1. What is the Common Fund? 

The NIH Common Fund supports bold scientific programs that catalyze discovery across all biomedical and behavioral research. It is managed by the Office of Strategic Coordination within the Office of the NIH Director, in collaboration with the NIH Institutes and Centers. Common Fund programs accelerate emerging science, enhance the biomedical research workforce, remove research roadblocks, or support high-risk high-reward science in ways that no other entity is likely or able to do. Read more about the NIH Common Fund.  

2. What is the relationship between the Nutrition for Precision Health program and the All of Us Research Program?
 
The NIH Common Fund-supported Nutrition for Precision Health program will undertake a multi-year precision nutrition study in collaboration with All of Us. Leveraging the NIH-funded All of Us Research Program will provide unprecedented opportunities to examine associations with a variety of long-term health outcomes. Nutrition for Precision Health and All of Us have a combined interest in precision medicine and nutrition research, however, each program has separate and specific individual goals and structure.
 

3. How will the program be managed?

The program will be managed by a trans-NIH collaborative work group (WG) drawn from NIH staff from All of Us, the Office of the Director, Office of Strategic Coordination (OSC) including the following institutes, centers and offices:

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Office of Behavioral and Social Sciences Research (OBSSR)
• Office of Research on Women’s Health (ORWH)
• Office of Dietary Supplements (ODS)  
•  National Center for Complementary and Integrative Health (NCCIH)
•  National Cancer Institute (NCI)   
•  National Heart Lung and Blood Institute (NHLBI) 
•  National Human Genome Research Institute (NHGRI)  
•  National Institute of  Aging (NIA)
•  National Institute of Biomedical Imaging and Bioengineering (NIBIB)
•  National Institute of Dental and Craniofacial Research (NIDCR) 
•  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
•  National Institute of Environmental Health Sciences (NIEHS)
•  National Institute on Drug Abuse (NIA)    
•  National Institute on Minority Health and Health Disparities (NIMHD) 

The WG has expertise in genetics, metabolic phenotyping, microbiome ecology, metabolism, nutrition, dietary assessment, energy balance, physiology, clinical trials, controlled feeding studies, biostatistics, artificial intelligence, and statistical genetics.

5. Who should I contact with questions about the Nutrition for Precision Health program?
All inquiries may be directed to: 

Holly Nicastro, Ph.D., M.P.H., NIH Office of Nutrition Research
Telephone: 301-435-0383 Email: nutritionresearch@mail.nih.gov

Christopher Lynch, Ph.D., NIH Office of Nutrition Research
Telephone: 301-827-3988 Email: nutritionresearch@mail.nih.gov

1.When will the Nutrition for Precision Health program start enrollment?

We anticipate that the program will begin enrolling participants by January 2023. 

2. Who will be eligible to enroll in the study? 

The Nutrition for Precision Health program plans to recruit participants from the All of Us Research Program, which currently enrolls adults 18 years of age and older, through a separate informed consent process. All of Us participants provide rich information through surveys, EHRs, biosamples, and digital health technologies. Through this study, a segment of All of Us participants will have the opportunity to provide additional information and samples that—in combination with data they already provide through All of Us—will enable more in-depth nutrition research.

If people are interested in potentially joining Nutrition for Precision Health in the future, but aren’t already part of All of Us, they’re welcome to visit joinallofus.org to learn more.

3.    Will the program enroll children?

Nutrition for Precision Health will enroll All of Research Program Participants. As of now, the All of Research Program is not enrolling children, and so it is anticipated there will not be children enrolled in Nutrition for Precision Health at this time. 
 

