Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory Research Opportunity Announcement

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• Overview Information
• Agency Contacts
• Background
• Award Information
• Program Formation and Governance

• Outline of this Opportunity
  1. Requirements - NBSxWGS Collaboratory Initiative
  2. Eligible Organizations
  3. Eligibility Requirements
  4. Multiple Principal Investigators and Partnerships among Applicants’ Institutions
  5. Project Manager/Director (PM/PD) Requirements
  6. Financial and Risk Assessment
  7. Cost Sharing
  8. Developing Applications
  9. Objective Review
  10. Special Award Terms and Information 

Overview Information #overviewinformation

Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Other Transactions Research Opportunity Announcement (OT ROA) is to support the Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory initiative. This research opportunity will be administered by the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), Office of Strategic Coordination (OSC), which administers the NIH Common Fund.
Research Opportunity Title	Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory (OT2)
Activity Code	This funding opportunity will use the Other Transactions Authority (OTA) governed by 42 U.S. Code § 282 (n)(1)(b). OT awards are not grants, cooperative agreements, or contracts and use an OTA, provided by law. Policies and terms for individual OTs may vary between awards. Each award is therefore issued with a specific agreement, which is negotiated with the recipient and may be expanded, modified, partnered, not supported, or later discontinued based on program needs, changing research landscape, performance, and/or availability of funds.
Research Opportunity Announcement (ROA) Number	OTA-25-004
Research Opportunity Purpose	The purpose of this announcement is to invite applications from eligible organizations to support the Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory, a milestone-driven feasibility study. With significant community involvement and input, this initiative will assess the feasibility of developing a collaborative model to allow incorporation of genomic sequencing, as a screening tool for select monogenic diseases that are actionable in early childhood, into the existing state-based U.S. public health newborn screening program that currently screens newborns for a small number of diseases having devastating consequences if not treated promptly.
Key Dates	Release Date of this Research Opportunity Announcement: Wednesday, March 5, 2025 Letters of Intent (LOI) Due Date: Friday, April 4, 2025, local time of applicant organization. LOIs are required to submit a full application. Application Due Date: Wednesday, May 14, 2025, by 5:00 PM local time of applicant organization. Late applications to this ROA will not be accepted. Award Negotiations: to begin on or about Monday, June 16, 2025. Applicants are expected to respond to written inquiries and attend videoconferences or teleconferences as requested.  Earliest Start Date: Friday, August 29, 2025 Informational Webinar: Webinar information will be posted on: https://commonfund.nih.gov/venture/NBSxWGS

Agency Contacts #agencycontacts

NIH encourages inquiries concerning this announcement and welcomes the opportunity to answer questions from potential applicants. 

Scientific Contacts

Dominique Pichard, M.D., M.S. Director, Division of Rare Diseases Research Innovation National Center for Advancing Translational Sciences (NCATS), NIH Email: [email protected]  Matthew Arnegard, Ph.D. Other Transactions Program Official Office of Strategic Coordination (OSC) Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) Office of the Director (OD), NIH Email: [email protected]

Financial/Agreements Officer Contact

Erna Petrich Other Transactions Agreements Officer Office of Strategic Coordination (OSC) Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) Office of the Director (OD), NIH Email: [email protected] (Subject line must include “NBSxWGS”)

Background #background

This initiative is part of the Venture Program, a new effort within the NIH Common Fund to support novel, short-term, bold initiatives that have the potential for significant impact in biomedical and behavioral research. Venture initiatives are innovative and nimble, introducing additional flexibility for the Common Fund to tackle a wider variety of research topics. Venture initiatives embrace scientific risk and have strong potential to accelerate science rapidly. These short-term initiatives will be supported for a maximum of 3 years and will include clearly defined goals and milestones to facilitate rigorous measurement of research progress. Each Venture initiative is expected to produce specific deliverables, which can be new knowledge, methods, technologies, or devices.

The overall purpose of the Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory  (see infographic on the Common Fund NBSxWGS webpage) is to assess the feasibility of a collaborative, multi-state model for newborn screening (NBS) that would use whole genome sequencing as a first-tier screening assay for analysis on a select group of genetic conditions that are actionable in the first year of life. With approximately 70 to 80% of the more than 10,000 known rare diseases stemming from genetic causes, and roughly 70% manifesting in childhood, the early identification of individuals affected by these conditions holds immense potential for altering disease trajectories by initiating interventions before symptoms emerge or early in the disease course when those interventions are most likely to improve health outcomes.

In the U.S., NBS is a public health program carried out by state public health laboratories (PHLs). For most conditions that are screened, the screening is done using biochemical assays carried out on dried blood spots (DBS) collected on filter paper. The Recommended Uniform Screening Panel (RUSP) is an evolving federal list of conditions developed by the Advisory Committee on Heritable Disorders in Newborns and Children that are recommended to be screened by all states to reduce heterogeneity across state screening panels, and currently consists of 38 core conditions. However, each state independently decides which of the diseases on the RUSP to screen for at birth, leading to differences in the conditions for which newborns are screened based on state resources and priorities. An even larger problem is that by focusing immense time and effort on determining which individual diseases should be added to the RUSP, condition by condition, current NBS programs are simply not compatible with rapid advances in emerging technologies such as gene therapy and gene editing, which are promising therapeutic platform approaches of broad applicability to monogenic diseases [1]. Maximizing the public health value of ongoing rapid clinical developments in these transformative treatment platforms requires enhancements to NBS that ensure universal access to the diagnosis of genetic conditions that are not included in the RUSP yet are actionable early in life.

There are multiple pilot projects assessing various aspects of whole genome sequencing (WGS) of newborn babies in the U.S. and in other countries. However, none of these newborn sequencing (NBSeq) programs are based within the setting of broader, multistate U.S. public health NBS programs. In contrast, the NBSxWGS Collaboratory specifically intends to assess the feasibility of incorporating genomic sequencing data from a WGS platform into U.S. NBS programs as a collaborative enterprise involving multiple state PHLs.

The goals of this feasibility study, which differ from the aforementioned NBSeq studies, are to assess the feasibility of incorporating WGS as a platform to potentially be used by all states in their public health NBS programs and to facilitate use of this technology as a screening tool for specified genetic disorders irrespective of the geographic, social, racial, ethnic, and other factors associated with newborns. Whole genome sequencing will be the platform on which the genomic data is obtained, but there will be a limited number of targeted genes that will be analyzed, as determined by an expert panel. To abide by the mission of a public health NBS program, the list of conditions selected for this study will be limited to those genetic conditions that result in serious or life-threatening childhood diseases and for which there are existing interventions or treatments available in the first year of life.

The NBSxWGS Collaboratory will have several components, each of which is relevant to assessing the feasibility as laid out in Section 1 (Requirements) below. An important component of assessing feasibility is to understand the impact of using genomic sequencing on the workflow of state PHLs that have different levels of experience or readiness for this approach. Potential concerns to be addressed include those related to the technical requirements, resources, and staff needed to carry out genomic sequencing; the lack of genetic counselors and geneticists to meet with families that receive positive screen results; and the lack of access to specialists that may be required for diagnostic testing. These are all important and relevant issues to learn about when assessing the feasibility of using WGS in the NBS setting.

Important to the success of this feasibility study is the inclusion of state NBS programs with different levels of research and genomic sequencing readiness. NIH staff will identify a roster of various PHLs from which the awardee will select 5-10 PHLs to partner with through subcontracts. This PHL selection process will be completed during the award negotiation process. There will be a sequencing function, which will be identified and described fully in the application, that will perform the WGS and conduct variant interpretation and calling for all participating states. Another important component of this Collaboratory is community engagement and examination of the ethical, legal, and social implications (ELSI) associated with NBSxWGS, which will be clearly identified and described in the application. There will be a Community Advisory Board (CAB) that will inform decisions about several aspects of the Collaboratory including the informed consent process, selection of genes to screen, return of results process, genomic data sharing and storage, and other relevant topics. NIH anticipates that members of the CAB will be identified and enlisted by the end of the first quarter of project year 1.

