Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Center for Advancing Translational Sciences (NCATS)
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Neurological Disorders and Stroke (NINDS)
Division of Program Coordination, Planning and Strategic Initiatives,
Office of Dietary Supplements (ODS)

Funding Opportunity Title

Rare Diseases Clinical Research Consortia (RDCRC) for Rare Diseases Clinical Research Network (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

Reissue of RFA-OD-08-001

Related Notices

  • August 29, 2013 - See Notice NOT-TR-13-008. Notice of Pre-Application Meeting.

Funding Opportunity Announcement (FOA) Number

RFA-TR-13-002

Companion Funding Opportunity

RFA-TR-13-003, U01 Research Project – Cooperative Agreements

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.121, 93.847, 93.855, 93.856, 93.865, 93.837,  93.838, 93.839, 93.853, 93.846

Funding Opportunity Purpose

The purpose of this FOA is to facilitate clinical research in rare diseases through support for 1) collaborative clinical research in rare diseases, including longitudinal studies of individuals with rare diseases, clinical studies and/or clinical trials; 2) training of clinical investigators in rare diseases research; 3) pilot/demonstration (proof of concepts) clinical research projects; and 4) access to information related to rare diseases for basic and clinical researchers, academic and practicing physicians, patients, and the lay public.  Items 1-4 must be addressed in the RDCRC application. Clinical data management for efficient data collection as well as data mining and data sharing across rare diseases will be addressed in the DMCC application. Another FOA will be published to address DMCC.

Key Dates
Posted Date

August 14, 2013

Letter of Intent Due Date(s)

October 7, 2013

Application Due Date(s)

November 7, 2013   

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2014  

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

November 8, 2013

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. See NOT-OD-13-075 and  NIH’s Applying Electronically website for more information.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description

This Funding Opportunity Announcement (FOA) invites applications  for the Rare Diseases Clinical Research Consortia (RDCRC) component of the Rare Diseases Research Network (RDCRN). The purpose of this cooperative agreement research program is to facilitate clinical research in rare diseases through support for 1) collaborative clinical research in rare diseases, including longitudinal studies of individuals with rare diseases, clinical studies, and/or clinical trials; 2) training of clinical investigators in rare diseases research; 3) pilot/demonstration (proof of concepts) clinical research projects; and 4) access to information related to rare diseases for basic and clinical researchers, academic and practicing physicians, healthcare professionals, patients, and the lay public. Clinical data management for efficient data collection as well as data mining and data sharing will be addressed through the Data Management and Coordinating Center (DMCC) component of the Rare Diseases Clinical Research Network (RDCRN).

Each RDCRC will perform collaborative multi-site clinical research in rare diseases, train new investigators in rare diseases research, and provide content for an internet resource site on rare diseases. Each RDCRC will consist of a consortium of clinical investigators, institutions, and relevant organizations, including patient advocacy group organizations and will focus on at least three related rare diseases, disorders or syndromes. Previous experience with the RDCRN has demonstrated that RDCRCs that both engage and integrate patient advocacy groups into their research program have achieved greater success in enrollment in studies. The RDCRC applicants at an institution with a Clinical and Translational Science Award (CTSA) are encouraged to use the resources available at their CTSA institution.

The focus of each RDCRC can be on particular defects, e.g., lysosomal storage diseases, amino acid metabolism defects; particular organ systems, e.g., primary immune deficiencies, neurodevelopmental delay and intellectual disability syndromes; or other groupings. Since rare diseases are diverse, the nature of clinical research that is feasible varies. The application must describe the group of rare diseases (at least three related rare diseases, disorders or syndromes) to be included, the rationale for this grouping, and the relevant expertise available in the proposed RDCRC. The individual RDCRCs will be responsible for the design and implementation of their clinical studies. The Data Management and Coordinating Center (DMCC) for RDCRN will provide the data management and support necessary for the RDCRCs to function optimally. There will be another FOA published to address DMCC.  The DMCC will work with each Consortium to integrate protocols, forms, and research tools into the Network. The biostatistician from RDCRC will provide statistical support for protocol development and assist in study design and analysis.

