National Institute of Mental Health (NIMH)
July 26, 2019 - Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-128
August 23, 2019 - Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
RFA-MH-20-340 , U01 Clinical High Risk for Psychosis Research Network (U01 Clinical Trial Not Allowed)
This Funding Opportunity Announcement (FOA) invites applications for a Data Processing, Analysis and Coordination Center (DPACC) to support aggregation and analysis of existing data related to Clinical High Risk for psychosis (CHR) and oversight and coordination of CHR research networks to be funded under RFA-MH-20-340 . The DPACC will provide executive management of two parallel lines of inquiry: 1) The aggregation of extant CHR-related data sets and subsequent secondary analyses for refinement of multi-modal biomarkers and development of biomarker algorithms that predict individual clinical trajectory and outcomes and 2) The management, direction, and overall coordination, including data processing and analysis, for a new multi-site network(s) focused on dissecting the heterogeneity of the CHR syndrome.
November 27, 2019
December 31, 2019
January 31, 2020
No late applications will be accepted for this Funding Opportunity Announcement.
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
This Funding Opportunity Announcement (FOA) invites applications for a CHR Data Processing, Analysis and Coordination Center (DPACC) to support and extend the work of the proposed Clinical High Risk for Psychosis Research Network to be funded under RFA-MH-20-340 . The DPACC will provide oversight and coordination of two parallel lines of inquiry: 1) The aggregation of extant CHR-related data sets and subsequent secondary analyses for refinement of multi-modal biomarkers and development of biomarker algorithms that predict individual clinical trajectory and outcomes and 2) The management, direction, and overall coordination, including data processing and analysis, for a new multi-site network(s) focused on dissecting the heterogeneity of the CHR syndrome. Toward achieving the first goal, the DPACC – in conjunction with NIMH and external working groups - will identify appropriate extant CHR data sets, aggregate and harmonize the data through development of a standardized processing and analysis pipeline for each data type, upload the data to the NIMH Data Archive (NDA), use computational techniques to identify and validate biomarker algorithms and/or risk calculators that predict the clinical trajectories and outcomes for individual patients, and establish a curated public data set that will serve as a resource for the research community.
Toward achieving the second goal of acquisition of new data via establishment of multi-site CHR cohort(s), the DPACC will provide the organizational framework for the management, direction, and overall coordination of a multi-site network(s) and will lead efforts, in conjunction with NIMH and external working groups to: (a) harmonize common data elements, standard measures, and uniform data collection procedures across multiple CHR/early psychosis research sites within the network; (b) assume responsibility for quality assurance and reliability assessments; (c) insure uniform standards for adverse event reporting, safety and protocol deviation monitoring; (d) build informatics infrastructure and pipelines necessary to gather, process and upload de-identified, patient-level data collected across all research sites to NDA; (e) develop data analysis, presentation, and reporting tools to facilitate analyses of clinical and biomarker date generated by the CHR networks described in RFA-MH-20-340 ; and (f) coordinate analyses of the newly acquired data for the identification of biomarkers or biomarker algorithms that are predictive of clinical trajectories and outcomes.
Clinical heterogeneity within the CHR population presents a substantial challenge for intervention development for this underserved population with unmet medical needs. Approaches for addressing this heterogeneity to enable future intervention trials require the development of tools to address: (a) defining a core set of clinical and functional outcomes beyond onset of psychosis to include affective, cognitive, and negative symptom domains and functional outcomes; (b) prospective stratification of CHR individuals into more homogeneous risk subtypes to predict the likelihood of clinical outcomes; and (c) testing of interventions that target hypothesized underlying mechanisms for emerging psychosis, mood syndromes, and functional disability.
RFA-MH-20-340 solicits CHR research network grant applications for studies that refine, test, and validate multi-modal biomarker approaches for predicting varied clinical trajectories or outcomes within a help-seeking CHR population and for CHR risk stratification to increase the likelihood of progression to specific clinical endpoints within a specified timeframe. To accomplish this goal, RFA-MH-20-340 invites applications for a CHR Network(s) consisting of multiple sites employing a common set of biomarker and clinical outcome measures to define CHR heterogeneity and underlying mechanisms that could be assessed in subsequent clinical trials. Each research network(s) will be responsible for study participant recruitment and retention and data acquisition using a common protocol consisting of to-be-determined multi-modal methods. Research network(s) may consist of a single institution serving as a consortium with sub-contracts to multiple institutions and/or community clinics, including non-U.S. sites or networks of clinics.