This study, if successful, will demonstrate the feasibility of adding WGS as a platform for genomic screening to the lifesaving public health screening available to all babies born in the U.S. regardless of geographic, social, racial, ethnic, or other factors. By using the evidence generated through this study, state NBS programs and the federal partners that support NBS would have the data necessary to assess the implementation of NBSxWGS in a public health setting. 

1. Gene‐Targeted Therapies: Early Diagnosis and Equitable Delivery: American Journal of Medical Genetics Part C: Seminars in Medical Genetics: Vol 193, No 1. https://onlinelibrary.wiley.com/toc/15524876/2023/193/1

Award Information #awardinformation

The NBSxWGS Collaboratory initiative will utilize Other Transaction (OT) awards. In addition to providing budgetary flexibility and accountability that are crucial to multidisciplinary, milestone‐driven projects, the use of OT is critical to allowing NIH staff, in consultation with other Federal partners, to identify the roster of PHLs that the prime recipient can partner with, as well as working with the prime to recruit a varied set of PHLs to maximize assessment of feasibility across different states.

Program Formation and Governance #programformation

Close interactions between the recipient and NIH will be required to maintain this complex program. The NBSxWGS Program governance will rest with the prime recipient in collaboration with the NIH NBSxWGS Working Group, which consists of NIH Program staff from multiple NIH Institutes and Centers as well as Common Fund staff in the Office of the Director. This working group will be primarily responsible for the stewardship of the Collaboratory. The NBSxWGS Working Group is co-chaired by the Director of the National Center for Advancing Translational Sciences (NCATS) and the Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It reports to the Directors of the Office of Strategic Coordination and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.

NIH will provide funds on a milestone‐driven basis assessed at least quarterly, and as agreed upon and included in the Terms and Conditions of Award. Funds may be increased, extended, reallocated, recovered, or terminated in cases where unexpected findings, bottlenecks, or roadblocks may modify plans or prevent completion of the project. Given the rapidly evolving landscape of WGS, the milestones proposed in the application and agreed upon during the negotiation process are likely to evolve and require adjustment as the NBSxWGS Collaboratory initiative moves forward. See Section 10 for special award terms and additional information about program governance.

Objective Review: NIH will convene an appropriate review group to evaluate applications. See the Objective Review section of this opportunity for further details.

Eligibility: See the Eligibility section of this opportunity.

Application Budget: The Common Fund may allocate up to $4,800,000 total (direct costs + Facilities and Administration (F&A)) costs per year for up to three years for the NBSxWGS Collaboratory initiative for one award. This award is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

The application budget should reflect the proposed activities and personnel needs of the project. The OT mechanism allows for significant flexibility to make budget adjustments as needed to meet NIH’s programmatic priorities. Award levels may increase or decrease over time based on funding availability, establishment or termination of sub-awards, recipient performance, and other programmatic priorities. It is anticipated that funds will be allocated on a yearly basis.

Cost sharing is not required but may be proposed. However, including a cost share will not impact an applicant’s chances of selection.

Anticipated Number of Awards: The Common Fund Venture Program NBSxWGS Collaboratory initiative anticipates making one prime award, with subawards to state PHLs and other entities.

Award Project Duration: Project duration is anticipated to be up to three (3) years, subject to program needs, scientific progress, and availability of funds. Research activities and the associated milestones may be shortened or extended as needed within that period. Workplans for research activities and the associated milestones will be negotiated with the NIH staff annually at a minimum.

Authority: Other Transactions awards will be made pursuant to current authorizing legislation, including Section 402(n) of the Public Health Service Act, 42 U.S.C. 282(n), as amended.

Outline of This Opportunity #oppoutline

1. Requirements - NBSxWGS Collaboratory Initiative
2. Eligible Organizations
3. Eligibility Requirements
4. Multiple Principal Investigators and Partnerships among Applicants’ Institutions
5. Project Manager/Director (PM/PD) Requirements
6. Financial and Risk Assessment
7. Cost Sharing
8. Developing Applications
9. Objective Review
10. Special Award Terms and Information

1. Requirements - NBSxWGS Collaboratory Initiative #requirements

The requirements outlined below are those that will be needed to carry out the NBSxWGS feasibility study. These are separated into four functions, as shown schematically in an infographic on the Common Fund NBSxWGS webpage. Each applicant must provide, as appropriate, either concrete or conceptual plans to address all four functions in the Research Strategy section of their application. If awarded, the successful applicant will be required to further develop these proposed plans into detailed, executable plans as part of the first milestone. A series of tasks are listed for each of the four functions. Applicants may provide alternative tasks but must indicate how these would replace the tasks listed below. The expectation is that the NBSxWGS Collaboratory will be built in a modular framework, so that the initial requirements will be scaled as state PHLs are added and as new analytic tools are identified and integrated into the project. Wherever possible, NBSxWGS should leverage work supported by previous/ongoing NBSeq projects. When designing the feasibility study, the use of implementation science frameworks is recommended to help identify facilitators and barriers to state PHL adoption of NBSxWGS across states with varying levels of WGS readiness. Applicants must describe the metrics they will measure to assess NBSxWGS feasibility.

Research involving vertebrate animals is not allowed under this Research Opportunity Announcement.

Function 1 – Project Administration and Coordination (i.e., Central Coordination Core):

The NBSxWGS Collaboratory will require collaboration across the different functions under the leadership of the prime recipient, who will be leading Function 1. Outputs from all functions will require management and dissemination. This will require organizing NBSxWGS meetings, establishing meeting agendas, capturing and distributing meeting minutes, and tracking follow-up action items. Additionally, a document tracking system must be established to maintain project documentation, such as a summary of activities and key decisions that can be used to report NBSxWGS progress to NIH Program leadership.

Function 1 Tasks

1. Project Management and Administration: Applicants must describe their overall approach for project management and administration of the Central Coordination Core. Applicants also must describe how they will meet NIH’s expectation that awardee(s) maintain excellent channels of communication with NIH Program staff involved in oversight of the NBSxWGS Collaboratory initiative, including staff from the NIH Office of Strategic Coordination/Common Fund. These administrative communications will include tracking budget spending, milestone progress or delays, and deliverables for the NBSxWGS Collaboratory, as well as ensuring that progress reports and other required materials are completed and submitted in a timely manner. NIH anticipates a quarterly frequency for the submission of written budget and milestone reports and monthly frequency for teleconference updates with NIH staff and the recipient (or more frequently if stated in the OT Agreement).
2. Coordination Across the Collaboratory: Applicants must describe how the Collaboratory will function in a coordinated manner, including anticipated channels and frequency of communications between the different functions of the Collaboratory. Interactions with the CAB specifically must be addressed as outlined under Function 4, Task iv.
3. Coordination of PHL Activities: As stated above, in order to facilitate the participation of a set of PHLs with varying levels of experience with WGS in this project, NIH staff will utilize their authority under the OTA mechanism to create a roster of more than 10 state labs from which the awardee can select during the award negotiation process, with input from NIH. However, applicants should describe any existing collaborations with NBS programs in PHLs that may be considered during the selection process of the 5-10 PHLs to be included in the feasibility study. Information on the budgetary implications of this design is included under Section 8.5 below.
4. Community of Practice: Applicants must describe how the PHLs will be provided with educational opportunities about incorporation of genomic sequencing into the NBS workflows as well as a platform to share their learnings (i.e., a Community of Practice).
5. Regulatory Approvals: Applicants must describe how they intend to obtain required regulatory approvals, including approval from an Institutional Review Board (IRB), for the different facets of the program (i.e., participant enrollment for sequencing, ELSI research studies) and all regulatory approvals required for whole genome sequencing (Function 3). If applicants already have such approvals, they must be described. Applicants must describe how they will utilize input from the CAB to inform the protocol development, including participant outreach and recruitment, informed consent process, return of results, and genomic data storage.
6. Outreach: Applicants must describe how they will develop and deliver communications to audiences that are external to the NIH to increase awareness of the NBSxWGS Collaboratory initiative and its progress, as well as how they will disseminate the final outcomes from the initiative. The target audiences will include but are not limited to federal agencies; researchers from academia and industry; professional societies and patient advocacy groups; parents and families; and other interested parties, including but not limited those concerned with genomic data privacy and confidentiality and with ensuring accessibility to medical screening options. Presentations at 2-4 conferences and scientific meetings are anticipated. Additional outreach efforts may include social media, newsletters, and workshops (either in-person or virtual). All outreach efforts must be coordinated with the communication platforms of the Common Fund and NIH partners on the NBSxWGS Collaboratory initiative.

