Section I. Funding Opportunity Description

Nature of the Research Opportunity

Pilot projects will be awarded in response to this FOA, PMIN-COBRE-003.  These projects will be in the general area of personalized medicine ranging from basic science to translational applications. The general focus is discovery and utility of genetic and epigenetic markers for personalized medicine, although projects with other model systems will be considered.

For the purposes of this FOA, "personalized medicine" is defined as incorporation of an individual patient's genetic and genomic information (as reflected by their own genotypic, sequencing, family history, physiological data, etc.,) into decision-making about preventative strategies or clinical care for people.

Background

At least 1 in 20 people will have a genetic disorder during their lifetime; thus, a large opportunity exists to apply routine genetic analysis in health and medicine (PMID:19010252). Fortunately, for many patients, exome (the exon regions) and genome sequencing is now an economically feasible diagnostic test. Sequencing the protein-coding regions of the human genome (the exome) costs about $300-$400 today. More than 1 million human exomes have been sequenced and consequentially the pace of DNA sequencing is exceeding Moore’s law for doubling of computational capabilities annually (PMID: 24567478). The challenge is to see how society can advance health through applications of genomics and genetic markers.

Although still largely a research endeavor, the use of genetic markers is becoming more commonplace in standard-of-care medical practice. Genetic markers have emerged with five general areas of overlapping clinical applications: (1) oncology; (2) Mendelian disorders; (3) prenatal screening and birth defects; (4) pharmacogenetics; and (5) undiagnosed diseases. Many genetic markers have already been identified—the

Genetic Testing Registry of the National Center for Biotechnology Information has genetic tests for 10,534 conditions in 5,034 genes developed by 481 laboratories (PMID: 29140470). Many of the loci on these genes (24,061 genetic loci) are in the genome-coding region (PMID: 23193275). Approximately 160,000 single-nucleotide polymorphisms are associated with disease (PMID: 26582918). Numerous genetic markers remain to be discovered, especially in the area of common disease where genetic risk scores (summarizing multiple variants of small effect sizes) are gaining wider acceptance.

Genetic markers can be used to assess an individual’s health through four phases of disease progression: (1) the presymptomatic condition; (2) the symptomatic condition; (3) the choice of therapy; and (4) response to treatment of the condition. Uses and advantages of genetic markers are:

In presymptomatic or healthy states, genetic markers are used for disease subtyping, carrier screening, and assessing for disease risk and the need for preventative screening. Based on the anticipated continued growth in the discovery and utility of genetic markers in medicine, the specific personalized medicine niche of our COBRE is the “Discovery and utility of genetic and epigenetic markers for personalized medicine. Although genetic markers are also commonly used in forensics and agriculture, we will focus on their medical and health applications. This emphasis reflects the growing interest in the prediction of complex disease susceptibility using genetic risk scores and variant panels (PMID: 26839113).

Potential limitations of initial approaches, and/or drawbacks of genotype-driven strategies, should also be assessed objectively.   

Scientific Knowledge to be Achieved

This funding opportunity will focus on the discovery and utility of genetic and epigenetic markers for personalized medicine, although all other aspects of personalized medicine will be equally considered. The discovery of genetic markers is interdisciplinary. As such, it involves (1) bioinformatics for analysis and interpretation of sequencing results; (2) genomics to help interpret results; (3) clinical trial and biostatistics research to drive new discoveries; (4) genetics to support clinical trials and to apply in clinical research and practice; and (5) medical informatics to collect, organize, and analyze human phenotypes.

Objectives of this Research Program

This FOA will support Pilot Projects to enhance or adapt ongoing successful basic science or translational personalized medicine projects, or initiate new ones, to expand the implementation of genetic and genomic medicine or preventative strategies. 

The programmatic goals of these pilot grants are:

• To generate new preliminary discoveries in personalized medicine
• To produce preliminary data that will enhance the competitiveness of a new or resubmitted application for an NIH R03, R15, R21, K01, K08, BSF career awards, or other small awards.
• To grow personalized medicine research in Nevada and the IDeA network
• To enhance the use of our COBRE research cores (www.unlv.edu/cobre/genomics-acquisition-analysis-core; https://www.nevadacntn.org/clinical-and-translational-research-core)
• To grow the Center of Excellence COBRE program by recruiting new participating members
• To identify candidate replacement projects and PIs as our new investigators graduate to independent funding.
• Recruit a pool PIs to be part of our phase II COBRE application.

Proposed pilot projects are not required, but may choose, to partner with experienced group(s) to expand sample size and generalizability and evaluate their proposed intervention(s) in different settings.  The inclusion of diverse settings such as community hospitals, primary care practices, specialty groups, and military or Veterans’ Administration hospitals, and under-served populations such as disadvantaged or non-European ancestry groups, is particularly encouraged, though the feasibility and advantages of such expansions should be clearly described.  Similarly, expansion to multiple different medical or hospital systems, rather than within current members of an existing system, is also encouraged.

