that generated data are, as appropriate: rigorous, comprehensive, quantitative, and/or reproducible?

How well defined are the prioritization/decision strategies for the selection of proteins that are likely to be relevant for clinical sample testing? How adequately do the milestones and timelines match to the goals of the project? How are other project management aspects and coordination of activities across multiple institutions and trials (if applicable) adequate to the activities anticipated?

How well do the research plans demonstrate an appropriate understanding of research opportunities in improving molecular knowledge on drug response prediction and resistance, and of the methodologies available to exploit these opportunities?

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 to this FOA: At what degree will the proposed PTRC be able to participate in inter- and trans-disciplinary team-based research efforts, including the potential for interactions with investigators from other clinical trials, other NCI-supported programs, and NCI staff members?

Additional Review Criteria

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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.

Vertebrate Animals

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.

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

Additional Review Considerations

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

Not Applicable.

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) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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.

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.

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

Applications will be assigned 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. 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.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 recipient'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: Recipient 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.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, 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 laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

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.

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.

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 award recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

  • Participating in an external evaluation process of the CPTAC program coordinated by NCI Program Staff;
  • Participating in various task-oriented working groups together with members from other CPTAC Centers that might be formed, as needed, e.g., as subcommittees of the CPTAC Steering Committee;
  • Overseeing, directing, and coordinating scientific and administrative activities of the PTRC;
  • Defining research goals, determining and/or approving experimental approaches, and setting project milestones and timelines;
  • Overseeing the conduct of research at the PTRC, including such aspects as: experimental activities, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of results for publications;
  • Ensuring the timely sharing of PTRC-generated data across the entire CPTAC program through the CPTAC DCC as appropriate, and upon request from NCI Program Staff;
  • Participating in the activities of the CPTAC Steering Committee as voting members;
  • Accepting and implementing all scientific and policy recommendations approved by the CPTAC Steering Committee to the extent consistent with applicable grant regulations;
  • Committing an effort to the PTRC of at least 2.4 person-months by each PD/PI;
  • Preparing for annual administrative site visits by NCI Program Staff;
  • Providing other information as might be requested by Project Scientist (e.g., on annual Center milestones, goals for throughput, procedures, etc.);
  • Monitoring the completion of established goals and benchmarks within the timeframe and budget proposed;
  • Coordinating and encouraging inter-network collaborations;
  • Participating in the semi-annual PD/PI meeting organized by NCI;
  • Working closely with the NCI Program Officials or Project Scientist (see below) on the coordination and management of CPTAC Program activities. These actions involve (but will not be limited to) participation in annual CPTAC Program investigators' meetings, working groups, and teleconferences with NCI scientific and program staff and other awarded investigators, as needed;
  • Ensuring that proper process management methods are executed for planning, monitoring, and managing the workload over the award period, and are expected to provide update reports to NCI Program Staff upon request;
  • Award recipients 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 DHHS, PHS, and NIH policies.

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

Designated NCI Program Staff members will have substantial programmatic involvement as Project Scientists. Specifically, the NCI Project Scientists will:

  • Serve as voting members of the CPTAC Steering Committee and its subcommittees as appropriate;
  • In collaboration with the PDs/PIs and the CPTAC Steering Committee, ensure the CPTAC program functions as a unified whole to achieve the goals of the program;
  • Coordinate collaborative research efforts that involve multiple PCCs, PGDACs and PTRCs when necessary;
  • Monitor the operations of the CPTAC program and make recommendations on overall project directions and allocations of project funds;
  • Assist in avoiding unwarranted duplications of effort across the CPTAC award recipients;
  • Review the progress of individual CPTAC award recipients and specific activities shared among them;
  • Assist the recipients as a resource in stimulating their broader interaction with other NCI and NIH programs, including non-NIH programs if appropriate, to disseminate results and outcomes from the CPTAC program and effectively leverage existing NIH/NCI resources and infrastructures;
  • Coordinate the supply of specimens and reagents for analyses by the CPTAC program through the CPTAC Research Resources whenever applicable;
  • Co-organize and participate in the semi-annual meeting of CPTAC investigators;
  • Organize and conduct regular meetings to share progress either by teleconference, videoconference, or face to face, as needed among the award recipients;
  • Ensure the availability of data and related resources developed during the course of the CPTAC program to the scientific community at large;
  • Participate in data analyses, interpretations, and co-authorship of CPTAC publications as appropriate and jointly agreed through the CPTAC Steering Committee;
  • Ensure that decisions, recommendations, and policies of the CPTAC Steering Committee are consistent with applicable grant regulations;
  • Provide technical assistance and advice to the recipients as appropriate (e.g., interpretation and reporting of the collected information);
  • Conduct periodic site visits for scientific and organizational discussions with the recipient research teams, observation of field data collection and management techniques, and other resource-related matters;
  • Facilitate interactions/collaborations between the recipients and other NCI-supported programs, investigators, or organizations that may contribute to the CPTAC goals;
  • Serve as a liaison between recipients and NCI staff members and investigators that may provide additional expertise and/or resources to the program;
  • Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

