Important information about RFAs, upcoming dates, frequently asked questions and helpful links.
- July 2nd, 2019 - Open Date (Earliest Submission Date)
- July 2nd, 2019 - Letter of Intent Due Date (optional)
- August 2nd, 2019 by 5:00 p.m. local time of applicant organization - Application Due Date
On June 13, 2019, NHGRI held a pre-application interactive Q&A webinar for the eMERGE Genomic Risk Assessment and Management Network funding opportunities.
Frequently asked questions from prospective applicants are provided below.
FAQ: Retrospective Validation
What information can be used to formulate a genomic risk assessment and management plan?
Each genomic risk assessment must include a genomic risk management plan. The risk management plan can include original research results, guidelines, or expert opinions. Each investigator will be responsible for presenting their recommended risk management guidelines to the Steering Committee. The final genomic risk assessment and management plan will be agreed upon by consensus of the Steering Committee.
Do the polygenic risk scores (PRS) proposed for genomic risk assessment have to be proven in non-European populations?
No, but applicants should address the applicability of the proposed PRS in non-European populations, such as providing evidence that the proposed variants will be present in non-European populations or describing how the information will be used in populations where the variants are not present.
Do I have to use eMERGE data in preparing my application?
No, any dataset can be used in preparing the application. Applicants should describe the source and availability of the data they have used.
Will PRS be developed and validated for non-European Ancestry (EA) individuals in Year 1?
Yes, applicants should propose how they will adapt, modify, and validate existing PRS to incorporate non-EA individuals during Year 1.
FAQ: Prospective Risk Assessment and Management
Do the proposed disease-specific genomic risk assessment and management plans need to be proven via randomized clinical trials or are interventions with other levels of evidence allowed?
Randomized clinical trial evidence is not required; other resources including expert panels and guidelines will be considered. Applicants should clearly describe the evidence available for the genomic risk assessment and management plans they propose and justify their choice of plans.
How will the outcome measures of genomic risk assessment and management be selected?
Investigators should propose the outcomes they think are most suitable for the condition being addressed by the genomic risk assessment and management plan. Outcomes suggested by awardees will be compiled during the first year after award by the Coordinating Center. The final list of outcomes will be reviewed and agreed upon by the Steering Committee.
If patients have already had genetic testing, can they still be included in the 2,500-person cohort?
The individual can be included as long as the results have not been returned to the patient or clinicians treating the patient. The goal is to capture the impact of genomic risk information on patients’ outcomes, which must be done prospectively through reporting and monitoring of these patients.
Can pediatric patients be included in this program?
Yes, they may, as long as it is possible to implement the genomic risk assessment and management plans across all of the sites and the proposed risk assessment and management plans in pediatric patients meet other criteria as explained in the RFA for generalizability, clinical importance, feasibility, potential impact, and cost. The inherent challenges with providing genomic risk information to pediatric patients and obtaining timely outcomes in them over a four-year follow-up period should be addressed when proposing genomic risk assessment and management plans for pediatric patients.
Is the goal to recruit patients with high PRS?
No, the goal is NOT to recruit patients with high PRS. The goal is to recruit a reasonably diverse and generalizable sample of persons across the spectrum of risk within a clinical care system and then calculate their genomic and clinical risk estimates to determine their risk for the 15 conditions selected by the Steering Committee. Assuming these conditions are largely independent, binomial probabilities can be used to estimate that ~25% of the population will be at the top 2% of risk for at least one of 15 conditions. But, the goal is NOT to preferentially recruit people with high-risk.
Is it possible to recruit families?
Where can applicants find the race/ethnic breakdown of all eMERGE participants?
The eMERGE website provides a breakdown of the self-identified race/ethnic background of all eMERGE participants.
Does NHGRI anticipate limiting return of secondary findings as described by the American College of Medical Genetics and Genomics (ACMG)?
No, applicants should expect to return all results that the Network determines actionable based on the Network’s collective expertise.
Should applicants include a detailed analytic plan with power calculations?
Yes, applicants should describe what approach will be used to validate the genomic risk assessment and outcomes. Applicants can explain their design in detail and some elements may fit into the clinical trial section.
Can sites focus recruitment on patients with a medical or family history that increases risk for one of the targeted phenotypes?
Yes, they may, if such a strategy is needed to provide a reasonably diverse and generalizable sample of persons across the spectrum of risk and can be achieved within the budgetary constraints of the RFA. Applicants should explain how such a strategy could be achieved across the entire Network and why it is a reasonable strategy to propose.
