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

Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions (R01)

Activity Code

R01 Research Project Grant

Announcement Type

New

Related Notices

  • October 03, 2014 - See Notice NOT-MH-15-002. Notice Announcing Updated Frequently Asked Questions Related to NIMH Policies for Applications Containing Clinical Trials
  • September 25, 2014 - See Notice NOT-MH-14-033. Notice of Information on High-Priority Research Areas to Understand and Reduce Mental Health Disparities.
  • July 8, 2014 - NIMH Focus for Intervention Studies Submitted Under the Stigma and Health Literacy Announcements. See Notice NOT-MH-14-016.
  • June 4, 2014 - Notice NOT-14-074 supersedes instructions in Section III.3 regarding applications that are essentially the same.
  • May 14, 2014 - See Companion RFA-MH-15-340, R01 Research Project Grant .
  • June 12, 2014 - See Notice NOT-MH-14-015, Data Sharing Expectations for NIMH-funded Clinical Trials.

Funding Opportunity Announcement (FOA) Number

RFA-MH-15-320

Companion Funding Opportunity

RFA-MH-15-325, Collaborative R01 Research Project Grant
RFA-MH-15-330, R34 Clinical Trial Planning Grant Program 
RFA-MH-15-300, R21/R33 Phased Innovation Award
RFA-MH-15-310, R33 Exploratory/Developmental Grants Phase II
PAR-14-107, U01 Research Project – Cooperative Agreements  

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.242  

Funding Opportunity Purpose

This Funding Opportunity Announcement (FOA) seeks to support investigator-initiated clinical trials to establish the effectiveness of interventions and to test hypotheses regarding moderators, mediators, and mechanisms of action of these interventions.  This FOA supports clinical trials designed to test the therapeutic value of treatment and preventive interventions for which there is already evidence of efficacy, for use in community and practice settings.  Applications might include research to evaluate the effectiveness or increase the clinical impact of pharmacologic, somatic, psychosocial (psychotherapeutic, behavioral), rehabilitative and combination interventions to prevent or treat mental illness.  This FOA also supports clinical trials to test patient-, provider-, organizational-, or systems -level services interventions to improve service access, engagement, quality, coordination, or delivery, with the goal of improved outcomes at the individual and population level.  The intervention research covered under this announcement is explicitly focused on practice-relevant questions.  Applications must justify the potential impact of the proposed intervention/services models on practice and public health in terms of the magnitude of likely improvements in key outcomes (e.g., effect size, safety/tolerability profile, value and efficiency, and dissemination potential), as compared to existing approaches.   

Key Dates
Posted Date

February 24, 2014

Open Date (Earliest Submission Date)

May 17, 2014

Letter of Intent Due Date(s)

30 days before the application due date  

Application Due Date(s)

June 17, 2014, October 17, 2014, and February 17, 2015, 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

October, 2014; March 2015; June 2015

Advisory Council Review

January 2015; May 2015; October 2015

Earliest Start Date

February, 2015; June, 2015; September, 2015

Expiration Date

February 18, 2015

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.


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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

The purpose of this FOA is to support research to test the therapeutic value of treatment, preventive, and services strategies for which there is already evidence of efficacy, for use in community and practice settings and to test hypotheses regarding moderators, mediators, and mechanisms of action of these interventions.  This FOA supports research to evaluate the effectiveness of pharmacologic, psychosocial (psychotherapeutic and behavioral), rehabilitative and combination interventions that show promise, compared to existing treatment approaches, for improving symptomatic and functional outcomes for mental disorders. Studies that address either acute or longer-term therapeutic effects are encouraged.  This FOA also supports clinical trials to test patient-, provider-, organizational-, or systems -level services interventions to improve service access, engagement, quality, coordination, or delivery, with the goal of improved outcomes for individual patients and as well as larger populations.  The intervention research covered under this announcement is explicitly focused on practice-relevant questions.  Applications should justify the potential impact of the proposed intervention/services models on practice and public health in terms of the magnitude of likely improvements in key outcomes (e.g., effect size, safety/tolerability profile, value and efficiency, and dissemination potential), as compared to existing approaches. 

