RESEARCH ON INTERVENTIONS FOR ANOREXIA NERVOSA (RIAN)

RELEASE DATE:  November 3, 2003

RFA Number:  RFA-MH-04-002 (This RFA has been reissued, see RFA-MH-05-009)

Department of Health and Human Services (DHHS)

PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
 (http://www.nih.gov/)

COMPONENTS OF PARTICIPATING ORGANIZATION:
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)

CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER(S):  93.242

LETTER OF INTENT RECEIPT DATE:  December 22, 2003
APPLICATION RECEIPT DATE:  January 22, 2004

THIS RFA CONTAINS THE FOLLOWING INFORMATION

o  Purpose of this RFA
o  Research Objectives
o  Mechanism(s) of Support 
o  Funds Available
o  Eligible Institutions
o  Individuals Eligible to Become Principal Investigators
o  Special Requirements 
o  Where to Send Inquiries
o  Letter of Intent
o  Submitting an Application
o  Supplementary Instructions
o  Peer Review Process
o  Review Criteria
o  Receipt and Review Schedule
o  Award Criteria
o  Required Federal Citations

PURPOSE OF THIS RFA

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 
for multi-site clinical trials.

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/events/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 (e.g., osteopenia and osteoporosis, 
cardiovascular complications, fluid and electrolyte changes and disruption in 
immune functioning).

Despite its gravity, very little is known about the effective treatment, and 
ultimately, the prevention 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.

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 
Steering Committee will provide scientific oversight and will be the principal 
decision-making body for the study.  Data management and analyses will be 
supported separately by NIMH.

This RFA also aims to provide research education and training for junior 
investigators and/or established investigators willing to redirect their effort 
to research in AN.

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.

o  Disorder-specific adaptations of treatments that have been successfully used 
to treat other disorders, including theory-based modifications of interventions 
that are efficacious with other disorders.

o  Pharmacological intervention studies focused on resolution of primary 
symptoms and consequent weight restoration.

o  Evaluations of strategies aimed at increasing compliance and minimizing 
drop-outs.

o  Research on family interventions for adolescents.

o  Studies of more effective relapse prevention procedures and maintenance or 
booster therapies.

o  Rigorous tests of multimodal interventions in the inpatient, outpatient, or 
partial hospitalization settings.

o  Studies that test developmentally-informed interventions for children and 
adolescents.

o   Interventions that incorporate alternate systems of delivery and therapeutic 
approaches (schools, nutritionists, psychologists, psychiatrists, etc.) alone or 
in combination.

o  Interventions that include a focus on specialized strategies for understudied 
groups, including ethnic minority groups and females.

o  Research targeting approaches to better assessing and managing suicide risk 
among persons with this disorder.

MECHANISM OF SUPPORT
 
This RFA will use NIH cooperative agreement (U01) award mechanism.  This RFA is 
a one-time solicitation.  The anticipated award date is September 2004.  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.

The NIH (U01) is a cooperative agreement award mechanism.  In the cooperative 
agreement award 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 "Cooperative 
Agreement Terms and Conditions of Award".

FUNDS AVAILABLE

The NIMH intends to commit approximately $1,250,000 total costs, in FY 2004, 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.  Please note that F&A costs on a subcontract are included in the total 
cost limit.  Although the financial plans of the NIMH provide support for this 
program, awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of meritorious applications.  

ELIGIBLE INSTITUTIONS

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

o  For-profit or non-profit organizations
o  Public or private institutions, such as universities, colleges, hospitals, 
and laboratories
o  Units of State and local governments
o  Eligible agencies of the Federal government
o  Domestic or foreign institutions/organizations
o  Faith-based or community-based organizations 

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

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.

SPECIAL REQUIREMENTS

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 a network should be designated as the coordinating center.  It will 
have oversight over all other sites regarding operations of the RIAN network.  
It can be located at one of the clinical sites as long as it functions with 
independent operation and authority.  The principal investigator at the 
coordinating center should have prior experience conducting multi-site trials.  

Individual sites will need resources to collect and transmit research data to 
the data management center.  The coordinating center should be able to provide 
assistance with the research design and statistical analyses.  The data 
management center will be supported separately by the NIMH.  It will manage the 
multi-site database and conduct statistical analyses in coordination with the 
investigators.

Each of the proposed clinical sites 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.  A 
rationale for the sample size and number of sites should be provided.  

Cooperative Agreements Terms and Conditions of Award

These special Terms of Award are in addition to and not in lieu of otherwise 
applicable Office of Management and Budget (OMB) administrative guidelines, 
Department of Health and Human Services (DHHS) grants administration regulations 
in 45 CFR part 74 and 92, and other HHS, PHS, and NIH grant administration 
policy statements.

