Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)

Funding Opportunity Title

Research to Improve the Care of Persons at Clinical High Risk for Psychotic Disorders (Collaborative R01)

Activity Code

R01 Research Project Grant

Announcement Type

New

Related Notices

  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number

RFA-MH-14-210

Companion Funding Opportunity

RFA-MH-14-211, R01 Research Project Grant

RFA-MH-14-212, R34 Clinical Trial Planning Grant Program

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.242

Funding Opportunity Purpose

Given the highly disruptive and disabling nature of psychotic disorders, early intervention has been recommended as a means of preventing psychosis onset among at-risk individuals, as well as averting other adverse outcomes such as mood syndromes, substance abuse disorders, and functional decline in social, academic, and vocational domains. This funding opportunity announcement, along with the companion announcements, aims to support research that will inform a step-wise approach to early psychosis intervention in the United States. The goals of this initiative are to encourage applications that (1) test the effectiveness of interventions that target symptomatic and functional difficulties associated with clinical risk states for psychosis; (2) test hypotheses regarding mediators/mechanisms of action of these interventions; (3) create an evidence base to inform stepped-care models of early psychosis intervention; and (4) determine the feasibility for implementing such approaches in community-based treatment settings.  

Key Dates
Posted Date

August 7, 2013

Open Date (Earliest Submission Date)

December 6, 2013

Letter of Intent Due Date(s)

December 6, 2013

Application Due Date(s)

January 6, 2014, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

April 2014

Advisory Council Review

August 2014

Earliest Start Date

September 30, 2014

Expiration Date

January 7, 2014

Due Dates for E.O. 12372

Not Applicable

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). 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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

Approximately 100,000 young persons in the United States experience a first episode of psychosis every year . During the same interval, it is estimated that over one million children and adolescents may experience problems in thinking, mood, and social functioning suggestive of a pre-psychosis risk state . Given the highly disruptive and disabling nature of psychotic disorders, early intervention has been recommended as a means of preventing psychosis onset among at-risk individuals, as well as averting other adverse outcomes such as mood syndromes, substance abuse disorders, and functional decline in social, academic, and vocational domains. Efficacy trials suggest that targeted preventive interventions can reduce psychosis risk over 12 months to a greater extent than routine monitoring or non-specific treatment . Increasing the effectiveness of preventive interventions, and extending the benefits of pre-emptive treatment beyond 12 months, should be a major focus of clinical research. More clinical trial data are necessary to determine the risks and benefits of various forms of intervention prior to psychosis onset, and the likelihood that promising interventions can be brought to scale. Accordingly, the goals of this initiative are to (1) test the effectiveness of interventions that target symptomatic and functional difficulties associated with clinical risk states for psychosis; (2) test hypotheses regarding mediators/mechanisms of action of these interventions; (3) create an evidence base to inform stepped-care models of early psychosis treatment; and (4) determine the feasibility for implementing such approaches in community treatment settings within the United States.

Background

Over the past two decades, several hundred published reports have explored the construct of a clinical high risk (CHR) state for psychosis. Research conducted in Australia, Europe, and North America has established the predictive validity of risk criteria based on the presence of attenuated psychotic symptoms, transient psychotic episodes, or trait vulnerability combined with functional deterioration.  A recent meta-analysis of transition to psychosis among approximately 2,500 individuals who met CHR criteria reported mean transition rates of 22% at 1 year, 29% at 2 years, and 32% at 3 years. A separate study reporting outcomes for CHR persons who did not develop overt psychosis over an extended period found that many experience ongoing problems with attenuated positive symptoms (41% at 2 years) as well as persistent functional disability. Accumulating evidence of poor or marginal recovery over time spurred a shift in the CHR research agenda approximately 10 years ago, with increasing emphasis placed on randomized controlled trials (RCTs) to explore indicated prevention approaches. 

