The Common Fund Venture Program is a new area of Common Fund support that provides a framework for development of short-term Common Fund initiatives that embrace bold approaches and are responsive to the shared priorities of NIH Institutes, Centers, and the Office of the Director.

Venture initiatives are Common Fund investments and so must meet Common Fund criteria, as expressed below. However, additional criteria also apply, emphasizing brief, modest investments that can be implemented quickly in response to emerging opportunities. Venture investments should be lightweight and nimble while having a strong potential to accelerate science quickly.

What makes Venture initiatives special?

• They are Bold: they are daring investments with potential for significant, outsized impact
• They are Nimble: they can be implemented rapidly in response to scientific opportunity
• They are Focused: they are limited to three years, up to $5 million annually to invest in a clearly defined research topic

What makes Venture initiatives consistent with the Common Fund?

• Common Fund criteria will apply to Venture investments, with accelerated timelines and nimble project management. Venture initiatives will be:
  • Transformative: projects have strong potential for exceptionally high and broadly applicable impact in biomedical/behavioral research
  • Catalytic: projects are time-limited investments of 10 years or less, designed to capitalize on new scientific knowledge or breakthroughs to accelerate and enable subsequent research
  • Goal-driven: projects include defined goals to develop specific deliverables (such as new knowledge, data sets, resources, methods, or technologies)
  • Synergistic: projects advance the missions of multiple ICOs, and are relevant to multiple diseases or conditions
  • Novel: projects pursue innovative solutions to specific scientific challenges important to the NIH mission but that no other entity is likely or able to address
• Venture initiatives are not:
  • Pilot programs to prepare for larger Common Fund investments
  • A means to address high-priority projects for individual ICOs
  • Support for exploratory, open-ended research without specific goals and milestones
• Governance:
  • Ideas for new Venture initiatives are submitted through the ICO Directors to the Office of Strategic Coordination, which oversees the NIH Common Fund, leveraging public input as appropriate. Initiative idea submissions can derive from any areas of biomedical and behavioral research. All proposals are evaluated for responsiveness to the Common Fund and Venture criteria, and are considered by the Venture Board, made up of ICO Directors. Promising ideas are recommended by the Board for full development. The NIH Director provides final approval. Updates on the progress of each Venture initiative will be described on their individual website. 

What is the Venture NBSxWGS initiative?

The overall purpose of the Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory is to assess the feasibility of a collaborative, multi-state model for newborn screening (NBS) that would use genomic sequencing as a first-tier screening assay for 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.  

What is the title of this Research Opportunity Announcement (ROA)?

Newborn Screening by Whole Genome Sequencing (NBSxWGS) Collaboratory (OT2)  

What is the announcement number of this ROA?

OTA-25-004

What is the purpose of this announcement?

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.

Whom can I reach out to with questions about this announcement?

All questions are welcome. Please reach out to Dominique Pichard and Matthew Arnegard with questions about the NBSxWGS initiative ([email protected]). Please reach out to Erna Petrich ([email protected]; subject line must include “NBSxWGS”) with financial or Other Transaction agreements questions.

What are the key dates for planning our application?

Research Opportunity Announcement Released	March 5, 2025
Technical Assistance Webinar View recording and slides	March 24, 2025, at 11 AM ET
Public Health Laboratories Webinar View recording and slides	March 31, 2025, at 1PM ET
Letters of Intent (LOI) Due LOIs are required. (Email confirmation will be provided 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.)	Friday, April 4, 2025, by 5 PM local time of applicant organization
Application Due	Wednesday, May 14, 2025, by 5 PM local time of applicant organization
Award Negotiations	To begin on or about Monday, May 16, 2025
Earliest Start Date	Monday, September 1, 2025

What organizations are eligible?

Please see ROA Section 2, Eligible Organizations, for the full listing of eligible organizations. 

Are foreign institutions eligible to apply for this initiative as the primary applicant?

