Part 1. Overview Information

Key Dates

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.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Purpose

Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) along with other participating Institutes encourages submission of applications proposing to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate cancer risk and related outcomes (e.g., risk prediction or reduction, survival, or response to treatment, etc.). The goal of this initiative is to address key scientific questions relevant to cancer by supporting the analysis of existing clinical, environmental, surveillance, health services, vital statistics, behavioral, lifestyle, genomic, and molecular profiles data. Applicants are encouraged to leverage and perform innovative analyses of the existing data. Applications may include new research aims that are being addressed with existing data, new or advanced methods of analyses, or novel combinations and integration of datasets that allow the exploration of important scientific questions in cancer research.

This NOFO runs in parallel with another NOFO of identical scientific scope, PAR-23-255, which utilizes the Exploratory/Developmental Grant (R21) mechanism.

Background and Rationale

NIH and other research funding organizations support numerous studies that generate a large amount of phenotypical, exposure, behavioral, clinical and genomic data, which continue to be made available to the scientific community. Many of these datasets have not been analyzed to their full potential and further investigation will provide opportunities to answer important research questions at a relatively low cost.

Several NCI programs support population science research that spans the cancer control continuum, e.g., in genomic, epidemiology, surveillance, health services, behavioral science, and cancer survivorship to understand and clarify cancer risk, progression, and outcomes. These studies generate a wealth of individual- and population-level data, including molecular, lifestyle, clinical, demographic, and environmental data. Leveraging these various types of existing data through innovative data modeling and analysis allows new questions to be addressed and helps to advance the field of cancer research. NIH has made it a priority to make data more Findable, Accessible, Interoperable and Reusable (FAIR) to researchers to further biomedical research, through several sharing policies, including the 2015 Genomic Data Sharing (GDS) Policy and the 2023 NIH Policy for Data Management and Sharing. Enhanced data sharing is also a key priority of the NCI, as highlighted by the NCI Cancer Moonshot Public Access and Data Sharing Policy and by the National Cancer Plan goal to maximize data utility by sharing and using available data to achieve rapid progress against cancer. NIH requirements for data sharing in grant proposals, combined with public and private sector initiatives by donors, journals, and foundations, have led to unprecedented amounts of available data for secondary research, which have been successfully utilized to discover novel biomarkers of disease and to find novel uses for existing therapeutics.

The goal of this initiative is to encourage applications from institutions/organizations that propose to conduct innovative secondary data analyses to address knowledge gaps in cancer control using innovative approaches and integration of existing datasets with the ultimate aim of further elucidating cancer risk and related outcomes.  The initiative will stimulate innovative methods and leveraging of existing data sources whose number is expected to continue increasing as more data becomes available through data sharing.  

Specific Research Objectives and Scope of the NOFO 

Analyses that incorporate the vast amount of genomic, clinical, environmental, surveillance, health services, vital statistics, behavioral, and other types of data obtained in recent years, have great potential to illuminate the complex interactions among the environment, behavior, genes, and gene products, to redefine cancer across the continuum, and to lead to novel hypotheses regarding prevention and treatment of cancer.

Applicants are encouraged to leverage existing data and perform innovative analyses of the existing data. Applications may include new aims that are being addressed with existing data, new or advanced methods of analyses, or novel combinations and integration of datasets that allow the exploration of important scientific questions.

Specifically, this NOFO encourages applications that leverage existing data and could include one or more of (but not limited to) the following aspects:

