MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTERS

RELEASE DATE:  September 23, 2002 (see addendum NOT-AR-03-001)
 
RFA:  AR-03-001 (see reissuance RFA-AR-04-008)

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)  
 (http://www.niams.nih.gov/)
National Institute of Child Health and Human Development (NICHD)  
 (http://www.nichd.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS) 
 (http://www.ninds.nih.gov/)
 
LETTER OF INTENT RECEIPT DATE: January 15, 2003

APPLICATION RECEIPT DATE: February 24, 2003
 
THIS RFA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this RFA
o Research Objectives
o Mechanism 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 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 establish Muscular 
Dystrophy Cooperative Research Centers (MDCRCs), in order to increase basic 
and clinical research on all forms of muscular dystrophy.  The National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the 
National Institute of Neurological Disorders and Stroke (NINDS), and the 
National Institute of Child Health and Human Development (NICHD) invite 
applications for MDCRCs that promote side-by-side basic, translational, and 
clinical research, provide resources that can be used by the national muscle 
biology and neuromuscular research communities, and provide training and 
advice about muscle diseases for researchers and physicians who provide 
initial diagnosis and treatment, including rehabilitation, care for cognitive 
and behavioral concerns, and therapy for other system complications.  Taken 
together, the centers will constitute a cohesive program, the MDCRC Program, 
operating under guidelines for NIH cooperative agreements.

The primary goal of this initiative is to establish research centers, each of 
which will bring together expertise, infrastructure and resources focused on 
major questions about muscular dystrophy.  Centers should use innovative 
research designs and state-of-the-art technologies.  Achieving high levels of 
expertise and resources may require multi-institutional consortia.  Centers 
are expected to provide an environment and core resources that will enhance 
collaborations of established basic, clinical, and behavioral science 
investigators to study muscular dystrophy research questions.  Further, the 
environment should promote cross-disciplinary research training.  Each center 
should develop in accordance with available expertise, interests, and 
resources, but should also be responsive to national needs related to 
muscular dystrophy.  Although the types of activities that should be included 
are indicated in these guidelines, specific approaches to accomplish them are 
left to applicants.

In addition to the self-contained activities of individual centers, the 
MDCRCs will collaborate with other centers, overseen by a Steering Committee 
involving representation from each center and from NIH.  The centers will be 
funded through NIH Cooperative Agreements with the goal of maximizing 
collaborative utilization of the unique resources in infrastructure, 
expertise, and clinical recruitment that will be created. 

Investigators interested in applying for support of muscular dystrophy 
research using mechanisms other than this RFA should see NIH PAS01-041, 
"Therapeutic and Pathogenic Approaches for the Muscular Dystrophies" at 
http://www.niams.nih.gov/rtac/funding/grants/pa/pas_01_041.pdf.

RESEARCH OBJECTIVES

Background and Rationale

Muscular dystrophies collectively have a high impact on health, affecting 
tens of thousands of people in the United States alone.  The diseases are 
characterized by progressive weakness and wasting of muscles.  Many cases of 
muscular dystrophy represent new occurrences of disease, where there is no 
prior family history.  Though research has recently revealed much about 
genetic defects associated with many forms of muscular dystrophy, treatment 
for the diseases has not changed significantly.  There is a need to learn 
more about pathogenesis of the diseases and improve early detection and 
screening, diagnosis, treatment, and prevention.

Duchenne muscular dystrophy (DMD) is most common, affecting approximately one 
in 3,500 male births.  This X-linked disease is characterized by muscle 
necrosis and regeneration.  The regenerative process cannot maintain normal 
muscle tissue and mass, resulting in progressive muscle fiber loss and 
considerable elevations in serum creatine kinase.  Affected boys usually must 
use wheelchairs by age 12, with death often occurring in the third decade 
from cardiac or respiratory problems.  The genetic defect leads to missing or 
abnormal dystrophin, an important structural protein unknown until the gene 
was discovered.  A milder variant, Becker muscular dystrophy (BMD), is caused 
by different defects in the DMD gene, that produce truncated but partially 
functional dystrophin.  NINDS, NIAMS and the NIH Office of Rare Diseases 
sponsored a workshop on Therapeutic Approaches for Duchenne Muscular 
Dystrophy (DMD), May 15-16, 2000, in Bethesda, MD.  The goals of this 
workshop were to address key questions in improving treatments for DMD and 
identify areas of needed scientific knowledge, impediments, and critical next 
steps to promote effective therapy. A summary of the workshop may be found 
at: http://www.ninds.nih.gov/news_and_events/dmdmtngsummary.htm.

Myotonic dystrophy (DM) is the most common form of adult onset muscular 
dystrophy.  It is dominantly inherited and characterized by muscle 
hyperexcitability (myotonia), progressive myopathy, cataracts, defects of 
cardiac conduction, neuropsychiatric impairment, and other developmental and 
degenerative manifestations.  Myotonic dystrophy is one of the growing number 
of triplet repeat disorders, it is associated with a CTG expansion in an 
untranslated region of 19q13.3.  Larger numbers of repeats are found in more 
severely affected individuals, and the number of repeats tends to increase 
from generation to generation, thus explaining earlier age of onset and 
increased symptoms in subsequent generations (anticipation).  Recently a 
second form of the disease, Myotonic Dystrophy 2 (DM2), has been shown to be 
due to a defect on chromosome 3.  DM2 appears to be caused by an expanded 
CCTG repeat, rather than the CTG repeat in DM1.  Manifestations of both forms 
of the disease are similar, though initial weakness is usually in different 
muscles.  One hypothesis for the pathogenesis of DM is that copies of the 
expanded region interfere with normal expression of unrelated proteins. 

Facioscapulohumeral (FSH) muscular dystrophy is an autosomal dominant form 
that initially affects muscles of the face, scapula (shoulder blades), and 
upper arms.  Symptoms may develop in early childhood and are usually 
noticeable in the teenage years.  A progressive skeletal muscle weakness 
usually develops in other areas of the body as well, often the weakness is 
asymmetrical.  Life expectancy is normal, but some affected individuals 
become severely disabled, and some families have an associated hearing loss.  
Nearly all cases are associated with a distal 4q35 deletion.  Because there 
are no known genes in this region, a novel position effect has been 
postulated to explain the disease phenotype. NIAMS, NINDS, and the NIH Office 
of Rare Diseases sponsored a Conference on the Cause and Treatment of 
Facioscapulohumeral Muscular Dystrophy, held on May 8-9, 2000, in Bethesda, 
MD.  A summary of this meeting may be found at 
http://www.niams.nih.gov/ne/reports/sci_wrk/2000/fshdexsummary.htm.

The limb-girdle muscular dystrophies (LGMD) are genetically heterogeneous, 
with both dominant and recessive forms reported.  All limb-girdle muscular 
dystrophies show a similar distribution of muscle weakness, affecting both 
upper arms and legs.  The recessive LGMDs are more frequent than the dominant 
forms, and usually have a childhood or teen-age onset.  The dominant LGMDs 
usually show an adult onset.  In addition to muscle weakness, the creatine 
kinase (CK) values are elevated in affected individuals, usually 4-10 times 
the normal laboratory values.  Four of the recessive forms have been 
associated with defects in genes coding for the sarcoglycan complex, which, 
along with dystrophin, helps anchor muscles to the extracellular matrix. More 
devastating mutations in these same genes can cause severe childhood 
autosomal-recessive muscular dystrophy (SCARMD).