No. Non-domestic (non-U.S.) entities (i.e., foreign applicants) are not eligible to apply. Non-domestic components of domestic organizations are also not eligible to apply.

Can an NIH Intramural Research Program (IRP) investigator submit an application for the NBSxWGS initiative? 

No. IRP investigators cannot apply as the prime recipient for the NBSxWGS initiative. However, IRP investigators can potentially participate in this initiative with certain limitations (see ROA Section 2, Eligible Organizations, and Section 8, Developing Applications, for details).

Can other federal agencies of the U.S. Government apply to the NBSxWGS initiative through Research Opportunity Announcement OTA-25-004? 

Yes, federal agencies of the U.S. Government other than NIH may apply to or be involved in the NBSxWGS initiative, provided that they have statutory authority to receive funding beyond their congressional appropriation. The applicant must include the citation of the agency’s statutory authority in the application. 

Can an application be submitted by an institution even if their state PHL is not planning to participate?

Yes. The NIH working group is developing the roster of state PHLs interested in potentially participating in this project, and it is quite possible that not all states will express interest in participating. During award negotiation the prime recipient, together with the NIH working group, will select 5-10 PHLs for actual participation in the project.

Are there any other eligibility restrictions?

Yes. Other eligibility requirements are detailed in the ROA in Section 2, Eligible Organizations, and Section 3, Eligibility Requirements.

May I apply for this opportunity without submitting a Letter of Intent (LOI)?

No. Interested applicants must submit a LOI. The LOI is needed so that NIH staff can plan the review panel and mitigate potential conflicts of interest. 

What content is required in the LOI?

The LOI may not exceed 4 pages and must contain the following (all combined into a single PDF):

• Heading: Project Title, Contact Principal Investigator (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.

How should Letters of Intent be submitted?

The LOI must be submitted by email as a PDF attachment to [email protected] by Friday, April 4, 2025, local time of applicant organization. The LOI may only be submitted by one of the 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 submitted LOI must be included in the full application. 

Will applicants receive evaluations of their LOIs or any feedback at all on their LOIs? 

No. The purpose of the LOIs is only to help NIH plan the review panel and manage all potential conflicts of interest during the Objective Review of applications. LOIs do not have any bearing on the scoring of your application. Because of the potential seriousness of conflicts of interest during Objective Review, we require each applicant to demonstrate that they submitted a LOI by attaching our email reply acknowledging receipt of your LOI in the “Project Information Summary” section of the full application. 

Do applicants need to be registered in eRA Commons prior to submitting an LOI? 

No. We instruct each interested applicant to submit their LOI to us by email as a PDF attachment, and eRA Commons is not required for this. However, applications must be prepared and can only be submitted using NIH eRA Commons ASSIST. The eRA Commons registration process can take several weeks, so applicants should begin registration as soon as possible. You risk missing the application deadline of Wednesday, May 14, 2025 (by 5:00 PM local time of applicant organization) if you wait until late April – May to register for eRA Commons. To submit a full application via ASSIST, the applicant organization must have already registered for and been granted the following, which could 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. 

What are Other Transactions (OTs)?

Other Transactions (OTs) are funding mechanisms, which are not grants, cooperative agreements, or contracts, authorized under the Other Transaction Authority (OTA) by the 21st Century Cures Act.

OTs are used by components within the NIH, including the Common Fund, which have been authorized by Congress to use them. They allow the NIH to:

• Seek participation of non-traditional research partners.
• Foster innovation and nimbleness to develop and engage in programmatic activities.
• Alter the course of the project in real-time to meet the overarching goal.
• Conduct objective review of applications.
• Expand, modify, partner, not support, or discontinue awarded activities based on performance and programmatic need.
• The Other Transactions Authority is governed by 42 U.S. Code § 282 (n)(1)(b). Other Transactions (OTs) are not grants, cooperative agreements, or contracts. They are used by the NIH to provide considerable flexibility in establishing policies for the awards. Policies and terms for individual OT awards may vary between awards, each negotiated with a specific agreement, which may be expanded, modified, partnered, not supported, or later discontinued based on program needs, changing research landscape, and/or availability of funds.