1. Should All of Us PIs be included on each grant application?
It is not required to include All of Us investigators on applications for RFA-RM-21-001, RFA-RM-21-002, RFA-RM-21-003, RFA-RM-21-004, or RFA-RM-21-006. Where geographically feasible, Clinical Center (RFA-RM-21-005) applicants should work with All of Us Health Care Provider Organizations (HPOs) to engage and enroll participants from the All of Us cohort to participate in the Nutrition for Precision Health study. If necessary, Clinical Centers should assist prospective participants with enrollment to All of Us prior to enrollment in Nutrition for Precision Health. Clinical Centers may propose collaborations with other institutions as needed to enhance research expertise, enrollment capacity, and diversity of participants to adhere to All of Us Research Program overall enrollment expectations (https://allofus.nih.gov/about/diversity-and-inclusion). Important to the Nutrition for Precision Health goals, participants in modules 1-3 should reflect the diversity of the United States population. Where it is not geographically feasible to partner with an existing All of Us HPO, Clinical Centers will implement the All of Us enrollment protocol (https://allofus.nih.gov/about/all-us-research-program-protocol) for new All of Us participants, including collection of participant-provided information, physical measurements, and biospecimens, and linking electronic health records. This will require regulatory onboarding steps including executing a reliance agreement, All of Us IRB approval, and an interconnection security agreement to share EHRs and implement the protocol. We encourage applicants interested in this option to contact us to discuss prior to your application. Clinical Center applicants are encouraged to consider inclusion of All of Us Health Care Provider Organization (HPO) personnel in the award structure when partnering with an existing HPO.

2. I don’t have an All of Us enrollment site at my institution. Can I still apply to participate in this program?
Where it is not geographically feasible to partner with an existing All of Us HPO, Clinical Centers will implement the All of Us enrollment protocol (https://allofus.nih.gov/about/all-us-research-program-protocol) for new All of Us participants, including collection of participant-provided information, physical measurements, and biospecimens, and linking electronic health records. This will require regulatory onboarding steps including executing a reliance agreement, All of Us IRB approval, and an interconnection security agreement to share EHRs and implement the protocol.
 

3. How will data be collected, stored, and analyzed in the study?
Data collection
Nutrition for Precision Health will be embedded in the All of Us Research Program. Clinical Centers will collect new primary data from participants, and Clinical Centers, Biobank, Dietary Assessment Center, Metabolomics and Clinical Assay Center, Microbiome and Metagenomics Center, and the Research Coordinating Center may all generate new data from participants’ biosamples, measurements, and provided information.

Data processing and curation
The Dietary Assessment Center, Metabolomics and Clinical Assay Center, and Microbiome and Metagenomics Center will all pre-process and clean data that they generate, and these centers may analyze their respective data separately. All data will then be curated by the Research Coordinating Center and Data and Research Center. The Data and Research Center will upload Nutrition for Precision Health Study data to the All of Us Researcher Workbench.
 

Data analysis and storage
All data will be stored within the All of Us Researcher Workbench. Nutrition for Precision Health investigators, including those with the Artificial Intelligence, Multimodal Data Modeling, and Bioinformatics Center, will analyze Nutrition for Precision Health data within the All of Us Researcher Workbench. The All of Us Researcher Workbench platform and its suite of custom tools are made available to approved researchers. The Researcher Workbench provides access to Registered Tier data. Its powerful tools support data analysis and collaboration. The workbench also provides integrated help and educational resources through the Workbench User Support Hub.
 

4. What is expected to happen at each module of the Nutrition for Precision Health Study?
Nutrition for Precision Health is a modular discovery science study:

Module 1will follow approximately 10,000 participants for up to 14 days to examine baseline diet and physiological responses to the test meal challenge. Module 1 is anticipated to consist of two clinic visits approximately two weeks apart, with remote data collection during the study period.

Module 2 is expected to be a free-living controlled feeding study that will examine responses to three short-term (~14 days) intervention diets in approximately 1,500-2,000 Module 1 participants. Additionally, after each intervention diet, physiological responses to the test meal will be assessed.

Module 3 is expected to be a domiciled controlled feeding study that will examine responses to the same three short-term (~14 days) intervention diets in approximately 500-1,000 participants from Module 1. Additionally, after each intervention diet, physiological responses to the test meal will be assessed.
 

In all 3 modules, investigators will collect dietary, microbiome, physiological, metabolic, behavioral, cognitive, environmental, and contextual data, and leverage standard All of Us collected genomic, electronic health, and survey data to model the impact of diet and dietary patterns on physiological responses.