Emery-Dreifuss muscular dystrophy (EMD) is a sex-linked form characterized by 
wasting of shoulder, upper arm, and shin muscles.  Joint deformities are 
common.  It also inflicts serious cardiac problems that can result in 
premature and sudden death.  Cardiac involvement may also cause premature 
death in female carriers.  The responsible sex-linked gene has been located 
(Xq28), and it has been found to code for a previously unknown protein, 
called emerin, associated with the muscle membrane.  Emerin is normally found 
in both skeletal and heart muscle.  Different mutations of this gene may 
result in the absence of emerin and thus the disease.  A few cases have been 
found in which emerin is normal, suggesting genetic heterogeneity.
 
Congenital muscular dystrophy (CMD) is a heterogeneous group of severe 
autosomal-recessive neuromuscular diseases with early clinical onsets.  
Manifestations of CMD are evident at birth or in the first few months of life 
and consist of muscle weakness and hypotonia, delayed motor milestones, 
severe and early contractures, and, often, joint deformities.  Some forms of 
CMD are associated with central nervous system (CNS) malformations.  Some 
cases of CMD have been attributed to the absence of merosin, a component of 
laminin. Laminin is the extracellular component of the complex that, together 
with dystrophin and associated glycoproteins, anchors the muscle cell.  The 
same gene is responsible for one of the animal models of muscular dystrophy, 
the dy/dy mouse.

Despite advances in knowledge about the genetic defects of these diseases, 
the life expectancy and quality of life for children and adults with muscular 
dystrophy have not improved significantly.  Recent workshops identified the 
need for shared research resources and increased collaborative studies, since 
individual researchers may not have the resources to perform critical 
research in these areas.
 
In May 2002, NIAMS, NINDS, and NICHD brought together a Muscular Dystrophy 
Research Task Force to identify ways to increase the level of understanding 
of muscular dystrophies and improve diagnosis and treatment approaches. A 
summary of the first meeting of the Task Force is available at: 
http://www.niams.nih.gov/ne/reports/sci_wrk/2002/mdmeet.htm.  Among other 
suggestions, the Task Force recommended support for research centers to 
promote the exchange of ideas and information between basic and clinical 
investigators.  Such centers should have a broad approach including 
components in training and plans to move new knowledge to a clinical setting.

Objectives and Scope

NIAMS, NINDS, and NICHD seek to establish multidisciplinary Muscular 
Dystrophy Cooperative Research Centers (MDCRCs) to serve as focal points for 
collaboration and expansion of research and training on muscular dystrophy.  
Each MDCRC is to support an integrated basic and clinical research program 
focused on improving knowledge and treatment of muscular dystrophy.  The 
close interaction between basic researchers and clinicians will accelerate 
the translation of fundamental advances to the clinic and the utilization of 
patient materials for basic research.

Collectively and in cooperation with NIH, the centers will be part of a 
national MDCRC Program.  The Steering Committee that is described below is to 
help coordinate this program.  For example, collaborative activities between 
funded MDCRCs, which may include full or pilot research projects, will be 
developed and monitored by the Steering Committee.  In addition, 
collaborations may be developed with other federally funded projects related 
to muscular dystrophy, such as the National Registry for Myotonic Dystrophy 
and Facioscapulohumeral Dystrophy (see 
http://www.niams.nih.gov/hi/registry/registry.htm#dystrophy) or recent 
initiatives from the CDC.  This does not preclude applicants from including 
such collaborations within proposed research projects.

The MDCRCs are to emphasize new ideas, novel approaches, and state-of-the-art 
technology to increase understanding of the basic mechanisms of disease 
pathogenesis and facilitate translation of that knowledge to design and 
evaluate clinical interventions to prevent or treat muscular dystrophy.  
Muscular dystrophy research requires multidisciplinary approaches, based on 
expertise in muscle biology, genetics, imaging, muscle plasticity, exercise 
science and physical therapy, nutrition, molecular biology, neuroscience, 
rehabilitation medicine, epidemiology, clinical trials, bioengineering, 
electrophysiology, psychology, and behavioral sciences.  Health care 
providers include neurologists, rheumatologists, cardiologists, orthopedists, 
pediatricians, medical geneticists, physiatrists, and rehabilitation 
practitioners, as well as nurses and primary care practitioners.  Applicants 
are encouraged to include researchers representing a broad range of 
approaches, including, as appropriate, skilled investigators who have been 
involved in areas other than muscular dystrophy. 

Centers should encourage specialized training of personnel in cross 
disciplinary approaches.  It is expected that the centers will be planned so 
as to facilitate the inclusion of trainees sponsored through separate 
mechanisms.  MDCRCs are to maximize the resources, technologies, 
investigators, disciplines, and concepts that will build a foundation for 
basic, applied and clinical research.  Likewise, these centers should promote 
education of diverse health care trainees in the diagnosis, treatment and 
prevention of the muscular dystrophies and their complications, and should 
model the utilization of multi-disciplinary management teams. 

Applicants are encouraged to use innovative and novel approaches to studying 
and treating disease.   Examples that illustrate possible areas of research 
are presented below. They are intended only to provide a broad direction for 
research and should be considered illustrative and not restrictive.   General 
examples of scientific topics are:

o  study pathogenic mechanisms leading from gene defects to muscular 
dystrophy phenotypes, 

o  clarify the role of inflammatory changes that accompany tissue 
degeneration, e.g., explore the relationship between inflammatory cells, 
muscle cell death, and blood vessels,

o  clarify relationships between genotype and natural history of disease,

o  develop improved outcome measures and methods to monitor changes due to 
treatment or disease progression, 

o  study the involvement of apoptotic cell death in the process of muscle 
fiber degeneration, 

o  develop methods and procedures, such as enhanced imaging that will provide 
for better monitoring of disease processes,

o  examine genetic heterogeneity, and search for additional candidate genes, 

o  examine genotype/phenotype correlations within and between families, 

o  determine if the dystrophin-glycoprotein complex has both a mechanical and 
signaling role,

o study properties of muscle cells derived from affected tissue,

o determine basis of differential involvement of muscles, reflected by the 
regional pattern of disease, 

o  pursue the development and sharing of appropriate animal models for 
muscular dystrophies, 

o  explore further development of new types of therapy, including gene 
transfer and gene correction,

o  pursue the development of improved pharmacological therapeutic approaches, 
and determine mechanisms of action,

o  improve techniques for possible gene transfer therapies, by optimizing the 
expression cassette, improving the design of viral vectors, clarifying and 
managing immunologic consequences, and optimizing gene delivery in terms of 
tissue targeting and efficiency of transfecting cells,

o  expand studies on alternative (non-viral) approaches that target either 
the utrophin gene or the endogenous dystrophin gene,

o  expand the use of muscle stem cells for possible therapy, through 
clarifying their origin and developmental state, 

o  improve conditions for culturing and expanding cell populations, 

o  determine if stem cells can be delivered through the circulatory system 
efficiently and effectively,

o  improve therapeutic value of protein expression from transplanted 
myoblasts,

o  promote bioengineering and other innovative research into rehabilitation 
of patients with muscular dystrophies,

o  expand research into the pathogenesis of non-muscle system associated with 
muscular dystrophies, and

o  encourage research into the psychosocial, emotional, behavioral and 
cognitive aspects of muscular dystrophy, including mental health concerns of 
affected persons and families. 

