Required Application Instructions

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

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 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.

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.

The PMI Cohort Program Biobank is responsible for:

• Shipping and receiving biospecimens and providing kits and return mailers for biospecimen collection
• Processing biospecimens using established protocols, to produce high-quality materials for subsequent analysis
• Storing biosamples under optimal conditions to minimize loss, damage, or contamination
• Maintaining facilities that comply with safety and biohazard containment guidelines and regulations, as well as applicable federal, state, and local laws for handling biosamples and current best practices
• Protecting research participant confidentiality
• Providing security and back-up systems and a plan for disaster recovery
• Maintaining high quality, robust, flexible, and secure information systems to allow detailed tracking of sample receipt, processing, storage and distribution, rapid retrieval of samples, and metadata associated with the sample
• Working closely with the CC to use Research Unique Identifiers (RUIDs) for linking the biospecimens with the metadata associated with the samples located at the CC
• Carrying out all the work in a high-quality manner, with rigorous quality control (QC) and quality assurance (QA) programs
• Establishing a succession plan.

Procedures must meet the applicable requirements of the Clinical Laboratory Improvement Amendments (CLIA), using processes consistent with CLIA for all steps of biospecimen handling and laboratory tests. Collection and handling of biospecimens using CLIA-compliant procedures will ensure that specimens will be attributed to the correct participant with a high degree of certainty. This will involve strict procedures at the time of collection and at every step along the path of processing, storage, retrieval, and analysis.

Use of automation is expected for efficient and accurate handling and processing of the anticipated daily volume of specimens, which will include acquisition and maintenance of robotic systems to separate, label, and store biospecimen components, including automated DNA extraction.

This section describes the technologies and services needed for the PMI Cohort Program Biobank in the Pilot Phase and Full Implementation Phase, which also includes Laboratory Services Automation.

Phase 1: Pilot Phase

During the pilot phase, the PMI Cohort Program Biobank will collect and receive saliva samples from at least 10,000 participants. The samples will be received from direct volunteers, individuals who independently enroll in the PMI Cohort Program and are not enrolled through a participating HPO.

In order to achieve the goals of the pilot phase in a timely and efficient manner, the Biobank will need to coordinate its activities closely with other PMI Cohort Program components. The Biobank will be responsible for providing direct volunteers with at-home kits for collection of saliva samples suitable for DNA extraction. The kits will be returned to the Biobank, which should use automated procedures to extract DNA from each saliva sample that is suitable for genotyping with current technologies.

Phase 2(a): Full Implementation Phase

During the full implementation phase, the Biobank will receive a full set of biospecimens from up to one million individuals and, in some cases, providing kits for sample collection and receipt. Biospecimens will be collected at more than 1,000 clinic sites, including sites at HPOs.

The Biobank will need to coordinate with other PMI Cohort Program components to provide clinics and/or participants with kits for blood and urine collection and to receive samples. It is anticipated that up to 60,000 kits will need to be provided each year of the full implementation phase. While the precise configuration of the kits will be determined after award, at this time it is anticipated that kits will include the following 13x100 blood collection tubes: 2 EDTA, one plasma separator, one serum separator, and one ACD, as well as one 13x75 EDTA blood collection tube. In addition, the kit will include collection materials for up to 10mls of urine, along with packing and shipping materials. The selected vial and storage format will be chosen after award in order to facilitate use of automated biobanking equipment in Phase 2(b).

The PMI Cohort Program Biobank is expected to use automated procedures to process the samples to create multiple aliquots of approximately 1 ml of serum, plasma, and urine. In addition, the Biobank will be responsible for extracting DNA from blood samples using automated procedures. The DNA must be suitable for genotyping with current technologies. The aliquoting scheme will be finalized after award, but is anticipated to yield a total of approximately 35, 1 to 2ml cryovials per participant, including aliquots of plasma, serum, urine, red blood cells, DNA, and buffy coats. Applicants are expected to propose an aliquoting scheme.

It is also anticipated that the Biobank will receive bulk shipments of frozen biosamples from PMI Cohort Program-participating facilities, such as HPOs. Thus, the Biobank will be responsible for coordinating with those facilities to ensure that uniform tubes and racks are used for all biosamples.

