Background

Intervention studies for autism spectrum disorder (ASD) are hampered by a lack of reliable and sensitive measures to assess treatment response, whether the interventions are behavioral or pharmacological in approach. Instead, treatment research commonly relies on subjective parent- and clinician-reported assessments that show inadequate psychometric properties, are highly susceptible to placebo effects, and may not be specific to ASD-related impairments. Some semi-objective clinician-administered measures are available, but these remain early in development or are not specific to ASD. A few objective measures, such as eye-tracking, have been used as treatment outcomes, but the psychometric properties and clinical meaningfulness of these measures have not been demonstrated adequately.

Objective outcome measures that are both reliable and sensitive to change would permit smaller and shorter studies and would help to minimize false-negative results. The greater statistical power afforded by such measures would also facilitate studies in subpopulations that might be more likely to benefit from a specific treatment approach.

A previous request for applications (RFA) for novel outcome measures research was issued by the Simons Foundation Autism Research Initiative (SFARI) in 2015. The grants awarded under that RFA, described here, enabled progress on several assessment approaches, but none are fully validated or ready for broad deployment at this time.

Objective of This RFA

Grants awarded through this RFA will support the development and validation of clinically relevant outcome measures that will sensitively and reliably distinguish treatment effects from placebo response on the core symptoms of ASD (i.e., impairment in social communication and social interaction; restricted/repetitive behaviors, interests and activities; and sensory symptoms).

The proposed research should determine whether an outcome measure meets the following criteria:

1. Reflects clinically meaningful differences in the core symptoms of ASD.
2. Has strong test-retest and inter-rater (inter-operator) reliability.
3. Demonstrates sensitivity to change.
4. Presents an acceptable burden for subjects and families.
5. Is scalable for multisite trials with up to 1000 subjects.

We especially encourage applications for outcome measures that:

1. Are applicable across a wide age range.
2. Are applicable across a wide range of functioning levels.
3. When possible, capture data in naturalistic environments.
4. Will be validated and ready for trial deployment within three to four years.

Examples of possible approaches to assessing communicative and social behavior in naturalistic settings include, but are not limited to, methods that employ wearable devices, centralized expert scoring, or automated assessment of language and other social behaviors. Examples of laboratory-based methods include, but are not limited to, standardized language sampling, elicitation and analysis of “social-motor” behaviors, eye-tracking, sensory challenges, psychophysics, or electroencephalography.

The application should include a justification for the age range and functional range of the subjects for whom the proposed outcome measures are intended. The rationale for subject inclusion and exclusion criteria should be provided. Sensitivity to change should be examined and may be demonstrable in the context of treatment or natural history. The relationship between change on the outcome measure and clinically meaningful change should also be examined. The sample size for the proposed research should be justified by power calculations that are based on appropriate assumptions. Robust data analysis plans are expected and may require collaboration with data scientists to explore novel methods for analysis of complex and/or naturalistic data.

Eligibility and Collaboration

All applicants and key collaborators must hold a Ph.D., M.D. or equivalent degree and have a faculty position or the equivalent at a college, university, medical school or other research facility. Applications may be submitted by domestic and foreign nonprofit organizations; public and private institutions, such as colleges, universities, hospitals, laboratories, or units of state and local government; and eligible agencies of the federal government. There are no citizenship or national residence requirements.

If the proposal includes investigators at more than one site, all investigators should have demonstrated prior success in similar collaborations.

Investigators who received grants in response to the 2015 RFA on Novel Outcome Measures may apply through this RFA as well.

Funding Period and Budget

The grant period is two or three years. The maximum budget is $300,000 per year, including indirect costs, for two or three years. Exceptions with strong justification will be considered but are not encouraged.

Webex Informational Sessions

Two Webex informational sessions to answer questions about this RFA were held at the following times:

• January 25, 2019, Noon–1 pm EST
• January 29, 2019, 3–4 pm EST

Video recordings of these sessions are available below.

