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 for Clinical Proteomic Tumor Analysis Consortium (U01)

Activity Code

U01 Research Projects – Cooperative Agreements

Announcement Type

New

Related Notices
  • December 16, 2015 - Notice of Pre-application Webinar for RFA-CA-15-022. See Notice NOT-CA-16-016.
  • December 9, 2015 - Notice of Changes to Funding Opportunity Announcement RFA-CA-15-022. See Notice NOT-CA-16-004.
  • NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications (November 18, 2015)
  • NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals (November 18, 2015)
  • NOT-OD-16-011 - Implementing Rigor and Transparency in NIH & AHRQ Research Grant Applications (November 18, 2015)
  • November 16, 2015 - Notice of Pre-application Webinar for Clinical Proteomic Tumor Analysis Consortium. See Notice NOT-CA-15-044.
Funding Opportunity Announcement (FOA) Number

RFA-CA-15-022

Companion Funding Opportunity

RFA-CA-15-021, U24 Resource-Related Research Project - Cooperative Agreements

RFA-CA-15-023, U24 Resource-Related Research Project - Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.393, 93.394, 93.396

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) is a part of the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC). This reissuance of the CPTAC program leverages recent advancements in cancer proteomics and genomics and accelerates research in these areas by disseminating research resources for the scientific community. 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 proteogenomic approaches will also be explored in translational research focused on clinically-relevant problems, such as the ability to predict which treatments are likely to be effective against a specific 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 clinically-relevant research projects. 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 use human biospecimens from clinical trials. The projects should also involve the use of relevant preclinical models of cancer. Proposed 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.

PTRCs will interact with additional CPTAC sub-programs that include:

  • Proteogenomic Data Analysis Centers (PGDACs, to be supported by RFA-CA-15-023) that will conduct integrative analyses of data across the entire proteomes and genomes of cancer types of focus 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-15-021) 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, cultured cells, and animal cancer models) will be provided by the NCI.
Key Dates
Posted Date

November 2, 2015

Open Date (Earliest Submission Date)

New Date April 11, 2016 per issuance of NOT-CA-16-004. (Original Date: December 27, 2015)

Letter of Intent Due Date(s)

30 days prior to application due date

Application Due Date(s)

New Date May 11, 2016 per issuance of NOT-CA-16-004. (Original Date: January 27, 2016), by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

No late applications will be accepted for this Funding Opportunity Announcement.

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

New Date October-November 2016 per issuance of NOT-CA-16-004. (Original Date: April - May 2016)

Advisory Council Review

New Date January 2017 per issuance of NOT-CA-16-004. (Original Date: August 2016)

Earliest Start Date

New Date April 2017 per issuance of NOT-CA-16-004. (Original Date: September 2016)

Expiration Date

New Date May 12, 2016 per issuance of NOT-CA-16-004. (Original Expiration Date: January 28, 2016)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options to submit your application to the agency through Grants.gov. You can use the ASSIST system to prepare, submit and track your application online. You can download an application package from Grants.gov, complete the forms offline, submit the completed forms to Grants.gov and track your application in eRA Commons. Or, you can use other institutional system-to-system solutions to prepare and submit your application to Grants.gov and track your application in eRA Commons. Learn more.

Problems accessing or using ASSIST should be directed to the eRA Service Desk.
Problems downloading forms should be directed to Grants.gov Customer Support.
Table of Contents

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information


Part 2. Full Text of Announcement
Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) is a part of the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC). This reissuance of the CPTAC program leverages recent advancements in cancer proteomics and genomics and accelerates research in these areas by disseminating research resources for the scientific community. 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 proteogenomic approaches will also be explored in translational research focused on clinically-relevant problems, such as the ability to predict which treatments are likely to be effective against a specific 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 clinically-relevant research projects. 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 use human biospecimens from clinical trials. The projects should also involve the use of relevant preclinical models of cancer. Proposed 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.

PTRCs will interact with additional CPTAC sub-programs that include:

  • Proteogenomic Data Analysis Centers (PGDACs, to be supported by RFA-CA-15-023) that will conduct integrative analyses of data across the entire proteomes and genomes of cancer types of focus 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-15-021) 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, cultured cells, and animal cancer models) will be provided by the NCI.

This FOA is open to all qualified applicants regardless of whether or not 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) are to be made publicly available to the research community through CPTAC's Data Coordinating Center (DCC), Assay Portal, and other 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.

