Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)
Department of Veteran's Affairs (VA) (http://www.research.va.gov/)

Components of Participating Organizations
National Institute of Mental Health (NIMH) (http://www.nimh.nih.gov)
Clinical Science Research & Development Service (CSR&D/VA) (http://www.research.va.gov/programs/csrd/)

Title:  Clinical Pharmacotherapy for PTSD: Single and Collaborative Studies (R34)

Announcement Type
New

Request for Applications (RFA) Number: RFA-MH-09-090

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four (4) weeks prior to the grant submission date. See Section IV.

Catalog of Federal Domestic Assistance Number(s)
93.242

Key Dates
Release/Posted Date: October 20, 2008
Opening Date:  December 15, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s):  December 14, 2008
NOTE: On-time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization).Application Due Date(s):  January 14, 2009
Peer Review Date(s):  May 2009
Council Review Date(s):  October 2009
Earliest Anticipated Start Date(s):  September 2009
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date:  January 15, 2009

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives


Section II. Award Information

1. Mechanism of Support

2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other-Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information

2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing   
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements and Information

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices

2. Administrative and National Policy Requirements
3. Reporting

Section VII. Agency Contacts
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

This Funding Opportunity Announcement (FOA) is intended to stimulate research grant applications focused on pharmacological treatments for PTSD. Medications along a continuum of development and testing (i.e., exploratory compounds ready for human testing, medications used in other areas of medicine and thought to be as useful for a new indication (PTSD), and psychiatric medications currently used off-label to treat PTSD), are appropriate as the focus of a research grant application in response to this FOA.  The sponsoring agencies seek to advance PTSD pharmacotherapy research by providing resources to better understand feasibility, tolerability, acceptance, safety, and in some instances, possible efficacy and risk/benefit ratios pertaining to symptoms and symptom severity, side effects, and treatment gains in functioning associated with available and novel medications. The sponsoring agencies anticipate the results of such studies will help identify potential medications suitable for larger scale efficacy, effectiveness and services research studies.

Accordingly, this FOA encourages two types of research grant applications.

1.  Single site R34 applications for studies to evaluate feasibility, tolerability, acceptability and preliminary safety of novel treatments and available/off-label treatments where rigorous RCT data do not exist.  The results would provide preliminary data useful for larger-scale efficacy or effectiveness studies.  In this context, applications might reasonably propose to work out the details of the experimental protocol, including the assessment protocol, the experimental intervention protocol (e.g., dosing, titration, wash out), and the comparison intervention protocol, if appropriate, examining feasibility of recruiting patients into the study conditions (various study arms), and developing supportive materials and resources.  In this type of project, applicants should incorporate relevant outcome measures but generally should not propose definitive tests of intervention outcomes (response rates, effect size), and should aim to accomplish developmental work that would enhance the probability of success in a larger trial.

2.  Collaborative R34 applications may be appropriate for evaluating feasibility, tolerability, acceptability and preliminary safety but also, depending on the stage of development and testing of a medication, to develop preliminary estimates of intervention parameters (e.g., effect size, attrition rates, response rates, side effects, adverse events) useful for larger-scale (efficacy or effectiveness) intervention and services research studies.  However, applicants proposing such projects should carefully address sample size considerations, sample characteristics/co morbidity issues and the likely meaningfulness, from a clinical perspective of anticipated outcomes.  Variability (instability) in small trial effect size estimates are likely to be considered problematic for projecting effect sizes for larger studies that are likely to involve greater heterogeneity in the sample. 

Applicants should be cautious in reporting and discussing effect sizes, including information about respective confidence intervals and the likelihood of clinical significance of effects.  This collaborative approach may be very helpful for applicants proposing to estimate intervention outcome parameters and employing broad inclusion and few exclusion criteria (where exclusion is based largely on concerns for participants' safety) and for overcoming challenges associated with recruitment, sample diversity (e.g., age, gender, ethnic minority status, and co morbidity) and other important dimensions to increase sample representativeness and potential generalizability.