• Link together and analyze through system epidemiology approaches longitudinal multi-level/domain data types, including genomic, other omics, biomarker, environmental, socio-demographic, behavioral, economic, clinical, health care delivery, disease, screening, and vital statistics (e.g., mortality) data to study specific cancer types and/or across cancers and related conditions; data can be obtained from registry, case-control, cohort, and clinical studies and should be appropriately combined and harmonized; linking could be performed by matching entities (e.g., people, direct links of the same respondents) or through external variables (e.g., geocodes, different geographic levels) to assess for multi-level influences (e.g., census tract, county, or state).
• Facilitate utilization of newly developed or updated resources, tools, and guidelines in population-scale cancer research (e.g., human genome reference or other molecular annotations, Informatics tools, or population descriptors guidelines).
• Employ innovative analytic techniques that demonstrate or promote methodological advances in genomic and epidemiologic cancer research and that accelerate population-scale genomics research, e.g., through integration of multiple data types derived from humans and obtained through various single cell and/or bulk tissue molecular techniques (germline and/or somatic genomics, transcriptomics, proteomics, metabolomics) to better understand complex interactions among genes and gene products in the context of cancer.
• Assess cancer-related behavioral health questions and risk factors (e.g., physical performance, anthropometric testing, dietary intake, exercise, physical and social environment, cancer screening, tobacco or alcohol use, sleep hygiene, etc.) through innovative methods, tools, or technology.
• Advance image analysis and extraction of behavioral and environmental information (e.g., street-level digital images, aerial images, medical images, etc.) and accelerate or automate geospatial data cleaning, processing, and analysis to address cancer related questions.
• Develop analytical strategies for cancer surveillance.
• Advance research in healthcare delivery to better understand factors that affect methods of cancer detection (screen versus symptom) and/or inequitable use of primary and secondary prevention strategies.
• Serve cancer survivors and their communities by predicting and assessing patients' diagnosis, trajectory, comorbidities, response to treatment, and symptom management.
• Address questions related to health inequities and disparities and augment implementation and translation of research findings into practice by generating or improving related methods, tools, or technology (e.g., for medical image processing in low resource settings to improve precision risk management, or for reducing machine learning biases from inaccurate data representation of the diversity of society).

This NOFO capitalizes on NCI and NIH past investments in several programs that have supported from basic biological to clinical biomedical research by leveraging the generated molecular, lifestyle, clinical, and environmental data to conduct new investigations in cancer control and population sciences, including cancer healthcare delivery, surveillance, behavior, epidemiology, and population-scale 'omics research. All data analyses must concern research designed to elucidate cancer etiology, incidence, prevalence, natural history, pathophysiology, or related outcomes, including cancer related conditions and disorders.

NCI focus. Applicants should consider the relevance of their proposed analyses to those NCI programs and priorities that can be tackled through the study of existing data. Potential applicants are encouraged to speak with the listed NCI program officials to discuss the relevance of the proposed research topic(s).

NIA focus. NIA welcomes applications that analyze and/or integrate genetic, 'omics, behavioral, social, and other datasets for the contribution of aging as a risk factor for the pathogenesis of adult cancers.&nbsnbsp; Potential applicants are encouraged to communicate with the NIA program officials to discuss their research interests and their relevance to this NOFO.

NIDCR focus. NIDCR supports secondary data analysis and data integration research in the assessment of cancer risk, progression, and outcomes that are relevant to oral, oropharyngeal, and salivary gland cancers. NIDCR will also consider applications that incorporate new statistical or computational methods to help improve the accessibility and/or speed of dissemination of data resources. Potential applicants are encouraged to speak with the listed NIDCR program officials to discuss the relevance of the proposed research topic(s).

NHGRI focus. NHGRI welcomes applications that develop new approaches for elucidating the genetic architecture of human health and disease which are broadly generalizable across diseases, phenotypes, and health outcomes (e.g., risk prediction or reduction, survival, or response to treatment) in addition to cancer. NHGRI is particularly interested in applications to develop novel methods for integrating multiple types of genomic data and other data types. Projects that focus only on tumor genomics will not be appropriate for NHGRI funding. NHGRI encourages leveraging data available through NHGRI’s Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL).

Data Sources

Applicants are encouraged to collaborate with investigators holding publicly as well as non-publicly available data sets, using innovative statistical strategies to harmonize and link methodologically comparable datasets and sharing with the research community the harmonized datasets.