This FOA will NOT support clinical trials (tasks such as development of study design, identification of collaborators and enrollment sites, development of the clinical protocol and informed consent, development of the statistical analysis plan, development of the data management plan, etc.).

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 a human biospecimen or a preclinical model (cultured cell or animal model). 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 intersection 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 "comprehensive proteomic characterizations" means the generation of proteome-wide experimental data using human specimens/model samples, whereas "proteomic/proteogenomic data analysis" refers to the use of bioinformatic approaches and computation 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:
  • 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;
  • Targeted Proteomics Research - Analysis of raw experimental data to generate quantitative results on peptide/protein concentrations of the selected targets from Discovery Proteomics Research.
  • Level 2: Integration of genome-proteome data at the linear sequence level (DNA, RNA, peptides/proteins with relative quantitation obtained from Discovery Proteomics Research using personalized genomic data).
  • Level 3: Integration, visualization and analysis of omics data mapped onto networks and pathways obtained from Discovery Proteomics Research.
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 basic discovery and clinical impact.

The CPTAC program (RFA-CA-07-012) began in 2006 as a part of the Clinical Proteomic Technologies for Cancer initiative at the NCI, the purpose of which was to understand and address the experimental and analytical sources of error in existing proteomics technologies, in order to complement genomic and transcriptomic analyses used to improve diagnostics, therapeutics, and prevention for cancer. Program highlights include the standardization of mass spectrometry (MS) methodologies for untargeted protein analyses (discovery proteomics), standardization of multiple reaction monitoring (MRM) mass spectrometry in targeted protein analyses (targeted proteomics), adoption of a MRM assay for thyroglobulin by clinical reference laboratories, development of an open-source computational tool (Skyline) for designing MRM assays that is supported by major instrument vendors, development of mock 510(k) device clearance documents using targeted proteomic platforms in coordination with the Food and Drug Administration (FDA) and the American Association for Clinical Chemistry (AACC), and development of open data sharing policies in proteomics that are supported by peer-reviewed journals.

To begin to apply these outputs, the second phase of CPTAC was initiated in 2011 (RFA-CA-10-016) as a pilot collaborative network to utilize CPTAC’s state-of-the-art standardized proteomic workflows to study genomically-characterized tumors (such as those from The Cancer Genome Atlas (TCGA) and others) to add an additional layer of biology to cancer. The goal was to apply deep proteomic analysis to tumors that have undergone comprehensive genomic characterizations, to gain additional biological insights that would have been difficult or impossible to obtain solely through genomics approaches. All data and analytical tools were made broadly available to the research community through public databases (CPTAC's Research Resources: Data Portal, https://cptac-data-portal.georgetown.edu/cptacPublic; Assay Portal, https://assays.cancer.gov; Antibody Portal, http://antibodies.cancer.gov), in order to democratize proteomics science. The current CPTAC program is composed of Proteome Characterization Centers (PCCs) with expertise in proteomics, genomics, cancer biology, oncology and clinical chemistry that perform coordinated research projects to comprehensively characterize and analyze cancer specimens selected for study. PCCs have interrogated three cancer types (colorectal, ovarian and breast tumors), while successfully demonstrating the scientific benefits of integrating proteomic research with genomics to produce a more unified understanding of cancer biology, while creating open community resources that are widely used by the cancer community. Such an integrated proteogenomics approach is now bringing key insights into genomic abnormalities manifested at the protein network and pathway level.

Overall CPTAC Structure and Functions

The CPTAC program will consist of the following sub-programs:

  • Proteome Characterization Centers (PCCs). To improve the molecular understanding of cancer biology, PCC awards (RFA-15-021) 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 awards 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 capability, and a proteogenomic-based research approach. Research would support cancer research model studies (comprehensive proteogenomic discovery research), clinical trial sample acquisition, followed by targeted assay development and application on clinical trial samples. 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). In collaboration with the PCCs and the PTRCs, PGDAC awards (RFA-15-023) will support innovative bioinformatics development and application to integrate data analyses across the entire proteome and genome. 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 beyond the scope of this FOA) available to CPTAC awardees:

To facilitate the activities of individual PCCs and other research sub-programs of the CPTAC program, additional NCI-supported resources beyond the scope of this FOA will be provided to awardees. These include:

