NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

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

The purpose of this Funding Opportunity Announcement (FOA) is to invite applications for the Consortium on Biomarkers and Outcome Measures in Autism Spectrum Disorder (ASD) that will implement the Consortium project. The Consortium project will generate objective tools for use in clinical trials of behavioral or pharmacologic interventions to address social impairments in ASD.

The FOA will establish a team of clinical investigators (the Clinical Investigation Unit, CIU) to conduct a multi-site study to begin to qualify biomarkers and outcome measures to assess social impairment in ASD. The CIU will assess the following:

• whether lab-based measures of specific domains of social impairment in ASD are more sensitive indicators of clinical status compared to commonly used clinician and caregiver assessments of social impairment for their potential use as outcome measures in clinical trials;

• whether eye-tracking, electrophysiological (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;

• the relationship (correlation) of lab-based measures of domains of social impairment to eye tracking or EEG (resting state and task-based) paradigms;

• the relationship (correlation) of lab-based measures of domains of social impairment to commonly used clinician and caregiver assessments of social impairment; and

• as a resource aim, collect blood (DNA) samples from all subjects, including the parents of ASD subjects, including the parents of ASD subjects, for future genomic analyses.

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.

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. A significant need exists for validated outcome measures to assess treatment-mediated changes in core and associated symptoms. Progress in the field is also 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.

Biomarker research in ASD has yielded a number of exploratory findings utilizing a variety of technology platforms, task-based paradigms, and biosensors. Recent results from several labs have demonstrated preliminary success in developing biomarkers for use as risk markers of ASD. However, these initial biomarker findings have not been replicated across different labs using identical (standardized) protocols and their potential utility as stratification or outcome measures in intervention studies or clinical trials has not been assessed.

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. 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.

This FOA will support a multi-site Consortium project to assess a well-justified set of standardized lab-based measures of domains of social impairment and biological measures (resting state and task-based EEG and eye tracking measures) that show promise in school age individuals with ASD (ages 6-11, with the possibility of adding adolescent or toddler groups) at baseline, 6 and 24 week time points. The intent of the FOA is to qualify a set of measures that can potentially be used as stratification biomarkers and/or as sensitive and reliable objective measures for application in ASD clinical trials focused on social impairment. The FOA also aims to determine the relationship (correlation) of the lab-based measures to: 1) the biological measures (EEG and eye tracking measures); and 2) the commonly used clinician and caregiver assessments of social impairment.

In addition, one task-based EEG and eye tracking measure from the European Autism Interventions A Multicenter Study for Developing New Medications (EU-AIMS) will be included in the Consortium project to foster harmonization and independent replication of a common subset of biomarker measures in the U.S. Consortium and EU-AIMS projects.

Expected outcomes include:

• Identification of eye tracking and EEG biomarkers that can be used for stratification of school age ASD subjects in future ASD intervention trials.

• Ruling in or out the potential of the selected eye tracking and EEG biomarkers as early and/or more sensitive and reliable indicators (potential surrogates) of clinical outcomes for use in future ASD intervention trials.

• Utility of lab-based measures of domains of social impairment as objective predictors of clinical outcomes in future ASD intervention trials.

• An integrated data set of EEG, eye tracking, and clinical measures from ASD 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.

• A research model that establishes procedures for qualifying ASD biomarkers and measures that may be extended to other ASD cohorts and, potentially to other pediatric CNS disorders.

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 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.

The Director of the Administrative Core will participate as a member of the FNIH Biomarkers Consortium ASD Project Team and be responsible for maintaining appropriate communication with the Collaborating Implementation Sites, the DCC, the DAAC, and the FNIH Biomarkers Consortium.

Collaborating Implementation Sites The Collaborating Sites will work together as a team with overall coordination and management by the U19 PD/PI. The Collaborating Sites 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 Collaborating Site 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 Collaborating Site must agree to: execute the finalized protocol; utilize a central IRB; and work collaboratively with the PD/PI of the U19, the Sites 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 Collaborating Sites; securely storing and maintaining video, 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 Collaborating Sites 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 Collaborating Sites. The DCC is strongly encouraged to have an individual dedicated to coordinate data submissions to NDAR.

Eye Tracking and EEG 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 Sites will need to perform before uploading data centrally; data cleaning/artifact removal of biomarker datasets; ensuring proper file formatting; data processing of each Site’s biomarker data files to prepare for primary analyses; perform primary, interim, and final analyses of all the data; and provide statistical support.