Are OT applications reviewed by the standard NIH peer review process?

• Applications to Other Transactions Research Opportunity Announcements (ROAs), such as this one, are not reviewed by the standard NIH peer review process, but instead, they use custom review processes.
• Responsive, full applications submitted in response to the solicitation will be reviewed by subject matter experts (SMEs) via an Objective Review process. Objective Review will involve the submission of written critiques by SMEs against the Review Criteria listed in the ROA and may involve interactive discussions between those experts and NIH Program staff. The SME's may include NIH federal employees, NIH contractors, federal employees of other agencies, and outside experts, as needed.
• Components of the full applications may be accepted into the final plan in whole, in part, or may be omitted. The outcome of each review could result in a modified work plan for each application based on reviewers’ comments and recommendations.

What does the OT review process look like exactly, and who makes up the review panel? 

The review process is very similar to the way that NIH grant applications are reviewed, except for the fact that the NIH Program Team assembles the review panel and manages the conflicts of interests. One staff member at NIH fulfills the role of a scientific review officer to make sure that all the rules are being followed and that the review is objective. The review panel consists of experts in predefined areas, such as experts in data coordination and pediatric diseases. We have a review area for newborn screening and so forth. The reason we ask for the letters of intent (LOIs) is that we want to make sure to manage every possible conflict that might arise between one of the reviewers that we selected a priori and an incoming application. The process that is followed for Objective Review of OT applications is analogous to the standard review process for NIH grant applications. Yet, OT applications are not grant applications, so the NIH Program Team must assemble and manage its own review panel. However, nobody from the Program Team for this initiative will serve as a reviewer on the review panel.

Does the NIH Policy on Data Management and Sharing (NOT-OD-21-013) apply to this ROA? 

Not entirely. Typical government grant procurement regulations and policies do not apply to OT awards (see the NIH web page on Other Transactions to learn more). However, like other NIH-funded projects, the NBSxWGS Collaboratory initiative intends to maximize the amount of data from this initiative that may be made available to the public. 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 a Community Advisory Board (CAB) in multiple aspects of the initiative, including data sharing. Therefore, as indicated in the ROA, applicants are required to submit a draft Data Management and Sharing Plan (NOT-OD-21-013), 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. 

What is the budget for this opportunity?

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 should use their federally approved rate to calculate indirect 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.

How should the budget request be developed and organized?

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). Detailed quotations are required for equipment items exceeding $10,000.

Budgets must adhere to latest NIH salary limitation notice (See Salary Cap Summary (FY 1990 - Present) | Grants & Funding.)
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 a varied set of state PHLs (between 5-10) with varying degrees of experience, or no experience, with NIH funded research and WGS. 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 NIH anticipates that 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.

Where can I find the budget form?

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.

Should applicants try to anticipate budgets for working with the state PHLs or develop those after the award?

This question is answered by the Research Opportunity Announcement (ROA) as follows: “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."  

Can a function described in the ROA be performed by more than one team?  For example, the ROA states that the prime awardee must lead the Central Coordination Core (Function #1). But can certain tasks within that function (such as "Community of Practice") be performed through a subaward?

Yes, certain tasks can be performed through a subaward, and yes, a function described in the ROA can be performed by more than one team. However, there needs to be a clear and convincing leadership structure and plan, so that the Central Coordination Core can effectively administer and coordinate the whole project. 

Does the prime applicant need to propose all 4 of the functions (project administration, participant recruitment, sequencing, and CAB/ELSI)?

Yes. Each prime applicant needs to address all 4 functions in their proposal; however, they may choose to subcontract with other entities or investigators to serve as the lead for one or more of the functions.

Does each site run their own extraction from the dried blood spots and complete the genomic sequencing? Are either or both of these processes completed at the PHLs?