Function 2 – Participant Recruitment, Consenting / Return of Results (CONS-ROR):

The current U.S. NBS program operates via an opt-out mechanism: i.e., blood samples (from heel pricks) are collected from all newborns unless the family affirmatively chooses to opt out of the system by declining to allow sample collection. Because NBSxWGS is a research study, informed consent (opt-in) is mandatory. Based on the experience of other NBSeq pilot programs, having a representative of the research project meet with parents to explain the program and request consent results in a substantially higher rate of consented participants than more passive recruitment approaches. With this perspective, as well as the goal of minimizing the burden of this research activity on staff at state PHLs, applicants must address how this consenting process will be done.

Function 2 Tasks

1. Recruitment Plan Development: Describe the outreach to all prospective parents in participating states and the development of appropriate materials to inform and universally recruit prospective parents state-wide.
2. Development of the Informed Consent Process: Applicants must describe the process for obtaining informed consent from the parents or guardians of newborns. The protocol must also address the collection of DNA samples from parents if needed for confirmatory sequencing. The protocol must describe the qualifications and training of the individuals who request consent, and at what time in the prenatal and/or perinatal period this will be done. A description of how the applicant has developed similar forms and protocols in the past (if applicable) is desirable, although not required.
3. CAB Guidance on the Informed Consent Process: Applications must include a description of how CAB input will inform the development of the final informed consent protocol.
4. Communication with State PHLs: The application must also describe how information about individuals that have consented to participate will be communicated to the state PHL in a manner that minimizes the practical burden on state PHL staff, while ensuring accuracy of the information and integrity of the DBS punches that are transferred to the NBSxWGS Collaboratory for sequencing. Applicants must describe how they would interact with several state PHLs with varied levels of experience for their research on incorporating WGS into NBS as described in the Background section above.
5. Return of Confirmed Screen-Positive Results: In those cases where a WGS screen-positive result is confirmed, it will be necessary for staff supported by the NBSxWGS Collaboratory to return results to the family and “hand off” responsibility for the screen-positive infant to the state PHL for referral, work-up, and follow-up as is clinically indicated. The application must describe the qualifications of the individual(s) who will be performing the return of results, and whether the individuals are different from those who obtained consent. The application also must describe any other personnel involved with the project who will assist in this step, such as a genetic counselor or clinical geneticist.
6. Clinical Referral Centralized Resource: The application must describe a resource that guides state PHLs on the appropriate referral and clinical work-up recommendations for the diseases that will be included in the gene list, to be used in instances of screen-positive participants. Applicant must include a description of how clinical confirmation of screen-positive results will be tracked.

Function 3 – Whole Genome Sequencing and Analysis:

An essential and central feature of the NBSxWGS initiative is whole-genome sequencing of DNA extracted from DBS. Each step in the process of WGS, from sample acquisition and processing to data generation on an analytic technology platform, contains multiple variables. Raw sequence data usually undergoes quality control and then is converted to derived data, i.e., a list of variants, for transmission to the Central Coordination Core for assessment of whether the newborn is screen-positive or -negative. To address this workflow requirement, the application must describe in detail the WGS pipeline, as outlined below.

Function 3 Tasks

1. Isolation and Quality Assurance/Quality Control (QA/QC) of Genomic DNA from Dried Blood Spot (DBS) Punches: The first step in NBSxWGS is isolation of genomic DNA from punches obtained from DBS. Applicants must address the minimum number of DBS punches needed to obtain sufficient DNA for WGS and confirmatory testing, the method of purifying DNA from DBS, and quantitative criteria for assessing whether a sample is of sufficient quality and quantity for WGS.
2. QA/QC of Raw Sequence Data: Describe the procedure for assessing the quality of WGS data, as well as any filtering protocols to ensure that only high-quality sequence data are used for variant calling.
3. Variant Calling: For the Collaboratory, it is anticipated that only pathogenic and likely pathogenic variants in the designated gene list will be considered. Describe the analytic package for variant calling, including quantitative cutoffs, and the reference genome(s) used as comparator(s) to assess variants. Applications must also describe how they will address the interpretation of variants obtained from newborns of different racial and ethnic groups.
4. Molecular confirmation of screen-positive results: Applications must address the protocol for confirming screen-positive results from WGS using an orthogonal sequencing method (e.g. Sanger sequencing in a CLIA-approved laboratory).
5. Addressing Regulatory Requirements: Applications must address whether all aspects of the WGS pipeline meet all regulatory requirements for returning clinically actionable information to participants. Applications must describe if they have already addressed all the required regulatory requirements, or if not, how they plan to do so in the first year of the study as well as the anticipated timeline for approvals. Regulatory requirements may need to be tailored or modified to address the needs of the selected PHLs during the course of the project.
6. Determination of the Target Gene List: The initial list of target genes to be screened by the NBSxWGS Collaboratory must be limited to genes for which genetic variants are known to cause monogenic disease with early childhood onset and for which interventions or treatments are available. Applicants must describe the process by which they will determine the list of target genes for this project. Applicants also must describe how input from the CAB and other relevant parties will guide their determination of the target gene list and its optimization as the study progresses.
7. Handling and Storage of Genomic Data: Describe the process for storage of the whole-genome sequence data, including but not limited to length of time for storage and potential for re-interrogation if new genes are added to the gene list. Include how the CAB will be involved in establishing these processes. Data security encompasses confidentiality, data integrity, and availability. Confidentiality includes managing data access to maintain data security and making data accessible to authorized users only for authorized purposes. Data security protection and proper stewardship of controlled access data and other sensitive information stored and distributed are of the utmost importance. The NIH security best practices and provisions must be implemented to protect the privacy and confidentiality of research participants and prevent unauthorized access to data. Investigators are expected to develop policies and procedures for notifying NIH and managing and mediating any loss of data or compromise of data confidentiality.
8. Information Security: The awardee will be responsible for the information security of the data generated by the NBSxWGS Collaboratory. Specifically, the awardee-hosted information system must be compliant with NIST SP 800-53 as stated in NOT-OD-24-157.

Function 4 – ELSI and CAB Function:

To address the multifaceted ELSI considerations raised by this initiative, an embedded ELSI study of the applicant’s design is required that will examine the impact of NBSxWGS on newborns and families, state NBS programs, and/or public perceptions of NBS. Given the sensitivity around data collected on newborns and privacy concerns that have been raised as part of NBS programs in the U.S., a key feature of NBSxWGS is incorporating the perspectives of the CAB in multiple aspects of the initiative, including data sharing. To ensure the appropriate expertise and experience related to NBSxWGS are considered, the CAB will provide guidance on the NBSxWGS Collaboratory throughout the three-year initiative. The perspectives and lived experiences represented on the CAB should include but are not limited to those of birth parents, parents and guardians of newborns, family members, advocates, community leaders, healthcare providers, geneticists and genetic counselors, newborn screening professionals, bioethicists, and data privacy experts, in addition to any other relevant parties that the NIH Program staff and OT awardee deem to be necessary. Topics and activities for which the CAB is expected to provide guidance and advice include but are not limited to:   

• Acceptability of the study design by participants
• Participant recruitment
• Informed consent process
• Conditions listed on the expert panel-generated target disease/gene list
• Protocol for re-evaluating and revising the target gene list
• Protocol for return of results to study participants, including acceptability of confirmatory testing and reanalysis of samples if the target gene list is revised
• Genomic data sharing considerations, such as whether to share WGS data with the broader scientific community after the study ends
• Safeguarding the privacy of genomic information
• Messaging and communication strategies
• Outreach channels for reaching parents and guardians in each participating state

