NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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

In his State of the Union Address on January 20, 2015, President Obama announced his intention to launch the Precision Medicine Initiative (PMI) to bring us closer to curing diseases like cancer and diabetes, and to give all of us access to the personalized information we need to keep ourselves and our families healthier. In order to achieve the President’s ambitious plan, the PMI Cohort Program will build a national research cohort of one million or more U.S. volunteers that will provide the platform for expanding knowledge of precision medicine approaches and that will benefit the nation for many years to come. On September 17, 2015, the Precision Medicine Initiative Working Group of the Advisory Committee to the Director (ACD) presented a detailed design framework for building this national research participant group, which may be accessed at https://www.nih.gov/sites/default/files/research-training/initiatives/pmi/pmi-working-group-report-20150917-2.pdf. The framework was supported by the full ACD, and accepted by the NIH Director.

Applicants to this funding opportunity announcement (FOA) should familiarize themselves with the PMI Working Group report. All partners in the President's PMI are expected to adhere to the PMI privacy and trust principles developed by the White House, which may be accessed at https://www.whitehouse.gov/sites/default/files/microsites/Final%20PMI%20Privacy%20and%20Trust%20Principles.pdf.

The primary objective of the PMI Cohort Program will be to enroll one million or more volunteers into a cohort that broadly reflects the diversity of the U.S. population, and to follow their health and clinical outcomes over time. The PMI Cohort Program will provide an ongoing venue for testing new hypotheses, as well as for determining whether results from smaller cohorts generalize to the broader U.S. population. Through the design and implementation of the PMI Cohort Program, there will be opportunities to explore the interoperability of electronic health records (EHRs) and mobile health (mHealth) technologies, such as sensors, smartphone apps, and wearable devices. The PMI Cohort Program will also provide a transformative framework for exploring the utility of omics technologies and data, and for learning best approaches for facilitating individuals access to their own health data.

Enrollment of PMI Cohort Program participants will be through two distinct approaches: one leveraging the strengths of healthcare provider organizations (HPOs) with existing relationships with potential participants and the other opening enrollment directly to volunteers who are not part of a participating HPO.

In order to be part of the PMI Cohort Program, all volunteers will be asked at entry for consent to join the Cohort Program and to be contacted for future studies. They will be asked to complete a brief survey and to undertake a standard exam, to share their healthcare records, and to be willing to submit biospecimens, including blood, urine, and saliva. The program will also utilize a variety of data collection methods over the life of the Cohort Program including mobile technologies, additional research questionnaires, collection of baseline and longitudinal data from EHRs, and collection and analyses of other biospecimens. These data will make up the core dataset and will be stored in a secure computing environment under rigorous standards to protect individual privacy.

The PMI Cohort Program will provide the data needed to address a wide range of scientific questions. Examples of scientific areas include, but are not limited to:

• Developing quantitative estimates of risk for a range of diseases by integrating environmental exposures, genetic factors, and gene-environment interactions
• Identifying determinants of safety and efficacy for commonly used therapeutics
• Discovering biomarkers that predict risk of developing common diseases
• Using home sensors and mHealth technologies to correlate body measurements and environmental exposures with health outcomes
• Determining the clinical impact of loss-of-function mutations
• Developing new disease classifications and relationships
• Empowering PMI Cohort Program participants with data to improve their own health
• Enrolling PMI Cohort Program participants into clinical trials of targeted therapies.

The PMI Cohort Program is unique with respect to its very large intended sample size of one million or more U.S. volunteers; its principle of extensive study participant engagement in all aspects of the PMI Cohort Program; its focus on utilization of new mobile technologies to facilitate the collection of data on study participants; the potential for coordination across multiple organizational entities; and the many potential users of the data, including researchers, the study participants themselves, and the general public.

The PMI Cohort Program proposes a highly interactive participation model, which is untested for a project of this scale. Participants will be the primary source of research observations; providers of information about their health and experiences; contributors to research questions; mediators of access to their healthcare data; contributors to overall data quality control; donators of data from mobile and wearable devices; and recipients of their own as well as aggregate data and analysis results, according to their preferences.

Participants and their advocates will be central partners in the governance, design, conduct, oversight, dissemination, and evaluation activities of the PMI Cohort Program. The PMI Cohort Program will develop quantitative approaches to assess which strategies most effectively engage participants, particularly those historically underrepresented in biomedical research.

To ensure that maximal scientific benefit is derived from this significant public investment and to respect the investment of participants in sharing their time and information, the NIH Office of the PMI Cohort Program will establish policies and mechanisms that promote maximum accessibility of the data to the broad scientific community including citizen scientists. It is expected that data generated from analyses conducted over the life of the program will further enhance the value of the program and build a living, evolving resource.

The PMI Cohort Program will ensure the responsible return of personal results and information to the individual participants, according to their individual preferences. This expectation will exist for all participants regardless of whether they were enrolled through an HPO or as a direct volunteer.

In its full implementation phase, the PMI Cohort Program will consist of a Consortium of several highly integrated components. The major components are being solicited through this FOA and three other companion FOAs: (1) a central PMI Cohort Program Coordinating Center (CC); (2) healthcare provider organizations (HPOs), (3) a participant technologies center, and (4) a central Biobank.

