# SFARI 2016 grants cycle: choices, challenges, and priorities

Today, we’re announcing our annual request for applications (RFA) for SFARI Pilot and Research Awards. Letters of intent (LOIs), the short statements that precede full applications, are due no later than 9 October, 2015.

As we do every year, we’ve updated this column to provide a better picture of how the SFARI science team makes decisions on research proposals. Although the fundamentals remain the same, there have been a number of notable changes as a result of advances in the field and our evolving view of SFARI’s priorities.

### Cohorts:

We often receive applications proposing clever new ways of measuring various genetic, biochemical, psychophysical or neuroimaging parameters in individuals with ASD. Given that ASD is a behavioral diagnosis, we strongly encourage efforts to forge links between the behavior and the biology.

The trouble is, the first step for many of these investigators is to assemble a sufficiently large and diverse cohort of subjects. We’ve learned from assembling the SSC and Simons VIP cohorts, as well as from experiences of previous grants, that recruitment and retention is far more difficult and costly than many researchers anticipate. Unless there is a compelling reason for a new cohort, we recommend that researchers collaborate with existing teams that already have a study group, and pay careful attention to ascertainment biases that can influence the results.

We encourage investigators to use well-characterized cohorts, such as the SSC and the Simons VIP, in which multiple types of data (medical history, psychometric testing, genetic, brain imaging, etc.) can be layered to create a coherent picture and, importantly, be shared with the community to accelerate research. In addition, biospecimens are available for the SSC and Simons VIP, which can be used to elucidate the changes in molecular signaling that might be the link between genetics and phenotype. Some families that were recruited to the SSC ended up not being eligible for inclusion because of some of the criteria, such as having another family member with a psychiatric illness. In cases where biospecimens were collected before the exclusion was flagged (and some other circumstances), these specimens are now available in an ancillary collection that approved researchers can access via SFARI Base.

One more thought on cohorts: Genetic discovery is moving fast, and the potential for connecting genotype with phenotype seems especially promising. Our view is that it is no longer sensible to study individuals with ASD without knowing something about their genetic background or, at a minimum, including the collection of biospecimens for future studies and analyses. We will work with investigators who need advice about logistics on this subject.

### Reproducibility:

Proposals that focus on reproducing previous results are often at a disadvantage in review panels because, almost by definition, they don’t bring new ideas. But we are aware of the critical importance of replication, especially for potential clinical interventions. And if studies cannot be replicated, the ‘negative’ findings need to be swiftly communicated to the research community. In short, we will consider requests that involve replicating and expanding key findings.

### Data sharing:

We expect SFARI investigators to share renewable reagents and data developed using SFARI funds with other qualified investigators; a positive funding decision will depend on the quality of the data-sharing plan. (For more information, see section 17 of our Policies and Procedures document). In the case of several projects for which early release of data is critical, we make funding contingent on pre-publication sharing of results with other SFARI investigators. In these cases, we add important safeguards to ensure that the researchers are protected in various ways and can’t be scooped on their own data. In a News & Opinion Viewpoint published on SFARI.org, Randy Buckner articulates the critical need to share data and how best to balance this need with protecting investigators’ intellectual contributions.

### The LOI stage:

All applicants are required to submit an LOI. These are short (three-page) statements that are intended to save time — for applicants and SFARI science team members — compared with the effort required for full applications.

Applicants should familiarize themselves with the two types of annual awards that we offer, Pilot Awards and Research Awards, and should carefully consider which option is more appropriate given the state of their science and the extent of preliminary data.

At the LOI stage, we read applications primarily with an eye toward whether they are in line with SFARI’s mission and whether and how they complement our existing portfolio of awards.

Each LOI is read by at least two members of the SFARI science team, which includes our Director, Louis Reichardt, plus Marta Benedetti, Wendy Chung, Alice Luo Clayton, Pam Feliciano, Alan Packer, Julia Sommer, John Spiro and Steve Zukin, with additional advice from our former Scientific Director Gerald Fischbach. We seek advice from outside experts as needed, but by making this first-level decision in-house, we are able to streamline the process significantly.

