Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH), (http://www.nih.gov)

Components of Participating Organizations
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)

Title: Research on Interventions for Anorexia Nervosa

Announcement Type
This is a reissue of RFA-MH-04-002, which was previously released November 3, 2003.

Request for Applications (RFA) Number: RFA-MH-05-009

Catalog of Federal Domestic Assistance Number(s)
93. 242

Key Dates
Release Date: January 7, 2005
Letters of Intent Receipt Date(s): February 11, 2005
Application Receipt Date(s): March 11, 2005
Peer Review Date(s): June 2005
Council Review Date(s): September 2005
Earliest Anticipated Start Date: September 30, 2005
Expiration Date: March 12, 2005

Due Dates for E.O. 12372
Not applicable

Additional Overview Content

Executive Summary

The purpose of this Request for Applications (RFA) is to evaluate intervention(s) for treatment of anorexia nervosa (AN). To accomplish this goal the National Institute of Mental Health (NIMH) will support development of a collaborative network of qualified institutions. The infrastructure created through this network will have the capacity to conduct a moderate to large-scale evaluation of promising intervention(s) for AN. It is also intended to serve as a resource for future ancillary studies.

This network for Research in Anorexia Nervosa (RIAN) will be supported under a cooperative agreement (U01) mechanism. The NIMH intends to commit approximately $1,500,000 total costs in FY 2005, to fund one network comprised of multiple new cooperative agreement awards in response to this RFA.

Applications may be submitted by any individual with the skills, knowledge, and resources necessary to carry out the proposed research. Eligible domestic and foreign institutions/organizations include for-profit or non-profit; public or private; units of State and local governments; eligible agencies of the Federal Government; and faith-based or community-based organizations. Application materials are available at http://grants.nih.gov/grants/funding/phs398/phs398.html.

Each applicant may submit one application.

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

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(s) 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 Submission and Instructions
    1. Address to Request Application Information
    2. Content and Form of Application Submission
    3. Submission Dates and Times
      A. Receipt and Review and Anticipated Start Dates
        1. Letter of Intent
      B. Sending an Application to the NIH
      C. Application Processing
    4. Intergovernmental Review
    5. Funding Restrictions
    6. Other Submission Requirements

  Section V. Application Review Information
    1. Criteria
    2. Review and Selection Process
      A. Additional Review Criteria
      B. Additional Review Considerations
      C. Sharing Research Data
      D. Sharing Research Resources
    3. Anticipated Announcement and Award Dates

  Section VI. Award Administration Information
    1. Award Notices
    2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
        1. Principal Investigator Rights and Responsibilities
        2. NIH Responsibilities
        3. Collaborative Responsibilities
        4. Arbitration Process
    3. Reporting

  Section VII. Agency Contact(s)
    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

Background

A recent NIH workshop "The Development of Research Priorities for the Treatment of Anorexia Nervosa: Overcoming Existing Barriers" (summarized at http://www.nimh.nih.gov/scientificmeetings/ansummary.cfm) was held to discuss both the serious nature of the disorder and the obstacles that hinder progress in research on AN. The essential features of AN are a refusal to maintain a normal body weight, an intense fear of gaining weight, and a significant distortion in an individual's perception of the shape or size of his or her body. AN is a rare yet often chronic disorder frequently complicated by extensive comorbidity and a high mortality rate consequent to malnutrition and/or suicide. AN often co-exists with other forms of psychopathology including depression, anxiety disorders, personality disorders and substance-use disorders and has serious medical co-morbidity.

Despite its gravity, very little is known about the effective treatment of AN. The existing literature is comprised primarily of small, brief efficacy studies marked by substantial attrition and limited follow-up. Additional information is needed regarding the most effective types of interventions, the most appropriate approaches for different age groups, and the best systems for delivery. Psychosocial and pharmacological treatments should be studied across different settings (e.g., inpatient, outpatient, day treatment) and should target both the short and long-term phases of the illness, including the prevention of relapse. Given that the overwhelming majority of participants in research have been Caucasian females, there is a need to evaluate specialized interventions strategies for ethnic minority groups and for males. Developmentally informed interventions specifically targeting youths should also be examined. Clinical observations and limited epidemiological research have also suggested that persons with AN are at greater risk for suicidal behavior and death. Improved research approaches for better assessment and management of suicidal risk among persons with this disorder are needed. Ethical issues associated with the use of certain research designs (e.g., no-treatment control groups) are a concern in intervention research. This may necessitate that only active treatments can be compared in the context of this RFA.