In addition, in early 2016, NIH plans pilot activities including a direct volunteer pilot program focused on learning what prospective and enrolled participants like, need, and want; developing successful communications methods and content; understanding how to create and implement specialized data technologies, including website, apps, sensors, and clinical data; and building and testing research infrastructure for acquiring and managing biosamples. The output of the pilot phase will be knowledge needed to conduct successful long-term engagement with PMI Cohort Program volunteers, and scientific datasets of relatively limited scope and size. Prototype participant interaction and data acquisition technologies will also be tested in the pilot phase. If successful, these technologies may be transitioned to the full implementation phase Coordinating Center. The pilot phase is expected to start in early 2016 and extend through approximately January 2017, followed by transition to the full implementation phase.

PMI Cohort Program Organization and Governance Structure

The PMI Cohort Program will function as a consortium, with all awardees considered to be members of the Consortium with specific roles in its governance structure (See Terms and Conditions, Section VI.2). For example, the PMI Cohort Program Steering Committee will consist of the Program Directors/Principal Investigators (PDs/PIs) from each of the awards, the NIH Project Scientist(s), representatives of the research participants, and academic and private researchers representing scientists who will use the PMI Cohort Program platform. The Steering Committee will meet shortly after funding to review and further develop a draft protocol and to plan for its rapid implementation.

The Steering Committee will meet, at least monthly, to share information on planning, recruitment progress, data and biospecimen collection, preliminary results, and analyses in progress.

The PMI Cohort Program Consortium will include participant representatives in all aspects of its governance structure. Additional working groups will be established by the PMI Cohort Program Consortium Steering Committee to oversee the development and implementation of Consortium policies and goals.

The PMI Cohort Program will have a single Institutional Review Board (IRB), to the extent permitted by law, constituted to ensure prompt and thoughtful consideration of the evolving protocols in the PMI Cohort Program and the central importance of participants as research partners. The PMI Cohort Program IRB will include significant representation by members of the public and representatives of the participant community.

This FOA solicits applications for the PMI Cohort Program Coordinating Center (CC), which will provide centralized support and infrastructure for the entire PMI Cohort Program. The CC will be the primary administrative, operational management, and data coordinating center for the Cohort Program. The CC will consist of three cores: an Administrative Core; a Data Core; and a Research Support Core. Responsibilities of the CC include:

• overall Consortium communications and program coordination.
• manage Direct Volunteer engagement, enrollment, specimen collection, and oversee scheduling of physical exams for Direct Volunteer participants.
• acquisition, integration, and curation of data.
• creating and hosting data access and analysis tools in a secure computing environment.
• coordination with the biobank of collection of biosamples and laboratory analyses.
• development of mechanisms to provide information about PMI Cohort Program research.
• communicating individual results and aggregated findings to participants.
• establishment of program-wide participant engagement metrics and assessment tools to evaluate the status of inclusion and retention efforts.

Specific functions and tasks of the three cores are listed in the Research Plan section of this FOA. Applications should address each of the required functions and tasks with a description of how each will be accomplished. The lists represent minimum requirements, and applicants are free to propose additional activities that will contribute to successful operations of the PMI Cohort Program.

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

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.

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• 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) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• 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.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants can access 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Joni L. Rutter, PhD
NIH Office of the Director (OD)
Telephone: 301-827-2562
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core	12
Data Core	12
Research SupportCore	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required
• Data Core: required
• Research Support Core: required

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: Comprehensively address the goals of this FOA, and how the work proposed supports the overall Objectives of the PMI Cohort Program as described in Section I. Funding Opportunity Description.

Research Strategy: As part of this section, describe the following elements:

Significance and Innovation

• Specify how the proposed work will contribute to the development of the PMI Cohort Program as a resource to address a wide range of health issues.
• Specify innovative approaches that will be taken in coordinating all aspects of the PMI Cohort Program activities, including how the Coordinating Center will contribute to the transformative nature of the PMI Cohort Program.

Background

• Describe how the Coordinating Center will meet the general PMI Cohort Program objectives as a resource, and identify areas of focus that will contribute to the goal of enrolling one million or more volunteers inclusive of the diversity of the U.S. population, and following their health and clinical outcomes over time.
• Describe the overview of all components (the Coordinating Center as a whole, and the Cores) and their integration.
• Describe previous participation in large-scale research networks particularly those involving longitudinal cohort studies that have gathered electronic data from heterogeneous sources. Note where prior research efforts have included electronic health records, mobile health technologies, participant provided/reported information via phone, mailings, internet, or other sources.
• Describe previous experience and efforts of the CC in the following areas relevant to this FOA, including:
• Research consortium coordination and logistical management
• Research protocol development, implementation and monitoring
• Work with inclusion of children, families and difficult to reach and underserved populations
• Experience with participant engagement activities, surveys, and biosample collection
• Large-scale data coordination and analysis using centralized, federated and hybrid approaches
• Use of secure cloud architectures that enable elastic capacity for data acquisition, storage and analysis
• Experience with data de-identification and assessment of re-identification risks, curation and quality control, access, and security

Milestones and Timeline

Applicants should provide a timeline (Gantt chart) including quarterly (every 3 months) milestones in the first 2 years and bi-yearly (every 6 months) in subsequent years. Milestones must include decision points and include clear and quantitative objective criteria for success.

Applicants should:

• Provide appropriately detailed (quantitative) criteria by which milestone achievement will be assessed.
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
• Identify any impediments that could require modification of the research plan, milestones, or timeline with a discussion of alternative approaches.

