National Institutes of Health (NIH)
National Cancer Institute (NCI)
U24 Resource-Related Research Projects Cooperative Agreements
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
RFA-CA-17-005 - Cancer Immune Monitoring and Analysis Centers (CIMACs) (U24)
Through this limited competition Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites applications to continue support for the Cancer Immune Monitoring and Analysis Centers Cancer Immunologic Data Center (CIMAC-CIDC) Network. The CIMAC-CIDC is a network of laboratories (CIMACs) and a bioinformatics center (CIDC) established to perform correlative studies using biospecimens from cancer immunotherapy clinical trials. Applying a comprehensive set of state-of-the-art immunoprofiling assays and bioinformatics pipelines, the CIMAC studies encompass genomics, transcriptomics, proteomics, microbiomes, and phenotyping analyses of tumor, tumor microenvironment, blood, stool, and other types of biospecimens. The ultimate goal of the CIMAC-CIDC Network is to identify biomarkers of response, resistance, and adverse events to optimize immunotherapy approaches for patients with cancer. CIMACs work with clinical trial teams and CIDC on correlative studies examining the association of biomarker data from the assays with clinical data from the trials.
The CIDC will be composed of two separate components: a CIDC Informatics Core supported by this FOA, and an NCI-contracted CIDC Information Technology (IT) Core supported by a separate, NCI contract mechanism.
- The CIDC Informatics Core, funded by this FOA, will provide bioinformatics support to the Network, support assay-specific bioinformatics pipelines, perform data quality control (QC), facilitate data ingestion into the CIDC IT Core, and help develop standards for cross-trial analysis and data sharing.
- The NCI-contracted IT Core (Not part of this FOA) will provide the IT and database infrastructure for the CIMAC-CIDC Network. It will be responsible for ingestion of assay data sets and clinical data sets, data access control and distribution within the Network, and contribution of data to data-sharing repositories.
- In addition, the CIMAC-CIDC Network (Not part of this FOA) will be supported by an Operations Center funded through a separate contract mechanism to provide logistical services to the Network.
Not Applicable
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| Not Applicable | October 24, 2022 | Not Applicable | March 2023 | May 2023 | July 2023 |
All applications are due by 5:00 PM local time of applicant organization.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late application will be accepted for this Funding Opportunity Announcement
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Purpose
Through this Funding Opportunity Announcement (FOA), the National Cancer Institute (NCI) invites current CIMAC and CIDC sites to submit applications to renew their participation in the Cancer Immune Monitoring and Analysis Centers Cancer Immunologic Data Center (CIMAC-CIDC) Network. Together, the CIMACs and the CIDC will represent the primary units of the CIMAC-CIDC Network. Please note: The title of the CIDC will be changed from the "Cancer Immunologic Data Commons" to the "Cancer Immunologic Data Center". The CIDC will have two distinct components: a CIDC Informatics Core supported by this FOA, and a CIDC Information Technology (IT) Core supported by a separate NCI contract mechanism.
The overarching aim of the CIMAC-CIDC Network is to conduct both hypothesis-driven and hypothesis-generating correlative studies in immuno-oncology (IO) trials, with the goal of identifying candidate biomarkers to improve immunotherapy through achieving the following scientific objectives: (1) Enhance understanding of evolution of tumor, tumor microenvironment, and systemic analytes during treatment and their effects on response to therapy. (2) Enhance understanding of the mechanism of immunotherapy agents both alone and in combination with other immunotherapy agents and/or other modalities such as radiotherapy or chemotherapy. (3) Accelerate identification of clinically actionable biomarkers of response, resistance, and adverse events to aid in precision cancer treatment. (4) Further develop a database of clinically annotated biomarkers and facilitate sharing of these data. (5) Share guidelines for best practices in assay performance with the research community. (6) Enhance functioning of the Network through collaboration among CIMACs, CIDC, and clinical trial investigators.
The expected capacity of the renewed CIMAC-CIDC Network will be to provide comprehensive biomarker analyses for additional NCI clinical trials as well as NCI trials enrolled during the previous award period. CIMACs will send comprehensive biomarker data to the CIDC, and clinical trial teams will send clinical trial data to the CIDC. Correlative analyses based on assay data in conjunction with clinical data are then performed by the CIMAC-CIDC, in close collaboration with the clinical trial team, to evaluate associations between the biomarker and clinical data across multiple assays, both within and across multiple clinical trials.
The renewed Network will build upon the established CIMAC-CIDC Network's infrastructure and scientific knowledge gained in the previous funding period and leverage NCI-sponsored programs and resources, including NCI-supported clinical trial networks. The Network will have access to NCI's large portfolio of immunotherapy trials led by the NCI-supported clinical trial networks, from which candidate trials will be selected based on NCI programmatic decision in consultation with CIMAC-CIDC.
The CIDC Informatics Core, supported by this FOA, will provide informatics platforms for analysis of biomarker data, perform QC of biomarker data and clinical data, support cross-trial analysis, and work closely with the NCI-contracted CIDC IT Core. The CIDC IT Core, which will be supported by a separate NCI contract, will ingest assay data sets and clinical data sets QC ed by the CIDC Informatics Core to make data available to the Network and contribute data to data-sharing repositories. In addition, the CIMAC-CIDC Network will be supported by an Operations Center funded through a separate contract mechanism to provide logistical services to the Network. The CIMAC-CIDC Network will leverage and expand the centralized database for integration of clinical and assay data to facilitate identification of biomarkers to optimize immunotherapy approaches for patients with cancer.
Background
Immunotherapy approaches, including checkpoint blockade and combinations, engineered T cells, bispecific T-cell engagers, and oncolytic viruses, have shown remarkable success in treating cancers, yet clinical benefits are limited to a minority of cancer patients. To improve success rates, it is critical to identify immune signatures that are predictive of response and that yield insight into mechanisms of adaptive and intrinsic resistance as well as an immunosuppressive tumor microenvironment. Furthermore, biomarkers associated with immune-related adverse events (irAEs) are needed, as irAEs are increasingly recognized as barriers to immunotherapy efficacy. Although several genomic and immune predictors of response to anti-PD-1/PD-L1 pathway blockade have been reported, including PD-L1 expression, CD8+ T-cell density, tumor mutational burden (TMB), transcriptomic profiles, and microsatellite instability (MSI), the ability of these biomarkers to predict benefit from immunotherapy is limited to specific agents and tumor types.
There is a critical need to identify actionable biomarkers to improve efficacy and safety of immune checkpoint inhibitors and their combination with other approaches. However, the complex interplay between the cancer and the host immune system represents a scientific challenge to biomarker identification, one that is further confounded by inter-laboratory variability in assay performance and reproducibility, tumor and interpatient heterogeneity, and the small size of patient cohorts in clinical trials.
Given the complexities of the tumor immune system interface and treatment modalities, limited data exist to provide insight into mechanisms of response and resistance that are potentially actionable. This necessitates the deconvolution of such complexities by applying multimodal assay approaches integrating tumor, tumor microenvironment (TME), blood, and other biospecimens in parallel to identify biomarkers that accurately predict which patients will benefit from immunotherapy. In addition to determining predictors of response to immune checkpoint blockade, there is growing interest in understanding the mechanistic differences between different forms of immunotherapy.
To address these challenges and areas of critical need in immunotherapy biomarker research, the NCI established the CIMAC-CIDC Network. The Network has the following capabilities: (1) Innovative, comprehensive immune profiling and analysis using state-of-the-art, multimodal platforms to address the complexity of the tumor-immune system interface and treatment modalities; (2) Standardized and harmonized assays to address assay performance variables between laboratories to reduce data variability and enhance reproducibility; (3) Clinical outcome data and access to multiple clinical trials; (4) Centralized bioinformatics pipelines for data analysis at the CIDC Informatics Core; and (5) via a separate NCI-supported contract, a central database of molecular and cellular data with clinical outcomes. Assay harmonization and validation across CIMACs facilitate comparison of data across CIMAC sites and correlative studies. This harmonization and validation, coupled with use of centralized bioinformatics pipelines at the CIDC Informatics Core and the database at the NCI-contracted CIDC IT Core, will enable analysis of correlative data across multiple trials to identify biomarkers of interest. As the large database expands, it will allow for secondary analyses to address scientifically and clinically relevant biomarker questions.