In addition, the DAAC will monitor the central data repository at the DCC, and be responsible for uploading final processed biomarker, lab-based data, and clinical data into the central database. Note: All data analyses will be performed solely at the DAAC and not at any of the data collection sites to ensure standardization of statistical analysis procedures.

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 on a quarterly basis, every 3 months (on or before January 15, on or before April 15, on or before July 15, and on or before October 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 for access 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.

A key aspect of this FOA is the formation of a collaborative partnership with the FNIH Biomarkers Consortium. Successful applicants 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 (Simons Foundation Autism Research Initiative, Autism Speaks and other potential private sector partners) in order to finalize the protocols for the biomarker measures, time points for data collection, age ranges to be studied, sample sizes, data analysis plan, and timeline for sharing data.

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 (e.g., the EU-AIMS), 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.

Technical Assistance teleconferences will be held for potential applicants on Friday October 3, 2014, from 12:00pm 1:00 pm EST and Tuesday November 4, 2014, from 3:00 pm -4:00 pm. The dial in number is 866-692-3582 and participant code is 1550980. NIH staff will be available to answer questions related to this FOA. To obtain call-in information, please contact the [email protected] 24 hours in advance of the call. Questions gathered via email and on these technical assistance calls as well as their responses can be found at: http://www.nimh.nih.gov/funding/grant-writing-and-application-process/faqs-for-rfa-mh-15-800.shtml Applicants are strongly encouraged to refer to the FAQs available at the ASD Biomarkers and Outcomes website.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education

• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions

• Historically Black Colleges and Universities (HBCUs)

• Tribally Controlled Colleges and Universities (TCCUs)

• Alaska Native and Native Hawaiian Serving Institutions

• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)

• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses

• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments

• County Governments

• City or Township Governments

• Special District Governments

• Indian/Native American Tribal Governments (Federally Recognized)

• Indian/Native American Tribal Governments (Other than Federally Recognized)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

Other

• Independent School Districts

• Public Housing Authorities/Indian Housing Authorities

• Native American Tribal Organizations (other than Federally recognized tribal governments)

• Faith-based or Community-based Organizations

• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

All PD(s)/PI(s) must have an eRA Commons account. 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.

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.

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

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

• Of an application with a changed grant activity code.

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

[email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for Administrative Core)	6
Collaborating Sites (use for Collaborating Implementation Sites)	6 per Site
Data Coord Core (use for Data Coordinating Core)	6
Data Acq Anal Core (use for Data Acquisition and Analysis Core)	6

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

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

Administrative Core: 1 required

• Collaborating Implementation Site(s): minimum of 2, maximum of 6

Data Coordinating Core: 1 required

Data Acquisition and Analysis Core: 1 required

When preparing your application in ASSIST, 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 Sites 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:

• whether lab-based measures of specific domains of social impairment in ASD are more sensitive indicators of clinical status compared to commonly used clinician and caregiver assessments of social impairment for their potential use as outcome measures in clinical trials;

• whether eye-tracking, electrophysiological (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;

• the relationship (correlation) of lab-based measures of domains of social impairment to eye tracking or EEG (resting state and task-based) paradigms;

• the relationship (correlation) of lab-based measures of domains of social impairment to commonly used clinician and caregiver assessments of social impairment; and

• as a resource aim, collect blood (DNA) samples from all subjects, including the parents of ASD subjects, including the parents of ASD subjects, for future genomic analyses.

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

Overview:

1. The overview should describe the general objectives, and explain the proposed contributions of each of the Collaborating Sites, and of the Administrative, Data Coordinating, and Data Analysis Cores towards achieving the objectives of the Consortium project.

2. A clear description of how each Collaborating Site 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 description of the contribution of each to fulfillment of group objectives.

Study design:

1. 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. The proposed design should be based on the state-of-the science and include a well-justified rationale for selection of the biomarkers, lab-based measures, task-based paradigms, and clinical assessments.

2. Include a statement that the awardee and sub-awardees agree to develop the final protocol, in consultation with NIMH staff, based on feedback from the NIH, FDA, and the FNIH Biomarkers Consortium ASD Project Team after the award is made.