It should be apparent that these two different types of study mechanisms (single- and multiple-site R34 applications) are intended to allow for studies of medications along a continuum of development.  The single-site application is generally concerned with exploratory (novel) medications supported by a compelling translational theory that focuses on new molecular targets or putative brain pathways implicated in PTSD and which are ready for testing in PTSD patients and existing medications with suggestive efficacy data but where solid RCT data are absent.  In this type of investigation, the main focus is likely to be single site, rigorous studies designed to establish feasibility, tolerability, acceptability and/or preliminary safety and to work out the details of the experimental protocol.

The multi-site application is generally concerned with currently used medications approved for other conditions.  In this case, there should be some preliminary data (e.g., limited but encouraging data from open trials, case reports) and good reason to believe the medication may be effective for PTSD (off label). Where there are existing data suggesting clinically meaningful effects, efforts to update and expand the strength of these prior scientific observations or experiments by generating well controlled preliminary data on effect sizes, attrition rates, response rates among typical PTSD patients may be useful for planning larger scale evaluation (efficacy and effectiveness).  Off label medication use will require investigators to consult with FDA for guidance as to whether an Investigational New Drug (IND) application is needed.

Depending on the stage of medication development and testing and the goals of any particular application, applicants should choose primary and other outcome measures of clinical and functional relevance.  It will be important for early stage trials to carefully consider outcome measures that will be informative for future trials, including symptom based approaches and diagnostic status but also indices of functioning.  Indices of change in symptom domains and severity, co morbid conditions (e.g., depression, substance use/abuse), cognitive, occupational, family, and social functioning, emotional and behavioral regulation are clearly relevant.  Exploratory analyses might focus on testing mediation or moderation to determine a treatment’s effects across subpopulations, with an eye toward identifying intermediate or endophenotypes of PTSD.

Additional Guidance

Potential applicants to the FOA are strongly encouraged to review the results of a January 2008 meeting organized by the U.S. Department of Veterans Affairs (VA), the National Institute of Mental Health (NIMH), and offices of the Department of Defense (DoD) (Office of the Secretary of Defense for Health Affairs, Defense Center of Excellence, and Congressionally Mandated Research Program) to identify and address major challenges in PTSD clinical research and trials (Advancing Research Standards for PTSD Interventions: Suggested Approaches for Designing and Evaluating Clinical Trials”) http://www.research.va.gov/programs/csrd/ptsd-standards.pdf.

On January 22 and 23, 2008, the VA, NIMH, and DoD convened a group of scientific experts and research administrators to develop approaches for overcoming challenges in conducting rigorous interventional research in persons with PTSD.  Experts were asked to consider issues raised by the Institute of Medicine (IOM) report titled “Treatment of PTSD: An Assessment of the Evidence” (2008) and to address specific questions related to clinical trial design and analysis; the selection, use, and interpretation of measures designed to assess PTSD; and trial implementation.

At the 2008 meeting, discussions centered on clinical trial design and analysis, PTSD measurement, and trial implementation.  Suggested approaches focus on approaches to aligning study design and appropriate endpoints with study objectives, adherence to study protocol, inclusion criteria for study participants, appropriate selection of control groups, handling incomplete data in study results, applying prespecified strategies for addressing missing data, the use of self-report measures, and subject reimbursement.  Many of the suggested approaches may be applicable to applications developed in response to the FOA.

Significance/Background

The effects of experiencing traumatic stress, either as a victim or witness, are a major public health problem in the United States, with consequences of potentially severe psychological, behavioral, medical, and social dysfunction, including Post Traumatic Stress Disorder (PTSD).  There is also a growing awareness that posttraumatic psychopathology is linked to other serious health conditions (e.g., hypertension, smoking, heart disease, substance use and abuse).

Trauma affects a large number of people.  Self-report surveys suggest that millions of children are physically abused each year, and hundreds of thousands are victims of sexual abuse (National Clearinghouse on Child Abuse and Neglect Information) (http://www.childwelfare.gov/).  Each year many children and adolescents sustain injuries from violence, they lose friends or family members, or they are adversely affected by witnessing a violent or catastrophic event. 

