Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Cancer Institute (NCI)

Funding Opportunity Title

Validation of Molecular Diagnostics to Predict Patient Outcomes Using Specimens from Multi-Site Cancer Trials (R21)

Activity Code

R21 Exploratory/Developmental Research Grant Award

Announcement Type

Reissue of PA-08-133

Related Notices

  • June 3, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
  • May 30, 2013 (NOT-OD-13-074) - NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

Funding Opportunity Announcement (FOA) Number

PA-12-014

Companion FOA

PA-12-013, R01 Research Project Grant

Number of Applications

See Section III. 3. Additional Information on Eligibility

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

93.394, 93.395

FOA Purpose

This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), National Institutes of Health (NIH), encourages the submission of Exploratory/Developmental Research Project Grant (R21) applications from institutions and organizations to validate the clinical utility of new molecular diagnostics for determining prognosis or predicting response to therapy or toxicity for cancer. The Cancer Diagnosis Program (CDP) and the Cancer Therapy Evaluation Program (CTEP) at the NCI are cooperatively sponsoring this FOA with the purpose to transition of candidate biomarkers from initial correlative observations into diagnostics that are suitable for use in clinical trials to assess the clinical validity of a marker. This program will support pilot research projects to improve clinical decision-making in the care of cancer patients and as such will support studies that use tumor specimens linked to specific treatment and clinical outcome information. This FOA is not appropriate for molecular diagnostics discovery projects.

Key Dates
Posted Date

November 16, 2011

Open Date (Earliest Submission Date)

January 16, 2012

Letter of Intent Due Date

Not Applicable

Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Standard dates apply, by 5:00 PM local time of applicant organization.

Scientific Merit Review

Standard dates apply

Advisory Council Review

Standard dates apply

Earliest Start Date(s)

Standard dates apply

Expiration Date

January 8, 2015

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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Table of Contents

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

This Funding Opportunity Announcement (FOA), issued by the National Cancer Institute (NCI), National Institutes of Health (NIH), encourages the submission of Exploratory/Developmental Research Project Grant (R21) applications to perform pilot-scale validation of the clinical usefulness of new molecular diagnostics that are becoming critical components for determining prognosis or predicting response to therapy for cancer. Advances in cancer biology and powerful technologies are providing increased opportunities for analyzing aberrations in genes, proteins and molecular profiles and for developing more effective therapeutics and prognostic and predictive markers to inform their use for individual patients. However, prior to clinical laboratory implementation, the technical and analytical performance characteristics (e.g., stability, accuracy and reproducibility) of the assay for the marker need to be established. Secondly, determining clinical utility of a molecular diagnostic i.e., the evidence that the marker separates two subgroups of patients with different outcomes within a large population, requires correlation of laboratory test results with clinical parameters. Therefore, access to clinically-annotated specimens collected from multi-institutional, well-controlled clinical studies is absolutely essential for assessing the clinical usefulness of the test. The ultimate goal of this FOA is to evaluate the clinical utility of analytically validated molecular diagnostic tests to improve clinical decision-making in the care of cancer patients (e.g., to meet criteria for enrollment or to assign a specific treatment arm). This FOA is not appropriate for molecular diagnostics discovery projects.

This FOA will utilize the Exploratory/Developmental Research Grant (R21) award

mechanism, and is suitable for projects where proof-of-principle of the proposed technology or methodology has already been established. This FOA runs in parallel with an FOA of identical scientific scope, PA-12-013, which utilizes the Research Project Grant (R01) mechanism.

Background

Despite a large body of published reports on diagnostic and prognostic factors in cancer patients, the rate of acceptance of new markers to inform treatment decisions for cancer patients has been slow and very few such markers and laboratory assays are used in clinical practice. Prognostic biomarkers are indicators of the natural history of disease and the pathological process and estimation of probability of recurrence. Predictive markers are distinct from prognostic markers in that they provide an estimate of probability of response to therapy. Both types of markers are unlikely to be clinically useful unless their prognostic or therapeutic relevance is established in well-designed validation studies. The steps involved in test validation are meant to answer the key question whether the test is ready for implementation in the clinical laboratory. In order to answer this question the analytical performance characteristics must be established along with the clinical utility of the test.

Examples of Successful Predictive Markers. Recently, several anticancer therapies, including immunotherapy and targeted therapies, have provided alternative treatment options to cancer patients. A signaling pathway inhibitor Vemurafenib, which targets mutated BRAF, has conferred improved overall and progression-free survival in patients with advanced melanoma compared to standard chemotherapy, but only in those patients whose tumors harbor the mutated BRAF. Based on these results, Vemurafenib was approved by the FDA for treatment of patients whose metastatic melanoma carry BRAF V600E mutation, as determined by an FDA-approved test. The introduction of epidermal growth factor receptor (EGFR) inhibitors in the clinic led to the identification of molecular markers, i.e., EGFR activating mutations in patients with non-small-cell lung carcinoma (NSCLC) or gene amplification in patients with colorectal carcinoma, that predict sensitivity to EGFR inhibitors. Crizotinib was also recently FDA-approved to treat a small subset of NSCLC patients who have EML4-ALK fusion gene resulting in activated ALK kinase this drug targets.