The paucity of evidence about the effectiveness of interventions in AN can be explained, at least in part, by the substantial methodological challenges associated with small sample sizes (due to the relative rarity of the disorder), difficulties with patient recruitment, high attrition, and problems with patient compliance. Obstacles to delivering successful interventions in the community (including limited insurance coverage to pay for inpatient or long-term treatments) must also be considered when designing a research project to ensure that the findings obtained will be practical for translation to community practice. To address these challenges, the collaboration of a network of committed investigators with access to patients with AN is essential. A summary of research priorities for treatment of AN can be found in the “Report of the NIH Workshop on overcoming barriers to treatment research in anorexia” (Agras et al., 2004).

Objectives and Scope

The primary aim of the network is to facilitate a moderate to large-scale evaluation of promising treatment(s) for AN, including a long-term follow-up of research participants. The RIAN network will have the capacity to improve sample size, accelerate recruitment, and increase population diversity and representation beyond what could be accomplished at a single site. Each site will have its own principal investigator and it is expected that these investigators will jointly submit (as a group of U01s) a study plan similar to that which is required in “Collaborative R01s for Clinical and Services Studies of Mental Disorders and AIDS.” (http://grants.nih.gov/grants/guide/pa-files/PA-01-123.html). The sites will share common entrance criteria and assessment protocols, as well as a common standardized intervention protocol. One site will serve as a Coordinating Center that will manage the overall operations of the network. A Data Management Center will be responsible for maintaining the integrity of data collection and processing. A Steering Committee will provide scientific oversight and will be the principal decision-making body for the study.

Below are examples of research areas and questions that could advance scientific knowledge regarding interventions for AN. The list is not exhaustive, and it is expected that additional important research topics may be identified.

Section II. Award Information

1. Mechanism(s) of Support

This RFA will use the NIH cooperative agreement (U01) award mechanism. As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

The NIH (U01) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative and National Policy Requirements, "Cooperative Agreement Terms and Conditions of Award (Section VI. Award Administration Information)." This RFA is a one-time solicitation. Applications that are not funded in the competition described in this RFA may be submitted as NEW investigator-initiated applications using the standard receipt dates for NEW applications described in the instructions to the PHS 398 application. Future unsolicited, R01 applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer review procedures.

2. Funds Available

The NIMH intends to commit approximately 1,500,000 dollars in FY 2005 to fund one network comprised of multiple new cooperative agreement awards in response to this RFA. An applicant may request a project period of up to 5 years. The anticipated start date is September 30, 2005.

Although the financial plans of the NIMH provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

You may submit (an) application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Each site will have its own principal investigator (PI). Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution 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 programs.

2. Cost Sharing or Matching

This program does not require cost sharing as defined in the current NIH Grants Policy Statement at http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#matching_or_cost_sharing.

3. Other-Special Eligibility Criteria

This RFA will provide support for a network comprised of multiple sites for participant recruitment and study. Each site should be able to contribute to the development of a common detailed protocol, assemble and train a research team, recruit and enroll eligible patients, collect and transmit data to a data management center, conduct common interventions and follow patients over extended periods of time. Prior to submission, investigators of a collaborating network should agree on the proposed research plan and the procedures for site organization and coordination.

One site of the network should be designated as the Coordinating Center. It will have oversight over all other sites regarding operations of the RIAN network and will be responsible for insuring implementation of the study over the proposed time period. It can be located at one of the clinical sites as long as it functions with independent operation and authority. The coordinating center PI should have prior experience conducting multi-site trials.

