Expired RFA-HD-09-027: Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (U54)

Department of Health
and Human Services (HHS)

NIH... Turning Discovery Into Health^®

Part I Overview Information

Department of Health and Human Services

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

Components of Participating Organizations
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (http://www.niams.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI) (http://www.nhlbi.nih.gov)
National Institute of Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov)

Title: Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (U54)

Announcement Type
This is a reissue of RFA-NS-08-002.

Update: The following update relating to this announcement has been issued:

July 27, 2012 - This RFA has been reissued as RFA-AR-13-012.
September 16, 2009 - See Notice NOT-HD-09-023 Notice of Additional Information to Applicants.

Request for Applications (RFA) Number: RFA-HD-09-027

Catalog of Federal Domestic Assistance Number(s)
93.865, 93.846, 93.837, 93.853

Key Dates
Release Date: May 13, 2009
Letters of Intent Receipt Date: October 13, 2009
Application Receipt Date: November 10, 2009
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date(s): July 1, 2010
Additional Information to Be Available Date (Url Activation Date): June 16, 2009
Expiration Date: November 11, 2009

Pre-Application Information Call and On-Line Information

The NIH will hold a pre-application informational conference call on June 9, 2009, at 11:00 am EST, to which all interested prospective applicants are invited. Program and review staff will make presentations to explain the goals and objectives of the Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers and answer questions from call participants.

To obtain, the call-in information, please contact Dr. Ljubisa Vitkovic ([email protected] or 301-402-1822) at least 24 hours prior to the call.

By June 16, 2009, a Question and Answer document, based upon this informational call and other inquiries from potential applicants, will be posted at: http://www.wellstonemdcenters.nih.gov/.

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

Purpose. This funding opportunity announcement (FOA) solicits new (type 1) and competitive renewal (type 2) applications for the support of Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers (MDCRCs). Successful applicants will join a network of existing Centers to foster the translation of new scientific findings and technological developments into novel treatments for the muscular dystrophies. Each Center may contain a mixture of basic, translational, or clinical research, as long as efforts are directed toward the steps required for therapeutic development, including therapeutic target identification, characterization, and validation, development of diagnostics and biomarkers to characterize or stratify patient populations, in vitro assay development, animal model development and characterization, candidate therapeutic efficacy screening, preclinical therapeutic optimization and FDA-required activities leading to an investigational new drug (IND) application, clinical infrastructure and studies in support of a clinical trial, patient-oriented natural history studies, and early stage clinical trials for one or more types of muscular dystrophy. Applicants should propose multi-disciplinary and collaborative studies that address one or more gaps in the therapeutic development pipeline for muscular dystrophy. Research problems should require substantial collaborative efforts to solve, and thus are best carried out in a center setting.
Mechanism of Support. This FOA will utilize the U54 Specialized Centers Cooperative Agreement grant mechanism.
Funds Available and Anticipated Number of Awards. The NICHD, NIAMS, NINDS, and NHLBI anticipate commitment of up to $3,000,000 in direct costs in FY2010 through this announcement; 3 awards are anticipated.
Budget and Project Period. Applicants may request up to $1M in direct costs/year (exclusive of facilities and administrative costs of subcontracts with collaborating organizations). The total project period for an application submitted in response to this funding opportunity may not exceed 5 years. Awards issued under this FOA are contingent upon the availability of funds.
Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
Number of Applications. An individual may be a principal investigator on only one application submitted in response to this initiative.
Resubmissions. Resubmission applications are not permitted in response to this FOA.
Renewals. Renewal applications are permitted in response to this FOA.
Special Date(s). This FOA uses non-standard due dates. See Receipt, Review and Anticipated Start Dates.
Application Materials. See Section IV.1 for application materials.
Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY 301-451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

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

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

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

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Overview

The Muscular Dystrophy Community Assistance, Research, and Education Amendments of 2001 (the MD-CARE Act, Public Law 107-84) specified a number of provisions for expanding and intensifying research on muscular dystrophy. One provision of the MD-CARE Act was that the NIH establish centers of excellence for research on muscular dystrophy. The Muscular Dystrophy Cooperative Research Centers (MDCRCs) program was subsequently developed in honor of Senator Paul D. Wellstone, a champion of muscular dystrophy research. In the years following the MD-CARE Act, the NIH sponsored several Requests for Applications for MDCRCs that have led to the funding of the six active MDCRCs:

http://grants.nih.gov/grants/guide/rfa-files/RFA-AR-03-001.html;

http://grants.nih.gov/grants/guide/rfa-files/RFA-AR-04-008.html;

http://grants.nih.gov/grants/guide/notice-files/NOT-AR-05-006.html; and

http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-08-002.html.

Reauthorization of the MD-CARE Act in 2008 codified the MDCRCs as the Paul D. Wellstone MDCRCs. MDCRCs funded through this program have contributed toward the goal of improving the detection, diagnosis, and treatment of the muscular dystrophies. The currently active MDCRCs promote basic, translational and clinical research and provide important resources that can be used by the national muscle biology and neuromuscular research communities. The MDCRCs also serve as focal points for research collaborations in the muscular dystrophy field and provide training and advice about muscular dystrophy for basic and clinical researchers.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Heart, Lung, and Blood Institute (NHLBI) are now committed to continuing and enhancing the tradition of scientific excellence that has been fostered in the MDCRC program. While each center may contain a mixture of basic, translational, and clinical studies, the overall focus of this continuation of the MDCRC program is directly upon tightly integrated activities that foster the development of new therapies for the muscular dystrophies. Major review criteria for the MDCRC program include the degree to which an applicant demonstrates the potential to attack key problems in muscular dystrophy that require substantive collaborative efforts to solve and the ability of the applicant group to serve as a national infrastructure and training resource.

