Unlinked vs. Linked Applications
Research Sites FOA (RFA-DA-15-015)
Consortium Coordinating Center FOA (RFA-DA-15-014)
Data Analysis and Informatics Center (DAIC) FOA (RFA-DA-15-016)
• Do the funding amounts listed on the FOAs represent total costs (direct and indirect)?
o Answer: Yes, the amounts listed on the FOAs represent the total cost.
• Are there any caps on the facilities and administrative (F&A or indirect) costs?
o Answer: No, F&A costs cannot be capped; they are set via negotiations between HHS and the institution.
• Can a PI submit multiple applications?
o Answer: Although a PI can submit more than one application, the NIH will not accept duplicate or highly overlapping applications under review at the same time by the same applicant. Additionally, duplicate or highly overlapping applications will not be accepted from different institutions/applicants unless they are submitted as linked applications, per the instructions in the FOAs.
• Is there a percent effort requirement or expectation for PIs on the data analysis center and the research sites applications?
o Answer: No. However, the percent effort should be in keeping with achieving the goals of the project. There is a minimum percent effort requirement for the Consortium Coordinator that is specified in that FOA (4.2 months/year for a single PI; 2.4 months/year for multiple PIs).
• Can an individual or set of individuals be named as PI/PD on both an application for a Data Analysis and Informatics center and an application for a Research Site?
o Answer: Yes, provided they will have sufficient time to devote to each component.
• Are foreign components/foreign sites allowed?
o Answer: Foreign components and/or foreign sites are not allowed. Applications proposing any of these components will be considered non-responsive and will not be reviewed.
• Do you need to identify members of your advisory board?
o Answer: No, they should not be identified in the application. See: http://grants.nih.gov/grants/guide/notice-files/NOT-DA-15-051.html.
• Will late applications be accepted?
o Answer: No, late applications will not be accepted (exception: in cases of natural disaster). Further, if one or more applications from a set of linked applications is submitted late, it will not affect the review of the remainder of the linked applications. All applications, whether linked or not linked, will be reviewed individually and scored on the basis of their own merits.
• Can the purchase of a scanner be part of the requested costs?
o Answer: Yes, but it must be strongly justified, and feasible for the time-line of the study.
• Are applicants expected to retain the ABCD moniker in the applications and for the duration of the project?
o Answer: We would like to retain ABCD moniker, but this is not a requirement.
• Where and when do I apply to for a Certificate of Confidentiality?
o Answer: Through the primary funding institution, NIDA, and only after the grants have been approved for funding.
• Will one Letter of Intent (LoI) be sufficient for a set of linked applications (all components) or will each application need to submit its own LoI?
o Answer: One LoI will be sufficient, referencing all of the relevant information and personnel.
• What is the role of RUCDR in biospecimen collection for genetic/epigenetic analyses?
o Answer: RUCDR will provide materials for collecting samples and the samples will be shipped to Rutgers for future genetic/epigenetic analyses.
Andrew Brooks, PhD
COO, RUCDR Infinite Biologics
• Will RUCDR bank specimens for analyses other than genetics or epigenetics?
o Answer: RUCDR will provide banking of whole blood and blood related products in the form of cryopreserved lymphocytes, DNA, RNA, plasma, serum. These whole blood and blood related products can be then used for a variety of analyses—to be determined later. Saliva and blood spots are also accepted, but their use should be justified.
• Will a single study section review all three FOAs?
o Answer: Yes.
• What will determine whether a reverse site visit is conducted before the review?
o Answer: It will depend on the number and types of applications received (linked or unlinked), and the perceived need for additional information prior to the review.
• Will applications be streamlined (triaged)?
o Answer: It will depend on the number of applications received, and the capacity of the review panel.
• Can an appeal to a review decision be filed?
o Answer: No, appeals are not allowed on review decisions for the ABCD study.
Unlinked vs. Linked Applications:
• How can linked and unlinked research site applications be compared on merit when they may propose different approaches and methods?
o Answer: Each application will be evaluated independently and according to the review criteria specified in the FOA, regardless of linkage status.
• Is there an advantage to submitting linked applications?
o Answer: The FOAs allow for this flexibility so that qualified applicants that might not be able to join or form a consortium could still participate in this project. Thus, each application will be evaluated independently according to the review criteria in the relevant FOA.