Function 4 Tasks

1. CAB Composition and Member Recruitment: Applicants must describe the composition of the CAB in terms of the perspectives to be represented; how members will be recruited to serve on the CAB; duration of their service; and how CAB members will be replaced if necessary. Applicants must explain other perspectives, beyond the recommended perspectives listed above, that may be needed for the CAB to be effective. Each CAB member appointment requires the approval of the NIH NBSxWGS Working Group.
2. Relevant Expertise and Experience of the CAB: The awardee and project team must ensure that the CAB is composed of individuals of relevant expertise and experience, as detailed in the first paragraph under Function 4 (above).
3. Organization and Summary of CAB Meetings: Applicants must describe the expected frequency of the CAB meetings. The awardee will be responsible for preparing meeting minutes (i.e., summaries) for every CAB meeting, storing them in a document tracking system, and making them available for review by NIH Program staff and other members of the Collaboratory.
4. Communication with the Central Coordination Core: Communication and collaboration between the Central Coordination Core (see Function 1, Task iv) and the CAB are crucial to guide the design and/or execution of several key components and activities of the NBSxWGS Collaboratory. Applicants must provide a Communication and Collaboration Plan that details lines of communication among the CAB, NIH Program staff, and the Central Coordination Core, including and in addition to the regular CAB meetings. The Communication and Collaboration Plan must explain how key parties will communicate with each other, jointly make scientific and managerial decisions, and reach consensus regarding the NBSxWGS Collaboratory. The Communication and Collaboration Plan must also propose procedures for resolving conflicts when they arise during the collaborative decision-making process.
5. Design and Conduct an Embedded ELSI Research Study: Applicants must describe an embedded ELSI research study that aims to examine the impact of NBSxWGS on newborns and families, as well as on the state public health NBS programs. Example topics that applicants could focus on in their embedded ELSI research study include but are not limited to: the benefits and harms of the simultaneous addition of many new conditions to NBS; the reasons why parents and guardians of newborns decline to participate in NBSxWGS; the cost or resource allocation implications for adding a WGS component into state PHL NBS programs; or the impact of NBSxWGS on public/parental trust in NBS and public health. NIH anticipates that a final report for the overall project will be required to summarize findings of this embedded ELSI study, among several other final report components (see Section 10.4, Reporting and Project Meetings), subject to the OTA negotiation process. Accordingly, the embedded ELSI study should be completed in time for the potential inclusion of its conclusions in the final project report.

Data Management and Sharing

NIH promotes the responsible sharing of scientific data consistent with protecting research participant privacy. As outlined in NOT-OD-22-213 (Supplemental Information to the NIH Policy for Data Management and Sharing: Protecting Privacy When Sharing Human Research Participant Data), respect for and protection of participant privacy is the foundation of the biomedical and behavioral research enterprise. NIH and the institutions it funds must protect the privacy and confidentiality of every participant as described in informed consent and in line with all applicable laws, policies, and regulations. There may be justifiable limitations to sharing scientific data under the DMS Policy. The DMS Policy outlines factors that might limit sharing, including when sharing would compromise the privacy or safety of participants and when limitations are explicitly described in informed consent documents. A variety of federal, Tribal, state, and local laws impose obligations on the disclosure and use of scientific data from research (including HIPAA and the Common Rule, as well as state laws that may prohibit disclosure of certain types of information). Researchers and their institutions should understand the applicability of relevant laws, regulations, and policies on their research.

Applicants are required to submit a draft Data Management and Sharing Plan (NOT-OD-21-013) with their application that outlines and justifies any potential limitations needed to protect the privacy and confidentiality of newborn participants, with the understanding that the final Data Management and Sharing Plan will be developed in consultation with the CAB and the NIH NBSxWGS Working Group. For any NBSxWGS Initiative data that are shared, use of relevant NIH-supported data repositories (e.g., database of Genotypes and Phenotypes [dbGaP], ClinVar) and synergies with other NIH-supported studies and resources (e.g., Gabriella Miller Kids First Pediatric Research Program, Clinical Genome Resource [ClinGen]) should be maximized to the extent possible according to the final Data Management and Sharing Plan.

2. Eligible Organizations #eligible

Non-domestic (non-U.S.) Entities (Foreign applicants) are not eligible to apply.

Non-domestic components of domestic organizations are not eligible.

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

Any public or private non-domestic entity is ineligible to apply for this program as a primary applicant. Additionally, any non-domestic components of U.S. Organizations are ineligible to apply for this program as a primary applicant. Public or private non-domestic entities and non-domestic components of U.S. Organizations are eligible to be listed as sub-contractors/recipients, so long as they are not excluded from applying for Federal programs throughout the U.S. Government (unless otherwise noted) and from receiving certain types of Federal financial and nonfinancial assistance and benefits.

Letters of Intent (LOIs), due by the “Letters of Intent Due Date” shown at the top of this notice, are required.

The following entities are eligible to apply under this ROA:

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)
• Faith-based or Community-based Organizations
• Regional Organizations

For-Profit Organizations

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

Governments   

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• American Indian/Native American Tribal Governments (Federally Recognized)
• American Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government having statutory authority to receive funding beyond their congressional appropriation.
• U.S. Territory or Possession

Other

• Independent School Districts
• Native American Tribal Organizations (other than Federally recognized tribal governments)

Applications that are submitted by or involve federal agencies other than NIH must include the citation of the agency's statutory authority to receive funding beyond their congressional appropriation.

NIH Intramural Research Program (IRP) investigators are not eligible to apply as the prime recipient agency Principal Investigator but may collaborate with extramural investigators on the project as co-Investigators, collaborators, or consultants if the IRP investigator(s) have expertise that could contribute to the goals of the initiative. Applications that include IRP investigators must include a signed letter from their Scientific Director that describes the intramural aim(s), the staff time in person months for the IRP investigator(s), and any requested budget and justification for the intramural activity. See additional information in Section 8. Developing Applications.

3. Eligibility Requirements #eligrequirements

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Principal Investigator(s) (PI(s)) is/are invited to work with their organization to develop an application for support.

A successful NBSxWGS Collaboratory application will involve teams of individuals, including those with expertise in the following:

• Community engagement in research, including genomic research
• Direct work experience in PHL Newborn Screening programs
• Bioethics, particularly regarding ELSI issues related to genomic research data and/or newborn screening
• Regulatory approvals and compliance necessary for informed consent of human subjects and return of genomic sequencing results
• Human genomic sequencing pipeline development and refinement, including expertise with extraction from DBS punches for WGS
• Human genomic sequencing analysis
• Management and security of personally identifiable research data
• Clinical management of monogenic diseases in childhood
• Administration and project management of complex research projects involving federated teams

4. Multiple Principal Investigators and Partnerships among Applicants’ Institutions #pis

More than one individual may be named Principal Investigator (PI) in the application. One individual must be identified as the contact Principal Investigator. The contact PI must be employed by or affiliated with the applicant organization. The PI and any multiple PIs (MPIs) must collectively commit a total of at least 20% level of effort to the project. Each Function Director must commit at least 10% level of effort to provide leadership for that function. If a multiple Principal Investigator (MPI) application is submitted, an MPI Leadership plan is required.

Partnerships among institutions with investigators having complementary skills and expertise to meet the requirements of this ROA are not required but are allowed.

5. Project Manager/Director (PM/PD) Requirements #pm

NIH expects the proposed project to include an individual that will serve as the PM/PD for the project, with the appropriate scientific expertise and project management experience, who would support the PI(s) with project management and organizational oversight. Such an individual must commit at least 50% level of effort to the project.

6. Financial and Risk Assessment #assessment

Applicants may be subject to financial analysis and risk assessment conducted by NIH staff.

7. Cost Sharing #costsharing

Cost Sharing is not required but may be proposed. Those proposing to develop commercial applications or who are using other state or government resources may consider identifying a cost share percentage. Applicants may voluntarily choose to propose a financial plan that includes non-federal resources. The budget submission must clearly identify and justify the use of these resources. Any voluntary cost share must be supported in the application by including a letter of support from the providing organization(s)/individual(s). Inclusion of cost sharing will have no influence on application selection.

8. Developing Applications #developingapplications

8.1    Application Submission Instructions

Complete applications must be submitted under OTA-25-004 via NIH eRA Commons ASSIST no later than the “Application Due Date” shown at the top of this notice, by 5:00 PM local time of applicant organization.

Late applications submitted to this ROA will not be accepted.

For further information, please consult the FAQ page: https://commonfund.nih.gov/venture/NBSxWGS/faqs

Questions about the scientific scope of this announcement should be addressed to: [email protected]

Letters of Intent (LOIs), due by the “Letters of Intent Due Date” shown at the top of this notice, are required.

