Department of Health and Human Services
Part 1. Overview Information

 

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Neurological Disorders and Stroke (NINDS)

National Institute on Deafness and Other Communication Disorders (NIDCD)

Funding Opportunity Title

Limited Competition: Consortium on Biomarker and Outcome Measures of Social Impairment for Use in Clinical Trials in Autism Spectrum Disorder (U19 Clinical Trial Not Allowed)

Activity Code

U19 Research Program – Cooperative Agreements

Announcement Type

Reissue of RFA-MH-15-800

Related Notices

NOT-OD-19-128, Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research.

NOT-OD-19-137, Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research.

Funding Opportunity Announcement (FOA) Number

RFA-MH-20-325

Companion Funding Opportunity

None

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.242, 93.865, 93.853, 93.173

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to further validate promising EEG and eye tracking measures that showed promising performance in the recently-completed Autism Biomarkers Consortium for Clinical Trials (ABC-CT) study. The intent of the FOA is to qualify a set of measures that can be used as biomarkers to reduce heterogeneity, and/or as sensitive and reliable objective measures of social impairment in autism spectrum disorders (ASD) clinical trials. 

The FOA will support a multi-site consortium to conduct a study with three primary aims to replicate and extend previous characterization of the most promising EEG and eye-tracking measures, incorporating suggestions and guidance from the FDA Biomarkers Qualification Program (BQP). 

A key goal of the Consortium project is to provide a community resource for broad sharing of all data generated including processed/analyzed data, with rapid and timely deposition of data into the National Database for Autism Research (NDAR). All data generated in this project are expected to be deposited in NDAR and will be accessible for use by all qualified investigators. In addition, blood (DNA) samples are expected to be deposited in the NIMH Repository and Genomics Resource for future research use.

The Consortium project will assess the following: (1) whether eye-tracking, EEG paradigms, or a combination of the two, have potential utility as stratification biomarkers and/or as sensitive and reliable measures of change in ASD clinical trials; (2) the relationship (correlation) of validated clinical measures (including measures of social impairment)  to eye tracking or EEG paradigms; and (3) the feasibility of collecting the same biomarker measures in a younger cohort. 

Key Dates

 

Posted Date

November 7, 2019

Open Date (Earliest Submission Date)

December 9, 2019

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

January 9, 2020  

All applicants 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 corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Funding Opportunity Announcement.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

March 2020

Advisory Council Review

May 2020

Earliest Start Date

July 2020

Expiration Date

January 10, 2020

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). 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.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information


    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description

    Purpose

    The purpose of this Funding Opportunity Announcement (FOA) is to further validate promising EEG and eye tracking measures that showed promising performance in the recently-completed Autism Biomarkers Consortium for Clinical Trials (ABC-CT) study. The intent of the FOA is to qualify a set of measures that can be used as biomarkers to reduce heterogeneity, and/or as sensitive and reliable objective measures of social impairment in autism spectrum disorders (ASD) clinical trials. 

    The FOA will establish a team of clinical investigators (the Clinical Investigation Unit, CIU) to assess the following:

    (1) whether eye-tracking, EEG paradigms, or a combination of the two, have potential utility as stratification biomarkers and/or as sensitive and reliable measures of change in ASD clinical trials;

    (2) the relationship (correlation) of commonly used clinician and caregiver assessments of social impairment to eye tracking or EEG paradigms; and

    (3) the feasibility of collecting the same biomarker measures in a younger cohort. 

    A key goal of the Consortium project, which is a resource generating initiative, is to provide a community resource for broad sharing of all data generated, including processed/analyzed data, with rapid and timely deposition of data into the National Database for Autism Research (NDAR). All data generated in this project are expected to be deposited in NDAR and accessible for use by all qualified investigators (http://ndar.nih.gov/access.html). Blood samples from all subjects, including the parents of ASD subjects, are expected to be deposited in the NIMH Repository and Genomics Resource for future genomic analyses of what will be a well-characterized cohort of ASD individuals.

    Background

    Autism Spectrum Disorders (ASD) are marked by impairments in reciprocal social interaction, and the presence of stereotyped or repetitive behavior, interests, or activities. These complex disorders are usually of lifelong duration and affect multiple aspects of development, learning, and adaptation at home, in school, and in the community, thus representing a pressing public health need. The etiologies of these disorders are not yet understood, but likely include a combination of genetic and environmental influences.

    Treatment research in ASD has been challenging, as the disorder is heterogeneous and the cluster of impairments for these individuals is complex. There are many potential targets for intervention, and little agreement regarding the most tractable components. Progress in the field is hindered by the lack of sensitive, validated biomarkers for stratification of subjects into treatment-relevant subgroups. Such markers would serve to reduce heterogeneity in samples and substantially increase the ability to determine efficacy. A significant need also exists for validated outcome measures to assess treatment-mediated changes in core and associated symptoms.

    The Biomarkers Consortium is a public-private biomedical research partnership managed by the Foundation for the National Institutes of Health (FNIH) that endeavors to discover, develop, and qualify biomarkers to support new drug development, preventive medicine, and medical diagnostics. In 2012, the Neuroscience Steering Committee of the Biomarkers Consortium convened an ASD Biomarkers Working Group, which includes representatives from NIMH, pharmaceutical companies, nonprofit organizations, and the Food and Drug Administration (FDA), to assess opportunities for collaborative partnerships to further the qualification of biomarkers for use in ASD clinical trials. The working group obtained feedback from a wide range of stakeholders and undertook a review of the published literature to assess the readiness of biomarker candidates for potential use in ASD clinical trials. Resting state and task-based EEG as well as eye tracking measures emerged as the top biomarker candidates of interest for assessing application to studies of social impairment in ASD.  Moreover, these measures are noninvasive, relatively inexpensive, and implementable from early infancy throughout the lifespan.

    In 2015, the National Institutes of Health (NIH) established the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) through a cooperative agreement, co-funded by the National Institute of Mental Health (NIMH), the National Institute of Neurological Disorders and Stroke (NINDS), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).  Additional co-funding was provided by the Clinical Research Associates of the Simons Foundation Autism Research Initiative (SFARI), through the Foundation for NIH (FNIH). The ABC-CT project was accepted by the Biomarkers Consortium Executive Committee (BCEC) as an official BC project, establishing it as a pre-competitive private-public partnership and facilitating coordination with the Food and Drug Administration (FDA), industry partners, and international efforts in biomarker development.  