Research Objectives and Requirements
Applications in response to this FOA must propose to support the capabilities of either a CIMAC or the CIDC Informatics Core. Only the current award recipients under RFA-CA-17-005 and RFA-CA-17-006 are eligible to submit applications in response to this FOA. The award recipients under RFA-CA-17-005 are eligible to submit applications for CIMACs and the award recipient under RFA-CA-17-006 is eligible to submit an application for CIDC.
Each CIMAC should provide scientific guidance and artificial intelligence methods, yielding a prolific biomarker discovery that will inform precision medicine-based decision-making. Efforts are needed for the efficient integration of results from multiparametric analyses from individual studies through sustained investments in data sharing, standardization practices, and state-of-the-art assays. Each CIMAC will perform comprehensive analyses using state-of-the-art platforms with fit-for-purpose assays in specimens from clinical trials and will correlate the biomarker data with clinical outcome data. Each CIMAC should be able to integrate novel, deep-profiling analytic approaches and interpret the data, including statistical and bioinformatic evaluation. CIMACs will work to identify biomarkers of response, resistance, and toxicity and elucidate mechanisms of action of immunotherapy agents, including combination therapies.
The purpose of the CIDC is to provide bioinformatics and cloud-based IT support for the CIMAC-CIDC Network. The CIDC is envisioned as two collaborative components that integrate bioinformatics tools and database-support capacity. The CIDC Informatics Core is the component supported by this FOA and will work closely with each CIMAC center and the NCI-contracted CIDC IT Core. The CIDC IT Core will be the second component of the CIDC and will be maintained by a separate, NCI-contracted service provider. The CIDC IT Core will maintain a database to fulfill data ingestion, data distribution, data sharing, and other IT services for the Network, including security and access control.
I. Cancer Immune Monitoring and Analysis Centers (CIMACs)
Required assay capacity for immunoprofiling:
High-throughput technologies using unbiased/unsupervised discovery approaches will increase the ability to identify novel biomarker candidates as well as composite biomarkers with potential clinical value. Therefore, each CIMAC should be prepared to provide a wide range of multiplexed analyses using state-of-the-art, well-established assays in addition to providing scientific expertise in data analysis and correlative research that will require competence in clinical investigation, translational study design, biostatistics, bioinformatics, and computational biology.
Required assay capacities are listed in tiers as follows. Note: This FOA does not support the development of new assays. Only after prior consultation with NCI would the funding be provided for the validation of assays.
Tier 1 assays: All CIMACs will be required to demonstrate the capacity to perform and interpret a majority of the following "Tier 1" set of validated assays (negotiable between CIMACs and NCI), which will be included in most trials collaborating with the CIMAC-CIDC Network:
Tier 1 assays:
- Whole exome sequencing (WES)
- RNA-seq
- Multiplex immunohistochemistry/immunofluorescence (mIHC/IF)
- Singleplex PD-L1 IHC (including use of immunotherapy agent-specific antibodies)
- Cytometry by time-of-flight (CyTOF)
- Soluble analytes immunoassay (e.g., Olink)
- TCR-seq (sequencing of TCR repertoire)
Harmonization of Tier 1 assays: Except for assays performed at a single CIMAC, harmonization of any new Tier 1 assays across CIMACs will be required to generate comparable data for biomarkers across CIMAC sites in the Network. Additionally, CIMACs must apply longitudinal reference materials to ensure a high level of agreement of Tier 1 assay performance over time and across CIMAC sites.
Tier 2 assays: In addition, cumulatively the CIMACs will be required to perform and analyze all "Tier 2" assays that address trial-specific hypotheses and are used in selected trials in the Network:
Examples of Tier 2 assays:
- cfDNA
- MIBI or other tissue-imaging platforms
- Grand Serology ELISA
- ATAC-seq
- 16s microbiome sequencing
- Other assays that address trial-specific hypotheses
Tier 3 assays: Moreover, each CIMAC is expected to introduce novel, "Tier 3" assays reflecting state-of-the-art technologies for comprehensive analysis of specimens. "Tier 3" assays are considered exploratory and should provide a deep dive into immune system complexity. Such assays include both quantitative and qualitative methods for immunoprofiling and need to be well-established in the laboratory. While assay development is beyond the scope of this FOA, some financial resources of this funding opportunity can be used for assay validation purposes. These assays can be specific to each CIMAC and will complement Tier 1 and 2 assays, with an aim to expand scientific capacity for the Network.
Examples of Tier 3 assays:
- Single-cell ATAC-seq
- Single-cell RNA-seq
- Single-cell TCR-seq
- CITE-seq
- Spatial transcriptomics
- Spatial tissue imaging
- ELISPOT
- HLA tetramers
- DNA Methylation
Specific Areas of Research Interest of the CIMACs include but are not limited to those listed below:
Comprehensive characterization of tumors and TME to identify candidate biomarkers:
- Dissect genetic changes in tumor and TME to understand tumor and TME evolution and to identify new targets, including neoantigens, by taking advantage of longitudinally collected samples;
- Perform differential gene expression analysis (DGEA) to evaluate genes and immune phenotypes that are associated with sensitivity to immunotherapies and downstream immune profiles by applying various deconvolution algorithms;
- Evaluate immunosuppressive mechanisms of resistance such as the tumor i) failing to elicit an immune response ( immune desert ); ii) preventing infiltration of immune cells ( immune excluded ); or iii) suppressing immune function despite adequate immune presence ( inflamed );
- Identify actionable predictors of response, resistance, and adverse events to individual immune-modulating as well as combination therapies, facilitated by randomized trials that compare multiple drug modalities;
- Understand the differential effect of distinct checkpoint blockade and immunomodulatory agents to inform combination therapy approaches by developing integrative models and algorithms jointly with the CIDC;
- Study mechanisms and biomarkers of immune-related adverse events (irAEs) (e.g., through evaluation of synthetic cohorts with irAEs);
- Evaluate cell-free DNA (cfDNA) in the blood as a biomarker of tumor evolution and for monitoring response; and
- Address gaps and critical needs in unique cohorts of patients with rare tumors and understudied populations.
Profiles of the host systemic response to immunotherapy:
- Cellular phenotypes (e.g., lymphocytes, neutrophils, myeloid cells, etc.); TCR clonality and T-cell repertoire phenotype and function (cytotoxic, effector, memory, exhausted T cell, etc.);
- Humoral components of immune response (e.g., cytokines, chemokines, and antibody repertoire);
- Germline DNA sequencing to detect genetic polymorphisms that contribute to response or resistance to, or toxicity of, immunotherapy;
- Laboratory tests to inform efficacy of novel cancer immunotherapy approaches, including treatments with CAR T cells, bispecific T-cell engagers, and antibody-drug conjugates; and
- Evaluation of stool microbiota/microbiome in tumor response, irAEs, and therapeutic outcome.
Methods for high-dimensional immunoprofiling of tumor and immune system:
Methods include novel approaches and technologies focusing on multiplex, multidimensional readouts of mechanisms of response or resistance to immunotherapies. Examples include but are not limited to the following:
- In-depth proteomic profiling of the tumor and TME, including phenotype of various immune and non-immune cell subsets (T cells, NK cells, MDSC, Tregs, TAMs) using multiplex tissue imaging approaches, allowing for evaluation of spatial architecture and relationships of tumor cell infiltrates [e.g., mIHC, mIF, MIBI, cyclic immunofluorescence (CycIF), CO-Detection by indexing (CODEX)], and spatial imaging technologies (e.g., GeoMx Digital Spatial Profiling [DSP], etc.);
- Identification and quantification of systemic T-cell and B-cell immune subsets and their function using multiplex immunophenotyping technologies (e.g., CyTOF, phospho-flow profiling, multiplex cytokine/chemokine release, cytotoxicity, tetramers, etc.);
- Identification and quantification of secreted products of lymphocytes such as cytokines/chemokines and immunoglobulins (e.g., Olink, ELISA);
- TCR clonality and antigen-specific reactive T cells;
- High-throughput epitope discovery, including structural and functional characterization of HLA class I and II epitopes (e.g., WES, mass spectrometry, tetramers, etc.);
- Bioinformatic algorithms to predict potential for immunogenicity and understand tumor immune escape, immunoediting, and sensitivity to immune checkpoint inhibitors;
- Genomics and transcriptomics, including approaches with high multiplex capacity beyond sequencing;
- Epigenome profiling (e.g., chromatin organization ATACseq, histone modifications, DNA methylation (global, restriction enzyme scanning, etc.);
- Liquid biopsy approaches (e.g., cfDNA) to identify biomarkers based on genomic and epigenetic alterations; and
- Single-cell genome/transcriptome technologies such as sequencing and proteomic profiling of tumor and immune response components (e.g., scRNA-seq, scTCR-seq, scATAC-seq, CITE-seq, spatial transcriptomics [e.g., GeoMx Digital Spatial Profiling (DSP), Visium 10x, etc.], RNA FISH) for use especially in FFPE and cryopreserved specimens.