Annually, approximately 500,000 persons report rapes and sexual assaults.  Other forms of physical assault are widespread (Department of Justice http://www.usdoj.gov/).

Data from the National Co morbidity Survey (Kessler et al. 1995) indicate that many Americans will experience one or more major traumatic events (e.g., physical attack, house fire, rape, witness to death) in their lifetime.

A recent review of disaster studies highlights that natural disasters, technological disasters, and mass violence, including terrorism in the U.S., other developed countries, and in developing countries, can have severe impacts on those affected (Norris et al, 2001 (updated 2005).  Mental health outcome data regarding the U.S. terrorist attacks of September 2001 underscore the capacity of man-made disasters to cause clinically significant, enduring and episodic psychobiological disorders, emotional distress, and impairment.  Data from studies initiated after the 2005 U.S. Gulf Coast disaster indicate that a substantial percentage of survivors were and are struggling with new and exacerbated disorders, including PTSD.

Data from the U.S. Department of Defense (DOD) reveals that hundreds of thousands of recently deployed service members report extreme and intense traumatic experiences and have been identified as in need of mental health services. Prior research has demonstrated that mental disorders are a leading source of occupational morbidity and reason for transition out of military service for active-duty military personnel, with as many as one third of enlisted soldiers having difficulty in their first term of enlistment, most often due to mental, psychosocial, and behavioral problems.

Data from the U.S. Department of Veterans Affairs (VA) reveals that more than 240,000 veterans of the Iraq and Afghanistan conflicts have become eligible for VA benefits and that 20 percent of these new veterans have received health care at a VA facility since returning home. Possible mental disorders have been reported in 26 percent and the most common diagnoses were adjustment disorders, among them PTSD.  Thus, effective PTSD treatment is a priority for the VA healthcare system for the newest generation of veterans as well as those with chronic cases of PTSD from prior deployments such as Vietnam.

The World Health Organization report on Violence and Health (2000) highlights the heavy cost of violence and trauma in health effects, in both financial losses from injury and decreased productivity as well as psychological and behavioral problems that may extend to permanent physical and mental disability.

In making funding decisions, the sponsoring agencies intend to take into account and coordinate where possible with other relevant clinical trial initiatives underway.  For example, DOD offices (e.g., CDMRP) have made substantial investments in psychological health research in recent years.  Consultation and coordination with such programs is intended to maximize efficiency in infrastructure, ensure scientific attention to important knowledge gaps, and maximize complimentarity of research programs.

Post-Traumatic Stress Disorder (PTSD)

The mental health sequelae of exposure to traumatically stressful events, including Posttraumatic Stress Disorder (PTSD), have been the focus of research for several decades. PTSD, recognized as a leading organizing construct for many posttraumatic adjustment difficulties, is a psychiatric disorder that can occur following the experience or witnessing of life-threatening events such as military combat, natural disasters, terrorist incidents, serious accidents, or violent personal assaults.

PTSD is a potentially chronic and debilitating disorder with lifetime prevalence rates ranging from 3% to 40% depending on the population of study (i.e., 3-8% in community samples, 10-30% in disaster samples, 15-27% in war/combat veteran samples, 20-40% in sexual assault samples).  PTSD has a clear impact on health, health care service utilization, overall functioning and quality of life. Given the prevalence of PTSD and its associated costs to society, identifying efficient and effective treatments is critical.

People who suffer from PTSD often relive the experience through nightmares and disturbing intrusive thoughts, have difficulty sleeping, feel detached or estranged, and struggle with irritability and aggression problems.  PTSD is often associated with impairment in social, educational, occupational and family functioning and when symptoms are severe, the disorder can significantly impair the person's daily life. Problems with posttraumatic adjustment are complicated by the fact that they are frequently accompanied by disorders such as depression, substance abuse, problems of memory and cognition, and other problems of physical and mental health.