ORGANIZATION OF MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTERS

Each MDCRC will include at least one basic research project and one clinical 
research project, with a minimum of three individual, but interrelated, 
research projects.  At least one project should be collaborative or discussed 
in terms of its ability to be expanded through collaborations.  There will be 
an Administrative Core and at least one Scientific Research Resource Core 
that will serve as a resource for the national muscular dystrophy research 
effort. Research projects should have high scientific merit and clear 
research objectives, and be organized around a central theme related to 
muscular dystrophy.  Research projects should have mutually supportive 
interactions between basic scientists and clinical investigators. 

NIH defines human clinical research as: (1) Patient-oriented research. 
Research conducted with human subjects (or on material of human origin such 
as tissues, specimens and cognitive phenomena) for which an investigator (or 
a colleague) directly interacts with human subjects. Excluded from this 
definition are in vitro studies that utilize human tissues that cannot be 
linked to a living individual. Patient-oriented research includes: (a) 
mechanisms of human disease, (b) therapeutic interventions, (c) clinical 
trials, or (d) development of new technologies. (2) Epidemiologic and 
behavioral studies. (3) Outcomes research and health services research. 

Each MDCRC will have a Center Director (the Center Principal Investigator) 
who will make scientific and administrative decisions relating to the center, 
will oversee identification and selection of key personnel, and will be 
responsible for allocation and monitoring of MDCRC funds.  The Center 
Director will work closely with a Co-Director. It is recommended that the 
Director and Co-Director separately provide leadership in basic and clinical 
research.  The Director and Co-Director should have a demonstrated capability 
to organize, administer and direct the center.  It is expected that the 
Director and Co-Director will have a substantial investment in the center and 
be its scientific leaders.  Thus, each should have a minimum total time 
commitment (including core and project activities) of 20% to the MDCRC.  
Direction and decisions for each center will be undertaken with the advice of 
its own executive committee and Scientific Advisory Committee, as described 
below. 

Each center will have a team of appropriate investigators.  Involvement of 
several departments and disciplines will broaden the scientific basis of 
muscular dystrophy research.  Collaborations among different institutions are 
encouraged, if scientifically appropriate. To make an application competitive 
for support, there should be substantial and appropriate infrastructure and 
departmental and institutional support set in place that will allow the 
proposed center to accomplish the goals of the MDCRC Program.

MDCRC support is not intended to be a substitute for individual grant 
support.  It is, therefore, expected that project and core leaders will have 
independent, peer-reviewed research support.  It is desirable for MDCRC-
supported research to complement other funded research related to muscular 
dystrophy taking place at the applicant institution, including activities 
supported by R01, P01, and other mechanisms. It is anticipated that resources 
and projects that are in place with funding from sources other than the MDCRC 
Program will synergistically interact with MDCRC infrastructure, cores, and 
projects.  The application should explain how MDCRC support would facilitate 
the development and progress of related projects that may not be an integral 
component of the MDCRC itself.

o  Administrative Core  

The successful operation of each MDCRC will require the integration of the 
activities of several projects and cores, as well effective organization of 
the efforts of scientific and professional personnel from a variety of 
disciplines and subspecialties.  This requires substantial effort by the 
principal investigator and the presence of an administrative structure to 
organize the flow of information, distribution of effort, allocation of 
resources, and to implement other necessary administrative functions.  This 
will require an administrative core or its equivalent.  The administrative 
requirements of each MDCRC will necessitate the assistance of an 
administrator with business management expertise.  It is important that such 
an individual be identified and directly involved with the fiscal and 
administrative aspects of the MDCRC application and award.  It is expected 
that the MDCRC administrative structure will facilitate the following:

1) coordination and integration of MDCRC components and activities, 

2) planning and review of the utilization of funds,

3) provide support and advice for the MDCRC Director and Co-Director in 
his/her oversight of the activities of the center,

4) interact with the scientific and lay communities to develop relevant goals 
for the MDCRC within the immediate environment of the Center,

5) interact with other MDCRCs and the Centers" NIH Science Officers to 
develop trans-MDCRC research activities.  The Science Officer is the NIH 
representative who implements the NIH aspects of the Cooperative Agreement in 
each Center,

6) promote the use of the core facilities among researchers within the parent 
institution and among investigators in other institutions.   Information on 
the activities and opportunities present at the MDCRC should be made 
available to as broad a community as possible, through websites or other 
appropriate mechanisms.

o Scientific Research Resource Core(s)

The Scientific Research Resource Cores are to serve as resources for the 
national muscular dystrophy research effort in addition to supporting 
research within the MDCRC.  Sharing of unique and powerful research tools is 
expected to foster collaborations across departments or schools at a single 
institution, as well as among investigators at several institutions. They 
should be designed to attract researchers and foster interactive approaches 
to questions relevant to muscular dystrophy. The MDCRC will show how 
scientific research resource cores will develop to provide research resources 
for investigators not affiliated with the center. 

Examples of scientific cores include, but are not limited to: medical imaging 
(fMRI, PET, MRS, optical imaging), statistics and research design (clinical 
trial design, database management, patient registries, epidemiology), special 
animal facilities (primate centers, transgenic/knockout technology), 
bioengineering/biomechanics (gait analysis, tissue engineering, 
biomaterials), or molecular biology (genetic screening, gene discovery, 
bioinformatics).  Resources could include development and sharing of model 
organisms for muscular dystrophies, bioinformatics and computational services 
for information relevant to muscle disease, DNA chips and similar devices for 
microarray analysis of gene expression, improved imaging of healthy and 
diseased muscle, and high-throughput mass spectrometric analysis.  Please 
refer to the summaries of NIH sponsored meetings on muscular dystrophy for 
further examples and discussions of resources:  
http://www.niams.nih.gov/ne/reports/sci_wrk/2002/mdmeet.htm, 
http://www.ninds.nih.gov/news_and_events/dmdmtngsummary.htm, 
http://www.niams.nih.gov/ne/reports/sci_wrk/2000/fshdexsummary.htm.

o  Executive Committee  

In order to assist the Center Director and Co-Director in making scientific 
and administrative decisions, each center will establish an executive 
committee, composed of the Center Director, Co-Director, project leaders, 
core directors, and the administrator. The executive committee should be 
encouraged to seek outside advice and consultation, both from within the 
institution and from other institutions, in its monitoring and development of 
the scientific content and direction of the program.

o  Scientific Advisory Committee (SAC)  

Each MDCRC will also establish a SAC consisting of scientists from outside of 
the institution or consortium to advise the Director and Co-Director 
regarding the activities of the Center.  The inclusion of public members is 
encouraged.  Final appointment of SAC members will require NIH approval. This 
committee will be used to evaluate the programs of the Center, research 
progress, the effectiveness of communications within the Center, and any 
other activities for which outside expertise is required or desirable.  The 
committee should meet at least annually and the NIH Science Officer for that 
Center and the Program Officer for the MDCRC Program should be invited to 
attend each meeting as observers.  The SAC will prepare an annual report 
including recommendations to assist the Center.  Copies of the SAC"s report 
will go to the Director, Co-Director, the appropriate NIH Science Officer, 
and to the Program Officer. 

o  Genetics Data Sharing in the MDCRC Program

NIH has a strong interest in the sharing of data and other resources produced 
through its funding, and has long-standing policies in this area (for the 
most recent statement, see the NIH Grants Policy Statement, page II-62, 
"Unique Research Resources," published in October 1998, related to the 
distribution of unique research resources produced with DHHS funding 
(http://grants.nih.gov/grants/policy/nihgps/). 