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

• All applications, regardless of the amount of direct costs requested for any one year, are required to provide a Data Sharing Plan and Genomic Data Sharing Plan.
• The NIH is committed to the principle of rapid data, model, and software release to the scientific community
• A key feature of the PMI Cohort Program is the involvement of engaged participants. A data sharing policy will be developed by the NIH Office of the PMI Cohort Program that allows for free data exchange according to participant preferences across sites.
• The PMI Cohort Program will ensure the return of personal results to the individual participant and sharing of aggregate findings from its investigation with participants so all stakeholders may have opportunity to benefit from the science.
• The PMI Cohort Program CC will manage the primary process of approving access to and use of biospecimens.
• A committee that includes substantial representation from the participant community will be established to advise the by the NIH Office of the PMI Cohort Program the development and implementation of policies related to the return of aggregate and individual results to participants.
• A standardized and centralized electronic consent protocol should be used with all PMI Cohort Program participants to ensure consistency, minimize organizational burden, and maximize participant recruitment
• The NIH Genomic Data Sharing Policy will apply to any large scale human or non-human genomic data, as well as the use of these data for subsequent research (https://gds.nih.gov/03policy2.html).

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.

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Budget for the Administrative Core should include travel for U2C PD(s)/PI(s), core leaders and other designees to the Steering Committee meetings. In addition, this Core should include a budget for standard physical exams and specimen collections for direct volunteer enrolled participants.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Identify general objectives planned for the Administrative Core along with the main benchmarks that would indicate the accomplishment of these objectives.

Research Strategy: Applicants should describe their overall vision for the organization and operation of the Administrative Core, as well as their proposed approach to implementing the specific functions and tasks listed. As noted above, the PMI Cohort Program will begin with a Pilot Phase involving Direct Volunteers that will start prior to the award of the Coordinating described in this solicitation. Applicants are to indicate how the Administrative Core of the CC will interact with the other Cores, including the coordination of efforts and lines of responsibilities.

Describe how the following functions will be conducted in support of the full implementation phase of the overall Cohort Program:

A. General Functions

• Ensure transition of PMI Cohort Program operations from Direct Volunteer Pilot Phase to full implementation phase
• Oversee PMI Cohort Program enrollment and retention planning and execution via Direct Volunteer and HPO enrollment methods, including the following:
• Monitor and establish reporting metrics for each step in the enrollment process, from inquiry as a potential participant to full cohort member. Enrollment data should be gathered across the Cohort and for specific populations including families, children, difficult to reach and underserved populations.
• Create metrics to monitor ongoing participant engagement and retention, in close coordination with the PTC awardee. These metrics should include stratification by major demographics.
• Describe expectations for baseline attrition rates for different demographics.
• Maintain editorial content of PMI Cohort Program Internet storefront website and print and electronic publications.
• Ensure continuously improving processes for the conduct of the PMI Cohort Program, including enrollment, participant engagement, and research access.
• Provide oversight, with the Steering Committee, on data flow into, and out of, the Consortium, including the following:
• Track progress in data acquisition.
• Develop and implement policies for responsible return of individual and aggregate results to participants.
• Provide expertise on protocols and implementation requirements for all classes of data in the PMI Cohort Program (initially self report measures, baseline health exam, EHR data, biospecimens and mHealth data), and with the Steering Committee establish priorities and protocols for acquisition of new data and data classes.
• Facilitate research, with Steering Committee, using PMI Cohort Program resources, including the following:
• Monitoring utilization by researchers of PMI Cohort Program resources.
• Tracking publications.
• Describe plans for strategic oversight and coordination of effort among the components.
• Describe plans for collaboration and coordination with other parts of the larger PMI Cohort Program Consortium.
• Provide administrative program leadership, including the following:
• Managing Consortium-wide communications and coordination.
• Provide Steering Committee and Working Group logistical support, and liaison to external advisory committee.
• Ensure implementation of privacy and security policies by all components and users.
• Ensure breach notification in cases of loss of data or compromise of data privacy.

B. Direct Volunteer Operations of Administrative Core

• Manage Direct Volunteer recruitment and engagement after Pilot Phase, including the following:
• Overall design and management of ongoing Direct Volunteer operations, including plans for enrollment of families, children, difficult to reach and underserved populations in future years of the Cohort Program.
• Develop and evaluate Direct Volunteers, including the following:
• Schedule, track, and fund biospecimen acquisition for Direct Volunteers.
• Schedule, track, and fund clinical exams for Direct Volunteers.
• Provide toll-free help desk number for Direct Volunteer customer support.

C. HPO-related Operations of Administrative Core

• Provide program leadership for data sharing with HPOs, including the following:
• Create and administer Memoranda of Understanding (MOUs) and Data Use Agreements with participating HPOs.
• Create data submission policies and schedules for HPOs, including determination of which classes of data will be submitted by HPOs to Data Core vs. queried in situ at HPOs by federated approaches.
• Monitor HPO-related accrual, retention, and tracking of timeliness and completeness of HPO data submissions.
• Provide program leadership for participant engagement and interaction with HPOs, including the following:
• Liaison to PMI Cohort Program participant engagement leads in affiliated institutions and consortia.
• Creation and dissemination of co-branded recruitment materials, and ongoing co-branded engagement strategies.