Since 2002, eleven RCTs have been conducted to test the efficacy of psychological, pharmacologic, nutritional, and multi-component psychosocial interventions for preventing psychosis onset among help-seeking persons who meet CHR criteria. Meta-analyses of these studies suggest that cognitive-behavioral therapy exerts a moderate effect on transition to psychosis at 12 months (50% risk reduction compared to supportive counseling), and that multi-component treatment, including family therapy, also delays or reduces transition to psychotic illness at one year. Although no clear evidence supports pharmacological interventions for persons at high clinical risk, one study suggests a potentially beneficial effect of nutritional supplementation (i.e., omega-3 fatty acids). While groundbreaking, efficacy trials have not generated knowledge that is readily translatable to clinical practice in U.S. community care settings. 

Additional RCTs are required to expand knowledge regarding effective interventions during the CHR period, and to build an evidence base to support high quality community care. Clinical staging or stepped care models have been suggested as a framework for future effectiveness studies . In these models, first-line interventions are selected according to a person’s position along a continuum of illness, with changes in therapy (i.e., stepping up or down) depending on outcomes attained with initial treatment. Step-wise care requires reliable strategies for determining an individual’s illness state; evidence-based treatments of differing intensity that “match” the person’s risk state; and procedures for monitoring clinical progress against pre-determined response criteria (e.g., stabilization, recovery, or worsening). The current initiative aims to support research that will inform a step-wise approach to CHR care in the context of the U.S. healthcare system. Anticipated outcomes from this program of research might include, but are not limited to:

Research Objectives

This Funding Opportunity Announcement (FOA) solicits research grant applications for randomized controlled trials that will test the effectiveness of interventions for CHR states within a stepped care framework. To accomplish this goal, the initiative will support RCTs that (a) segment the CHR population according to degree of psychosis vulnerability; (b) select well-specified CHR subgroups for study; (c) test interventions that address defining features of the selected CHR subgroup; and (d) determine the effectiveness of stage-specific treatments based on a priori definitions of recovery, stabilization, and worsening. In aggregate, this program of research will inform a step-wise approach to CHR care that features lower intensity/lower risk treatments as first-line interventions, with decisions regarding discharge, maintenance therapy, or step-up to more intensive care based on objective measures of treatment outcome. 

Responsive applications will select study samples on the basis of validated interview measures that assess key CHR features, e.g., the Comprehensive Assessment of At-Risk Mental States; the Structured Interview for Prodromal Syndromes , or the Bonn Scale for the Assessment of Basic Symptoms . In addition, the application must specify which methods will be applied to segment the CHR population into coherent subgroups. Several strategies have been proposed for stratifying the CHR population according to early versus later stages of psychosis risk, severity of attenuated positive symptoms and functional impairments, and neurocognitive status. Other approaches to risk stratification are permissible, including biomarkers or biosignatures of emerging illness. In all cases, however, the applicant must justify the choice of stratification method on empirical grounds, and provide evidence that subgroup classification can be accomplished reliably.  Investigators should have a history of successfully working with populations at clinical high risk for psychosis.  Applications should include information demonstrating the investigator’s capacity to identify, recruit, and randomize individuals who meet CHR subgroup criteria in numbers sufficient to support a well-powered RCT.  Investigators should also demonstrate experience in clinical trials management.

For the purposes of this FOA, applicants may propose novel approaches to CHR treatment or phase-specific adaptations of interventions with established efficacy for other conditions or illness phases.   In either case, applicants should propose interventions that target the illness or disability features that characterize the selected CHR subgroup. Interventions may be psychological, rehabilitative, or pharmacologic in nature. Whatever the intervention, the application should specify which psychological constructs, neurocognitive operations, or biological variables (i.e., “mechanisms") are thought to underlie CHR illness or disability.  Applicants must describe how the proposed intervention is expected to impact hypothesized mechanisms, and how this relationship will be measured.  Depending on the nature of the intervention, the “targets” and change mechanisms might involve specific neurobiological entities (e.g. brain circuits) or psychological or behavioral processes.  Applications should justify the plan for assessment of targeted mechanisms using valid measures that are as objective and direct as is feasible (e.g., using  neurophysiological and/or behavioral measures or laboratory tasks that have been previously validated as reflecting underlying behavioral, psychological or neural targets/mechanisms, as appropriate and feasible). When relevant, investigators are encouraged to conceptualize their research using the constructs and units of analysis defined in the Research Domain Criteria framework (http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml).

