No, COBRE-E/S funds cannot be used to support NIH-defined clinical trials. According to the National Institutes of Health (NIH) website, a clinical trial (CT) is a research study in which human participants are prospectively assigned to one or more interventions to evaluate the effects on health-related biomedical or behavioral outcomes. As organizations consider the focus of the COBRE, if the broad area of science relies on SIs (Science Research Program Investigators) conducting clinical trials, then the organization may want to reconsider the COBRE’s focus. COBRE-E/S applications that propose a broad scientific area reliant on clinical trials will be withdrawn prior to review.

The IDeA-CTR program focuses on building clinical trial capacity. Please see the IDeA-CTR NOFO PAR-27-056 for more information.

Yes, COBRE-E/S allows human subject (HS) research but not clinical trials. As a reminder, research focusing on CTs versus HS research as part of an SI’s research program is outside of the scope of the NOFO.

Clinical trials are an important part of NIH’s mission. Clinical trials are expensive and often have methodology or design issues that can yield inconclusive or misleading results. Additionally, participant recruitment and retention frequently undermine trial integrity. This can delay trial timelines, increase costs, and compromise the generalizability of the findings. Other issues such as inappropriate selection of study endpoints, lack of blinding, or poor patient adherence to the study protocol can introduce bias or render the results unreliable.

The IDeA-CTR NOFO PAR-27-056 better addresses some of these challenges by facilitating well-planned clinicals through preparatory studies. Although scientific literature or preliminary data may provide the rationale for conducting a clinical trial, investigators often lack critical information about the study population, accrual challenges, intervention, outcome/ endpoints, data/statistical challenges or operational risks necessary to finalize the trial protocol completely. These information gaps can result in multiple protocol changes before and after trial start-up, leading to the need for additional time and expenses that may prevent study completion. Further, the suitability and feasibility of new trial designs, which minimize infrastructure and reduce costs may need to be tested in the context of a particular intervention, at-risk group, symptom or setting. Preparatory studies may fill information gaps and address unknowns this can include a pilot/feasibility clinical trial if necessary, improving trial design and rigor.

If an existing COBRE has a core that supports CT research, then in the new COBRE-E/S structure this core is no longer viable given that CT are not allowed in COBRE-E/S. Work involving CTs may not transition to either COBRE-E or COBRE-S.

Yes, provided the program of research conducted by the SI during the COBRE project period does not involve a clinical trial.

NIH does not consider Basic Experimental Studies involving Humans (BESH) to be clinical trials. BESH studies are allowed by COBRE-E/S. Mechanistic clinical trials are considered clinical trials and are not allowed in COBRE-E/S.

Yes, provided these IRB approvals do not involve clinical trials.

No.

Active COBRE Phase 1 grants, including those in No-Cost Extension (NCE), are eligible to transition into COBRE-E. Active COBRE Phase 2 grants, including those in NCE, are eligible to transition into COBRE-S. COBRE Phase 3 grants do not transition into another COBRE. These grants will end at the conclusion of the project period.

Yes, the requirement to apply for a COBRE-S is to hold an active Phase 2 or COBRE-E award.

Limited Competition designation means only institutions IDeA states and territory are eligible to apply to COBRE-D-E-S.

The cap of 4 active COBREs per institution, including those in NCE, still applies. COBRE Phase 1, COBRE Phase 2, COBRE-D, COBRE-E, and COBRE-S awards count towards the total institutional cap. The four-COBRE eligibility restriction applies to NEW COBREs only. If an institution has four active COBREs (including those in NCE), applications will be accepted for centers transitioning Phases (1 to E or 2 to S) because that would not increase the institution’s total above the cap. Those institutions cannot apply for a “New” COBRE-E because that would exceed the four-COBRE cap.

Yes, all applications submitted to PAR-27-055 are considered “New” applications. This has several implications:

• All applications will receive a new grant number.
• Do not apply as a “Resubmission” of an unsuccessful Phase 1 application (A1) or a “Renewal” (T2) of a Phase 1 or Phase 2.
• New applications do not allow carryover of funds between Phase 1 and COBRE-E or Phase 2 and COBRE-S. A Phase 1 COBRE and a COBRE-E or a Phase 2 COBRE and a COBRE-S awards may run concurrently provided there are no overlapping activities between the awards.