Applicants are encouraged to leverage the large volume of data publicly available to the scientific community. Some examples currently include (but are not limited to) the following:

• Genotype and phenotype datasets deposited in the database of Genotypes and Phenotypes (dbGaP);
• Gene expression profiles deposited in Gene Expression Omnibus (GEO) and high-throughput functional genomics experiments and assays deposited in the ArrayExpress archive;
• DNA/RNA binding and DNA accessibility/methylation experiments deposited in the Encyclopedia of DNA Elements (ENCODE);
• Genotype and RNA-seq data across tissue sites and cell lines deposited in the Genotype-Tissue Expression (GTeX) and Developmental GTeX (dGTeX) projects;
• Proteomic data measured by mass spectrometry in cancer biospecimens from CPTAC and ICPC deposited in the Proteomic Data Commons (PDC);
• Multidimensional maps of genomic changes across cancer types based on paired tumor and normal tissue sets collected from cancer patients deposited in The Cancer Genome Atlas Program (TCGA);
• Sequencing data from human samples deposited in the NCBI Short Read Archive (SRA) and in the NCI Cancer Data Service (CDS);
• Harmonized cancer genomic datasets deposited in the NCI Genomic Data Commons (GDC);
• Imaging information linked to clinical and genomic data across cancer sites available in The Cancer Imaging Archive (TCIA) and the NCI Imaging Data Commons (IDC);
• Data on therapy outcomes from clinical trials and patient registries such as the Pediatric Proton Consortium Registry (PPCR);
• Epidemiological, clinical, and molecular data from established cancer cohorts such as the follow-up of the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial and others in the Cancer Epidemiology Descriptive Cohort Data (CEDCD), as well as from newer cancer cohorts such as the Connect for Cancer Prevention Study;
• The Surveillance, Epidemiology, and End Results (SEER) Program Data & Software, including SEER*Stat, SEER-Medicare, SEER-Medicaid, SEER-CHAPS, and SEER-MHOS;
• Data from the NCI funded research network of US healthcare delivery systems Population-based Research to Optimize the Screening Process (PROSPR) DataShare, the Patterns of Care (POC) initiative, the Social Determinants of Health Dataset, and other healthcare delivery datasets;
• Population-level health survey data such as the National Health Interview Survey (NHIS), the National Health and Nutrition Examination Survey (NHANES), the Behavioral Risk Factor Surveillance System (BRFSS), the Medical Expenditures, Panel Survey (MEPS), the Health Information National Trends Survey (HINTS), the Tobacco Use Supplement to the Current Population Survey (TUS-CPS), TUS-CPS datasets linked to other US Census Bureau research datasets and National Death Index registry (e.g., the Tobacco Longitudinal Mortality Study (TLMS) and sub-linkages);
• Behavioral and social science data in the Inter-university Consortium for Political and Social Research (ICPSR) data repository;
• Genetic and health information from half a million UK participants stored in the UK Biobank;
• Electronic Health Record (EHR) data, genomic data, physical measurements, survey responses and wearable data collected from the All of Us Research Program participants;
• Data available through the Data and Specimen Hub (DASH), including the Environmental influences on Child Health Outcomes (ECHO) data;
• The NIH Common Fund-supported Gabriella Miller Kids First Data Resource Center and the trans-NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Data Coordinating Center Data Hub;
• Genetic, lifestyle, and exposure data from Veterans partners in the Million Veteran Program (MVP);
• Genomic, other 'omic, and phenotype data available through NHGRI’s Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (AnVIL);
• Other datasets, including those listed in the NIH resources page and HHS data hub page.

This mechanism can also be used to retrospectively harmonize measures across disparate datasets and to merge secondary data sets with other data sets to better address important research hypotheses. For example, if allowed by informed consent, genetic datasets could be matched with hospital datasets or vital statistics.

Applicants who plan to utilize data not currently in their possession (originated from another party) should confirm availability of the data and the willingness and permissibility of the original investigators to share the data for the purposes of the secondary analyses (letters of support and/or data access approval are encouraged), in accordance with all applicable rules for the protection of human subjects.

Collaborations and Authorship

Projects developed in response to this NOFO should include complementary and integrated expertise and experience to conduct the proposed data analyses. Any publications resulting from awards funded under this NOFO must include acknowledgment of the source of shared data and any funding sources which supported the initial data collection. If appropriate, applicants should discuss co-authorship plans with original and/or contributing investigator(s) prior to submitting an application.