• Is there a possibility that U01s and U24s may be re-sorted to create a new consortium?
o Answer: Yes, applications that are selected for funding may be re-sorted after review, including accommodating unlinked applications.
• What happens if the methods in a well-scored unlinked application do not correspond well with those of a linked set of applications that is funded?
o Answer: Following issuance of the grant awards, a meeting will be convened with the grantees, the External Scientific Advisory Board, and NIH staff to refine/revise and negotiate the final protocol to be conducted by the full consortium. Furthermore, it is stated in the cooperative agreement terms of award that each U01 PI agrees to abide by the policies and rules set up by the consortium. Awardees will be required to attend consortium committee meetings and participate in the cooperative nature of the consortium. See more at “Cooperative Agreement Terms and Conditions of Award at http://grants.nih.gov/grants/guide/rfa-files/RFA-DA-15-015.html
• Can Centers (Coordinating or Data Analysis and Informatics: U24s) come in as unlinked applications?
o Answer: Yes.
• How do you become part of a self-forming consortium?
o Answer: You can identify self-forming consortia by reaching out to investigators who are publishing and/or are funded to conduct work in this topical area. Alternatively, NIH RePORTER (http://projectreporter.nih.gov/reporter.cfm) lists all NIH funded research grants; this can be searched to identify relevant investigators.
Research Sites FOA (RFA-DA-15-015):
• Is a single-cohort design required or would other models be considered (e.g., a sequential-cohort design)? If a strictly longitudinal design is required, and the award period is only for 5 years, how are applicants expected to follow subjects over the intended 10 year time period?
o Answer: Applications must use a single-cohort longitudinal design. It is anticipated that there will be a second award period to cover the subsequent 5 years; however, it will depend, at least in part, on the availability of funds.
• How will a second 5 years of support be considered to extend the longitudinal design?
o Answer: It will be based on the issuing of a new funding opportunity announcement and on the competiveness and productivity of the submitted applications.
• What is the hub and spoke model and how should it be organized for the application submission?
o Answer: This arrangement allows for one lead (or hub) institution (that submits a single application) and other institutions (the spokes to the hub) that will work with the lead Institution to achieve the ABCD study goals. Under this arrangement, a subcontracting mechanism could be used to achieve this goal. For example, one institution may have the imaging expertise but other institutions may be able to recruit from rural areas, but not be capable of imaging. By applying together, the appropriate subjects can be recruited and the full research protocol can be completed. For additional guidance on how to prepare the application, see the SF 424 application instructions, section 4.8, “Special Instructions for Preparing Applications with a Subaward/Consortium.”
• How much does standardization need to be reflected in individual research site applications within a linked set?
o Answer: The linked sites are expected to submit a common protocol, with description/explanation of how the sites are the same/different. The FOAs contain information on reporting the differences between the individual sites as part of the linked set.
• What can a research site add to the ABCD study beyond the basic protocol?
o Answer: The site can explore whatever research questions are within the parameters of their expertise and relevant to the overall goals of the ABCD study.
• Does the $25 million in costs include payment for subject participation?
o Answer: Yes.
• How often should the subjects be scanned within the five-year period?
o Answer: A key objective of the study is to conduct neuroimaging scans at intervals that are sufficiently regular to assess meaningful change throughout the period of risk, but to do so in a way that is feasible from a cost perspective. According to our estimates, we believe that conducting scans at approximately 2-year intervals strikes the right balance. Scanning assessments should occur initially at baseline (entry into study) and at two-year intervals thereafter. For example, one wave of participants could be scanned in years 2 and 4, while the second wave of participants could be scanned in years 3 and 5. It will be important to fully justify all design decisions, including the interval between scanning assessments.
• How much emphasis should there be on neuroimaging versus other measures of brain development?
o Answer: There is a long list of measures to be assessed, and neuroimaging is just one of the important parts of the protocol. Moreover, the behavioral and clinical assessments (e.g., neuropsychological, clinical assessments, and substance use questionnaires) should be administered at shorter intervals (for example at 3 or 6 month intervals) than the neuroimaging assessments. As noted above, it will be important to fully justify all design decisions, including the interval between assessments.