The goal of COBRE is to build the research capacity at the applicant institution. COBRE-E/S gives organizations the flexibility to leverage the existing faculty base across the organization while allowing the hiring of individuals to address critical capacity needs based on the organization’s strategic goals.

COBRE-E is intended for institutions that have already developed some level of research capacity. In general, this means they have been successful in the past at developing faculty and infrastructure in specific areas of research. This is demonstrated by either:

1. holding a COBRE Phase 1 that has been productive and can transition to the next Phase by expanding the work being carried out or
2. have faculty and infrastructure that can be redirected to the newly proposed broad scientific area of the center.
3.  

If an applicant organization already has a sizeable number of faculty in the planned broad research area along with substantial institutional infrastructure and/or support, then capacity already exists and may not warrant COBRE support. The key is to propose a COBRE-E that is broad in scientific scope versus one that is narrow.

In this case, the institution already has a solid level of research capacity in the area which would obviate the need for COBRE support; therefore, a COBRE application in “X” would be of low programmatic priority. The intent of “New” COBRE-E centers is to repurpose existing research capacity into a new area amenable to growth and sustainability in alignment with institutional priorities.

No. COBRE-E and COBRE-S are intended to support research capacity at the applicant institution; therefore, joint applications involving two institutions are not allowed.

No. PAR-27-055 states that the proposed COBRE PD/PI “be the PD/PI on at least one active, peer-reviewed, and externally funded research grant within the general scientific area of the COBRE.”

Any NIH RPG (e.g., R01, R03, R15, R16, R21, R35) that supports the PI’s research program is sufficient to confer eligibility. The Principal Investigator is evaluated as part of the review criteria, and NIH peer review may consider the quality and extent of their support.

NIH does not recognize the term co-PI. To continue as a COBRE PI, an investigator must be the PD/PI on at least one active, peer-reviewed, and externally funded research grant within the general scientific area of the COBRE. This requirement applies to all PD(s)/PI(s) in an MPI application.

Yes, the COBRE PI must serve as the Administrative Core Director.

Management and administration of Research Core services must be carried out by individuals employed by the applicant institution.

NThe costs associated with the recruitment of faculty members should be included in the Administrative Core.

It is up to each grantee to decide how to structure the administrative aspects of the COBRE. Each core director must be appointed at the applicant organization.

Pilot project programs are not allowed in COBRE-E/S.

Voucher programs for Core usage may be proposed at the time of the application and at the discretion of the applicant organization.

Yes, this is acceptable if the SI commits a minimum of 6.0 PM to their COBRE-supported research program. Applicant organizations should note that it is generally not advisable for an SI to be heavily involved in any administrative duties of the center. The success of the center is for SIs to transition to independence.

Unlike previous COBRE NOFOs, COBRE-E/S does not require great specificity regarding the A&R activities. The description should be sufficient to justify the expense.

A primary appointment requires that the individual be employed by the applicant institution, with at least 51% salary support and dedicated laboratory space at the applicant organization.

The description of each core is limited to 6 pages.

Subawards for personnel (PI, SI, core director) are not allowed as they are required to be appointed at the applicant institution.

No.

It is up to each applicant organization to decide. Institutions should ideally develop their own capacity to do self-assessments of their progress in meeting self-determined milestones and benchmarks.

No. If the resources already exist, it is not necessary to propose it as a separate component in the COBRE application. Funds can be allocated to make use of the existing core without proposing it as part of the COBRE. An arrangement of this sort demonstrates that the institution is leveraging existing research capacity and infrastructure.

Yes, this is allowed.

The SRP Core Director should be listed as key personnel. Do not list SIs as key personnel.

Yes, each core is required to have a named director, including the SRP Core.