This initiative may support studies using animal models but must be combined with a human study component.

Program Formation and Governance

The awards funded under this FOA will be highly collaborative. Close interaction among awardees and a cadre of COBRE grant members will be required to meet the obligations of this program.

Shortly after award, the awardees will meet with COBRE leadership and existing awardees as a consortium to share research plans; identify commonalities in approaches, barriers, and solutions; and present their research project or grant applications at NevBio, Science Café, Grant club, and/or COBRE seminar series if asked; and work with the COBRE group by regularly attending COBRE journal club, research core workshops, mentoring panel quarterly meetings. 

Given the expected commonalities in infrastructural and institutional needs across Pilot Projects, awardees will have access to the COBRE research cores (Genome Acquisition to Analysis, and Clinical Trials cores; www.unlv.edu/cobre/genomics-acquisition-analysis-core) and shared laboratory research space and equipment in the Nevada Institute of Personalized Medicine.

External Input into the Personalized Medicine Center of Excellence

The Pilot Projects, as part of the Personalized Medicine in Nevada COBRE award, will be approved by, and report to an External Advisory Board (EAB). The EAB is appointed by and will advise NIGMS. The COBRE Advisory Board members will meet with awardees once a year in-person and once a year through teleconference and provide feedback on all pilot projects.

Data Sharing Under this Initiative

To increase the value of the significant public investment in personalized medicine projects data produced under this FOA should become publicly available. Award recipients will adhere to NIH guidelines on sharing research data (see notice NOT-OD-03-032). Genomic data from Genome-Wide Association Studies (GWAS) will be deposited and available through dbGAP consistent with NIH policy for sharing of data obtained with NIH-supported Genome-wide Associate Studies (GWAS) (see notice NOT-OD-07-088).

Section III. Eligibility Information

1. Eligible Applicants (Principal Investigator)

All Nevada investigators who are eligible to apply for independent NIH funding, but have not been the PI of an R01 or similar senior level grant from another agency, and who have no conflict of interest, will be eligible to apply. Applicants cannot concurrently hold a COBRE, INBRE or CTR-IN award. These individual(s) should have the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Applicants must hold a full-time faculty position at the rank of Assistant or Associate Professor. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and ERA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations, which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

Any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement) will not be reviewed, except for submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid
• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid; or
• Of an application with a changed grant activity code.

Section V. Application Review Information

Applications will be reviewed by applying standard NIH review criteria.

1. Criteria

Only the review criteria described below will be considered in the review process. All submitted applications are evaluated for scientific and technical merit following the NIH peer review system.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the potential for this pilot project to lead to impactful funded research and the potential for this pilot to produce the key preliminary data for a successful grant application.

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have a major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How likely is the project to improve the assessment and expand the implementation of personalized medicine?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? How suitable is the research team to perform personalized medicine research and assess its impact? How likely is the PI to leverage this support into a new funded grant award?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? How likely is the proposed project to contribute valuable new information to the evidence base on personalized medicine?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? Are criteria for success, a plan to leverage the pilot project into future grant applications and next steps for the project clearly defined? Are definitive early results likely to be available for a grant application within six months of the end of the award?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Does the applicant take advantage of the COBRE cores and research team?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

The awardee may apply for a competitive renewal for an additional year of funding.

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Personalized Medicine in Nevada COBRE.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.
• Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by External Advisory Board and NIGMS. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to COBRE program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be emailed his or her Summary Statement (written critique). Information regarding the disposition of applications is available in the NIH Grants Policy Statement. Award dates are expected to be on, or about June 1, 2020. The RFA is expected to be adapted and reissued in December 2020.

Section VII. Center Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

Email: martin.schiller@unlv.edu

Online Pilot Grant Application Portal

Grants Information (Questions regarding application instructions and process, finding NIH grant resources)

Telephone: 301-710-0267
TTY: 301-451-5936
Email: grantsinfo@nih.gov

Scientific Research Contact

Martin Schiller, Ph.D.

Nevada Institute of Personalized Medicine, UNLV
Telephone: 702-895-5546
Email: martin.schiller@unlv.edu

Peer Review Contact(s)

Edwin Oh, Ph.D.

School of Medicine, UNLV
Telephone: 702-895-0509
Email: edwin.oh@unlv.edu

Financial/Grants Management Contact(s)

Mrs. Amy Gros-Louis

Nevada Institute of Personalized Medicine, UNLV
Telephone: 702-895-1363
Email: amy.gros-louis@unlv.edu