• Are there specific assessment tools that should be selected for phenotypic assessments?
o Answer: The RFAs state that investigators involved in human-subjects studies are strongly urged to employ a common set of tools and resources that will promote the collection of comparable data across studies. Among these are: the core and specialty collections available in the Substance Abuse and Addiction Collection of the PhenX Toolkit (www.phenxtoolkit.org); NINDS’ common data elements (http://www.commondataelements.ninds.nih.gov/#page=Default); the NIH Toolbox (http://www.nihtoolbox.org/Pages/default.aspx) and others available through the National Library of Medicine’s Common Data Element Resource Portal: http://www.nlm.nih.gov/cde/summary_table_1.html .
• Other than being a 3T, are there any other specific requirements for the scanner?
o Answer: No. However, harmonization of data from different machines should be considered in linked applications. The FOA includes the requirement for linked applications that at least 2 sites are using the same machine to be able to distinguish site versus scanner effects.
• What are the expectations for parental involvement in the study?
o Answer: There are several expectations:
- Regarding informed consent, HHS regulations require that one or both parents or a guardian must provide consent and children capable of assent must also express their willingness to participate (45 CFR 46 Subpart D, http://www.hhs.gov/ohrp/policy/faq/children-research/special-requirements-children-research.html).
- However, parental involvement is also expected as part of the information gathering for the study participant. It will be necessary to obtain relevant parental medical history (including information about the pregnancy); and optionally, biospecimen collection from the parents could contribute to future genetic/epigenetic analyses as well.
• Would fewer (or more) than 10 research sites across a linked set be acceptable?
o Answer: Yes, it is up to the applicant to explain how they plan to accomplish the objectives of the study. More information on this may be found in the summary of the expert panel on the management of sites and project feasibility: http://addictionresearch.nih.gov/summary-expert-panel-meeting.
• Would it be allowed for multiple PD/PI to be listed on many/most or all research site applications in a set of linked applications?
o Answer: Yes.
• Is there a limit to the number of co-PIs across the consortium applications?
o Answer: No; however the number of co-PI’s should be kept to a manageable number.
• Do individual U01 applications need a data analysis section?
o Answer: All U01 applications are expected to have a data analysis section. Linked applications may provide a summary and reference to the Data Analysis and Informatics Center linked application.
• Can a subset of sites address specific research questions than are not addressed by the remaining sites?
o Answer: The basic protocol must be standardized across all research project sites in the final consortium. Each research site or group of sites may propose and conduct additional studies relevant to the overall goals of the ABCD Study.
• Would a group specializing in twin studies be acceptable as part of an overall consortium?
o Answer: Although we do not envision the ABCD study as a twin study, twin research participants will be allowed. Also, the ABCD study could be enriched by other types genetically informative designs.
• Is the sample size of 10,000 a firm number?
o Answer: No, a smaller sample may be proposed if justified by feasibility and statistical-power analyses to accomplish the aims of the study.
• The FOA indicates that the age of the participants at baseline should be 9-10 years old. Is this a firm requirement? Could the range be extended downward or upward?
o Answer: Epidemiologic data suggest that this age range maximizes the sampling of youth who are naïve to substance use at baseline, but who are at increased risk of substance use during the following years of the study. Any deviation from the 9-10 age range requires strong justification.
• Is a two-year window at start-up the only allowed period for site enrollment?
o Answer: Subject enrollment is to be conducted during a two-year period following establishment of the final consortium protocol and the standardization of all research project sites.
• Are all linked sites expected to use the same sampling methodology?
o Answer: Yes, there should be a unified study-wide sampling design. This will facilitate merging of the data at the end of the study.
• Is oversampling required?
o Answer: The primary sampling objective of the ABCD study is to recruit a sample of adolescents who are broadly representative of 9-10 year-olds living in the United States in 2015. Oversampling may be a useful strategy to enrich the sample for risk of substance use during adolescence to ensure that the ABCD has sufficient statistical power to address the overall objectives. However, oversampling is not required.
• What happens if some applications (or sets of linked applications) propose a school-based sampling design, whereas other applications (or sets of linked applications) propose a household-based sampling design? How will these different applications be evaluated?
o Answer: There are pros and cons to any sampling design. Therefore, applicants should propose the strongest, most feasible sampling design to achieve the objectives of the ABCD Study. Ultimately, the ABCD Study will adopt a single unified study-wide sampling design. As noted above, following issuance of the grant awards, a meeting will be convened with the grantees, the External Scientific Advisory Board, and NIH staff to refine/revise the protocol to be conducted by the full consortium.