    The ABC-CT conducted an early stage validation study of a set of eye tracking and EEG measures to determine their potential for use as stratification biomarkers or indicators of change in clinical status.  The naturalistic, multi-site study collected biomarker and clinical data from 399 participants (280 ASD, 119 typically developing) ages 6 – 11 years. Data were collected at baseline, 6 weeks, and 6 months.  A primary aim of the ABC-CT is the establishment of a community resource. Clinical and biomarker data are shared through the National Database for Autism Research (NDAR) and DNA has been deposited in the NIMH Repository and Genomics Resource (NRGR) for future sequencing. With input from the Biomarkers Consortium partners, including review of feasibility study results and interim analyses, the study protocol was pruned to include the most promising biomarker measures.  Candidate biomarkers were evaluated for feasibility of implementation, construct validity, reliability, discriminant validity, stratification, and sensitivity to change in comparison to conventional symptom measures. In May 2019, the FDA Biomarker Qualification Program approved a Letter of Intent submission for an EEG biomarker (N170 latency response to upright human faces as measured via EEG) as a potential drug development tool to identify ASD subgroup for enrichment in clinical trials, encouraging submission of a Biomarker Qualification Plan that addresses the scientific issues and recommendations outlined in the FDA LOI Decision Letter. Another Letter of Intent to pursue biomarker qualification for an eye tracking biomarker measure was submitted to the FDA and is pending review. 

    This FOA will support a continuation of the ABC-CT to further develop and validate the N170 biomarker under the guidance of the FDA Biomarker Qualification Program, and to pursue the development and validation of other promising EEG and eye tracking biomarkers, with the goal of obtaining the evidence needed for FDA registration of one or more biomarkers for use in clinical trials of treatments for ASD.  Continued coordination with the FNIH Biomarkers Consortium will be pursued.  All new data and biospecimens will be deposited and shared through the NDAR and NRGR, enhancing the existing community resource. 

    Objectives

    This FOA will support a multi-site Consortium project to further develop and validate the N170 to upright faces biomarker under the guidance of the FDA Biomarker Qualification Program, and to pursue the development and validation of promising eye tracking biomarkers. The objectives will be to extend the follow-up of the longitudinal cohort from the previous study to one additional timepoint; evaluate the correlation of these measures with phenotypic and clinical characteristics; replicate findings from the previous study with a new cohort under the same rigorous standardization procedures; evaluate the feasibility of collecting the same biomarker measures in a preschool-age cohort; and explore subgroup analyses on the combined cohort to evaluate the impact of factors such as age, sex, and ethnicity on the biomarker measures. 

    Expected outcomes include:

    • Further development and validation of the N170 to upright faces biomarker for use as a stratification measure to reduce heterogeneity in 6- to 11- year-old ASD participants in clinical trials of interventions to mitigate social deficits. Incorporation of guidance from the FDA Biomarker Qualification Program (BQP) to obtain evidence needed for qualification.
    • Further development and validation of promising eye tracking (ET) biomarkers for use as stratification measures to reduce heterogeneity in 6- to 11- year-old ASD participants in clinical trials of interventions to mitigate social deficits. Incorporation of guidance from the FDA Biomarker Qualification Program (BQP) to obtain evidence needed for qualification.
    • Evidence on the utility of EEG and ET measures of domains of social impairment as objective predictors of clinical outcomes in future ASD intervention trials.  
    • An integrated data set of longitudinal EEG, eye tracking, and clinical measures from ASD and typically developing (TD) subjects, as well as blood (DNA) samples from ASD subjects and their parents, made available for data analyses by qualified investigators through NDAR and the NIMH Repository and Genomic Resource.

    Program Structure of the Clinical Investigation Unit (CIU)

    Administrative Core - The Director of the Administrative Core will be the overall PD/PI for the U19. The Administrative Core will work closely with the Collaborating Implementation Sites (CIS, also see below) to implement the Consortium on Biomarkers and Outcome Measures in ASD (Consortium project) and coordinate with the Data Coordinating and Data Acquisition and Analysis Cores. The Administrative Core will manage subcontracts with the Sites and Cores. The Administrative Core is responsible for managing all aspects of the Set-up, Implementation and Data Analyses phases.

    The Administrative Core is responsible for: establishing a central IRB; developing standard operating procedures (SOPs); implementing Good Clinical Practice (GCP) standards across sites; recruiting a Project Manager (with private sector experience in implementing GCP standards at academic sites) to oversee operational management of the project; maintaining fidelity to research procedures; monitoring recruitment and study milestones; ensuring quality control (QC) for data and blood (DNA) collection; timely submission of data to NDAR; and overseeing the analyses of all data by the Data Acquisition and Analysis Core (DAAC).

    The Director of the Administrative Core will be responsible for maintaining appropriate communication with the CIS, the Data Coordinating Core (DCC), and the DAAC.  The Director of the Administrative Core will co-lead (with NIH) activities to pursue continued coordination with the FNIH Biomarkers Consortium.

    Collaborating Implementation Sites – The CIS will work together as a team with overall coordination and management by the U19 PD/PI (Admin Core). The CIS will take part in the Set up and Implementation phases of the project, assemble ASD cohorts, and obtain comprehensive clinical, and laboratory data and blood (DNA) samples to enable measurements of promising biomarkers related to social deficits in ASD.

    Each CIS must be able to demonstrate: capabilities for robust recruitment consistent with the demands of the project; ability to conduct all aspects of the project; expertise to implement all measures and aspects of the study protocol; and ability to work within a Consortium. 

    Each CIS must agree to: execute the finalized protocol; utilize a single IRB; and work collaboratively with the PD/PI of the U19, the CIS and the Cores within the Consortium project.

    Data Coordinating Core – The DCC will be responsible for: organization and management of all data collected from the CIS; securely storing and maintaining, eye tracking and EEG data; data documentation; data cleaning and file formatting; central data QC procedures; data backup procedures; development of computerized forms for site data collection; site visits to the CIS to monitor the quality of record keeping, source documentation and the accuracy of data entry; generating real time reports including subject recruitment reports; and preparation of data submissions to NDAR. The DCC will operate independently from the CIS. The DCC is strongly encouraged to have an individual dedicated to coordinate data submissions to NDAR.

    Data Acquisition and Analysis Core - The Data Acquisition and Analysis Core (DAAC) will have the responsibility for statistical design and analyses of all data generated by the Consortium project. Activities of the DAAC include: specifying the data preprocessing/clean-up that the CIS will need to perform before uploading data centrally; data cleaning/artifact removal of biomarker datasets; ensuring proper file formatting; data processing of each CIS biomarker data files to prepare for primary analyses; perform primary, interim, and final analyses of all the data; and providing statistical support.

    In addition, the DAAC will monitor the central data repository at the DCC, and will be responsible for uploading final processed biomarker and clinical data into the central database. Note: All data analyses will be performed solely at the DAAC to ensure standardization of statistical analysis procedures. 