8.2    Letter of Intent

Interested applicants must submit a Letter of Intent (LOI), which will allow NIH staff to plan the review panel and identify any unique scientific expertise that needs to be included. The information in the LOI also will be used to identify and mitigate potential conflicts of interest (COIs) for prospective reviewers. LOIs will only be accepted from entities listed in the Eligible Organizations section of this Announcement that meet the criteria listed in the Eligibility Requirements. LOIs submitted from organizations not included in the Eligibility section will not be considered.

LOI (4-pages): The following must be combined into a single PDF:

• Heading: Title, Contact PI, Business Official, and Applicant Institution.
• Project Summary/Abstract (1-page): The Project Summary/Abstract must briefly summarize the proposed project, including its scientific rationale, specific aims, major milestones, scientific approach, endpoints/outcome measures, and expected impact. Literature citations are allowed but not required.
• List of Key Personnel (3-pages): List all key personnel for the proposed project and for any subprojects with proposed budgets. Provide each person’s name, current title and affiliation, and a concise statement of their role(s) and responsibilities for the proposed project. As applicable, also provide each key person’s eRA Commons ID; briefly state their prior experience in obtaining IRB and other regulatory approvals for studies involving the return of genetic sequencing results to research participants; and briefly summarize their history of receiving awards from NIH and any other federal agencies.

The LOI must be submitted by email as a PDF attachment to [email protected] by the “Letters of Intent Due Date” shown at the top of this notice. The LOI may only be submitted by one of the applicant institution PIs (either the Contact PI or other PI) or by the institutional Signing Official (SO) or Recipient Business Official (RBO) for the prime recipient’s application. LOIs submitted by other means or from other parties will not be considered.

Email confirmation will be provided (as a “reply all” response) acknowledging receipt of the LOI. The email from NIH confirming receipt of the LOI must be included in the “Project Information Summary” section of the full application.

8.3    Full Application

Only applicants who have submitted an LOI are eligible to apply. Applications will be accepted only from entities listed in the Eligible Organizations section of this Announcement and only from applicants who meet the criteria listed in the Eligibility Requirements. Applications submitted from organizations not included in the Eligibility section will not be reviewed. Applications must be prepared and submitted using NIH eRA Commons ASSIST. For instructions on how to submit through ASSSIST, refer to ASSIST-Instruction-Guide-for-NIH-Other-Transactions.docx. Complete applications must be submitted by the Recipient Business Official (RBO). The organization must be registered in eRA Commons with one person designated as the contact PI and one person designated as the RBO. The registration process can take several weeks, so applicants should begin registration as soon as possible. Failure to complete registrations in advance of the due date is not a valid reason for a late submission. The RBO’s signature certifies that the applicant has the ability to provide appropriate administrative and scientific oversight of the project and agrees to be fully accountable for the appropriate use of any funds awarded and for the performance of the OT award-supported project or activities resulting from the application.

Application Format

Full applications must include the following components. All attachments must be submitted as PDF using formatting standards provided at https://grants.nih.gov/grants/how-to-apply-application-guide/format-and-write/format-attachments.htm#papersizeandmargins. Do not include additional project data, images, graphics, etc. in sections other than Research Strategy in order to circumvent page limits. The required application components (with page limits in parentheses) are the following:

• Abstract (1 page): Provide a summary of the planned activities and approaches and key achievable goals.
• Specific Aims (1 page): Describe the specific aims and objectives the application proposes to achieve.
• Project Information Summary (3 pages): Provide the information about (note: do not upload this into the “Cover Letter Attachment” field in the ASSIST form but provide it as part of the Attachments section in the form):
  • Project Title.
  • Number and title of this Research Opportunity Announcement.
  • Principal Investigator(s) first and last name, title, institution, mailing address, email address, and phone number. If multiple Principal Investigators are named, the Contact Principal Investigator must be clearly identified.
  • Name and address of the submitting organization and department, if any, with the organizational Unique Entity Identifier (UEI) number and employment identification number (EIN) provided.
  • Recipient Business Official/Signing Official first and last name, title, institution, mailing address, email address, and phone number.
  • Proposed budgets per year for 3 years (direct, indirect, and total costs).
  • Proposed project period dates.
  • Full names (last name, first name) of all key personnel, email address, institutional affiliation, title, percent effort, and role in the project.
  • Additional entities or organizations proposed to receive subawards and their roles.
  • Identify if the work involves human subjects.
  • Email from NIH confirming receipt of an LOI.
• Research Strategy (no more than 23 pages total): The Research Strategy shall be organized in the following manner:
  • Overview, including scientific rationale and anticipated impact (no more than 3 pages):
    Include an outline and/or diagram of the structure of the program and description of how the components are interrelated and integrated.
    • Describe how information sharing and communication among the components will be facilitated to enhance attainment of project goals.
    • Describe the anticipated impact of the proposed work on assessing the feasibility of incorporating genomic sequencing as a primary screening methodology to be used in the U.S. public health NBS program.
  • Detailed Research Plan: This section may not exceed 20 pages total and must be organized into subsections corresponding to the different Functions (no more than 5 pages per function). Each subsection must begin with a header that names the Function being described. The Detailed Research Plan must include:
    • Preliminary data that supports the proposed effort (with relevant literature citations).
    • Descriptions of past efforts (if any) by the applicant organization and/or the project team that are similar in scope and objectives to the project being proposed in the current application.
    • Description of how all of the requirements associated with the tasks outlined under Functions 1 – 4 (see Section 1) will be met, including methods, metrics, and expected outcomes.
    • Advantages and strengths of the proposed approaches.
    • Descriptions of potential pitfalls and alternative approaches to address those pitfalls.
• Intellectual Property (IP) Strategy (1 page): Applicants must describe the IP landscape surrounding the proposal. This should include known constraints, if any, that could impede the development of the NBSxWGS Collaboratory (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar technologies that are under patent and/or on the market, etc.) and how these issues could be addressed as appropriate and consistent with achieving the goals of the program. If patents pertinent to the NBSxWGS Collaboratory have been filed, the applicants should indicate the details of filing dates, what types of patents were filed, application status, and associated United States Patent Office (USPTO) links, as applicable. Applicants must also discuss future IP filing plans.
• Leadership Plan (3 pages): Applicants must include:
  • Organizational and reporting structure as well as leadership responsibilities for each function.
  • Relevant past performance of project team members in terms of working in and leading large projects and managing across teams (labs, companies, consortia), and any prior experience that the proposed team has had working together.
  • Relevant existing collaborations or working relationships with newborn screening programs in state PHLs in the U.S.
  • Description of how the proposed team meets the eligibility requirements stated above.
  • Multiple Principal Investigator (MPI) Leadership Plan, if applicable.
• Milestones and Deliverables (5 pages): All applications must provide detailed information on milestones and deliverables for planned activities and partnerships, as further described below in Section 8.4.
• Biosketches (5 pages per individual): Provide a biosketch of each named key individual. The information in the biosketch should include the name and position title; education/training including institution, degree, date (or expected date), and field; list of positions and employment in reverse chronological order (including dates); list of relevant publications; and a personal statement that briefly describes the individual’s role in the project, proposed level of effort, and why they are well-suited for this role. Providing successful examples from past work on similar infrastructure building projects, as appropriate to illustrate the relevant experience, is desired. The format used for an NIH grant application is acceptable: https://grants.nih.gov/grants-process/write-application/forms-directory/biosketch
• Other Support (no page limitation): Provide Other Support for all key personnel using the NIH grant application format as found here: https://grants.nih.gov/grants-process/write-application/forms-directory/other-support
• Equipment and Facilities (2 pages): Provide the information about the equipment and other physical resources available to the project team to adequately complete the project milestones.
• Institutional Letter of Support (2 pages): Provide a letter of support from the applicant organization indicating institutional commitment for the project (e.g., relaying support for contributions, including, but not limited to, support for training activities, licenses, and other resources) and preparations to enter into a negotiated Other Transaction Agreement.
• Additional Letters of Support (no page limitation): Letters of support will be reviewed. Only include letters from persons who have an assigned role in the project.
• Budget and Budget Justification (no page limitation): All applications must provide detailed budget information for planned activities and partnerships, as further described below in Section 8.5.
• Bibliography (no page limitation).
• Resource Sharing Plan (no page limitation): Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
• Data Management and Sharing Plan (2 pages): All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Follow the guidance provided above in Section 1, Requirements, Data Management and Sharing. Note that the final Data Management and Sharing Plan will be developed in consultation with the CAB and the NIH NBSxWGS Working Group.
• PHS Human Subjects and Clinical Trials Information (up to 25 pages): When involving human subjects research, clinical research, and/or NIH-defined clinical trials, follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
  • If human subjects are involved, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
  • All instructions in the SF424 (R&R) Application Guide must be followed. Additional information can be found here: Study Record - Section 1 Basic Information (nih.gov)
  • Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

8.4    Milestones and Deliverables

The expected project duration is 3 years. Provide a table of milestones and deliverables for each year of the three-year application. Milestones must be specific, quantifiable, and scientifically justified. Milestones, due dates, and estimated costs must be provided in the table. An example table template is provided below for reference.