We anticipate that at a minimum, each state will send its DBS punches to the centralized sequencing facility for DNA extraction, sequencing, and variant interpretation and calling across the Collaboratory, as outlined in Function 3. That said, an applicant can propose an alternate workflow for PHLs based on their varying capabilities.

What is the desired population size? Given that this will be a consented project, our group was wondering if there are a certain number of infants that are desired per site. 

NIH does not have a particular expectation about a specific number of babies to be screened. However, applicants are asked to “include an estimate of the total number of anticipated babies to be sequenced” in their application. NIH’s expectation is that the number of babies to be sequenced would be supported by the available budget for this initiative, would be distributed across 5-10 participating state PHLs, and would enable the assessment of the feasibility of a collaborative, multi-state model for newborn screening 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. We encourage recruitment state-wide so as to have a representative sample from each state.

Are the variants called by the sequencing function?

Yes, the Whole Genome Sequencing and Analysis Core (Function 3) will develop a strategy for workflows and variant calls that it will apply to all the samples submitted. 

From the ROA section that describes Function 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.”
As a long-term, capacity-building goal of the Collaboratory, a Community of Practice will assist the state PHLs in developing strategies for incorporation of genomic sequencing, including variant calling, into their NBS workflows.

Is there a preference or expectation that a certain approach to recruitment/consent should be used for this study? 

We do not have an expectation for a specific system that should be set up to handle recruitment and consent under this ROA. What is proposed should be as feasible as possible while allowing recruitment state-wide. Whatever you propose will need to be adapted based on what is feasible and available for the individual states that will be selected during the negotiation phase of the award. The focus of this ROA is on developing a pragmatic workflow for PHLs to incorporate WGS into their capacity, so the scope is somewhat limited.

The timeline for the grant is very short given the infrastructure that will need to be built across the states. Is it assumed then that applicants are not expected to look at clinical outcomes of the babies within the scope of this proposal? Perhaps that will need to be the focus of other grants?

The clinical outcomes of the babies is not the focus of this award. While we expect states to continue to track outcomes to the best of their ability, we recognize that the time frame will not allow for long term outcomes monitoring. However, we do want confirmatory diagnostic testing to enable closure of positive cases.

Without knowing what states this will operate in, how can applicants propose the set of sites (e.g., hospitals) that will recruit and consent participants and collect their blood samples? Are applicants expected to have clinical partners lined up in all 50 states?

No. We're not expecting applicants to have clinical partners lined up in 50 states, but we are expecting applicants to propose the framework for recruitment and consent, including thinking of incorporating these actions with the screening programs that already exist and being thoughtful about the consenting part of it. So, applicants will have to be broad in their applications. Once those states are identified during the negotiation phase, these details can be further fleshed out in collaboration with the NIH NBSxWGS Working Group.

Regarding confirmatory testing on positives, what are acceptable methods of molecular testing?

It is up to the applicants to propose what they would plan to do for confirmatory testing.

Will the NIH NBSxWGS Working Group handle the recruitment of participating parents and newborns, or is participant recruitment considered part of the project scope, requiring the awarded project team to manage it?

Each applicant is responsible for proposing a Participant Recruitment, Consenting / Return of Results (CONS-ROR) Function (Function 2) that must include, but is not limited to, proposing an approach for participant recruitment and consenting that could be implemented across 5-10 participating states and would have the ability to reach parents from multiple backgrounds across each entire state.

The NBSxWGS Working Group (i.e., NIH Program Team) will not handle or carry out the recruitment of participating parents and newborns. Carrying out this task will be the responsibility of the prime awardee. Terms and conditions regarding participant recruitment (and all other aspects of the project) will be agreed upon during award negotiation.

Under Function 2 in Section 1 of the ROA (Requirements), Task v. states the following regarding the 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.” Would it be out of scope for state PHL staff to return results directly to participating families, as is typical for traditional newborn screening?

No, it would not be out of scope for state PHL staff to return results directly to families. Ultimately, it is up to the applicant to propose what they think is the best way to handle return of screen-positive results to the participating families.