D. Participant Engagement Plan: Key principles of the PMI Cohort Program include: 1) an inclusive philosophy of engagement that enables participation by individuals who have widely varying socioeconomic status, age, geography, health literacy, racial identity, ethnic heritage, personal competence with information technologies, and includes both healthy individuals and those with a wide range of health conditions and disabilities; 2) A philosophy about individual data access that includes immediate feedback to respondents on the data they have submitted as well as archival access to scientific data related to them as an individual that is maintained by the project; 3) An expectation that some research participants will participate in the design process, and serve as testers of the technologies and methods.

Applicants must outline a plan for including participant engagement informed by these principles. The plan should:

• Detail approaches for partnering with research participants and their advocates in the governance, design, conduct, oversight, dissemination, and evaluation activities in the CC.
• Establish standardized participant engagement and recruitment evaluation approaches and data collection for work done at the CC and in the PMI Cohort Program overall.
• Identify and/or develop instruments designed to assess participant engagement, including specific instruments designed for families, children, difficult to reach and underserved populations.
• Develop novel and innovative quantitative approaches to assess impact of effective community engagement on the PMI Cohort Program, including work done in conjunction with the communications and outreach component, and with the PTC.
• Develop and implement, in close collaboration with the PTC, the communications group, and the steering committee, a participant retention program.

It is important to note that the above list is not exhaustive, and applicants should identify and address any other topics or forward-looking approaches they think would be needed for skillful and successful implementation of the PMI Cohort Program CC.

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.

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.

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

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

When preparing your application in ASSIST, use Component Type Data Core.

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

SF424 (R&R) Cover (Data Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Data Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Core)

Specific Aims: Identify general objectives planned for the Data Core along with the main benchmarks that would indicate the accomplishment of these objectives.

Research Strategy

Describe how the following functions will be conducted by the Data Core in support of the full implementation phase of the overall PMI Cohort Program:

A. General Functions

• Design, implement, and maintain the shared scientific data and computational resources for PMI Cohort Program operations that feature elastic computing capability for compute-intensive and data intensive analyses.
• Assume responsibility and management of any data and participant-facing methods and technologies developed during the Direct Volunteer Pilot Phase (prior to award of CC).
• Develop and implement methods to acquire and store participant consent and preferences for specific PMI Cohort Program activities such as self-report measures, clinical data, biospecimens, and return of results.
• Develop and curate a core dataset, including the following:
• Design or adopt existing Common Data Models (CDMs) and Common Data Elements (CDEs) for both Direct Volunteer data acquisition and organizationally mediated data exchange involving HPOs, PTC, and PMI Biobank.
• Develop strategies for mapping of heterogeneous existing data to CDMs.
• Design and/or select ontologies, controlled vocabularies, and knowledge representation standards for data communications.
• Design and implement Natural Language Processing technologies for clinically derived text and documents.
• Integrate self-reported data, geolocation and other environmental data, EHR data, claims data, mobile technology (mHealth) data, genomics and other omics data to create a unified PMI Cohort Program core data resource.
• Implement an authoring system that enables content experts who are not programmers to easily create research questionnaires.
• Develop and implement methods for data linkages, data privacy, and data security, including the following:
• Develop and implement methods for assignment and maintenance of a Research Unique Identifier for each participant.
• Design and implement data privacy methods, including data de-identification and privacy-preserving data linkage.
• Implement approaches to maintaining essential person-identifiable information for purposes such as participant contact, separate from de-identified research data.
• Implement explicit data linkage methods between participant records for family members (including at minimum first and second degree relatives) who consent to being linked.
• Design and implementation of technical and policy safeguards to ensure data security, defined as limiting data access to authorized users for authorized purposes, and maintenance of data integrity.
• Develop and implement methods that enable research using the PMI Cohort Program resource (including citizen scientists), including the following:
• Methods for controlled and open access.
• Technical implementation of a data query and analysis environment using functional specifications developed in collaboration with Administrative and Research Support Cores.
• Technical support for public and private web resources that support CC operations.
• Manage ongoing maintenance of resources, including the following:
• Data quality control and auditing.
• Ongoing monitoring for breaches of data security or privacy.
• Data and communications systems operation and maintenance.
• Data back-up and disaster recovery.

B. Data Core Operations Related to Direct Volunteers

• Develop methods to collect and track data directly supplied by Direct Volunteer participants, including the following:
• Design and implement participant-specific automated communications systems employing SMS text messaging, e-mail, automated phone reminders and similar technologies to support participant engagement.
• Track completeness of self-report data submissions by Direct Volunteer participants.
• Develop software tools to process incoming S4S/Blue Button clinical data for inclusion in core data resource.

C. Data Core Operations Related to HPOs

• Facilitate flow of data from HPO to Data Core, including the following:
• Create data Extract, Transform, and Load (ETL) services for bulk data submitted by HPOs to the PMI Cohort Program core data resource.
• In collaboration with HPO partners, design and implement Applications Programming Interfaces that support peer-to-peer data submission and federated data query by PMI Cohort Program partner organizations.
• Track completeness of self-report data submissions by HPO participants.

Applicants should describe their overall vision for the organization and operation of the Data Core, as well as their proposed approach to implementing the specific tasks listed in items A-C above.