NIH anticipates that there will be a necessary sequence of events for effective project performance. For example, the CAB must first be established before the initial target gene list, the final Data Management and Sharing Plan, or the informed consent process can be established. In turn, these activities that depend on CAB input, as well as the awarding of PHL subcontracts in the first project year, must be finalized before the IRB approval request can be submitted. Applicants must provide their plans to account for dependencies among these and any other sequentially dependent activities that are noted in their Milestones and Deliverables table and project timeline. NIH encourages the awardee to meet all requirements for participant enrollment within the first 6 months of the award, such that enrollment and screening could begin in the third quarter of project year 1.

Example table of milestones and deliverables:

• Note 1: Applicants must ensure that the total budget request is consistent with the sum of item budget estimates in Milestones and Deliverables table for the project.
• Note 2: Provided costs for the task should include all the costs for personnel, facilities, other resources, travel, and other associated costs.
• Note 3: Total cost (the sum of direct and indirect) for the tasks must be provided.

Milestone	Tasks/ Subtasks	Start Date and Due Date (Months After Award)	Milestone Definition	Estimated Total Cost (Direct plus Indirect Cost) for the Task
1	1.1	0, 3	Milestone Name/Description a. Bulleted list of tasks to complete b. Bulleted list of deliverables (including data sharing) c. Completion criteria for the task d. Potential risk factors and decision points	$100,000
1	1.2	1, 3	Milestone Name/Description a. Bulleted list of tasks to complete b. Bulleted list of deliverables (including data sharing) c. Completion criteria for the task d. Potential risk factors and decision points	$100,000
2	2.1	2, 6	Milestone Name/Description a. Bulleted list of tasks to complete b. Bulleted list of deliverables (including data sharing) c. Completion criteria for the task d. Potential risk factors and decision points	$100,000

8.5    Budget Details

The Common Fund Venture Initiative may allocate up to $4,800,000 (direct + F&A) costs per year for up to three years per award. Support of one project is anticipated. The funding will depend on (1) the objectives for the project proposed by the applicants and how well they fit with the goals of NBSxWGS Collaboratory initiative, (2) the quality of the applications received, (3) availability of funds, and (4) programmatic priorities. The NIH may elect to negotiate any or all elements of the proposed budget. Institutions with an established F&A rate must use their federally approved rate to calculate F&A costs with the following exceptions:

• F&A costs for genomic sequencing including reagents, consumables, sequencing platform and instrument maintenance, sample preparation, bioinformatics analysis etc., will have a cap of fifteen (15) percent. This supersedes the institutionally established F&A rate. The institutionally established F&A rate will apply to personnel costs, including those related to genomic sequencing.
• F&A costs on foreign components will be reimbursed at a rate of eight (8) percent of modified total direct costs, exclusive of tuition and related fees.

In ASSIST Core tab, applicants should enter the total dollar number in the field of Total Requested Funds. For budget details, applicants must download the form from https://commonfund.nih.gov/OTforms and then complete SF424 budget forms on their own computers instead of in internet browsers. The prime applicant is responsible for including all third parties’ budgets and budget justifications. In order to successfully upload budget forms as an attachment into ASSIST, the applicant should flatten the fillable PDF. There are a number of methods to flatten a PDF, the easiest of which is to print it as a PDF.

The detailed budget request must provide the overall expected cost for each of the following categories and for each of the three years: personnel, travel, funds for third parties (i.e., subrecipients such as PHLs) if applicable, other direct costs, and total costs (with F&A costs included).

For the purpose of preparing an application, the following considerations and assumptions are provided to allow applicants to develop a proposed budget: 

• A key goal of this project is to include state PHLs (between 5-10) with varying levels of experience, or no experience, with NIH funded research and WGS. As stated above, applicants are not expected to include the names of collaborating state PHLs in their application but may list preferred options or those PHLs with which they have relevant experience. The list of PHLs will be finalized during negotiation with program staff prior to award.
• Because PHLs will not be identified in the initial application and some budgetary considerations may not be fully apparent at the time of application submission, applicants are expected to submit estimated budgets for the PHLs. Applicants should provide the rationale and justification for the estimated PHL budgets for use in the negotiation process.
• Include an estimate of per newborn sequencing costs, including analysis and personnel costs. Note: F&A rates for DNA sequencing costs (not including staff salaries) will be limited to 15%.
• Include an estimate of the total number of anticipated babies to be sequenced.
• Include a budget estimate for confirmatory sequencing of screen-positive babies. Assume ~2% of all babies sequenced will screen positive based on published experience of sequencing asymptomatic newborns in the U.S.
• Include standard budget estimates to support the remaining activities.

Budgets must adhere to latest NIH salary limitation notice (See Salary Cap Summary (FY 1990 - Present) | Grants & Funding).

Intramural Research Program Investigator Involvement
Intramural Research Program (IRP) investigators can participate in the Venture Program NBSxWGS Initiative, with certain limitations. Intramural investigators may collaborate with extramural investigators when both have expertise that could contribute to the goals of the program.

When submitting a full application, a justification must be provided for all requested support. In addition, a justification must be included for federal employees who will be committed to the project although no funds are requested in the application. The number of person months and justification for all federal employees who will be committed to the project, even though no funds are requested, must be included. This will allow the reviewers to evaluate the suitability of proposed staff to conduct the work.

Rather than requesting IRP funds within the project budget, a separate letter originating from and signed by the IRP investigator’s Scientific Director must be included in the application. The letter must describe the intramural aim(s) and include requested budget for the intramural activity. Funds may be requested for IRP investigator participation and will be limited to the costs required for carrying out the proposed work if those costs can be specifically identified with the Venture Program NBSxWGS Initiative project. They may include:

• Salary for staff to be specifically hired under a temporary appointment for the project
• Consultant costs
• Supplies
• Travel
• Other items typically listed under Other Expenses.

Any support requested from federal agencies, including the NIH intramural program, may not include any salary and related fringe benefits for career, career conditional or other federal employees (civilian or uniformed series) with permanent appointments under existing position ceilings or any costs related to administration of facilities support.

Do not include any IRP investigator costs in the OT budget request or budget justification. The amount provided for successful recipients for the IRP investigator participation and the OT award will be determined in negotiation and will not exceed the total cost of the allowable budget. IRP investigator funds will be issued through an IAA/MOU.

8.6    Systems Registration

Applicants must submit the full application via the NIH eRA Commons ASSIST system no later than the “Application Due Date” shown at the top of this notice, by 5 PM local time of applicant organization. Here are instructions for submitting via the NIH eRA ASSIST system including specific guidance for OTAs: https://www.era.nih.gov/help-tutorials/assist/era-training-assist.htm. Technical assistance is available from the eRA Service Desk: https://www.era.nih.gov/need-help.

To submit a full application via ASSIST, the applicant organization must have already registered for and been granted the following, which may take several weeks to complete: 

• System for Award Management (SAM): https://sam.gov/content/home – Applicants must complete and maintain an active registration, which requires renewal at least annually.
• Unique Entity Identifier (UEI): A UEI is issued as part of the SAM.gov registration process.
• eRA Commons: Once the unique organization identifier (UEI after April 2022) is established organizations can register with eRA Commons (https://www.era.nih.gov) in tandem with completing their full SAM and Grants.gov registrations.