Research Objectives

In general, prior to effectiveness testing, results from more highly controlled studies provide empirical support regarding the intervention’s efficacy and the mechanism that underlies clinical benefit (i.e., evidence that the intervention engages its intended neurobiological or psychological targets, and changes in these targets lead to functional improvement and clinical benefit).  Effectiveness trials in response to this FOA should be designed not only to test the intervention effects on outcomes of interest, but also to explicitly address whether the intervention engages associated change mechanisms that were previously identified under more controlled, efficacy conditions, thereby reconfirming the intervention targets and testing whether previously identified changes mechanisms are operative in the effectiveness context (see NIMH web page on Clinical Trials).  For studies that involve preventive or therapeutic interventions, the study should take into account RDoC or RDoC-like constructs when defining the subject eligibility (inclusion), intervention targets or mechanisms, and outcomes, as appropriate and feasible in the effectiveness setting (see the RDoC webpage http://www.nimh.nih.gov/research-funding/rdoc/nimh-research-domain-criteria-rdoc.shtml for more details).  In this manner, the results of the effectiveness trial will advance knowledge regarding therapeutic change mechanisms and have utility regardless of trial outcomes (e.g., in the event of negative results, information about whether the intervention was successful at engaging its targets can facilitate interpretation).    

Depending on the nature of the intervention, the “targets” or mechanism of action might involve specific neurobiological entities (e.g. brain circuits) or psychological or behavioral processes (e.g., attention bias, cognitive control, stress regulation).  In the case of services interventions, targets might involve consumer or provider behaviors that are intervened on in order to improve intervention access, engagement, quality or outcomes.  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, or using validated proxy measures as alternatives).

With appropriate justification, there could be an exception to the requirement for strong efficacy evidence before an intervention is tested in an effectiveness trial.  To reduce the alarming fall-off in effect sizes from efficacy to effectiveness studies, and to expedite translation from intervention development to practice-ready interventions, this FOA encourages investigators to conduct highly-controlled trials in community settings as early as possible in the intervention development sequence.  Depending on the intervention type and measurement involved, and with strong justification, this announcement seeks trials with high internal validity, albeit with community therapists and typical community patients in community settings, as an alternative to traditional early efficacy trials (e.g., in laboratory settings).  As with other studies in response to this FOA, under this approach, trials should be designed to examine, not only the intervention effects on outcome, but also to reconfirm the intervention’s targets or mechanism of action. Measures should be as direct and objective as possible, and the application must include fidelity assessment and monitoring procedures.

Research responsive to this announcement must involve trials with prospective data collection in which patients are assigned to specific intervention conditions.  While random allocation to intervention conditions is expected in most cases, depending on the study question, practical constraints, and ethical considerations, quasi-experimental designs with non-randomized comparison groups might be appropriate, with strong justification.  In all cases, applications should address how the selected research design minimizes confounders that may limit the ability to infer causality.  Randomized Controlled Trials (RCTs) in response to this FOA should be designed consistent with CONSORT guidelines (http://www.consort-statement.org/).  Studies that address questions regarding the impact of interventions using archival or observational/naturalistically collected data are not considered responsive to this FOA; applicants are encouraged to contact Scientific/Research staff with questions regarding responsive trial designs and alternative FOAs. 

Comparison or control conditions may include treatment-as-usual or other standard or experimental interventions of proven efficacy.  However, placebo or sham interventions might be used where appropriately justified, for example, in studies of augmentation strategies (blinded) added to existing treatments (generally open-label).  In contrast to efficacy trials, it is anticipated that effectiveness trials might not be double-blind; while self- and clinician-ratings can be informative and may reasonably be collected, unless otherwise justified, raters responsible for key outcome measures should be blinded as to subjects’ treatment assignment.  Primary outcome measures should be validated and generally accepted by the field.  Given the emphasis on practice relevant questions, outcomes of interest extend beyond symptom reduction to include short- and long-term assessment of functioning across domains (such as school, work, family, peer functioning) for children, adolescents, and adults, and also might include other outcomes of interest to key stakeholders (e.g., efficiency and value of new intervention and services approaches).  It is recommended that treatment protocols and manuals be completed and available for reviewers upon submission of applications under this announcement.  In addition, the application should include provisions for the assessment and monitoring of the fidelity of intervention delivery via procedures that are feasible and valid.    

Given the focus on practice-relevant questions in community and practice settings, collaborations between academic researchers and clinical or community practice partners or networks are expected.  Applications are expected to maximize efficiencies in effectiveness research and should explicitly address how efficiencies are incorporated.  When possible, studies should capitalize on existing infrastructure (e.g., practice-based research networks, electronic medical records, administrative data bases, patient registries, institutions with Clinical and Translational Science Awards) to increase the efficiency of participant recruitment (i.e., more rapid identification and enrollment) and to facilitate the collection of moderator data (e.g., clinical characteristics, biomarkers), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, value and efficiency of intervention approaches); cost-sharing, including in-kind support, is encouraged. 

It is expected that most projects should request and be completed in a 3- or 4- year budget period.  Applicants are strongly encouraged to contact Scientific/Research staff in advance if they anticipate requesting 5 years of support.  All applications should provide a detailed justification for the project timeline. Studies that build in efficiencies to expedite enrollment and the delivery of practice-relevant results will be considered of higher priority by the NIMH.