Aggregation and analysis of extant CHR data to refine and validate multi-modal biomarkers and develop biomarker algorithms.
The DPACC will aggregate relevant CHR data sets, which may also include first episode psychosis (FEP) phenotypic data sets, and create a curated data set with a common bioinformatics structure to support computational analyses (i.e., “data mining”) to address key questions such as: Can the marker, alone or in combination with others, be used to reliably predict varied clinical outcomes within a help-seeking CHR population, including psychosis, persistent cognitive and functional impairments, mood/anxiety disorder symptoms, and substance use disorders? Applicants should identify existing data sets that they propose for inclusion in aggregate analyses; however, the final decisions regarding which data sets will be included in the analyses will be made in consultation with NIMH and relevant external working groups. Appropriate data sets include cohort studies of CHR individuals that include assessment of a variety of outcomes, and potentially biomarker studies of illness trajectory in FEP, and could include data sets that are held within or outside of the U.S. NIMH will consult with the awardee regarding relevant data that might feasibly be obtained from public databases, population registries, existing large-scale consortia (e.g., the Psychiatric Genomics Consortium), or other private or government sources and will work with the awardee to establish data access agreements as needed.
The DPACC will perform secondary data analyses to identify multi-modal biomarkers and algorithms that predict clinical course and functional outcomes of help-seeking CHR subjects at the level of individuals. These multi-modal biomarkers/algorithms will undergo replication and validation in the CHR Network cohort(s) and will be disseminated to allow replication and validation outside of the NIMH-funded network(s). The aggregated and curated data collection will be a public resource, made available via the NIMH Data Archive (NDA). The NDA will make resources available to store the data in a cloud-based environment and will provide access management for the data and make data available to qualified investigators according to policies established by NIMH in consultation with an external working group.
The NDA will aid the awardee in setting up data analysis workflows in conjunction with NIMH and an external working group, but this will be a joint responsibility with the awardee. The awardee will be responsible for the compute costs for the analysis of the data sets as well as for any download costs. The awardee will work with NIMH to solve issues related to data sets that are not consented for broad data sharing and/or are not permitted by local regulations to be shared. Any such restrictions about potential existing data sets should be discussed in the data sharing part of the application.
Management, direction, and coordination for a new multi-site CHR research network(s)
The DPACC will provide the organizational framework for the management, direction, and overall coordination of the multi-site CHR network(s). The DPACC team should include: a director (or co-directors) and one or more associate directors to ensure that the wide scope of activities are seamlessly coordinated; as well as individuals with bioinformatics and data processing expertise appropriate to establish and carry out the procedures for collecting, processing, and analyzing specialized biomarker data types, including multi-modal data analysis.
Activities related to this objective include the following:
1. Coordination and monitoring of CHR network(s) activities
The DPACC will support and enhance the recruitment of a large cohort of CHR individuals and establish and implement harmonized research methods across the multi-site network(s). Specifically, the DPACC will: (i) establish standardized methods for uniform participant recruitment, enrollment, and retention; (ii) establish standardized methods for data collection and aggregation; (iii) train staff in data collection methods and implement fidelity monitoring and performance improvement activities across network research sites; (iv) coordinate the integration of technological advances, software, and data collection methods across research sites; (iv) ensure that ethical and human subjects protections are in place and supervise the reporting of and responses to adverse events; and (v) prioritize and coordinate network-based data analyses and publications of scientific findings in conjunction with NIMH and external working groups.
The DPACC will conduct ongoing monitoring and periodic reporting of the rate of subject recruitment and retention, demographic characteristics, and trends in cumulative data collection.
The DPACC will establish a Steering Committee to oversee these activities. The DPACC will be responsible for organizing, providing logistical support, and running Steering Committee meetings. This will include a kickoff meeting in Bethesda, MD within the first year of the award in conjunction with NIMH and the external working groups and annual progress review meetings thereafter. In-person meetings will include all Steering Committee members, representatives from network research sites, and external working group members, as required. The DPACC will organize monthly phone and/or web-based teleconferences to maintain communication and collaboration among Steering Committee members, NIMH, and the external working groups. The costs associated with annual meetings and monthly teleconferences should be factored in the DPACC budget.