  • NCI-supported Biospecimen Resources:
  • Tissue Source Sites (TSS), which collect human biospecimens and clinical data.
  • Biospecimen Core Resource (BCR) that serves as a centralized laboratory(s) that receives, processes, qualifies, and distributes treatment-naïve tumor and matched normal control human biospecimens to the PCCs. 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. Note: only PCC awardees will receive NCI-collected specimens.
  • Genomic Characterization Center (GCC) that will genomically characterize NCI-provided CPTAC biospecimens to be characterized and analyzed by the PCCs.
  • Clinical Data Resource (CDR) that will receive, qualify, store, and distribute clinical data.
  • Quality Management System (QMS). The QMS works with all CPTAC awardees to define quality processes and metrics, and to track nonconforming events.
  • Data Coordinating Center (DCC): All CPTAC awardees will have to 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 and quality control of data. The DCC will also implement the CPTAC common data analysis pipeline, consisting of quality control metrics applied to genomic and proteomic data and peptide/protein identification and quantification for proteomic data.
  • CPTAC Research Resources. The CPTAC program currently has three dedicated public resources for disseminating its research findings. Applicants are encouraged to consider using the items in these portals, as appropriate. These resources include:
  • Data Portal (https://cptac-data-portal.georgetown.edu/cptacPublic), which serves as a centralized repository for the dissemination of proteomic data collected by the CPTAC program.
  • Assay Portal (https://assays.cancer.gov), which serves as a public repository of well-characterized, targeted proteomic assays. The Assay Portal contains analytically validated assays and standard operating procedures (SOPs) that can be used to compare results across the board. Assays in the portal adhere to “Fit-for-Purpose” validation guidelines distinguished by their performance and extent of analytical characterization (Tiers 1-3). (http://proteomics.cancer.gov/newsevents/newsannouncements/archive/2013/standardstargeted).
  • Antibody Portal (http://antibodies.cancer.gov), which serves as a community resource of unbiased renewable antibodies (monoclonal) with all associated SOPs and characterization data made publicly available to the research community.
  • Proteomic informatics tools (http://proteomics.cancer.gov/resources/softwaretools). Various informatics tools (developed or refined by CPTAC investigators) are available (e.g., for analytical metric quality control, along with data visualization, analysis and integration of cancer-relevant networks and pathways, etc.).
  • Other NCI research resources: Applicants for one or more of the CPTAC sub-programs are encouraged to consider establishing partnerships with other groups, and divisions and programs within NCI that may benefit the overall program goals. For example, the awardees could take advantage of the TCGA (http://cancergenome.nih.gov), Cancer Target Discovery and Development Network (CTD2; http://ocg.cancer.gov/programs/ctd2), Early Detection Research Network (EDRN, http://edrn.nci.nih.gov), the Cancer Diagnosis Program (CDP, http://www.cancerdiagnosis.nci.nih.gov), and Division of Cancer Treatment and Diagnosis (DCTD)'s Cancer Therapy Evaluation Program (CTEP, http://ctep.cancer.gov) including the National Clinical Trials Network (NCTN) and Experimental Therapeutics Clinical Trials Network (ET-CTN), and databases of clinical studies of human participants such as publicly supported clinical trials around the world (https://clinicaltrials.gov). For this FOA only: new investigational agents brought into NCI's DCTD/CTEP for development as high priority therapeutic agents approved by the NCI Experimental Therapeutics Program (NExT) can serve as a point of reference for future clinical trials (http://ctep.cancer.gov/initiativesPrograms/docs/Phase2ProgramBSA.pdf).
 
Research Objectives and Main Requirements for this FOA

Applicants seeking PTRC awards must be able to:

  • Perform comprehensive proteomic and genomic characterizations in preclinical cancer models and/or clinical specimens in response to therapeutic agents under study using analytically validated, high-throughput technologies/platforms. These characterizations may enable better evaluation of novel targeted therapeutics and identification of predictive biomarkers in early stages of drug development/treatments.
  • Conduct proteogenomic data analysis for the selection of protein targets specific for the cancer therapeutic agents under study for further testing in preclinical cancer models and clinical trial samples using targeted proteomic technologies.
  • Operate as an interactive group that leverages the data and knowledge from other CPTAC sub-programs. Use of information from comprehensive characterization datasets such as The Cancer Genome Atlas (TCGA, http://cancergenome.nih.gov) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC, http://proteomics.cancer.gov) are highly encouraged.

Note: All cancer types with unmet translational and/or clinical question(s) will be considered under this FOA.