CPTAC Steering Committee. CPTAC Steering Committee will serve as the primary governing body of the CPTAC program. The Committee will be jointly established by all the awarded PDs/PIs of the PCCs, the PGDACs, the PTRCs and the NCI Program Staff members. The CPTAC Steering Committee will provide strategic coordination for the activities of the PTRC network and the CPTAC program overall.

Details on the composition, functions, and responsibilities of CPTAC Steering Committee are following.

Voting members of the CPTAC Steering Committee will include:

  • One representative from each PCC;
  • One representative from each PGDAC;
  • One representative from each PTRC; and
  • One representative from the NCI Office of Cancer Clinical Proteomics Research.

Non-Voting Members:

  • The CPTAC Steering Committee may decide to add non-voting members as needed, e.g., representatives from NCI-supported research resources, scientific experts and/or patient advocates.

It is anticipated that the CPTAC Steering Committee will formulate strategic decisions and policies for consortium-wide activities. The CPTAC award recipients will be required to accept and implement these decisions and policies to the extent consistent with applicable grant regulations. The activities of the CPTAC Steering Committee are expected to include the following:

  • Establishing operational guidelines, quality control procedures, and consistent policies to meet the goals of the CPTAC network and monitoring the implementation of these guidelines and policies;
  • Developing quality assurance goals for all network functions, specimens, technology and data for the CPTAC network;
  • Reviewing progress of the CPTAC Centers on a regular basis;
  • Following-up on action items from the CPTAC Steering Committee in a timely fashion;
  • Prioritizing and recommending pilot studies for execution;
  • Organizing semi-annual meetings of CPTAC investigators;
  • Establishing subcommittees composed of a set number of members of the CPTAC Steering Committee (or their nominees), NIH/NCI Program Staff members and additional scientific experts as deemed necessary and appropriate to accomplish CPTAC goals.

CPTAC External Scientific Evaluation Panel. The CPTAC Steering Committee will help establish a panel of external experts (i.e., individuals with appropriate expertise who are NOT affiliated with any of the CPTAC award recipients). The primary role of the External Scientific Evaluation Panel will be to provide independent assessment of research directions and progress of the CPTAC award recipients. The External Scientific Evaluation Panel will annually evaluate research conducted by the CPTAC members, including the review of the overall program metrics, progress of individual recipients, strategic plans, etc. The panel may also recommend to the Steering Committee new research opportunities to explore, adjustments in priorities, and/or approaches as well as other steps/actions to advance the overall CPTAC goals.

Clinical Trial Review Committee (for this FOA only). This committee consisting of NCI Project Scientists from OCCPR and DCTD in coordination with PTRC PDs/PIs, as well as additional scientific experts as deemed necessary, will review the use of any additional samples from clinical trials proposed to be initiated post award during the course of the entire funding period (see pilot studies, Section IV).

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 recipient. This special dispute resolution procedure does not alter the recipient'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.

3. Reporting

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.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Scientific/Research Contact(s)

For general aspects of the entire Clinical Proteomic Tumor Analysis Consortium, contact:

Henry Rodriguez, M.S., Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-781-3370
Email: rodriguezh@mail.nih.gov

For issues pertaining specifically to Proteogenomic Translational Research Centers, contact:

Eunkyung An, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-215-0826
Email: eunkyung.an@nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

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

Section VIII. Other Information

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.

Authority and Regulations

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.


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