More specific policies have been promulgated from time to time to address the 
needs of particular areas of research.  For example, NIH has worked with 
journals and databases to encourage the rapid placement of unpublished DNA 
sequence data and crystallographic coordinates into public databases.  The 
National Human Genome Research Institute has a policy that all genomic data, 
whether published or not, should be shared as rapidly as possible and placed 
in the public domain 
(http://www.nhgri.nih.gov/Grant_info/Funding/Statements/RFA/new_data_release.html).
For grantees engaged in large-scale sequencing, the policy specifies data 
release within 24 hours of generation 
(http://www.genome.gov/page.cfm?pageID=10000910). 

Each application for MDCRC support must include a plan for the sharing of 
genetic materials and data.  This plan will be evaluated during the peer 
review of the application.  This sharing plan should address the issues 
raised in the following paragraphs.  The timeline for sharing of genetic data 
will be compatible with the timeline for sharing of other types of data as 
described under 6. Public Domain of Data (below).

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) specialized 
cooperative research center (U54) award mechanism, in which the Principal 
Investigator retains the primary responsibility and dominant role for 
planning, directing, and executing the proposed project, with NIH staff being 
substantively involved as a partner with the Principal Investigator, as 
described under the section "Cooperative Agreement Terms and Conditions of 
Award."  Applicants should request five years of support.  It is anticipated 
that competitive renewal applications for a second 5-year period will be 
allowed. 

Use of the Cooperative Agreement Mechanism

The use of a cooperative agreement mechanism for this RFA is intended to 
enhance coordination among MDCRCs in order to increase the impact of the 
MDCRC Program on the public health issues of muscular dystrophy.  The U54 
mechanism implements a process of NIH coordination, guidance, and ongoing 
evaluation. For example, it will permit NIH participation in a process of 
standardizing diagnostic and other tools across the MDCRCs in collaboration 
with the Center Directors and investigators.  It will permit awardee and NIH 
participation in the Steering Committee (described below) that will make 
decisions about collaborative studies that will use the resources of multiple 
centers, thus exceeding the capabilities present in any one center. 

FUNDS AVAILABLE
 
NIAMS, NINDS, and NICHD intend to commit approximately $4,500,000 in FY 2003 
to fund 2 to 3 new grants in response to this RFA. An applicant must request 
a project period of 5 years.  The direct costs requested cannot exceed  
$1,000,000 each year (exclusive of facilities and administrative costs of 
subcontracts with collaborating organizations).  Because the nature and scope 
of the proposed research will vary from application to application, it is 
anticipated that the size and duration of each award will also vary. Although 
the financial plans of NIAMS, NINDS, and NICHD 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. It 
is anticipated that this RFA will be reissued in 2004 for funding in FY 2005.
 
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
 
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS   

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

Note: The Following website has been established as an information resource 
for this RFA:  
http://www.niams.nih.gov/rtac/funding/grants/muscular_dystrophy_coop.htm.

To be funded, an MDCRC must include at least three highly meritorious 
scientific projects approved for five years. One of these must have the MDCRC 
Director as the principal investigator, and the highly meritorious projects 
must include one that is basic research and one that is clinical research.  
At least one project should be collaborative or discussed in terms of its 
ability to be expanded through collaborations.  There should be an 
Administrative Core and at least one Scientific Research Resource Core that 
will serve as a resource for the national muscular dystrophy research effort.

The Director, Co-Director, and all project and core PIs should be prepared to 
devote at least 20 percent effort to the MDCRC.  

The Administrative Core Budget should include 5 percent of the total budget 
(up to $50,000 per year) for Travel and Collaborative Activities developed 
through the Steering Committee and for Travel, including travel by the 
Director and Co-Director to an annual one-day meeting with NIH staff in 
Bethesda, Maryland. 

MDCRCs must commit to cooperate fully and to share data concerning patients, 
control subjects and specimen resources within the MDCRC Program, and with 
the broad scientific community, as specified by NIH.

COOPERATIVE AGREEMENT TERMS AND CONDITIONS OF AWARD

As part of the U54 Cooperative Center Grant process, the following Terms and 
Conditions of Award and details of the arbitration procedures pertaining to 
the scope and nature of the interaction between the NIH staff and the 
participating awardees will be incorporated into the Notice of Grant Award 
and provided to the Principal Investigator and the institutional official at 
the time of award.  These procedures will be in addition to the customary 
programmatic and financial negotiations that occur in the administration of 
grants.

Cooperative agreements are assistance mechanisms subject to the same 
administrative requirements as grants.  The special Terms and Conditions of 
Award are in addition to, and not in lieu of, otherwise applicable OMB 
administrative guidelines, HHS Grant Administration Regulations at 45 CFR 
Part 74 and 92, and other HHS, PHS, and NIH grant administration policies and 
procedures.  Cooperative Agreements are subject to the administrative 
requirements outlined in pertinent OMB, HHS, PHS, and NIH guidelines, with 
particular emphasis on HHS regulations at 42 CFR Part 52 and 45 CFR Part 74. 
Facilities and Administrative Cost (indirect cost) award procedures will 
apply to cooperative agreement awards in the same manner as for grants. 

The administrative and funding instrument used for this program is a 
Cooperative Agreement (U54), an "assistance" mechanism (rather than an 
"acquisition" mechanism) in which substantial NIH scientific and/or 
programmatic involvement with the awardee is anticipated during performance 
of the activity.  Under the cooperative agreement, the NIH purpose is to 
support and/or stimulate the recipient"s activity by involvement in and 
otherwise working jointly with the award recipient in a partner role, but it 
is not to assume direction, prime responsibility, or a dominant role in the 
activity.  Consistent with this concept, the dominant role and prime 
responsibility for the activity resides with the awardee(s) for the project 
as a whole, although specific tasks and activities in carrying out the 
studies will be shared among the awardees and an NIH Science Officer. 

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

Awardees have primary authorities and responsibilities to define objectives 
and approaches, and to plan, conduct, analyze, and publish results, 
interpretations, and conclusions of their studies.  The primary 
responsibilities of the awardees are to:

o  Define the research objectives

o  Design the necessary research protocols

o  Conduct specific studies

o  Analyze and interpret research data

o  Propose protocol modifications as required

o  Establish a Scientific Advisory Committee to the Center 

o  Provide information to the NIH Science Officer and NIH Program Officer 
concerning progress
 
o  Interact with the Food and Drug Administration (FDA) concerning clinical 
investigations, when appropriate 

o  Maintain career development opportunities to encourage new investigators 
to work in the field of muscular dystrophy research

o  Serve on the MDCRC Steering Committee

o  Participate in MDCRC collaborative activities approved by the Steering 
Committee

o  Agree to sharing of data and biological materials in accordance with 
approved sharing plans

o  Agree to participate in any centralized data facility that may be 
established according to Steering Committee policies

o  Abide by all scientific, practical and policy decisions of the Steering 
Committee

Awardees will retain custody of and primary rights to their data and 
intellectual property developed under the award, subject to current 
government policies regarding rights of access as consistent with current 
HHS, PHS, and NIH policies and subject to the terms and conditions of this 
RFA.  All research publications shall be submitted to NIH for administrative 
and policy review prior to submission for publication.  This review shall not 
be for the purpose of scientific oversight, but rather to ensure that NIH 
policies and/or representations that may imply NIH endorsement of clinical or 
research standards are not proposed.  These reviews may not unreasonably 
delay submission for publication.