To be responsive to this FOA, the scientific scope of work of research projects proposed must be within one of the two areas listed below:

Area 1: Elucidation of the proteogenomic determinants of tumor responses and resistance to cancer therapeutic agents. Projects in this area may include an appropriate combination of correlative studies using clinical biospecimens and mechanistic studies in preclinical model systems to elucidate the roles that specific genes/proteins/pathways may have as factors affecting clinical outcomes to treatments. Proposed projects should integrate comprehensive proteogenomics data to design rational approaches exploring the knowledge of cancer-related pathways in order to improve clinical outcomes for cancer patients. Studies can also explore directly molecular responses to therapeutic agents of interest at the proteomic and genomic levels by comparing preclinical or clinical samples before and after exposure to such agents. This aspect is desirable and strongly encouraged, if feasible (but is not required for the Clinical Research Arm).

Area 2: Characterizing alterations in proteins involved in cancer-related pathways. (including, the development and application of targeted proteomic assays). Proteins/pathways to be studied should be relevant to the therapeutic agents received by patients from whom clinical trial samples are to be studied in the PTRC project.

To be responsive, applications must cover BOTH preclinical studies (using cancer model systems) and studies with clinical biospecimens. Accordingly, each PTRC must propose research in a Preclinical Research Arm and Clinical Research Arm defined as follows.

  • Preclinical Research Arm refers to studies that include (1) comprehensive characterizations of proteins and their additional forms (e.g., variants and/or PTMs) along with genomic characterization in a preclinical cancer model sample; and (2) quantitative proteomic determinations of selected, cancer-relevant protein targets identified and prioritized through (1). 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.
  • Clinical Research Arm refers primarily to the development and application of quantitative proteomic assays 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 that meet the criteria described in Section IV.2. These specimens are to be accompanied with well-annotated clinical data and genomic characterization. These types of targeted measurements should be conducted in a high-throughput manner and be deployable at the start of the project.

Note. Human biospecimens from clinical trials and preclinical cancer models are to be provided by each applicant.

Preclinical cancer models. PTRCs are expected to comprehensively characterize preclinical cancer models such as cell lines and patient-derived xenografts (pre- and post-treatments) in Preclinical Research Arm. Preclinical cancer models must be well defined and well characterized. Models must have corresponding genomic characterization which meets TCGA or equivalent platform and data quality standards (http://proteomics.cancer.gov) (analyses including but not limited to: whole exome sequencing; RNA sequencing; genotyping and DNA copy number). 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.

Human biospecimens. In the context of this FOA, human specimens refer to individual patient's tumors to be analyzed in the Clinical Research Arm. These specimens must be accompanied with detailed medical data and genomics data which meet TCGA or an equivalent platform and data quality standards, including whole exome sequencing; RNA sequencing; genotyping and DNA copy number, etc. (http://proteomics.cancer.gov). At the time of application submission, research projects must have access (written approval) to characterize such specimens from NCI-sponsored clinical trials at the start of the program. 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-driven SOPs (e.g., CPTAC's collection protocols at http://proteomics.cancer.gov) in order to minimize pre-analytical variables such as ischemia. Other types of human biospecimens from non-NCI-sponsored clinical trials may be used in an auxiliary role.

To foster the development of collaboration among these investigators (e.g., proteomics and clinical trial researchers), a Teaming Website has been developed. Investigators interested in collaboration are encouraged to register at http://proteomics.cancer.gov.

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 and genomic analyses 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 and testing in additional samples;
  • Expertise in computational proteomic and proteogenomic analysis methods for Level 1-3; and
  • Ability to perform complex bioinformatic analyses and interpretation of omics data in conjunction with clinical data.

Pilot Studies

Applicants must have appropriate resources and flexibility to develop pilot studies to enhance and expand upon the main project proposed.

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. However, all data produced by the PTRCs for transfer to the PGDACs is expected to enable more extensive and comprehensive integrative analyses to enhance deeper data visualization, analysis and interpretation. 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 data release to the public (see Section IV).

Governance of the NCI Clinical Proteomic Tumor Analysis Consortium

The CPTAC program will be governed by 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 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 Panel (ESP) (as described in Section VI).