Data Sharing

Awardees are expected to broadly share the cleaned and harmonized datasets, software, programmed codes, and analysis tools developed for the analysis of the data, when appropriate and consistent with the participant informed consent. Costs for making data publicly available, when appropriate and not already available, may be included in the budget, as long as the archival activities are pertinent to the proposed secondary analyses. Plans for archiving must include adequate dataset documentation and explanation so that it can be used by researchers not associated with the original study.

Other Requirements 

Applications can be related to but must be distinct from the specific aims and methods of the original data collection.

The primary analyzed data can be derived/redefined from existing data but should not be newly collected from study participants nor newly generated from existing biological specimens.

The NOFO will allow up to 10% of the budget towards new data generation for validation of key findings.

Non-Responsive Applications

The following types of studies are outside the scope of this NOFO and applications describing them will be considered non-responsive:

• Studies that propose to collect or generate new data for purposes other than limited validation of key findings;
• Studies that propose to analyze only data obtained from non-human samples;
• Studies that propose to carry out currently ongoing data analysis or to maintain and distribute data sets.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

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

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

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

Federal Government

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (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 eligible to apply.

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

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted 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 Grants.gov registration; 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 their 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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

3. Additional Information on Eligibility

Number of Applications

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 How to Apply - Application Guide except where instructed in this notice of funding opportunity 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 NOFO.

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.

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

R&R or Modular Budget

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

The NOFO  will allow up to 10% of the budget towards new data generation for validation of key findings.

R&R Subaward Budget

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:

Research Strategy: All applications should include an overall strategy that leverages existing clinical, environmental, surveillance, vital statistics, behavioral, lifestyle, genomic, and molecular profiles data. All data analyses must concern research designed to elucidate cancer etiology, incidence, prevalence, natural history, pathophysiology, or related outcomes, from basic biological research to clinical cancer research and cancer control and population sciences, including cancer healthcare delivery, surveillance, behavior, epidemiology, and population-scale 'omics research.

The study design should incorporate at least one of the following features: development or application of novel analytical approaches; exploration and integration of multiple clinical, environmental, surveillance, vital statistics, behavioral, lifestyle, genomic, and molecular data types; incorporation of additional studies or alternative datasets; and/or investigation of phenotypes not studied before using the proposed existing dataset.

Applications should clearly describe the proposed analytical methods, their feasibility, and innovation in comparison to other existing methods and include possible method evaluation and validation plans. Applicants should demonstrate knowledge of the proposed dataset(s) and include details on data source, number of individuals, number and type of samples, type of clinical, environmental, surveillance, vital statistics, behavioral, lifestyle, genomic, and molecular information available and included in the analysis. Applicants should address (including through statistical power calculations) how the proposed dataset(s) are suitable and sufficient to fulfill the research aims and describe approaches to overcome challenges associated with small sample sizes, be these cancer types, cell types, or unique human populations. The proposed analyses should be feasible within the timeline proposed.

Addressing health disparities and improving inclusion is an area of interest across NCI and NIH, and research is needed to better understand the underlying factors contributing to disparities in cancer. While some progress has been made towards improving the inclusion of diverse populations in research studies, several racial, ethnic and other groups remain underrepresented in these studies, with implications regarding the accurate interpretation of findings across populations. While it is expected and understood that the research proposal will be constrained by the limited availability of existing data in groups currently underrepresented in biomedical research, the research plan should nevertheless adequately describe the investigators efforts, successes, and challenges in finding and including in the analysis any relevant available datasets representing these populations, as well as address the translational relevance of findings to these populations and/or specific needs for follow-up studies based on data to become available in the near future.

This NOFO is tailored to cost-effective studies that reutilize existing resources for secondary data analysis, which may lead to findings that warrant experimental, clinical, or other validations. Any proposed new data generation within these applications should be limited (<10% of the budget) to the validation of key findings. If appropriate to the proposed science, applicants should describe how their findings could be further tested or validated in a follow-up independent study.