Multi-marker signatures and cross-trial analyses (working jointly with CIDC):
- High-throughput technologies (-omics) and artificial intelligence methods, yielding a prolific biomarker discovery;
- Cross-trial analysis of biomarker and clinical data across multiple assays and trials;
- Models incorporating different data types to increase predictive ability of the classifiers for treatment response and resistance;
- Integrative models and algorithms to inform combination therapy approaches; and
- Algorithms to integrate multiparametric assay analyses to determine association with immunotherapy response/resistance.
Additional capabilities required of each CIMAC include but are not limited to:
Clinical trials eligible to collaborate with CIMACs:
Clinical trials collaborating with CIMAC-CIDC must be NCI-supported trials that include a form of immunotherapy (single-agent immunotherapy, combination immunotherapy, as well as combinations of immunotherapy with immunomodulatory agents such as chemotherapy, radiation, targeted agents, vaccines, oncolytic virus, cell therapies, interleukin, or other forms of immunotherapy).
Trials can be phase I through III trials (e.g., phase I, I/II, II, II/III, III) and must be trials from the following NCI-supported trial networks/mechanisms:
- National Clinical Trials Network (NCTN) (e.g., Alliance, CCTG, COG, ECOG-ACRIN, NRG Oncology, SWOG);
- Experimental Therapeutics Clinical Trials Network (ETCTN);
- Cancer Immunotherapy Trials Network (CITN), including the Pediatric CITN (Ped-CITN);
- Pediatric Brain Tumor Consortium (PBTC);
- Other immunotherapy-related Networks supported by NCI; and
- NCI-supported trials with funding from NCI research grants[e.g., Cancer Center P30 grants, Specialized Programs of Research Excellence (SPORE) P50 grants, R01, R35, P01, U01, U19, U54, UG3/UH3 awards].
Trials will be referred to the CIMAC-CIDC Network through programmatic selection of candidate trials by NCI and CIMAC-CIDC.
Preferred types of clinical trials include trials with specimens and clinical outcome data ready for analysis by 2026 at the latest; trials with longitudinal tissue and blood collections (e.g., collected at baseline, during treatment, and at progression); trials that involve biomarker-driven approaches for patient selection; trials with randomized design; trials with neoadjuvant treatment options; and/or trials that demonstrated biological effect and/or clinical benefit.
Performance of correlative studies and collaboration with the clinical trial teams:
- Each CIMAC will work collaboratively with the clinical trial teams, including the clinical trial statistician, from design through execution of the correlative studies. The process will include: development of the translational research proposal and incorporation into the clinical trial protocols; generation and analysis of biomarker data from assays; assisting identification of clinical data needed for the correlative study; generation of correlative study results; and publication of the correlative study.
- Each CIMAC leading a collaboration with a given trial will be responsible for the entire correlative study for that trial, including completion and cost (as appropriate) of all CIMAC assays in that trial.
- Each CIMAC will work with the clinical trial team to incorporate the correlative study into the NCI clinical trial protocol or a separate proposal document for review by the NCI.
- Each CIMAC will work with the CIDC to deposit assay data and correlative data to the CIDC.
- Each CIMAC and clinical trial group/biorepository will use the NCI Correlative Sample Management System (NCI CSMS) when sending/receiving specimens for CIMAC analysis.
- CIMACs will facilitate regulated submission of data to NIH data-sharing repositories for sharing with the general research community. This includes ensuring timely submission of all published data following NCI and Network policies, working with the CIDC to collect and standardize data for data sharing, and working with clinical trial teams to satisfy public data-sharing requirements.
Working with the NCI-contracted CIDC IT Core, CIMACs will facilitate the transfer of data to the NCI Cancer Research Data Commons (CRDC), or similar public controlled-access databases, for sharing with the general research community when such analyses and sharing are permitted by NCI policies and agreements.
- CIMACs will collaborate with NCI CIMAC-CIDC Operations Center staff to ensure that correlative studies are initiated and tracked; assay performance is reviewed and approved; specimen and clinical data requests are submitted; Human Material Transfer Agreements (HMTAs) are signed; and other functions are performed as allocated by NCI.
Assay quality assurance:
- Each CIMAC must offer analytically validated assays and provide detailed documentation of assay validation as described in Section IV of this FOA. Tier 1 and Tier 2 assays will require documentation of assay validation parameters. Although Tier 3 assays do not require validation, they require documentation of analytical performance as described in Section IV.
- As needed, each CIMAC will be required to harmonize Tier 1 assays to generate comparable results across the CIMACs.
- To monitor assay performance variability over time across CIMACs, longitudinal reference material testing will be required for Tier 1 assays and other assays as appropriate. Assay-specific reference standards can be used in bridging studies following a transition to an updated analysis platform or modification of an existing assay.
II. Cancer Immunologic Data Center (CIDC)
Specific Areas of Research Interest of the Cancer Immunologic Data Center (CIDC)
The purpose of the CIDC is to provide bioinformatics and cloud-based IT support for the CIMAC-CIDC Network. The CIDC is envisioned as two collaborative components that integrate bioinformatics tools and database-support capacity. The CIDC Informatics Core is the component supported by this FOA and will work closely with each CIMAC center and the NCI-contracted CIDC IT Core. The CIDC IT Core will be the second component of the CIDC and will be maintained by a separate, NCI-contracted service provider. The CIDC IT Core will maintain a database to fulfill data ingestion, data distribution, data sharing, and other IT services for the Network, including security and access control.
The CIDC Informatics Core component supported by this FOA will be expected to provide an informatics environment for integrative multi-dimensional analysis across different studies. The CIDC Informatics Core should also enhance data sharing through standardization of data collection methodologies and the use of metadata standards suitable for immune-related biomarkers, for the purposes of integration with other existing biomarkers and clinical databases. The CIDC Informatics Core will work closely with each CIMAC on the standardization of data collection methods and integration across different studies.
In general, the CIDC Informatics Core supported by this FOA will be expected to:
- Adopt, enhance, or develop data collection standards for key assay platforms and related database modules. This will be done in collaboration with CIMACs, the NCI-contracted CIDC IT Core, and other data-sharing collaborators.
- Support collection, QC, linkage, and management of biomarkers and associated clinical data. This includes integration with the CIDC IT Core, which will manage the database for the Network.
- Provide, maintain, and enhance bioinformatics tools for multi-dimensional analysis within and across trials in the CIMACs, jointly with the CIMACs.
- Maintain and enhance bioinformatics infrastructure support for analytic pipelines, algorithms, and tools needed for multi-dimensional analysis.
- Provide bioinformatics support for the design and analysis of cross-trial projects.
- Support harmonization and preparation of data, including following of data standards and guidelines for various data sets intended to be shared using NIH data-sharing repositories.
Expected capacities of the CIDC Informatics Core include, but are not limited to, the following:
- Provide bioinformatics and informatics pipelines support to CIMACs and other data-sharing collaborators, including integration with the NCI-contracted CIDC IT Core.
- Provide QC service for clinical data and biomarker data to be ingested by the CIDC IT Core.
- Assemble specialized teams to complete projects, including software engineers, bioinformaticians, clinicians, statisticians, and data scientists.
- Evaluate, standardize, and harmonize clinical data elements across trials: Collect, curate, and QC clinical data; perform relevant gap analyses to identify Network data needs, and work with the NCI Cancer Research Data Commons (CRDC) Data Standards Service.