It is advantageous for clinical studies of diseases in small populations to use a multi-centered approach.  However, this requires approvals from multiple IRBs, which prolongs the protocol approval process and delays patient recruitment.  Moreover, there are other regulatory requirements when participating centers are in different countries and additional approvals necessary from the RDCRN and NIH.  Applicants should present a plan for how the proposed RDCRC will try to streamline the protocol approval process.  Specifically, applicants are strongly encouraged to consider models that will facilitate “shared review” such as IRB Share or a central IRB of record for multisite trials and provide plans for implementation.  Having a central IRB of record for multisite trials is preferred and may even improve patient safety and scientific validity, as well as trial efficiency.  Member institutions of the consortium would agree to a) accept the findings of the central IRB, b) accept the central IRB findings with modifications, or c) convene their own IRB.  If a central IRB or IRB Share is not feasible, applicants should discuss systems for making the protocol approval process as rapid and efficient as possible.

This FOA allows RDCRC applications for all rare diseases research relevant to the mission of the participating NIH ICs. Prospective applicants are urged to consult with the Scientific/Research Contacts of the NIH early in the preparation of the application (see Section VII. Agency Contacts).

Background

 Approximately 25 million people in the United States are affected by an estimated 7,000 rare diseases or conditions leading to significant morbidity and mortality. 'Rare disease' is defined through an Amendment to the Orphan Drug Act of 1983 (Orphan Drug Act, P.L. 97-414; Health Promotion and Disease Prevention Amendments, P.L. 98-551) as a condition affecting fewer than 200,000 Americans or a disease with a greater prevalence but for which no reasonable expectation exists that the costs of developing or distributing a drug can be recovered from the sale of the drug in the United States.

In 1999 the NIH Office of Rare Diseases, now referred to as Office of Rare Diseases Research (ORDR) at the NCATS, convened a Special Emphasis Panel, comprised of academic scientists, representatives of voluntary patient support groups, pharmaceutical, biotechnology and device industries, and other Federal agencies. This panel made recommendations regarding the special research opportunities and health care issues posed by rare diseases. These recommendations encompassed four major areas: 1) Stimulating Research on Rare Diseases and Conditions with specific emphasis on clinical research and training of clinical research scientists, establishing diagnostic and treatment centers with informatics support, and promoting the collaboration of the voluntary patient support groups, health care systems, and industry; 2) Utilizing Research Resources with the NIH-supported GCRCs (now supported by Clinical and Translational Science Awards, CTSAs), the development of a centralized information database containing research resources, made available to research investigators, physicians, and patients for their use; 3) Coordination of Rare Diseases Research and Development Activities, with a primary responsibility of ORDR to coordinate activities and act as a liaison between the rare diseases community and the NIH, including the public, and intramural and extramural investigators at the NIH ICs and other Federal agencies, manufacturers, and voluntary organizations; and 4) Identifying Emerging Opportunities in Rare Diseases Research, specifically through the establishment of specialized research and diagnostic centers to attract the interests of industry to promote advances and products for the prevention, diagnosis, and treatment of rare diseases. These recommendations are contained within the Department of Health and Human Services National Institutes of Health “Report on Steps to Coordinate Rare Diseases Research Programs," January 2001 http://rarediseases.info.nih.gov/html/reports/fy1999/SEP.html

In November 2002, the Rare Diseases Act of 2002 (Public Law 107-280) directed ORDR at NIH to support regional centers of excellence for clinical research into, training in, and demonstration of diagnostic, prevention, control, and treatment methods for rare diseases. This law provides the legislated mandate for this FOA to address the needs of rare disease clinical research.

Investigations into rare diseases offer promising leads for scientific advancement. Many rare diseases represent single gene defects whose abnormalities in specific genes or proteins offer insight into normal biologic function. Other rare diseases are complex, resulting from the interaction of two or more genes. Understanding the pathogenesis of rare diseases may advance our understanding of more common medical disorders.