### The full application stage:

If an LOI passes the internal review stage described above, the investigator will be invited to submit a “full application,” a six-page proposal detailing planned experiments. Full applications are sent out for peer review. Our referees are a diverse group of scientists who evaluate the scientific merits of a proposal (including the study plan, investigators’ track records, quality of preliminary data, data-sharing plan and budget). Some referees have been with us for many years, but each year we also rotate a number of the peer-reviewers to ensure that the scientific expertise of the panel fits well with the scope of the current proposals. In the past few years, we’ve included some SFARI investigators. After an initial electronic pre-review, in which referees submit written comments (proposals that do poorly at this initial stage are triaged without full discussion), we hold a two-day meeting to discuss the grants in-person. At that meeting, referees present grant proposals, and together with the SFARI science team, debate strengths and weaknesses and then rank scores for each proposal. Conceptually related proposals are discussed in batches in order to facilitate direct comparisons.

We don’t divide the committee into subgroups by expertise. All members are present for discussion of all proposals — except, of course, when potential conflicts of interest exist. This approach may be more time consuming than that of a specialized subcommittee, but it offers a check against overspecialization unduly influencing decisions.

The referees and SFARI science team both have substantial flexibility in suggesting changes to the scope, experimental design and budget of a grant application. The feedback that we get from referees about this flexibility has been very positive compared with other types of review committees that are less interactive.

We try to give investigators we do not fund a summary of the reasons for the decision. However, we ask applicants to keep in mind that referees are not asked to prepare formal remarks for the applicants, and it can be challenging to summarize the verbal discussions.

### Returning investigators and percent effort:

We try to balance the needs of new investigators with continuation applications from current investigators. We have always been enthusiastic about bringing in investigators who have a strong track record in another research area and can offer a fresh approach to autism research.

In general, we prioritize new grant applications and only in rare cases provide limited funding for renewal of three-year Research Awards. After three years of support, grantees are encouraged to seek continued funding from the National Institutes of Health and other agencies; when justified by exceptional progress, we will consider limited transitional funding. We will continue to welcome former grantees’ attendance at SFARI-sponsored meetings, workshops and other activities. We do encourage recipients of SFARI Pilot or Explorer Awards who have achieved success in their initial studies to apply for three-year Research Awards.

We seek applications from independent investigators who can devote a substantial portion of time to their SFARI project. Although we do not require a minimum Principal Investigator effort, we expect the investigator to commit to a level of effort that reflects a leading role in the project.

Proposals are judged to some degree on whether the budgets are reasonable given the potential risks and rewards of the research (larger budgets raise the bar for funding and are subject to heightened scrutiny) and whether there is funding from other sources. At the full application stage, we are especially vigilant about how specific aims overlap with other current or pending grants. We also work with successful applicants to adjust budgets after the review process.

### Explorer Awards:

In addition to our annual RFA cycle described above, we also have SFARI Explorer Awards. Unlike Pilot Awards granted through the annual RFA, applications for Explorer Awards are accepted throughout the year on a rolling basis, are for a duration of one year only, and are capped at \$50,000 in direct costs.

Explorer Awards are intended to provide resources to support exploratory and high-risk/high-reward experiments that strengthen hypotheses and lead to competitive applications for larger-scale funding from SFARI or other organizations. We review the applications internally with a response time as short as 30 days. What distinguishes both Explorer and Pilot Awards from Research Awards is that they place less emphasis on preliminary data.

### Feedback

We always welcome feedback about our decision-making process. The more specific the feedback, the better. “I can’t believe my grant didn’t get funded; you guys make lousy decisions”, is less helpful than a reasoned critique of some of the criteria we have outlined above. We use your feedback to improve our review process. You should not expect that we will change our decision on your proposal as a result of your feedback.

Also, please keep in mind that a negative decision this round is not a broad judgment about the quality of work emerging from a lab, or a blanket statement about the potential for future SFARI funding. It’s simply that the abundance of high-quality grants and a finite budget force us to make tough decisions.

### References:

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8. Simons VIP Consortium. Neuron 73, 1063-1067 (2012) PubMed
9. De Rubeis S. et al. Nature 515, 209-215 (2014) PubMed
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