- Support bioinformatics pipelines: Work with CIMACs to implement/maintain bioinformatics pipelines for relevant CIMAC assays, as well as have the capacity to add additional pipelines for novel assays. These include assay-specific pipelines additional to the existing pipelines for RNA-seq, WES, NanoString, TCR-seq, CyTOF, Olink, ELISA, mIHC/mIF, and microbiome.
- Provide bioinformatics tools and platforms whereby CIMAC and clinical trial investigators can perform correlative analysis. These tools should be able to support the integration of multiplex and high-dimensional biomarker data for the identification of markers/signatures correlated with clinical outcomes.
- Collaborate with the CIDC IT Core to ensure ingestion of assay data and clinical data into the database, including novel assay data.
- Perform central monitoring of assay performance across CIMACs using data from reference materials.
- Work with CIMACs to support cross-trial analyses, including determining the availability of clinical data attributes and biomarker variables across multiple trials, considerations for single- versus multiple-assay analysis, and feasibility review for proposed cross-trial analyses.
- Collaborate with NCI CIMAC-CIDC Operations Center staff to keep apprised of planned correlative studies, the progress of correlative studies, and the progress of clinical data requests.
Data sets hosted by CIDC will include the following:
|
Data type |
Description |
|
Clinical data from clinical trials |
Demographics, patient history, disease details including pathology and staging, treatment details including prior therapies, clinical outcomes, adverse events, specialized data, redacted pathology reports, and lab tests (including data dictionary and other supporting documents). |
|
Assay reference standards |
Standards included in assays to monitor longitudinal assay performance (spike-in, tissue microarray, etc.). |
|
Assay data |
Assay output files, analysis output files, metadata, reference standards, software details + analysis pipeline parameters, and slide images (e.g., H&E). |
|
Clinical test data (e.g., molecular panels, cytology) from clinical trials |
For select trials: targeted sequencing panels, and molecular and cytological markers may be collected as supplementary data (particularly mutations relevant to disease or immunotherapy, tumor-relevant cytogenetic abnormalities, and disease-specific markers). |
|
Correlative results data |
Data standardized for correlative analysis publications. |
|
Cross-trial results data |
Data standardized for cross-trial analysis publications. |
|
Publicly shared datasets |
Data used in publications that are submitted to a public data-sharing repository. |
Non-responsive Applications
The following limitations are placed on potential applications and projects. Applications not following these guidelines will be deemed non-responsive and returned without review:
- Development of new assays.
- Studies proposing clinical trials.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
Only the current award recipients under RFA-CA-17-005 and RFA-CA-17-006 are eligible to submit applications in response to this FOA. The recipients under RFA-CA-17-005 are eligible to submit applications for CIMACs and the recipient under RFA-CA-17-006 is eligible to submit an application for CIDC.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
The NCI intends to commit $7.92 million in total costs in FY 2023 to fund up to four Cancer Immune Monitoring and Analysis Center (CIMAC) awards.
The NCI intends to commit $1.4 million in total costs in FY 2023 to fund one Cancer Data Immunologic Center (CIDC) Informatics Core award.
NOTE: Only the current award recipients under RFA-CA-17-005 and RFA-CA-17-006 are eligible to submit applications in response to this FOA. The award recipients under RFA-CA-17-005 are eligible to submit applications for CIMACs and the award recipient under RFA-CA-17-006 is eligible to submit an application for CIDC. The NCI-contracted Cancer Data Immunologic Center (CIDC) IT Core, also part of the CIMAC-CIDC Network, will be supported by a mechanism independent of this FOA. The NCI intends to commit $1.4 million in total cost via contract to the IT Core in FY 2023.
Each CIMAC application budget is limited to no more than $1,188,000 in direct costs for any budget year.
Each CIDC application budget is limited to no more than $839,800 in direct costs for any budget year.
The budget must reflect the actual needs of the proposed project.
The total project period for an application submitted in response to this FOA may not exceed 5 years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
1. Eligible Applicants
Only the current award recipients under RFA-CA-17-005 and RFA-CA-17-006 are eligible to submit applications in response to this FOA. The award recipients under RFA-CA-17-005 are eligible to submit applications for CIMACs and the award recipient under RFA-CA-17-006 is eligible to submit an application for CIDC.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
- System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
- NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
- Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
- eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their full SAM and Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
- Grants.gov Applicants must have an active SAM registration in order to complete the Grants.gov registration.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women 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.
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
Only one application per institution (normally identified by having a unique UEI or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
1. Requesting an Application Package
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
2. Content and Form of Application Submission
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources:
CIMACs: Describe the infrastructure in the laboratory and available resources to support research activities at the CIMAC. Specifically, provide information on the available equipment (indicate any unique instruments/methods) and assay capabilities. For each assay or type of analysis, provide current and achievable rate of sample processing (e.g., number of samples per month). Provide information about computing facilities including digital services including HPC (High-Performance Computing Core) services and major desktop programs. Provide such information for all performance sites that will be included if a multi-site application is considered (subcontracts, cores, etc., if applicable). In addition, describe access to centralized resources at the institution.
CIDC Informatics Core: Describe the infrastructure and resources that will be available to the CIDC Informatics Core, including, specifically, the documentation of resources relevant to the goal of the CIDC Informatics Core with regard to attributes such as capacities, robustness, and scalability.
Other Attachments for CIMACs:
Attachments listed below must be provided or the application will be incomplete and will not be peer-reviewed. Upload these attachments using the filenames indicated.
Attachment I. Assay Validation Procedure and Data (use filename "Analytical Validation").
Please attach analytical validation documentation for all assays that each CIMAC is proposing to use in the CIMAC-CIDC Network. For each analytically validated assay, the documentation must provide detailed information on the assay’s analytical performance parameters/characteristics. Tier 1 and Tier 2 assays must be analytically validated, and the documentation provided for them must include the information listed below. For Tier 3 assays, the following information should be provided to the extent possible. Limited validation reports can be provided for well-established and commercially provided platforms.
The first part of the report should summarize data documenting the adequacy of the following assay performance characteristics:
- Intended use of the assay
- Analyte(s)
- Technical platform(s)
- Reagents, positive and negative controls, calibrators, reference standards
- Quality control parameters for specimens/analytes (e.g., cell viability, RNA/protein quality/integrity)
- Any critical pre-analytic variables
Analytical performance characteristics for the assay, including:
- Accuracy
- Precision
- Analytical sensitivity
- Analytical specificity including interfering substances
- Reportable range of assay results for the assay system
- Scoring procedures and type of data to be acquired:
- quantitative/continuously distributed
- semi-quantitative/ordered categorical
- qualitative/non-ordered categorical
- Reference ranges/intervals (normal values) with controls and calibrators
- Standardization, harmonization, reproducibility, and ruggedness of analytical performance if the assay is to be performed in multiple laboratories
- Throughput (estimated number of samples in a given time period)
- Turn-around time and failure rate of the assay
- Run-to-run variation (Coefficient of Variation, CV)
- Statistical methods for assay results interpretation
- Establishment of appropriate quality control and improvement procedures
The second part of the report must describe results of the validation study undertaken to define the assay's performance characteristics, including the number of samples used to define reproducibility, run-to-run variability and CV, inter-laboratory variability in the measurements and how these sources of variation are minimized to prevent drift or bias in the assay, quality control metrics, and criteria and metrics for defining significant changes (e.g., between time points, between responders and non-responders). Please describe how reference materials are used for longitudinally monitoring performance of the assay.
Evidence should be provided that demonstrates a high degree of assurance that a specific assay method, and the instruments included in the method, will consistently yield expected results.
Attachment II. Assay Standard Operating Procedures (SOPs) (use filename "Assay SOPs"). Please attach SOPs for all assays that each CIMAC is proposing to use in the CIMAC-CIDC Network. Include information on the appropriate storage and handling of specimens for the assays.
Attachment III. Team's Collaborative Clinical Trials (use filename "Clinical Trial Collaborations"). Document the collective team capabilities for collaborating with clinical trials on correlative studies. For example, list ongoing and/or past collaborations with clinical trials, preferably with at least one of the NCI-supported clinical trial networks/consortia listed earlier in this FOA. Provide key details such as correlative study designs and types of assays used, etc. As applicable, the documentation under this attachment may include letters from such collaborating clinical networks documenting the applicants' record of participation.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
The budget should address the following FOA-specific items:
For CIMACs:
- Program Director/Principal Investigator (PD/PI) Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 calendar-months effort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.