Is it possible to have two groups of patients: some of whom would receive genomic predictors and others who would have these data held back as a control?
NHGRI is not expecting to include a control group of recruited and consented participants. Applicants can consider proposing a comparator group with relevant available data if that can be achieved within the budgetary constraints of the RFA.
The RFA indicates that the Clinical Site will be expected to return secondary findings not included in the reported PRS. What are secondary findings within the context of this RFA?
Secondary findings are genetic test results that are not part of the primary purpose for performing the selected genomic risk assessments.
Will sites be required to implement all 15 genomic risk assessments?
Yes, all 15 genomic risk assessments are expected to be implemented for all patients.
Are costs for genetic testing allowable?
All Network-wide genetic testing for the genomic risk assessment and management plan will be done in a Clinical Laboratory Improvement Amendments (CLIA) environment and coordinated through the Coordinating Center. When Network-wide genetic testing is required, it is expected that the testing will be paid and coordinated through the Coordinating Center. Additional testing outside this for routine medical care, not covered by the patient’s existing insurance plan, can be budgeted by the Clinical Sites as outlined in the Research and Related (R&R) or Modular Budget section of the RFAs.
Will the cost of medical care for the underinsured or uninsured be covered by the grant?
Yes, at least in part. The grants will assist with covering the cost of care in high-risk individuals as outlined in the R&R or Modular Budget section of the RFA. Investigators should provide a plan for providing indicated medical services to individuals when funds are not adequate to cover the cost of the risk management plan.
Are clinical sites responsible for the cost of the genetic test?
No, the Network-wide genetic tests will be covered by the Coordinating Center. However, if there is individual follow-up genetic testing needed, then that will be covered by the Clinical Site.
Do the $900-$1100 per patient costs include blood draws and DNA extraction for the Network-wide genetic tests?
No, that will have to be included as part of the Clinical Site budget.
Do the $900-$1100 per patient costs cover medical services only for certain socio-economic status patients?
No, this is meant to pay for services not covered by the patients’ current insurance.
FAQ: Program Formation and Governance
Why does this program meet the NIH definition of a clinical trial?
In 2015, NIH broadened its definition of clinical trials to include non-randomized implementation of interventions such as genetic testing where results are reported back to participants. These definitions are described int NOT-OD-15-015 and other useful materials are available at the NIH Office of Extramural Research website. Please note that the eMERGE Genomic Risk Assessment and Management Network is not intended to be a traditional randomized controlled clinical trial. The goal of this Network is to implement genomic medicine risk assessment into a cohort of 20,000 individuals and measure the impact this has on clinical outcomes. Applicants should respond to this defined purpose as outlined in the RFAs, regardless of differing perspectives on what may or not constitute a clinical trial.
What is the impact on investigators as a result of classifying this program as a clinical trial?
This expanded definition and the policies accompanying it were implemented to ensure that the public investment in clinical trials research is shared among a larger audience. Applicants should familiarize themselves with requirements for NIH defined clinical trials when submitting a response to RFA-HG-19-013, RFA-HG-19-014 or RFA-HG-19-015.
NIH requires appropriate data and safety monitoring for clinical trials. Are eMERGE applicants expected to include plans for a Data Safety Monitoring Board (DSMB) at their institutions?
No, applicants are not expected to plan or budget for a DSMB. As described in the eMERGE RFAs, an External Scientific Panel (ESP) and Steering Committee will evaluate the progress of the eMERGE Genomic Risk Assessment and Management Network. The ESP's role will include central data and safety monitoring of eMERGE patients on behalf of the eMERGE consortium. Twice-yearly meetings of the ESP will be supported through RFA-HG-19-015 (eMERGE Coordinating Center) and will include data and safety monitoring.
Are applications with multiple Principal Investigators permitted?
Yes, for institutions/organizations proposing multiple PDs/PIs, visit the NHGRI Multiple Program Director/Principal Investigator website for further information.
Are foreign institutions eligible to apply?
Are foreign components allowed under this RFA?
Yes, foreign components as defined in the NIH Grants Policy Statement are permitted as part of applications from domestic institutions.
The main difference is the sociodemographic composition of the populations from which patients are recruited for the Network to ensure acceptable levels of study power. RFA-HG-19-013 requires a minimum of 35% of patients to come from racial or ethnic minority populations, underserved populations, or populations who experience poorer medical outcomes, while RFA-HG-19-014 requires a minimum of 75% of such patients. The available funds for RFA-HG-19-014 are also higher than for RFA-HG-19-013 due to the expected increased costs of recruiting, following, and providing medical services in underserved populations.
