2019 Novel Outcome Measures in ASD Request for Applications

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 sfgrants@simonsfoundation.org 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 sfgrants@simonsfoundation.org.

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.