Under the cooperative agreement, the NIMH purpose is to support and/or stimulate 
the recipients’ activities by involvement in and otherwise working jointly with 
the awards recipients in a partner role, but it is not to assume direction, 
prime responsibility, or a dominant role in the activity.  Consistent with the 
above concept, the dominant role and prime responsibility for the activity 
reside with the awardees for the project as a whole, although specific tasks and 
activities in carrying out the study will be shared between the awardees and the 
NIMH scientific collaborators or designee.  By acceptance of these awards, the 
awardees agree to abide by decisions and policies of the project Steering 
Committee and the other terms and conditions listed below or referenced in the 
Notice of Grant Award.

Under the cooperative agreement, a relationship will exist between the awardees 
and the NIMH, in which the performers of the activities are responsible for the 
requirements and conditions described below and agree to accept program 
assistance from NIMH staff collaborators in achieving project objectives.  
Failure of the awardees to meet the performance requirements, including these 
special terms and conditions of award, or significant changes in level of 
performance, may result in a reduction of budget, withholding of support, 
suspension and/or termination of the awards.

1.  Awardee Rights and Responsibilities

The awardees have the primary authority and responsibility for defining 
objectives and approaches and for planning, conducting, analyzing, and 
publishing results, interpretations, and conclusions of the study.  The awardees 
shall retain custody of and primary rights to the data developed under this 
award, subject to Government rights of access and consistent with current HHS, 
PHS, and NIH policies; however, the data base will be put into the public domain 
no more than 36 months after the last wave of data has been cleaned.

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.  
Management of the multi-site database and final statistical analyses will be 
conducted at the data management center.  However, some capability of data 
management functions will need to be present at each site.  These functions will 
include:  (1) ongoing monitoring of the data collected at the site for clarity, 
completion, and accuracy as compared with the source documents; (2) transferring 
of data to the central database by batching, copying, and mailing the data, or 
faxing them to the data management center; and (3) addressing possible queries 
from the data management center about the data.

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.  NIMH Responsibilities

At least one NIMH staff collaborator 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.  
In addition to the NIMH staff collaborator(s), an NIMH Project Officer will be 
responsible for normal stewardship, and will provide technical assistance, 
programmatic monitoring, and assistance in the coordination of the overall 
project, but will not be a voting member of the project Steering Committee.

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 
the 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.

3.  Collaborative Responsibilities

The project Steering Committee 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.  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 representative of the contracted 
database management component will participate on the Steering Committee, but 
will not be a voting member.  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.  Any 
project Steering Committee member who considers a committee decision 
unacceptable may appeal by following the arbitration procedure described below.  
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.

4.  Arbitration Procedures

If a decision related to a scientific or programmatic issue between the awardees 
and the NIMH staff collaborator(s) or NIMH is not acceptable to the awardee(s), 
the awardee may, within 30 days of notification of the decision, request a 
review by an arbitration panel composed of one arbitrator nominated by the 
awardee(s), one nominated by NIH, and one chosen by the first two nominees.  
This panel will make a decision within 60 days of the request.  Failure to 
comply with the decision of the panel may result in termination of support for 
the awardee(s) by NIMH.  This arbitration procedure in no way affects the right 
by the awardee(s) to appeal any adverse action in accordance with PHS 
regulations at 42 CFR Part 50, subpart D, and HHS Grant Administration 
Regulations at 45 CFR Part 74, section 304, and HHS regulations at 45 Parts 16 
and 75.  

WHERE TO SEND INQUIRIES

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

o  Direct your questions about scientific/research issues to:

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

o  Direct your questions about peer review issues to:

Michael Kozak, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6138, MSC 9609
Bethesda, MD  20892-9608
Telephone:  (301) 443-1340
FAX:  (301) 443-4720
Email:  kozakm@mail.nih.gov

o  Direct your questions about financial or grants management matters to:

Joy R. Knipple
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6115, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-8811
FAX:  (301) 443-6885
Email:  jknipple@nih.gov

LETTER OF INTENT

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

o  Descriptive title of the proposed research
o  Name, address, and telephone number of the Principal Investigator
o  Names of other key personnel 
o  Participating institutions
o  Number and title of this RFA 

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, Room 7160, MSC 9635
Bethesda, MD  20892-9635
Telephone:  (301) 443-0651
FAX:  301-594-6784
Email:  Lstreet@nih.gov

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  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 DUNS 
number can be obtained by calling (866) 705-5711 or through the web site at 
http://www.dunandbradstreet.com/.  The DUNS number should be entered 
on line 11 of the face page of the PHS 398 form.  The PHS 398 document is 
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.