Proposed treatments should be justified on conceptual and empirical grounds with pilot data that demonstrate feasibility as well as the potential for clinical benefit. The clinical trial should be designed to provide a definitive test of an intervention’s effectiveness and to evaluate whether changes in hypothesized mechanisms are associated with subsequent changes in functional outcomes.  For novel approaches to CHR treatment, there should be sufficient pilot data supporting the approach. In cases where pilot data are lacking, investigators should consider applying to the companion intervention development FOA, RFA-MH-14-212, Research to Improve the Care of Persons at Clinical High Risk for Psychotic Disorders (R34).

Applicants are not required to propose interventions for more than one CHR subgroup. That is, RCTs focusing on a single step of care for a well-defined subgroup will be considered responsive to this FOA. However, it is also acceptable to propose tests of multi-step interventions where second-line treatments are offered to individuals who do not respond to initial interventions. RCTs that propose tests of multi-step interventions should consider sequential multiple assignment randomized trial (SMART) designs to test the value of adaptive treatment approaches. 

Applications must propose subgroup-specific primary and secondary endpoints based on a priori definitions of (1) recovery, (2) stabilization, and (3) worsening. The RCT should be powered to detect clinically significant differences between treatment and control groups on the primary outcome of interest.  Primary and secondary outcome measures for the RCT should be selected on the basis of recovery criteria relevant to the selected CHR subgroup.  For example, reversal of moderate attenuated psychotic symptoms, or restoration of normal social/academic performance, are reasonable recovery outcomes for persons in an ‘early’ or ‘low-severity’ CHR state. Alternately, reducing the intensity of attenuated positive symptoms and averting transition to psychosis are acceptable outcomes for individuals in a ‘late’ or ‘moderately severe’ CHR state. Finally, rapid remission of psychosis is a logical clinical endpoint for interventions that address brief limited intermittent psychotic symptoms or are intended to reverse an initial psychotic episode. Although studies may lack sufficient power to evaluate psychosis conversion as a primary outcome, transition to active psychosis should be operationalized and tracked as a secondary outcome in all investigations.

Finally, while it is acceptable for RCTs to occur within the context of academic or CHR research based clinics, applicants must recognize that the ultimate goal of this initiative is to test practical interventions that could be feasibly implemented and sustained in community treatment settings in the United States. Consequently, applicants are encouraged to (a) anticipate the characteristics of ‘real-world’ community settings that could affect uptake of effective treatments and (b) take these features into account when developing and testing intervention strategies . Responsive applications will include information related, but not limited, to the feasibility of methods for segmenting the CHR population into coherent subgroups, staff training and supervision requirements, practical approaches for monitoring treatment fidelity, resource requirements, and practical measures of quality and outcome.

This collaborative R01 FOA should be selected when two or more sites are needed to complete the study.  The collaborating sites share a specific protocol across the sites and are organized as such in order to increase sample size, accelerate recruitment, or increase sample diversity and representation.  In studies with a large number of sites, it is expected that one site may be submitted as a coordinating site for data management and/or other centralized administration.  For a linked set of collaborative R01s, each site has its own Program Director/Principal Investigator (PD/PI) and the program provides a mechanism for cross-site coordination, quality control, database management, statistical management, statistical analysis and reporting.

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIMH intends to commit approximately $5 million in FY 2014 to fund an estimate of 5-6 awards in response to this FOA and the companion announcements.

Award Budget

Application budgets are not limited, but need to reflect the actual needs of the proposed project.

Award Project Period

The total project period for an application submitted in response to this FOA may not exceed five years.

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

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.

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

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

Eligible Individuals (Program Director/Principal Investigator)

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 requires the use of the linked NIH Collaborative Research Project Grant (R01) activity code and there has been some confusion with regard to the applicability to the NIH multiple PD/PI policy.  Multiple PDs/PIs are allowed on any single application and the policy for doing so is included in this FOA.  Because the collaborative R01 activity code already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply.  PD(s)/PI(s) from each linked application should NOT be designated as multiple PDs/PIs on each application of a collaborative set.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download 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.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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.