Background

Muscular dystrophy refers to a group of hereditary, progressive degenerative disorders causing weakness of the skeletal or voluntary muscles. There are many different forms of muscular dystrophy, which differ in their age of onset, penetrance, severity, and pattern of muscles affected. Most types of muscular dystrophy are not simply muscle disorders, but rather multi-system disorders with manifestations in a variety of body systems, including the heart, gastrointestinal system, endocrine glands, skin, eyes, brain, and other organ systems. The major forms of muscular dystrophy include congenital, distal, Duchenne/Becker, Emery-Dreifuss, facioscapulohumeral, limb-girdle, myotonic, and oculopharyngeal. Although some forms first become apparent in early childhood, others may not appear until middle age or later, but all have a significant clinical, economic, and psychosocial burden of disease.

While several therapeutic development strategies have shown promise in cell-based or animal models, and some early stage clinical trials in humans have begun, few therapies are effective in even slowing the progression of any form of muscular dystrophy. Moreover, there is currently no consensus as to which of several potential therapeutic strategies, or combination of strategies, may ultimately prove successful in reducing patient morbidity and mortality. Symptomatic treatment, though not able to stop disease progression, may improve the quality of life for some individuals. Recent advances in genetics, pathogenic mechanisms, therapeutic technology, and patient diagnostics do provide compelling opportunities for advancing translational and clinical science in the muscular dystrophies. The Action Plan for the Muscular Dystrophies (http://www.ninds.nih.gov/find_people/groups/mdcc/MDCC_Action_Plan.doc), approved and released in January 2006 by the interagency Muscular Dystrophy Coordinating Committee (http://www.ninds.nih.gov/find_people/groups/mdcc/index.htm), is a consensus document with input from patients, advocacy groups, basic scientists, clinicians, and Federal agencies that highlights many of these scientific opportunities and the need for broad cooperation in seeking effective treatments for the muscular dystrophies.

Specific Objectives of the Research Program

NICHD, NIAMS, NINDS, and NHLBI seek to further develop the MDCRC program to foster the translation of new scientific findings and technological developments into the clinical research setting. This FOA solicits both new (type 1) and competitive renewal (type 2) applications for MDCRCs. Under the FOA, each Center may contain a mixture of basic, translational, or clinical research, as long as efforts are directed toward the steps required for therapeutic development. These may include, but are not limited to therapeutic target identification, characterization, and validation, development of diagnostics and biomarkers to characterize or stratify patient populations, in vitro assay development, animal model development, candidate therapeutic efficacy screening, preclinical therapeutic optimization and FDA-required activities leading to an investigational new drug (IND) application, clinical research infrastructure, patient-oriented natural history studies, clinical outcome measure validation, cohort characterization, and other studies in support of clinical trials, and early stage clinical trials for one or more types of muscular dystrophy. The proposed research, including a consideration of the balance between basic, translational and clinical research, should be feasible within the budget limits described elsewhere in this FOA. Applicants should emphasize multi-disciplinary and collaborative studies that address one or more gaps in the therapeutic development pipeline. In addition, research problems should require substantial collaborative efforts to solve, and thus are best carried out in a center setting. Each MDCRC should involve clinical research and should engage muscular dystrophy patients and patient advocates in educational programs or as advisors.

Applicants with projects that are stand-alone, single-component translational research programs or clinical trials in muscular dystrophy should instead consider the following Program Announcements:

Exploratory/Developmental Projects in Translational Research for Neuromuscular Disease (R21) (PAR-08-228);
Cooperative Program in Translational Research for Neuromuscular Disease (U01) (PAR-08-229);
Preliminary Investigations Leading to Optimal Trials in Neurology (R01) (PAR-07-294);
NINDS Clinical Trial Planning Grant Program (R34) (PAR-06-460).

Collectively and in cooperation with the NIH, the MDCRCs form part of a coordinated national program. Applicants are expected to emphasize new ideas, novel approaches, and state-of-the-art technologies to address any or all of the steps in the pipeline from identification of mechanistic targets for therapeutic development to translation of that knowledge into clinical interventions for the prevention or treatment of muscular dystrophy. Multidisciplinary collaborative efforts, in particular those involving basic scientists and clinicians with appropriate expertise, are expected for the components of an MDCRC. MDCRC applicants should also propose resource core facilities and training activities that will have national impact upon research in muscular dystrophy.

Areas of interest for MDCRC components under this FOA are, but not limited to, the following:

Disease mechanisms:

continue gene identification and biochemical characterization in the various forms of muscular dystrophy to identify novel pathogenic mechanisms and validate new targets for therapeutic development;
identify and validate primary or downstream pathogenic mechanisms as putative targets for therapeutic development;
develop and validate model organisms as mechanistic models for muscular dystrophy in humans.

Diagnostics and biomarkers:

develop and validate gene tests or minimally invasive diagnostic techniques for muscular dystrophy, to allow identification and/or stratification of cohorts for clinical studies and trials;
develop and validate diagnostic tools and biomarkers as outcome measures for clinical trials, particularly tools/biomarkers that may provide short-term surrogates for the prediction of the long-term impact of a candidate therapeutic.