- Under Personnel Costs, list all personnel involved and the expertise provided with the anticipated effort levels for the CIMAC operation.
- In the Budget Justification, provide a breakdown of the following two types of efforts:
-
- Effort levels and salary support reflecting the personnel costs portion of the biospecimen analysis costs, study design personnel, statistician effort, bioinformatics, laboratory supervising and technical staff, dedicated project manager(s), etc. (see note on Specimen Analysis Costs below); and
-
- Base effort levels for resource function(i.e., efforts that will be needed regardless of the number and types of specimens processed in any period by the CIMAC). The allowable "fixed" efforts may correspond to salary support for: PD/PI (as instructed above), personnel needed for the resource computational and biostatistical function, a technician effort to regularly maintain instrumentation used for the biospecimen analysis (but only to the extent not covered by other sources), laboratory personnel involved in analytical validation of some assays (if such validation is proposed), personnel involved in monitoring longitudinal performance of assays, oncologists/scientists/pathologists/bioinformaticians/statisticians to provide ongoing advisement for correlative study development and implementation, personnel involved in cross-trial development and analysis pipelines or enhancement of existing pipelines, personnel involved in data curation and QC of data for purposes of correlative or cross-trial analysis, personnel involved in submission of data to NIH data sharing repositories, and dedicated project manager(s) to continually coordinate progress of the CIMAC's activities.
NOTE: Effort levels and salary support must reflect the work described in this FOA, and should indicate which aspects of CIMAC work are covered. Staffing effort not related to the work described in this FOA should not be included. Staffing levels should be justified and allow sufficient funding to remain for assays to be performed on the projected number of samples (see note on Specimen Analysis Costs below).
- Base effort levels for resource function(i.e., efforts that will be needed regardless of the number and types of specimens processed in any period by the CIMAC). The allowable "fixed" efforts may correspond to salary support for: PD/PI (as instructed above), personnel needed for the resource computational and biostatistical function, a technician effort to regularly maintain instrumentation used for the biospecimen analysis (but only to the extent not covered by other sources), laboratory personnel involved in analytical validation of some assays (if such validation is proposed), personnel involved in monitoring longitudinal performance of assays, oncologists/scientists/pathologists/bioinformaticians/statisticians to provide ongoing advisement for correlative study development and implementation, personnel involved in cross-trial development and analysis pipelines or enhancement of existing pipelines, personnel involved in data curation and QC of data for purposes of correlative or cross-trial analysis, personnel involved in submission of data to NIH data sharing repositories, and dedicated project manager(s) to continually coordinate progress of the CIMAC's activities.
- Under "Other Direct Costs", list:
-
- The costs of supplies (e.g., reagents, consumables) and other expenses needed for the biospecimen processing and performance of the assays (see note on Specimen Analysis Costs below).
-
- A modest level of supplies and other fixed expenses unrelated to the number and types of specimens processed in any period by CIMAC. These costs (which should not exceed approximately $60,000 a year) may include, for example, supplies needed for analytical assay validation or new assay harmonization, established assay upgrade (if proposed), minor instrumentation upgrades, replacement of small equipment, repairs, etc. Requests for capital equipment (defined as items above $5,000-unit cost) are not allowed.
- Note on Specimen Analysis Costs and Budget Justification.
-
- All elements of costs related to biospecimen analyses (personnel and non-personnel) must be calculated and budgeted assuming the conduct of comprehensive correlative analyses (i.e., using a panel of several complementary assays for each biospecimen - this usually involves most Tier 1 assays, plus selected Tier 2 or Tier 3 assays depending on the study) in multiple specimen collection timepoints per patient for the projected number of 120 patients per year. This projected yearly number is an estimate; actual number of specimens received and processed by a given CIMAC for analyses may vary. Importantly, depending on the actual number of specimens processed, type of assays, and number of assays performed, the award may be adjusted accordingly. Recommended: Approximately 60% of funding should cover assays, and 40% should cover staffing.
-
- In Budget Justification provide unit costs per assay for each assay type proposed and explain how these unit costs are calculated.
-
- Specialized assays reflecting the CIMAC's unique technical capabilities: Applicants for a CIMAC that will have a capability to conduct a unique assay type not likely to be available from other CIMACs should expect that the Network’s Laboratory Coordinating Committee (LCC) may ask them to perform, if appropriate, such unique type of analysis for specimens coming from clinical trials for which that CIMAC is not the lead CIMAC for the collaboration. If applicable, applicants should include in the Budget Justification their estimate of the number of such assays per year that the entire CIMAC-CIDC Network might need.
- Travel Funds. The budget should also include travel funds for PD(s)/PI(s) and other senior investigators (up to four people) to attend the annual Network meetings.
CIDC Informatics Core:
- Program Director/Principal Investigator (PD/PI) Effort Commitment. Any PD/PI (whether designated as contact or not) must commit a minimum of 1.2 person-months effort per year to the award. This commitment cannot be reduced in later years of the award. Note that this is a minimum effort level that should be increased as appropriate to meet the needs of the work.
- The budget request should account for the efforts of computational biologist(s), bioinformatics scientist(s), clinical informatician(s), and other software engineering personnel to be involved in data curation, data QC, and data collection efforts by the Informatics Core. Staffing should be provided for project management, subject matter experts, and staff support as needed to cover Informatics Core goals and objectives. Staffing efforts should also cover pipeline-related enhancements as needed. The effort levels should be well justified in the context of the FOA needs.
- The budget request may include the costs of additional computational hardware, software, and data storage upgrade costs if necessary to meet the needs of the Informatics Core. However, such upgrade items must be well justified, and their combined costs must not exceed $120,000 in any year of project period. Capital equipment (i.e., with unit cost over $5,000) is not allowed.
- Travel Funds. The budget should include travel funds for PD(s)/PI(s) and other senior investigators (up to three people) to attend the annual Network meetings and for a Technical Lead and/or Project Manager to interface with the CIMAC leads on data/standards requirements. Applicants may also request modest funds for senior Informatics Core personnel for travel associated with interactions with CIMACs.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
For CIMACs:
Specific Aims: Describe the specific aims of the proposed Cancer Immune Monitoring and Analysis Center (CIMAC) and identify the areas of translational research focus.
Research Strategy: Provide an overview of the goals proposed for the CIMAC. Address all the specific aspects indicated below using the sub-sections as defined:
Sub-section (A) Significance and Innovation: In addition to standard items, address all the following specific aspects:
- Highlight new, innovative scientific concepts proposed to assess the biomarker candidates for predicting and monitoring responses and resistance to cancer immunotherapies. Scientific concepts may include deep-profiling approaches, new methods for analyzing data, multi-omic analyses, etc.
- Describe how the CIMAC will support the overall mission of the CIMAC and the Network and explain how the anticipated contributions of the proposed CIMAC to the understanding of the tumor-immune system interface and the mechanisms of drug action can inform individualized approaches for immunotherapy of cancer patients.
- Describe the key technical and bioinformatic capabilities for deep profiling that build upon prior studies to support innovative research for biomarker testing, including any novel approaches and/or methods to understand the interaction of the tumor and immune system.
- Outline the specific aims for the CIMAC explaining how the inclusion of the proposed assays may benefit the studies of biomarkers for immunotherapy response and advance the concept of personalized medicine in cancer immunotherapy.
Sub-section (B) Investigative Team.
- Summarize the major collective strength of the team in the proposed area of scientific and technical expertise.
- Without repeating information from individual bio sketches, explain how the specific expertise of team members (e.g., cancer biology and immunology, pathology, genomics, biomarker experts, assay developers, computational biology, biostatistics, and others) will be used to advance the proposed laboratory translational research program.
- Describe the team experience in research related to clinical trials, especially conducting correlative studies.
- Describe the environments (e.g., academic or other research) of the research team members and how they will support the mission of the proposed CIMAC.
- Describe how a dedicated project manager(s) will coordinate CIMAC activities.
- Describe the critical experience of the PD(s)/PI(s) and the team in coordinating multidisciplinary and multi-institutional programs.
- Describe how the CIMAC envisions collaborations with clinical trial investigators, other CIMACs, and CIDC.