Are PHLs responsible for the sequencing and variant calling?

No, the Function 3 activity (Whole Genome Sequencing and Analysis) would be centralized across all the participating states (5-10) for the sequencing of samples, as well as variant interpretation and calling.

Can you confirm the minimum number of states required/preferred?  Is there a preference as to whether participating states are located in the same region/close to each other?

The minimum number of participating states is 5. One of the goals is to include state NBS programs with different levels of research experience and genomic sequencing readiness. There may be state PHLs that have not previously participated in NIH-funded research, and that’s perfectly fine. There may be states that have no prior experience with WGS, and that’s fine, too. We’re also hoping to include PHLs from different geographic regions of the country, so no, we don’t want all participating states to be in the same region. Basically, we want the set of participating PHLs to be a representative sample of the country as a whole.

Is a PHL that performs NBS for multiple states considered a multiple-state collaboration?

Yes. However, we would not anticipate that only one PHL would be included in the awarded Collaboratory, even if it does serve as the regional lab for multiple states. But yes, a PHL like that would be considered a multiple-state collaboration.

Newborn screening is a whole system with multiple essential partners. Why does the ROA refer just to “state public health labs (PHLs)” when other entities are involved in newborn screening, and when the makeup of these entities varies a lot across states?

The NIH Program Team acknowledges that our use of “state PHL” in the ROA is shorthand for the entire system of newborn screening, and that this system is complex and varies across the states. For example, follow-up with patients is a critical component of the newborn screening system, and entities other than the PHLs perform this follow-up in some states. Applicants should know and may rest assured that the NIH program is aware that assessing the feasibility of including WGS into the NBS must include the entire NBS system, not just the labs.  During the award negotiation process, we will ensure that the NBSxWGS Collaboratory will include interactions among all components of the participating state newborn screening systems necessary to assess feasibility.

Our institution works closely with our Department of Public Health to implement NBS, especially follow-up. How do we express interest in being one of the 5-10 participating states or in applying to be one?

We already sent out information through APHL to the state labs with details on how they can contact us to share their interest and get on the roster of PHLs that are interested in potentially participating in this initiative. Any PHL representative can e-mail us at [email protected] if they're interested in in being on the list, and we’ll be happy to start a discussion with them.

Suppose our clinical team is based in Massachusetts, but all of the chosen PHLs are from other states. In that case, would our Massachusetts-based clinical team be expected to perform recruiting/consenting of patients located in the states where the PHLs reside?

Applicant(s) must to propose a consent process that could be implemented in other states and has the ability to reach parents statewide. The reason is that we are aiming to assess the feasibility of this as a program that could be implemented statewide across multiple states. Ultimately, we would like to understand what the barriers are to incorporating this approach into newborn screening, which, of course, is statewide. We're trying to cast a very broad net in terms of including PHLs on the list. If we had the outcome we're hoping for, we would have all PHLs on the list. We're going to try to get the Massachusetts PHL on the list.

Is the goal of the program to establish NBSxWGS widely at the start or to scale the program to multiple states?

The goal of the program is to establish the feasibility of incorporating WGS into state NBS PHLs with a broad array of capacities for WGS. We anticipate that it will start small, although there might be opportunities to scale this up more broadly depending on the results and lessons learned from the Community of Practice.

What is the anticipated size of the effort (number of enrolled parents, number of WGS sequenced)?

The number of enrolled infants who are sequenced is dependent on the budget available and the overall project plan.

Can consent be obtained after the blood spot is drawn for NBS?

Yes, this would be possible. However, the consent timeline will be proposed by the prime awardee in their application and should be finalized during negotiations (with input from CAB and PHLs). Any consenting process proposed needs to accomplish the aims of the program in a timely manner.

Are you prepared to work with state PHLs that only have an opt-out process for NBS consent or do not have an existing consent interaction with parents? What difficulties do you see in working with these states?

Yes, we want to include PHLs with different levels of experience and different NBS consent protocols. We want to identify the challenges that occur in states that may not have an existing consent process.