The past decade has witnessed considerable progress in expanding our knowledge of the neurobiological underpinnings of PTSD and in refining effective clinical interventions for PTSD.  Several effective treatments for PTSD have been reported; evidence from well-controlled trials with a variety of PTSD patients indicates that several forms of psychotherapy, including cognitive behavioral and cognitive processing therapies, are effective. Accordingly, researchers are actively studying how to identify the most helpful components, timing, and “dose” of these and other treatments as well as how to make them accessible, practical, and transportable so that patients and providers in diverse contexts can benefit from them.

With regard to pharmacotherapy, the U.S. Food and Drug Administration (FDA) has approved two medications for treating PTSD in adults; sertraline and paroxetine, both selective serotonin reuptake inhibitors. While data support the use of these medications, not everyone treated pharmacologically improves. Moreover, there appears to be poor correspondence between the PTSD treatment evidence-base and practices of clinicians. Data from limited but important surveys of treating clinicians reveals that physicians’ preferred treatment of symptomatic persons is pharmacological treatment. The use of medications that have limited data to support their efficacy and with undesirable side effect profiles identifies an important area for additional research.  The gap between evidence and practice is particularly important in the context of community-based health care settings where disaster victims, accident survivors, returning veterans, and others trauma survivors may seek and receive care.

Among the most promising new approaches for understanding PTSD and, in turn, improving clinical treatments, lies in research that is mapping the neural circuitry involved in response to danger.  Extreme environmental forces are clearly capable of changing the function and structure of the brain and these changes can now be quantified using imaging techniques with high resolution.  An exciting area receiving renewed attention focuses on fear conditioning models of PTSD.  These compelling models implicate the central importance of fear conditioning and the role of extinction learning in the etiology and maintenance of PTSD.  Emerging data from animal and human studies are pointing toward improved, more precise fear extinction paradigms.  The ability to target specific brain regions implicated in acquiring conditioned responses and extinction-learning (challenging the conditioned fear response) may provide improved mechanisms or targets for PTSD treatment.

Accumulating knowledge about basic brain processes and complex gene and environmental interactions offer the promise for predictive, personalized, and preventative approaches to intervention and rehabilitation.  While pursuing these leads, NIMH and the VA recognize the critical needs of those patients/veterans who are suffering today and thus appreciate the importance of supporting clinical trials of established and new therapeutic approaches to assist victims and survivors of trauma.

This FOA is responsive to the NIMH Strategic plan (http://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml) and in particular, Strategic Objective 3, to Develop New and Better Interventions for Mental Disorders that Incorporate the Diverse Needs and Circumstances of People with Mental Illness.  This FOA is also responsive to a 2006 VA, NIMH, and DOD research agenda meeting Mapping the Landscape of Deployment Related Adjustment and Mental Disorders (http://www.nimh.nih.gov/research-funding/scientific-meetings/2006/mapping-the-landscape-of-deployment-related-adjustment-and-mental-disorders.pdf), which identified the critical need for multiple small scale treatment studies that would examine whether interventions improve outcomes and identify promising interventions that require larger scale testing.  Similarly, a 2008 Institute of Medicine report “Treatment of PTSD: An Assessment of The Evidence,” (http://www.iom.edu/CMS/3793/39330/47389.aspx) called for rigorous research on safety and efficacy of current and new treatments and identifies several promising but poorly studied medications.

Reports and reviews conducted by the IOM, NIMH, VA, DOD, as well as scholarly reviews of the literature and various professional practice guidelines reveal data from small scale and open trials, case studies and clinical reports suggesting that several classes of medications may be helpful – depending on the patient population, for loss of diagnosis/remission, relief from specific symptoms/ dimensions of PTSD, and improved functioning.