Can follow-up genetic testing be used as part of a genomic risk management plan?
Yes, pharmacogenomic or other genetic testing can be included as part of the risk management plan if, for example, specific follow-up testing is indicated for persons identified in etwork-wide testing as being at risk. As an illustration, a patient at high risk of coronary disease might be identified by the genomic risk assessment. Pharmacogenetic testing for lipid-lowering therapy might then be indicated (if not already included in the initial genomic testing). If the genetic testing is expected to be performed across the Network, this testing would be expected to be managed and paid through the Coordinating Center to ensure standardization and reduce the cost of this testing.
Where can I find out more about the eMERGE Network?
The eMERGE Network has established a Projects website website that includes past Steering Committee Notes & ESP packets, lessons learned, the current data use agreement, studies available in dbGaP, and publications. Additional information can also be found on the Resources tab on the main website.
How will the genomic risk assessment be calculated?
The Steering Committee will need to establish a process and analysis pipeline that receives and combines the genetic and clinical covariates to calculate a genomic risk estimate. The CC will be responsible for coordinating this effort and ensuring a consistent calculation among all the sites. The Clinical Site will be responsible for integrating the result into the EMR and the electronic Clinical Decision Support (eCDS).
When is prospective recruitment expected to begin and end?
Prospective recruitment will begin toward the end of Year 1 and continue into Year 4
Is the plan to have a central consent form which will be used by all clinical sites?
Yes, there will be a central consent form that might need slight modification based on local IRB requirements. The sites are expected to have a single IRB submission as instructed in the RFA.
The RFA indicates that 15 genomic risk assessments will be incorporated into the EMR and returned to patients. When and how will these 15 conditions be selected?
During the first year, the Steering Committee will select 15 conditions that will have genomic risk assessment and management plans developed and implemented across the Network.
Why is FDA approval required for the genotyping technology?
The FDA approval is required due to the clinical implementation component of the program. The one-year protocol development period is insufficient for developing and validating a custom array; the eMERGE Network will need an array that is essentially off the shelf and CLIA and FDA approved for clinical use.
FDA has approved some panels, but they sometimes require confirmatory testing for results that are returned to patients. Has this been addressed?
No, the Steering Committee will need to address this once the genotyping panel is selected.
Are sub-projects allowed or is this meant to be a Network-wide single project where opportunities to do sub-projects are discouraged? Applicants are encouraged to submit ideas for sub-projects. But, it is important to recognize that resources are limited and the primary purpose of this RFA is to understand the impact of genomic risk assessments on the 20,000-patients and their clinicians.
Are Electronic Medical Records (EMRs) required for sites who participate in this Network?
Yes, a key aspect of this study is to understand how and what information can be presented to the clinician and patient using the EMR. Each clinical site will be judged on, among other things, the quality, comprehensiveness, and ease of modification of its EMR. Each clinical site should describe and budget accordingly to have the necessary clinical and informatics expertise to incorporate the genomic risk assessment and management plan into their EMR.
Is NHGRI’s AnVIL expected to be the central repository for the datasets generated by this Network?
Yes, AnVIL is expected to be the data repository for the eMERGE Network. It is anticipated that Network members will work with AnVIL staff to identify and implement methods to leverage this resource to reduce barriers for implementing genomic medicine. AnVIL is expected to be open to the public by the end of fourth quarter of 2019.
Is there a cost associated with using AnVIL?
Applicants should budget for using the AnVIL resource to address their analysis needs. Costs related to compute and egress charges are expected to be covered by applicants. In regard to storage costs, applicants who deposit datasets in AnVIL, for the explicit goal of having those datasets made available via open-or controlled access to any researcher consistent with AnVIL data use policies, will have the cost associated for storing those datasets covered by AnVIL. All other uses of AnVIL will require applicants to budget for storage costs. For budgeting purposes, charges associated with AnVIL will be similar to large-scale cloud providers such as those described at:
If a single protocol has not been defined, how can applicants describe how they will integrate the protocol with in their EHR systems?
Applicants should describe how they would integrate their proposed genomic risk assessment and management protocols into their own EHR systems and their systems’ flexibility, processes, and timeline for implementing the risk assessment and management protocols decided upon by the Steering Committee.
What is Fast Healthcare Interoperable Resource (FHIR) and how are will it be used for the eMERGE Network?