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.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NCI intends to commit $4.5 million in FY 2016 to fund up to 3 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 $910,000 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 in response to 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)

Governments

  • State Governments
  • County Governments
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
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) (formerly CCR) – 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

This FOA requires applications with more than one PD/PI, or multiple PDs/PIs, designated due to the "team science" approach of the projects.  Applications must designate at least two PDs/PIs: one expert in proteomics and another expert in clinical trials..

An individual designated as a PD/PI on an application in response to the PGDAC FOA, RFA-15-023, cannot be designated as a PD/PI under this FOA. However, an individual designated as a PD/PI on an application in response to the PCC FOA (RFA-CA-15-021) can be designated as a PD/PI under this FOA.

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

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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, MS, PhD, MBA
Office of Cancer Clinical Proteomics Research
Center for Strategic Scientific Initiatives
Office of the Director
National Cancer Institute
31 Center Drive, Room 10A52, MSC 2580
Bethesda, MD 20892
Telephone: 301-451-8883
Fax: 301-496-7807
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 facilities, core resources, and services that each team member will provide towards achieving the objectives of the proposed studies.
  • 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 PTRC network, the CPTAC program, and public access.
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, 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&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed. Additional guidance applies, as specified below.

Total Costs for Assays and Specimens. Applicants should describe the budget for genomic characterization, discovery and targeted proteomic assays to be developed and applied in Preclinical Research and/or Clinical Research Arms (e.g., total cost of a targeted proteomic assay per sample). In addition, a description of the budget for tumor procurement from clinical trials (excluding the costs for clinical trials) should be included whenever applicable.

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

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 be focused on studies with preclinical cancer models and at least one of the Specific Aims on studies using human tumor biospecimens.

Research Strategy: Instead of the standard sub-sections defined in 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 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 group expertise of the Team including proteomics, clinical trials, translational activities, genomics, cancer biology, clinical oncology, biostatistics, experimental design, bioinformatics, and clinical laboratory science/clinical chemistry contributes to achieving the objectives of the proposed studies. Highlight how the diverse group 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. In addition to academic and non-profit domestic organizations. The role of such partners should be clearly delineated.
  • Innovation. Highlight the particularly innovative aspects in terms of the clinical problems to be addressed, general strategies, technologies, etc. Outline the strategies proposed to develop pilot studies that enhance a specific PTRC’s efforts in advancing its overarching aims to identify opportunities to initiate future clinical trials related to additional cancer therapeutic agents to be studied (No specific pilot studies are to be described in the application). See Subsection D below for additional instructions.
  • 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 submitting an application, 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 targeted assays are being or have been developed at the time of this FOA application, describe the current state of assay development and its use in preclinical and/or clinical development where applicants should demonstrate 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).

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 should examine responses to therapeutic agents of interest at the proteomic and genomic levels by comparing samples before and after exposure to such agents. Applicants should plan accomplishing respective preclinical goals early enough  to allow for sufficient time (such as at least 2-3.5 years) 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 technolog(ies)/platform(s). A technology platform must be reproducible, quantitative and sensitive for comprehensive proteomic characterizations (discovery). For the purpose of this FOA, a discovery 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 (published in a peer-reviewed journal); and 2) is capable of generating reproducible results within and across laboratories using standards and metrics in high-throughput, large-scale proteomic research studies. Similarly, a platform/technology for targeted assays is expected to be reproducible, quantitative and multiplexed targeted methodology. A technology platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed in at least one other laboratory reproducibly (published in a peer-reviewed journal); and 2) are high-throughput assays capable of sampling the depth of proteomes studied that spans a wide dynamic range. Specifically, it should be able to measure protein/peptide concentrations in the range of low femtomole/microgram to low femtomole/milligram (proteins). 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 (http://assays.cancer.gov). Other platforms/technologies are highly encouraged provided that they meet the specified analytical requirements. It is expected that a minimum of a Tier 2 analytical characterization for mass spectrometry (http://proteomics.cancer.gov/newsevents/newsannouncements/archive/2013/standardstargeted) or an equivalent for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place).

Describe the plan for the proposed proteogenomic characterizations of preclinical cancer models 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 (wet tissue weight of patient-derived xenografts and total number of cells for cell culture).

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 (http://proteomics.cancer.gov).

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 also 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 (assays 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 technolog(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 are envisioned 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-15-023) for the entire CPTAC program possibly with different computation omics tools, joint analysis activities are to be coordinated between PTRCs and PGDACs to avoid duplication of target selection.