The PMI Cohort Program Biobank will serve as the archive for all biosamples, storing them under optimal conditions to preserve quality and minimize loss, damage, or contamination, and will be able to retrieve them efficiently for distribution. The Biobank will also utilize a management plan that provides participants with certain protections and rights to revoke consent and direct destruction of specimens or data from future research use.

Phase 2(b): Full Implementation Phase: Laboratory Services Automation

During Phase 2(b), the PMI Cohort Program Biobank will transition to automated storage and retrieval of biosamples by acquiring cost-effective and reliable modular automated equipment to store up to 35 million cryovials in several stages. The Biobank will be responsible for creating specifications for the automated equipment such that minimal sample reformatting will be required.

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 must obtain 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.

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

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

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]

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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

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

The Budget for the Biobank should include travel for Biobank leaders to the Steering Committee meetings.

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

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

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

Specific Aims: Provide the overall goals for the application.

Research Strategy: Organize the Research Strategy in the subsections identified below.

1) Background and Significance

Provide a compelling justification for the resources proposed for development in the context of the PMI Cohort Program and the ultimate potential impact on human health.

2) Preliminary Data

Applicants should present any preliminary studies along with demonstrations of feasibility, pitfalls, and alternative approaches including, but not limited to, the following:

• Providing kits for receipt of biospecimens from a large number of sites carrying out clinical research
• Tracking and receipt of biosamples from a large number of collection sites, including tubes that may not arrive in the PMI Cohort Program Biobank kits
• Processing of blood samples to create multiple aliquots of serum, plasma, buffy coats, red blood cells, and DNA
• Distribution of large numbers of biosamples to a large number of recipients
• Use of automation for sample processing, storage, retrieval, and, if requested, removal/destruction.

3) Approach

Describe the plans, procedures, and processes to establish the PMI Cohort Program Biobank:

Proposed plans should describe how valuable biosamples will be received, processed, stored, and distributed by the PMI Cohort Program Biobank. Plans should address how the proposed procedures and processes will ensure efficient, cost-effective, standardized biobanking, and distribution of verified and high-quality samples that will advance biomedical research. Procedures must meet the applicable requirements of the Clinical Laboratory Improvement Amendments (CLIA), using processes consistent with CLIA for all steps of biospecimen handling and laboratory tests.

Address each of the following key areas:

Receipt of samples Describe the general procedures that will be used to provide to participants or sites with blood and urine sample collection kits that contain collection materials, labels and relevant packaging, and that include marking and shipping systems that are in accordance with standard industry practice, FDA requirements, approved standard operating procedures, city, state, and/or federal regulation. It is expected that samples will be received within 24 hours of collection, 6 days a week. Therefore, the Biobank must describe a plan to coordinate shipping and to receive samples to accommodate this requirement, including on weekends and holidays, if necessary.

The application should also describe planned systems to document the handling and archiving of all shipments, including collection kits and biosamples. In collaboration and coordination with the CC, the Biobank should include notification systems to anticipate shipments and be responsible for recording and monitoring the location of all specimens or collection kits that are being shipped to minimize delay or loss. Describe plans to evaluate received shipments within 4 hours of receipt for obvious damage, breakage, spillage or thaws; record and maintain this information about the samples; and develop notification systems to report delay or loss promptly.

Shipments Describe the approach to establishing arrangements with commercial vendors to provide timely and cost-effective shipping of biosamples among multiple sites, the Biobank, and designated analytic laboratories.

Sample processing Describe plans to process saliva, blood, and urine biospecimens using established protocols to produce high-quality materials, including plasma, serum, red blood cells, buffy coats, and DNA, and other potential biospecimens or cell derivatives for subsequent analysis. The plans should take into account the future use of Biobank automation and use barcoded tubes and racks that conform to the ANSI SLAS 1-2004 (R2012) standard SBS dimensions.

Storage Describe the facilities and plans to store biosamples under optimal conditions to minimize loss, damage, or contamination. The application should include information about the suitability of the facility to perform the proposed work and achieve biohazard containment, complying with all safety guidelines and regulations, as well as federal, state, and local laws.

