Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U01 Research Project Cooperative Agreements
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:
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.
Not Applicable
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.
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:
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.
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:
The cooperative centers are:
Additional resources supported by the NCI:
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.
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:
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.
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.
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.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
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.
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.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
An individual designated as 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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
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.
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:
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: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources: In addition to standard items, applicants must describe the following:
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
In addition, the following specific requirements must be addressed:
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: 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:
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:
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:
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:
Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.
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:
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.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this 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.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: 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?
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?
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?
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?
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?
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
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.
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:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the 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.
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.
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:
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:
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:
Non-Voting Members:
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:
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.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (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: [email protected]
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: [email protected]
For issues pertaining specifically to Proteogenomic Translational Research Centers, contact:
Eunkyung An, Ph.D.
National Cancer Institute (NCI)
Telephone: 301-215-0826
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.