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. In addition, describe how the raw data will be transferred to the PGDACs for additional visualization, interpretation, and protein candidate prioritization for confirmatory (targeted) 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.  PTRCs will submit their raw data, metadata and analysis results to the DCC.

Sub-Section C. Approach for Clinical Research Arm

The clinical studies using human tumor biospecimens and proposed under Approaches for Clinical Research Arm are expected to be focused primarily on targeted assays for specific proteins implicated in the responses to therapeutic agents of interest. Therefore, these studies should strongly be supported by applicants' own preliminary data and/or other available information. If such data are unavailable or limited, the clinical studies should be preceded by appropriate characterizations under Preclinical Research Arm. All studies proposed under Clinical Research Arm must be consistent with the secured and documented specimen availability (see below under "Letters of Support" for details). 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 treatments by the therapeutic agents of interests with therapeutic outcomes after such treatment(s);
  • Comparative proteogenomic analyses using specimens collected before AND after treatment by the therapeutic agents of interests (e.g., pharmacogenomic determinations to examine the effects of drug treatment on specific protein targets or pathways).

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

a) Proteomic technolog(ies)/platform(s). A platform/technology for targeted assays is expected to be reproducible, quantitative and multiplexed targeted methodology. A technology platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed in at least one other laboratory reproducibly (published in a peer-reviewed journal); and 2) are high-throughput assays capable of sampling the depth of proteomes studied that spans a wide dynamic range. Specifically, it should be able to measure protein/peptide concentrations in the range of low femtomole/microgram to low femtomole/milligram (proteins). 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 (http://assays.cancer.gov). Other platforms/technologies are highly encouraged provided that they meet the specified analytical requirements. It is expected that a minimum of a Tier 2 analytical characterization for mass spectrometry (http://proteomics.cancer.gov/newsevents/newsannouncements/archive/2013/standardstargeted) or an equivalent for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place).

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 (http://proteomics.cancer.gov).

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

d) Quality Assurance/Quality Control criteria for proteomic technolog(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.

e). 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.

f) 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 so as to maximize the PTRC network's throughput and the benefit of molecular knowledge.

Sub-Section D. Effort Coordination and Pilot Studies

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

  • 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 sub-programs, 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.
  • Pilot Studies:
  • Program management using appropriate process management methods for planning, monitoring, and managing workload (including strategies for monitoring and reporting progress in reaching specific milestones).
  • Strategies for communication within the PTRC network and in all CPTAC sub-programs.
  • List the areas/possible directions for which pilot studies are anticipated. Justify these choices by explaining why additional efforts in these areas/directions might be needed. Indicate how the concepts for such studies will be formulated. Pilot studies may focus on, for example, innovative clinical trial design, trial sample accrual, and proteogenomic analysis. The network pilot studies are expected to involve exchange of expertise (i.e., investigators inside or outside a specific PTRC), as well as shared materials and/or equipment. Note that concepts for such studies to be formulated by the awardee will be expected to reflect the individual needs of that awardee. Nonetheless, these individual concepts will be evaluated and coordinated by the CPTAC Steering Committee to optimize the efforts at the Network level. As pilot studies proposed by each Center (post-award) will require beyond normal stewardship (i.e., Project Scientists responsible for the U24 awards in coordination with the CPTAC Steering Committee, see Cooperative Agreement Terms and Conditions of the Award, under "Areas of Joint Responsibilities" in Section VI.2), a description of the process to obtain the approval of such studies, which may be collaborative, should be included for peer review in order to determine fairness at the time of application.  Subsequently, the CPTAC Steering Committee and the involved Project Scientists should advise which studies would be supported to enhance and accelerate the overall goals of the program.  (No pilot studies are to be proposed in the applications submitted in response to this FOA).
  • For pilot studies to initiate future clinical trials, it is anticipated that studies  in the Preclinical Research Arm be completed by the end of Year 3. Upon approval of new clinical trials, patient tumor accrual is expected to be completed by the end of Year 4, allowing sufficient time for proteogenomic analyses. Wherever feasible, new trial specimens should be collected using proteomics-driven SOPs (e.g., CPTAC's protocols at http://proteomics.cancer.gov) to minimize pre-analytical variables such as ischemia.

Note: Applicants considered for funding will be required (as a Just-in-Time requirement) to identify at least one local patient advocate as a consultant. For assistance in identifying such individuals, applicants are encouraged to contact the NCI Office of Advocacy Relations. (http://advocacy.cancer.gov).