Despite the advances and opportunities for research in rare diseases, difficulties remain in clinical diagnosis, clinical trials methodology, and clinical management. Diagnoses may be straightforward as a result of well-described phenotypes or due to the availability of diagnostics tests, or conversely, they may be challenged by a lack of well-defined diagnostic criteria. Furthermore, there are insufficient characterizations of the natural history of many rare diseases. Treatment can be equally challenging with many questions concerning clinical management, and a lack of therapeutic options. Rare diseases pose unique challenges to identification and coordination of resources and expertise for small populations dispersed over wide geographic areas. Rare diseases research often requires collaboration of scientists from multiple disciplines sharing research resources and patient populations. Rigorous characterization and longitudinal assessment are needed to facilitate discovery of biomarkers of disease risk, disease activity, and response to therapy. In addition, systematic assessment could help to improve and develop an evidence base for current treatment strategies. Well described patient populations will be important to bring promising therapies to the clinic.

Purpose

This initiative should facilitate identification of biomarkers for disease risk and disease severity/activity, and measures of clinical outcome applicable to clinical trials.  It should encourage development of new approaches to diagnosis, prevention, and treatment of rare diseases.

The Rare Diseases Clinical Research Network (RDCRN) will consist of all funded Rare Diseases Research Consortia (RDCRC) and a single Data Management and Coordinating Center (DMCC). This initiative will support the continuation of a collaborative and coordinated network of RDCRCs comprised of investigators at multiple institutions/sites and patient advocacy groups committed to investigation of rare diseases working in partnership to enhance communication and sharing of resources in a multidisciplinary approach. The reissuance of the RDCRC FOA is open to new as well as existing RDCRCs. The RDCRN (Network) focuses on the collection of clinical information to develop biomarkers and new approaches to diagnosis, prevention, and treatment and promote the training of new clinical investigators in rare diseases research. The Network supports a comprehensive and integrated approach to data collection, storage, and management, and the integration of clinical data with other unique data, including genetic, imaging, pathologic, and laboratory data. This will incorporate new approaches to distributed computing and federated databases.

Each RDCRC within the Network will consist of a consortium of clinical investigators, multiple institutions, and relevant organizations, including patient advocacy groups and will focus on at least three related rare diseases, disorders, conditions or syndromes that are relevant to the interests of the participating NIH Institutes and Centers (ICs).  The three diseases, disorders, conditions or syndromes proposed for inclusion in an RDCRC could be defined on the basis of differences in etiology (genetic, genomic, acquired), pathogenesis, affected molecular, biochemical, cellular, physiological features, or organ system involvement, natural history, distinguishing signs and symptoms and/or prognosis.  For example, disease-causing variants in the same gene leading to divergent phenotypes or variants in diverse genes leading to overlapping phenotypes could form the basis for a unified RDCRN application. Finally, successful applicants for RDCRCs are expected to synergize clinical research activities across diseases, so the thematic focus and rational basis for the diseases included should be both clear and compelling, and consistent with commonly accepted definitions of disease within the relevant biomedical research community. 

Organization and Management of the Rare Diseases Clinical Research Network

A Steering Committee, composed at a minimum of the Program Director/Principal Investigator (PD/PI) of each RDCRC, the PD/PI of the DMCC, the chairperson of the Coalition of Patient Advocacy Groups (CPAG), and the NCATS, Office of Rare Diseases Research Program Coordinator for RDCRN will establish the procedures for the function of the RDCRN, as outlined in Section VI. Awards Administration Information under "Network Steering Committee." Membership of CPAG will include all participating patient advocacy groups.