The RIAN network will also have responsibility for data management, which can be separate from or combined with coordination activities. The site that serves this function (referred to as the Data Management Center) must have a previously demonstrated capacity to manage a multi-site database and to conduct statistical analyses in coordination with the investigators. It can be physically located at the Coordination Center site, at an independent site, or at one of the clinical sites as long as a strong firewall exists between the operation of the clinical site and the operation of the data management center.

If any single site provides multiple functions (i.e., collection of clinical data, study coordination and/or data management), a clear separation must be made between investigators with decision-making responsibilities that affect the overall study and those that are responsible for the collection and accumulation of data at that particular site.

Section IV. Application Submission Instructions

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. 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

Applications must be prepared using the PHS 398 research grant application instructions and forms. Applications must have a Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

See Section VI.2 Administrative and National Policy Requirements for additional information.

3. Submission Dates and Times
Applications must be mailed on or before the receipt date described below (Section IV.3.A). Submission times not applicable.

3.A. Receipt, Review and Anticipated Start Dates

Letter of Intent Receipt Date: February 11, 2005
Application Receipt Date(s): March 11, 2005
Peer Review Date: June 2005
Council Review Date: September 2005
Earliest Anticipated Start Date: September 30, 2005

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 at the beginning of this document.

The letter of intent should be sent to:

Linda Street, Ph.D.
Division of Services and Intervention Research
National Institute of Mental Health
6001 Executive Boulevard, MSC 9635, Room 7160
Bethesda, MD 20892-9635
Rockville, MD 20852 (for express/courier service) Telephone: (301) 443-0651
FAX: 301-594-6784
Email: Lstreet@nih.gov

3.B. Sending an Application to the NIH

Applications must be prepared using the PHS 398 research grant application instructions and forms as described above. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Jean Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9663
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-3367
FAX: (301) 443-4720
Email: jnoronha@mail.nih.gov

Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date listed in the heading of this funding opportunity. If an application is received after that date, it will be returned to the applicant without review. Applications will be evaluated for completeness by CSR.

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

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.

Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within eight (8) weeks.

4. Intergovernmental Review
This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm (see also Section VI.3. Reporting).

6. Other Submission Requirements

The general instructions in the PHS 398 form should be followed with the exceptions noted below. E ach application should include the following three sections and give headings as follows: 1) Research Plan, 2) Operations, and 3) Training Capabilities. The combined page limit for these three sections may not exceed 30 pages, however, the application(s) for the coordinating center and/or data management center may each include up to three extra pages to describe their unique content.

Research Plan

This section should include a description of the proposed intervention study. It should describe the design and conduct of the treatments that are to be tested by all institutions of a particular collaborating network. Where there are even minor variations in the research plan or operations between sites, these should be highlighted in a subsection with the heading, “Elements Unique to this Site”.

The description of the intervention study should include the rationale, methods, experimental design, time line of objectives to be accomplished, plans for data acquisition and a general analytical plan. The experimental hypotheses proposed should be supported by preliminary data sufficient to warrant testing in a moderate to large-scale multi-site study. Realistic estimates of patient enrollment and effect size of interventions should be made to support estimates of statistical power to address these hypotheses. The steps involved with multi-site collaboration should be illustrated including methods for cross-site training of the intervention and assessment instruments and procedures for measuring protocol adherence. Outcomes should include quality of life, social adaptation, comorbidity of medical and psychiatric diagnoses and costs or cost-effectiveness of care. Particular attention should be directed at strategies for participant retention and for long-term follow-up. Mediators and moderators of outcome should also be evaluated.

The application should characterize the full range of expertise needed to successfully carry out this research and indicate how this expertise will be obtained. A rationale for the sample size and number of sites should be provided. It should describe overall managerial and administrative responsibilities and the functions of the Steering Committee.

Operations

Clinical Site Applications: The application for each of the clinical sites should include a section that addresses operational issues specific to implementing the trial at each site, as well as each site's functioning within a multi-site trial, e.g., relationship to each other, ability to adhere to a common protocol, cooperation with coordinating center leadership, etc.