    Sharing of Data Generated by the Consortium Project

    All data resulting from this project are expected to be submitted to the National Database for Autism Research (NDAR), along with appropriate supporting documentation to enable efficient use of the data. Data are expected to be submitted to NDAR every 6 months (on or before January 15, and on or before July 15). Cumulative submission of data is expected during each submission cycle, accommodating any changes. Individual subject-level data rather than summary/aggregate data are expected.

    All submitted data (both descriptive/raw and analyzed data) will be made available for access by members of the research community according to the provisions defined in the NDAR Data Sharing Policy. The data sharing policy is intended to allow investigators sufficient time for verification of the data collected.

    All research data are made available to other researchers within four months or less after submission, allowing the PD/PI/Director and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures. Descriptive data on banked blood (DNA) samples are expected to be shared in NDAR when the sample is banked at the NIMH Repository and Genomics Resource.

    Any deviations from the above in terms of timelines or types of data to be shared must be negotiated with the NIH program officer for the grant (or other award mechanism) before the award is made.

    Governance and Coordination of the Consortium Project

    A key aspect of this FOA is the continuation of a collaborative partnership with the FNIH Biomarkers Consortium. The successful applicant will participate in a collaborative effort between the NIMH and the FNIH Biomarkers Consortium to qualify biomarkers and outcome measures of social impairments in ASD for use in intervention studies and clinical trials. Applicants must agree to incorporate feedback from the NIMH, the FDA and the FNIH Biomarkers Consortium funding partners. 

    The FNIH Biomarkers Consortium will serve as a collaborative environment in which to promote standardization and harmonization of biomarkers across multiple research sites, coordination with the NIH, FDA, international efforts, and engagement with non-profit foundations, industry, and regulatory agencies to qualify potential biomarkers of social impairment for their proposed context of use in ASD intervention studies and clinical trials.

    See Section VIII. Other Information for award authorities and regulations.

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.  

    Application Types Allowed

    Renewal

    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.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials  

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The following NIH components intend to commit $7.4 million in FY 2020 for 1 award:

    National Institute of Mental Health (NIMH)

    National Institute of Neurological Disorders and Stroke (NINDS))

    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    National Institute on Deafness and Other Communication Disorders (NIDCD)

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    Award Project Period

    The maximum project period is 5 years.

    NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Only the current awardees of the Consortium on Biomarker and Outcome Measures of Social Impairment for Use in Clinical Trials in Autism Spectrum Disorder (U19), funded under RFA-MH-15-800, can apply.

    Foreign Institutions

    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.

    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) – 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.
    • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. 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.  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.

    Eligible Individuals (Program Director/Principal Investigator)

    Any individual(s) with 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. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

    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.

    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.

    The NIH will not accept duplicate or highly overlapping applications under review at the same time.  This means that the NIH will not accept:

    • A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
    • A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
    • An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

    Letter of Intent

    Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

    By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

    • Descriptive title of proposed activity
    • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
    • Names of other key personnel
    • Participating institution(s)
    • Number and title of this funding opportunity

    The letter of intent should be sent to:


    ASDBiomarkers@mail.nih.gov

    Page Limitations

    Type

    Page Limits

    Overall

    12

    Admin Core (Use for Administrative Core)

    6

    Core (use for Data Coordinating Core and for Data Acquisition/Analysis Core)

    6 (per core)

    Project (use for each Collaborating Implementation Site)

    6 (per Project)

    Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

    Instructions for the Submission of Multi-Component Applications

    The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

    The application should consist of the following components:

    • Overall: Required, maximum one
    • Administrative Core: Required, maximum one
    • Collaborating Implementation Site(s): Required, minimum one and maximum five
    • Data Coordinating Core: Required, maximum one
    • Data Acquisition and Analysis Core: Required, maximum one
    Overall Component

    When preparing your application, use Component Type ‘Overall’.

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Overall)

    Complete entire form.

    PHS 398 Cover Page Supplement  (Overall)

    Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

    Research & Related Other Project Information (Overall)

    Follow standard instructions.

    Project/Performance Site Location(s) (Overall)

    Enter primary site only.

    A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

    Research & Related Senior/Key Person Profile (Overall)

    Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

    A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

    Budget (Overall)

    The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.  

    A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

    PHS 398 Research Plan (Overall)

    Specific Aims: Concisely state the aims of the multi-site Consortium project to qualify biomarkers and outcome measures of social impairment in ASD. Outline how the Collaborating Implementation Sites (CIS) and Cores will contribute to attaining the objectives.

    Research Strategy: High-quality and reproducible studies that are reported to the scientific community in a transparent manner are an essential cornerstone of the research enterprise. Attention to principles of study design and transparency are essential to enable reviewers, the scientific community, and NIH to assess the quality of scientific findings. In support of this important goal, investigators are strongly encouraged to implement rigorous study designs and reporting. Examples of the critical elements of a well-designed study are summarized at http://www.nimh.nih.gov/research-priorities/policies/enhancing-the-reliability-of-nimh-supported-research-through-rigorous-study-design-and-reporting.shtml.

    The Research Strategy section should summarize the overall research strategy for the multi-component application. The overall Consortium Project goals and objectives should address the following requirements:

    (1) whether eye-tracking, EEG paradigms, or a combination of the two, have potential utility as stratification biomarkers and/or as sensitive and reliable measures of change in ASD clinical trials;

    (2) the relationship (correlation) of commonly used clinician and caregiver assessments of social impairment to eye tracking or EEG paradigms;

    (3) the feasibility of collecting the same biomarker measures in a younger cohort; and

    (4) as a resource aim, collect blood (DNA) samples from participants with ASD and their parents, for future genomic analyses.   

    The following information should be included in the Research Strategy section of the Overall Research Plan.

    Overview:

    1.  Describe the prior studies supporting proposed research objectives, including preliminary results.

    2. Describe the general objectives and explain the proposed contributions of each of the CIS, and of the Administrative, Data Coordinating, and Data Analysis Cores towards achieving the objectives of the Consortium project.

    3. Describe how each CIS is required for the attainment of the Consortium project's objectives, including available professional and technical personnel to permit efficient and successful conduct of the proposed research, and describe the contribution of each CIS to the fulfillment of group objectives.

    Study design:

    Provide an overview/outline of the proposed design and design considerations for the Consortium project study taking into account the Framework for the study design outlined below. 

    Framework for the Consortium project study design:

    The following assumptions must be incorporated in the proposed study design:

    1. Standardized inclusion/exclusion criteria across sites defined by DSM-5 criteria, and supported with data from ADOS-2 and ADI-R.