The DMCC for RDCRN will be established under another FOA. The DMCC will serve as a Network resource, working with and providing expertise for the RDCRCs. All RDCRCs are expected to work with the DMCC from the beginning to assure compatibility of data collection systems and consistent data standards. It will provide a scalable coordinated clinical data integration of developed and publicly available datasets for data mining at RDCRCs, web-based recruitment and referral, and a user-friendly resource site for the public. The DMCC will provide a management system for collection, storage, as well as a portal and tools for research scientists and clinicians. In addition, the DMCC, in conjunction with the NIH, will provide logistical and administrative assistance for Network activities; produce and/or maintain Network Operating Policy and Procedures, documents, worksheets, and data collection forms; and monitor Network compliance while addressing privacy and confidentiality issues related to database management, and multi-level data sharing. In order to participate in this Network each RDCRC is expected to use the DMCC supported by RDCRN for the above mentioned activities. To enhance recruitment in clinical studies each RDCRC is expected to utilize the Contact Registry developed by DMCC. The RDCRN Contact Registry is a method by which patients with rare diseases can register themselves with the RDCRN in order to be contacted in the future about clinical research opportunities and updates on the progress of the research projects. The contact registry is anonymous and free of charge. Contact Registry can also be used by the investigators to facilitate the rapid enrollment of subjects in survey protocols. All RDCRCs will be expected to collaborate with the DMCC throughout the course of their study in order to assure compatibility and standardization of data management approaches.

The RDCRN will require cooperation among the NCATS, ORDR Program Coordinator for RDCRN, the participating IC Project Scientists, Directors of the RDCRC and their collaborators, and the Director of the DMCC to maximize their effectiveness.

Research Areas of Interest

National Cancer Institute (NCI)

The NCI seeks clinical research teams studying rare cancers.  Examples include, but are not limited to the following rare cancers: carcinoid, primary CNS-lymphoma, sarcomas, thyroid cancer and urinary bladder cancer.

National Eye Institute (NEI)

The NEI supports research in rare eye diseases including, but not limited to, inherited retinal degenerations such as Bardet Biedl syndrome and Usher syndrome, retinitis pigmentosa and related disorders, anophthalmia, microphthalmia, and Behçet's Disease. Priority will be given to applications that align with the NEI audacious goal http://www.nei.nih.gov/audacious/

National Heart, Lung and Blood Institute (NHLBI)

The NHLBI is interested in rare diseases and conditions of the blood, lungs and heart.  Below are some examples only, other rare heart, lung, and blood diseases may also be appropriate. Examples of rare blood diseases: Acquired aplastic anemia, Antiphospholipid syndrome, Creutzfeldt-jakob disease (CJD), Cooley’s Anemia, Fanconi Anemia, Hemophagocytic lymphohistiocytosis, Hemophilia, Hereditary Hemorrhagic Telangiectasia (HHT), Heparin-induced Thrombocytopenia (HIT), Lymphedema, Myelodysplastic Syndrome (MDS), Myeloproliferative Disorders (MPD), Paroxysmal Nocturnal Hemoglobinuria (PNH), Rare Bleeding Disorders, Rare Nutritional Anemias, Rare Thrombotic Disorders, Rare Hemolytic Anemias, Sickle cell disease, Thalassemia, Thrombocytopenias of Different Etiologies, Thrombotic Thrombocytopenic Purpura (TTP). Examples of rare lung diseases:Alpha-1-Antitrypsin deficiency (A1AT), Alveolar proteinosis, Congenital cysts and lobar emphysema, Congenital hypoventilation syndromes, Congenital Lymphangiectasia, Cystic Fibrosis (CF), Idiopathic pulmonary arterial hypertension, Idiopathic pulmonary fibrosis (IPF), Lymphangioleiomyomatosis (LAM), Pediatric interstitial lung disease, Primary Ciliary Dyskinesia (PCD), Sarcoidosis, Surfactant protein deficiencies. Examples of rare heart diseases: Marfan Syndrome , Peripartum Cardiomyopathy , Inherited channelopathies (Long-QT Syndrome, Brugada Syndrome) , Rare Inherited Cardiomyopathies (Arrhythmogenic Right Ventricular Dysplasia) , Hereditary Hemorrhagic Telangectasia (HHT), Supravalvular Aortic Stenosis (SVAS), Klippel-Trenaunay-Weber Syndrome (KTWS).  A list of rare diseases that are relevant to the research mission of the NHLBI can be found at: http://www.nhlbi.nih.gov/funding/inits/rd_list.htm