The SRP section of the application should not include detailed project descriptions nor Specific Aims. It should describe the SI pool, including potential hires, and the general scientific program of the potential SIs. The description should address the broad research area of the COBRE and how the activities will advance the career of the SIs while building the research capacity at the applicant organization.

The language in the NOFO indicates that a detailed budget (SF424 R&R budget) is required. For the SRP budget the applicant may request a lump sum with the proper justifications. A detailed budget will be submitted once SIs are chosen and prior approval for funding is submitted.

Prospective Advisory Committee (AC) members should not be named in the application. Advisory Committee members who served in a prior Phase may continue into the new one. Biosketches are not required for AC members who will continue into the new COBRE Phase.

The role of AC is to critically evaluate the SI’s research plan in terms of significance of the scientific problem, alignment with agency priorities and ensure that the proposed experiments are not leading to possible dangerous gain-of-function (DGOF) research and other high-risk life sciences work that could significantly endanger public health or national security. AC must provide such evaluation report to COBRE PI before the SI research plan is submitted to NIGMS for prior approval.

AC responsibilities also include but are not limited to providing the annual evaluation of the Center, recommendations to the PD(s)/PI(s) to improve the Center's performance, feedback to the SIs, their mentors, feedback on the progress of the Sustainability Plan.

The applicant organization will identify, prior to award, individuals from a pool of existing investigators to be supported by the COBRE's Scientific Research Program (SRP). It is the responsibility of the organization to establish the qualifications of the prospective SRP Investigators (SIs) before they are supported by the program. SIs must:

• Be an Early Stage Investigator (ESI), New Investigator (NI), a mid-career investigator working towards the renewal of their first research project grant, or an "at-risk" investigator who will have no substantial research grant funding in the upcoming fiscal year,
• Hold an independent multi-year faculty appointment (or equivalent at research institutes) at the applicant organization, and
• Lead their own research program within the broad scientific area of the Center.

Investigators on a research-only track are eligible if they are not on time-limited contracts or whose appointment is contingent on the success of the COBRE application.

As a reminder, PAR-27-055 does not prescribe the number of SIs. It is up to PI and the applicant organization to decide on the optimal number of SIs to ensure the growth of institutional research capacity in the broad area of research and place the SIs on a path towards independence. Under this NOFO, the designation of RPL no longer exists.

The Personal Statement should include the investigator’s current research and administrative activities at the institution, progress toward independence, and a statement of how participation in the COBRE will help to achieve these goals. Do not include Specific Aims or describe specific projects, but rather, include a broad description of the proposed SI’s research program. The biographical sketch should include a summary of the investigator’s contributions to science and of impactful research conducted over the last 5 years, including work in the scientific area of the COBRE.

Graduation means obtaining a R01-like RPG award that secures the SI’s research independence. Please note, obtaining a K (Mentored Research Scientist Development Award), R03, or R21 award, or leaving the COBRE program without any substantial R01-like funding are not considered as graduation.

If a current RPL’s (in COBRE Phase 1 or Phase 2) research falls within the scope of the newly proposed COBRE-E or COBRE-S, then yes, they can be part of the pool. The maximum length of time an individual may receive COBRE support is 5 years. RPLs who left the COBRE program for any reason, including graduation or removal, cannot be part of the SI pool nor be reinstated as SIs.

The RPL from the external institution may continue in the original COBRE as part of a NCE. An investigator who is not at the applicant organization can neither be included as part of the SI pool nor be selected as an SI.

If an RPL has spent less than 5 years on a previous Phase of the COBRE and the RPL’s project falls within the scope of the new COBRE this person may continue as an SI.

Two reminders:

• Research projects should not be described in detail as part of the application.
• RPLs who have graduated from an earlier version of the COBRE cannot be included in the pool of potential SIs.

SIs must submit a New (ESIs, NIs, "at-risk" investigators) or a Renewal (mid-career investigators, "at-risk" investigators) version of an independent investigator-initiated, peer-reviewed research project grant (RPG) application by the end of the SI’s second year of COBRE support.

To be considered, an SI must have a tenure-track appointment, receive at least 51% of salary support from the applicant organization and have dedicated laboratory space at the applicant institution.