Sub-section (C) Approach. In addition to standard items, address all the following specific aspects:
- Outline how the proposed CIMAC will serve as a resource for immunotherapy clinical trials to provide highly specialized and comprehensive molecular analyses using appropriate clinical biospecimens.
- Provide key information on assays proposed, including the rationale and criteria for prioritization of assay selection for specific types of studies.
- Note any unique approaches, equipment, etc., reflecting the CIMAC's unique technical capabilities that may be of broader interest to various immunotherapy clinical trials but may not be available in other CIMACs.
- Provide a timeline for crucial elements of the CIMAC's operation (e.g., readiness for sharing SOPs for assays, platform availability, etc.) to complete the studies. If a proposed assay still requires analytical validation or standardization across other sites, provide justification and plans to complete such activities.
- Consider updating the CIMAC’s capabilities with emerging technologies and more advanced methods that could benefit biomarker identification.
- Study design and scientific rigor: Under a separate heading "Approach to Study Design and Scientific Rigor", explain how the proposed CIMAC will approach the design of relevant correlative research in collaboration with other CIMACs. The description could be based on prior work or may reflect a generalized proposed workflow, decision tree, steps, and considerations that will be used. Explain how the CIMAC will interrogate the proposed biomarkers to generate results that are meaningful and can inform future immunotherapy clinical trials. A clear rationale should be given for the details of the experimental design and technical methodologies proposed. The description must address statistical considerations and approaches to data analyses. Under this heading, address the general aspects of scientific rigor as well.
Sub-section (D) Computational and Biostatistical Function:
- Outline the organization and function of the biostatistics, bioinformatics, and computational portions of the CIMAC.
- Incorporate the plans for specific computational activities including data analysis and developing algorithms for multi-parametric assays (if appropriate) for correlation with clinical outcome.
- In addition, leverage systems for tracking of specimens and managing projects. Usage of the software(s) such as the required Correlative Sample Management System (CSMS) allowing searches on multiple parameters is required. Each CIMAC should be able to monitor the sample and the results of the analyses via tracking.
For CIDC Informatics Core:
Specific Aims: List the Specific Aims for the proposed CIDC Informatics Core along with key strategic milestones.
Research Strategy: Describe the proposed CIDC Informatics Core using the FOA-specific sub-sections as defined below:
Sub-section A. Overall Vision of CIDC Informatics Core. Explain how the CIDC Informatics Core will facilitate the efforts of the CIMAC-CIDC Network by providing informatics infrastructure and basic project management support. The description should include the following specific aspects:
- Explanation of priorities, feasibility, key milestones, etc., in terms of advancing the overarching goals of the CIMAC-CIDC Network;
- General framework and strategy for coordinating with the NCI-contracted CIDC IT Core, which will provide database infrastructure and data distribution support for the Network;
- Level of readiness and strategies to implement the informatics resources that will be required for the CIDC Informatics Core to properly serve the Network;
- Strategy to engage CIMACs in the implementation of uniform approaches to standardization of molecular profiling and clinical data to facilitate data sharing among CIMACs, as appropriate and consistent with achieving the goals of the program;
- Highlights of any innovative aspects of the proposed CIDC Informatics Core;
- Strategic ways to maximize the potential of the CIDC Informatics Core in advancing the field of immunotherapy (during the award period and beyond).
Sub-Section (B) Scientific and Technical Capabilities:
Address the following specific aspects, emphasizing the collective abilities (without repeating information from individual bio sketches):
- Summarize the major collective strengths of the team and the experiences that will be vital for the proposed Informatics Core;
- Explain the team collective capabilities and expertise in data QC and standardization relevant to immune biomarkers and clinical data; and integration with other databases, as required for multidimensional analysis;
- Illustrate the leadership capability for coordinating complex analyses of immune markers, which will be required for collaboration among the CIMACs biostatistics and computational components;
- If the proposed Informatics Core will involve partnering institutions and/or multiple, geographically spread facilities, explain how the efforts will be coordinated and integrated.
- Without repeating information from Facilities & Other Resources, explain the strengths of your technical capabilities including information technology and bioinformatics hardware, software, and other tools.
Sub-section C. Informatics Infrastructure and Bioinformatics Support Functions of CIDC Informatics Core:Provide details on how the proposed Informatics Core will provide the informatics support, pipeline infrastructure, etc., to implement an efficient data analysis environment serving biomarker studies across CIMACs. Address the following specific items, discussing such aspects as availability of specific infrastructures or functions (or their development/adaptation/updates).
- Plans for establishing/adapting standards for data elements and formats that will be used for data collection protocols for various data types for key tumor- and immune-profiling platforms. Data types to consider should include those used for genomic, phenotypic, or functional characterization of the host immune system and tumor microenvironment. Examples of high-priority assay platforms that are likely to be used by CIMACs can be found earlier in this FOA, under Part 2, Section I. The plans should ensure that the CIDC Informatics Core and the CIDC IT Core will be able to handle data types identified for central pipeline analysis, including, but not limited to, the following:
- Protein profiling based primarily on multiplex assays;
- Transcriptional profiling;
- Functional characterization of immune responses; and
- Genomic characterizations (DNA and RNA sequencing, genotyping, etc.).
- Plans for maintaining or enhancing a data analysis platform and interface that can integrate multiple biomarker modules as well as clinical data, to facilitate multi-dimensional and integrative analysis within and across trials;
- Plan for alignment and integration with data platforms and modules from the NCI-contracted CIDC IT Core;
- Other bioinformatics resources and/or strategies proposed to support the Bioinformatics Functions of the CIDC Informatics Core.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
- The plan should be consistent with the requirement for all CIMACs to share resources, reagents, methods, and SOPs as appropriate, with other awardees across the Network.
- Data Sharing Plan is expected to adhere to the guidelines in the NCI Genomic Data Sharing Policy (https://www.cancer.gov/grants-training/grants-management/nci-policies/genomic-data).
- CIMACs and CIDC must adhere to the terms of the "CIMAC-CIDC Human Material Transfer Agreement (HMTA)" (https://cimac-network.org/about/documents/).
- For research activities using biospecimens from NCI/CTEP clinical trials, Data Sharing Plans must also comply with the following rules:
If the biospecimens are from a clinical trial that was conducted under a binding collaborative agreement with NCI or a pharmaceutical company (for example, with a company that supplied the drug), data sharing may have to await the timelines stipulated in those agreements. All studies supported by NCI (whether NCI IND or other) are subject to the terms of the CTEP Intellectual Property (IP) Option (http://ctep.cancer.gov/industryCollaborations2/guidelines_for_collaboration.htm) as well as the terms of the CTEP Collaborative Agreement under which the study is conducted. Similarly, studies conducted under a NCTN Group or Company IND will also be subject to the terms of the agreement between the Collaborators. Any discoveries from research performed on such specimens will be subject to the CTEP IP Option. Applicants should include information in the Data Sharing Plan that may delay or prevent broad and timely sharing of research data, and provide alternative sharing plans, if feasible. NCTN Group studies are subject to the NCTN/NCORP Data Archive requirements.
NCI program staff members will work with NCI’s Office of Data Sharing (contact: [email protected]) to implement appropriate data sharing policies and guide applicants with Data Sharing Plans aligned with policies to maximize secondary use of NCI-funded research data. Prior to funding, NIH program staff may negotiate modifications of data sharing plans with the applicants and their associated institutions. Any data sharing plans represent a commitment by the institution (and its subcontractors, as applicable) to support and abide by the plan. The final version of any accepted data sharing plans will become a condition of the award.
Additional instructions for CIDC Informatics Core:
- A software dissemination plan, with appropriate timelines, is expected to be included in the application. The plan should address the following:
-
- The software (including bioinformatics tools) should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories; unless they represent commercial products.
- The terms of software availability should permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
- To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
- The terms of software availability should include the ability of researchers to modify the source code and to share modifications with other colleagues.