National Institute of Allergy and Infectious Diseases (NIAID)

NIAID research activities on rare diseases are classified into four areas: infectious diseases, primary immunodeficiency diseases, autoimmune diseases, and allergic diseases.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Many arthritic, rheumatic, musculoskeletal and skin diseases affecting adults and children that are of importance to NIAMS are considered rare.  NIAMS is interested in supporting research into the causes, treatment and prevention of these rare diseases.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

The NICHD conducts and supports research on topics related to health of children, adults, families, and populations.  Many disorders that affect children and their families are rare and/or neglected diseases.  NICHD has supported research in at least 80 rare disorders.  Many of these diseases have a genetic basis, and many affect cognitive development.  NICHD encourages applications in rare disorders, including (but not limited to):

National Institute of Dental and Craniofacial Research (NIDCR)

The NIDCR is interested in rare oral and craniofacial diseases and disorders that severely impact oral health and salivary gland function. Examples include:

Note that the NIDCR will not support any interventional clinical trials or biomarker validation studies through this program.  Applicants seeking funding for clinical trials or biomarker validation studies should apply to the R34 / U01 NIDCR Clinical Trials Program (see http://www.nidcr.nih.gov/Research/DER/ClinicalResearch/ClinTrials.htm). The NIDCR encourages clinical studies that define the natural history of rare diseases, establishes registries for individuals with rare diseases of IC interest, and establishes important clinical outcomes that could be used for future interventional studies.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

The NIDDK supports research on rare diseases and conditions resulting in endocrine, metabolic, digestive, hematologic and kidney disorders.  Below are some examples of rare diseases that may be appropriate. Rare digestive diseases would include liver, pancreas and gastrointestinal diseases. Example of bowel diseases include Inflammatory Bowel Diseases (IBD) in children, including Crohn’s disease, with subphenotypes of small bowel only or colon only disease, ulcerative colitis, with subphenotypes of limited colitis and pan colitis, and patients with indeterminate colitis. Examples of rare metabolic diseases include aminoacidopathies, cystic fibrosis, lysosomal storage diseases, and urea cycle defects.  Examples of rare hematologic, kidney and urologic diseases include inherited and acquired systemic amyloidosis, inherited bone marrow failure syndromes, Minimal Change Disease, ARPKD (Autosomal Recessive Polycystic Kidney Disease), Primary Hyperoxaluria, and renal disease associated with Tuberous Sclerosis. NIDDK will not support phase III trials through the RDCRN.

National Institute of Neurological Disorders and Stroke (NINDS)

The NINDS seeks to support clinical research on rare neurological disorders that affect the central and peripheral nervous systems. Examples of groupings of rare forms of neurological conditions include cerebrovascular diseases, neurometabolic disorders, neuromuscular and neurodegenerative disorders, movement disorders, epilepsies and episodic disorders, channelopathies, mitochondrial encephalopathies, and childhood developmental and/or genetic syndromes involving autism or intellectual disability.  However, interest is not limited to these conditions.  A list of diseases that is relevant to the research mission of the NINDS can be found at http://www.ninds.nih.gov/disorders/disorder_index.htm; applicants are encouraged to contact the NINDS to discuss potential applications and disease areas of interest.

The Office of Dietary Supplements (ODS)

ODS co-funds research with other NIH institutes and centers to investigate the potential roles of dietary supplements in promoting health and reducing the risk of chronic disease. ODS also engages its federal partners in activities to fill essential needs that would not otherwise be addressed.  Through the initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), ODS is interested in applications that pertain to conducting research on the inborn errors of metabolism (IEM) that utilize nutrition and dietary supplement interventions as their primary management modality.  These conditions include, but are not limited to those identified through the Secretary of Health and Human Services’ Recommended Uniform Screening Panel for newborn screening and encompass disorders of amino acid, organic acid, fatty acid, and carbohydrate metabolism.  Applications should aim to:

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal

The OER Glossary and the PHS 398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The participating ICs intend to commit approximately $17.5 million in FY 2014 to fund up to fourteen awards. If additional IC funds become available, more consortia may be funded.