Letter of Intent

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:

The letter of intent should be sent to:

Amy B. Goldstein, PhD
National Institute of Mental Health
6001 Executive Blvd.
Room 7133, MSC 9633
Bethesda, MD 20892-9633
Email: goldsteinam@mail.nih.gov
Office: 301-496-7227
Fax: 301-443-4045
Address for FedEx, UPS, etc:
6001 Executive Blvd, RM 7144
Rockville MD, 20852

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Application Title

To allow NIH to identify a group of applications as a related set of collaborative R01s, the titles for each R01 in the set must have the following format:  a “1/N” indicator + Identical title (e.g., “1/6-Multisite Comparison of Drug A vs. Drug B for Treatment of Disorder X”, 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 80 characters in length, including the tag, e.g., 1/6, at the beginning of the title.

Cover Letter

The PHS398 Cover Letter is one pdf file only.  Therefore, it must include the information requested below on the collaborative sites.   The following collaborative information is required in the Cover Letter:  a listing of all the applications that are a part of the set of collaborative R01s being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., “1/6”), and 3) the Applicant Institution.  Each site should submit an identical listing

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Facilities and Other Resources: This section should address not only physical resources, but also the intellectual and collaborative resources for executing the project and can be utilized to address relevant Resource-related collaborative issues. Instructions for this section include the following language:

Other Attachments: A list of the collaborative applications as described in the Cover Letter must also be included Other Attachments.  The information provided in this attachment MUST include a listing of all the applications that are a part of the set of collaborative R01s being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., “1/6”), and 3) the Applicant Institution.  Each site should submit an identical listing.  This file should begin with a heading called “Collaborative Applications”.  When saving the file, please name the file “Collaborative_Applications” as well, to ensure this section of the application is bookmarked appropriately.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: The collaborative mechanisms currently require an Overview section that is part of the specific aims. This Overview section should be identical for all applications that are linked together for the collaborative R01. The requirements of the Overview are as follows:

The overview should provide an overall rationale for applying as a collaborative study; the role of each site; the approach to project management; and elements unique to any of the sites.

This information is required in order to address the sixth review criterion, Collaboration.

The application from each site must contain an identical RESEARCH PLAN -.  The Research Plan must describe those aspects of the project that are common to all sites of the collaboration.  All variations in the research plan between sites, no matter how minor, should be highlighted in a subsection of the Research Plan with the heading "Elements Unique to This Site."  In this subsection PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc.

Applications must describe a feasible mechanism for scientific integration of research procedures, overall managerial and administrative responsibilities, and cross-site comparability of training to assure reliability and quality control.  The PDs/PIs may or may not wish to designate a Steering Committee or other decision making body, or identify one individual as the contact person for the group as a whole, for purposes of NIMH correspondence. Plans for ensuring access to data by all sites, analytic resources, publication and authorship rights, the possibility of public use research materials and data, or other means of distributing research materials to the wider scientific community, and a means of arbitrating disagreements on publication and other issues should be included in the application.

Any 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.

Research Strategy: As part of the research strategy, applications should present:  (1) an empirically justified approach to specifying and stratifying the clinical high risk population that is reliable and valid; (2) an approach to intervention that targets specific mechanisms of illness; (3) functional outcome measures related to mechanisms of illness; and (4) operationalized definitions of recovery, stabilization and worsening, with specific outcome measures for each.

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.

Consistent with NIH efforts to establish and promote the use of common standardized measures and methods, the harmonization of data across sites, and the sharing of data with the wider research community, applications are expected to include a Data Sharing Plan that addresses:

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

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

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

The ultimate aim of this initiative is to test interventions that can be feasibly implemented in the United States.  As a result, while foreign institutions are eligible to apply, foreign investigators should collaborate with a US investigator in the submission of an application and, in the application, describe how data collected in the foreign site will be relevant to, and will inform, the US healthcare system.

3. Submission Dates and Times

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. 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. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

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

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) 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. See Section III of this FOA for information on registration requirements.

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. 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 NIMH, 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 nimhreferral@mail.nih.gov} when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

Additional Information about Linked Applications

Applications must be submitted as a linked group or set of R01s, usually one R01 per participating PD/PI.  For each set of linked collaborative R01 applications, it is expected that each application will be coordinated and interlocked with the others as each application will contribute an essential component to the overall study.  In the case of multi-site clinical trials, it is anticipated that the same protocol will be submitted by each site. However, there are likely to be elements unique to some sites (e.g., data coordination, fidelity assessment, statistical analyses), and for intervention trials with large numbers of sites, a separate, independent coordinating and data management center may be warranted.   