5. Is being a grantee of the All of Us program a prerequisite or an advantage for successful application to any of these RFA’s? 
 No, being an existing grantee of the All of Us Research Program is not a pre-requisite for NPH applications and being a grantee of an All of Us award is not a criterion for peer     review for any of the RFAs. Applicants should describe in their applications how they will work with All of Us, as required in individual RFAs.

6. Can an institute submit multiple applications for the same RFA?
Yes, Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time. 

7. Can different investigators from the same institution submit applications to multiple RFAs?
    Yes.
8. Will all participant interface/enrollment happen within Clinical Centers?
   Yes, Clinical centers will be involved in recruiting and enrolling participants. 

9.  Are the award budgets listed in the FOAs total costs or direct costs?
     These number refer to total (direct + indirect) costs, and are estimates and maximum allowable costs.

10. Will NPH awardees return any results to participants? 
      Details on returning results to participants, including any potential algorithms or personalized recommendations, will developed during the planning year. Return of results             will likely be conducted in collaboration with the All of Us components of NPH.

11. We can reduce costs substantially if the biorepository is able to ship specimens in a specific type of tube. Will we have the opportunity for this type of negotiation with the biorepository?
       Yes, these activities will occur during the planning year. Negotiations will occur post award with funded PIs.

12.  Do I need to request special permission to submit an application totaling more than $500K in direct costs in a given year, or will I need the administering IC to send CSR an Awaiting Receipt of Application (ARA) form?
     No. ARA budget rules do not apply to an RFA as the funds are set aside and budget limitations are stated in the published FOA.

13. What is the Common Fund Data Ecosystem (CFDE)?
The NIH Common Fund (CF) programs are intended to provide resources that accelerate discovery across many different biomedical research fields. These resources include large data sets and associated digital tools needed to mine and analyze the data. To maximize their impact, data sets and tools generated by the CF programs must be usable together. Towards achieving this goal, the Common Fund created the Common Fund Data Ecosystem (CFDE), a data management infrastructure where the interconnected ecosystem facilitates scientific advances by ensuring CF data and digital objects are usable and useful both within a program and in combination with data from other programs. Aims of the CFDE are to enhance the ability to ask scientific questions; enable the uptake, reuse, and addition of data sets generated by the future, current and ended CF programs and support their sustainability; and provide training that maximizes scientists’ ability to use the CF data sets and tools. The CFDE is composed of a CFDE Coordination Center (CFDE-CC) and the data coordinating centers (DCCs) of the participating CF Programs. CFDE teams will work towards standardizing the data deposition/structuring/handling to make data FAIR, adapting data and metadata standards to enable interoperability, and providing training about the available CF resources to the scientific community. New CF programs (e.g., Nutrition for Precision Health) are expected to engage in the CFDE from the start. This can be achieved by designing the program components such that they: i) construct a data infrastructure which ensures FAIRness of the data, and ii) adapt the appropriate data and metadata standards to enable interoperability of the generated data with other data sets. The Nutrition for Precision Health Research Coordinating Center will be the primary point of contact with the CFDE. Applicants are expected to discuss their plans for ensuring compatibility with the CFDE and other Common Fund datasets and resources (e.g., via the CFDE portal, Metabolomics Workbench and the MoTrPAC Data Hub) in their proposal.

14. What is STRIDES?
The NIH Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) initiative has established partnerships with commercial cloud service providers (CSPs) Google and Amazon Web Services (AWS) to provide favorable pricing for cloud-based costs. The NIH Common Fund, managed by the Office of Strategic Coordination, is using the STRIDES partnerships to provide in-kind support for CSP costs. For more details, please see NOT-RM-20-009.
 

15. Who should I contact if I have questions about RFA-RM-21-001, RFA-RM-21-002, RFA-RM-21-003, RFA-RM-21-004, RFA-RM-21-005, RFA-RM-21-006?
For individual RFAs, Scientific and Research contacts are indicated in each announcement and these individuals should be your first contact for questions related to that RFA. In addition, the Common Fund Nutrition for Precision Health Program is administered via a team of NIH program experts. The NIH Working Group members and their affiliations are listed at: https://commonfund.nih.gov/nutritionforprecisionhealth/members.