Award Budget

Application budgets are limited to $1.25 million total cost per year.

Award Project Period

Applicants request for 5 years of support.

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


Eligible Organizations

Higher Education Institutions

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her 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.

Applications with multiple PDs/PIs are not allowed.

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct and the rare diseases represented in the applications are distinctly different.

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

The letter of intent should be sent to:

Rashmi Gopal-Srivastava, Ph.D.
Telephone: 301-402-4336
Fax: 301-480-9655
Email: gopalr@mail.nih.gov

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and 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)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Carol Lambert, Ph.D.
Office of Scientific Review
NCATS, NIH
6701 Democracy Blvd.
Bethesda, MD 20817
Telephone: 301-435-0814
Email: lambert@mail.nih.gov

Page Limitations

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the PHS 398 Application Guide, and should be used for preparing a multi-component application.

The application must consist of the following components:

Overall Component

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:)

Describe the overall proposed clinical research program of the RDCRC indicating the goals and objectives of the individual clinical research projects. Describe the nature of the multidisciplinary team and approach for the consortium of clinical investigators, institutions, and relevant organizations, including patient advocacy groups, focused on a subgroup of at least three rare diseases. Each RDCRC must provide statistical and clinical support. Describe the role of the patient advocacy group(s) and other relevant organizations for patient recruitment and as well as activities appropriate for the level of Patient advocacy group.

Table of Contents (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Do not use the Form PHS 398 Table of Contents. Create a Table of Contents appropriate for the RDCRC application. This is paginated to follow the list of Key Personnel. Do not use letters (e.g. 4a, 4b, 4c, etc.). The Table of Contents should specifically list the locations of the overall budgets, biographical sketches and various narrative sections. Also, list projects and components of the programs for which funding is sought with the title and project/program leaders. Include the number and title for each project. For example, Project 1: Phase I clinical trial for the treatment of rare disease X. PI: John Doe, M.D.

Detailed Budget for Initial Budget Period (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Justify and document all costs for current and future years, using a composite summarizing all individual budgets (that is, under personnel, total the personnel costs for ALL components and continue for the other budget items.) No details need be given for the individual categories.

Budget for Entire Proposed Period of Support (Overall)

All instructions in the PHS 398 Application Guide must be followed.

Provide a composite summarizing all individual budgets (that is, under personnel, total the personnel costs for ALL components and continue for the other budget items). For the purpose of establishing future year budget requests, the applicant should not use cost escalations.

Biographical Sketch (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Biographical sketches are required for all professional level personnel who are listed with a measurable effort (including consultants) in the RDCRC application. Place the Program Director (PD)/Principal Investigator (PI) and Administrative Director biographical sketches first, followed by the other individual biographical sketches in alphabetical order. These pages should not be duplicated in other components, projects, etc. Key patient advocacy group partners must be included in the biographical sketches.

Resources (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated institutions and units, rare diseases patient populations, geographic distribution of space and personnel, and consultative resources. Each RDCRC must provide biostatistical support.  Describe institutional capability for statistical and clinical support. The RDCRC applicants at an institution with a Clinical and Translational Science Award (CTSA) are encouraged to use the resources available at their CTSA institution.