QA and QC systems Describe the quality control (QC) and quality assurance (QA) programs that will be implemented for all aspects of PMI Cohort Program Biobank operations, including but not limited to:

• Receipt, processing, and storage of biosamples
• Mechanical functioning of freezers and other storage equipment, including alarm and back-up systems
• Preservation of biological properties of biosamples during storage
• Packaging and shipping of material
• Accuracy of data entry and database maintenance in the inventory database
• Timely shipment, receipt, and processing of biosamples.

Security and back-up Describe the proposed security and back-up systems and a plan for disaster recovery following a natural or man-made disaster. The plan should include provisions to maintain an adequate number of empty, functional storage units to serve as back-up units in the event of freezer failures, and to create a back-up facility located at a second site, in case of catastrophic loss. The application should describe the fire, smoke, and mechanical failure alarms, and fire control equipment, as well as the plan to alert key personnel at any time in the event of fire, mechanical failure of one or more freezers, or other emergency.

In addition, describe the proposed emergency back-up generator system that is capable of handling the complete power supply, in the case of electrical power failure, with a minimum of 72 hours of fuel available for the generator(s), and the plans for maintaining the back-up system to ensure proper operation.

Describe plans to prevent access to samples and data by unauthorized individuals.

Information systems - Describe the proposed robust information systems that will allow detailed tracking of sample receipt, processing, storage and distribution, rapid retrieval of samples, and metadata associated with the sample, and that permit efficient, rapid, and flexible reporting. Include information about the ability to rapidly and efficiently download and upload information, to readily transfer information to researchers or other entities submitting or receiving samples, and to efficiently handle sample and data destruction per participant revocation of consent. Describe plans to ensure state-of-the-art security for all electronic databases. Describe how the information systems will interface with each of the participating PMI Cohort Program sites.

Succession plan Describe plans to arrange transfer of samples for storage, or appropriate elimination of samples, as may be directed in writing by the NIH Project Officer.

Additional Application Elements:

Applicants must also address each of the following key elements:

Milestones Specific milestones should be presented that will be met in order to accomplish the aims. Annual milestones must be provided in the context of a study timeline. These milestones will provide clear indicators of a project’s continued success or emergent difficulties. Milestones are goals that include clear and quantitative criteria for success. Milestones should include timely provision of kits; timely receipt, processing of sample submissions, and distribution; accuracy of inventory; quality of processed samples; quality and yield of extracted DNA; and clear communication and data transfer timelines with NIH and other components of the PMI Cohort Program. Achievement of milestones will be evaluated by NIH, and funding of non-competing award years will depend on milestone accomplishment, among other considerations.

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.
• The PMI Cohort Program CC will manage the primary process of approving access to and use of biospecimens.
• 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 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.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by 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 project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

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

Does the proposed Biobank address the needs of the PMI Cohort Program? Are the proposed activities 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 Biobank? Do they have appropriate experience and training and an ongoing record of accomplishments in building and maintaining a large and complex biobank? Do the investigators have significant experience in collaborating effectively with multiple entities? If the Biobank is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; is their leadership approach appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Does the application propose novel approaches and technologies that will provide cutting-edge biospecimen receipt, processing, storage, and retrieval?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate? 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 activities of the Biobank? Are the milestones and timelines appropriate to meet the goals of the PMI Cohort Program? Have the investigators presented adequate plans to privacy and security? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Resources and Data Sharing Plan

The reviewers will comment on the appropriateness and adequacy of the proposed Resources and Data Sharing Plan to meet the goals of the PMI Cohort Program, including providing individuals with their own data and rapid sharing of data with the broad scientific community, as appropriate.

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

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: Sharing Model Organisms.

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 comment on the plans proposed for compliance with CLIA.

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 PMI Cohort Program Advisory 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, IAB, 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. Accordingly, the grantee will have custody and management control of the PMI Cohort Program Biobank and its biospecimens and related data while this cooperative agreement is in effect, but NIH will own the PMI Cohort Program Biobank and its biospecimens and related 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 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, 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 CenterTelephone: 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 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.