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 (consider the possibility of enriching enrollment for individuals with a pre-specified range of social impairment)

2. Inclusion of a typically developing control group

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

4. Data collection for biomarkers, lab-based, and clinical assessments of social impairment at baseline, 6 weeks and 24 weeks to assess stability of the measures at time points in which clinical benefit would be expected to be observed in pharmacologic intervention studies

5. 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

6. Standardized protocol for collection of blood for future genomic studies (as specified by the NIMH Repository and Genomics Resource)

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

Biomarker and lab-based measures to be included:

1. Eye tracking - tasks should include a dynamic video tracking task

2. EEG - resting state EEG and visual and auditory task-based EEG measures

3. Lab-based measures of specific domains of social impairment (e.g., videotaped measures of social communication) to demonstrate the hypothesized relationship between biomarkers and specific domains of social impairment.

4. One task-based EEG and one eye tracking measure from the European Autism Interventions A Multicenter Study for Developing New Medications (EU-AIMS) study must be included among the set of proposed biomarker paradigms (i.e., the upright and inverted faces task for EEG and the emotion-matching task for eye tracking).

Effect size and power analyses:

The sample size should be based on a power analysis taking into account the effect size for the biomarkers and lab-based measures and planned analyses. The following sample sizes are estimates based on publications that have examined the effect size for eye-tracking biomarkers in adolescents with ASD.

Sample size:

1. 150-200 ASD subjects, ages 6-11 with IQ in the range of 50-115 (with the possibility of adding adolescent or toddler groups which would require a larger sample size)

2. 50 typically developing control subjects

3. Subgroups of ASD based on IQ or other clinical measures should include a minimum of 50 subjects

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 6 week and 6 month time points

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.

1. The Set up phase should describe the timeline and procedures needed for the Consortium to initiate execution of the full protocol.

2. Applicants should propose a Technical Feasibility Study to be carried out by each Collaborating Site prior to initiating the Implementation phase of the project.

a. The Technical Feasibility Study should demonstrate each Collaborating Site's ability to carry out standardized collection and QC of biomarker data from an initial sample, to include subjects with ASD, across each of the sites within a timeframe of 3 months.

3. Advancement of each Collaborating Site into the Implementation phase will be contingent upon NIH approval, and will be based on timely recruitment and data collection and QC analysis of the data by the DCC.

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 Collaborating Site staff, d) standardization of equipment and SOPs across sites.

2. For implementation, include a timeline for enrolling 25%, 50%, 75% and 100% of the sample size within the 3-year timeframe of the project.

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

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 (Collaborating Sites), 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.

3. 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).

4. 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.

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 (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:

• All applications, 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 3 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Admin 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)

• The Administrative Core Director must be the PD/PI of the application.

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.

• Describe expertise in research management across different institutions.

• Describe the expertise and private sector experience of the Project Manager in managing multi-site projects should have a PhD and at least 2 years of private sector experience in implementing 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 Collaborating Sites, and the Core Directors to participate in an annual face-to face Steering Committee 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 Collaborating Sites' and Cores' teams. Describe how the components of the 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 Collaborating Site, 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 (including the Technical Feasibility Study), Implementation and Data Analyses phases. Describe plans for: establishing a central 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 (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:

• All applications, 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 3 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Collaborating Site

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 Site)

Complete only the following fields:

• Applicant Information

• Type of Applicant (optional)

• Descriptive Title of Applicant’s Project: The titles for each Collaborating Site in the set must have the following format: a 1/N indicator + identical title (e.g., 1/6-Collaborating Site for ASD Biomarkers and Outcome Measures , where the 1/6 means this is site 1 of 6 sites in the set. The other sites will be labeled 2/6, 3/6, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/6, at the beginning of the title.

• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Collaborating Implementation Site)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Collaborating Implementation Site)

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.

Facilities and Other Resources: Applicants are advised that the Facilities and Other Resources section, which should address not only physical resources, but also the intellectual and collaborative resources for executing the project, can be utilized to address relevant resource-related collaborative issues. Instructions for this section include the following:

• Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport). In describing the scientific environment in which the work will be done, discuss ways in which the proposed studies will benefit from unique features of the scientific environment or the subject populations, or will employ useful collaborative arrangements.

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

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 Site)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Collaborating Site 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.

Budget (Collaborating Implementation Site)

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 decribed in the Overall Research Strategy. Describe how the Collaborating Site will contribute to the aims. The specific aims should be identical for each of the Collaborating Sites. .