Several other genetic alterations (i.e., mutations, fusion genes, insertions/deletions or gene amplifications) within a tumor directly activate an oncogene, e.g., activating mutations in KIT gene in gastrointestinal stromal tumor and ERBB4 gene in cutaneous melanoma, mutations and internal tandem duplication in the FLT3 gene in acute myeloid leukemia, BCR-ABL fusion gene in chronic myelocytic leukemia and HER2/neu gene amplification in breast carcinoma. In these examples, the presence of a specific DNA alteration within the tumor predicts a positive therapeutic response to a particular drug because the drug targets a protein encoded by oncogenic drivers that are critical for tumor growth. Another type of genetic marker predicting response is mutation downstream of the drug’s target. As an example, metastatic colon cancers with mutated KRAS gene are refractory to treatment with EGFR-specific monoclonal antibody therapy. These molecular defects would inform stratification of cancer patients into actionable molecular subtypes who are likely to respond to specific treatment for their improved outcome.

Although these molecular subtypes of cancer patients selected for treatment by the presence of specific molecular marker often experience impressive responses to molecularly targeted therapy, most will suffer from disease progression and recurrence. Therefore, acquired alterations such as new mutations or gene amplification that lead to the development of drug resistance are also critical for molecularly characterizing tumors and to predict drug response.

Principles of Test Validation. Assay validation has both analytic and clinical components. It is essential that analytical performance of the assay is established before the evidence of clinical utility is obtained. Analytical performance characteristics of the assay need to address the following parameters:1) specificity and sensitivity, 2) accuracy i.e., closeness of the test result to the true value, 3) intra- and inter-assay variability, 4) upper and lower limit of detection, 5) cut-off points and 6) reproducibility. Analytical validation process should establish parameters for the assay to correctly classify biologic samples as positive or negative for the marker.

Clinical validation study design and analysis however must address the specific intended clinical use for the assay, such as determining prognosis or predicting response of the particular tumor to generic class of treatments (e.g., endocrine or chemotherapy) or specific agent (e.g., targeted therapy or immunotherapy). Thus, it requires correlation of analytically validated assay with clinical data from for example case-control studies, retrospective data collection or prospective clinical trials. The study should also address how well the marker predicts outcome, i.e., difference of outcomes for patients who are “positive” versus those who are “negative” for the marker. The magnitude of the marker effect to influence outcome or treatment decisions and cut-off points need to be validated to establish clinical utility of the test.

Clinically Annotated Specimen Collections. Availability of specimens with associated clinical annotation is an important consideration for reliably establishing the clinical utility of the prognostic or predictive markers. Specimens collected within multi-site clinical trials are especially suitable for retrospective and prospective analyses of associations between outcomes and molecular characteristics. Archived specimens from a large population of untreated patients should be adequate to estimate recurrence in marker-defined subgroups of patients. Specimens from randomized trials with a survival or progression-free survival endpoints are required to establish the clinical validity of marker for predicting response to specific treatment. Tissue specimens should be available in sufficiently large numbers to permit statistically powered analyses and to ensure that the patients included in the biomarker study are representative of the patients that will be used in clinical testing in the community. Large numbers of archived specimens (i.e., peripheral blood mononuclear cells, marrow, tumor tissue, lymph nodes, plasma/serum) from uniformly treated patients that are associated with carefully annotated demographics, diagnosis, overall and progression-free survivals, and toxicity are available from the NCI sponsored Cancer Centers and multi-institutional research programs and also the NCI Clinical Trials Cooperative Oncology Group Program, an integrated national network of clinical investigators and institutions that conduct phase II and III clinical trials. Archived specimens associated with clinical data can therefore be of great importance for establishing the medical utility of prognostic or predictive biomarkers and offer improved diagnostics for use in cancer patients’ care.

Specific Research Objectives

The objective of this FOA is to promote pilot-scale validation studies for molecular diagnostics to prove their clinical usefulness to improve cancer patients’ outcome. Therefore, the specific purpose of this FOA is to develop assays that will be suitable for validation in clinical trials to assess the clinical validity of a marker and to provide evidence that the use of marker improves outcomes.

Examples of clinical utility of molecular diagnostics include, but are not limited to the following:

Analytically Validated Tests. R21 projects should be designed to determine whether analytically valid assay results are associated with clinical endpoints using retrospective or prospective tissue collections in clinical settings similar to the proposed use of the assay. Analytical validation of the assay involves a systematic evaluation to ensure that the assay meets acceptable standards of performance to be used for analyses of clinical specimens. Applicants should demonstrate that the proposed assay has the sensitivity, specificity and reproducibility adequate to answer the clinical question. Procedures for standardization of an assay should be established and the assay should be completely developed including cut-off points to measure prediction accuracy before the clinical utility validation step.

