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

Innovative Pilot Studies of Novel Mechanism of Action Compounds for Treating Psychiatric Disorders (U01)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

New

Related Notices

Funding Opportunity Announcement (FOA) Number

PAR-11-316

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.242

FOA Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to encourage cooperative agreement grant applications to support experimental medicine-based first in human (FIH) and proof of concept (POC) studies of new mechanism of action, IND-ready candidate medications to treat mental disorders. The objective of the FOA is to accelerate the development of innovative pharmacological treatments through support of early phase human clinical testing.  FIH pharmacology studies should assess target engagement, pharmacological effects, safety, and tolerability of novel compounds in order to build a pipeline for initial POC or efficacy trials in patients. POC studies of novel compounds should use pharmacologically based dosing, with assessment of target engagement and evaluation of the impact of compounds on clinically relevant physiological systems as well as clinical indicators of effect. The overall objective is to facilitate rapid collection of data to "de-risk" novel mechanism of action or combination treatments and to attract private funding for further clinical and commercial development of candidate medications. Partnerships between academia and industry are strongly encouraged.

Key Dates
Posted Date

August 18, 2011

Open Date (Earliest Submission Date)

September 5, 2011

Letter of Intent Due Date

30 days prior to the application due date(s).

Application Due Date(s)

Standard dates apply , by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Standard dates apply

Scientific Merit Review

Standard dates apply

Advisory Council Review

Standard dates apply

Earliest Start Date(s)

Standard dates apply

Expiration Date

(New Date January 8, 2012 per NOT-MH-12-002), Original Date, September 8, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (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

Although many promising novel therapeutic targets for treating mental disorders have been discovered in recent years, the translation into effective treatments has been unacceptably slow. For those compounds advancing to clinical testing, the success rate of new drug approvals for mental disorders has been poor, with candidates often failing in late stage clinical trials after a significant investment. In too many cases, the reasons for trial failures remain unclear but might include, for example, patient heterogeneity, unfavorable drug characteristics (toxicity, poor target engagement, sub-optimal pharmacokinetic/pharmacodynamic parameters), or inappropriate biological target for the disorder. This situation has contributed to the decrease in pharma’s investment in psychiatric drug development and enlarged the “valley of death” for drug development (see SM Paul et al, How to improve R&D productivity: the pharmaceutical industry's grand challenge, Nature Rev Drug Discovery 9:203-214, 2010). 

The NIMH and NIH provide funding support and research resources to facilitate drug discovery/development of novel medications for mental disorders through several avenues, http://www.nimh.nih.gov/research-funding/therapeutics/index.shtml.  A recently published report of the National Advisory Mental Health Council’s Workgroup, entitled, From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illness evaluated NIMH’s portfolio, and funding opportunities/resources for drug discovery/development in light of the current trend of pharmaceutical companies and venture capital to decrease their investments in clinical trials for CNS disorders.  A main recommendation identified by the workgroup was for NIMH to invest in early stage clinical trials of novel compounds which act on novel molecular pathways (receptors, enzymes, second messengers, etc.) that are not targeted with currently available psychiatric drugs, and that have a strong justification as a novel mechanism for the treatment of psychiatric disorders.  In addition, a recommendation was made that such trials include biological/behavioral measures to assess target engagement in brain and evaluate the compound’s mechanism of action in humans. The incorporation of these additional measures into standard trials is intended to provide very early signs of potential failure or success of the compound and help inform whether further later stage trials should be considered. This FOA is an attempt to address these gap areas.

Specific Areas of Research Interest

The intent of this FOA is to advance the clinical development of new mechanism of action candidate medications to treat mental disorders through first in human (FIH) and proof of concept (POC) studies using experimental medicine approaches. It is expected that successful applications will likely include multi-disciplinary teams of scientists with appropriate expertise to further the clinical development and experimental evaluation of novel compounds. Scientists from both academia and pharmaceutical industry are encouraged to participate; scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects.

Research Scope

The objective of this FOA is to support innovative early phase clinical testing of chemical entities acting at novel molecular or clinical targets implicated in the pathophysiology of mental disorders.

FIH pharmacology studies should assess compound:  1) safety and tolerability, 2) target engagement, and 3) pharmacological effects on physiological systems (see AF Cohen, Developing drug prototypes:  pharmacology replaces safety and tolerability? Nature Reviews Drug Discovery 9, 856-865, 2010). These data are expected to be sufficient for the determination of optimal clinical dose range in POC and efficacy trials.