2. Data management, processing, and archiving
Research network grant applications submitted to RFA-MH-20-340 are required to present a conceptual model of CHR for psychosis clinical features and propose measures of clinical trajectories and predictive biomarkers for various clinical outcomes, including methods for identifying subgroups of subjects based on their predicted trajectories that could be applied in a future treatment trial. The set of specific measures and tools to be used for data collection will be determined by the network in consultation with NIMH and relevant external working groups, but the anticipated core and specialty data types should include the following: interview-based and self-report ratings of clinical symptoms, diagnoses, behavioral measures of neurocognition, structural and functional MRI, EEG/ERPs, blood-based markers, genetics (including polygenic risk scores), speech/language, self-report or clinical ratings of functioning, and ambulatory and/or device- or web-based assessment of symptoms, mood, cognition, and movement.
Applications in response to this FOA are encouraged to engage thought leaders in bioinformatics and large-scale multi-site longitudinal studies of multi-modal biomarker predictors for subject selection, course of illness, and clinical and functional outcomes to inform selection of CHR participants for future clinical trials as well as research studies of the underlying biological mechanisms. The data center will make the data findable, accessible, interoperable, and reusable (FAIR, https://www.force11.org/group/fairgroup/fairprinciples) to enable secondary analyses by the scientific community.
The DPACC will be responsible for managing two different types of data: data from existing studies and newly collected data from a network of research sites. The challenges for aggregating these different types of data are distinct, and the application will need to propose appropriate ways to deal with the different problems raised by legacy data aggregation as well as new data collection. For legacy data, the original informed consents or other administrative issues may prevent the sharing of all data at the individual subject level. The awardee will be expected to make as much of that data available as possible, within these constraints. In cases where the original subject level data cannot be made available, the awardee will make available aggregated results and as much derived data at the subject level as possible. For new data, the consents will be such that all data can be shared with the research community.
Overall, the DPACC will develop, implement and maintain a data management system that incorporates best practices in bioinformatics for large-scale multi-site longitudinal studies including:
The DPACC will have responsibility for depositing patient-level data collected under this award in the NDA. All network data will be deposited into NDA and made available to qualified investigators through data access agreements without any further delay. The DPACC and the network of research sites will use the NIMH Global Unique Identifier (GUID) infrastructure to create unique identifiers that protect the anonymity of the individual-level patient data. Staff at the NDA will be responsible for helping the DPACC export the GUID infrastructure to all the network research sites.
3. Data analysis and presentation
The DPACC will be responsible for the development and implementation of an informatics infrastructure, analytic methods, and data visualization tools that: (i) leverage multi-modal information collected from CHR network participants; (ii) explore variations in patient characteristics for identification of predictive sub-types; and (iii) plot individual research site performance against outcomes observed across all network research sites. These methods may include automated machine learning algorithms and “big data” reporting tools, including those used in other CNS multi-modal biomarker data analysis initiatives.
These activities will be planned and carried out in consultation with the Steering Committee, NIMH, and relevant external working groups. The DPACC will develop a procedure for selecting and prioritizing analyses to be performed, planning for publications, and resolving disputes among involved parties. Research supported by this FOA is to be used only for precompetitive purposes and individuals given access to the raw or analyzed data will be required to provide assurance that they agree not to file patent applications on research discoveries made using data collected by the network(s).
To promote scientific investigation across the network of research sites, the DPACC will serve as the main locus of cloud expertise for the network(s) and will develop an informatics infrastructure that should include a secure, cloud-based interface that allows network investigators, including those who may be located outside of the U.S., to access aggregated de-identified patient-level data, conduct distributed analyses, and collaboratively build, edit, and run data workflows. The DPACC will also be responsible for developing, in consultation with the Steering Committee, a metadata repository for the network with access controls that are independent of the data itself.
Successful applicants will have demonstrated experience with the coordination of large multi-dimensional, multi-modality biomarker data sets; leading-edge data analytic tools for analysis of clinical, biomarker, and multi-modality data; and openness regarding new models of data management and attribution, including cloud-based methods. Other desirable qualities include demonstrated use or development of data citation models. It is expected that anatomical and physiological experts on the DPACC team will play a key role in developing the framework for storing, organizing, managing, and tracking access to data and resources in conjunction with the NIMH and external working groups.
4. Dissemination of DPACC resources
Applications should describe plans for establishing and maintaining a website that conveys the aims and activities of the DPACC and the CHR research network(s) in plain language, describes the network(s)' study protocol (including details about the data collection methods and tools), provides updates about data releases, data processing pipelines, data analysis tools, and links to the project’s publications. The website will direct users to the workflows to analyze the data. Applicants are encouraged to maintain all relevant workflows and documentation in a single location. If necessary, applicants are encouraged to contact program staff to discuss their plans to implement their workflows at the NDA. The DPACC will aid with dissemination of data-driven and validated biomarkers for prediction of CHR clinical trajectories and outcomes and will provide support to relevant working groups for planning potential future clinical trials.