Potential applicants are strongly encouraged to contact Scientific/Research staff as far in advance as possible to discuss the match between potential research applications and current NIMH priorities and relevant funding mechanisms.

Information about the mission, strategic plan and research interests of the NIMH can be found at the NIMH website (http://www.nimh.nih.gov) including http://www.nimh.nih.gov/research-priorities/strategic-objectives/index.shtml.  Applicants are also strongly encouraged to review the information on the NIMH website focused on clinical trials http://www.nimh.nih.gov/funding/clinical-trials-for-researchers/index.shtml.

Please note, per NOT-MH-14-007 NIMH will not accept R01, R21, or R03 applications that include clinical trials of potential therapies for mental disorders, under the NIH parent R01 Funding Opportunity Announcement (FOA) PA-13-302, NIH parent R21 FOA PA-13-303, and NIH Parent R03 FOA PA-13-304, and subsequent reissuances of these FOAs.

Priorities and Considerations for Effectiveness Trials Research

Given the resources necessary to launch large-scale trials and conduct intervention research in community/practice settings, studies must be justified in terms of potential impact; potential to inform understanding of mediators/mechanisms of action and personalized strategies; and use of innovative platforms (e.g. registries) and designs (e.g., time and cost efficiencies for enrolling representative patient samples via networks or other existing infrastructure). NIMH strongly discourages large scale trials designed to detect incremental gains in established effects; expensive trials of on-patent medications without demonstrated superiority over off-patent medications; and trials adapting currently available treatments for new subpopulations, without strong empirical justification.

When planning and preparing a clinical trial research application in response to this FOA, investigators should consider the following:

Examples of clinical trials that would be considered responsive to the goals of this FOA include but are not limited to:

Examples of studies that are not responsive to this FOA and will not be reviewed include the following:

Updated priorities for NIMH clinical trials research are detailed on the NIMH Clinical Trials website.  Intervention research that addresses objectives outlined in the NIMH Strategic Plan and NIMH Strategic Research Priorities is encouraged.  Additional priorities for intervention research are detailed in the NAMHC Workgroup Report "From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses."  Research on services interventions that addresses objectives outlined in Objective 4 of the NIMH Strategic Plan and NIMH Strategic Research Priorities is encouraged.  Additional Priorities for services research are outlined in the NAMHC Workgroup Report “The Road Ahead: Partnerships to Transform Services.”  

Scale and Scope of Studies Covered Under this Announcement

This FOA is intended to support trials that are statistically powered to provide a definitive answer regarding the study intervention’s effectiveness in comparison to usual care practices or alternative intervention/services approaches.  The study should also be designed to address hypotheses regarding predictors and moderators of effectiveness and questions regarding the action of mediators and mechanisms that underlie clinical benefit.

Please see the NIMH Clinical Trial web page for FOAs covering other stages of intervention research.

While this FOA provides support for fully-powered effectiveness studies via the R01 grant mechanism, accrual of participants and data collection at multiple sites via subcontracts is permissible, with appropriate provisions for cross-site coordination and quality control.  Such a study with multiple sites through subcontracts is strongly encouraged to use a centralized IRB.  Applicants interested in submitting multi-site effectiveness trials (e.g., to answer primary effectiveness questions and key questions regarding moderators/mechanisms, to ensure geographic and demographic diversity) are directed to RFA-MH-15-325 "Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions (Collaborative R01)".  

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
Resubmission
Revision

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 $9 million dollars across FY 2015 and FY 2016 to fund 5-10 new 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 maximum project period is 5 years; however, applicants are strongly encouraged to limit their proposed project period to 3-4 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.

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:

NIMHClinicalTrials@mail.nih.gov

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.  

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.

Facilities and Other Resources: The description of the resources and environment should address how the study utilizes existing infrastructure (e.g., CTSAs, practice-based research networks, electronic medical records, administrative data bases, patient registries) or utilizes other available resources to increase the efficiency of participant recruitment and data collection or provide a justification in the event that such efficiencies cannot be incorporated. 

Other Attachments: Applicants should upload a single attachment that includes the following information relevant to the proposed clinical trial.  It is recommended that this attachment include no more than 4 pages.  Applicants should use the headers below in their description.

I.  Participant Recruitment and Retention Procedures:  Applications must provide a clear description of:

II. Milestones and Timeline:  Applications must provide a clear description of:

SF424(R&R) Senior/Key Person Profile

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

As appropriate, Senior/Key Personnel should demonstrate their experience and expertise at collaborating with community practice partners/providers, consumers, and relevant policy makers to conduct effectiveness studies. 