SIs are neither expected nor required to work on joint research projects. SIs should focus on developing their own independent research programs.

No. The subject matter of existing Phase 1 COBREs may continue into COBRE-E in a similar fashion a Phase 1 would transition to a Phase 2: by demonstrating progress in building research capacity and expanding the scientific reach of the center. If an institution is proposing a “New” COBRE-E, it should focus on an area different from the existing Center.

We suggest paying attention to the NIH Unified Funding Strategy, as that will guide the principles under which awards will be funded. Phase 1 COBREs transitioning to COBRE-E should demonstrate productivity in developing faculty and biomedical research infrastructure in the chosen area. “New” COBRE-E applicants should demonstrate the existence of research capacity that can be repurposed into a broad area of strategic interest to the institution.

The PI of the COBRE should carefully read the review criteria to better understand how the review panel will assess scientific merit. The applicant should clearly convey to the reviewers the achievements and successes during the previous phases of the COBRE.

No, a vertebrate animals section is not required because no research is being proposed. Information on the use of vertebrate animals will be requested as part of the Just-in-Time process.

Research project descriptions are not allowed or required in either COBRE-E or COBRE-S. Proposed SIs should describe their research program in their biographical sketch.

Yes, applicant organizations should include information about progress made during the previous phase in the Overall section of the application as part of the justification for the proposed center.

Yes. All COBRE-E/S components should include Specific Aims page. The aims describe the goals of the COBRE and its individual components.

Ideally, an applicant organization will have more than one senior institutional leader suitable to write a letter of support. If there is no other suitable institutional leader, then the letter of support may come from the institutional leader serving on the Advisory Committee.

Unlike RPLs in Phase 1 or Phase 2, SIs are not reviewed individually. The SI pool is reviewed in its entirety for cohesion and adherence to the scope of the proposed scientific area of the center. This is to ensure that there is sufficient scientific breadth. The applicant organization should discuss existing gaps that are intended to be filled with proposed faculty hires. Applicants should be mindful of the eligibility requirements of SI investigators when writing the application.

Typically, the grant making process takes and least 9 months.

HSCT forms and IRB approvals are not required at the time of submission. The HSCT and IRB will be requested as part of the JIT if an SI’s research program involves research with human subjects.

The PD/PI and the COBRE Advisory Committee (if applicable) select the slate of SIs from the pool proposed in the application. SIs cannot begin their research until NIGMS approves them via the prior approval process. See Section VI (Award Administration Information) of the NOFO for additional information.

No. It is up to the organization to ensure sufficient grant funds are budgeted for each SI it supports. The support must be reasonable and appropriate within the context of the research environment.

Yes, a new faculty member can be added to the SI pool after an award is made. This is likely to occur if the hiring of a faculty member is part of the grant proposal. Additions of new SIs require Prior Approval as outlined in Section VI (Award Administration Information) of the NOFO.

Yes, a new faculty member can be added to the SI pool after an award is made. This is likely to occur if the hiring of a faculty member is part of the grant proposal. Additions of new SIs require Prior Approval as outlined in Section VI (Award Administration Information) of the NOFO.

For organizations transitioning from COBRE Phase 1or COBRE Phase 2 into COBRE E or COBRE S, respectively, the first group of SI research plans will be reviewed by the existing AC upon receipt of a Just-In-Time (JIT) request. For “New” COBRE-E grants, the first group of SIs will be selected by the PI at the time of JIT request before the AC is constituted.

This will vary by SI candidate. If an SI is an early-career investigator, the past 5 years may include postdoctoral and graduate training. This information is appropriate given their career stage. For a more experienced investigator, the relevant activities from the last five years will look different.

Yes, the grants submitted under the new NOFO are “New” applications. Grants under the former COBRE structure are eligible for No-Cost Extensions.

We recommend applying as close as possible to the earliest possible funding date preceding the end of the existing funding period. It is not advisable to apply more than one year ahead of the conclusion of the current project period.

COBREs are not eligible for multi-year funding.