POC studies will assess the clinical efficacy signal of novel compounds using pharmacologically based dosing, with validation of target engagement in brain, and will include biological measures of impact of the compound on clinically relevant physiological systems to assess the link between hypothesized drug mechanism/target and clinical effect (see HD Soares, The use of mechanistic biomarkers for evaluating investigational CNS compounds in early drug development.  Current Opinion in Investigational Drugs 11:795-801, 2010).  POC studies are not expected to be sufficiently powered to test efficacy but rather will provide sufficient data for projects to be "de-risked" to attract private funding to support further clinical development of promising compounds.

Overall, these studies will: 1) accelerate the development of new therapeutics for mental disorders by building a pipeline of promising therapeutic candidates that have been sufficiently de-risked, 2) facilitate the validation of biological targets for therapeutic development, and 3) provide data assessing the relationship between clinical measures and biological indicators (mechanistic biomarkers) of effect. 

It is anticipated that the interaction of academic and non-profit research institutions with NIH and pharmaceutical industry will facilitate timely clinical evaluation and development of novel therapeutics. Applicants should outline proposed plans for further development of promising clinical candidates that are tested in the FIH and/or POC studies through this program.

Compounds to be tested should be IND ready.  The testing of established or well-studied agents for the treatment of mental disorders is not appropriate for this FOA. Only FIH and clinical POC studies are appropriate for this announcement. Projects proposing such FIH or POC studies within a broader multi-project therapeutic development effort for mental disorders that includes, for example, earlier phase discovery and/or preclinical testing components are directed to the National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction UM1 and U19 FOAs.

Cost-sharing, including in-kind support, is encouraged.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are not limited, but need to reflect 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 not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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/Principal Investigator (PD/PI) 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 SF 424 (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 in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the SF 424 (R&R) Application Guide.

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:

Lois Winsky, Ph.D.
6001 Executive Boulevard. Room 7185, MSC 9641
Bethesda, MD  20892-9641
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-443-5288
Email: lwinsky@mail.nih.gov

Required and Optional Components

The forms package associated with this FOA includes all applicable components, mandatory 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.

Page Limitations

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

PHS 398 Research Plan Component

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

For both FIH and POC studies, a clear description should be included of the approach for determining pharmacological dose/response relationships and target engagement of the drug candidate. For POC studies, a compelling scientific rationale for biological measures (mechanistic biomarkers) used to assess the link between hypothesized drug mechanism/target and clinical effect should be provided.

In addition, subject selection should be well justified and would ideally ensure the individuals have the abnormality in the CNS pathway being studied.  POC studies are expected to incorporate conventional diagnostic criteria in determining inclusion criteria as well as clinical rating scales to assess potential efficacy signal. However, applicants are encouraged to incorporate concepts and paradigms consistent with the NIMH RDoC approach to patient classification http://www.nimh.nih.gov/research-funding/nimh-research-domain-criteria-rdoc.shtml. Indeed, RDoc associated biological targets may be informative for generating mechanism-based hypotheses regarding biological targets contributing to therapeutic effects.

A plan should be described for decision-making regarding identification and evaluation of promising drug candidates for development.  Specifically, if the proposed research includes both FIH and POC studies in patients, specific milestones and go/no-go criteria should be described for assessing the appropriateness of progressing to POC studies.

Pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts.

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 modifications:

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.

Foreign Institutions

Foreign (non-US) 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 in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via 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.

Applicants are responsible for viewing their application 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 SF 424 (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/PIs must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(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.

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 Central Contractor Registration (CCR). 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, NIH.  Applications that are incomplete will not be reviewed.

 Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact NIH program staff at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF 424 (R&R) Application Guide.  

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115..

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/priority 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?  Will sufficient data be collected to de-risk the candidate therapeutic for further clinical development? Does the therapeutic candidate fill an important need or gap in our armamentarium of interventions for mental disorders?  Does the intervention approach hold promise for altering a symptom or domain of function (see http://www.nimh.nih.gov/research-funding/rdoc.shtml) that is commonly disrupted in mental disorders? Does the experimental compound hold promise of being utilized in clinical practice?

Investigator(s)    

Are the PD/PIs, 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?  Is there evidence of proven expertise in recruiting subjects and conducting the FIH and/or POC trial and performing pharmacological and functional measures of target engagement?   

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?  Are the therapeutic targets, mechanisms, or measures to assess target biology novel? 

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? 

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?  Is there a compelling scientific rationale for the clinical target? Is there a strong justification for the approach for determining pharmacological effects and target engagement of the drug candidate? Is the approach feasible?  Is there a compelling scientific rationale for the biological measures (mechanistic biomarker) used to assess the link between hypothesized drug mechanism/target and clinical effect?  Are subject inclusion criteria well justified and likely to show abnormality in the CNS pathway being studied?  Are the recruitment strategy and plan well justified and feasible?  Are the clinical measures appropriate?  If the application plans to include both FIH studies in normal subjects and POC studies in patients, are specific milestones and go/no-go criteria described for assessing the appropriateness of progressing to POC studies?