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:

Research Strategy: The Research Strategy should include the following information.

Significance:

Innovation:

Approach:

Protections of Human Subjects: Describe key features of a safety monitoring plan including plans for efficient IRB review and approval including the use of centralized IRB models when multiple clinical sites are planned.

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:

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.

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.

Use of Common Data Elements in NIH-funded Research

NIH encourages the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies.  CDEs are data elements that have been identified and defined for use in multiple data sets across different studies.  Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.  NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository).  NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection.  The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.  Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

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 justify the practical impact of the intervention or service approach in terms of the estimated hypothesized effect size (in terms of key outcomes, such as clinical benefit, safety/tolerability, value and efficiency, or scalability), compared with already available approaches?

If the approach is successful, is it scalable and could it be disseminated into practice given typically available resources (e.g., trained, skilled providers), typical service structures (including health care financing), and typical service use patterns?

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? 

As appropriate, does the trial involve collaborations and/or input from community practice partners/providers, consumers, and relevant policy makers in a manner that informs the research and helps to ensure the results will have utility?

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? 

Does the design/research plan include innovative elements (e.g., adaptive sequential randomization, equipoise stratification), as appropriate, that enhance its sensitivity and potential for information?

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? 

Is the study designed to explicitly address whether the intervention engages the mechanism that is presumed to underlie the intervention effects (the mechanism that accounts for changes in clinical/ functional outcomes, changes in provider behavior, etc.)?  Does the application provide justification for the plan for assessing intervention mechanisms in terms of the appropriateness and feasibility of the measures?  Is the study sufficiently powered to examine mediators of intervention effects? 

When appropriate, for studies that involve preventive or therapeutic interventions, does the study take into account RDoC or RDoC-like constructs when defining the subject eligibility (inclusion), intervention targets or mechanisms, and outcomes, as feasible in the effectiveness setting?

Does the application include provisions for the assessment and monitoring of the fidelity of intervention delivery via procedures that are feasible and valid for use in community practice settings? 

Are proposed outcome measures validated and generally accepted by the field; are stakeholder-relevant outcomes included, as appropriate (e.g., functioning, health services use)?

Are the trial design and description of the research protocol consistent with CONSORT guidelines (http://www.consort-statement.org/), as appropriate?

Will the trial contribute to advancing the personalization of mental health care?  Does it include collection of clinical and biological variables (e.g., blood for genetic analysis, other potential biomarkers), as appropriate, that might be used to inform or test algorithms for more prescriptive approaches?  Will the study have either adequate statistical power to test for moderators or the potential to contribute information to larger databases for future use?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion 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?   

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.

Milestones and Timeline

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessments?  Is the project timeline feasible and well justified?  Does the project incorporate efficiencies and utilize existing resources (e.g. CTSAs, practice-based research networks, electronic medical records, administrative data bases, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? 

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 human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. 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

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

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.

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  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.

Given the resources necessary to launch and conduct large-scale trials in community/practice settings, the award and continuation of funding are subject to milestones to be specified in the notice of grant award according to NIMH policies regarding recruitment and retention of research participants.  The Terms and Conditions for the award for such clinical trials will include overall recruitment milestones expected to be met by the study at specific time periods, accrual goals for women and minorities (as appropriate), and any other identified requirements for completion of the approved research.  As with any award, continuation, even during the period recommended for support, is conditional upon satisfactory progress. If, at any time, recruitment falls significantly below the projected milestones for recruitment, the NIMH will consider ending support and negotiating a phase-out of the award. The NIMH retains the option to obtain periodic external peer review of progress.

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. 

Recruitment Reporting and Trial Registration

NIMH requires reporting of recruitment milestones for participants in clinical trials as noted at http://grants.nih.gov/grants/guide/notice-files/NOT-MH-05-013.html.  While trials in response to this FOA may not seek 150 subjects or more (the level at which this reporting has been required), we expect reporting for all trials, even those with less than 150 subjects.  

The NIMH expects the registration and results reporting for all NIMH-supported clinical trials in ClinicalTrials.gov, regardless of whether or not they are subject to FDAAA (see http://grants.nih.gov/ClinicalTrials_fdaaa/at-a-glance.htm).  We plan to include language regarding this expectation in the notice of grant award.

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 CenterTelephone: 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)

For Studies involving therapeutic and preventive interventions:

Joel Sherrill, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-2477
Email: jsherril@mail.nih.gov

For Studies involving services interventions:

Denise Juliano-Bult, M.S.W.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1638
Email: djuliano@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 (NIMH)
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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