FAQ for RFA-CA-20-049 and RFA-CA-20-050

Frequently Asked Questions (FAQ) for RFA-CA-20-049, New Cohorts for Environmental Exposures and Cancer Risk (UG3/UH3)

What is the purpose of this FOA?

This Funding Opportunity Announcement (FOA) invites grant applications to support innovative scientific research in new prospective cohorts that addresses knowledge gaps in cancer etiology and carcinogenesis processes with a focus on environmental exposures. It is anticipated that the new cohorts will provide scientific evidence related to environmental exposures and cancer risk.

This RFA is to support new cohorts that use innovative strategies and approaches to address knowledge gaps between environmental exposures, and cancer development, taking into consideration potential confounding and modifying factors, in the most appropriate populations and during relevant time periods or windows of susceptibility.

What is the expectation of this FOA regarding environmental exposures?

In this FOA, environmental exposures refer to physical, chemical, and biological factors external to a person, and related behavioral factors. However, the focus of the RFA will be on environmental chemical and physical exposures.

What is the UG3/UH3 mechanism that the FOA uses?

This RFA will support UG3/UH3 phased award research projects. Applicants in response to this FOA must apply for both the UG3 and UH3 phases together in the single application. The UG3 Planning-Exploratory Phase is focused on the recruitment of study participants and data collection, and the UH3 Implementation Phase is focused on completing the research agenda.

UH3s will be awarded pending administrative review of eligible UG3s that have met the scientific milestones necessary for the UH3 phase, depending on the availability of funds. Recruitment is not required to be completed in the UG3 phase, but reasonable progress should be demonstrated to ensure that all aims will be completed in the UH3 phase.

Although studies may differ, the UG3 phase is up to 2 years, whereas the UH3 phase will be up to 4 years (for a total of up to 6 years).

How should applications organize specific aims in the UG3/UH3 phases?

Applicants must provide the overall goals for the entire application and indicate separately Specific Aims to be accomplished in the UG3 Planning-Exploratory Phase and the UH3 Implementation Phase. Applicants are referred to details in the FOA under “Research Plan” which provide instructions regarding the “Specific Aims,” “Research Strategy,” etc.

Are there budget caps?

The budget of the UG3 phase cannot exceed $750,000 in direct costs per year. There is no specified budget cap for the UH3 phase; however, budgets must reflect only the work necessary to complete the aims and are subject to available NCI and NIEHS funds.

What is the expectation of this FOA regarding participants in the cohorts?

While the applications will be driven by the science proposed, it is expected that the cohorts will address cancer risk across diverse populations and during relevant time periods or windows of susceptibility. Applicants are strongly encouraged to include diverse and understudied populations to address scientific gaps in knowledge related to environmental exposures and cancer risk.

What is the definition of environmental exposure for this FOA?

Environmental exposures are defined broadly for this FOA. However, the focus is on environmental chemical and physical exposures.

What is the expectation of this FOA regarding measurements of environmental exposures and outcomes?

Applicants are encouraged to use validated and reproducible innovative technologies to assess exposures and outcomes as relevant to the proposed scientific aims. Advances in technologies enable capture of a wide variety of exposures and offer an unprecedented opportunity to understand the contribution of environmental exposures to cancer etiology, especially in the most vulnerable populations.

Are there specific requirements for the cohorts?

There are specific requirements for this RFA as outlined in the “Research Objective and Requirements” section of the FOA. For example, this initiative calls for research questions that can be addressed in both the short-term and longer-term with prospective observational study design. The study must include specific requirements such as scientific justification of the research gap to be addressed in both exposures and outcomes; evidence of community engagement in the development and conduct of the proposed research; justification of the study population and sample size given the proposed science; willingness to collaborate on a core set of data related to environmental exposures and cancer etiology; description of critical milestones, performance metrics, and a timeline for completion of milestones; description of the sustainability and preservation of cohort resources that extend beyond the life of the award; and detailed data/resource sharing plans that are consistent with NIH policy and follow Findable, Accessible, Interoperable, Reusable (FAIR) principles (see https://www.go-fair.org/fair-principles/External Web Site Policy).

Can existing research resources and cohorts be used to form a new cohort?

This FOA is specifically for new research-based prospective cohorts to study new and understudied environmental exposures with innovative designs and measures. Existing established cohorts are not appropriate for this mechanism and investigators are encouraged to apply to other grant mechanisms (R01, R21, R03) for research support. This FOA is not a mechanism to support existing infrastructure.  However, any population-based resource can be utilized to build an applicable new cohort, once scientifically justified. Any proposed new cohort must meet the criteria established in Section I: Research Objectives and Requirements section.

The FOA states that the new cohorts should consider innovative designs to address both short-term and longer-term questions. Can I also enroll new cancer cases to conduct case-control studies in the short-term as I build my new prospective cohort?