The current and anticipated demand for effective PTSD treatment is a driving force for rigorous evaluations of currently used but understudied medications.  While it is responsible to test medications currently in use, including those used to treat conditions whose symptoms overlap with PTSD, as we understand the complexity of PTSD better –how it unfolds at a biological level – it’s reasonable to ask if observed abnormalities or differences can be targeted to improve outcome.  In recognition that the drug discovery process is lengthy, it is appropriate to emphasize that findings on the neurobiology of PTSD should be leading to exploratory studies of new medications that can be tested in PTSD patients. Based on the state of the science, this FOA seeks to encourage exploration of additional medications that might be administered in the immediate aftermath of a traumatic event; medications that might be used over time to target symptom domains not adequately addressed by current first line treatments; and still others that might be used to augment psychotherapy. The sponsoring agencies recognize that the development of PTSD-specific drugs may require additional understanding and synthesis of the neurobiology of PTSD.  However, this FOA encourages innovation, where there are plausible hypotheses, based on current knowledge.

Given the current state of science and practice regarding the treatment, and prevention of PTSD, the sponsoring agencies are encouraging applications on topics including, but not limited to:

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This FOA will use the NIMH R34 award mechanism and includes the option of collaborative R34 applications where two sites will collaborate/participate.  The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

Where there are collaborative R34 applications (maximum of two), it is expected that each application will be coordinated and integrated with the other as each application will contribute an essential component to the overall study.  In most instances, it is anticipated that the same protocol will be submitted by both sites. However, there are likely to be elements unique to one site (e.g. data coordination, fidelity assessment, statistical analyses). 

This FOA uses “Just-in-Time” information concepts (see SF424 (R&R) Application Guide). It also uses the modular as well as the non-modular budget formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, a U.S. organization submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs) must use the PHS398 Modular Budget component.

U.S. applicants requesting more than $250,000 in annual direct costs and all Foreign applicants must complete and submit budget requests using the Research & Related Budget component.

2. Funds Available

The NIMH intends to commit approximately $2,000,000 in FY 2009 to fund 5 to 8 applications in response to this FOA. The VA Office of Research and Development, depending upon availability of funds, estimates committing up to $2,000,000 for this initiative.  The total project period for an application submitted in response to this FOA may not exceed three years.  R34 applications are limited to $450,000 per application for direct costs over an R34 three year period, with no more than $225,000 per application in direct costs allowed in any single year.  In the case of collaborative R34 applications (limit of two), direct costs are also limited to $450,000 for each application over an R34 3-year period, with no more than $225,000 per application in direct costs allowed in any single year.  Applications (single or collaborative) may request one, two, or three years of support.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds.

Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation. See NOT-OD-05-004.

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

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

1.B. Eligible Individuals

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her organization/VA facility research office 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.  Individuals applying for VA funding must meet all VA eligibility criteria.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions). All PD/PIs for VA consideration must have approved eligibility.

The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering the multiple PD/PI option, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Applicants are not permitted to submit a resubmission application in response to this FOA.

Renewal applications are not permitted.  However, it is anticipated that grantees funded through this program may seek continuing support for their projects through the R01 or other funding mechanisms.

Applicants may submit more than one application, provided each application is scientifically distinct.

IND requirements: Off label medication use will require investigators to consult with FDA for guidance as to whether an Investigational New Drug (IND) application is needed. In circumstances where an IND is required, applicants should be aware that funding to any successful application will be restricted until IND approval has been obtained from the FDA.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH eRA Commons.

Several additional separate actions are required before an applicant can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Registered

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PDs/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo -- Telephone 301-435-0714; Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. Some fields within the SF424 (R&R) application components, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application has several components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY includes all applicable components, required and optional. A completed application in response to this FOA includes the data in the following components:

Required Components
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.)

Optional Components
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-Domestic [non-U.S.] Entities)

NIH policies concerning grants to Foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.

Applications from Foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States (U.S.) or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership plan approach for the proposed project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” [Section 14 of the Research Plan Component in the SF424 (R&R)], must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component.  All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form.  See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only.  Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: December 14, 2008 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): December 14, 2008
Application Due Date(s): January 14, 2009
Peer Review Date(s): May 2009
Council Review Date(s): October 2009
Earliest Anticipated Start Date(s): September 2009

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Farris Tuma, Sc.D.
Division of Adult Translational Research and Treatment Development
National Institute of Mental Health
6001 Executive Boulevard, Room 7111, MSC 9632
Bethesda, Maryland 20892
Telephone: 301-443-3648
Email: ftuma@mail.nih.gov

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp  and follow Steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the NIMH Referral Office by email (NIMHReferral@mail.nih.gov) when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the due date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday – Friday, excluding Federal holidays) to view the application image to determine if any further action is necessary.