FHIR is a Health Level 7 (HL7) interoperable specification for healthcare interoperability. The eMERGE Network plans to leverage FHIR for capturing and returning structured genotyping and clinical reporting of health information.
Currently, EMRs are allowing extremely limited inbound FHIR connections. Are applicants required to support inbound FHIR?
No, it is understood that there are limitations to FHIR, especially related to genomics information. When a FHIR standard has been established, it will be expected that sites use the FHIR standard to incorporate the information. eMERGE has adapted and led efforts to establish FHIR standards for genetic testing reporting. It is expected that eMERGE sites will continue to be leaders in these types of efforts.
Can applicants propose to develop methods for electronic (e-) phenotyping?
Yes, applicants can propose e-phenotyping protocols, including Natural Language Processing (NLP). It is expected that eMERGE will continue its important work expand and validate the eMERGE library of e-phenotypes such as those available in eMERGE Phenotype KnowledgeBase (PheKB), by focusing on phenotypes related to the common, complex diseases selected for genomic risk assessment and management.
Please clarify the classes of data needed to be abstracted from a site’s EMR (e.g. imaging data).
The data extracted should be commensurate with the data needed to perform Network-wide outcome analyses, as determined by the Steering Committee.
What data will be required to be deposited into a central repository like AnVIL?
Clinical data (including medical history and exam findings, family history, laboratory findings, imaging, etc. as relevant), genomic data, calculated clinical and genomic risk scores—all de-linked from Personally Identifiable Information (PII)—required to perform Network-wide analyses as determined by the Steering Committee will be deposited in a central repository like AnVIL.
Given the requirement for providing risk estimates to patients through electronic Clinical Decision Support (eCDS) incorporated into the EMR and the requirement to use online tools for patient-entered family history, does this RFA require integration with patient portals?
No, patient portals are not specifically required but applicants are encouraged to include end-to-end processes for capturing and disseminating information to patients and clinicians.
What kind of research is envisioned for the small two-year ethical, legal, and social implications (ELSI) research study?
The ELSI study should be designed to provide foundational and novel research findings that can inform the development and implementation of the PRS protocol proposed by the Clinical Site or Enhanced Diversity Clinical Site. The proposed ELSI research may utilize a variety of methodologies including empirical, legal and/or normative approaches as appropriate for the research question. The proposed ELSI study must be specific to the unique ELSI research questions raised by the calculation, return, understanding, use, and utility of polygenic risk scores in the diverse populations enrolled in eMERGE. In addition, the ELSI research study should be integrated into the larger eMERGE protocol such that the ELSI research informs the subsequent implementation of PRS.
How much detail is required about the ELSI study?
Applicants are encouraged to include a clear statement of the unique ELSI questions related to PRS, a brief description of the methodologies that will be used to study those questions, relevant ELSI expertise on the project team, and a concise description of how the ELSI research will be integrated into and inform the overall study design.
Is an ELSI research study required to apply to RFA-HG-19-013 or RFA-HG-19-014?
While an ELSI research study is not required to apply to either the eMERGE Clinical Sites or Enhanced Diversity Clinical Sites RFAs, inclusion of an ELSI research study is welcomed.
FAQ: Genetic Testing
Must a genomic risk assessment include genetic testing?
Yes, the genomic risk assessment must include at least one, and preferably many, assayed or imputed genomic variants. Use of other information besides genetic testing in the genomic risk assessment is acceptable and encouraged.
Will the genetic testing be a high-density phenotyping array, sequencing panels, or whole genome sequencing, or is that yet to be decided?
Genetic testing will be determined based on the availability and cost of funding at the time of award but is likely to be limited to clinically existing arrays. Applicants should consider that most variants that have approved clinical uses can be tested using lower cost methods.
RFA-HG-19-015: The Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network – Coordinating Center (U01 Clinical Trial Required
Expiration Date: Aug 03, 2019
- NOT-HG-19-023: Notice of Pre-Application Webinars for The Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network, Clinical Sites (RFA-HG-19-013), Enhanced Diversity Clinical Sites (RFA-HG-19-014), and Coordinating Center (RFA-HG-19-015).
RFA-HG-19-014: The Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network – Enhanced Diversity Clinical Sites (U01 Clinical Trial Required)
Expiration Date: Aug 03, 2019
RFA-HG-19-013: The Electronic Medical Records and Genomics (eMERGE) Genomic Risk Assessment and Management Network – Clinical Sites(U01 Clinical Trial Required)
Expiration Date: Aug 03, 2019
Last updated: June 20, 2019