In addition, applicants should address the following points:

• Discuss use of existing data standards to accept data from HPOs and individuals, including best available standards or implementation specifications identified in the Office of the National Coordinator for Health Information Technology Interoperability Standards Advisory (available from https://www.healthit.gov/standards-advisory) as final in regards to standards process maturity and required in regulation (including Medicare and Medicaid EHR Incentive Programs and Health IT Certification Rules).
• Describe potential utilization of current and emerging standards to facilitate data exchange and analysis, such as:
• Standards for capture and representation of family health history such as SNOMED CT and HL7 Version 3 Implementation Guide: Family History/Pedigree for familial relationships.
• HL7 DIGITizE Actions Collaborative draft LOINC specification for pharmacogenomics.
• HL7 Clinical Genomics WG standards including CDA R2 Clinical Genetics Reporting, Clinical Genomics Pedigree Model, HL7 Genetic Testing Results Message (V2), and Clinical Sequencing Domain Analysis Model (DAM).
• SMART on FHIR Genomics standards to support development of clinico-genomic apps to communicate clinical genomics data between EHR systems.
• Open ID Connect, OAuth and UMA for individual authorization and authentication
• More complete authorization standards (e.g., IHE XUA, IUA, etc.) to ensure authorization standards are compatible across disparate networks.
• Global Alliance for Genomics and Health (GA4GH) standards to address computable consent for research.
• Describe approaches for standardization of data for age, race and ethnicity, sexual orientation, sex and gender.
• Describe how data will be curated at the CC including:
• Approaches to applying Natural Language Processing (NLP) to unstructured data derived from clinical documents in order to create structured data, including concept identification, whether concepts are asserted or negated, and confidence levels for NLP-derived data elements.
• Methods to be employed for implementing and revising phenotype algorithms, including central implementation of such algorithms for easy access to users and methods to extract information from structured, unstructured and narrative sources. Include an estimate of the number of new phenotype algorithms that will be generated per year.
• Development of methods for receiving and hosting curated data, and algorithms developed by other researchers outside of the CC. Include sharing of algorithms in open access repositories.
• Approaches to retrieval of medical claims data from CMS, insurers and other sources, to use along with participant EHR data, and other PMI Cohort Program core data elements.
• Design and implement the technical and policy safeguards to ensure Data Security, defined as limiting data access to authorized users for authorized purposes, and maintenance of data integrity, including:
• The overall elements of a Systems Security Plan that addresses physical, technical, and policy elements of mainlining overall security; applicants may wish to consult the National Institute of Standards and Technology Security and Privacy Controls for Federal Information Systems and Organizations at http://csrc.nist.gov/publications/drafts/800-53-rev4/sp800-53-rev4-ipd.pdf for details. Note: it is expected that the research data acquired from the PMI Cohort Program project may be subject to Federal Information System Management Act (FISMA) Moderate security requirements (or their functional equivalents) as outlined at: https://ocio.nih.gov/aboutus/publicinfosecurity/acquisition/Pages/table3.aspx. A FEDRAMP (Federal Risk and Authorization Management Program) compliant cloud-architecture, with protections equivalent to FISMA Moderate, is envisioned as an appropriate environment for data acquisition, storage and analysis but applicants may propose other data management approaches that provide equivalent or better security functionality.
• Approach to design and implement the technical and policy safeguards needed to facilitate Data Privacy, defined as minimizing risks of re-identification of de-identified data.
• Support for help desk questions related to data access, data deposition, and data privacy within the PMI Cohort Program (see Administrative Core)

It is important to note that the above list is not exhaustive, and applicants should identify and address any other topics or forward-looking approaches they think would be needed for skillful and successful implementation of the PMI Cohort Program CC.

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.

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

Planned Enrollment Report (Data Core)

Not Applicable

PHS 398 Cumulative Inclusion Enrollment Report (Data Core)

Not Applicable

When preparing your application in ASSIST, use Component Type Research SupportCore.

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

SF424 (R&R) Cover (Research Support Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Support Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Support Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Support Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Support Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Research Support Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Support Core)

Specific Aims: Identify general objectives planned for the Research Support Core along with the main benchmarks that would indicate the accomplishment of these objectives.

Research Strategy:

Describe how the following functions will be conducted by the Research Support Core in support of the full implementation phase of the overall PMI Cohort Program:

• Provide analytical capabilities within the PMI Cohort Program secure computing environment, including the following:
• Develop and implement phenotype selection algorithms applicable to PMI Cohort Program data.
• Acquire and where necessary, develop de novo analytical software tools for PMI Cohort Program datasets.
• Develop mechanisms for archiving and sharing of analytical algorithms, tools, and results datasets.
• Generate basic descriptive summaries and cross tabulations for PMI Cohort Program project management, and selected aggregate results for return to participants.
• Develop a research support framework, including the following:
• Serve as initial point of contact for users at all levels of sophistication, including citizen scientists, study participants and academic researchers, to design and implement studies using the PMI Cohort Program datasets.
• Collaborate with Data Core in user interface design for researcher-focused information services, such as piloting potential research questions that may be asked of the core dataset. For example, describe how to generate RUID numbers and selected information for all participants with a specific condition or disease.
• Provide help desk function for researchers to assist with use of PMI Cohort Program data and analysis tools, and consult on experimental design via web, email, and phone inquiries.
• With the Steering Committee, plan and implement Cohort-wide laboratory analyses.

Applicants should describe their overall vision for the organization and operation of the Research Support Core, as well as their proposed approach to implementing the specific tasks listed above

As with other cores, the above list is not exhaustive, and applicants should identify and address any other topics or forward looking approaches they think would be needed for skillful and successful implementation of the PMI Cohort Program CC.