1. What is the appropriate expertise for applicants?
Applicants should assemble a multi-disciplinary team with expertise in biomedical data science, systems biology, artificial intelligence, and nutrition as well as other biological and physical science expertise.
 

2. Study data won’t be available until years 2 or 3 of the award. What activities will be conducted by the Artificial Intelligence, Multimodal Data Modeling, and Bioinformatics (AIMDMB) Center in each year of the award?
Applicants are encouraged to identify other data sets of value to driving development of their tools, technologies, platforms, or algorithms. Leveraging existing, relevant data sets of sufficient similarity (e.g., All of Us, or other), to guide and / or optimize Center’s informatic platform development, data integration, algorithm development or data visualization tools prior to study data delivery will be important to successful projects. The data types will also be collectively determined during the initial years, by the consortium, and this will enable specific platforms to targeted or optimized towards those data types – keep in mind that many data types and measurements are already determined by the nature of the Nutrition for Precision Health consortium structure yet many will be determined after the final recipients, clinical centers, and all collective projects are awarded. As such, the first several years should be targeted towards: development of tools with non-study data; collaboration with the consortium; formulation of AI-specific gold standards for all data types; participating in development of the clinical study protocol, in collaboration with Steering Committee, for defining data standards, curation, and provenance needs; development of transparent, ethical protocols and procedures for working with study data within the All of Us Researcher Workbench; and other aspects specific to the AIMDMB Center project’s proposed in the application.

3. The RFA states that the AIMDMB Center’s Administrative and Coordination Core must include pilot projects. How should these be structured?

AIMDMB Center’s Administrative and Coordination Core must include pilot projects that have significant potential to address developing needs and opportunities identified by way of the collective decision, as to their focus and needs, from the Nutrition for Precision Health consortium's Steering Committee. This will be determined after the awards have been made and continuing on through the study timeline. As such, no pilot needs to be outright defined or developed to be included in the application. Applicants may suggest (few sentences identifying) example projects that could be undertaken by the AIMDMB Center relative to its structure, proposed projects, or leveraging existing collaborations that will make it unique to other applications.
 

4. AI algorithm performance and robustness, in terms of its use for human data, is coupled to sample size and ethical incorporation of a broad set of population demographics. Will the Nutrition for Precision Health study be both large and broad?
You are encouraged to read FAQ above “What does modular mean?” for sample size. The study is anticipated to include participants from multiple demographic backgrounds that include a sampling of the total U.S. population. Further, the AIMDMB Center will be central to the study in defining data requirements, provenance, and clinical protocols to prospectively define needs for optimal AI performance and robustness during the first year(s) of the study.

5.How will AIMDMB interact with pre-existing data from All of Us Workbench, such as genomics and clinical?  
The AIMDMB Center will use existing data in the Researcher Workbench in combination with new NPH data to develop algorithms, inform about interoperability, reduce bias/noise, and many other functions of value to the NPH Study.  

6.Will AIMDMB host any pre-existing data, or will pre-existing data continue to be hosted separately in the All of Us Workbench environment and AIMDMB will only need to integrate with those data through APIs? 
The AIMDMB may work with other data sets to develop/optimize tools, methods and workflows. We expect this will be most valuable in the early stage of the program – prior to study data being generated. Although, all NPH and All of Us data will be hosted in the All of Us Researcher Workbench and not on separate servers of the AIMDMB Center.

7. Is the pilot program intended to give sub-awards to any investigator within the Consortium or also outside of the Consortium? Can industry receive pilot grants?
Pilot projects to be suggested in the application should focus on needs of the consortium and can be used for any meritorious project/investigator within or outside of the NPH Consortium. All pilot projects will be presented to the NPH Consortium Steering Committee for authorization to proceed after the program has begun. This is to ensure that the projects that are run under the AI Center are in the best scientific interests to drive the goals of the NPH Study. For-profit organizations can receive pilot grants as a sub-awardee to the Center.

