Q1: Can a U54 Center be formed within the same organization?
A: Yes. It is up to each U54 Center to decide how to assemble/integrate necessary expertise and capabilities required to achieve the research objectives. They may establish the Center via a multi-institutional arrangement or multi-laboratory arrangement within its own organization.
Q2: Is each U54 Center expected to have an Informatics group?
A: Yes. U54 Informatics group will support informatic analyses for the Center's research projects as needed and will establish and maintain project specific database.
Q3: For data storage and public dissemination, will these functions be performed by U54 CAP-IT Center?
A: U54 Centers will establish project specific databases. For public dissemination of results and resources, each U54 Center will follow policies developed and approved by CAP-IT SC and NIH sharing policies.
Q4: What is the relationship between U24 DRCC and U54 Informatics group?
A: Each U54 Center informatics group will work with U24 DRCC, which is tasked to establish and maintain a centralized database for intra-network data sharing and a centralized information hub for network-shareable digitally identifiable research tools and resources in accordance with the policies established by the CAP-IT SC.
Q5: Are there any requirements for each U54 Center-specific internal/external advisory boards?
A: No. NCI plans to form internal and external advisory panels for the entire program.
Q6: Target discovery is not part of CAP-IT research?
A: Correct. However, U54 Centers' research projects can include the identification and prioritization of targets that can be exploited for preventive or interceptive interventions through collaborations with NCI or other programs with a research focus on molecular profiling of precancer, early cancer, and/or oncogenic signaling pathways.
Q7: What would be considered high-risk populations?
A: In the context of the RFAs, high-risk populations are defined as individuals with an increased risk of cancer such as those with hereditary cancer syndromes (e.g., Lynch syndrome, hereditary breast and ovarian cancer syndrome, Li-Fraumeni syndrome, etc.) and those with precursor abnormalities that place individuals at a higher risk of cancer. These individuals may have been exposed to carcinogens or have other conditions known to increase the cancer risk.
Q8: How long can a project last?
A: Up to 4 years.
Q9: Should each U54 Center pick one target pathway as their focus or can each independent research project focus on a different molecular target?
A: Either is acceptable. It is up to each U54 Center to decide.
Q10: Does a U54 research project need to start at target validation?
A: Projects can start at any point within the scope of CAP-IT research.
Q11: Are med chem activities for lead compound optimization allowed in U54 research projects?
A: No. Research activities involving iterative chemical optimization for lead compound identification are outside the scope of the expected activities.
Q12: What would “agent screening” in CAP-IT research projects be like?
A: Screening of focused chemical libraries with well-characterized compounds, such as FDA-approved drug library, NIH Clinical Collection libraries, and/or pathway-specific libraries of drug-like small molecules with validated biological activities would be allowed. High-throughput screening of large compound libraries is outside the scope.
Q13: Can we use human biospecimens, such as cell lines or tumor specimens, for target validation and other research within CAP-IT?
A: Yes.
Q14: What would be the final products coming out of CAP-IT?
A: The successful final products coming out of CAP-IT will be agents that show intended functional activities in relevant animal models without signs of overt toxicity and can be advanced to further preclinical development.
Q15: Can we collaborate with non-CAP-IT investigators after the program launch?
A: Yes. Administrative supplements are planned for years 2 ~ 4 of the program.
Q16: Can we have a project PI who is based in a foreign country?
A: Yes.
Q17: Can one propose additional cores or alternatives to the informatics core?
A: Yes, as long as they fulfill the requirements described in the RFAs.
Q18: Regarding oncotarget validation, suppose we identified 30 genes with bioinformatics. Some are under-investigated; some are investigated in other cancer or in other context (eg. aging etc). Does the NIH have preference on the types of oncotargets to be investigated? Novelty or repositioning?
A: Our preference is that you prioritize genes or potential targets for validation, which can be linked to a specific group of high-risk individuals described earlier. It does not have to be a single group, as some oncotargets may be linked to multiple high-risk groups.
Q19: Can CAP-IT U54 have an internal advisory board in addition to the network wide one?
A: It is not required; however, it is allowed.
Q20: Do we have to submit a budget with each of the first two proposed projects?
A: Please follow NIH SF424 (R&R) instructions.
Q21: Is synergy a review criterion or it will just be taken into consideration for scoring overall application?
A: Yes, synergy is a very important component, as we emphasize on building multi-disciplinary teams for each U54 center Research Project. Reviewers will provide an overall Impact Score for the entire U54 Center (Overall component). The Overall Impact Score will reflect the synergy and integration provided by inclusion of each CAP-IT Center component. Please see Section V in the FOA for more details.
Q22: Can the informatics core be part of the administrative core, or does it have to be a separate core?
A: It is up to each U54 Center. it can be part of the administrative core or any other subunits such as agent screening group.
Q23: Will med chem be allowed for novel molecule design and synthesis to develop a lead compound?
A: No. New chemical entity (NCE) related med chem research projects will be considered non-responsive to the FOA. (Please also see Q11)
Q24: Do you foresee any R01-style funding opportunity for individual investigators?
A: Yes and No. We are planning administrative supplements, which will allow CAP-IT Centers to collaborate with non-CAP-IT investigators through their existing grants such as R01.
Q25: Is cervical intraepithelial neoplasia (CIN) considered a high-risk population for this mechanism?
A: Yes.
Q26: If iterative molecule lead optimization is out of the scope of this FOA, what is the line NCI is using to demark between lead optimization and lead molecule development? For example, is rational design of analogs for lead molecule development allowed?
A: If the objective is to rationally optimize existing well characterized compounds to improve efficacy or reduce toxicity, this should be acceptable. The objective needs to be specified and justified. NCE optimization efforts are not allowed. (Please also see Q11 and Q23)
Q27: Is institutional support, for example, providing additional seed money to support/develop a third project, a requirement or beneficial during the review process?
A: Additional seed money to develop a third project (after the program launch) would be beneficial but not required. If this is the case, factors such as a clear plan in securing additional funding, Center's multi-disciplinary team composition and how they will be scientifically advantageous to advance the Program's goal should be specified in the application.
Q28: Is specific aims page a part of the overall component (12 pages) or a separate page?
A: Please refer to the standard NIH grants application guide:
Q29: Regarding future Project (3) in year 2 or later, are there any specific budget guidelines or use just anticipated budget?
A: Our expectation for U54 Center Research Projects is that the cost for different phases of discovery research projects will differ and thus each Center will be able to carry out multiple projects in parallel and/or in a staggered manner over the 5-year period, and that not all Projects will last 5 years. Please follow NIH SF424 (R&R) instructions for budget proposals.
Q30: For multi-PI leadership proposal, will a letter of intent from contact PI be sufficient or should multiple PIs need to submit a separate letter of intent?
A: Please send one LOI per one U54 application. No need to send separate LOIs. You may list PI and co-PI, if applicable.