- To further enhance the potential impact of their software, applicants may consider proposing a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This application for funding may include a plan to incorporate the enhancements into the core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. Accordingly, awardees are encouraged to manage and disseminate their source code through an open revision control and source code management system such as GitHub.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
3. Unique Entity Identifier and System for Award Management (SAM)
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
5. Intergovernmental Review (E.O. 12372)
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile form. 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 unique entity identifier provided on the application is the same identifier 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, and/or non-compliant will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
1. Criteria
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
Each CIMAC will be evaluated based on various metrics, including accomplishments in the previous funding period, conceptual framework and overall scientific leadership and contribution to the Network’s goals beyond the single site’s progress, advancement and impact on the field, innovative assays and analyses offered by the CIMAC, number of samples assayed by the CIMAC, number of collaborations with clinical trials led by the CIMAC, number and quality of publications (abstracts, manuscripts), timely submission of published data to NIH data-sharing repositories, scientific engagement with the Network and its collaborators to enhance the Network progress, and involvement in proposing and performing cross-trial analysis. The CIDC Informatics Core will be evaluated on its ability to keep pace with data submissions, to provide computational methods to support analyses, to QC and evaluate data, to integrate data, and to standardize data.
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 proposed Center address the needs of the research Network in which it will participate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research Network?
Specific for this FOA
For CIMACs:
To what extent does the study have transformative potential to address critical issues for immunotherapy approaches for cancer? What is the likelihood that the proposed research will contribute to the understanding of the tumor-immune system interface and the mechanism of immunotherapy agents that can inform individualized approaches for immunotherapy of cancer patients? How well does the CIMAC address issues related to disseminating research results?
How strongly is the scientific rationale for the proposed studies supported by data generated in the prior award? How well does the proposed CIMAC’s activity contribute to the overall goal of the Network to identify biomarkers for prediction, resistance, and toxicity in response to immunotherapy?
For CIDC Informatics Core:
How well does the proposed Informatics Core address the informatics needs of the CIMAC-CIDC Network? How suitable is the scope of activities proposed for the Informatics Core for supporting data standardization and cross-trial analysis?
How well does the proposed Informatics Core address the bioinformatics needs for effective biomarker studies and data sharing across CIMACs? How sufficient is the bioinformatics infrastructure to support the proposed activities?
Investigator(s)
Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing such research? Do the investigators demonstrate significant experience with coordinating collaborative research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?
Specific for this FOA
For CIMACs:
How sufficient are the backgrounds, multi-disciplinary expertise, and commitments of the PDs/PI(s) and other key persons for the proposed scope of activities and how in line are they with the overarching goals of the CIMAC-CIDC Network? How significant is the team’s record of accomplishments that have advanced the field?
How well-integrated is the investigators' team to work efficiently to meet milestones and timelines for the proposed future studies? How extensive is the involvement of statisticians, bioinformatician(s), clinicians, pathologists, and assay experts to ensure completion of the proposed correlative studies? How appropriate is the team members expertise in study coordination, data management, and organizational leadership for coordinating the activities of the Network?
For CIDC Informatics Core:
How strong is the expertise of key personnel in the areas of information technology and biomedical data acquisition, processing, and integration? How sufficient are these competencies to ensure that the system can serve as a resource to Network investigators? How adequate are levels of effort of such personnel to support the proposed functions of the CIDC Informatics Core?
Innovation
Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network the Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?
Specific for this FOA
For CIMACs:
How well does the design/research plan include innovative elements that enhance its potential to advance scientific knowledge in the field and information dissemination? To what extent do the applicants propose novel concepts to assess the biomarker candidates for predicting and/or monitoring responses to cancer immunotherapies?
How well does the proposed CIMAC employ novel, validated, and standardized approaches and/or methods to understand the interaction of the tumor and immune system? How well does the proposed CIMAC adapt or employ novel bioinformatics methods for data analysis? How well do the proposed projects provide methods for integration of multi-omics data and cross-trial analysis?
For CIDC Informatics Core:
How well does the application propose novel, effective computational aspects and cross-trial analysis concepts or strategies to support the research of the CIMACs?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific for this FOA
For CIMACs:
How well-reasoned and appropriate are the overall strategy, methodology, and analyses to accomplish the specific aims of the project? What study design and biomarker selection strategies facilitate addressing primary and secondary outcome variable(s)/endpoints that will be relevant to the hypothesis being tested?
How appropriate are planned methodologies, analyses, and statistical approaches for the proposed correlative study design? How well does the proposed CIMAC take advantage of multi-disciplinary approaches to advance the understanding of the mechanisms underlying response to immunotherapy? How well will the CIMAC benefit from the past collaborative effort across the Network during the previous funding period?
How well will the investigators apply the tools developed during the prior work? How appropriate are the proposed plans to address challenges in the rigor of prior research supporting the proposed project?
How well-planned are mechanisms for sharing of resources, reagents, methods, and SOPs across the Network? How well-established are the proposed processes for communicating with biorepositories, clinical trials groups, statisticians, and CIDC regarding the corelative studies, specimen requests, clinical data, assay data uploading, and facilitating of data sharing? How well-matched are the timelines with the goals of the CIMAC and the Network?
For CIDC Informatics Core:
How well will the Informatics Core (as proposed) have all the requisite capabilities, infrastructures, resources, etc., to maintain and implement informatics pipelines, support cross-trial analyses, support multi-dimensional analysis, and QC data?
Environment
Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
Specific for this FOA
For CIMACs:
How supportive will the scientific environment be for the CIMAC multi-disciplinary research? Is there evidence of sufficient institutional resources and support for the proposed CIMAC in the applicant institution and, if applicable, other participating institutions? What centralized resource at the institution will be available to the CIMAC investigators? How efficient and well-coordinated will be the activities of the proposed CIMAC (especially if the proposed CIMAC involves multiple institutions ex. subaward)? How adequate is the CIMAC’s project management staffing? How strong is the evidence of ongoing productive interactions among participating investigators/institutions and what is the likelihood that such productive interactions will emerge? How well-articulated are the plans to interact with other CIMACs and CIDC? Will the environment of the proposed CIMAC contribute meaningfully to the capabilities of the CIMAC-CIDC Network as a resource for NCI-supported immunotherapy clinical trials?
For CIDC Informatics Core:
To what extent will the institutional environment in which the CIDC Informatics Core operates to contribute to the success of achieving the CIMAC-CIDC Network goals? How adequate for the proposed CIDC Informatics Core functions are the institutional support, equipment, and other physical resources? How adequate is the Center’s project management staffing? How well will the CIDC Informatics Core benefit from the support of the institutional environment, infrastructure, or personnel?
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.
Study Timeline (for CIMAC): How will the study timeline be adapted, considering different trials accrual status, the anticipated rate of specimen availability, and planned analyses? Is the projected timeline feasible and well justified for the scope of work proposed? Does the project incorporate efficiencies and utilize processes involving the Correlative Sample Management System (CSMS), biorepositories, clinical trials, and clinical data access, etc., to sustain efficiency of generating correlative analyses and to avoid suspension of the award? Are respective processes, challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
Not Applicable
Renewals
For Renewals, the committee will consider the progress made in the last funding period.
Revisions
Not Applicable
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For [programs/projects/networks/consortia/resources] involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Cancer Institute (NCI), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to NCI. 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.
- Accomplishments in the previous funding award period.
- Demonstrated capacity to perform multi-modal study in clinical trials.
- Demonstrated scientific leadership and innovation in accomplishing the goals of the program.
3. Anticipated Announcement and Award Dates
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
1. Award Notices
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Recipients must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
2. Administrative and National Policy Requirements
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identify, sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, 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 recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH's 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 reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibilities for:
- Providing scientific and organizational leadership for the applicant’s CIMAC or CIDC center and the Network;
- Determining the CIMAC's/CIDC's scientific directions, coordinating research approaches and procedures, and overseeing the analyses and data interpretation;
- Overseeing the timely release, publications, and sharing of data according to the approved plans and timelines;
- Reporting the progress at the periodic programmatic conference calls and in annual Network meetings;
- Contributing to the CIMAC-CIDC Network Laboratory Coordinating Committee (LCC) activities;
- Cooperating with NCI Project Scientists, clinical investigators, and statisticians;
- Contributing to the enhancement of the scientific and practical aspects of the Network functions;
- Submitting annual progress reports to NCI;
- Preparing for administrative site visits by NCI staff members;
- Collaborating with other CIMACs, CIDC, and biobanks to advance the Center’s and the Network’s research efforts;
- Facilitating execution of the CIMAC-CIDC Human Material Transfer Agreement (HMTA) for individual projects, as well as any other related agreements. The CIMAC-CIDC HMTA is found at https://cimac-network.org/about/documents/. This HMTA describes the terms of collaboration to which CIMACs, CIDC, and clinical trial groups must agree before specimens or data are transferred for a correlative study using CIMAC-CIDC. The HMTA covers transfers of specimens, assay data, and clinical data to the CIMAC-CIDC Network, stipulating terms for specimen and data use, data exclusivity periods for the correlative analysis team, use of the CTEP IP Option, confidentiality, future data sharing with the general research community, and other terms; and
- Executing agreements for accessing correlative data from approved parties outside the CIMAC-CIDC Network.