Therapeutic development:

establish and implement the use of molecular and cellular assays and animal models where none exists or where such models are insufficient, in order to facilitate therapeutic target identification and/or preclinical therapeutic development efforts;
evaluate in preclinical models and human testing the efficacy of FDA-approved drugs that may be potentially useful for treatment of muscular dystrophy;
identify and test novel mechanisms to either promote muscle regeneration or reduce muscle wasting in muscular dystrophy;
evaluate, through basic and preclinical translational studies, the therapeutic potential of muscle progenitor or stem cells;
determine optimal gene constructs, promoters, and delivery vehicles for the application of systemic gene therapy to muscular dystrophy;
develop agents for gene modification or repair in the muscular dystrophies and devise and test means for their systemic delivery;
develop technologies and/or implement strategies for small molecule therapeutic strategies in muscular dystrophy;
develop combination therapies that rely upon two or more existing or novel therapeutic strategies in muscular dystrophy;
establish standardized endpoints for preclinical trials in animal models of muscular dystrophy and ensure that the capacity is available for testing of therapeutic strategies;
ensure the availability and use of large animal models for late stages of preclinical development.

Clinical trial infrastructure, clinical trials, and patient management:

establish patient registries and repositories (genetic, tissue, genotype/phenotype, etc.) to facilitate clinical studies and trials in muscular dystrophy;
evaluate existing quality of life instruments and develop and validate new instruments as outcome measures for clinical trials in muscular dystrophy;
conduct natural history studies to characterize disease onset and progression and to assess the interrelationship of outcome measures for all of the dystrophies;
develop and validate new tools, or more carefully evaluate existing tools, to measure the quality of life and burden of clinical disease as necessary for clinical trials in muscular dystrophy;
determine the sensitivity of clinical endpoints to changes in disease severity and determine the magnitude of changes in endpoints that are clinically meaningful to muscular dystrophy patients;
assess the incidence and prevalence of secondary conditions in muscular dystrophy;
perform early stage proof of concept or safety clinical trials in muscular dystrophy.

These and other potential research directions for MDCRC applicants are described in detail in the Action Plan for the Muscular Dystrophies (http://www.ninds.nih.gov/find_people/groups/mdcc/MDCC_Action_Plan.doc). Potential applicants are strongly encouraged to refer to the Action Plan and to discuss plans for the research project and core resource components of MDCRCs with NICHD, NIAMS, NINDS, and NHLBI program staff.

General Description of MDCRC and Center Components

The organizational structure of the proposed MDCRC should facilitate the flow of new scientific findings and technologies into translational and clinical research. Each center may contain any combination of basic, translational, or clinical studies research with an emphasis placed upon moving the research field forward toward novel or improved therapies for muscular dystrophy. Each center should include clinical research as defined in the PHS398 Supplemental Instructions Part II (http://grants1.nih.gov/grants/funding/phs398/phs398.html). This includes patient-oriented research, for which an investigator directly interacts with human subjects, epidemiologic, behavioral studies, outcomes and health services research. Studies are not considered clinical research if they involve only human specimens without information identifying the subjects. Although guidance is provided in this FOA for interventional clinical trials in MDCRCs, clinical trials are NOT a required component of an MDCRC.

There is no requirement of the number of projects within each MDCRC, and centers could be structured as several distinct, synergistic projects, or as one large multifaceted or multi-site project. Each MDCRC should include collaborative research that addresses any of the stages of preclinical or clinical development for one or more types of muscular dystrophy. The proposed research project(s) should address problems that require a substantial collaborative research effort to solve, preferably involving both basic scientists and clinical investigators. Applicants are strongly encouraged to consider a multi-disciplinary research team approach and propose fewer, scientifically comprehensive and collaborative projects, rather than a larger number of small projects that might be easily accomplished outside of the center mechanism. Collaborations should be arranged to bring the best expertise to bear on a problem, whether the proposed collaborations are all on-site or utilize consortium agreements with off-site investigators at existing MDCRCs or off-site investigators not affiliated with an MDCRC.

MDCRCs are encouraged to serve as catalysts for new, competitive NIH applications that will extend the knowledge that they create to all relevant (related) neuromuscular research. (This should encompass everything from new technologies via scientific discoveries to therapies.) While the scope of this FOA relates to the muscular dystrophies and emphasizes translational research, it is critical to recognize that these are multi-system disorders requiring comprehensive research strategies and innovative approaches. Just as there are fields of research relevant to MD that are relevant to other neuromuscular disorders (e.g. rehabilitation research, newborn screening, behavioral/cognitive/developmental investigation), research on these topics related to these other disorders may be relevant to MD and infrastructure necessary for the conduct of translational research is shared to a substantial degree by all neuromuscular conditions. While a broader focus encompassing research on all neuromuscular disorders is beyond the scope of activities supported in the Centers themselves under this FOA, this should not be construed to limit or discourage the Center investigators from pursuing additional separate funding in coordination with the Center to enhance its research depth and breadth in ways that enhance overall scientific progress. Limited use of Center administrative and communications resource to achieve such collaborative goals can be considered in consultation with program staff.

The minimal structural requirements of a Wellstone MDCRC under this FOA are:

One or more projects involving collaborations of investigators and focused on translational or clinical aspects of muscular dystrophy;
One or more clinical research component(s) to a project(s), such as studies involving the direct interaction of center investigators with MD patients;
A Center Director and Co-Director, responsible for scientific and administrative oversight of the center;
An Administrative Core that promotes a center environment through enhanced communication and collaboration of investigators. The Administrative core will establish a Center Advisory Committee including external scientific and lay members (individuals should not be named in the application).
One or more Scientific Research Resource Cores, at least one of which constitutes a unique resource for the national muscular dystrophy research community. The need for the core and its national users group should be well documented. Other cores must support a majority of projects in the center.
A Research Training and Education Core to provide a training environment and stipend support for predoctoral and postdoctoral investigators, and to engage the patient and lay communities in educational and research activities.