8. Is the $250,000 per year for pilot project support included in the AIMDMB Center budget, or is it additional?
The $250K support per year should be built into the Center budget – it falls under the yearly total cost limits of support. 

9. How are the activities of the Research Coordinating Center distinct from those of the AIMDMB Center?
The RCC will be responsible for the overall coordination and administrative management (logistics, communication, and organization) of NPH, clinical study administration (Coordinate the development and approval of the clinical protocols, manual of operation, data and safety monitoring plan, data entry/case report forms for clinical centers to complete, and management of the Central IRB oversight process for the clinical studies) and data and biospecimen administration (collect the data from clinical and data generation centers and transmit the data to All of Us Research Program, track biospecimen collection and shipping, be the primary point of contact between NPH and the Common Fund Data Ecosystem and the All of Us Research Program). 

The AIMDMB will be responsible for incorporating and building all methods, tools, and models to develop actively learning algorithms from the multimodal data stored in the All of Us Researcher Workbench (i.e., the collective post-transmission output of study / participant data); acting as a resource for understanding the needs, standards, ethical concerns etc. needed to inform standardized metrics/protocols for ‘AI-ready’ biomedical data; pilot studies or projects that are of interest and need to the overall NPH Consortium; and, ultimately, in silico human dietary response replicates or user-tailored, high-fidelity models that incorporate demographic, environmental, behavioral, multi-omic, social, cultural, clinical or other data to predict health trajectories.  More details are listed in FOA for other desirable aspects of the AIMDMB Center. 

We anticipate that during the planning year (year 1) the Steering Committee, including representation from all NPH awards including the RCC, AIMDMB, All of Us Data and Research Center, will work closely to determine who will be responsible for each step of data curation, data quality control, data standardization, data transformation, etc. that are required to complete the project. 

1. Should Metabolomics and Clinical Assays Center (MCAC) applicants plan to run both unbiased metabolomics and targeted MS/MS on ALL samples? Or is the workflow such that discovery is performed for Module 1 and targeted MS/MS in modules 2 and 3?
MCAC applicant should plan to run both targeted and untargeted metabolomics on all samples. The specifics of actual numbers and workflows would be decided by the Steering Committee during the initial planning phase.

2. Should MCAC applicants budget for biospecimen collection materials, shipping, and courier logistics?
No, these costs will be built into the budget for the Biobank.

1.When is it estimated that the extraction, library prep and sequencing of the estimated 17,500 samples will occur during the funding period? Will the processing of the samples occur all at once to avoid batch effect or will they be submitted for processing to the Microbiome and Metagenomics Center (MMC) as samples are collected as they are obtained during the entire funding period?
Analysis of samples will have to occur within the project period. Discussions related to processing of samples and other measures to avoid variations in measurements will take place and be agreed upon by the NPH Steering Committee during the planning year.

2. For the proposed pilot projects within the Microbiome and Metagenomics Center, do they need to be limited to the task/ responsibilities of the center (i.e. extraction, sequencing and data QC) or can they include additional tasks be i, i.e. bioinformatic approaches to use/analyze microbiome seq data or relate it to other data types, other applications of data generated, relating new data to existing datasets, etc?
The MMC may propose pilot studies to support innovative methodologies that may improve existing methods to ensure high resolution microbiome compositional and functional information or enable more affordable analytical methods.

3. Does the sequencing approach need to include 16S amplicon sequencing for all samples and then a subset be for metagenomic and metatranscriptomics? or can it focus on metagenomic, metatranscriptomics, epigenetics and single cell sequencing?
We are looking for both high throughput 16S amplicon approaches as well as metagenomic and metatranscriptomics on subset of samples. You may propose more advanced approaches and as appropriate and supported by the budget.

4. Should Microbiome and Metagenomics Center applicants’ budget for biospecimen collection materials, shipping, and courier logistics?
 No, these costs will be built into the budget for the Biobank.