    2. Inclusion of a typically developing control group for Aims 1-3.

    3. Uniform collection of verbal and non-verbal IQ, adaptive functioning, medical history, family history

    4. For the extension of the original cohort: data collection for biomarkers and clinical assessments of social impairment at approximately 2 years post-enrollment.

    5. For the replication study: data collection for biomarkers, and clinical assessments of social impairment at baseline, 6 weeks and 24 weeks under the same standardization conditions as the original study. 

    6. Longitudinal, naturalistic study with no controlled intervention(s) but address rationale for inclusion of subjects who are receiving known pharmacologic treatment(s) that have direct effects on EEG-based measures.

    a. Address criteria for the appropriate length of time subjects are receiving stable medication to be included in the study

    b. Describe ways to statistically account for medication effects on EEG biomarker measures

    7. Standardized protocol for collection of blood for future genomic studies (as specified by the NIMH Repository and Genomics Resource), for all newly-enrolled ASD participants and their parents.

    8. Uniform, broad-based consent to allow for data sharing and analyses, including blood (DNA) samples for future genomic analyses

    Biomarker Measures to be included:

    1. Eye tracking - tasks should include replication of the most promising eye tracking results using the paradigms and procedures used in the original study.  Paradigms may be adapted for the feasibility study with younger children.

    2. EEG – tasks should include replication of the paradigm for N170 to upright faces.  Paradigms may be adapted for the feasibility study with younger children. 

    Effect Size and Power Analyses:

    The sample size should be based on a power analysis, taking into account the specific aims, the effect size for the biomarkers, and planned analyses.

    Performance: 

    1. Standardized data acquisition across sites

    2. Standard case report forms (CRFs)

    3. Analytical and clinical validation of biomarker measures in both male and female ASD subjects

    4. Use of compatible standard, non-customized equipment across sites to enable accessibility for use in additional sites in future trials

    5. Examination of sources of technical and biological variability in the biomarker measures, including:

    a. Test-retest reliability (intra-subject, inter-site, between site)

    b. Task-specific brain activation (signal strength)

    c. Measurement stability at time points appropriate for each Aim.

    d. Sensitivity to detect a difference between ASD and typically developing controls over time

    e. Data quality

    f.  Data analyses

    Set up, Implementation and Data Analysis Phases:

    Successful implementation of this Consortium project will depend on standardization of procedures to minimize technical variability. The Consortium project is expected to progress in three phases: Set up, Implementation, and Analysis.

    Milestones and Timeline

    Establish milestones, deliverables, and timelines to assess progress of the Set-up and Implementation phases

    1.  For Set up, include a timeline for: a) obtaining centralized IRB approval for the protocol, b) finalizing the study protocol, c) training participating CIS staff, d) standardization

    of equipment and SOPs across sites.

    2.  For implementation, include a timeline for ensuring completion of the project within the 3-year timeframe of the project.

    3.  Include go/no go decision points for assessing data collection efforts at each of the CIS.

    4.  Include milestones and timeline for data QC, data management, making data available in NDAR, interim analyses, and final analyses. 

    Overall Coordination

    Describe the general plan to assure the maintenance of close collaboration and effective communication among members of the Consortium project.

    1.  Provide an overall organizational chart for the CIU that clearly presents the functions and responsibilities of the Admin Core, Collaborating Implementation Sites (CIS), Data Coordinating Core (DCC) and the Data Acquisition and Analysis Core (DAAC), including the data analysis and data management functions.

    2.  Provide a statement that awardees, and sub-awardees, will agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.

    Operational Plan for Data Collection: Good Clinical Practice (GCP) and Project Management

    1.  Describe the general approach for implementing GCP standards and Project Management to ensure QA/QC of the clinical study at each of the sites.

    2.  Describe the general plans for ensuring that all sites are meeting the performance objectives for the Consortium project (e.g., maintaining recruitment, data quality, making data available in NDAR).

    3.  Describe the plans to remove any CIS that fails to meet the performance objectives as well as plans to select and add a site to enhance the rate of recruitment if needed.

    Letters of Support: A letter from the institution describing the relevant expertise, experience and accomplishments of the applicant organization in planning, coordinating and managing the activities and functions provided for in the FOA, particularly with respect to ASD. Document any institutional commitment to support the Consortium project (e.g., CTSA resources or staff support) and any other resources or sources of funding (and amounts) expected to be available to support the goals and objectives of the Consortium project (e.g., equipment, technical support from vendors, etc.).

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    •   The application, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    •   All data (including raw data) from this Consortium project are expected to be shared broadly and be made available in the National Database for Autism Research (NDAR) as soon as data QA/QC is complete. NDAR staff will be involved to facilitate sharing. Centralized coordination and local data management for data cleaning and entry, as well as bio-statistical consulting will be the responsibility of the awardee Data Coordinating Core (DCC).

    •   Data are expected to be submitted to NDAR every 6 months and made available for access to other researchers within four months or less after submission, allowing the DCC and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures.

    •   For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/

    •   Blood (DNA) samples for future genomic analyses are expected to be deposited in the NIMH Repository and Genomics Resource (https://www.nimhgenetics.org/).

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Overall)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) Application Guide must be followed

    Delayed Onset Study

    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

    PHS Assignment Request Form (Overall)

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Administrative Core

    When preparing your application, use Component Type ‘Administrative Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Administrative Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Administrative Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Administrative Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Administrative Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Administrative Core)
     
    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core Director’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. 
    • The Administrative Core Director must be the PD/PI of the application.
    • Describe expertise in research management across different institutions.
    • Describe the expertise and private sector experience of the Project Manager in managing multi-site projects.  Project Manager should have a PhD and the project management team should include an individual with at least 2 years of private sector experience in facilitating GCP standards at academic sites    
    Budget (Administrative Core)

    Budget forms appropriate for the specific component will be included in the application package.

    The Admin Core should budget for the overall PD/PI, one Director of the CIS, and the Core Directors to participate in an annual face-to face Steering Committee meeting; and for the PD/PI to participate in person at one annual FNIH Biomarkers Consortium meeting in the Bethesda, MD/Washington, DC area.  

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Administrative Core)

    Specific Aims: Provide a concise description of the Administrative Core aims.

    Research Strategy:  Describe how the Administrative Core will contribute to the goals of the Consortium project as well as any novel features of the Administrative Core that enhance the collaborative effort, including optimizing communication, decision-making and sharing between the CIS' and Cores' teams. Describe how the components of the Clinical Investigation Unit (CIU) will interact and ensure efficient cooperation, communication and coordination, and how the proposed organization will create an integrated entity capable of performing the functions specified in the FOA. Describe how each CIS, DCC and DAAC will draw upon the Administrative Core and how it in turn will respond to Site or Core needs.