The following additional responsibilities will also apply to each Center recipient:
- Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies and the CIMAC-CIDC Human Material Transfer Agreement (HMTA); and
- All participating Centers will be expected to exchange with other members of the CIMAC-CIDC Network, as appropriate and needed, scientific expertise, research reagents, technical procedures, and/or any other resources resulting from the award.
The following staffing requirements also apply for each Center recipient as appropriate for the type of Center:
CIMAC staffing:
- Each CIMAC should assemble multidisciplinary teams of investigators and capacities at the same institution to fulfill the need for highly specialized expertise, including in study design, oncology, immunology, pathology, biostatistics, bioinformatics, and computational biology.
- Exceptional laboratory scientists with defined research scope, technologies, and extensive research expertise to effectively address the research questions are required;
- Data scientists (statisticians and bioinformaticians) with significant effort in data queries and data management are required;
- Staff support for core facilities at the institution that serves the research program can be included; and
- Each CIMAC must also have dedicated staffing of CIMAC Project Manager(s). For each clinical trial collaboration led by a CIMAC, the Project Manager for that CIMAC will:
- Coordinate the correlative studies led by their CIMAC with the clinical trial team and other CIMACs.
- Ensure proposed correlative studies are reviewed by the LCC.
- Ensure the correlative study is incorporated in either the clinical trial protocol document or as a stand-alone proposal for review by NCI.
- Work with NCI and the biorepository to request specimen inventories and specimens for the correlative study and follow up on specimen transfers.
- Use the NCI Correlative Sample Management System (NCI CSMS) for specimen transfers.
- Work with the NCI CIMAC-CIDC Operations Center staff to assist in tracking of correlative study progress.
- Other relevant project management duties to support their CIMAC.
CIDC staffing:
CIDC Informatics Core staffing may include software engineers, data QC staff, bioinformaticians, clinicians, statisticians, scientists, and dedicated project manager(s). The CIDC Informatics Core Project Manager(s) will keep up to date on which CIMAC correlative studies are planned and underway and which assays and clinical data are involved in each study.
In addition, the recipients must ensure that all the activities under the award are consistent with the following rules and regulations:
- Research projects using biospecimens from NCI/CTEP clinical trials are subject to the requirements in NIH policies for data sharing and public access to publications, listed below, and to any applicable requirements of binding collaborative agreements.
- If the biospecimens are from a clinical trial that was conducted under a binding collaborative agreement with NCI or a pharmaceutical company (for example, with a company that supplied the drug), data sharing may have to await the timelines stipulated in those agreements. All NCI supported clinical studies are subject to the terms of the CTEP IP Option (http://ctep.cancer.gov/industryCollaborations2/guidelines_for_collaboration.htm) as well as the terms of the CTEP Collaborative Agreement under which the study is conducted. Similarly, studies conducted under a NCTN Group or Company IND will also be subject to the terms of the agreement between the Collaborators. Any discoveries from research performed on such specimens will be subject to the CTEP IP Option.
- The CIMAC-CIDC Human Material Transfer Agreement (HMTA) , found at https://cimac-network.org/about/documents/.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
An NCI Program Director, acting as a Project Scientist, will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. The NCI Project Scientist will be the main NCI contact for all facets of the scientific interaction with the recipients and will provide advice to the recipient on specific scientific and/or analytic issues in addition to programmatic issues. As needed, additional NCI scientific staff members with relevant expertise may also become substantially involved in the CIMAC-CIDC Network activities as Projects Scientists.
The specific roles of the substantially involved NCI staff members include the following activities:
- Assisting to coordinate collaborative research efforts that involve multiple centers;
- Assisting in avoiding unwarranted duplications of effort across the Network;
- Monitoring the operations of the Centers and making recommendations on overall project directions; this activity may include on-site visits to the Centers;
- Reviewing the progress of individual Centers and specific activities shared among the CIMACs and CIDC Informatics Core;
- Participating in the development and evaluation of cross-Network activities;
- Assisting the Network recipients as a liaison in stimulating their broader interactions with other NCI and NIH programs to disseminate results and outcomes and effectively leverage existing NIH/NCI resources and infrastructures (e.g., databases); and
- Assisting each CIMAC to assess implementation of SOPs and other quality control/quality assurance measures.
- Serving as members of the LCC.
In addition, NCI staff members will be substantially involved in selection of candidate trials for the CIMAC-CIDC Network. In this context, NCI Project Scientists will assist with the following:
- Negotiating with each CIMAC recipient the optimal usage of scientific and technical capabilities for each trial.
- Advising on workload balance across CIMACs and use of assays in each trial.
- Reviewing and approving the correlative studies associated with the selected trials.
- Advising the LCC on prioritization of correlative studies for clinical trials protocols.
Additionally, an NCI Program staff member will be responsible for the normal scientific and programmatic stewardship of the award and will be named as Program Official in the award notice.
Areas of Joint Responsibilities include:
The CIMAC-CIDC Network Laboratory Coordinating Committee (LCC) will serve as the main governing body of the CIMAC-CIDC Network in both a scientific and organizational capacity. The LCC will consist of the following voting members:
- The PD(s)PI(s) of each awarded CIMAC (or a PD/PI and a designated senior investigator) who will collectively have one vote for each CIMAC;
- The PDs/PIs of the CIDC Informatics Core (or a PD/PI and a designated senior investigator) who will collectively have one vote for CIDC; and
- The NCI Project Scientists, who will represent three relevant NCI programs (Cancer Therapy Evaluation Program, Cancer Diagnosis Program, and Center for Biomedical Informatics and Information Technology) and who will collectively have one vote for the NCI.
A chair of the LCC will be elected at the first LCC meeting from the CIMAC-CIDC representatives (the LCC chair should not be an NIH representative.) The LCC chair can alternate between the CIMACs and CIDC PIs and may be elected for a 1-year term or longer. The LCC chair should understand the overall goals of the Network and will be responsible for scientific and governance leadership for the Network.
LCC will have the following primary responsibilities:
- Providing scientific leadership to the Network that encompasses guiding and motivating the teams to accomplish the Network’s goals in a timely manner;
- Establishing the vision for the Network, including fostering innovation in approaches taken and collaboration among the sites;
- At the start of each year, LCC should develop a plan, establish timelines, list priorities, and develop criteria to evaluate the Network’s commitments;
- Overseeing the overall Network scientific program and reviewing its research progress on a continuous basis;
- Evaluating and prioritizing all clinical protocols and correlative studies proposed for inclusion in the CIMAC-CIDC Network portfolio;
- Soliciting and prioritizing novel biomarker assays across the Network;
- Making recommendations for termination of analyses that become unpromising or unproductive;
- Developing the content for the annual LCC/Network meetings; and
- Making other recommendations to enhance Network scientific capacity, as appropriate.
The LCC will meet during monthly meetings and once a year in a face-to-face meeting to review needs/challenges of the Network activities and evaluate progress. (Monthly LCC meetings should be logistically supported by the Project Manager of the CIMAC chairing the LCC.)
LCC may invite additional individuals as non-voting members, as needed, e.g., to serve in an advisory capacity. These additional members may include other NCI and NIH Program Staff members and/or Program Staff members from other Federal agencies or Academic Centers.
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
3. Reporting
When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
For general inquiries regarding the CIMACs portion of this FOA:
Magdalena Thurin, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-5973
Email: [email protected]
Minkyung (Min) Song, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6139
Email: [email protected]
For inquiries regarding the CIDC portion of this FOA:
David Patton
National Cancer Institute (NCI)
Telephone: 240-276-5177
Email: [email protected]
For inquiries regarding the NCI-supported Clinical Trials Networks and Consortia:
Helen Chen, M.D.
National Cancer Institute (NCI)
Telephone: 240-276-6106
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
and Human Services (HHS)