Certainly, innovative study designs are encouraged in this RFA. In the initial design, investigators may recruit new cancer cases along with population-based healthy controls to address applicable questions in the short-term by case-control or case-cohort study designs. However, , investigators must also design a prospective longitudinal cohort study to address research questions that can only be addressed with a fully prospective study in the longer-term.

Can methodological research be built into the cohorts in the short-term?

Yes.

Are there requirements to work collaboratively with the Coordinating Center and NIH?

Awardees are expected to work collaboratively across the cohorts and with the CEECR Coordinating Center and NIH Program Staff to establish an agreed-upon core set of data to be collected across the cohorts. Grantees will work together to develop a core set of questions that will be required to be included within data collection tools across cohorts.

What are the requirements related to community engagement?

Applicants are expected to include details of community engagement activities designed to inform research, enhance recruitment and retention efforts, and disseminate results. Applicants are expected to have meaningful engagement with key stakeholder groups throughout the process from study design, through the conduct of the study, to communication and dissemination of results. The budget should accommodate support for community engagement activities. Examples of community partners are described in the announcement.

Are there sample size requirements for the cohorts?

The sample size and proposed data collection must be driven by the scientific questions proposed. The collection of biological samples and the frequency of collection should be guided by the proposed research.

What is the requirement for data/resource sharing?

Detailed data/resource sharing plans that are consistent with NIH policy and follow Findable, Accessible, Interoperable, Reusable (FAIR) principles (see https://www.go-fair.org/fair-principles/External Web Site Policy) are required. Applications should describe the management and decision-making process that promotes data sharing, the timeline for sharing, the repository where the data will be located, the process for accessing data, any limitations, etc. Applicants are expected to provide broad access to the data through controlled-access data repositories. This FOA encourages the deposition of data to an NIH data repository. See the NIH Genomic Data Sharing Policy:

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html

Awardees are also required to contribute cohort information to a cancer epidemiology cohort descriptive cohort database (CEDCD) (https://cedcd.nci.nih.gov).

Are there meeting requirements of the CEECR Program?

Applicants are required to budget funds for PD/PI(s) for travel to attend an annual grantee meeting in Bethesda or Rockville, Maryland within the grant period. The purpose of these meetings will be to bring together investigators to share knowledge, progress, and findings, and allow for rapid translation of results.

What is the governing structure of the CEECR Program?

The CEECR will be governed by a Steering Committee comprised of representatives from the funded cohorts, the Coordinating Center, and NIH program staff. Though the Steering Committee will make recommendations, NIH Staff will have final authority to approve any proposed recommendations, and activities must comply with NIH, DHHS, and Federal Guidelines.

What are non-responsive applications?

The following types of activities remain outside the scope of this FOA, and applications proposing them are non-responsive to this FOA and will not be reviewed:  approaches that do not include human populations; approaches that are based on secondary use of existing cohort data; approaches that use a study design that will not lead to a prospective cohort; applications from foreign countries that do not show direct relevance to the U.S. population (applications for foreign countries are eligible but must show relevance to U.S. populations); and non-compliant data/resource sharing plans and not following FAIR principles.

Is a letter of intent required?

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. By the date listed in “Part 1. Overview Information,” prospective applicants are asked to submit a letter of intent that includes the following information: descriptive title of proposed activity; name(s), address(es), and telephone number(s) of the PD(s)/PI(s); names of other key personnel; participating institution(s); and number and title of this funding opportunity.

The letter of intent should be sent to:
Somdat Mahabir, Ph.D., M.P.H.
National Cancer Institute (NCI)
Telephone: 240-276-6941
Email: mahabir@mail.nih.gov

In Section IV, subsection D (Approach) and E (Milestones and Timelines), applicants are asked to provide sample size calculations. Is there a need to provide this information in both sections?

Sample size is driven by the scientific questions proposed and the overall approach should describe the sample size calculations. Repetitions are not recommended.

In Section IV, there is a subsection F (Data Sharing and Dissemination) and a separate subsection “Resource Sharing Plan.” Since subsection F falls under the Research Plan, should applicants include the Data Sharing and Dissemination under the “Resource Sharing Plan”?

Yes, applications should provide the required details pertinent to data sharing and dissemination under the Resource Sharing Plan section of the applications.

Is there a minimum number of participants to be recruited in years 1-2?

No. Recruitment must be based on the science proposed. The UG3 planning-exploratory phase will be focused on the recruitment of study participants and data collection. Milestones to be accomplished in the UG3 phase for transition to the UH3 phase will be proposed by the applicants and require NCI/NIEHS review and approval before the grant is awarded and must include a timeline for recruitment and data collection. Requirement is not required to be completed in the UG3 phase, but reasonable progress should be accomplished to ensure that UG3 aims are completed. All the proposed milestones will be monitored closely by NCI/NIEHS. Transition decisions will be based on achievements of study milestones.