    Describe the Administrative Core's role in managing all aspects of the Set up, Implementation and Data Analyses phases.  Describe plans for: establishing a single IRB; developing standard operating procedures (SOPs); implementing Good Clinical Practice (GCP) standards across sites; recruiting a Project Manager to oversee operational management of the project; maintaining fidelity to research procedures; monitoring recruitment and study milestones; ensuring quality control (QC) for data and blood (DNA) collection; timely submission of data to NDAR; and overseeing the analyses of all data by the DAAC. Describe the plans for ensuring that all sites are meeting the performance objectives for the Consortium project (e.g., maintaining recruitment, data quality, making data available in NDAR). Describe the plans to remove any Site that fails to meet the performance objectives as well as plans to select and add a site to enhance the rate of recruitment if needed.

    The description of the Administrative Core should clearly indicate the facilities, resources, services and professional skills that the Administrative Core will provide. Moreover, information must be provided about how the collective operations of the Admin Core will be effected in a coherent manner.   

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    • The application, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • All data (including raw data) from this Consortium project are expected to be shared broadly and be made available in the National Database for Autism Research (NDAR) as soon as data QA/QC is complete. NDAR staff will be involved to facilitate sharing. Centralized coordination and local data management for data cleaning and entry, as well as bio-statistical consulting will be the responsibility of the awardee Data Coordinating Core (DCC).
    • Data are expected to be submitted to NDAR every 6 months and made available for access to other researchers within four months or less after submission, allowing the DCC and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures.
    • For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/
    • Blood samples for future genomic analyses are expected to be deposited in the NIMH Repository and Genomics Resource (https://www.nimhgenetics.org/). NIMH staff members who oversee the repository will provide specifications for collection of blood samples.

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Administrative Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    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 a 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

    Delayed Onset Study

    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

    Collaborating Implementation Sites

    When preparing your application, use Component Type ‘Collaborating Implementation Sites.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Collaborating Implementation Sites)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates

    PHS 398 Cover Page Supplement (Collaborating Implementation Sites)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Collaborating Implementation Sites)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Collaborating Implementation Sites)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Collaborating Implementation Sites)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

    Budget (Collaborating Implementation Sites )

    Budget forms appropriate for the specific component will be included in the application package.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Collaborating Implementation Site)

    Specific Aims:  Concisely state the aims described in the Overall Research Strategy. Describe how the CIS will contribute to the aims. The specific aims should be identical for each of the CIS.

    Research Strategy:   Each CIS component must contain a Research Strategy that clearly describes the aspects of the project that are common to all CIS.

    Any variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site." In this subsection, Directors should describe, for example, how the research site has a unique role, strength, or expertise in the collaboration.

    • Describe a feasible mechanism for scientific integration of research procedures, overall managerial and administrative responsibilities, and cross-site comparability of training to assure data reliability and QC. 
    • Any CIS that contracts out some portions of this work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose and oversight of this contractual arrangement.

    This section should also address the following items:

    • Background and Significance
    • Clearly state the objectives of the Clinical Investigative Unit (CIU)
    • Describe the findings from the initial project period that support the selection of the eye tracking and EEG biomarker paradigms, and the clinical/social functioning measures

    Preliminary data

    • Document experience in assembling relevant ASD cohorts (age and IQ), collecting and analyzing EEG and eye-tracking data, and ability to retain subjects for test-retest data collection.  
    • Provide evidence on the extent to which the sites involved with data collection have comparable equipment and instrumentation for data collection and QC.
    • Note: No equipment purchases are allowable costs unless needed for standardization of data collection or scale up. 
    • Provide any evidence that the recruitment/data collection sites have worked together effectively with other sites to meet recruitment goals on previous projects.

    Approach 

    • Describe the approach for the Consortium project taking into account the framework parameters specified in the FOA
    • Specify the proposed design to address the aims and objectives of the project
    • Specify the inclusion/exclusion criteria for the sample and the set of task-based paradigms for eye-tracking and for EEG measures, and clinical/social functioning measures chosen for the Consortium project
    • Specify how the longitudinal collection of biomarker measures and clinician and caregiver assessments will be executed (i.e., what data will be collected at each timepoint, for each of the project’s Aims.)
    • Specify the approach for Setup, Implementation and Data Analysis phases of the project
    • Specify the Set up plan objectives and deliverables
    • Specify the criteria that the site must meet to establish readiness to advance to the Implementation phase
    • Specify the Implementation plan for completing data collection within the specified time period for each of the project’s Aims.
    • Specify how the Site will collect, document, clean, format and QC the different types of data that will be collected and coordinate with the DCC and DAAC for data sharing, management and analysis

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

    • The application, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • All data (including raw data) from this Consortium project are expected to be shared broadly and be made available in the National Database for Autism Research (NDAR) as soon as data QA/QC is complete. NDAR staff will be involved to facilitate sharing. Centralized coordination and local data management for data cleaning and entry, as well as bio-statistical consulting will be the responsibility of the awardee Data Coordinating Core (DCC).
    • Data are expected to be submitted to NDAR every 6 months and made available for access to other researchers within four months or less after submission, allowing the DCC and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures.
    • For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/
    • Blood samples for future genomic analyses are expected to be deposited in the NIMH Repository and Genomics Resource (https://www.nimhgenetics.org/). NIMH staff members who oversee the repository will provide specifications for collection of blood samples.

    Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions  

    PHS Human Subjects and Clinical Trials Information (Collaborating Implementation Site)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    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 a 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

    Delayed Onset Study

    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

    Data Coordinating Core

    When preparing your application, use Component Type ‘Data Coordinating Core'.

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Data Coordinating Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates

    PHS 398 Cover Page Supplement (Data Coordinating Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Data Coordinating Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Data Coordinating Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Data Coordinating Core)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.    

    Budget (Data Coordinating Core)

    Budget forms appropriate for the specific component will be included in the application package.

    There is a cost associated with contributing quality data to NDAR. Costs vary based on the type of data contributed, the number of submissions performed, and the number of subjects enrolled. Based upon these constraints, we have provided a cost model. For NIH applications sharing data with NDAR, the results of this cost model should be included in the budget of your application

    (http://ndar.nih.gov/contribute_cost_estimation.html).

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Data Coordinating Core)

    Specific Aims:  Provide a concise description of the Core aims.   

    Research Strategy: Describe how the DCC will contribute to the goals of the overall Consortium project as well as how each CIS will interact with the DCC.