Upon receipt, applications will be evaluated for completeness by the CSR and responsiveness by the IC. Incomplete and non-responsive applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons acknowledgments. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

Note: Since email can be unreliable, it is the responsibility of the applicant to check periodically on the application status in the Commons.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an “Introduction” describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

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. NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see the NIH Grants Policy Statement).

6. Other Submission Requirements and Information

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD(s)/PI(s) to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component.

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

Although each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts, and with the following additional requirements:

Special Instructions for Optional Collaborative R34 Applications

This FOA offers the option of linked collaborative R34 applications when two sites are collaborating/participating.  If linked collaborative applications are being submitted multiple PIs are allowed on any single application.  Because collaborative R34 applications already support a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply.  PIs from each linked application should NOT be designated as multiple PIs on both of the applications of a collaborative set.

Application Title (required format):  To allow NIH to identify two applications as a related set of Collaborative R34s, the titles to each R34 of a set must have the following format:  a “1/N” indicator + Identical title (e.g., “1/2-Multisite Study of Drug A for PTSD”, where the 1/2 means this is site 1 of 2 sites in the set.  The other site will be labeled 2/2) Titles may not exceed 80 characters in length, including the tag, e.g., 1/2, at the beginning of the title.

PHS398 Cover Letter (required):  The PHS398 Cover Letter is one pdf file only.  The following Collaborative information is required in the Cover Letter:  a listing of both applications that are a part of the set of Collaborative R34s being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., “1/2”), and 3) the Applicant Institution.  Both sites should submit an identical listing.

Research & Related Other Project Information Component (required):  A list of the two collaborative applications as described for the PHS398 Cover Letter must also be included in Item 11, “Other Attachments,” of the Research & Related Other Project Information component.  The information provided in this attachment MUST include a listing of all the applications that are the set of Collaborative R34s being submitted, including for each: 1) the PD/PI(s) names, 2) the Title (including the tag, e.g., “1/2”), and 3) the Applicant Institution.  Both sites should submit an identical listing.  This file should begin with a heading called “Collaborative Applications”.  When saving the file, please name the file Collaborative_Applications as well, to ensure this section of the application is bookmarked appropriately.

PHS398 Research Plan Component Sections:  The application from each site must contain an identical OVERVIEW that is no longer than 2 pages and is placed prior to the Specific Aims, but included with the Specific Aims attachment. With this additional 2 page Overview, a total of 27 pages is allowed for the research plan (Items 2-5). The overview should provide an overall rationale for applying as a collaborative study; the role of each site; the approach to project management; and elements unique to any of the sites.

The application from each site must contain an identical PHS398 RESEARCH PLAN - Section 2, Items 2-5. The Research Plan must describe those aspects of the project that are common to all sites of the collaboration  Investigators should use this section to describe the research procedures or protocol, the study population from which samples are drawn, resources, data analyses, and any other characteristics that support each site’s importance to the overall project. All variations in the research plan between sites, no matter how minor, should be highlighted in a subsection of Section 2, Item 5, with the heading "ELEMENTS UNIQUE TO THIS SITE." In this subsection PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc.

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

Any site that contracts out some portions of this work should list this fact under "ELEMENTS UNIQUE TO EACH SITE," and provide a full description of the nature, purpose and oversight of this contractual arrangement.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide (See http://grants.nih.gov/grants/funding/424/index.htm).

Do not use the Appendix to circumvent the page limitations of the Research Plan component. An application that does not comply with the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value and further the advancement of the research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.)

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact (see Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.)

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources or state appropriate reasons why such sharing is restricted or not possible (see Sharing Model Organisms Policy, and NOT-OD-04-042.)

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (e.g., blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Foreign Applications (Non-Domestic [non-U.S.] Entities)

Indicate how the proposed project has specific relevance to the mission and objectives of the NIH/IC and has the potential for significantly advancing the health sciences in the United States.