2.  NIH Responsibilities

NIH Science Officers:

NIH Science Officers will be NIH program staff that will have substantial 
scientific involvement during the conduct of this activity, through technical 
assistance, advice, and coordination above and beyond normal program 
stewardship for grants.  Each Center will have a designated NIH Science 
Officer, and a given individual may be the NIH Science Officer for more than 
one Center.  The NIH Science Officers will be selected by the NIAMS, NINDS, 
and NICHD.  The degree of involvement by the NIH Science Officers will 
include the following: 

o  Assist in coordinating collaborative research efforts that involve 
multiple centers and
avoiding unwarranted duplication of effort across centers, 

o  Review and comment on critical stages in the research program before 
subsequent stages are implemented,

o  Assist in the interaction between the awardee and the FDA, when 
appropriate,

o  Assist in the interaction between the awardee and investigators of other 
institutions, as well as between the awardee and potential commercial 
sponsors,
 
o  Retain the option of recommending termination of studies if technical 
performance falls below acceptable standards, or when specific lines of 
research cannot be effectively pursued in a timely manner,

o  Retain the option to recommend additional research endeavors within the 
constraints of the approved research and negotiated budget, 

o  Serve on the MDCRC Steering Committee.

NIH Program Officer:

NIAMS, NINDS, and NICHD will jointly appoint a Program Officer who will have 
program oversight responsibilities for each Center and for the entire MDCRC 
Program.  This individual will not be a Science Officer.  The Program Officer 
will: 

o  Exercise the normal stewardship responsibilities of an NIH Program Officer 

o  Carry out continuous review of all activities to ensure objectives are 
being met

o  Have the option to recommend withholding support to a participating 
institution if technical performance requirements are not met 

o Will not be a member of the MDCRC Steering Committee

3.  Data Safety and Monitoring Board

NIH will facilitate establishing a Data Safety and Monitoring Board (see 
http://www.niams.nih.gov/rtac/clinical/safe_monitoring_plan.htm). 

4.  Collaborative Responsibilities/Steering Committee

Overall coordination of the MDCRC Program, consistent with the stated intent 
of the RFA, will be done by a Steering Committee consisting of the Principal 
Investigators of each MDCRC, NIH Science Officers, a public member, and a 
bioethicist.  An NIH grants management representative will serve as liaison 
to the Steering Committee.  Each Center Director (or designee) and Science 
Officer will have one vote.  Center membership on the Steering Committee 
becomes effective upon issuance of the Notice of Grant Award.  The Steering 
Committee may establish additional bylaws, subcommittees, or workgroups for 
specific tasks.  Science Officers may not chair any committee or 
subcommittee.  The Steering Committee meetings will be convened at least once 
yearly.  The purpose of these meetings is to share scientific information, 
assess scientific progress, identify new research opportunities, and discuss 
strategy and potential avenues of collaborations such as with industry, 
private foundations and/or NIH intramural scientists, establish priorities 
that will accelerate the translation of preclinical findings into clinical 
applications, reallocate resources and conduct the business of the 
cooperative research program.  Decisions will be made by a majority vote of a 
quorum, with an attempt for consensus when possible.  A quorum is the 
presence of a majority of the Center Directors and at least one Science 
Officer.  The Steering Committee can convene through telephone conferences or 
in person.  Outside consultants/experts may be asked to participate in these 
discussions as nonvoting advisors.  Collaborative projects among the MDCRCs 
will require Steering Committee approval.  It is expected that new 
collaborative programs will not replace the projects originally proposed in 
applications for MDCRC support, but will be supported by the funds set aside 
in the Administrative Core budget for this purpose. The Steering Committee 
may also be used to endorse research instruments that will be used across 
multiple centers. 

Steering Committee members will abide by all scientific, practical, and 
policy decisions of the Steering Committee.  Any Center Director who 
considers a Steering Committee decision unacceptable may appeal by following 
the arbitration procedure described below. 

5.  Arbitration Process

When agreement between an awardee and NIH staff or between awardees cannot be 
reached on scientific/programmatic issues that may arise after the award is 
made, an arbitration panel will be formed.  The arbitration panel will 
consist of one person selected by the Directors of the Centers, one person 
selected by the NIH, and a third person selected by both NIH staff and the 
Directors.  The decision of the arbitration panel, by majority vote, will be 
binding.  The special arbitration procedure in no way affects the right of an 
awardee 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. 

6.  Public Domain of Data

The data from this cooperative agreement will first be available to be 
analyzed and interpreted by the collaborators in the project.  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, the awardees will make data of all types available to the larger 
research community no more than 24 months from the date after which the final 
waves of data for a particular project have been collected and cleaned.  More 
rapid sharing of data is encouraged.

7.  Scientific Advisory Board

The Steering Committee will recommend a Scientific Advisory Board (SAB) of 
independent experts in the research areas represented among the centers. The 
SAB will be appointed by and report to NIH (namely NIAMS, NINDS, and NICHD).  
It will advise the Steering Committee on the scientific aspects of MDCRC 
activities, including providing review of collaborative studies that will 
need to be approved by the Steering Committee before being implemented.  The 
SAB will participate in the annual meeting of the Steering Committee and be 
consulted as necessary.  There should be at least seven members of SAB, at 
least one a public member.   There may be overlap between the SAB and the NIH 
Muscular Dystrophy Research Task Force (see 
http://www.niams.nih.gov/ne/reports/sci_wrk/2002/mdmeet.htm).

8.  Progress Reviews

Progress of the MDCRC will be reviewed annually by the NIH Program Officer at 
the time each continuation application is considered for funding to assure 
that satisfactory progress is being made in achieving the project objectives 
and that each site is following the procedures recommended and approved by 
the Steering Committee.  During the first year of funding, and during 
subsequent years, if deemed necessary by the Program Officer, reviews will be 
more frequent.  Human subject enrollment should be reported every six months.  
Should problems arise in the conduct of the Center, the NIH Program Officer 
may require that the awardee submit quarterly reports on progress and fiscal 
matters.  By acceptance of this award, the awardee agrees to abide by 
decisions and policies of the Steering Committee and the other terms and 
conditions listed above or referenced in the Notice of Grant Award.