    Describe the DCC's role in: organization and management of all data collected from the CIS securely, including experience in storing and maintaining eye tracking and EEG data; data documentation; data cleaning and file formatting; central data QC procedures; data backup procedures; development of computerized forms for site data collection; sites visits of the CIS to monitor the quality of record keeping, source documentation and the accuracy of data entry; generating real time reports including subject recruitment reports; and preparation of data submissions to NDAR. Describe the DCC's plan, including staffing, to coordinate timely data submissions to NDAR as specified in the expectations for data sharing (Section I - Funding Opportunity Announcement).

    The description of the DCC should clearly indicate the facilities, resources, services and professional skills that the facility will provide including experience in storing and maintaining eye tracking and EEG data. Moreover, information must be provided about how the collective operation of the Core will be effected in a coherent manner. Describe how the DCC is independent and functionally separate from the CIS. Identify measurable milestones and a timeline of the activities for the DCC over the life of the project.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

    • The application, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • All data (including raw data) from this Consortium project are expected to be shared broadly and be made available in the National Database for Autism Research (NDAR) as soon as data QA/QC is complete. NDAR staff will be involved to facilitate sharing. Centralized coordination and local data management for data cleaning and entry, as well as bio-statistical consulting will be the responsibility of the awardee Data Coordinating Core (DCC).
    • Data are expected to be submitted to NDAR every 6 months and made available for access to other researchers within four months or less after submission, allowing the DCC and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures.
    • For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/
    • Blood samples for future genomic analyses are expected to be deposited in the NIMH Repository and Genomics Resource (https://www.nimhgenetics.org/). NIMH staff members who oversee the repository will provide specifications for collection of blood samples.

    Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions   

    PHS Human Subjects and Clinical Trials Information (Data Coordinating Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    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 a 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.

    Delayed Onset Study

    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

    Data Acquisition and Analysis Core

    When preparing your application, use Component Type ‘Data Acquisition and Analysis Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Data Acquisition and Analysis Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates

    PHS 398 Cover Page Supplement (Data Acquisition and Analysis Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Data Acquisition and Analysis Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Data Acquisition and Analysis Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Data Acquisition and Analysis Core)

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

    Budget (Data Acquisition and Analysis Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Data Acquisition and Analysis Core)

    Specific Aims:  Provide a concise description of the DAAC aims. 

    Research Strategy: Describe how the DAAC will contribute to the goals of the overall Consortium project as well as how each individual CIS will draw upon the DAAC.

    • Describe the statistical and bioinformatics approaches and methodologies for the analyses of eye tracking and EEG data and clinical/social functioning measures to address the aims of the Consortium project.
    • Specify eye tracking and EEG data acquisition formats and preprocessing/clean-up that the CIS will need to perform before uploading data centrally. Describe plans for coordinating with the CIS and DCC for: data cleaning/artifact removal of biomarker datasets; ensuring proper file formatting; and data processing of each Site’s biomarker data files to prepare for data analyses.
    • Describe plans for monitoring the central data repository at the DCC and uploading final processed biomarker and clinical data into the central database.
    • Describe plans and timelines for performing primary, interim, and final analyses of all the data and statistical support to the CIS.
    • The description of the DAAC should clearly indicate the facilities, resources, services and professional skills that the facility will provide. Moreover, information must be provided about how the collective operation of the Cores will be effected in a coherent manner. Identify measurable milestones and a timeline of the research activities for data QC, data management, interim analyses, and final analyses over the life of the project.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

    • The application, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
    • All data (including raw data) from this Consortium project are expected to be shared broadly and be made available in the National Database for Autism Research (NDAR) as soon as data QA/QC is complete. NDAR staff will be involved to facilitate sharing. Centralized coordination and local data management for data cleaning and entry, as well as bio-statistical consulting will be the responsibility of the awardee Data Coordinating Core (DCC).
    • Data are expected to be submitted to NDAR every 6 months and made available for access to other researchers within four months or less after submission, allowing the DCC and their team sufficient time to complete appropriate quality assurance/quality control (QA/QC) procedures.
    • For more information on NDAR, please visit http://ndar.nih.gov/ndarpublicweb/
    • Blood samples for future genomic analyses are expected to be deposited in the NIMH Repository and Genomics Resource (https://www.nimhgenetics.org/). NIMH staff members who oversee the repository will provide specifications for collection of blood samples.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Data Acquisition and Analysis Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    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 a 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.

    Delayed Onset Study

    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.

    3. Unique Entity Identifier and System for Award Management (SAM)

    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.

    4. Submission Dates and Times

    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) using ASSIST or other electronic submission systems. 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.

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. Funding Restrictions

    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.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

    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.

    Important reminders:

    All PD(s)/PI(s) and component Project Leads 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.

    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 (SAM). 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.

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

    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.

    Overall Impact - Overall

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Consortium project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Consortium project proposed).

    Scored Review Criteria - Overall

    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 major scientific impact. For example, a Consortium project that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Consortium project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous?  If the aims of the Consortium 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? Are the aims sufficiently clear, with specified degrees of power, to know the extent to which findings are strong enough to drive decisions about subsequent biomarker studies? For example, will the results rule in or out the performance characteristics as sufficient to apply as stratification and/or outcome measures?     

    Overall Goals

    How well will the proposed research plan determine whether eye-tracking, EEG paradigms, or a    combination of the two, have potential utility as stratification biomarkers and/or as sensitive and reliable measures of change in ASD clinical trials?

    How well will the proposed research plan evaluate the relationship (correlation) of commonly used clinician and caregiver assessments of social impairment to eye tracking or EEG paradigms? How well will the proposed research plan examine the feasibility of collecting the same biomarker measures in a younger cohort? 

    Milestones and Timeline

    Are clear, actionable milestones and timelines proposed for a Set up Phase including: organization and development of SOPs and standardization of measures for subject phenotyping (including biomarker paradigms, and clinical measures)?

    Are specific milestones and go/no-go criteria described to assess readiness to initiate the full Consortium project protocol?

    Are clear, actionable milestones and timelines proposed to assess performance and progress in the Implementation Phase? Are the milestones for go/no go decisions quantitative when appropriate? Are the plans for continuous QC and analysis of data appropriate and feasible for the data collection period of the Consortium project and the subsequent data analysis period? 

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Consortium project? If Early Stage Investigators or those 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? Is there evidence of proven expertise in recruiting the ASD cohort (age and IQ) and retaining subjects in studies to enable for test-retest data collection?  Does the investigative team, Collaborating Implementation Sites (CIS) and Data Acquisition and Analysis Core (DAAC), have sufficient technical (e.g. collecting and analyzing EEG and eye-tracking data), methodological, and statistical expertise (e.g., handling repeated measures designs, missing data, effect size) in the study to perform the biomarker measures and clinical/social functioning measures performed at the same site and across sites? What is the evidence that the investigators at the proposed CIS have collaborated among themselves and/or with other researchers in ASD studies before?