Are PHLs required to be screening programs with access to bloodspots or can other entities (academic medical centers) in collaboration with state screening programs apply?

The goal of the program is to assess feasibility of adding WGS into the PHL workflow. To the extent that PHLs work with other entities, those other entities can be involved.

What is the expectation of returning results to parents? Will materials be developed on each of the disorders?

Yes, the screen-positive results would be returned to parents and/or providers. The prime recipient would develop the materials for sharing with the PHLs for return of results.

To participate is there a specific number of specimens or birth facilities per state that would be required to submit? If we are able to get one or two hospitals to work with us (PSHL) for obtaining consent would that be sufficient for submitting specimens for testing for this project?

There is no minimum number of birth facilities, but the goal of the program is to screen state-wide in order to have a representative sample from the entire state.

Will an IRB be needed to participate?

Yes, this is a research project involving human research participants and identifiable data, so IRB approval will be needed.

Do you anticipate that PHLs will continue their regular screening methods for some of the disorders, as I imagine there will be overlap. If so, will you collect data on time to reporting to PCP/diagnosis compared to these more standard methods?

Yes, this project will not interfere with traditional NBS, and we expect this to continue as normal with all participating PHLs. Primes could propose to collect data on time to reporting to PCP/diagnosis, but that is not a requirement of the ROA. The prime could propose to look at traditional biomarker screening relative to WGS-based screening, but this is not required.

Is NIH prepared to fund the participating PHLs for the modifications needed to LIMS, to staffing for retrieval, to staffing for convening the follow up working groups?

Yes, prime recipients should be considering factors like these when developing their budget estimates for PHL subawards. Exact subaward budget will be finalized during negotiations.

Could the consent be obtained after the blood spot is drawn?

Yes, the applicant could propose that the consent be obtained after the blood spot is drawn and just address this and how that consenting process would look in the application.

Is there an expectation of minimum sample volume? 

The sample required consists of punches from a dry blood spot card. One of the requirements for the sequencing function is to do a quality control to ensure that the dried blood spot punches provide a sample of sufficient quality and quantity for WGS and confirmatory testing. An applicant’s proposal should include what they think is the minimum number of punches required in order to adequately perform WGS and confirmatory testing as needed.

Does WGS mean Illumina short read technology?

We are platform agnostic.

Can next-generation sequencing (NGS) approaches other than WGS be proposed?

Our intent is to use WGS as the platform. There will be an expert panel that selects a list of conditions and target genes that will be used for screening. There is also flexibility to revise and optimize the target gene list as the study progresses. We want to allow the possibility for reinterrogating the WGS data should the target gene list change mid-study, which is why WGS has been proposed.

Are only dried blood spots (DBS) allowed, or are any other sample types accepted?

The main goal of this initiative is to evaluate the feasibility of incorporating genomic sequencing into the existing newborn screening program, which uses DBS. Accordingly, only DBS will be accepted because this research study will not modify the existing approach for collecting samples from newborns.

Can you confirm that you're proposing to use only leftover dried blood spots from existing NBS cards, without recommending any additional cards for this project?

That is correct. We are not proposing the collection of additional cards for any newborn. In addition, this is a prospective study, so we are not proposing the use of stored NBS cards from individuals born in the past.

What is the expected duration of the project?

The expected project duration is 3 years.

Are milestones and deliverables required for each project year?

Yes. Applicants are required to 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 should be provided in a table, an example of which is provided in ROA Section 8.4, Milestones and Deliverables.

Can you provide an example table of milestones and deliverables?

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, equipment, facilities, other resources, travel, and other associated costs.
• Note 3: Total cost (the sum of direct and indirect) for the tasks should 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 Bulleted list of tasks to complete Bulleted list of deliverables (including data sharing) Completion criteria for the task Potential risk factors and decision points	$100,000
1	1.2	1, 3	Milestone Name/Description Bulleted list of tasks to complete Bulleted list of deliverables (including data sharing) Completion criteria for the task Potential risk factors and decision points	$100,000
2	2.1	2, 6	Milestone Name/Description Bulleted list of tasks to complete Bulleted list of deliverables (including data sharing) Completion criteria for the task Potential risk factors and decision points	$100,000

What are the critical dates for submission of the full application?