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.

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

Planned Enrollment Report (Data Core)

Not Applicable

PHS 398 Cumulative Inclusion Enrollment Report (Data Core)

Not Applicable

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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

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

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

This initiative is not subject to intergovernmental review.

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

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

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). 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 NOT-OD-13-030.

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

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the CC 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 CC proposed).

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

Does the proposed CC address the needs of the research that the PMI Cohort Program will coordinate and enable? Is the scope of activities proposed for the CC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the PMI Cohort Program?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the CC? Do they have appropriate experience and training, and an ongoing record of accomplishments in managing large-scale research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the CC is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; is their leadership, coordination, organization, data management and analysis of large-scale research studies involving multiple data source, appropriate for the CC? Does the applicant have experience overseeing selection and management of subawards, if needed? How extensive is their past participation in collaborative research projects?

Does the application propose effective organizational concepts, management strategies, or data analytics in coordinating the research consortium the CC will serve? Does the application contribute to the PMI Cohort Program goal of promoting creativity in their approach to participant engagement and communication? Do they have novel and effective ways of coordinating, acquiring, curating, and packaging data for research use, as well as allowing access for research?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the PMI Cohort Program? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the PMI Cohort Program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the CC activities? Are the proposed milestones and timeline appropriate? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of human subjects?

If the CC involves human subjects and/or NIH-defined clinical research, are the plans for participant engagement and diversity appropriate to meet the goals of the PMI Cohort Program?

• How well does the proposed administrative structure address the need for a high levels of coordination and efficiency within the CC, and across the larger PMI Cohort Program Consortium?
• Do the milestones and timelines allow for the PMI Cohort Program to stand up quickly and enable easy use of the cohort data by researchers and citizen scientists, to answer research questions?
• Do the proposed research support services address the needs of users at varying levels of sophistication?
• How effectively will the CC enable the transfer and implementation of data and data collection activities from the direct volunteer pilot phase?
• How effectively will the Participant Engagement Plan meet the goals of the PMI Cohort Program, including integrated participant involvement?

Will the institutional environment in which the CC will operate contribute to the probability of success in facilitating the PMI Cohort Program? Are the institutional support, equipment and other physical resources available to the investigators adequate for the CC or Core proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel?

Will the environment provide infrastructure that could allow the project to scale for both increasing numbers of participants, and expanding data collections?

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. The functions of an Administrative Core may not be innovative yet may be essential to advance a field.

Significance

Does the proposed core address the needs of the research that the PMI Cohort Program will coordinate and enable? Is the scope of activities proposed for the Core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the PMI Cohort Program?

Investigator(s)

Are the Core Director(s) well suited to their roles in the Core? Do they have appropriate and complementary experience and training to provide leadership, coordination, and organization, appropriate for the Core? Do they have an ongoing record of accomplishments in managing large-scale research? Do the Core Director(s) demonstrate significant experience with coordinating collaborative clinical research? Do the investigators have experience overseeing selection and management of subawards, if needed? How extensive is their past participation in collaborative research projects?

Innovation

Does the application propose effective organizational concepts, management strategies, or data analytics in coordinating the research consortium the Core will serve? Does the Core contribute to the PMI Cohort Program goal of promoting participant engagement and communication? Do they have novel and effective ways of coordinating, acquiring, curating, and packaging data for research use, as well as allowing access for research?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the PMI Cohort Program? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the PMI Cohort Program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the Core activities? Are the proposed milestones and timeline appropriate? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex?

If the Core involves human subjects and/or NIH-defined clinical research, are the plans for participant engagement and diversity appropriate to meet the goals of the PMI Cohort Program?

• How well does the proposed administrative structure address the need for high levels of coordination and efficiency within the CC, and across the larger PMI Cohort Program Consortium?
• Do the milestones and timelines allow for the Core to stand up quickly and enable easy use of the cohort data by researchers and citizen scientists to answer research questions?
• Do the proposed research support services address the needs of users at varying levels of sophistication? Do the plans proposed adequately address privacy and data security?
• How effectively will the Core enable the transfer and implementation of data and data collection activities from the direct volunteer pilot phase?
• How effectively will the Participant Engagement Plan meet the goals of the PMI Cohort Program program, including integrated participant involvement?

Environment

Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the PMI Cohort Program? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed? Will the Core benefit from unique features of the institutional environment, infrastructure, or personnel?

Will the environment provide infrastructure that could allow the project to scale for both increasing numbers of participants, and expanding data collections?

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.

Significance

Does the proposed Core address the needs of the research that the PMI Cohort Program will coordinate and enable? Is the scope of activities proposed for the core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the PMI Cohort Program?

Investigator(s)

Are the Core Director(s) well suited to their roles in the core? Do they have appropriate experience and training, and an ongoing record of accomplishments in managing large-scale research? Do the Core Director(s) demonstrate significant experience with coordinating collaborative clinical research? Does the Core team have complementary and integrated expertise and skills; is their leadership, coordination, organization, data management and analysis of large-scale research studies involving multiple data sources appropriate? Does the applicant have experience overseeing selection and management of subawards, if needed? How extensive is their past participation in collaborative research projects?

Innovation

Does the application propose effective organizational concepts, management strategies, or data analytics in coordinating the research consortium the Core will serve? Does the Core contribute to the PMI Cohort Program goal of promoting participant engagement and communication? Do they have novel and effective ways of coordinating, acquiring, curating, and packaging data for research use, as well as allowing access for research?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the PMI Cohort Program? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the PMI Cohort Program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the Core activities? Are the proposed milestones and timeline appropriate?