Applicants are strongly encouraged to consult with NIMH staff when developing plans for an application (see Agency Contacts, Section VII). This early contact will provide an opportunity to clarify NIMH policies and guidelines and identify whether the proposed project is consistent with the purpose of this FOA.
A technical assistance teleconference will be held for potential applicants on Tuesday December 17, 2019 at 3:00 pm EST. NIMH staff will be available to answer questions related to this FOA during this teleconference. To obtain call-in information, please send a request to firstname.lastname@example.org at least 24 hours in advance of the call. Prospective applicants are encouraged to submit their questions or comments in advance to email@example.com. Participation in the teleconference is neither required nor necessary for a successful application. A summary of the teleconference will be provided upon request via email to firstname.lastname@example.org. For more information on the teleconference see https://www.nimh.nih.gov/funding/opportunities-announcements/clinical-high-risk-for-psychosis.shtml.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
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NIMH intends to commit up to a total of $4 million in FY20 to fund 1 award under this FOA.
The scope of the proposed project should determine the project period. The maximum project period is 5 years.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
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.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. 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.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
PD/PIs submitting an application under this FOA will not be eligible to submit an application as a PD/PI under RFA-MH-20-340.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:email@example.com
All instructions in the SF424 (R&R) Application Guide must be followed.
The application must include only its own budget, including any subcontract budgets associated with it. Separate itemized budgets must be prepared for each anticipated subcontract.
Include estimated costs for owners of 4-6 existing datasets to prepare their data for harmonization of common data elements, and for centralized common data pipeline processing of selected data types, and data analyses based on key questions identified by NIMH and the external working groups.
The costs associated with annual meetings and monthly teleconferences should be included in the proposed DPACC budget.
Significance: Explain why the proposed approach to analysis of aggregated CHR data and management and coordination of the research network are optimal to achieve the scientific objectives of the DPACC.
Describe the novel organizational concepts and management strategies the DPACC will use in coordinating the CHR research network(s). How are the concepts and strategies novel to a specific type of research program and/or applicable in a broad sense?
Describe plans to employ unique or novel methodologies that will enhance the analysis of extant data. Explain how the DPACC plans to use current best practices to improve the knowledge and/or skills of the research network it will support.
Provide a detailed plan to deploy cloud-based analytic tools appropriate for analyses of the proposed CHR biomarker and clinical data types.
Describe an overall strategy, operational plan, and organizational structure that is well-reasoned and appropriate to accomplish the goals of the CHR research network(s). The research approach should include strategies to ensure a robust and unbiased scientific approach across the network and include discussion of potential problems, alternative strategies, and benchmarks for success. The description of the proposed strategy should adequately establish feasibility and a plan to manage the risks associated with the activities of the network. An appropriate plan for work-flow and a well-established timeline and project milestones should be included.
Propose an organizational structure that includes a director (or co-directors) and one or more associate directors to ensure that the diverse activities are well-coordinated.
For existing data, propose a detailed plan for the rapid aggregation and analysis of legacy data and uploading of original raw data and data at the subject level derived from this raw data into NDA. If sharing of subject-level data is precluded (e.g., by Institutional Review Board), aggregated data can be made available to the research community either through NDA or via a portal created by the awardee or both.
For new data, propose a detailed plan for transferring data from the network sites, conducting quality control on that data, and then transmitting the cleaned data to NDA.
Provide a detailed plan for developing and carrying out the various administrative and project management activities, including standardization of study protocols, training of staff, site monitoring, establishment of data processing pipelines, coordination of analyses, and production of reports.
Propose a data management system that includes the data infrastructure and pipelines necessary to gather, combine, store, and manipulate de-identified biomarker and clinical data as well as combined/multi-modal data from multiple network sites in a timely manner.
Describe how the DPACC will coordinate with the CHR network leadership, NIMH and external working groups to develop a procedure for shared decision-making, selecting and prioritizing analyses to be performed, planning for reports (including progress toward milestones) and publications, and resolving disputes among DPACC and CHR network teams.
The PD/PI (or Multi-PDs/PIs) of the DPACC must be experienced in the coordination and management of multi-site clinical studies, including success in meeting milestones and timelines. The experience of each PD/PI and all Key Personnel must be carefully documented and roles and responsibilities must be well-defined. A DPACC requires a multidisciplinary team and the application should reflect the team's background in hands-on involvement in the steps needed for data acquisition, processing, aggregation and analyses of multi-modal biomarker and clinical data, as well as study coordination (including establishing study protocols and maintaining reliability of procedures), and data management, analysis and dissemination.