Post-Submission Materials

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

Section V. Application Review Information

1. Criteria

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.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the 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 project proposed).

Scored Review Criteria

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 project that by its nature is not innovative may be essential to advance a field.

Significance

Does the 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? Does the application address strategies for increasing the effectiveness of preventive interventions for psychosis risk states, or extending the benefits of pre-emptive treatment beyond 12 months? Do the investigators propose an approach to intervention that, if effective, could substantially improve symptomatic and functional difficulties associated with risk states for psychosis?  Would the research contribute meaningfully to an evidence base that would, ultimately, inform stepped-care models of early psychosis intervention?  If shown to be effective, are the interventions to be tested feasible; i.e., could the interventions tested be brought to scale and delivered in community treatment settings? Will the study, as designed, provide important information for future program development, even if the results are negative? (i.e., fast-fail principles) 

Investigator(s)     

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? 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?  Do the investigators have a history of successfully working with populations at clinical high risk for psychosis?  Does the investigative team have a demonstrated record of successfully identifying, recruiting, and randomizing CHR individuals in other research studies? Do the investigators demonstrate expertise in clinical trials management?     

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? Is the intervention approach proposed novel? Are novel strategies or methods used in stratifying subgroups?    

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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? Does the application include an approach to selecting study samples that is based on validated interview measures of psychosis risk?  Is the methodology selected for segmenting the CHR population specified, reliable, and valid?  Does the intervention target psychological constructs, neurocognitive operations, or biological variables that are thought to underlie CHR illness or disability?  Are there clearly specified strategies for measuring the relationship for mechanism of illness and functional and symptomatic outcomes?  Does the plan for assessment of targeted mechanisms use valid measures that are as objective and direct as is feasible?  For novel interventions, are there sufficient pilot data regarding impact on psychological constructs, neurocognitive operations, or biological variables that are thought to underlie CHR illness or disability? Does the application include operationalized definitions of recovery, stabilization, and worsening?  Does the application include an operationalized definition of, and approach for tracking, transition to psychosis?  If the RCT tests a multi-step intervention, has the investigator considered sequential multiple assignment randomized trial (SMART) designs to test the value of adaptive treatment approaches?  Is there sufficient power to detect differences between treatment and control groups on the primary outcome of interest?  Does the application anticipate the characteristics of 'real world' community settings that could impact uptake of effective treatments?  To what extent are these factors taken into account when developing and testing intervention strategies?  Is information provided with respect to the feasibility of methods for segmenting the CHR population in coherent subgroups, staff training and supervision requirements, practical approaches to monitoring treatment fidelity, resource requirements, and practical measures of quality and outcome?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy 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? Does the application take into account 'real world' community settings that could affect uptake of effective treatments?    

Collaboration

Does the research plan justify the need for a collaborative multi-site project using this FOA? Are     sufficient and feasible mechanisms in place to ensure collaboration across sites to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results?  Are there adequate plans for shared decision making among PDs/PIs with regard to personnel, clinical decisions, changes in study protocol, and authorship?

Additional Review Criteria

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 clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. 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

Additional Review Considerations

As applicable for the 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

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources To what extent will data generated by the foreign organization be relevant to intervention implementation within US healthcare systems?.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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:

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines 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 National Advisory Mental Health Council. The following will be considered in making funding decisions:

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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. 

Section VII. Agency Contacts

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

Application Submission Contacts

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)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

Scientific/Research Contact(s)

Amy B. Goldstein, PhD
National Institute of Mental Health
Telephone: 301-496-7227
Email: goldsteinam@mail.nih.gov

Peer Review Contact(s)

David Armstrong, Ph.D.
National Institute of Mental Health (NIMH)
Telephone:  301-443-3534
Email:  armstrda@mail.nih.gov

Financial/Grants Management Contact(s)

Tamara Kees
National Institute of Mental Health
Telephone: 301-443-8811
Email:tkees@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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.


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