In addition, each site's application should provide documentation of their recruitment history for similar conditions as well as an estimate of participant flow for the particular group of AN patients whom they plan to enroll. The application should provide specific plans for enrolling and retaining these participants as well as strategies for recruiting a participant pool that is sufficiently representative with regard to sex, ethnicity, race or socioeconomic status. These plans might include a description of relevant materials to be prepared, treatment center staffing goals, staff training and community outreach. Some or all of the sites should be located in communities with diverse populations and have staff that represent these populations. The application should describe the number and types of trials competing for similar patients at each clinical site. Finally, applicants must demonstrate an awareness of the effects of the research design on their ability to recruit and retain a diverse sample of AN patients. Individual applications should also discuss procedures for dealing with human subjects issues, suicidality, etc., if they deviate in any way from those described in the coordinating center application.

Applications must also include a description of the available infrastructure and facility, including necessary clinic and/or laboratory equipment. Evidence of departmental and institutional support, documented by letters to the investigator, must be provided. Individual sites will need resources to collect and transmit research data to the data management center.

Coordinating Center Application: The application for the coordinating center should include the integration of the duties and functions of the coordinating center and the clinical sites. It should propose an organizational structure demonstrating independence and autonomy from the clinical sites and provide for it in the budget. Furthermore, it should describe (and take leadership for) human subjects issues particularly as they apply to the vulnerable population being studied. A plan for preventing suicide should also be described. The budget should include statistical consultation for design and analysis issues.

The Coordinating Center should demonstrate that is has the leadership experience and expertise to coordinate and monitor a multi-site clinical trial, both scientifically and administratively. The Coordinating Center should describe how it will handle reporting and tracking of adverse events and serious adverse events. Applications should also reflect a timeline that is realistic to accomplish all aspects of study start-up, enrollment, conduct, close-out, database cleaning and data analysis.

Data Management Center Application: The Data Management Center may be part of the Coordinating Center or separate from it, but in either case, should demonstrate its experience in multi-site trials and in working with a coordinating center. A budget should be prepared for its unique responsibilities. This Data Management Center application should: identify hardware and software to be used, describe a timeframe (including milestones) and procedures for development of a central database, production and distribution of data collection instruments, coordination of rater training and reliability assessments across sites and reliable entry of all study data. The data center should also monitor the quality of data collected across sites, perform appropriate statistical analyses in coordination with the Statistical Investigator, provide data summaries or statistical reports for the DSMB and for special meetings, as needed, and conduct other necessary functions related to data collection and management. A description of how the data management center will collaborate these efforts with the other sites (including the coordinating center) should also be provided.

Training Capabilities

Applicants should describe how the RIAN grants will provide research education and training for junior investigators and/or established investigators willing to redirect their effort to research in AN.

Budget

The following issues should be considered when preparing the application and should be addressed in the Budget Justification section:

Allowable costs in NIH cooperative agreements are governed by rules set forth in the NIH Grants Policy Statement (http://grants.nih.gov/archive/grants/policy/nihgps_2001/index.htm) and as stated on the Notice of Grant Award. Under these rules the PI may exercise flexibility to meet unexpected requirements by rebudgeting or requesting approval to rebudget among categories within the total direct cost budget of the RIAN grant (as shown on the Notice of Grant Award), within the ceilings set in these guidelines.

Items fundable through a RIAN cooperative agreement may include:

1. Personnel: Principal investigator and other senior investigators, junior investigators, research coordinator, data coordinator and others (time and effort as needed, with appropriate justification).

2. Support services directly related to the project: e.g., project-specific supplies, duplication costs, dedicated telephone line.

3. Clinical costs: Cost of clinical care that is directly related to the research project, and is not covered by other sources. Cost of pharmaceuticals to be used in the study, other pharmacy and laboratory costs, as justified by the research protocol.

4. Travel: Travel for the principal investigator and one co-investigator for a yearly network meeting; additional travel for training in multi-site protocols as needed.