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:

Richard W. Lymn, Ph.D.
Chief, Muscle Biology Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-5128
FAX:  (301) 480-4543
Email: LymnR@mail.nih.gov

James W. Hanson, M.D.
Chief, Mental Retardation and Developmental Disabilities Branch
Center for Research for Mothers and Children
National Institute of Child Health and Human Development
6100 Executive Blvd., Room 4B09    MSC 7510 
Bethesda, MD 20892-7510
Telephone:  (301) 496-1383
FAX: (301) 496-3791
Email: hansonj@mail.nih.gov

Giovanna M. Spinella, M.D.
Neurogenetics and Development Program
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd.  Rm. 2132
Rockville, MD 20892-9527
Telephone:  (301) 496-5745
FAX: (301) 401-1501
Email: gs41b@nih.gov

o Direct your questions about peer review issues to:

Alan Willard, Ph.D.
Chief, Scientific Review Branch, 
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd.  Rm. 3208
Rockville, MD 20892
Telephone: (301) 496-5390
FAX: (301) 402-0182
Email: aw135y@nih.gov

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

Melinda Nelson
Grants Management Officer
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd. Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  nelsonm@mail.nih.gov

Christopher Myers
Grants Management Officer
National Institute of Child Health and Human Development
Building 6100E/Room 8A17
6100 Executive Blvd. MSC 7510
Bethesda, MD 20892-7510
Email: cm143g@nih.gov

Sheila Simmons
Grants Management Officer
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd.  Rm. 3250
Rockville, MD 20892
Telephone: (301) 496-9231
FAX: (301) 402-0219
Email: simmonss@ninds.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 NIH 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:

Richard W. Lymn, Ph.D.
Chief, Muscle Biology Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
Telephone:  (301) 594-5128
FAX:  (301) 480-4543      
Email: LymnR@mail.nih.gov

PRE-APPLICATION MEETING

The NIAMS, NINDS, and NICHD anticipate holding a pre-application meeting in 
January 2003, through a teleconference to which all interested prospective 
applicants are invited.  Program and review staff will make presentations 
that explain their goals and objectives for the Muscular Dystrophy 
Cooperative Research Centers and answer questions from the attendees. 
Prospective applicants are urged to monitor the NIH Guide Notice for the date 
and time of the meeting at http://grants.nih.gov/grants/guide/index.html.  
Additionally, consult the following website, established as an information 
resource for this RFA:  
http://www.niams.nih.gov/rtac/funding/grants/muscular_dystrophy_coop.htm

SUBMITTING AN APPLICATION

Applications must be prepared using the PHS 398 research grant application 
instructions and forms (rev. 5/2001).  The PHS 398 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.
 
SPECIFIC INSTRUCTIONS FOR PREPARING AN APPLICATION

Use form PHS 398 (http://grants.nih.gov/grants/funding/phs398/phs398.html).  
Each budget unit (project or core) should be written in the style and within 
the page limitation described in the PHS 398 instruction kit. To aid in the 
review of these applications, the applicant should assemble the component 
units following the format described below.  Additional instructions for 
preparing an MDCRC grant application and sample formats are available at the 
following URL link:  
http://www.niams.nih.gov/rtac/funding/grants/muscular_dystrophy_coop.htm.  

Please note that each part of the application should be complete in itself, 
as different reviewers may review different parts.

SECTION I - GENERAL INFORMATION FOR THE ENTIRE APPLICATION

A.  FACE PAGE

This is Form Page 1 of the application, number succeeding pages 
consecutively. 

Complete all items on the face page as directed. In the title block, item 1, 
put "MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTER."  Mark item 2 "yes" and 
write in the RFA code AR03-001, as listed in the NIH Guide to Grants and 
Contracts, and "MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTERS" for the 
title.
 
B.  DESCRIPTION, PERFORMANCE SITES, AND KEY PERSONNEL

On Form Page 2, describe briefly the proposed program indicating the goals 
and objectives of the research projects and identify the purposes of the 
proposed cores.  Do not exceed the space allowed.  List key scientific and 
technical personnel participating in the Center.  Use continuation pages as 
necessary, numbering consecutively. 

C.  TABLE OF CONTENTS

Adapt this page from Form PHS 398 and write a Table of Contents appropriate 
for the MDCRC grant application, following these instructions. This is 
paginated to follow the list of Key Personnel. Do not use letters (e.g., 4a, 
4b, 4c, etc.).  The Table of Contents should list all projects and cores for 
which funding is sought.  Each project and core should be listed by the title 
and Principal Investigator.  Specifically list the locations of the checklist 
and the various requested supporting documents, e.g., animal and human 
subject assurances, and bibliographies.

D.  BUDGET ESTIMATES

To aid in the review of your application, it is suggested that the forms 
found as pages 4 and 5 in PHS Form 398 be used for all budgets. Justify and 
document all costs for current and future years throughout.  Prepare a series 
of composite Budget Tables for the Center as requested below. 

1.  Composite Budget

The direct costs requested cannot exceed $1,000,000 each year (exclusive of 
facilities and administrative costs of subcontracts with collaborating 
organizations).  The Administrative Core Budget should include 5 percent of 
the total budget (up to $50,000 per year) for Travel and Collaborative 
Activities developed through the Steering Committee.

a. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," of the PHS 
398 to present the total direct cost budget for all requested support for the 
first year.  For each category, such as "PERSONNEL," "EQUIPMENT," etc., list 
the amount requested for each research project and for each core unit. 

If consortium arrangements have been made involving other institutions or 
organizations, include total costs (direct and F&A) associated with such 
third party participation in the "CONSORTIUM/CONTRACTUAL COSTS" category. 
Costs for purchased services should be itemized under "OTHER EXPENSES." 

b.  Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of the PHS 
398 to prepare a budget, by category, that provides direct cost totals for 
each year of requested support.

E.  BIOGRAPHICAL SKETCHES

Biographical sketches are required for all key scientific and technical 
personnel participating in the research projects and core units as listed on 
Form Page 2.

Beginning with the Center Director and Co-Director, and following in 
alphabetical order, submit biographical sketches as described in the 
"Instructions for Form PHS- 398," using Form Page 6.

G.  ENVIRONMENT AND RESOURCES

Complete the "RESOURCES" section on Form Page 8 of the PHS 398 for the 
overall Center.  Briefly describe the features of the institutional 
environment that are or would be relevant to the effective implementation of 
the proposed program.  As appropriate, describe available resources, such as 
clinical and laboratory facilities, participating and affiliated units, 
patient populations, geographical distribution of space and personnel, and 
consultative resources.  Include information on the support and commitment of 
the parent institution for the Center. Use continuation pages as needed. 
Include any supporting letters from the Institution.

H. CENTER LEADERSHIP

The emphasis in this section should be on the qualification of the MDCRC 
leadership. Describe the qualifications of the MDCRC Director to lead the 
program, and that of the Co-Director to assist. 

I.  INTRODUCTORY OVERVIEW OF THE CENTER (10-page limit)

Provide an overview of the entire proposed Center describing the research 
central theme and goals.  Describe how the overall Center can achieve its 
major objectives.  Explain the proposed contribution of each of the projects 
in achieving the objectives of the Center.  Furthermore, the administrative 
arrangements and support necessary to effect the research should be carefully 
described in the application.  Shared resources should be described.  In 
addition, provide detailed information on collaborations, recruitment, 
facilities and resources.

1.  Purpose and Objectives of the Center.  Discuss the philosophy and 
objectives of the Center and general plans for the proposed grant period. 
Discuss the composite research program, highlighting its central theme.  List 
by title and investigator the component research projects and core units, 
showing the interrelationship between the research projects and the core 
units and their relationship to the central theme.  Describe relevant history 
leading up to the Center application.