Letters of Support: In addition to standard items, provide letter(s) of commitment for access to clinical trial specimens to be used in the proposed research. These letter(s) must clearly state that applicants will have access to clinical specimens needed for the research projects proposed and 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.);
  • Any other critical information about specimens must have access (written approval) to characterize such specimens from NCI-sponsored clinical trials at the start of the program.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modifications:

  • 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.
  • 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 sharing timing and frequency 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 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 PCC awardees will be expected to adhere to the general proteomic data sharing principles established such as in the Amsterdam Principles for mass spectrometry (http://proteomics.cancer.gov/resources/opendatapolicy) or an equivalent for other technologies/platforms.
  • Similar to TCGA and other programs, CPTAC data will be subject to a period of embargo (https://cptac-data-portal.georgetown.edu/cptac/aboutData/disclaimer).
  • 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.
  • Resources Sharing: 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; http://proteomics.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.

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.

Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

3. Submission Dates and Times

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

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 NCI, 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 NOT-OD-13-030.

Section V. Application Review Information

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

1. Criteria

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

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? 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? 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? 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 New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the 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: Are the quality and breadth of expertise of the PD(s)/PI(s) and the entire team adequate 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? Will these investigators be able to 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?

Specific to this FOA: Do the applicants propose novel or improved ways and/or methods to enhance or better conduct integrative proteogenomics for target prioritization, and subsequent proteomics research on clinical trial samples?

Approach

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

If the project involves 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 children, justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: Are the studies proposed in Preclinical and Clinical Research Arms sufficiently substantiated by available preliminary results? If studies under Clinical Arm depend on the accomplishment of the Preclinical Arms, are these plans (and their timing) appropriately justified and feasible? 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? Are these plans sufficient and optimal to increase the likelihood of successfully identifying and validating protein targets involved in response to cancer therapeutic agents?

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? Will higher level interpretations be sound and meaningful?

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

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-sponsored 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Children 

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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.

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 the NCI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Appeals of initial peer review will not be accepted for applications submitted 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

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 grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

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

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

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

  • Overseeing, 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 PTRC and the entire CPTAC program through CPTAC DCC;
  • 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;
  • Submitting a list of prioritized discovered high priority protein targets for consideration by the Protein Candidate Selection Subcommittee for subsequent confirmatory studies;
  • Coordinating and encouraging inter-network collaborations;
  • Participating in the semi-annual PD/PI meeting organized by NCI;
  • 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.

Awardees will be expected to participate in an external evaluation process of the CPTAC program coordinated by NCI Program Staff.

Investigators from each PTRC award will be expected to participate in various task-oriented working groups together with members from other CPTAC sub-programs that might be formed, as needed, e.g., as subcommittees of the CPTAC Steering Committee.

The primary PTRC awardee institution and all other institutions participating in a given PTRC must agree to share and release results, data, research materials, and any other resources necessary and relevant to the PTRC’s award. Awardees will retain custody of and have primary rights to the data and the software developed under these awards, subject to Government rights of access consistent with current HHS, 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 network 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 awardees;
  • Review the progress of individual CPTAC awardees and specific activities shared among the awardees;
  • Assist the awardees as a resource in stimulating their broader interaction with other NCI and NIH programs 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;
  • 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.

Additionally, an NCI Program Staff member acting as a Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. A Program Official may also have substantial programmatic involvement (as Project Scientist/Coordinator).

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.

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.

The CPTAC Steering Committee will elect three representatives (one each from the PCC sub-program, PGDAC sub-program, and PTRC sub-program) as its co-chairs (or alternating chairs) for a pre-determined length of time).

Non-Voting Members:

  • Additional representatives from other CPTAC research resources may also participate as non-voting members and as determined by the CPTAC Steering Committee.
  • The CPTAC Steering Committee may decide to add other non-voting members as needed, e.g., to provide specific scientific expertise and/or to include patient advocates.

CPTAC Steering Committee:

  • CPTAC Steering Committee will establish a Protein Selection Subcommittee (see below).
  • CPTAC Steering Committee may also establish other subcommittees as it deems appropriate.