1. What can I do if I don’t have an All of Us enrollment site at my institution?

Where it is not geographically feasible to partner with an existing All of Us HPO, Clinical Centers (CCs) will implement the All of Us enrollment protocol (https://allofus.nih.gov/about/all-us-research-program-protocol) for new All of Us participants, including collection of participant-provided information, physical measurements, and biospecimens, and linking electronic health records. This will require regulatory onboarding steps including executing a reliance agreement, All of Us IRB approval, and an interconnection security agreement to share EHRs and implement the protocol.

2. Will all awardees need to conduct all 3 modules of the study?
All CCs are expected to participate in Module 1 and at least one other module.

3. Which dietary patterns will be tested in the study?
In Modules 2 and 3, Clinical Centers will implement three specific, isocaloric dietary interventions that are meaningfully different from each other and which would be expected to elicit different and measurable responses over an approximately two-week intervention period. It is expected that the consortium, including the Clinical Centers, will make the final decision on which dietary interventions and measures will ultimately be deployed across the consortium.
 

4. What should applicants propose regarding dietary intervention and mixed meal challenges?
The same mixed meal challenge will be conducted in modules 1, 2 and 3. All Clinical Center applicants should propose one type of mixed meal challenge. The proposed mixed meal challenge should be designed to produce different metabolic responses among individual participants in order to provide individual-level dietary response information for precision nutrition algorithm develop. The same 3 isocaloric dietary intervention will be conducted in all participants in modules 2 and 3. All Clinical Center applicants should also propose 3 different, isocaloric diets. The 3 isocaloric dietary interventions should not be designed to induce weight loss, but should be designed to produce differential metabolic responses among individual participants in order to provide individual-level dietary response information for precision nutrition algorithm development.

5. Is there randomization or a clinical trial in Module 1?
    No.

6. What sample size should each Clinical Center applicant propose?
The RFA provides general guidance on the total sample size for modules 1-3. Each applicant should propose to enroll a feasible and justifiable number of participants.

7.What are the requirements for the inclusion of investigators from the All of Us sites? Do they need to be Principle Investigators (PIs) or should they be Co-Investigators?
Besides the requirement to include an All of Us investigator on the team, there is no specific requirement for how you should structure this collaboration. Applicants should propose and justify what works best for their team.

8.  What will be the inclusion and exclusion criteria for the study?
The study inclusion and exclusion criteria will be discussed within the consortium and agreed upon during the planning year. 

9. How long is the wash out period between the diets?
This will be agreed upon by the consortium during the planning year. Clinical Center applicants should propose and justify a reasonable washout period length in their application.

10. Should a standard diet be included as a major control arm?
Investigators should propose 3 different dietary patterns. The dietary patterns should be designed to produce differential metabolic responses among individual participants in order to provide individual-level dietary response information for precision nutrition algorithm development. There is no “control” diet.

11. Can Clinical Centers recruit and refer participants to All of Us?
Yes. Clinical Centers can enroll new participants into All of Us and subsequently enroll them into Nutrition for Precision Health.

1. Will the Research Coordinating Center (RCC) be responsible for data sharing?
The RCC will be responsible for managing data sharing workflows. Any proposed data sharing plan needs to be consistent with the All of Us Research Program’s data sharing policies (https://allofus.nih.gov/about/core-values). RCC awardee(s) will ensure that data are submitted in a timely fashion to the All of Us Researcher Workbench, that resources developed as part of this project are made publicly available according to consortium policies, and that results are disseminated in a timely manner. The PD/PI is responsible for the proper stewardship of the data, including accurate annotation, disclosure of any pre-processing, data use limitations, data provenance and other associated metadata as determined by any consortium and All of Us policies.

2. How will the RCC interact with the All of Us Research Program?
The RCC will work collaboratively, as part of the Nutrition for Precision Health consortium, to develop and implement research protocols and manage data sharing workflows. The RCC must also serve as a key partner with the All of Us Research Program, since it is anticipated that all participants enrolled in the Nutrition for Precision Health dietary studies will be participants in the All of Us Research Program, and all Nutrition for Precision Health data will be shared via the All of Us Researcher Workbench.