The following items are not fundable through a RIAN grant: Costs of routine clinical care that are not directly related to the research project, or are covered by other sources, rent, administrative or secretarial services.

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a plan for sharing research data in their application. The funding organization will be responsible for monitoring the data sharing policy (http://grants.nih.gov/grants/policy/data_sharing).

The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.

Section V. Application Review Information

1. Criteria

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

The following will be considered in making funding decisions:

2. Review and Selection Process

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

Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIMH in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of these criteria in assigning the application's overall score, weighting them as appropriate for each application. The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high 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 aspect of treatment of AN? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? Will the knowledge gained contribute to improved care?

Approach: Are the conceptual framework, design, methods, sample size and analyses adequately developed, well-integrated, and appropriate to the aims of the intervention study? Have the investigators accounted for the difficulties in enrollment, retention and follow-up? Does the applicant acknowledge other potential problem areas and consider alternative tactics? Are specific achievable performance objectives described for development of the network? Are the training and activities of research personnel adequately described?

Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies?

Investigator: Is the investigator 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 (if any)? Does the investigator at the coordinating center have experience in planning and conducting collaborative multi-center studies?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed site(s) have a sufficient flow of participants? What is the experience of the institution(s) in enrollment for clinical trials? Is there evidence of institutional support?

2.A. Additional Review Criteria:

Collaboration: Is there a feasible mechanism for collaboration to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and for data management, analysis and reporting of results?

Coordinating Center: Does the coordinating center plan describe the leadership of the project and have clearly defined administrative responsibilities? Does the coordinating center have the necessary scientific consultation available (e.g., in biostatistics)?

Data Management Center: does the data center have the necessary expertise available as well as a feasible plan for accomplishing its goals?

Training: Is there an adequate plan to provide training to junior investigators and/or established investigators who are willing to redirect their effort to research in AN?

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

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 also Section VIII - Other Information.

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 also Section VIII-Other Information.

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed.

2.B. Additional Review Considerations

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

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research Resources

NIH policy requires that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps/part_ii_5.htm#availofrr and http://www.ott.nih.gov/policy/rt_guide_final.html). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the Principal Investigator before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590). See Section VI.3. Reporting.

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 Principal Investigator will also receive a written critique called a Summary Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

A formal notification in the form of a Notice of Grant Award (NGA) will be provided to the applicant organization. The NGA signed by the grants management officer is the authorizing document.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NGA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

The NGA will be sent via email to the administrative official whose name is listed in Block 12 on the Face Page of the Form PHS 398.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the notice of grant award. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 ( U01 ), 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 above.

2.A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining objectives and approaches and for planning, conducting, analyzing, and publishing results, interpretations, and conclusions of the study. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

The awardees will be responsible for planning and participating collaboratively with NIMH under this cooperative agreement. Through participation in meetings of the Steering Committee for this project and conference calls, the awardees will work with the NIMH staff collaborators in the implementation of a multi-site protocol, and in the establishment of quality control and monitoring procedures which are to be reported in non-competing continuation applications. Clinical sites must be able to collect and transmit research data to the data management center , which will be responsible for overall protocol data collection and management functions as approved by the Steering Committee.

Investigators at the collaborating sites will have initial access to the data for analyses, interpretation and reporting. However since the creation of the data set is funded through public monies and because the data set will constitute a national scientific resource for the research community, a de-identified data set will be made available to the large research community no more than 36 months after the last wave of data have been cleaned.

2.A.2. NIH Responsibilities

At least one NIMH staff or a designee will have scientific involvement in the conduct of this activity, above and beyond normal program stewardship, through membership on the project Steering Committee. The participation of NIMH staff collaborator(s) is intended to assist the project Steering Committee in its efforts to ensure that the broad scientific goals of NIMH are reflected in the implementation, and reporting of results of the studies. Specifically, the staff collaborator(s) will participate in decisions about study design, instrumentation, and clinical assessment. The NIMH staff collaborator(s) will participate in all major project meetings and may cooperate with the awardees as author or co-author of resulting publications in accordance with publication policies developed by the Steering Committee of this project. Publications involving NIMH staff must follow NIH and NIMH publication policies.