If the Core involves human subjects and/or NIH-defined clinical research, are the plans for participant engagement and diversity appropriate to meet the goals of the PMI Cohort Program?

• How well does the proposed administrative structure address the need for a high levels of coordination and efficiency within the CC, and across the larger PMI Cohort Program Consortium?
• Do the milestones and timelines allow for the PMI Cohort Program to stand up quickly and enable easy use of the cohort data by researchers and citizen scientists to answer research questions?
• Does the application include plans that show adherence to using appropriate standards for data and meta-data?
• Are proposed data management resources and methods qualitatively and quantitatively appropriate for a more than one million person cohort project? Does the application include plans that show adherence to using appropriate standards for data and meta-data?
• How effectively will the Core enable the transfer and implementation of data and data collection activities from the direct volunteer pilot phase?

Do the plans proposed adequately address privacy and data security?

Environment

Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the PMI Cohort Program? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel?

Will the environment provide infrastructure that could allow the project to scale for both increasing numbers of participants, and expanding data collections?

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.

Significance

Does the proposed core address the needs of the research that the PMI Cohort Program will coordinate and enable? Is the scope of activities proposed for the core appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the PMI Cohort Program?

Investigator(s)

Are the Core Director(s) well suited to their roles in the Core? Do they have appropriate experience and training, and an ongoing record of accomplishments in managing large-scale research? Do the Core Director(s) demonstrate significant experience with coordinating collaborative clinical research? Does the Core team have complementary and integrated expertise and skills; is their leadership, coordination, organization, data management and analysis of large-scale research studies involving multiple data sources appropriate? Does the applicant have experience overseeing selection and management of subawards, if needed? How extensive is their past participation in collaborative research projects?

Innovation

Does the application propose effective organizational concepts, management strategies, or data analytics in coordinating the research consortium the Core will serve? Does the application contribute to the PMI Cohort Program goal of promoting participant engagement and communication? Do they have novel and effective ways of coordinating, acquiring, curating, and packaging data for research use, as well as allowing access for research?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the PMI Cohort Program? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the PMI Cohort Program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the Core activities? Are the proposed milestones and timeline appropriate?

If the Core involves human subjects and/or NIH-defined clinical research, are the plans for participant engagement and diversity appropriate to meet the goals of the PMI Cohort Program?

• How well does the proposed administrative structure address the need for a high levels of coordination and efficiency within the CC, and across the larger PMI Cohort Program Consortium?
• Do the milestones and timelines allow for the PMI Cohort Program to stand up quickly and enable easy use of the cohort data by researchers and citizen scientists to answer research questions?
• Does the application include plans that show adherence to using appropriate standards for data and meta-data?
• Are proposed data management resources and methods qualitatively and quantitatively appropriate for a one million or more person cohort project?
• Do the plans proposed adequately address privacy and data security?

Environment

Will the institutional environment in which the Core will operate contribute to the probability of success in facilitating the PMI Cohort Program? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Core proposed? Will the Core benefit from unique features of the institutional environment, infrastructure, or personnel?

Will the environment provide infrastructure that could allow the project to scale for both increasing numbers of participants, and expanding data collections?

As applicable for the CC 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.

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

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

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

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

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.

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

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.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the Center for Scientific Review in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned 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 NIH Council of Councils. 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.

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.

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

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

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

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

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75 and other HHS, PHS, and NIH grant administration policies.

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

Definitions

Director, Precision Medicine Initiative Cohort Program (Director, PMI Cohort Program): The Director of the PMI Cohort Program will direct the PMI Cohort Program office and report directly to the NIH Director; lead planning and decision making about new funding opportunities, collaborations, and funding plans; and coordinate with NIH Institute and Center (IC) leadership and offices, external stakeholders, and other Federal agencies. The Director of the PMI Cohort Program will be responsible for overall stewardship of the PMI Cohort Program.

Steering Committee (SC): The SC will provide coordination of activities of the PMI Cohort Program. The SC will include PDs/PIs from each of the awardees, research participants and their representatives, academic and private researchers who will use the PMI cohort platform and NIH programmatic staff. The SC will establish working groups to oversee the development and implementation of consortium policies. The number of NIH votes may not exceed one third of the total number of votes on the SC. One of the NIH Project Scientist along with the CC PI/PD will be the co-chairs of the SC.

Executive Committee (EC): The EC will be a small group of members of the SC, charged with overseeing development and implementation of the PMI Cohort Program, addressing and finding solutions to challenges and obstacles and making recommendations to the Director of the PMI Cohort Program. The EC will include participant representation. One of the PMI Cohort Program Project Scientists will serve as a voting member. Each full member will have one vote. The number of NIH votes may not exceed one third of the total number of votes on the EC. The PMI Cohort Program Director will serve as a non-voting co-chair with the PI/PD of the CC.

PMI Cohort Program Advisory Panel: The PMI Cohort Program Advisory Panel will be comprised of experts in areas of relevance to the PMI Cohort Program, including representatives of PMI Cohort Program participants. The Panel will meet to provide counsel and feedback to the Director, PMI Cohort Program, and the NIH Director.