2.  Administration, Organization, and Operation of the Center.  Include 
information on the support and commitment of the parent institution for the 
Center, the authority of the Director, the use of advisory committees, and 
the method of determining core access and space assignment.  Describe an 
organizational framework and provide an organizational chart. 

3.  Assurances and Collaborative Agreements.  Any arrangements for 
collaborative and cooperative endeavors or subcontracting should be 
highlighted.  Letters of Intent to Collaborate and Letters of Agreement from 
consultants should be referenced here and included at the end of the 
appropriate research project or core unit.

J.  PROGRESS REPORT/PRELIMINARY DATA PERTAINING TO THE WHOLE CENTER (5-page 
limit)

This section should be used to present, in condensed form, previously 
published and/or preliminary data that are relevant to proposed center 
activities and research projects that will be unique to the center and will 
involve collaboration across projects and/or cores within the center.  Since 
individual projects, and preliminary data relevant to them, will be described 
in the following section, only those collaborative activities/projects that 
bear directly on the proposed center activities should be summarized here. 
For ongoing projects or existing cores, list relevant publications published 
or accepted for publication during the past five-years.  The list of 
publications does not count against the page limit.

SECTION II. PROPOSALS FOR INDIVIDUAL PROJECTS AND CORES

A.  PROJECTS: Identify each project by an Arabic numeral (1, 2, 3, etc.) and 
a title.  For each component research project, a full description is to be 
provided following the format and page limits presented in Form PHS 398.  
Begin the presentation of each component research project on a separate cover 
page.  The description of each project must be complete in itself, as 
different reviewers may review different projects.  Each research project 
will receive a priority score.  At least one project should be collaborative 
or discussed in terms of its ability to be expanded through collaborations. 

For each project, include the following information using Form PHS 398:

1. Face Page.  Do not use Form 398 face page, instead, use plain paper, and 
include the following information:  
a.  Project Title
b.  Project Principal Investigator, degree, title, location
c.  Other investigators, consultants, and collaborators, degrees, titles 
(Associate Professor, Postdoctoral Fellow, student).

2. Description, Performance Site(s) and Personnel (use Form Page 2 of PHS 
398) 

3. Budget (use the budget pages from Form PHS 398)

a.  First year (use Form Page 4 of PHS 398 for each)

b.  Total project period (use Form Page 5 of PHS 398 for each) 

Consortium Budgets (if applicable) should be presented as described in Item 1 
(Composite Budget), including a budget for the entire proposed project 
period.  Total Direct and F&A costs of sub-awardees are to be shown under 
"CONSORTIUM/CONTRACTUAL COSTS" on individual research project or core budgets 
and a detailed consortium budget is to be inserted following the appropriate 
research project or core budgets.

Budget Justifications: Describe the specific functions of key scientific and 
technical personnel, consultants, collaborators, and support staff.  For all 
years, explain and justify any unusual items such as major equipment or 
alterations and renovations.  For future years of support requested, justify 
any significant increases in any category over the first 12-month budget 
period.  Identify such significant increases with asterisks against the 
appropriate amounts.

4. Resources and Environment (use the relevant pages from Form PHS 398)

5.  Research Project Plan (Do not exceed 25 pages for Sections a-d)  

Start with an Introductory remark addressing: (i) whether and how it is a 
clinical project, and (ii) its relevance to the overall theme of the Center.  
Then address the following:

a.  Specific Aims

b.  Background and Significance

c.  Preliminary Studies

d.  Research Design and Methods.  In addition to usual contents of this 
section, describe the research project"s use of core unit services, including 
need for the services, and the advantages and cost effectiveness of core unit 
usage for the project.

e.  Human Subjects.  For research involving human subjects, this section must 
address: Protection of Human Subjects, the inclusion of women, minorities and 
their subgroups, and children as research subjects, and Data and Safety 
Monitoring Plan as provided in the instructions for PHS 398.

f.  Vertebrate Animals

g.  Literature Cited

h. Consortium/Contractual Agreements: including pertinent letters of 
assurance and intent.

i.  Consultants: including pertinent letters of assurance and intent.

B.  CORES: Identify each proposed core unit by a letter (A, B, C..., core A 
being the Administrative Core and Core B will be a Scientific Research 
Resource Core) and a title (Administrative, Molecular/Cellular...). For each 
core, a full description is to be provided following the format and page 
limits presented in Form PHS 398.  Begin the presentation of each core on a 
separate cover page.  The description of each core must be complete in 
itself, as different reviewers may review different cores, without cross-
referencing.  Each core will be rated using an adjectival descriptor, such as 
outstanding, excellent, or poor.

A core is a shared central laboratory or clinical research facility, service, 
or resource.  A core may be a unit designed just for the MDCRC projects or 
may be an institutional core unit.  However, funds may only be requested for 
MDCRC use, and the core must serve a minimum of two projects within the 
MDCRC, with no project dominating use of the core.  Each core is directed by 
a faculty investigator (the Core Director) with substantial expertise related 
to the core. Applicants should document and describe briefly the projects 
that will depend upon resources provided by the cores (clinical cores, in 
particular).

Scientific Research Resource Cores should be able to support research for 
projects by researchers not in the MDCRC.  Two important and related 
considerations are (1) the degree to which currently funded investigators 
within or outside the center will use and benefit from core resources and (2) 
the degree to which the resources will promote new and/or expanded muscular 
dystrophy research efforts locally, regionally or nationally.  The core 
principal investigator should devote at least 20 percent effort to the core.  
 
For each core, include the following information using Form PHS 398:

1. Face Page.  Do not use Form 398 face page, instead, use plain paper, and 
include the following information:  
a.  Core Title
b.  Core Director, degree, title, location
c.  Other investigators, consultants, and collaborators, degrees, titles 
(Associate Professor, Postdoctoral Fellow, student).

2. Description, Performance Site(s) and Personnel (use Form Page 2 of PHS 
398) 

3. Budget (use the budget pages from Form PHS 398)

4. Resources and Environment (use the relevant pages from Form PHS 398)

5.  Research Plan. This part also should be presented using the headings a-i, 
as described for Projects above, taking care that the following ADDITIONAL 
points are addressed in appropriate sections: 

For Research cores:

a.  a decision-making process for use of the core unit
b.  plans for quality control
c.  a summary table for the first year of the proposed grant showing the 
quantitative use (percent) of the core unit by the component research 
projects
d.  cost effectiveness
e.  cost recovery, if any

For Scientific Research Resource Cores, also discuss:

f.  suitability as a resource for the national muscular dystrophy research 
effort
g.  plans for access by researchers outside the MDCRC
h.  plans for setting priorities of access and use

For the Administrative core, the following additional points should be 
addressed in the "Research Plan" Section:

a.  the authority of the Director
b.  advisory committees
c.  an organizational framework and organizational chart
d.  a contingency plan in case the Center director is unable to perform his 
responsibilities
e.  services that will be provided

The Administrative Core Budget should include 5 percent of the total budget 
(up to $50,000 per year) for Travel and Collaborative Activities developed 
through the Steering Committee.

SECTION III - CHECKLIST - As required in Form PHS 398

SECTION IV - APPENDIX

Include materials as appropriate (see PHS 398).  All appendix material must 
be clearly marked with the name of Center Director and the appropriate 
project or core.  Separate copies of appendix material should be supplied for 
each core or project to which it is applicable.