Applications must be submitted via Application Submission System & Interface for Submission Tracking (ASSIST) by Wednesday, May 14, 2025, by 5 pm (based on the local time of the applicant organization). Applications received past this date will not be accepted.
To submit a full application, applicants must have submitted an LOI by Friday, April 4, 2025, local time of applicant organization. In addition, the email from NIH confirming receipt of the LOI must be included in the “Project Information Summary” section of the full application.

What registrations are necessary to submit a full application?

Full applications must be submitted via the NIH eRA ASSIST system. To submit an 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.

How do I submit my application?

• Applications must be prepared and submitted using NIH’s eRA ASSIST. 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 Principal Investigator (PI) and one person designated as the RBO.
• Applicants must submit the full application via the NIH eRA Commons ASSIST system no later than Wednesday, May 14, 2025, 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.
• 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.

Will NIH provide feedback on my application?

• 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.

Should applicants demonstrate ability to leverage work supported by previous/ongoing newborn sequencing projects with letters of support from peer organizations and subject matter experts that do not (or do not yet) have a role on the project?

As noted in Section 8.3. of the funding opportunity regarding Additional Letters of Support, “Only include letters [of support] from persons who have an assigned role in the project.” In the Detailed Research Plan section of your application, applicants must include “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.” However, those descriptions (and all other required information) must fit within the page limitation of the Detailed Research Plan section of the application, which is 20 pages total and no more than 5 pages per function.

When will the first funding period open? 

We anticipate NBSxWGS projects to be funded starting in FY25, with a maximum of 3-year project periods. The start date is anticipated to be no earlier than August 29, 2025, but no later than September 25, 2025. All key dates can be found on pp. 1 and 2 of the Research Opportunity Announcement OTA-25-004. 

What will the review process be like and who will make up the review panel?

The panel for the Objective Review will be recruited based on their expertise in relation to the scientific topics in the LOIs. The review panel does not make funding decisions but will provide recommendations regarding scientific feasibility and innovation based on the review criteria in the ROA. Based on the Objective Review, the NBSxWGS Working Group will make the final recommendations for funding to the NBSxWGS Working Group Co-chairs and the Common Fund Director.

What is the typical budget size for a team with one PI or a team with a PI and clinician?

The application budget should reflect the proposed activities and personnel. The awarded budget size is dependent on the objectives proposed in the application and subsequently negotiated prior to award issuance. The maximum award amount is $4.8 million dollars total cost each year for 3 years, but the appropriate budget size depends on the negotiated proposal, scientific progress once funded, and funds available per congressional appropriation.

Can PIs submit multiple proposals?

PIs are welcome to submit multiple proposals so long as the scientific focus is unique for each proposal submitted. As such, the submission of multiple proposals is not encouraged or discouraged.

Can we expect the same Venture initiative funding a year from now, or will the funding be given once?

We do not anticipate reissuing this ROA next year. The NBSxWGS initiative is a one-time opportunity that will fund projects for up to $4.8 million per award in FY25 with the level of funding in Year 2 and Year 3 contingent upon scientific progress and congressional appropriation of funding. If funding for awarded projects were to go beyond the three-year period, it would be through different program(s) at individual NIH ICs rather than through the Common Fund.

How many awards do you anticipate to fund?

We anticipate funding one award by August 31, 2025.

How can I follow the NBSxWGS initiative?

The Please consider signing up for the NBSxWGS listserv. You can follow the Common Fund X account for details about this initiative as well as other Common Fund programs: @NIH_CommonFund.

Are Plans for Enhancing Diverse Perspectives (PEDPs) required?

No, they are not required at this time.