SUPPLEMENTARY INSTRUCTIONS

The general instructions in the PHS 398 form should be followed with exceptions 
as noted below.  Each 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 Research Plan for the coordinating center application may 
include up to three extra pages to describe its 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 application should characterize the full range of expertise needed to 
successfully carry out this research and indicate how this expertise will be 
obtained.  It should describe overall managerial and administrative 
responsibilities and the functions of the Steering Committee.

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.

Operations

This section should include the functions to be performed by individual sites 
and the integration of procedures across multiple sites.  This section may 
include both shared or common elements and those that are unique to each site.

Each of the proposed clinical sites 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.  A 
rationale for the sample size and number of sites should be provided.  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.  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 AN patients.

Applications must 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.

Coordinating Center Application:  For the one site designated as the 
Coordinating Center, it should propose an organizational structure and provide 
for it in the budget.  Statistical consultation for design and analysis issues 
should be available to the coordinating center.  The duties, functions, and 
integration of the coordinating center and clinical sites should also be 
described. 

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 and 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/grants/policy/nihgps_2001/) 
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.

USING THE RFA LABEL:  The RFA label available in the PHS 398 (rev. 5/2001) 
application form 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/label-bk.pdf.

SENDING AN APPLICATION TO THE NIH:  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
Bethesda, MD  20817 (for express/courier service)
 
At the time of submission, two additional copies of the application and all 
copies of the appendix materials 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

APPLICATION PROCESSING:  Applications must be received on or before the 
application receipt date listed in the heading of this RFA.  If an application 
is received after that date, it will be returned to the applicant without 
review.

Although there is no immediate acknowledgement of the receipt of an application, 
applicants are generally notified of the review and funding assignment within 8 
weeks.
 
The Center for Scientific Review (CSR) will not accept any application in 
response to this RFA 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 an RFA, it 
is to be prepared as a NEW application.  That is, the application for the RFA 
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.

PEER REVIEW PROCESS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the National Institute of Mental Health.  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 the National 
Institute of Mental Health in accordance with the review criteria stated below.  
As part of the initial merit review, all applications will:

o  Undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of the applications under review, will 
be discussed and assigned a priority score
o  Receive a written critique
o  Receive a second level review by the National Advisory Mental Health Council
 
REVIEW CRITERIA

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 evaluate 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 the following criteria in assigning the application’s 
overall score, weighting them as appropriate for each application.

o  Significance
o  Approach
o  Innovation
o  Investigator
o  Environment

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?

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

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 planning 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)?

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?

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 criteria included in the section 
on Federal Citations, below).
 
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.  Plans for the recruitment and retention of subjects will also be 
evaluated. (See Inclusion Criteria in the sections on Federal Citations, below).

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.

ADDITIONAL REVIEW CONSIDERATIONS 

SHARING RESEARCH DATA:  Applicants requesting more than $500,000 in direct costs 
in any year of the proposed research must include a data sharing plan in their 
application.  The reasonableness of the data sharing plan or the rationale for 
not sharing research data will be assessed by the reviewers.  However, reviewers 
will not factor the proposed data sharing plan into the determination of 
scientific merit or priority score. 
http://grants.nih.gov/grants/policy/data_sharing 

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:    December 22, 2003
Application Receipt Date:         January 22, 2004
Peer Review Date:                 May/June 2004
Council Review:                   September 2004
Earliest Anticipated Start Date:  September 2004

AWARD CRITERIA

Award criteria that will be used to make award decisions include:

o  Scientific merit (as determined by peer review)
o  Availability of funds
o  Programmatic priorities
 
REQUIRED FEDERAL CITATIONS 

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).  The establishment of data and safety monitoring 
boards (DSMBs) is required for multi-site clinical trials involving 
interventions that entail potential risk 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:  Starting with the October 1, 2003 receipt date, 
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, 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.

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 - 
Amended, October, 2001," published in the NIH Guide for Grants and Contracts on
October 9, 2001 
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); 
a complete copy of the updated Guidelines are 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 RESEARCH INVOLVING HUMAN SUBJECTS:  
The NIH maintains a policy that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  This 
policy applies to all initial (Type 1) applications submitted for receipt dates 
after October 1, 1998.

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 that is available at 
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 proposals for research involving human subjects.  
You will find this policy announcement in the NIH Guide for Grants and Contracts 
Announcement, dated June 5, 2000, at 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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).  Those 
who must comply with the Privacy Rule (classified under the Rule as “covered 
entities”) must do so by April 14, 2003 -(with the exception of small health 
plans which have an extra year to comply).

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 RFA 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 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.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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