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, 
including all appendix material, must be sent to:

Richard W. Lymn, Ph.D.
Chief, Muscle Biology Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
One Democracy Plaza
6701 Democracy Blvd., Suite 800
Bethesda, MD  20892-4872
[Bethesda, MD 20817 (for express/courier service)]
 
APPLICATION PROCESSING: Applications must be received by 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.
 
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.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed. This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must 
include an Introduction addressing the previous critique.

PEER REVIEW PROCESS  
 
Applicants should keep in mind that the written application is the basis for 
the merit review.  Site visits are not anticipated. Upon receipt, 
applications will be reviewed for completeness by the CSR and responsiveness 
by the NIH program staff. Incomplete and/or non-responsive applications will 
be returned to the applicant without further consideration.

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 NIH in accordance with the review criteria stated below.  As part 
of the initial merit review, all applications will:

o Receive a written critique
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 second level review by the National Advisory Councils for NIAMS, 
NINDS, and NICHD. 

REVIEW CRITERIA

The criteria to be used in the evaluation of grant applications are listed 
below.

The Centers must include three or more individual research projects, which 
reflect hypothesis-driven research, plus shared research resources (cores).  
The application must represent more than an interesting collection of 
projects.  It is critical that there is evidence of the potential for a 
meaningful center with a real theme and identity.

A.  RESEARCH PROJECTS

Reviewers will evaluate each research project using the criteria listed below 
and assign a priority score.  Each criterion will be addressed and considered 
by the reviewers in assigning the overall score for project merit: 

(1) SIGNIFICANCE:  Does your study address an important problem? If the aims 
of your application are achieved, how do they advance scientific knowledge?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(2) APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?

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

(4) INVESTIGATOR: Are you appropriately trained and well suited to carry out 
this work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(5) ENVIRONMENT:  Does the scientific environment in which your work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

B. SHARED RESOURCES (CORES)

Each core will be evaluated and assigned an adjectival descriptor.

1. Adequacy of the justification for each specialized resource relative to 
its essential need for the conduct of MDCRC research and MDCRC collaborative 
projects.

2. Adequacy of qualifications and performance (if applicable) of managers of 
resources to conduct high quality, reliable resource operations. 

3. Appropriateness of the requested budgets to conduct each resource 
operation.

4. Adequacy of plans for oversight of resources and the prioritization of 
work.

SCIENTIFIC RESEARCH RESOURCE CORES

In addition to the above, the following criteria will be addressed:

5.  Value as a national resource for research on muscular dystrophy.

6.  Accessibility to researchers not a part of the MDCRC.

7.  The quality of the system to set priorities for access and use as a 
shared resource.

C.  ADDITIONAL REVIEW CRITERIA SPECIFIC TO MDCRC PROGRAM 

Listed below are additional review criteria to be used in the evaluation of 
MDCRC applications, these criteria will be applied to applications by 
evaluating preliminary work to organize the center, history of muscular 
dystrophy research by the applicants, and plans for implementation of the 
proposed program.

Applicants should clearly demonstrate the ways in which the MDCRC would 
contribute to the growth of local research programs, support ongoing 
projects, cooperate with other MDCRCs in collaborative research, and attract 
both senior and new investigators to muscular dystrophy.

It is anticipated that inclusion of a "weak" or "nonessential" project in the 
application will reflect poorly on the overall program.  In addition, NIH 
retains the right to delete individual projects when making final funding 
decisions regarding MDCRC applications, for example, those that score below 
the current R01 funding level.  It will be mandatory for each successful 
application to include at least three fundable research projects.  At least 
one of the fundable projects must be clinical research as defined above.

Specific Review Criteria:

Each project will receive a priority score. This score reflects not only the 
feasibility of the project and adequacy of the experimental design, but also 
the design of the project to advance both the theme of the MDCRC and the 
interaction between basic research and clinical investigation.

1. How the proposed MDCRC combines basic and clinical research into the 
scientific goals and research theme,     

2. Scientific merit of each proposed project.

3. Scientific merit of combining the component parts into an MDCRC,

4. Technical merit and justification of each core unit, will each core 
enhance collaborative and/or interdisciplinary research within the MDCRC and 
the wider research community? 

5. Competence of the investigators to accomplish the proposed research goals, 
their commitment, and the time they will devote to the research program,

6. Adequacy of facilities to implement the goals of the MDCRC Program and 
perform the proposed research, including laboratory and clinical facilities, 
instrumentation, and data management systems, when needed,

7. Adequacy of plans for interaction among investigators, the integration of 
the various projects and core units, and potential for interaction with 
scientists from other departments and components,
 
8. Qualifications, experience and commitment of the MDCRC Director and 
his/her ability to devote time and effort to provide effective leadership, 
evidence for the scientific and organizational vision,

9. Scientific and administrative structure, including internal and external 
procedures for monitoring and evaluating the proposed research and for 
providing ongoing quality control and scientific review,
 
10. Effectiveness of the proposed center in meeting the purpose of the RFA, 
namely, does it promote side-by-side basic, translational, and clinical 
research, provide resources that can be used by the national muscle biology 
research community, and provide training and advice about muscle diseases for 
researchers and physicians who provide initial diagnosis and treatment?  What 
are the potentials for collaborations with other MDCRCs and investigators?

11. Management capabilities for the Center that include fiscal 
administration, procurement, property and personnel management, planning, and 
budgeting,

12. Institutional commitment to the program, and the appropriateness of 
resources and policies for the administration of an MDCRC, including faculty 
positions for muscular dystrophy research.

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your 
application will also be reviewed with respect to the following:

o PROTECTIONS:  The adequacy of the proposed protection for humans, animals, 
or the environment, to the extent they may be adversely affected by the 
project proposed in the application.

o INCLUSION:  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 
included in the section on Federal Citations, below).

RECEIPT AND REVIEW SCHEDULE

Letter of Intent Receipt Date:   January 15, 2003
Application Receipt Date:        February 24, 2003
Scientific Review Date:          May/June 2003
Advisory Council Date:           September 2003
Earliest Date of Award:          September 2003

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, including balance between muscular dystrophy 
research and scientific resource areas.

REQUIRED FEDERAL CITATIONS 

MONITORING PLAN AND DATA SAFETY AND MONITORING BOARD: Research components 
involving Phase I and II clinical trials must include provisions for 
assessment of patient eligibility and status, rigorous data management, 
quality assurance, and auditing procedures.  In addition, it is NIH policy 
that all clinical trials require data and safety monitoring, with the method 
and degree of monitoring being commensurate with the risks (NIH Policy for 
Data Safety and Monitoring, NIH Guide for Grants and Contracts, June 12, 
1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html).  

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 AMENDMENT "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.

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research 
on hESCs can be found at http://grants.nih.gov/grants/stem_cells.htm 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 (see http://escr.nih.gov).   
It is the responsibility of the applicant to provide 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 RFA 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.

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 Nos. 93.846 (NIAMS), 93.853 (NINDS), and 93.865 
(NICHD) and is not subject to the intergovernmental review requirements of 
Executive Order 12372 or Health Systems Agency review.  Awards are made under 
authorization of Sections 301 and 405 of the Public Health Service Act as 
amended (42 USC 241 and 284) and administered under NIH grants policies 
described at http://grants.nih.gov/grants/policy/policy.htm and under Federal 
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. 

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

	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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