The Center Director and Co-Director should have a minimum commitment of 20% (2.4 calendar months) effort to the MDCRC. They should develop and maintain a center environment that fosters traditional and novel approaches to multi-disciplinary research collaborations and training. The Center Director and Co-Director cannot serve as project Principal Investigators on another active MDCRC award.

The Administrative Core should provide for the integration and management of activities within the MDCRC. Applicants should specify appropriate administrative/business management staff and oversight mechanisms by the Center Director, Center Co-Director, a local Executive Committee, and an external Center Advisory Committee (CAC) with scientific, clinical and patient advocate representation, composed of at least five members. The final establishment of the CAC, and its operational features, will require NIH approval. Funded MDCRCs are expected to utilize the Administrative Core to establish and maintain a website to communicate the Center missions and the availability of training opportunities and Scientific Research Resource Core services.

The Scientific Research Resource Cores should be designed and managed to support the specific research projects of the MDCRC, as well as serving as a resource for muscular dystrophy research community efforts. At least one of the Scientific Research Resource Cores should have substantial value as a national/international resource, as documented by support letters from basic and clinical scientists outside of the MDCRC. Applicants may wish to consult the Action Plan for the Muscular Dystrophies (http://www.ninds.nih.gov/find_people/groups/mdcc/MDCC_Action_Plan.doc) for consensus statements on infrastructure needs of the muscular dystrophy research community.

As nationally recognized centers of excellence in muscular dystrophy, the MDCRCs are expected to play leadership roles in training of new researchers for the muscular dystrophy field and educating the patient and lay communities regarding research activities. Each center should include plans for a Research Training and Education Core to establish and maintain a training environment for predoctoral and postdoctoral investigators in muscular dystrophy research, and to engage the patient and lay community in educational and research activities. Utilization and adaptation of existing training programs is encouraged. The training environment for the center may include formal training on manuscript writing and reviewing, grantsmanship, team science approaches and lab management and must include training on the ethical conduct of research. Other features of the training environment may include a seminar program, retreats for presentation of trainee research, journal clubs or other activities that contribute to the preparation of junior investigators for careers in muscular dystrophy research. Lab rotations for predoctoral students should involve exposure to translational and clinical research when ever possible and may include rotations at other Wellstone centers. In order to promote awareness of muscular dystrophy research and the Wellstone centers program in the patient and lay communities, this core should develop educational activities or materials such as seminars, web-based information, or lab tours involving patients and their families interacting with junior and senior investigators.

This core may also request funds to support one predoctoral and one postdoctoral training slot in addition to the positions associated with each project. Funds for these slots may include salary, fringe benefits, tuition, travel and trainee related expenses. Each trainee must be engaged in full-time research and training activities and may occupy one of these slots for no more than 2 years in total. Trainees appointed to these slots do not require United States citizenship or permanent residence status. Selection of candidates for these slots should be determined by the center’s CAC and based on selection criteria to be described in the application. Appointment of the candidates will require approval from the program staff of the NIH institute supporting the center, based on the merits of the candidate and recommendation of the CAC. Selection of clinician-scientists with MD and/or MD/PhD degrees who will learn to conduct clinical research and clinical trials in MD is especially encouraged. Individuals from underrepresented racial and ethnic groups, individuals with disabilities, and individuals from disadvantaged backgrounds are always encouraged to apply for NIH support.

Recipients of MDCRC awards will become part of a national program in muscular dystrophy and will be expected to participate in MDCRC activities, including regularly scheduled Steering Committee (MDCRC Directors and Co-Directors) conference calls and an annual MDCRC meeting that rotates among the MDCRC sites.

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

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the U54 Specialized Centers Cooperative Agreement award mechanism(s).

The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project

This FOA uses Just-in-Time information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". NIH plans beyond the current funding opportunity are indefinite.

2. Funds Available

The estimated amount of funds available for support of up to 3 projects awarded as a result of this announcement is $3 million in direct costs for fiscal year 2010. Future year amounts will depend on annual appropriations.

Applicants may request up to $1 million per year in direct costs (exclusive of facilities and administrative costs of subcontracts with collaborating organizations). The total project period for an application submitted in response to this FOA may not exceed 5 years.

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

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation; see NOT-OD-05-004.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

1. A. Eligible Institutions

The following organizations/institutions are eligible to apply:

Public/State Controlled Institutions of Higher Education
Private Institutions of Higher Education
Hispanic-serving Institutions
Historically Black Colleges and Universities (HBCUs)
Tribally Controlled Colleges and Universities (TCCUs)
Alaska Native and Native Hawaiian Serving Institutions
Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
Small Businesses
For-Profit Organizations (Other than Small Businesses)

1. B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her 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 support.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit only one application in response to this FOA.

Resubmissions. Resubmission applications are not permitted in response to this FOA.

Renewals. Renewal applications will be permitted for this FOA.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: October 13, 2009
Application Receipt Date: November 10, 2009
Peer Review Date(s): February/March 2010
Council Review Date: May 2010
Earliest Anticipated Start Date(s): July 1, 2010

3. A.1. Letter of Intent

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

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

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

The letter of intent should be sent to:

Ljubisa Vitkovic, Ph.D.
Center for Developmental Biology and Perinatal Medicine
Eunice Kennedy Shriver National Institute of Child Health and Human Development
6100 Executive Boulevard
Room 4B09 MSC 7510
Bethesda, MD 20892
Telephone: (301) 402-1822
Fax: (301) 496-3791
E-mail: [email protected]

3.B. Sending an Application to the NIH

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

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

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

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

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Boulevard
Bethesda, MD 20892-9529
(Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-9223
Fax: (301) 402-0182
E-mail: [email protected]

3. C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at NIH Grants Policy Statement.

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

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Special Requirements

Each applicant institution will name an MDCRC Center Director (Program Director/Principal Investigator) who will be the key figure in the administration, management, and coordination of the Center grant. The Director will be responsible for the organization and operation of the center. The Director should be a recognized scientific leader experienced in the field of muscular dystrophy research and must be able to coordinate, integrate, and provide guidance in the establishment of research programs. A Co-Director should also be named who will be involved in the administrative and scientific efforts of the Center.