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

• Ensuring compliance with overall Consortium practices
• Providing effective leadership and management of this complex program
• Meeting goals, timelines, and milestones
• Conducting all aspects of proposed activities, including determining research approaches, conducting research and implementing the PMI Cohort Program
• Collaborating with other PMI Cohort Program awardees in the development and design of research methods, tools and strategies
• Partnering with research participants and their advocates in the governance, design, conduct, oversight, dissemination, and evaluation activities in their individual site, as well as in the PMI Cohort Program as a whole
• Abiding by policies and rules set up by the Consortium
• Accepting and implementing recommendations made by the SC, EC, PMI Cohort Program Advisory Panel, and PMI Cohort Program Director
• Ensuring participation by their site in the SC, the EC, and working groups as appropriate
• Submitting operations updates in real-time, and as established by the SC that include information such as: enrollment, biospecimen, and exam completion, and other operations updates
• Ensuring that the CC has the information necessary for publishing according to PMI Cohort Program policies and that those results are published in a timely manner
• Sharing data with other PMI Cohort Program sites according to PMI Cohort Program policies, and as appropriate and consistent with participants consent
• Promoting the participatory and cooperative nature of the collaborative research process
• Adhering to physical, technical, and policy safeguards for data that will ensure state-of-the-art security for all PMI Cohort Program data and systems.

Rights to Subject Inventions: Under the Bayh-Dole Act, awardees generally retain the right to elect title to inventions made by its employees as a result of the work performed under the award. The Bayh-Dole Act also allows for a different disposition of such subject inventions, when the agency determines that exceptional circumstances exist such that restriction or elimination of the right to retain title to any subject invention will better promote the policy and objectives of the Act. NIH intends, to make such a Determination of Exceptional Circumstances ( DEC ) for this award, to assure that patents directed to inventions made under this award cannot be used to block access by the research public to this important resource and associated technology.

• A fundamental objective of this cooperative agreement is to ensure that this valuable resource remains available without interruption to the research public for many years to come, even in the event that awardees withdraw or are terminated or otherwise can no longer manage the resource, or when the associated scientific grants, discussed elsewhere in this FOA, are expired. NIH will own the resources generated by the Cohort Program CC, as well as biospecimens and data, and may take exclusive custody and control of them at its reasonable discretion upon termination or expiration of this cooperative agreement.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NIH staff will interact with the PD(s)/PI(s) on a regular basis to monitor progress and negotiate goals. Monitoring may include: regular communication with the PD/PI and his staff, periodic site visits for discussion with the awardees research team, observation of data collection and management techniques, fiscal reviews, and other relevant stewardship matters.

The Director of the PMI Cohort Program will be responsible for the overall stewardship of the PMI Cohort Program, taking into account the advice and inputs of the EC and PMI Cohort Program Advisory Panel described in these Terms and Conditions, and with the concurrence of the NIH Director.

For each grant award there will be an NIH Program Official (PO), a member of NIH staff responsible for the normal scientific and programmatic stewardship of the award. The PO will be named in the award notice. The NIH will also retain its typical stewardship role, including its authority and discretion to withhold or reduce support or take other enforcement action, such as if the awardee fails to achieve its goals or fails to comply with the Terms and Conditions of the Award.

In addition, there will be an NIH Project Scientist assigned to the award. The Project Scientist will have substantial scientific and programmatic involvement during the conduct of this activity. The Project Scientist will have primary responsibility for:

• Serving as a voting member on the SC and its working groups, including the EC, as appropriate and participating in the group process of setting research priorities and deciding optimal approaches and protocol designs
• Serving as a liaison(s) between the awardees and the PMI Cohort Program Advisory Panel, and the appropriate NIH IC National Advisory Councils
• Providing technical assistance, advice, and coordination
• Assisting the SC in developing and drafting operating policies and policies for dealing with recurring situations that require coordinated action.

Areas of Joint Responsibility include:

The awardees, NIH staff and other stakeholders will convene as a SC in person three times a year, and monthly via conference calls. The PMI Cohort Program Coordinating Center PD/PI will co-chair the SC with the Project Scientist(s). The PMI Cohort Program director will participate, but will not have voting rights. The SC will:

• Discuss progress and evaluate project milestones
• Develop recommendations for uniform procedures and policies in the PMI Cohort Program
• Form working groups to oversee the development and implementation of consortium policies
• Coordinate between working groups in order to achieve the operation objectives.

The EC will have weekly conference calls, and will meet in person three times a year, at dates concurrent with the SC meetings. The EC will be responsible for the day-to-day activities as well as higher-level opportunities and obstacles. The EC will work to ensure seamless development and implementation across awardees. The PMI Cohort Program Coordinating Center PD/PI will chair or co-chair the EC. The PMI Cohort Program Director will serve as a non-voting co-chair of the EC.

The PMI Cohort Program Advisory Panel will meet periodically, generally at dates concurrent with the SC in-person meetings, and will be chaired by a member(s) of this independent committee. The PMI Cohort Program Director, PMI Project Scientist(s), and members of the EC or SC may join these meetings at the discretion of the PMI Cohort Program Advisory Panel.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will be: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardees right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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.

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 registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Joni L. Rutter, PhD
NIH Office of the Director (OD)
Telephone: 301-827-2562
Email: [email protected]

Noni Byrnes, PhD
Center for Scientific Review (CSR)
Telephone: 301-435-1023
Email: [email protected]

Teresa Marquette
National Institute of Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-2562
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.