Describe the study team members’ experience and expertise in the following areas:
The following modifications also apply:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Human subjects research activities to be conducted under grants awarded in response to this FOA are considered to meet the criteria for Exemption 4 and are not considered clinical research as defined by NIH; therefore, the NIH policies for addressing inclusion of women, minorities and children do not apply to research that is determined to meet the criteria for Exemption 4. Please see the application guide to understand which sections of the PHS Human Subjects and Clinical Trial Information form should be completed for research meeting the criteria for Exemption 4.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement .
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at firstname.lastname@example.org when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Does the proposed DPACC address the needs of the CHR research network(s) that it will coordinate? Is the scope of activities proposed for the DPACC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network(s)?
Are the PD(s)/PI(s) and other personnel well suited to their roles in the DPACC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multi-site, multi-modal biomarker research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the application is multi-PD/PI, do the investigators have complementary and integrated expertise and skills? Are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the DPACC? Does the applicant have experience overseeing selection and management of subawards, if needed?
Does the study team demonstrate multidisciplinary expertise and a track record of hands-on involvement in aggregation and analysis of multi-modal biomarker and clinical data, study coordination (including establishing study protocols and maintaining reliability of procedures), and data management, cloud-based data analyses and dissemination? Does the study team include individuals with experience and expertise in bioinformatics and large-scale multi-site studies, including cloud computing and data science? Does the study team include individuals with expertise and experience in establishing cut-points that define subjects, at the individual level, who meet criteria for biomarker prediction/outcomes? Does the study team include individuals with expertise and experience in multi-modal biomarker predictors for subject selection, course of illness, and clinical and functional outcomes to inform selection of CHR subjects for future clinical trials as well as research studies of the underlying biological mechanisms?
Does the application propose novel organizational concepts and management strategies in coordinating the CHR research network(s) the DPACC will serve? Are the concepts and strategies novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts and management strategies proposed?
Does the application describe plans to employ unique or novel methodologies that will enhance the analysis of extant data? How does the DPACC plan to use current best practices to improve the knowledge and/or skills of the CHR research network(s) it will support?
Does the application include a description of plans to deploy cloud-based analytic tools appropriate for analyses of the proposed CHR biomarker and clinical data types?
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the CHR research network(s) the DPACC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? Does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Does the application include an appropriate plan for work-flow, and a well-established timeline, and project milestones?
Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects ?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Regarding PHS Human Subjects and Clinical Trials Information section: Note that applicants are asked to provide responses only to Section 1 (Basic Information) and Section 3 (Protection and Monitoring). Responses to Section 3 should focus on data privacy and protection (but not data collection procedures or participant eligibility criteria).
Will the institutional environment in which the DPACC will operate contribute to the probability of success in facilitating the CHR research network(s) it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the DPACC proposed? Will the DPACC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
For research that involves human subjects but does not involve one of the 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 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 Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
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).
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) Genomic Data Sharing Plan (GDS).
The applicant should provide specific plans for data and resource sharing and distribution in the Research Strategy section of the application.
In addition, reviewers will comment on the reasonableness of the Resource Sharing Plans with regard to:
For resources involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
In addition, reviewers will consider the following:
Are budgeted costs for the following activities appropriate?
• all DPACC activities, including subcontracts
• preparation of existing datasets for harmonization and centralized processing of selected data types and analyses based on questions identified by NIMH and the external working groups
• annual meetings and monthly teleconferences
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIMH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Mental Health Council.
The following will be considered in making funding decisions:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibilities as described below:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NIH Project Scientist(s) will:
The NIH Program Officer will:
Areas of Joint Responsibility include:
CHR Steering Committee. The CHR Steering Committee (SC) will serve as the operational governing board for this project, the DPACC, and for the CHR network award(s) funded under RFA-MH-20-340. The SC will include: the PD(s)/PI(s), the PD(s)/PI(s) of award(s) funded under RFA-MH-20-340, External Working Group members (to be named after award), NIMH Project Scientist(s), and NIMH Program Officer.
The CHR SC will:
External Working Group (EWG):
The EWG will be composed of four to six senior scientists with relevant expertise and whom are not directly involved with the DPACC or CHR network; the membership may be adjusted on an ad hoc basis as needed.
The EWG will:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Sarah Morris, Ph.D.
National Institute of Mental Health (NIMH)
Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
National Institute of Mental Health (NIMH)
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