Additionally, an agency program official or IC program director, called the NIMH Project Officer, will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

After the initial year, for which the NIMH requires a mid-year report, progress of the project will be reviewed by the NIMH Project Officer annually at the time of each continuation application. These reports will be assessed to assure that satisfactory progress is being made in achieving the project objectives, especially with respect to enrollment and quality of data collection, and that the site is following the procedures recommended and approved by the project Steering Committee.

The NIMH will appoint an independent panel of experts in clinical trials to constitute a Data Safety and Monitoring Board (DSMB). The DSMB will report to NIMH. The DSMB will monitor safety, quality of data collection, and integrity of the study. The costs of the DSMB will come from an NIMH source independent of the cooperative agreement. The study data will be reviewed by the DSMB every 3-6 months. The DSMB will receive a report from the data management and statistical center usually about 4 weeks before each review date. Such a report will include the major variables necessary for monitoring safety and quality of data collection and integrity of the study. As study protocol and consent forms are relevant to safety and quality of data, the DSMB will also review these documents before the onset of the study. Based on this review, the DSMB has the authority to prevent the study from starting or to stop the study after it has started.

2.A.3. Collaborative Responsibilities

The project Steering Committee, which will consist of up to 3 persons from each awardee site and the NIMH staff collaborator(s), will be the principal decision-making body for the study. It will have overall responsibility for the study and will make modifications in the protocols as necessary. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee. The NIMH staff collaborator(s) will jointly have one vote on the project Steering Committee. Each awardee will jointly have one vote, although up to three persons from each site may be members of the project Steering Committee. A quorum will require one NIMH staff collaborator or designee and at least four representatives, each from one of the participating sites. The project Steering Committee will elect a chairperson, and may establish additional by-laws, subcommittees, or workgroups for specific tasks, including a Publications Committee to develop policies on publication and authorship. An NIMH staff collaborator may not chair any committee or subcommittee. Membership on the project Steering Committee becomes effective for the site upon receipt of the notice of award. Decisions will be made by majority vote of a quorum, with an attempt for consensus when possible. The project Steering Committee will meet annually, and convene through telephone conferences or in person, as needed, for the duration of the study.

Responsibilities of the project Steering Committee members (collaborators) include: (1) collaboratively finalizing the study plan, including design, assessment instruments, component protocols, and detailed implementation procedures; (2) abiding by and directing the study plan determined by the project Steering Committee; (3) monitoring the study and developing and implementing quality control procedures; (4) conserving grant funds in the service of the common objectives and of the research plan agreed on by the project Steering Committee; (5) facilitating the analysis of data and the eventual release to the larger scientific community (see “Public Domain” below); submitting data on time in the form and on the schedule determined by the project Steering Committee; (6) evaluating and reporting study results: defining rules regarding access to data and publication of findings from analyses of the data set; and (7) abiding by all scientific, practical, and policy decisions of the project Steering Committee.

2.A.4. Arbitration Process

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 arbitration. An Arbitration 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

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 two areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Linda Street, Ph.D.
Division of Services and Intervention Research
National Institute of Mental Health
6001 Executive Boulevard, MSC 9635. Room 7160
Bethesda, MD 20892-9635
Rockville, MD 20852 (for express/courier service) Telephone: (301) 443-0651
FAX: 301-594-6784
Email: Lstreet@nih.gov

2. Peer Review:

Not applicable

3. Financial or Grants Management Contacts:

Joy R. Knipple
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD 20892-9605
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-8811
FAX: (301) 443-6885
Email: jknipple@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 (45CFR46) 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, June 12, 1998: 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 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.

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/guide/notice-files/NOT-OD-04-042.html). 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 http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, 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.

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 new PHS Form 398; 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.

Public 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 public 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 PA 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.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) 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 DHHS 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. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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 PA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov.

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 or Health Systems Agency review. 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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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/.


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