Will this RFA accept existing cohorts to which we can add participants?

No. Please review the section under “Non-Responsive Applications” – Non-responsive: Approaches that are based on secondary use of existing cohort data. This is not a cohort infrastructure grant mechanism. Existing established cohorts are not appropriate for this mechanism and investigators are encouraged to use other grant mechanisms (R01, R21, R03) for research support. This FOA is specifically for new research-based prospective cohorts to study new and understudied environmental exposures with innovative designs and measures.

The timeline of the grant is very short for cancer outcomes. For the new cohorts, if cancer is the endpoint, large populations will need to be studied for long periods of time to achieve results. Could intermediate endpoints be considered?

Intermediate endpoints are expected, and the concept accommodates new cohorts that will incorporate research questions that can be addressed in both the short-term and longer-term. In the short-term, for example, the research may use the IARC framework to assess biological mechanisms to support classification of environmental exposures such metabolic activation (DNA and protein adducts), genotoxicity (DNA damage, gene mutations, cytogenetic changes), epigenetic signatures, induction of chronic inflammation markers (elevated WBCs, altered cytokine/chemokine production); altered cell proliferation (cell proliferation, angiogenesis), etc. (Ref. 12 in concept: Smith MT et al. 2016).

One of the advantage of collaborations from the start is that collectively the cohorts will have the ability to look at some cross-cutting issues.

What is the definition of environmental exposure for this FOA?

In this FOA, environmental exposures refer to chemical, physical, and biological factors external to a person, and related behavioral factors. However, the focus of the RFA is on environmental chemical and physical exposures that occur in the general population, which may include individuals with specific exposures in the work setting. However, the focus is not on specific occupational cohort.

Are the individual applications for new cohorts required to propose multiple projects?

No. Applicants to the cohort RFA should propose a single study with research aims – not multiple projects. This is not a P01 type mechanism. See P01 NCI Program Project Applications: https://grants.nih.gov/grants/guide/pa-files/par-20-077.html

Frequently Asked Questions (FAQ) for RFA-CA-20-050, New Cohorts for Environmental Exposures and Cancer Risk (CEECR) Coordinating Center (U24)

What is the purpose of the CEECR Coordinating Center (CC)?

The purpose is to facilitate coordination among new Cohorts for Environmental Exposures and Cancer Risk (CEECR). The CEECR is described in RFA CA-20-049.

What is the NIH U24 mechanism?

The NIH U24 mechanism is a Cooperative Agreement to support research projects contributing to improvement of the capability of resources to serve biomedical research.

What are the main responsibilities of the CC?

The Coordinating Center will have several responsibilities, including, but not limited to: provide administrative support to the CEECR program, create standard operating procedures and best practices to collect core common data elements and biological samples, facilitate communication across cohorts, provide meeting support, create and maintain the CEECR program websites, ensure data from the UG3/UH3 cohorts are shared in accordance with the required data sharing plans, and facilitate deposition of data to NIH repositories. The CC, in conjunction with NIH staff, will facilitate collaborations among the cohorts and community partners. See details in RFA-CA-20-050.

What are the expectations of the CC Research Team Expertise and Composition?

To fulfill the main responsibilities outlined in RFA-CA-20-050, the CC team will be expected to have appropriate expertise and experience—in such areas as management of large-scale cancer research, data management using applicable tools, stakeholder engagement and outreach activities, successful partnerships with multiple study teams across diverse settings and regions—in the design, implementation, and completion of large research studies. In addition, the CC team must have effective communications across scientific teams, community engagement stakeholders, and NIH; experience in website development, file management, organization, and maintenance; and familiarity with organization of scientific meetings and meeting travel planning. Knowledge of NIH data sharing and experience with deposition of data to NIH repositories are important requirements.

The team is expected to include senior members who have considerable leadership skills and experience in productive collaborations with large research teams and/or multi-stakeholder groups (e.g., cancer consortia, other health consortia, or community-based organizations) in diverse settings (e.g., rural or urban).

How many new cohorts will the CC be expected to coordinate?

The CEECR will include approximately five new cohorts of multidisciplinary research teams with community engagement activities (RFA-CA-20-049). Cohort awardees will be required to interact closely with the CEECR CC.

How will the CC be governed?

The CEECR will be governed by a Steering Committee comprised of representatives from the funded cohorts, the Coordinating Center, and NIH program staff. Though the Steering Committee will make recommendations, NIH Staff will have final authority to approve any proposed recommendations, and activities must comply with NIH, DHHS, and Federal Guidelines.

Are there travel requirements for meetings?

Applicants are required to budget funds for PI(s) for travel to attend annual meetings in Bethesda or Rockville, Maryland within the grant period. The purpose of these meetings will be to bring together investigators to share knowledge, progress, and findings, and allow for rapid translation of results.