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance.

9. Objective Review #objectivereview

The intent of the Objective Review for the NBSxWGS initiative is to determine whether the proposed activities meet the goals and vision of this project.

Applications to Other Transactions Research Opportunity Announcements, such as this one, are not reviewed by the standard NIH peer review process, but use custom processes referred to as Objective Review. Responsive, full applications submitted in response to the ROA will be reviewed by subject matter experts via an Objective Review process. Objective Review will involve the submission of written critiques by subject matter experts against the Review Criteria described below and may involve interactive discussions between those experts and NIH Program staff. The subject matter experts will include NIH staff, other federal staff, and may include individuals external to the federal government. Applications may be accepted into the final plan in whole, in part, or not at all. The outcome of each review could result in a modified work plan for each application based on reviewers’ comments and recommendations. The modified workplan, as shaped by the review process, will serve as a blueprint for the final negotiated terms and milestones for the resulting award(s).

NIH will NOT provide feedback on applications, except as a part of follow-up on an as-needed basis.
NIH will not accept an appeal of the Objective Review or funding decision outcomes.

9.1     Review of Full Applications

Full applications will undergo Objective Review by subject matter experts including NIH federal employees, NIH contractors, federal employees of other agencies, and outside experts, as needed.
The Overall Impact will be assessed by the Review Criteria outlined below:

Review Criteria

Overall Criteria:

• To what extent are the planned activities likely to advance the goals of the NBSxWGS initiative to assess the feasibility of incorporating genomic sequencing using a WGS platform into the public health program for U.S. newborn screening?
• To what extent are the planned activities likely to successfully address the four key functions listed in Section 1?
  • Project Administration and Coordination
  • Participant Recruitment, Consenting / Return of Results
  • Whole Genome Sequencing and Analysis
  • ELSI and CAB Function
• Are the milestones, deliverables, and timeline for fulfilling the planned activities for Functions 1 through 4 achievable within the three-year project time frame?
  • Do the milestones and deliverables have meaningful/quantifiable success criteria?
  • Does the applicant provide an adequate plan for identifying and mitigating technical and management risks?
• Are the leadership plan and (if applicable) the multiple PI plan appropriate?
• Is the overall organizational and reporting structure appropriate?
• Are the expertise, demonstrated capabilities, and past performance of the PI(s), PM/PD(s), and key personnel appropriate for the proposed activities and the successful execution of the proposed project, and are these qualifications adequately demonstrated with relevant examples from past work? Specific areas of expertise are:
  • Work experience in or with a PHL NBS program
  • Experience in bioethics, particularly regarding genomic research data and/or newborn screening
  • Experience in human genomic sequencing pipeline development and refinement as well as human genomic sequencing analysis, including expertise in identifying pathogenic or likely pathogenic variants in an asymptomatic population with high genetic variability
• Are the proposed facilities, computing infrastructure, backup plans, physical security of any data, communication networks, relevant other equipment, and project management tools adequate to support the successful execution of the proposed work, and do they meet relevant and current data security standards?
• Is the proposed budget reasonable and commensurate with the proposed work?
• Will the estimated number of babies to be sequenced in this project allow the goals of the NBSxWGS Collaboratory initiative to be achieved successfully?
• Are there adequate protections for Human Subjects in research?

Function-Specific Criteria:

Function 1 (Project Administration and Coordination) - How well does the proposal address the requirements as outlined below?

• History of organizing and managing large, collaborative, multidisciplinary team(s) focused on NBS and WGS, including:
  • Project management
  • Coordinating across multidisciplinary teams
  • Obtaining regulatory approvals
  • Public dissemination of results

Function 2 (Participant Recruitment, Consenting / Return of Results) - How well does the proposal address the requirements as outlined below?

• History of successful recruitment and retention of participants from the general public or across an entire state
• Experience working with one or more state PHLs, with a specific focus on NBS and WGS
• Return of clinically relevant genetic information to asymptomatic individuals

Function 3 (Whole Genome Sequencing and Analysis) - How well does the proposal address the requirements as outlined below?

• Establishment and management of a WGS pipeline that includes:
  • Generating high-quality WGS data
  • Assessing, interpreting, and calling pathogenic and likely pathogenic variants for various racial/ethnic groups
  • Secure handling and storing of genomic data
  • Addressing relevant regulatory requirements

Function 4 (ELSI and CAB Function) - How well does the proposal address the requirements as outlined below? 

• Are the proposed categories of experience of the CAB members appropriate to the project?
• Do the applicants have experience in addressing ELSI considerations around NBS and WGS?
• Do the applicants have experience with recruiting, maintaining, and managing external advisory groups that include members with varied perspectives on and lived experiences with NBS and WGS?

As needed, NIH Program staff may follow up with top-scoring applicants by allowing them an opportunity to respond to the weaknesses identified by the Objective Review, and any additional concerns identified by NIH Program staff. Interviews may be conducted if appropriate. A funding decision will be made based on the results of the review and any subsequent responses from the applicants.

9.2     Post-review Funding Plan

NIH intends to fund one (1) award.

The level of funding for the award made under this solicitation will depend on (1) the objectives proposed by the applicants and how well they fit with the goals of the NBSxWGS Collaboratory initiative, (2) the quality of the applications received, (3) availability of funds, and (4) programmatic priorities. The OT mechanism allows for significant flexibility to make budget adjustments as needed to meet NIH’s programmatic priorities. Award levels may increase or decrease over time based on funding availability, establishment or termination of subcontracts, recipient performance, and other program priorities.

Following the review of applications, NIH may assemble teams from all or parts of applications to establish the NBSxWGS Collaboratory. Individual components from distinct applications may be selectively funded to achieve the goals set forth herein. Additionally, if, over the duration of the project, some of the components either gain relevance or lose relevance to programmatic goals, the funding for such components may be increased, decreased, or be discontinued.

At any relevant point in the process, including the Objective Review, NIH reserves the right to:

1. Select for negotiation all, some, one, or none of the applications received response to this solicitation.
2. Accept applications in their entirety or select only portions of the application for award.
3. Invite all, some, one, or none of the Principal Investigators (PIs) submitting applications in response to this solicitation to present their application in a web-based videoconference or a teleconference.

Appeals of the Objective Review will not be accepted for applications submitted in response to this ROA.

10. Special Award Terms and Information #specialawardterms 

10.1    NIH Discretion

The OT award mechanism allows significant ongoing involvement from NIH Program and Project Managers and OT Agreements Officer and Agreements Staff and provides the NIH the flexibility to alter the course of the project in real-time to meet the overarching goals. This may mean an awarded activity could be expanded, modified, partnered, not supported, or discontinued based on program needs, emerging methods or approaches, performance, or availability of funds.

Performance during the award period will be reviewed on an ongoing basis and course corrections will be made, as necessary. As a result, the NIH reserves the right to:

1. Fund projects in increments and/or with options for continued work depending on agreed upon milestones;
2. Specify milestones that either result in project continuation if achieved, or termination if not achieved, by the specified milestone timepoint;
3. Fund a project composed of entities included in different applications as part of a reorganized collaboration, teaming arrangement, or other means acceptable to the government and recipient;
4. Request additional documentation (certifications, etc.), and;
5. Remove participants from award consideration should the parties fail to reach a finalized agreement by addressing the concerns identified in the Objective Review, and any additional concerns identified by NIH Program staff, or the proposer fails to provide requested additional information in a timely manner.

Applications selected for award negotiation may result in the issuance of an OT award based on the nature of the work proposed, the required degree of interaction between parties, and other factors. The NIH reserves the right and sole discretion to engage in negotiation with the selectees submitting a full application under this solicitation.

10.2    Award Governance

The NIH will actively engage with awardee(s) to establish the vision and capabilities for the NBSxWGS Collaboratory initiative and to oversee the effort of the awardee to achieve that vision. The NIH staff involved in award governance are the Other Transactions Agreements Officer (OTAO); the Other Transactions Agreements Specialist (OTAS); the Other Transactions Program Official (OTPO); and the NIH Working Group, which is composed of members from NCATS, NICHD, and the National Human Genome Research Institute (NHGRI). Information on the respective responsibilities of these NIH roles will be provided in the OT Agreement.