Applicants must commit to cooperate fully and to share specimens and redacted data with qualified research scientists, both within and outside the MDCRC network, and should ensure that such data are HIPPA compliant.

Subjects who participate in MDCRC clinical research projects should be fully informed, under informed consent procedures. The consent form for funded projects should specifically addresses the following: (1) disclosure that biological materials and clinical data will be distributed to other researchers; (2) assurance that such data will be stored and maintained without personal identifiers; (3) disclosure that analyses of these data will be conducted by other scientists currently not included within the current research team, potentially including those with commercial interests; (4) that the data collected by the researchers may be used to study their specific disorder as well as other disorders.

In order to assure active collaboration with other Centers, the MDCRC Director, Co-Director, and other staff should attend annual meetings of the MDCRC Steering Committee, participate in planning for cooperative research, or help to refine and standardize operating procedures among the Centers. The Administrative Core of the MDCRC application should include up to $5,000 per year direct costs for travel of the Director, Co-Director, and other Center investigators to the annual MDCRC Steering Committee meeting and for visits of Center investigators or trainees to other MDCRCs or other collaborative sites for the exchange of scientific ideas, planning of multi-Center research projects, and to receive training in specialized techniques.

At least one Scientific Research Resource Core with clearly documented national/international need and impact must be proposed. Additional cores may be proposed if they are needed to advance the local research effort and if they fit within the budget limits described elsewhere in this FOA. Applicants should document and describe briefly the projects, both existing and planned, that will depend upon resources provided by the requested cores.

The Training and Education Core budget should include 10 percent of the total Center budget (up to $100,000/year) for the purpose of establishing and maintaining a conducive environment for recruiting and training next generation muscular dystrophy researchers. Included in this core budget should be support for one predoctoral and one postdoctoral fellow as well as support for activities that educate and/or engage patients and patient advocates in the research conducted by the center.

To be funded, an MDCRC must include at least one highly meritorious scientific project, at least one Scientific Research Resource Core with national impact, and a Training and Education Core approved for five years. The Program Director/Principal Investigator must lead one of the approved projects.

Guidance for Applicants Submitting a U54 MDCRC

Applicants should use the following guidance, in addition to the instructions accompanying the PHS 398 form.

Program Introduction and Statement of Objectives: Describe the major theme of the Center, its goals and objectives, background information and the overall importance of the research to therapeutic development in the muscular dystrophies. A successful U54 Center grant application will include a well-integrated research plan that clearly shows how the proposed projects and cores will foster preclinical and or clinical development of novel therapeutics for muscular dystrophy. The program should be viewed as a group of interrelated research projects, each of which is not only individually scientifically meritorious but is also complementary to the other projects, and related to the overall theme developed for the Center.

Describe the rationale for the total proposed program. Explain the strategy for achieving the goals defined for the overall program and how each research project and core relates to that strategy.

Explain how different components of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how combined resources create capabilities that are more than the sum of the parts. Very clear evidence must be presented in the application that: (a) the proposed projects are such that they require an intensive collaborative effort to succeed and (b) that key personnel will collaborate effectively.

Progress Report for Last Funding Period: This section is required only for competitive renewal (type 2) applications and it should refer to the goals enunciated in the RFA AR-04-008. Describe the overall accomplishments of the MDCRC during the last funding period. Applicants should include a discussion of the leadership that the MDCRC has exerted in the muscular dystrophy field; a brief synopsis of the goals and accomplishments of projects from the last funding period, including the overall scientific/clinical merit and impact of those projects and of the MDCRC as a whole; the synergy the MDCRC has fostered among the participating investigators and with new collaborators; the effectiveness of the core resources and facilities; and brief synopsis about people trained with MDCRC support. Also include a listing of published and in press original articles, reviews, and book chapters that acknowledge the U54 support and were, therefore, a direct result of studies funded in the last MDCRC project period (this listing does not count against the section page limit). Detailed descriptions of the progress of any projects that are proposed for competitive renewal should be included with the appropriate project section and not included in this section.

This section is limited to 5 pages.

Organizational and Administrative Structure: Describe in detail and by diagram, if appropriate, the organizational structure of the MDCRC including administrative and management plans that achieve an integrated, coordinated product-oriented multidisciplinary research program. A diagram may be useful in demonstrating the interactions between the different program components. Describe how the Center Advisory Committee will contribute to oversight of the research projects, core facilities and training environment of the Center.

Describe the role of the Director, who is the Principal Investigator for MDCRC, the Co-Director and the investigators responsible for the subprojects.

A successful U54 MDCRC application will include a well-integrated project plan. Within the Administrative Core, the specific administrative and organizational structure that is needed to support the research and the synergies enabled by the Center needs to be clearly articulated. MDCRC projects will be multidisciplinary and will draw from a variety of resources. Thus, a well thought out and carefully described organizational structure will be required.

A narrative description should be provided that includes the planning and coordination of research activities; the integration of cross-disciplinary research; the oversight of fiscal and resource management; and the maintenance of ongoing communication. Indicate who will be responsible for each of these activities.

This section is limited to 15 pages.