    Is there documentation relating the proposed level of effort, as appropriate to specific recruitment and biomarker study Consortium project timelines?

    Are the governance and organizational structure appropriate for conducting the Consortium project study as proposed? Evaluate the knowledge and expertise provided by any potential consultants.    

    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? Are there aspects of data analysis and design that break new ground in terms of measures that can be applied to potentially detecting effects of interventions in ASD?  Are there unique aspects of the way in which the multi-site Consortium project collaboration is organized that may address any cross-site variance in subject selection, application of biomarkers, rating of severity, etc.?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Consortium project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?  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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

    If the Consortium 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?

    Is there a compelling scientific rationale for the biomarkers proposed as likely to play a role in some specified aspect(s) of social impairment? Is there a strong justification for the approach for standardizing biomarker and clinical/social functioning measures across CIS, setting up the sites, and implementing the project? Is the approach feasible within the desired time frame? Is the number of Sites proposed for timely subject recruitment appropriate, and yet taking into account the need to minimize variability of data collection across CIS?

    Is there a clear description of the measures, the subject eligibility criteria, and the recruitment and retention strategies with special emphasis on subject burden and ability to participate in all aspects of the study? Does the application address whether expectation or other sources of bias are likely to influence any of the measures should they be utilized as potential outcomes in future studies?  Are the clinical measures appropriate in terms of generating data that allows comparison to subject trajectories from prior studies as well as testing the relationship of the biomarker measures with clinical measures and/or change in level of social impairment within the Consortia project?

    Are proposed statistical methods appropriate for the study design? Is there a clear rationale for sample size based on power calculations that specify confidence limits for ruling in or out the ability of the measures to detect specified degrees of change over time? Are plans for analyses, data management, and quality control adequate? Is the approach feasible in terms of realistically having in place everything necessary to carry out data acquisition in a timely manner and within the project timeline of five years?

    Are subject inclusion criteria well justified? Are the recruitment strategy and plan well justified and feasible? Are the subject accrual goals feasible? Are likely problems anticipated? Did the applicant provide strategies, pitfalls and alternative approaches to expedite IRB review and approval and to ensure timely recruitment and data acquisition? Is a centralized IRB 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? What is the extent to which the proposed CIS have facilities and resources to carry out eye-tracking and EEG measures with subjects within the specified age and IQ ranges? Does the Data Coordinating Core have experience in storing and maintaining eye tracking and EEG data? Are there dedicated full-time professional (PhD level) operational staff members at the institution who have carried out the relevant coordinating activities for biomarker studies?     

    Additional Review Criteria - Overall

    As applicable for the Consortium 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.

    Overall Goals

    How well will the proposed research plan determine whether eye-tracking, EEG paradigms, or a    combination of the two, have potential utility as stratification biomarkers and/or as sensitive and reliable measures of change in ASD clinical trials?

    How well will the proposed research plan evaluate the relationship (correlation) of commonly used clinician and caregiver assessments of social impairment to eye tracking or EEG paradigms?

    How well will the proposed research plan examine the feasibility of collecting the same biomarker measures in a younger cohort? 

    Milestones and Timeline

    Are clear, actionable milestones and timelines proposed for a Set up Phase including: organization and development of SOPs and standardization of measures for subject phenotyping (including biomarker paradigms, and clinical measures)?

    Are specific milestones and go/no-go criteria described to assess readiness to initiate the full Consortium project protocol?

    Are clear, actionable milestones and timelines proposed to assess performance and progress in the Implementation Phase? Are the milestones for go/no go decisions quantitative when appropriate? Are the plans for continuous QC and analysis of data appropriate and feasible for the data collection period of the Consortium project and the subsequent data analysis period? 

    Overall Coordination

    Does the overall organizational chart clearly present an overview of the performance sites, data analysis and data management functions and responsibilities of the Admin Core, CIS, DCC, and the DAAC?  Are the roles clearly defined and divided among the different entities? Is there a clear and sound plan for communication and coordination across entities demonstrating an integrated CIU capable of performing the functions specified in the FOA? Is there a history of a successful analogous organizational structure at the overall PD/PI institution?

    Is clear evidence presented that the PD(s)/PI(s) has performed effective research management across different institutions and has requisite expertise in statistics and analytical measurements of the data being collected?  

    Operational Plan for Data Collection: Good Clinical Practice (GCP) and Project Management

    Does the Admin Site Project Manager have at least two years' experience coordinating across-site biomarker studies, as well as a PhD (or equivalent research training background) in a discipline related to brain-based physiological and clinical biomarkers?  Does the proposed individual have prior experience of managing studies that aim to “qualify” biomarkers as potential surrogate measures of clinical outcome or subject stratification?

    Is there an adequate plan for implementation of Good Clinical Practice (GCP) standards and Project Management to ensure QA/QC of the study at each of the CIS, including training, site visits, and close management of data collection? Are the roles of the Admin Site, the DCC, and the DAAC with regard to data management and quality control clearly delineated?

    Is there an adequate plan for collecting an integrated data set of longitudinal EEG, eye tracking, and clinical measures from ASD and TD subjects, as well as blood (DNA) samples from ASD subjects and their parents?

    Is the Admin Site’s plan for removing any CIS that fails to meet the performance objectives appropriate? Is there an adequate plan for selecting and adding a new CIS and swiftly ramping up if needed? 

    Protections for Human Subjects

    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.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan  

    When the proposed Consortium 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.

    Vertebrate Animals

    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.

    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

    Not Applicable

    Renewals

    For Renewals, the committee will consider the progress made in the last funding period.

    Revisions

    Not Applicable

    Additional Review Considerations - Overall

    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) Genomic Data Sharing Plan.

    Is an adequate plan in place for the data to be made available for analyses by investigators through NDAR and the NIMH Repository and Genomic Resource?


    Authentication of Key Biological and/or Chemical Resources

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    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 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.

    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 be assigned on the basis of established PHS referral guidelines 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 appropriate National Advisory Council or Board. 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 program priorities.
    • Compliance with data and resource sharing policies.
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

    Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

    Section VI. Award Administration Information
    1. Award Notices

    If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described 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.

    Prior Approval of Pilot Projects

    Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.  

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    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.

    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.html; and https://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.

    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.

    Cooperative Agreement Terms and Conditions of Award

    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 Part 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 responsibility for:

    The PDs/PIs will have the primary responsibility for the scientific and administrative leadership and coordination of the project at the awardee and sub-awardee institutions, as noted below.  