It is anticipated that the CPTAC Steering Committee will formulate strategic decisions and policies for consortium-wide activities. The CPTAC awardees 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 and policies to meet the goals of the CPTAC network and monitor the implementation of these guidelines and policies;
  • Reviewing progress of the CPTAC sub-programs on a regular basis;
  • Developing quality assurance goals for all network functions, specimens, technology and data for the CPTAC network;
  • Following-up on action items from the CPTAC Steering Committee in a timely fashion;
  • Approving recommendations and development plans from the Protein Candidate Selection Subcommittee (see below);
  • Prioritizing and recommending pilot studies for execution;
  • Organizing semi-annual meetings of CPTAC investigators.
  • Coordinating the development of a standard data reporting system by the CPTAC Steering Committee (e.g., updating the reporting system currently used in CPTAC);
  • Developing operating guidelines, quality control procedures, and consistent policies for the CPTAC network.

Protein Candidate Selection Subcommittee. The members of the Protein Candidate Selection Subcommittee will include 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 by the committee.

The activities of the Protein Candidate Selection Subcommittee will include the following:

  • Consolidating the lists of prioritized proteins from each CPTAC sub-program’s inventory and prioritization process, including reviewing scientific justifications for developing multiple targeted proteomic assays against the same protein originating from a given "parent gene," such as its protein variants, modified forms, etc.
  • Recommending a biological- and clinical-based selection of protein candidates for clinical research studies;
  • Recommending reagents and specimens to be used for the selected protein candidates.

Recommendations by the Protein Candidate Selection Subcommittee will be reviewed and approved by the CPTAC Steering Committee.

CPTAC External Scientific Panel. The CPTAC Steering Committee will establish a panel of external experts (i.e., individuals with appropriate expertise who are NOT affiliated with any of the CPTAC awardees). The primary role of the External Scientific Panel will be to provide independent assessment of research directions and progress of the CPTAC awardees. The External Scientific Panel will annually evaluate research conducted by the CPTAC members, including the review of the overall program metrics, progress of individual awardees, 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, as well as additional scientific experts as deemed necessary, will review any additional proposed clinical trials to be initiated post award during the course of the entire funding period (see pilot studies, Section IV). Pending approval, restricted funds pertinent to the parent grants will be released to facilitate newly proposed preclinical cancer research projects for new therapies prior to requesting the approval of future clinical trials and subsequent activities associated with clinical trials if approved, including study design, protocol review, patient accrual, specimen procurement and molecular characterizations and analyses.

Dispute Resolution Process:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution.  A Dispute Resolution Panel composed of three members will be convened.  It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee.  This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 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. In addition to the annual RPPR, a detailed interim Center progress report will be required once a year. This report should be submitted directly to the NCI Project Scientist. The interim report will be required to be formatted following standardized guidelines developed by the NCI Program Staff and may be changed according to programmatic needs based on discussions among the CPTAC Steering Committee members.

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

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

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 Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-435-0714

Scientific/Research Contact(s)

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

Henry Rodriguez, MS, PhD, MBA
National Cancer Institute (NCI)
Telephone: 301-451-8883
Email: rodriguezh@mail.nih.gov

For issues related to proteomics/genomics research, contact:

Emily Boja, PhD
National Cancer Institute (NCI)
Telephone: 301-451-1079
Email:  bojae@mail.nih.gov

For issues related to clinical research, contact:

Mehdi Mesri, PhD
National Cancer Institute (NCI)
Telephone: 301-451-2149
Email:  mesrim@mail.nih.gov

For issues related to CPTAC public resources, contact:

Tara Hiltke, PhD
National Cancer Institute (NCI)
Telephone: 301-451-8511
Email:  hiltket@mail.nih.gov

For issues related to National Clinical Trials Network (NCTN), contact:

Elise Kohn, MD
National Cancer Institute (NCI)
Telephone: 240-276-7163
Email: kohne@mail.nih.gov

For issues related to Phase I Experimental Therapeutics Clinical Trials Network (ETCTN), contact:

S. Percy Ivy, MD 
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: ivyp@ctep.nci.nih.gov

For issues related to Phase II Experimental Therapeutics Clinical Trials Network (ETCTN), contact:
Jeffrey Moscow, MD 
National Cancer Institute (NCI)
Telephone: 240-276-6565
Email: jeffrey.moscow@nih.gov

For issues related to Diagnostic Biomarkers and Technology, contact:

James Tricoli, PhD
National Cancer Institute (NCI)
Telephone: 240-276-5725
Email: tricolij@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Mutema Nyankale
National Cancer Institute (NCI)
Telephone: 240-276-5987
Email: nyankalem@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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