Institutional Commitment: Each RDCRC must provide a statement that addresses how the institutional commitment will be established and sustained, and how the RDCRC research effort will be given a high priority within the institution. The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the RDCRC Director, assignment of research space, cost sharing of resources, protected time for the investigators to pursue clinical research and mitigate the demands of providing patient care, and/or other ways proposed by the applicant institution. The primary institution is strongly encouraged to demonstrate its commitment to RDCRC by providing financial support to the Training Component and Pilot/demonstration (proof of concepts) clinical research projects on an awarded RDCRC, as well as other programmatic needs identified as high priority on the original application. Letters from high-level institution official(s) (e.g., Dean of the School of Medicine, President, and Vice President for Research) should be included confirming this commitment. For the consortium, the institution that submits the U54 application must receive a formal written agreement(s) from the other participant organization(s) and submit them with application. This agreement should clearly delineate the institutional commitment of the participating organization(s) (in the ways outlined above) to the RDCRC Program.

Provide documentation for established consortium agreement with other institution(s) to provide adequate access to clinical specimens (e.g., tissues, blood, and urine) and/or patients at another site(s).

Research Plan (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims:  Describe specific aims of the RDCRC.

Research Strategy:

1. RDCRC Program Introduction and Statement of Objectives

Describe the group of rare diseases to be included, the rationale for this grouping, and the relevant expertise available in the consortium. Each RDCRC should include a group of at least three related rare diseases, disorders or syndromes. State the clinical research objectives of the proposed RDCRC and the research focus of the application. Describe the rationale for the proposed clinical research program on the proposed group of diseases, and explain the strategy for achieving the objectives of the overall program, how each project relates to the strategy, and how the diseases relate to one another. Briefly describe the clinical research projects and the rationale for each within the RDCRC.

2. RDCRC Scientific and Administrative Leadership:

The emphasis in this section should be on the qualification of the RDCRC leadership. Describe the qualifications of the PD/PI of the application (RDCRC Director) to lead the program. Qualifications and role of the Administrative Director should also be included in this section.

3. Multidisciplinary Team Involving Patient Advocacy Groups and collaborations

Describe the nature of the multidisciplinary team and approach for the consortium of clinical investigators, institutions, and relevant organizations, including patient advocacy groups, focused on a subgroup of at least three rare diseases. Include a plan to fully incorporate the Patient Advocacy Groups’ representation in the organizational structure and consortium interactions (conference calls, meetings, etc). Describe advocacy participation across the planned objectives (e.g., in addressing clinical design, recruitment, and education).The proposed patient support organization’s activities should be appropriate for the level of advocacy capabilities.

It is important to indicate prior collaborative arrangements between investigators in the group and patient advocacy groups, to emphasize the events that have led to the current application, and to predict the anticipated unique advantages that the research within the proposed RDCRC would gain. Describe how the RDCRC will utilize the members of the consortium fully within the confines of the resources and the rare diseases to be studied, and how the scientific community and patient advocacy groups will be integrated within the consortium. Renewal applicants must demonstrate the ability to collaborate by providing examples of previous and/or ongoing collaborations. A supporting letter from collaborating patient advocacy groups is recommended.

4. Environment and Website for Education and Research

Each application must include a description of resources to be included in a web site for education and research in rare diseases. These resources should include a description of materials for lay public, patients, basic and clinical researchers, and clinicians. Do not include URLs within the application itself; reviewers will be instructed not to visit external links during their review of the application. Examples include but are not limited to: patient registries; contacts for animal models; tissue, serum, specimens, DNA, etc; antibodies and research reagents; genetic resources; registries; education materials; and/or diagnostic flow charts. The actual design and implementation of the site will be a collaborative activity of the DMCC and all RDCRC through the Steering Committee. The RDCRC and DMCC must agree to work cooperatively to develop the web site resource and provide content related to its focused rare diseases. Institutional and outside support for this program is encouraged.

5. Rare Diseases Patient Population

Each RDCRC must document access to a substantial patient population in the rare diseases focus of the application and provide reasonable assurance that the patients and human specimens needed for clinical research are readily available. Each RDCRC must describe in detail how patients will be identified and recruited for study. Resources for outreach, recruitment and retention of these patients should be provided.