    • Managing and executing all aspects of the Consortium project, including Set up, Implementation and Data Analyses phases.
    • Timely acquisition of all approvals and materials needed for the awardee to perform the project.
    • Establishing a Single IRB, developing standard operating procedures (SOPs), and implementing Good Clinical Practice (GCP) standards across sites.
    • Complying with all federal regulations and NIH policies related to clinical research involving human subjects.
    • Serving as a voting member of the Consortium Project Steering Committee (SC), and participating, along with critical staff, in SC meetings including one annual face-to face meeting in the Bethesda, MD/Washington, DC area.
    • Inviting external scientist(s) to serve as advisors on the SC as needed, in consultation with the NIH Program Official and NIH Project Scientist(s).
    • Chairing the SC, organizing and circulating a written agenda in advance of conference calls and meetings, and preparing and circulating minutes that delineate decisions and action items resulting from the calls or meetings.
    • Providing periodic reports to the SC summarizing: the progress of the project in the Set up, Implementation and Data Analysis phases; obstacles encountered and solutions; monthly recruitment updates; and quarterly progress on milestones or milestone updates. The reports should be provided in a format decided upon by the SC.
    • Adhering to the Consortium guidelines and other policies that might be established, as agreed upon by the SC and the NIH Program Official.
    • Apprising the NIH Program Official of any potential impediments to execution of the goals of the Consortium project.
    • Ensuring that primary and secondary data, protocols, and procedures are made available to all participants in the project to meet the goals of the Consortium.
    • Participate in administrative site visits by NIH staff.
    • Be required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sec. 200-212 (Bayh-Dole Act).

    The awardee institution, and sub-awardee institutions, will agree to accept the close coordination, cooperation, and participation of the NIH Project Scientist(s) and the NIH Program Official in the aspects of scientific and technical management of the project 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:

    • Assist in the design, development, and coordination of the different stages of the study within their role as a participant on the SC.
    • Retain the option to update the timeline and milestones of the project as necessary within the constraints of the approved research and negotiated budget. To help carry out these duties, the Project Scientist may consult with non-NIH experts in the field.
    • Coordinate and review with the assistance of the PD(s)/PI(s) the timeline for processing procedures, data submission and integration, and distribution to approved investigators.
    • Coordinate with the awardees in monitoring issues relating to: design of the recruitment, adherence to the protocols, adjustment of study protocols, and management and technical performance.
    • Participate in SC activities, including conference calls, subcommittees and special committees as a voting member; however, NIH voting membership will not exceed one-third of the total committee membership. 
    • Participate in the project update meetings and conference calls with the PD/PI on a weekly or monthly basis, as dictated by the needs of the Consortium Project. 

    The NIH Program Officer will:

    • Be responsible for the normal scientific and programmatic stewardship of the award.
    • Participate in SC meetings and conference calls as a non-voting participant.
    • Approve modifications to the research plan and/or study protocol(s), in consultation with the SC, based on emerging data and/or other issues that impact progress of the project.
    • Determine if the awardee has met/achieved requirements for transition of the project from Set up to Implementation stages.
    • Reserve the right to obtain periodic external peer review and recommend reviewers for an assessment of progress and achievement of milestones and deliverables. 
    • Monitor recruitment, performance, and compliance with NIH procedures.
    • Reserve the right to remove a non-performing CIS for any of the following reasons: (1) inadequate progress in meeting the pre-negotiated milestones and timelines; (2) failure to meet the go/no go milestone(s) for transition from Set up to Implementation; (3) slow accrual; or (4) failure to comply with the Terms and Conditions of Award.

    Areas of Joint Responsibility Include:

    The Consortium Project Steering Committee.  The Consortium Project Steering Committee (SC) will serve as the operational governing board for the Consortium project. The SC will include: the PD/PI, one Director of the CIS, Core Directors, the NIH Project Scientist(s) (voting), the NIH Program Officer (non-voting member), and external scientists (non-voting, identified by the PD/PI in conjunction with the NIH Program Official).

    The Consortium Project Steering Committee (SC) will:

    • Participate in reviewing scientific progress of the Consortium project, assessing recruitment, and progress of the go/no go milestones.
    • Applicants should hold at least one in person Investigators’ meeting annually that includes NIH staff.  
    • Hold teleconferences to address operational issues on a weekly or monthly basis, or as dictated by the needs of the study.
    • Establish workgroups for specific tasks as the SC deems appropriate. The workgroups will make recommendations to the SC.
    • Ensure timely sharing of data among the Consortium project participants and reporting of results and with the broader scientific community in a timely manner at scientific meetings and other venues as per the data sharing plan and the SC recommendations.

    The FNIH Biomarkers Consortium Functions. Continued collaboration with the FNIH Biomarkers Consortium (BC) will be pursued.  If the awarded project is accepted as a FNIH Biomarkers Consortium project, the FNIH Biomarkers Consortium will provide a collaborative environment to coordinate any project(s) awarded under this FOA. An FNIH Biomarkers Consortium Project Team will be established. The FNIH Biomarkers Consortium Project Team (BC PT) will include: the PDs/PIs, NIH Project Scientist(s) and Program Official, an FDA scientist(s), the BC funding partners, and the BC Project Manager.

    The FNIH Biomarkers Consortium Project Team (BC PT) will:

    • Convene conference calls and meetings to establish a safe harbor for communication and interactions between the PDs/PIs with the NIH, FDA, and BC funding partners.
    • Provide feedback to finalize the design of the Consortium project protocol and data analysis plan.
    • Review progress of the project and timely sharing of data.
    • Promote coordination of the Consortium project with efforts of international groups, non-profit foundations, industry, and regulatory agencies to qualify biomarkers and outcome measures for use in clinical trials.
    • Applicants must agree to incorporate feedback from the BC PT, in consultation with the NIH Program Official, to finalize the protocol and data analysis plan for the Consortium project.

    Dispute Resolution:

    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 Autism Biomarkers Consortium for Clinical Trials 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.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

    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.

    Section VII. Agency Contacts

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

    Application Submission Contacts

    eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

    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)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Lisa Gilotty, Ph.D.
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-3825
    Email: gilottyl@mail.nih.gov

    Peer Review Contact(s)

    Nicholas Gaiano, Ph.D
    National Institute of Mental Health
    Telephone: (301) 827-3420
    Email: nick.gaiano@nih.gov

    Financial/Grants Management Contact(s)

    Terri Jarosik
    National Institute of Mental Health (NIMH)
    Telephone: 301-443-3858
    Email: tjarosik@mail.nih.gov

    Section VIII. Other Information

    Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

    Authority and Regulations

    Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.    

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