NIH anticipates rebudgeting in project year 1, following terms and conditions of the OT award, as decisions are made with respect to data management and sharing, consent, protocols, and other matters yet to be decided.

10.3    OT Agreement Governance

Other Transactions (OT) are a special type of legal instrument other than contracts, grants, or cooperative agreements. Generally, these awarding instruments are not subject to the regulations for federal contracts or grants, unless otherwise noted for certain provisions in the terms and conditions of award. They are, however, subject to the OT authorities that govern the initiative and/or programs as well as applicable legislative mandates. The NIH and its components, including OSC, have been authorized by Congress to use them. They provide considerable flexibility to the government to establish terms and conditions of the OT Agreement.

For the awards funded under this ROA, the NIH will engage in negotiations, and all agreed-upon terms and conditions will be incorporated into the OT Agreement. Either a bilateral agreement or a Notice of Award (NoA) will be used as the official OT Agreement. The signature of the RBO certifies that the organization complies, or intends to comply, with all applicable terms and conditions, policies, and certifications and assurances referenced (and, in some cases, included) in the application instructions.

10.4    Reporting and Project Meetings

The terms and conditions of award will address these criteria as appropriate based upon the final negotiated terms and agreed upon budget. However, the recipient and key project team members will be required to:

• Participate in an initial virtual kick off meeting with NIH staff and NBSxWGS Collaboratory collaborators.
• Participate in site visits or reverse site visits as deemed necessary by the OTPO.
• Participate in virtual progress meetings with NIH staff to ensure the initiative continues to achieve objectives and to discuss progress and strategies.
• Submit written budget and milestone reports.
• Submit final report: By the end of the 3-year period, we would expect to have a much better understanding of the feasibility of incorporating WGS into the U.S. NBS program based on experience with state PHLs with varying degrees of “readiness” for incorporating this disruptive technology. NIH anticipates that the final report will be required to summarize the findings of the overall assessment of NBSxWGS feasibility as well as the embedded ELSI study, but these requirements will depend on the OTA negotiation process. Also subject to the OTA negotiation, the final report may be required to address questions such as, but not limited to, the following:
  • What is the reach, uptake, acceptability, feasibility, and potential sustainability of NBSxWGS across states with varying levels of WGS readiness?
  • What strategies might be necessary to facilitate broad adoption and uptake of NBSxWGS across the country, including ways to provide education about NBSxWGS to parents and healthcare providers?
  • What are the ELSI considerations that states need to be aware of and proactively address as they consider whether to adopt NBSxWGS?
  • How many screen-positive infants were identified for each screened gene, how many positive screens were confirmed to be cases, and how can the false positive rate for NBSxWGS be reduced?
  • What are the lessons learned from the NBSxWGS Collaboratory, and what are the “best practices” that state NBS programs can adopt if they decide to implement NBSxWGS?
  • How do the participating state PHLs think a Collaboratory model would help reduce implementation barriers? How much more confident do they feel in their ability to implement NBSxWGS after the end of the Collaboratory?
  • What strategies can states use to reduce the burden of adding many new conditions simultaneously on their follow-up staff?
  • What is the acceptability of using NBSxWGS to parents and guardians of newborns, state NBS programs, healthcare providers, and the public?
  • Were screen-positive infants able to be referred to appropriate specialists and access appropriate treatments and interventions?
  • What are effective strategies for ensuring parents/guardians are providing informed consent, and how effective are these strategies for use in communities across each participating state and potentially across the entire U.S.
• Attend national and/or international NBS or NBSeq meetings to report back on progress on the NBSxWGS Collaboratory, as well as Federal Advisory Committees such as the Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC), when appropriate.
• Actively participate in NBSxWGS Collaboratory-wide working group and committee activities.

Costs associated with these activities must be appropriately reflected in the proposed budget.

10.5    Management Systems and Procedures

Recipient organizations are expected to have systems, policies, and procedures in place by which they manage funds and activities. Recipients may use their existing systems to manage OT award funds and activities as long as they are consistently applied regardless of the source of funds and across their business functions. To ensure that an organization is committed to compliance, recipient organizations are expected to have in use clearly delineated roles and responsibilities for their organization’s staff, both programmatic and administrative; written policies and procedures; training; management controls and other internal controls; performance assessment; administrative simplifications; and information sharing.

10.6    Financial Management System Standards

Recipients must have in place accounting and internal control systems that provide for appropriate monitoring of other transaction accounts to ensure that obligations and expenditures are congruent with programmatic needs and are reasonable, allocable, and allowable. The systems must be able to identify unobligated balances, accelerated expenditures, inappropriate cost transfers, and other inappropriate obligation and expenditure of funds, and recipients must notify NIH when problems are identified. A recipient’s failure to establish adequate control systems constitutes a material violation of the terms of the award.

10.7    Organizational Conflicts of Interest (OCIs)

Applicants are required to identify and disclose all facts relevant to potential OCIs involving subrecipients, consultants, etc. Under this section, the proposer is responsible for providing this disclosure. The disclosure must include the PI/Collaborators’, and as applicable, proposed member’s OCI mitigation plan. The OCI mitigation plan must include a description of the actions the proposer has taken, or intends to take, to prevent the existence of conflicting roles that might bias the proposer’s judgment and to prevent the proposer from having an unfair competitive advantage.

The government will evaluate OCI mitigation plans to avoid, neutralize, or mitigate potential OCI issues before award issuance and to determine whether it is in the government’s interest to grant a waiver. The government will only evaluate OCI mitigation plans for applications that are determined selectable. The government may require applicants to provide additional information to assist the government in evaluating the proposer’s OCI mitigation plan. If the government determines that a proposer failed to fully disclose an OCI or failed to reasonably provide additional information requested by the government to assist in evaluating the proposer’s OCI mitigation plan, the government may reject the application and withdraw it from consideration for award.

10.8    Monitoring

Recipients are responsible for managing the day-to-day operations of OT award-supported activities using their established controls and policies. However, to fulfill their role in regard to the stewardship of federal funds, NIH staff will monitor their OT awards to identify potential problems and areas where technical assistance might be necessary. This active monitoring is accomplished through review of reports and correspondence, audit reports, site visits and other information, which may be requested of the recipient. The names and contact information of the individuals responsible for monitoring the programmatic and business management aspects of awards will be provided to the recipient at the time of award.

Monitoring of a project or activity will continue for as long as NIH retains a financial interest in the project or activity as a result of property accountability, audit, and other requirements that may continue for a period of time after the OT award is administratively closed out and NIH is no longer providing active OT award support.

10.9    Audit

NIH OT recipients for the Program are subject to the audit requirements of OMB 2 CFR 200, Subpart F – Audit Requirements, as implemented by DHHS 45 CFR, Subpart F. In general, 45 CFR 75, Subpart F – Audit Requirements requires that a state government, local government, or non-profit organization (including institutions of higher education) that expends $750,000 or more per year under federal awards must have a single or program-specific audit conducted for that year in accordance with the provisions in Subpart F. Please consult the provisions within Subpart F to determine requirements for the program-specific audit requirements.

For-profit organizations have two options regarding the type of audit that will satisfy the audit requirements. The recipient either may have (1) a financial-related audit (as defined in, and in accordance with, the Government Auditing Standards (commonly known as the “Yellow Book”), GPO stock 020-000-00- 265-4, of a particular award in accordance with Government Auditing Standards, in those cases where the recipient receives awards under only one DHHS program, or (2) an audit that meets the requirements of 45 CFR 75, Subpart F-Audit Requirements.

Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. If a recipient has failed to materially comply with the terms and conditions of award, NIH may take one or more enforcement actions, which include disallowing costs, withholding of further awards, or wholly or partly suspending the OT award, pending corrective action. NIH may also terminate the OT award.

10.10    Public Policy Requirements and Objectives

NIH intends to uphold high ethical, health, and safety standards in both the conduct of the research it funds and the expenditure of public funds by its recipients. The signature of the RBO on the application certifies that the organization complies, or intends to comply, with all applicable policies, certifications, and assurances.