Individual Research Project(s): Follow the instructions in the PHS 398 for the Research Plan for describing each research project. Each project should clearly state its overall objective and explain its relevance to the central theme of the Center. In addition, an explanation should be included describing how the project relates to and both complements and enhances the other research projects and cores of the program. Why the project is best suited to be carried out in the Center environment should be highlighted. Specify the overall biomedical significance of the work proposed. Specify the niches filled by each project in advancing a candidate therapeutic for muscular dystrophy.

The research plan (25 page limit per project) includes:

Specific Aims List the specific aims of the research project and indicate the priority of each aim in the overall research plan.

Background and Significance Review the most significant previous work and describe the current status of research in this field and document with complete references.

Progress Report/Preliminary Studies For new MDCRC applications (type 1), provide information on preliminary studies that support the proposed project. For competitive renewal (type 2) applications, provide both a progress report of activities under the prior funding period and any preliminary studies that support the proposed project.

Research Design and Methods - Give details of the research plan, including a description of the experimental or other work proposed; present the methods and techniques to be used; note the limitations, if any, of the procedures proposed. Describe the experiments in the sequence in which they would be conducted. Provide an overall time line for the project.

For applications proposing a collaborative, multi-disciplinary and/or multi-site research project, applicants may use up to 50 pages for the research plan of this project. The total number of pages devoted to research plans of all proposed projects should not exceed 100.

Core Facilities: Follow the instructions in the PHS 398 Research Plan as is appropriate for describing Scientific Research Resource Cores. Information that should be included is as follows:

Describe the function of the core as a resource to the program. This section must clearly present the facilities, techniques, and professional skills that the core will provide. As justification for the core, briefly indicate the specific Research Projects that will use the resources of the core. A core is principally designed as a service or resource component; it would be highly unusual to include research in a core (a possible exception would be methodology development). Please contact the Institute staff if you require guidance on this issue.

Describe the role of the core as a resource to the program as a whole. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program. To aid in the review of your application it is recommended that you prepare in tabular form information concerning the research projects that each facility core unit would serve and the proportion of the cost of the facility core unit associated with each research project involved. For at least one of the proposed Scientific Research Resource Cores, describe how it meets a need for the national muscular dystrophy research community and document this need with detailed support letters from local, national, and/or international individuals who are potential users of the core. These letters should be included in the appendix.

The page limit for each core is 15 pages.

Guidance for Clinical Trials in MDCRCs: Clinical trials proposed within MDCRCs should be designed to provide specific data that will be necessary to design a subsequent definitive efficacy trial. The proposed study must address questions that, when answered, will optimize the design of the eventual definitive clinical trial rather than simply address the clinical question with lower power. Examples of relevant clinical research include, but are not limited to, the following:

Studies to optimize the intervention strategy: for example, studies designed to investigate dose-concentration, dose-response, or concentration-response relationships may contribute to optimal dosage selection for definitive trials.
Studies to assess the appropriate delivery system or parameter settings of an electronic device or surgical technique;
Studies to assess the safety and tolerability at various doses or concentrations of a specific intervention;
Studies designed to evaluate whether an intervention produces sufficient evidence of short-term activity (e.g., biomarker activity) in humans as to justify an efficacy trial;
Studies designed to select the best of two or more potential interventions or dosing regimens to evaluate in a subsequent definitive trial, based on tolerability or evidence of biological activity;
Studies to identify inclusion and exclusion criteria to be applied in the phase III clinical trial.

Research Plan Page Limitations

Strictly follow page limits in instructions above.

Appendix Materials

All paper PHS 398 applications submitted for May 25, 2008 and subsequent due dates must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

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

Resource Sharing Plan(s)

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

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

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

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

Section V. Application Review Information

1. Criteria

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

2. Review and Selection Process

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

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

Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score.
Receive a written critique.
Receive a second level of review by the appropriate National Advisory Council.

The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as determined by peer review
Availability of funds
Relevance of the proposed project to program priorities

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach. Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition to the above review criteria, the following criteria will be applied to applications in the determination of scientific merit and the impact/priority score.

Centers should be designed to include the following components: one or more scientific project(s), an Administrative Core, a Scientific Research Resource Core with national impact, and a Research Training and Education Core. Applications may include additional core facilities within the overall budget cap. After the review of the individual components, an overall impact/priority score will be assigned to the center application. The overall score will reflect a) the scientific merits of the research project(s), b) the overall effectiveness and adequacy of core resources and facilities, c) the qualifications of the Center Director and Co-Director, d) the quality of the plans for management and oversight of the Center, e) the institutional commitment, and f) the synergy among the components and overall impact of the Center. For applications for renewal of previously funded Wellstone Centers, the productivity of the Center and its impact on the muscular dystrophy research field over the period of Center funding will also be taken into consideration when determining the overall score. The overall score for the center application may be higher or lower than the average of the individual components based on the assessment of whether the whole is greater than the sum of its parts.

Center Director and Co-Director: Are the qualifications, experience, and commitment of the MDCRC Director adequate to lead the Center program and are they devoting sufficient time/effort to achieve Center goals? Does the Center Director have sufficient authority and credibility within the institution and broader community as a base for serving a national leadership role in muscular dystrophy? Does the Center Co-Director have appropriate complementary and integrated experience/expertise to help lead a multi-disciplinary center effort? Are there adequate plans for interaction among Center personnel and any off-site investigators? Is the Center scientific and administrative structure sufficient, including its internal and external procedures for monitoring and evaluating the proposed research? Are the proposed financial administration, procurement, property and personnel management, planning, and budget functions adequate? Are resource and informatics management plans adequate? Is the Center Advisory Committee activity plan appropriate to provide guidance for the central objectives of the Center?