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. 

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.  
• Awardees are expected to broadly share the cleaned and harmonized datasets, analysis tools and any other software developed for the secondary analysis and integration of the data, when appropriate and consistent with the participant informed consent. Sharing of adequate documentation and explanation is also expected so that data and tools can be used by researchers not associated with the original study.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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.

Foreign Institutions

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

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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact

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

Scored Review Criteria

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

Significance

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

Specific to this NOFO: 

What is the likelihood that the focus of the proposed secondary analyses will contribute significantly to cancer biomedical research? Have the investigators adequately addressed the translational relevance of the potential findings across populations?  

Investigator(s)

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

Innovation

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

Specific to this NOFO:

How novel are the developed or applied analytical approaches? How well are multiple clinical, environmental, surveillance, vital statistics, behavioral, lifestyle, genomic, and molecular data types explored and integrated in the analyses? Which additional studies or alternative datasets are incorporated into the analyses? Are the investigators proposing to analyze phenotypes that have not been studied before using the same existing datasets?  

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this NOFO:

How well described and feasible are the proposed analytical methods? How will novel methods be compared and evaluated against other existing methods? How complete is the provided information on the proposed dataset(s) and data sources in terms of number and characteristics of the individuals/samples to be analyzed? How strong is the likelihood that the proposed dataset(s) are suitable and sufficient to fulfill the research aims? How adequately have the investigators described their efforts, successes, and challenges in finding and including in the analysis any relevant available datasets from underrepresented populations? How effective are the proposed methods to overcome challenges associated with small sample sizes, be these cancer types, cell types, or unique human populations? If the investigators are proposing new data generation, is it limited to the validation of key findings?  If applicable, how feasible are follow-up independent studies proposed to further validate and/or translate findings across populations using data available in the near future? How likely is the proposed project to be completed within the proposed timeline?

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals 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

For Renewals, the committee will consider the progress made in the last funding period.

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.

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

Applications from Foreign Organizations

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 Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

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

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 NOFO. 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:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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:

• Federal-wide Standard Terms and Conditions for Research Grants
• 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 will be required to complete an HHS Assurance of Compliance form (HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. 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 NOFO.

• 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 providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/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 religious nondiscrimination laws and 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.”

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. 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 NOFOs 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.

Section VII. Agency Contacts

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: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Melissa Rotunno, Ph.D.
Division of Cancer Control and Population Sciences (DCCPS), National Cancer Institute (NCI)
Telephone: 240-276-7245
Email: rotunnom@mail.nih.gov

Jiayin (Jerry) Li, M.D., Ph.D.
Division of Cancer Biology (DCB), National Cancer Institute (NCI)
Telephone: 240-276-6210
Email: jiayinli@mail.nih.gov

 Miguel R. Ossandon, Ph.D.
Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI)
Telephone: 240-276-5714
E-mail: ossandom@mail.nih.gov

 Wendy Wang, Ph.D.
Division of Cancer Prevention (DCP), National Cancer Institute (NCI)
Telephone: 240-276-7117
E-mail: wangw@mail.nih.gov

 Raquel Sitcheran, Ph.D.
National Institute on Aging (NIA) 
Telephone: 301-555-1234
Email: raquel.sitcheran@nih.gov

Noffisat O. Oki, Ph.D.
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-402-6778
Email: noffisat.oki@nih.gov

Erin Ramos
NHGRI - NATIONAL HUMAN GENOME RESEARCH INSTITUTE
Phone: 301.480.3288
E-mail: ramoser@mail.nih.gov

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

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov

Jessi Perez
National Institute on Aging (NIA) 
Telephone: 301-402-7739
Email: jessi.perez@nih.gov 

Diana Rutberg, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-594-4798
Email: rutbergd@mail.nih.gov

Deanna L Ingersoll
NHGRI - NATIONAL HUMAN GENOME RESEARCH INSTITUTE
Phone: 301-435-7858
E-mail: deanna.ingersoll@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.

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 2 CFR Part 200.