Validation of Clinical Utility. The aim of clinical validation studies should be to define marker sensitivity and specificity for clinical endpoint determination and to support its clinical utility. Successful responses to this FOA should clearly describe the clinical question that the proposed marker will address and describe how the prognostic or predictive strategy will impact existing approaches on the care of patients.

Preliminary data from the applicants’ own laboratory are not required for R21 exploratory/developmental research projects. However, the project must be based on a strong rationale and the applicant must provide evidence that the proposed diagnostic strategy is promising. If preliminary data from the applicants’ own laboratory are not available, the application must provide current evidence from the literature or from other investigators to substantiate the potential clinical utility of the proposed strategy. The applicant should provide a power analysis to indicate that the number of specimens is statistically significant to assess association between the results of the validated assay and the clinical endpoint within the context of the intended use.

Since R21s are considered pilot projects, the association of assay results with outcome in a given data set might not ensure that the findings can be confirmed in other data sets. However, these projects are useful to establish the feasibility of a marker before proceeding to full validation using two independent specimen cohorts from multi-site trials i.e., training and validation sets of specimens resulting in clinically valid diagnostics. Fully developed validation research projects qualify for the support by the Research Project Grant RO1 mechanism whereas the use of R21 mechanism is recommended for projects that would not satisfy requirements for R01 applications.

Clinical Specimens. The applicant should secure the access to high-quality clinical specimens that are uniformly treated in multi-center trials so that candidate biomarkers identified in discovery research that are important for tumor prognosis or response to therapy are validated and transitioned into diagnostics to be used in subsequent clinical trials. Generally, well-annotated tumor and other biospecimen cohorts collected retrospectively during large multi-institutional treatment trials are especially suitable for these studies. Prospective collections seem more suitable in the context of ongoing projects; thus the investigators need to provide specific information about the arrangements for collection and analysis of patients’ outcome data especially if follow-up will be required beyond the end of the award period.

This FOA is not appropriate for molecular diagnostics discovery projects. The emphasis of this program is on the transition of discovery research into new assays for the clinical management of patients with cancer. Therefore, studies to pursue initial exploration of the relationship between candidate markers and clinical parameters are not appropriate to this FOA. Assays/markers generated through this FOA could be further validated into clinically applicable assays through the support of the parallel PA-12-013 with the same focus using Research Project Grant (R01) mechanism supporting full validation studies.

Section II. Award Information
Funding Instrument

Grant

Application Types Allowed

New
Resubmission
Revision

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

The combined budget for direct costs for the two-year project period may not exceed $275,000. No more than $200,000 may be requested in any single year.

Award Project Period

The maximum project period is two (2) years.

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

Section III. Eligibility Information

1. Eligible Applicants
 
Eligible Organizations

Higher Education Institutions:

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are t eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF 424 (R&R) Application Guide.

More than one PD(s)/PI(s) (i.e., multiple PD(s)/PI(s)), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD(s)/PI(s) model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PD(s)/PI(s) must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a grant with a single PD(s)/PI(s) or multiple PD(s)/PI(s)grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PD(s)/PI(s) will require additional information, as outlined in the instructions below. When considering the multiple PD(s)/PI(s) option, please be aware that the structure and governance of the PD(s)/PI(s) leadership team as well as the knowledge, skills and experience of the individual PD(s)/PI(s) will be factored into the assessment of the overall scientific merit of the application. Multiple PD(s)/PI(s) on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD(s)/PI(s) is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PD(s)/PI(s), please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory and optional.  Please note that some components marked optional in the application package are required for application submission. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Page Limitations

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

PHS 398 Research Plan Component

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

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

Appendix

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

Foreign Organizations

Foreign (non-US) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide.  Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the Central Contractor Registration (CCR). 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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?   

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?   

Approach

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

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?   

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/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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) Genome Wide Association Studies (GWAS).

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), in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council or Board. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

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

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the  NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

Not Applicable.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

Magdalena Thurin, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Room 6035A, MSC 7420
Bethesda, MD 20892-7420 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 496-1591
Fax: (301) 402-7819
E-mail: thurinm@mail.nih.gov

Minkyung (Min) Song, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD)
National Cancer Institute (NCI)
6130 Executive Boulevard, EPN Suite 7009, MSC 7432
Bethesda, MD 20892-7432 (for U.S. Postal Service express or regular mail)
Rockville, MD 20852 (for express/courier delivery)
Telephone: (301) 496-8866
Fax: (301) 480-4663
E-mail: songm@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Shane Woodward
Branch Chief
Office of Grants Administration
National Cancer Institute (NCI)
6120 Executive Boulevard, Suite 243
Bethesda, MD 20852)
Telephone: 301-496-8791
Fax: 301-496-8601
Email: woodwars@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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