January 25 session:

January 29 session:

Application Requirements

1. Proposal narrative, not exceeding four pages (excluding references, figures and figure legends). Proposals should include specific aims, background relevant to the application, significance of the proposed studies, preliminary results, experimental design, pitfalls and alternative strategies, and a timeline with milestones.
2. Biosketches for principal investigator(s) and key collaborators.
3. Current and pending support for principal investigator(s) and key collaborators.
4. Budget. While a budget cap is not required, budgets will strongly factor into the competitiveness of an application. Budgets of more than $300,000 annually, including indirect costs, will need convincing justification. It is unlikely that we will make an award larger than this amount. Proposals should include a realistic budget sufficiently detailed for evaluation of needed resources. We will work closely with investigative teams with competitive applications to arrive at a suitable budget. Indirect costs are limited to 20 percent of the modified total direct costs (see Simons Foundation policies).Applications with multiple principal investigators from different institutions who would like to be paid separately must include a signed signature page, budget template and budget justification for each principal investigator. Applications with subcontracts must include a budget and budget justification for the subcontracts. The budget template and budget justification are available for download in the Proposal Attachments section of proposalCENTRAL’s full application.
5. Research environment and resources. Investigators should demonstrate access to appropriate resources for high-capacity data collection and analysis, although we will work with awarded investigators to provide additional informatics support as needed.
6. Data-sharing plan. The plan should include sharing of raw and analyzed data and consent for storage of raw data at the Simons Foundation with distribution of raw data to the research community. We will work closely with awarded investigative teams to ensure that the plan includes timely dissemination of data with reasonable embargo provisions.

Application Deadline and Instructions for Submission

We request that investigators who intend to submit a proposal send an email by February 15, 2019, with the intended investigators’ names and affiliations and their intended proposal’s title to [email protected] with the subject line: “Novel Outcome Measures RFA Notice of Intent”.

Applications must be completed electronically and submitted using forms provided at proposalCENTRAL, which will be open for applications beginning on January 14, 2019.

The deadline for applications is March 1, 2019, 5 p.m. EST. No extensions will be given. If you have any difficulties, please contact [email protected].

Competitive applications will undergo external peer review. Funding for these awards will be made by the Simons Foundation; notification of award is expected by June 4, 2019, with funding expected to begin on July 1, 2019.

Details concerning application requirements and submission can be found in the “How to Apply” tab or on proposalCENTRAL. If you have other questions, please review our FAQ.

The deadline for application submission is Friday, March 1, 2019, at 5 p.m. EST.

proposalCENTRAL Login Information
Applications must be submitted via proposalCENTRAL (pC). To start an application in pC, users must first log in to their pC account.

To submit an application, you must complete the following proposalCENTRAL sections:

1. Title Page: Enter the proposal title in this section.
2. Download Templates and Instructions: All templates necessary to complete your proposal are available for download in this module (or the Proposal Attachments module, where attachments are submitted as PDF-only files; see the Proposal Attachments section below for more details).
3. Enable Other Users to Access This Proposal: This section allows you to give other users access to your grant application. You have the option of giving them one of three levels of permission: View, Edit or Administrator.
4. Applicant/PI: The principal investigator (PI) should be listed here. For grants with multiple PIs, the contact PI should be listed here.
5. Organization/Institution: Contact information for the signing official and the financial/fiscal officer from your institution is required; select the correct person or enter new names in this
6. Key Personnel: Indicate key personnel, including but not limited to: PIs, co-investigators, consultants and postdoctoral research associates. In rare circumstances, the applicant organization may designate multiple PIs who share the authority and responsibility for leading the project, intellectually and logistically. For more information on the responsibilities of PIs, please refer to the Simons Foundation policies.
7. Abstract: Enter your abstract as text in this section.
8. Budget Period Detail: Enter your budget period detail in this section.
   1. Award start date: Proposals selected for funding will be announced by June 4, 2019, and funding will begin on July 1, 2019.
   2. Indirect costs (IDC): IDCs are limited to 20 percent of direct costs. The following items may not be claimed as IDCs: equipment, tuition, and any subcontracts with budgets including IDCs. IDCs paid to a subcontractor may not exceed 20 percent of the direct costs paid to the subcontractor. While IDCs on most equipment are not allowable, IDCs on small equipment (costing up to $10,000) are permissible.
   3. Equipment: The Simons Foundation (SF) will own equipment purchased with SF grant funds with a unit cost of $50,000 or more. At the end of the grant funding period or in the case of grant termination for any reason, SF reserves the right to retain ownership or cede ownership to the PI’s institution. Equipment with a unit cost of less than $50,000 shall be the property of the institution.
   4. Budget: The maximum budget is $300,000 per year, including indirect costs, for two or three years. Exceptions with strong justification will be considered but are not encouraged.
   5. Multiple PIs:
      1. Please note that the applicant PI will be the designated contact PI for the project. The contact PI will be responsible for directing the project and will coordinate all administrative deliverables.
      2. Applications with multiple PIs from different institutions who would like to be paid separately must upload in the Proposal Attachments section:
         1. Signed signature page for each PI (available for download in the Proposal Attachments and Download Templates and Instructions sections).
         2. Budget template for each non-applicant PI (available for download in the Proposal Attachments and Download Templates and Instructions sections).
         3. The direct and indirect costs for all non-applicant PIs. Direct costs must be included in section 8 (Budget Period Detail) in the Consortium & Contractual Direct section, and indirect costs should be included in the Indirect Costs section. Please add a separate line for direct costs and one for indirect costs for each non-applicant PI.
      3. Applications with multiple PIs from different institutions who will be paid directly by the contact PI’s institution are considered subcontracts. Please refer to the subcontract instructions in section 8f below.
      4. Applications with multiple PIs from the same institution do not need to submit additional materials. Additional non-applicant PIs should be listed as key personnel in section 6 (Key Personnel) and section 8 (Budget Period Detail), and only one signature page is needed.
   6. Subcontracts:
      1. Applications with subcontracts (including PIs who will be paid directly by the contact PI’s institution) must submit:
         1. Subcontract detailed budget (available for download in the Proposal Attachments and Download Templates and Instructions sections) for each subcontract.
         2. Subcontract direct and indirect costs. Subcontract direct costs must be included in the Consortium & Contractual Direct section, and subcontract indirect costs should be included in the Indirect Costs section. Please add a separate line for direct costs and one for indirect costs for each subcontract.
9. Budget Summary: The budget summary will populate from the saved detailed budget.
10. Organization Assurances: Indicate use of human participants or vertebrate animals in this section and status of approval from the institutional review board or Institutional Animal Care and Use Committee. Grants cannot activate without current human participant and/or animal research ethical approval.
11. Proposal Attachments: The following documents are to be uploaded in this section, where they are also available for download:
    1. Proposal narrative: The proposal narrative should not exceed four pages (excluding references, figures and figure legends). Proposals should include specific aims, background relevant to the application, significance of the proposed studies, preliminary results, experimental design, pitfalls and alternative strategies, and a timeline with milestones. SFARI’s preference is for figures to follow the narrative rather than be embedded in the text.
    2. Biographical sketch of key personnel.
    3. Budget justification.
    4. Budget templates:
       1. Multiple PIs: Applications with multiple PIs from different institutions who would like to be paid separately must submit a signed budget template for each PI institution.
       2. Subcontract: Applications with subcontracts must submit a budget template.
    5. Research environment and resources.
    6. Renewable reagents and data-sharing plan.
    7. Current and pending support: Please upload current and pending support both for PIs and for key personnel.
    8. Signed signature page: Applications with multiple PIs from different institutions who would like to be paid separately must submit a signed signature page from each PI institution.
12. PI data sheet: Your professional profile will populate this section of the application. If revisions are required, please select “Edit Professional Profile” and go to section 4 (Personal Data for Applications).
13. Validate: You must click the “Validate” button to check for any missing required information or files. All missing required information will be listed on the screen. Please supply any missing information before proceeding to the next step.
14. Signature page(s): The signed signature page is available for download in this section and must be signed by the signing official, then re-uploaded in the Proposal Attachments section. Applications with multiple PIs from different institutions who would like to be paid separately must submit a signed signature page for each PI institution.
15. Submit: You will be unable to submit if you have not provided all the required information. Any missing information will be listed on the screen. If your submission is successful, you will receive a confirmation message on the screen and a confirmation email.

Please note that narratives exceeding the four-page limit (not including references, figures and figure legends) will not be reviewed.
No extensions will be given.