Section V. Application Review Information


1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to this FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIMH and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

Applications submitted in response to this FOA will compete for available funds with all other recommended applications submitted in response to this FOA. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, and weighted as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a meritorious priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important issue relevant to clinical pharmacotherapy for PTSD?  If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that relate to clinical pharmacotherapy for PTSD?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and aligned with the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? For applications designating multiple PDs/PIs, is the leadership approach, including the designated roles and responsibilities, governance, and organizational structure, consistent with and justified by the aims of the project and the expertise of each of the PDs/PIs? Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?  For collaborative R34 applications, is each application justified in terms of the use of collaborative R34 applications outlined in the research objectives of this FOA? Is each application coordinated and integrated with the other and are any elements unique to one site (e.g. data coordination, fidelity assessment, statistical analyses) adequately described?

Innovation:  Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?  

Investigators: Are the PD(s)/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Do(es) the PD(s)/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)?  

Environment:  Do(es) the scientific environment(s) in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?  

In addition to the above review criteria, the following criteria will be addressed and considered in the determination of scientific merit and the rating.

Is the project likely to advance PTSD pharmacotherapy research by evaluating feasibility, tolerability, acceptance, dosing, safety, and/or possible efficacy and risk/benefit ratios associated with available and novel medications?

Will the project help to expand (or narrow) the range of potential medications suitable for larger scale efficacy, effectiveness and services research studies?

In the case of collaborative R34 applications:  are sufficient and feasible mechanisms in place to ensure collaboration across sites to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results?  Are there adequate plans for shared decision making among PIs with regard to personnel, clinical decisions, changes in study protocol, and authorship?

2.A. Additional Review Criteria

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the rating:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed.  See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R)
 
Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed.

2.C. Resource Sharing Plan(s)

When relevant, reviewers will be instructed to comment on the reasonableness of the following Resource Sharing Plans, or the rationale for not sharing the following types of resources. However, reviewers will not factor the proposed resource sharing plan(s) into the determination of scientific merit or priority score, unless noted otherwise in the FOA. Program staff within the IC will be responsible for monitoring the resource sharing.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

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 NIH eRA Commons

If the application is under consideration for funding, NIH and/or the VA will request "just-in-time" information from the applicant.  For details, NIH applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

For NIH awardees, a  formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official. For VA awardees, the Office of Research and Development will issue a contract to be signed by the Principal Investigator; a final approval letter will be issued to the VA Medical Center once all administrative issues are resolved.

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. See Section IV.5., “Funding Restrictions.”

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.

3. Reporting

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 Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research (program), peer review, and financial or grants management issues:

1. Scientific/Research Contact(s):

Farris Tuma, Sc.D.
Division of Adult Translational Research and Treatment Development
National Institute of Mental Health
6001 Executive Boulevard, Room 7111, MSC 9632
Bethesda, Maryland 20892
Telephone: 301-443-3648
Email: ftuma@mail.nih.gov

Terri Gleason, Ph.D.
Clinical/Biomedical R&D Services (121E)
Department of Veterans Affairs
810 Vermont Avenue, NW
Washington, DC 20420
Telephone: (202) 254-0498
FAX: (202) 254-0521
Email: thereas.gleason@hq.med.va.gov

2. Peer Review Contact(s):

David Armstrong, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9606
Bethesda, MD 20892-9606
Telephone: (301) 443-3534
FAX:  (301) 443-4720
Email: armstrda@mail.nih.gov

3. Financial/Grants Management Contact(s):

Rita Sisco
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Telephone: (301) 443-2805
FAX: (301) 480-1956
Email: siscor@mail.nih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing). Investigators should seek guidance from their institutions, on issues related to institutional policies and local institutional review board (IRB) rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are: (1) first produced in a project that is supported in whole or in part with Federal funds; and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the SF424 (R&R) application; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov/). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH must submit or have submitted for them to the National Library of Medicine’s PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic version of their final, peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html). For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (HHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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