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

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 Collaborating Site 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 CIU

• Describe the rationale for the selection of the eye tracking and EEG biomarker paradigms, lab-based measures of social impairment, and the clinical and caregiver assessments of social impairment

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, lab-based measures, task-based paradigms, and clinical assessments chosen for the Consortium project

• Specify the sample size and recruitment plan, including timelines for recruitment

• Specify how the longitudinal collection of biomarker measures, lab-based measures and clinician and caregiver assessments will be executed (i.e., what data will be collected at baseline, 6 week, and 24 week time points)

• Specify the approach for Setup, Implementation and Data Analysis phases of the project

• Specify the Set up plan objectives and deliverables

• Specify the parameters of the Technical Feasibility Study and 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 3-year time period

• 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:

• All applications, 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 3 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Collaborating Implementation Site)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Collaborating Implementation Site)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Data Coord 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 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.

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 Collaborating Site will interact with the DCC.

Describe the DCC's role in: organization and management of all data collected from the Collaborating Sites securely, including experience in storing and maintaining video, 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 Collaborating Sites 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 video, 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 Collaborating Sites. 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:

• All applications, 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 3 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Data Coordinating Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Data Coordinating Core)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Data Acq Anal 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 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.

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 Collaborating Site will draw upon the DAAC.

Describe the statistical and bioinformatics approaches and methodologies for the analyses of eye tracking and EEG data, lab-based measures of social impairment, and clinical measures of social impairment to address the aims of the Consortium project.

Specify eye tracking and EEG data acquisition formats and preprocessing/clean-up that the Collaborating Sites will need to perform before uploading data centrally. Describe plans for coordinating with the Collaborating Sites 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, lab-based data, 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 Collaborating Sites.

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:

• All applications, 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 3 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: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report (Data Acquisition and Analysis Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report (Data Acquisition and Analysis Core)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

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

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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).

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? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 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?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Consortium project t? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? 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 Sites and Data Acquisition and Analysis Core) 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 measures of social function performed at the same site and across sites? What is the evidence that the investigators at the proposed Sites have collaborated among themselves and/or with other researchers in ASD studies before? Have any such collaborations involved any of the proposed biomarker or lab-based clinical measures of social impairment?

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? Is there a description of the expertise needed 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? 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?

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 children, 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 measures across sites, 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 sites?

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 proposed lab-based measure(s) 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 three 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 Sites have facilities and resources to carry out eye-tracking, EEG and video-taped evaluations of subjects with some interactive tasks (as an analogue of any proposed lab-based evaluation of social impairment) within the specified age and IQ ranges? Do the proposed Administrative Core, Data Coordinating Core and/or Data Acquisition and Analysis Core reside within an institution(s) that has documented success in other collaborative multi-site biomarker studies of clinical state or change? Does the Data Coordinating Core have experience in storing and maintaining video, 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?

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, lab-based and clinical measures)?

Are specific milestones and go/no-go criteria described for the Technical Feasibility Study 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 three year data collection period of the Consortium project and the subsequent data analysis period (one year or less)?

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, Collaborating Sites, Data Coordinating Core and the Data Acquisition and Analysis Core? 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?

Did the applicant 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

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 Collaborating Sites, including training, site visits, and close management of data collection? Are the roles of the Admin Site, the Data Coordinating Core (DCC), and the Data Acquisition and Analysis Core (DAAC) with regard to data management and quality control clearly delineated?

Is there an adequate plan to ensure that all Collaborating Sites are meeting the performance objectives for the Consortium project (e.g., maintaining recruitment, data quality, making data available in NDAR)?

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

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

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 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

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.

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

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.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 central 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 technical feasibility 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 Collaborating Site(s) 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 Collaborating Sites, 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.

• Convene quarterly meetings (in person or by video or audio teleconference) to monitor progress on the project and to address issues or activities that impact the project. Applicants should hold at least one in person meeting annually in the Washington, D.C. area to allow attendance of 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. The FNIH Biomarkers Consortium (BC) is a participating component in this FOA and will provide a collaborative environment to coordinate any project(s) awarded under this FOA. An FNIH Biomarkers Consortium Project Team will be established at the time of the NIH award. 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 (Simons Foundation Autism Research Initiative, Autism Speaks and other potential private sector 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 (e.g., the EU-AIMS), 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 BSM Network 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.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: [email protected]

[email protected]

Linda Brady, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3563
Email: [email protected]

Lisa Gilotty, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3825
Email: [email protected]

Margaret Grabb, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3563
Email: [email protected]

Ann Wagner, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3633
Email: [email protected]

Alice Kau, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-496-1385
Email: [email protected]

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3534
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

Bryan Clark
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: [email protected]

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.

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 Parts 74 and 92.