Administrative Core: Is the management proposed appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting, etc.? Is there an appropriate plan for establishing and maintaining effective communications and cooperation among Center investigators and with investigators outside the Center? Is the Center scientific and administrative structure sufficient, including its internal and external procedures for monitoring and evaluating the proposed research projects and core facilities/resources? Are there appropriate plans for management and sharing of data, animal models and other resources? Are there appropriate plans for establishing the Center Advisory Committee and will this Committee contribute to the oversight of Center research projects, the national service core, the training and education core and other components?

Center Synergy and Impact: Will the Center be effective in meeting the stated goals of the FOA? Is the aggregate quality and novelty of the Center’s research base sufficient and are the proposed research projects highly relevant to the overall goal of advancing therapeutic development in muscular dystrophy? Is there clear scientific merit and thematic identity to combining the component parts into an MDCRC? Are there appropriate plans for the Center to collaborate and otherwise contribute to the national MDCRC program, through participating in the annual meeting, workshops, training, collaborative efforts, or other MDCRC-wide activities? Is there clear evidence that the Center will have national impact on research in muscular dystrophy, through both its scientific projects and resource cores?

Scientific Project(s): For each scientific project, peer reviewers will evaluate the significance, approach, innovation, investigators and environment as described above. The following additional criteria will also be considered in determining the score. Is the proposed project sufficiently novel and meritorious and the research plan feasible, in addressing one or more stages in the development of therapies for one or more type of muscular dystrophy? Are the experimental design and methods adequate to achieve the research objectives? For disease mechanism/therapeutic target identification and validation projects, is a plan provided as to how these efforts help to support the therapeutic development pipeline? For preclinical translational research projects, is there a clear step-by-step plan, including adequate milestones, to track and evaluate the therapeutic development effort? For clinical studies or trials, is there a clear need for the data or resource for future clinical trials or is there clear justification for moving the selected candidate therapeutic(s) forward with proof of concept or safety trials? Are there appropriate plans for the rigorous management and quality control of any research data or materials to be obtained from human subjects? For all types of research projects, do the problems to be addressed require both a center atmosphere and an intensive collaborative effort for successful completion? Do the participating investigators have sufficient experience and expertise for the proposed project and are time/effort commitments sufficient? Do the collaborative efforts require substantial, and not token, contributions from the partners for successful completion? Are the proposed protections for humans, animals, or the environment, to the extent they may be adversely affected by the projects proposed in the application, adequate?

Clinical Trials (if applicable): Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Has the applicant addressed both the significance of the eventual definitive clinical trial AND the significance of this study in providing knowledge needed to proceed to the definitive clinical trial? Is there a sufficient body of high quality preclinical or clinical research that supports the rationale for the proposed study? What is the state of equipoise in the medical and patient communities with respect to the proposed intervention? What is the potential impact of the proposed intervention on health care and quality of life? If the aims of the study are achieved, how will these results contribute to the design and implementation of the definitive clinical trial? Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the applicant acknowledge potential problem areas and consider alternative tactics? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Have appropriate agreements with participating industry sponsors, if any, been established?

Scientific Research Resource Cores: Are the core activities capable of effectively and efficiently supporting research productivity and collaborations and are they essential to the mission of the Center? Is there adequate scientific and technical merit to justify the core? Does the core provide adequate leadership and technical expertise to ensure that it meets its stated goals? Are the staffing, allocated space and equipment, and budget that are available to the core sufficient to meet the anticipated demand on its services? Is there strong evidence (via the core description and associated external letters of support) that at least one Scientific Research Resource Core will serve as an important national/international resource for the muscular dystrophy research community? If designed as a fee-for-service facility, are the projected fees appropriate for recovery of only the variable costs (supplies, service contracts, etc.) and do not assess the fixed costs of personnel and equipment? Is there a strong commitment to provide services to the national muscular dystrophy community and are plans for oversight and prioritization of user requests for core services adequate and fair?

Training and Education Core: Are there adequate plans to involve predoctoral students, postdoctoral research associates, and junior faculty in proposed and emergent research projects? Is an appropriate plan proposed for effective recruitment and selection of trainees and use of the designated Center training funds? Does the MDCRC have access to a sufficient pool of academically strong trainees and commensurate experience and well-qualified mentors to justify the proposed training activities and make effective use of the designated Center training funds? Are there adequate planning and infrastructure for trainee recruitment, selection, and retention? Is there an adequate plan for providing training in the responsible conduct of research? Are there appropriate plans for activities that will contribute to the education and/or direct involvement of patients and patient advocates in the research conducted by the Center?

Institutional Commitment: Is there tangible institutional commitment to the establishment and growth of the MDCRC? Will the institution provide incentives and rewards to promote the mission of team-based research? Is there substantial institutional commitment to tenured faculty positions, dedicated space and other resources, and sufficient time release to allow the investigators to pursue the goals of the MDCRC? Is the physical distribution of Center investigators and core resources conducive to the synergy necessary for a successful MDCRC? Will existing NIH-supported core facilities be shared with the MDCRC? Do the institutional administration and environment provide opportunities for Center growth? If applicable, are there sufficient commitment and support on the part of institutions associated with the MDCRC through consortium agreements?

NIH considers the following in evaluating Center grant applications:

The scientific and technical merit of the proposed program;
The qualifications and experience of the center director and other key personnel;
The statutory and program purposes to be accomplished;
The extent to which the various components of the proposed program would be coordinated into one multi-disciplinary effort within the center;
The extent to which the center's activities would be coordinated with similar efforts by other organizations;
The administrative and managerial capability of the applicant; and
Other factors which the awarding IC considers appropriate in light of its particular statutory mission.

Additional Review Criteria. As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia.