Consortium Coordinating Center FOA (RFA-DA-15-014)
• Are multiple PDs/ PIs allowed for the consortium coordinating center?
o Answer: Yes.
• Can a Consortium Coordinator(s) serve as a single PI or as one of multiple PIs on any other component within the consortium?
o Answer: No. As stated in the RFA, "The Consortium Coordinator(s) cannot be a PD/PI on another component of the consortium." Moreover, although having the Consortium Center PI serve in another capacity on any of the other components of a consortium is not expressly prohibited in the ABCD RFAs, doing so would create a conflict of interest for the Consortium Center PI in the decision-making process for distribution of funds and resources to the consortium components. Such a circumstance may be viewed by reviewers as a weakness in the approach [a review criterion] and may be also viewed as a weakness by NIH staff making funding decisions.
• How will funds be allocated for the “opportunity fund”?
o Answer: The Coordinating Center will be responsible for developing policies and procedures related to distributing funds for promising/unanticipated projects that arise during the course of the project.
• Will the Coordinating Center be responsible for reimbursement of travel-related expenses for Steering Committee and other project-related meetings or should those expenses be included in individual applications?
o Answer: Yes, the Coordinating Center is responsible for reimbursement of travel-related costs, and these expenses should be covered as part of the study costs.
• How many meetings per year should be anticipated?
o Answer: The FOAs state the minimum number of meetings per year that are expected for the full consortium (1/yr) as well as the steering committee (2/yr).
• What is expected regarding consent for data sharing?
o Answer: All consenting participants (parents of the children who are the study subjects) must consent to broad data sharing, including secondary data analyses beyond the prescribed endpoints of the ABCD study. Personally identifiable information (PII) will not be shared.
Data Analysis and Informatics Center (DAIC) FOA (RFA-DA-15-016)
• Are applicants required to use the National Database for Autism Research (NDAR) data repository?
o Answer: Yes.
• Will the data be analyzed by NDAR?
o Answer: No, NDAR functions only as a data repository.
• What is the relationship between the DAIC and NDAR?
o Answer: The DAIC receives data from the research project sites, performs processing and quality control, and will upload the data to NDAR. NDAR will work with the DAIC to transfer the data and to design a front-end interface for the research community that will allow for data sharing. The NDAR team will also work with the DAIC to find efficient ways to allow the research community to use workflows and analysis packages developed by the Center.
• If NDAR is the ultimate data repository, must the NDAR standard terminology be used for all variables?
o Answer: NDAR standard terminology is not required. The NDAR team will work with the DAIC to create the data dictionaries that will be used in the ABCD study.
• How will patient confidentiality be protected through NDAR?
o Answer: A special version of the NDAR Global Unique Identifier (GUID) software will be made available to all of the data collection sites. That GUID will be used throughout the ABCD project as the single identifier for a research participant.
• Given that there is a Data Analysis and Informatics Center, what is expected of the research sites in terms of statistical/ data management capabilities?
o Answer: Each research site must provide the raw data to the DAIC for quality assurance, processing, and analysis.
• How soon will the data be made available to qualified researchers?
o Answer: Data from the ABCD study must be released to the research community as soon as it has undergone basic quality assurance procedures. The applicant is expected to develop policies, methods, and standards for rapid data sharing, which is critically important for the ABCD study.
• Are there limitations on the purchase of equipment for data processing and storage?
o Answer: No, other than the use of NDAR as the requirement for data repository.
• Can intramural (IRP) researchers participate in the ABCD study?
o Answer: Yes, but there are restrictions on how they would be funded. An IRP investigator can participate in two ways: 1) they can submit an application as PI on an ABCD component, but must state that they will only use intramural funds to cover all costs; or 2) they can be a collaborator or Co-Investigator on a component where the PI(s) are extramural investigators. In that case, the grant would be issued to the extramural grantee institution, and the extramural grantee institution could subcontract to the Intramural Research Program for services. The subcontract could fund temporary or visiting post-doctoral appointments, including consultant costs, and budgetary items typically included in Other Costs, e.g. scanning costs, equipment, supplies, travel, etc. However, the subcontract cannot provide salary funds to Federal employees. In either case, the IRP investigator must indicate the amount of effort that will be devoted to ABCD study activities, even though there would be no salary support associated with such effort.