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?  When pharmaceutical partners are involved, are key personnel included who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts?    

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/priority 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 Human Subjects Protection and Inclusion Guidelines.

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 Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

Not Applicable.

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

For Renewals, the committee will consider the progress made in the last funding period.

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/priority score.

Applications from Foreign Organizations

Not applicable

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. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Mental Health Council l. 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, CCR 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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The PD/PI will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research, including the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The Principal Investigator will be a member of the Steering Committee.

Intramural research scientists participating as collaborators have the same rights and responsibilities as other members of the Group (see below for Participation of NIH Intramural Scientists).

The Awardee Institution and/or Research Project Leader's Institution will retain primary custody of and have primary rights to data as specified under the NIMH approved Intellectual Property Patent Rights Agreements for New Chemical Entities or the data and research resource sharing plans (described above). The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies. Timely publication of major findings by the Group members is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Project Scientist(s) interacts scientifically with the Group and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, presenting experimental findings to the Group from published sources or from relevant contract projects, participating in the design of experiments agreed to by the Group, participating in the analysis of results, and advising in management and technical performance. The Project Scientist(s) will be a member(s) of the Steering Committee. However, the total membership by NIH staff will not exceed one-third (1/3) of the membership of the Steering Committee. In all cases, the role of NIMH will be to assist and facilitate and not to direct activities.

FIH and POC studies will be reviewed by the appropriate NIH Institute's Data and Safety Monitoring Board (DSMB) to ensure the safety of participants and the validity and integrity of the data.  The study protocol(s) and consent form(s) will be reviewed by the DSMB prior to initiation of the project.  The DSMB will review study reports on a regular basis to monitor subject enrollment and retention, safety, quality of data collection, and integrity of the study. 

Additionally, an NIMH Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.

Participation of NIH Intramural Scientists. An NIH intramural scientist may not serve as the PD/PI but may participate as a collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. The Intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project. The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH Project Scientist. For applications that include NIH intramural components, the intramural resource level will be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy. http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm 

Areas of Joint Responsibility include:

A governing Steering Committee composed of the PD/PI, key personnel, NIH Project Scientist(s), and NIH Program Official will be established to assist in monitoring and developing the scientific content and direction of the program. The Steering Committee members will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings, not fewer than two per year, will be determined by the PI/PD who will be responsible for scheduling the time and place (generally at one of the performance sites) and for preparing concise proceedings or minutes (two or three pages) which will be delivered to the members of the Group within 30 days of the meeting.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Intellectual Property and Patent Rights for New Chemical Entities

Since the development of new pharmacological treatments for mental disorders is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and would be facilitated by the existence of appropriate patent coverage, it is expected that applicants provide plans to address the handling of intellectual property for new chemical entities under this FOA.

Under the earlier National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Drug or Alcohol Addiction program, successful applicants were required to supply the following confidential materials to the NIMH Program Official listed under Section VII. Agency Contacts:

1. Each applicant must provide a detailed description of the approach to be used for handling intellectual property and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents [http://grants.nih.gov/grants/intell-property.htm].

2. A formal statement of Intellectual Property among the PD/PI and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, must be signed and dated by the organizational official authorized to enter into intellectual property arrangements for each Group member and member institution. The signed agreement must be submitted prior to award to the appropriate NIMH staff at the addresses provided under Section VII. Agency Contacts.

3. Prior to the award, the PD/PI must provide a signed statement of acceptance of the participation of NIMH staff during performance of the award as outlined under "NIH Staff Responsibilities" in Section VI.2 - Cooperative Agreement Terms and Conditions of Award.

Note: Do NOT submit documents 1-3 above with the application.  However, awards will not be made until these documents are received and approved by NIMH.

Similar to the NCDDG, applicants are expected to address the three items noted above under this FOA, consistent with achieving the goals of this program.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually 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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
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

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

General questions about this FOA or about first in human studies should be directed to:

Lois Winsky, Ph.D.
National Institute of Mental Health
Telephone: 301-443-5288
Email: lwinsky@mail.nih.gov

Questions about proof of concept studies for novel therapeutics for mental disorders in adult populations should be directed to:

Mi Hillefors, M.D., Ph.D.
National Institute of Mental Health
Telephone: (301) 443-2738
Email: hillefom@mail.nih.gov

Questions about proof of concept studies for novel therapeutics mental disorders in children and adolescents should be directed to:

Margaret Grabb, Ph.D.
National Institute of Mental Health
Telephone: 301-443-3563
Email: mgrabb@mail.nih.gov

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Rebecca Claycamp, M.S., CRA
National Institute of Mental Health
Telephone: (301) 443-2811
Email: rclaycam@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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