Renewals. When reviewing a Renewal application (formerly called a competing continuation application), the committee will consider the progress made in the last funding period.

Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Additional Review Considerations. As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.

Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Select Agent Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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

2.A. Cooperative Agreement Terms and Conditions of Award

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

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

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for: defining objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies. The Principal Investigator will serve as Center Director and together with a Center Co-Director, will be responsible for the integration and management of activities within the MDCRC.

The Center Director shall be responsible for organizing a local Executive Committee for day-to-day management of the MDCRC, and an external Center Advisory Committee, with scientific, clinical and patient advocate representation (final membership to be approved by the NIH). The role of these Committees will include the solicitation, review, and selection of proposals for trainee positions and collaborative projects, and the selection and prioritization of projects that will use resources and services that are provided for through the MDCRC.

The Center Director and Co-Director of each MDCRC also serve as members of the MDCRC Steering Committee (see below) and are required to participate in its activities, to include regular conference calls and an annual MDCRC face-to-face meeting.

Awardees agree to participate in the overall coordination of NIH research efforts in muscular dystrophy. This participation may include collaboration and consultation with other NIH awardees, the sharing of information, data, and research materials, and participation in NIH efforts to standardize and harmonize pre-clinical and clinical data collection.

Awardees with a clinical trial component in their MDCRC agree to review of associated data, abstracts, and other publications by the DSMB and the NIH prior to their release.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2.A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Each MDCRC will have the support of Project Scientists, representing each participating Institutes, and a Program Official from NIH staff who are assigned administrative roles for the muscular dystrophies being studied and have expertise in the implementation of the MDCRC Program.

The NIH Project Scientists will have substantial scientific-programmatic involvement during conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. The NIH Project Scientists also will assist in the interaction between the awardee and investigators of other institutions, as well as between the awardee and other Federal agencies and/or potential commercial sponsors. The NIH Project Scientists will be members of the MDCRC Steering Committee. The NIH Project Scientists retain the option to recommend additional research endeavors within the constraints of the approved research and negotiated budget.

An important part of the NIH MDCRC Program is the coordination of research efforts across different funding mechanisms and research structures, and coordination among efforts aimed at different muscular dystrophies. The NIH Project Scientists will have the primary responsibility for this overall coordination.

The NIH may appoint an MDCRC External Advisory Committee (EAC), consisting of scientific and public members. The EAC may function in an advisory role to the NIH as necessary on issues that arise related to the MDCRC program. EAC members may participate in the annual meeting of the Steering Committee and be consulted as necessary.

The NIH Project Scientists representing NINDS, NIAMS, NICHD, and NHLBI will, collectively, have a single NIH vote on the MDCRC Steering Committee (see below). NIH Project Scientists will abstain from voting on any issue where they are unable to reach a consensus.

The NIH will establish one or more Data Safety Monitoring Boards to provide oversight and to advise the NIH on any clinical trials that are supported by the MDCRC awards.

Additionally, an NIH Program Official will be primarily responsible for program oversight. The Program Official assigned to each MDCRC will exercise the normal stewardship responsibilities of an NIH Program Official, including assessment of the progress of the projects toward the accomplishment of specified objectives. NIH Program Officials also 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. This Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

Overall coordination of the MDCRC Program will be done by a Steering Committee. The MDCRC Steering Committee will make strategic decisions with regard to goals and research implementation, including the establishment and development of collaborations.

The Steering Committee will consist of the Center Directors and Co-Directors of each MDCRC, NIH Project Scientists and a public member. The Steering Committee will be chaired and co-chaired by MDCRC Center Directors, who are elected by vote of the Steering Committee for staggered two-year terms. The Chair and Co-Chair will be responsible for conduct of regular conference calls. The Steering Committee will hold a face-to-face meeting at least annually. Each MDCRC and the public member will have one vote on the Steering Committee and the NIH Project Scientists, collectively, will have a single NIH vote.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

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

1. Scientific/Research Contacts:

James W. Hanson, M.D.
Director, Center for Developmental Biology and Perinatal Medicine
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 4A05A
Bethesda, MD 20892-7510
Telephone: (301) 496-8535
Email: [email protected]

Glen H. Nuckolls, Ph.D.
Director, Muscle Disorders and Therapies Program
Musculoskeletal Diseases Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
One Democracy Plaza
6701 Democracy Boulevard, Suite 800
Bethesda, MD 20892-4872
Telephone: (301) 594-4974
Email: [email protected]

John D. Porter, Ph.D.
Program Director, Neurogenetics Cluster
National Institute of Neurological Disorders and Stroke (NINDS)
6001 Executive Blvd., Room 2142
Bethesda, MD 20892 (use Rockville, MD 20852 for express/courier service)
Telephone: (301) 496-5739
FAX: (301) 402-1501
Email: [email protected]

Jonathan R. Kaltman, M.D.
Heart Development and Structural Diseases Branch
Division of Cardiovascular Diseases
National Heart, Lung, Blood Institute (NHLBI)
Two Rockledge Center
6701 Rockledge Drive, Room 8222
Bethesda, MD 20892-7940 (use Zip Code 20817 for express/courier service)
Telephone: (301) 435-0510
FAX: 301-480-1454
Email: [email protected]

2. Peer Review Contacts:

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Room 3201, MSC 9529
6001 Executive Boulevard
Bethesda, MD 20892-9529
(Rockville, MD 20852 for express/courier service)
Telephone: 301-496-9223
FAX: 301-402-0182
Email: [email protected]

3. Financial or Grants Management Contacts:

Bryan S. Clark, M.B.A.
Chief Grant Managements Officer
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 8A01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 435-6975
FAX: (301) 402-0915
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

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

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

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

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

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

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

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for 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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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