6. Plan for Streamlining Protocol Approval Process

Applicants should present a plan for how the proposed RDCRC will try to streamline the multi-site protocol approval process.  Specifically, applicants are strongly encouraged to consider models that will facilitate “shared review” such as central IRB of record or IRB Share for multisite trials and provide plans for implementation.  Having a central IRB of record for multi-site trials is preferred and may even improve patient safety and scientific validity, as well as trial efficiency.  The central IRB might logically reside at the RDCRC PD/PI’s institution.  Member institutions of the RDCRC would agree to a) accept the findings of the central IRB, b) accept the central IRB findings with modifications, or c) convene their own IRB.  If a central IRB or IRB Share is not feasible, applicants should discuss systems for making the protocol approval process as rapid and efficient as possible. 

7. Renewal Applications: Additional Material Required

All applications for renewal must provide information documenting the impact of the clinical research from the original application.

Resource Sharing Plan:Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Applications for RDCRC cooperative agreement awards are expected to include a data and research resources sharing plan. The plan should outline how final research data will be shared by the members of individual RDCRC, as well as with the research community at large, or state why this is not possible.

The NIH also encourages the timely sharing of biomedical resources by grant recipients. Therefore, the plan should also describe how unique research resources will be distributed, e.g., through the institution, a repository, or national coordinating center. During the 5-year funded period, if a RDCRC proposes to collect biospecimens, the RDCRC is expected to register contact information regarding its Biorepository with the Biospecimen/Biorepositories Website RD-HuB (http://biospecimens.ordr.info.nih.gov/).  RDCRCs are also encouraged to upload information about their biospecimen into the RD-HuB specimen locator on this website to help researchers utilize available specimens. Describe your plans.

Clinical Research Projects for Observational/Longitudinal Studies or Clinical Trials

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed.

These projects should be numbered consecutively with use of only integers (i.e., Project 1, Project 2, Project 3, Project 4, etc.); project numbers should not have suffixes (e.g., Project 1A or 1a, Project 1B or 1b, etc.). Each research project should be clearly identified by the same title as that provided in the Table of Contents.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Describe the clinical research project.

Table of Contents (Clinical Research Projects for Observational/Lomgitudinal Studies or clinical Trials)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Do not use the PHS 398 Table of Contents.  Create your own Table of Contents using the the form headings below.    

Detailed Budget for Initial Budget Period (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed.

Budget for Entire Proposed Period of Support (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed.

The project leader should devote at least 1.8 calendar months to the research.

Biographical Sketch (Clinical Research Projects)

All Biographical Sketches should be included in the Overall section.

Resources (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Clinical Research Projects)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe specific aims of the project.

Research Strategy:  Describe the research section in enough detail so the scientific merit can be judged on the basis of the written proposal. Begin each project with a short section that clearly states how that project contributes to the objectives of the RDCRC as a whole.

Applicants are required to submit clinical research projects that can characterize and more completely define the disease and its course for the rare diseases that are encompassed in their consortia. These, in general, will be observational (non-interventional) such as longitudinal or natural history studies of patients with the given disease. These can be clinical trial-readiness projects (e.g., development of biomarkers for clinical trials, clinical outcome measures, etc.) and/or clinical trials (At least two projects are required and one of them must be a longitudinal study): Describe the rationale for the planned clinical studies and longitudinal assessment of subjects. Strategies for recruitment, retention, assessment, and analysis must be included. Data supporting the recruitment numbers is recommended. The study design and objectives should take into consideration what information regarding the rare disease population would be needed in order to pursue clinical trials in that rare disease. The applicants should approach the longitudinal study with the question: what knowledge/tools are needed regarding the rare disease in order to design efficient efficacy trials for this rare disease? Even if there are no treatments currently proposed for the rare diseases under study, the longitudinal study should be designed with the consideration that if a treatment were suddenly available for this rare disease, what knowledge (outcome measures, features of disease course, markers of disease or subpopulations of the rare disease that may alter disease course, etc.) about the rare disease over time would be important to have in order to design an appropriate treatment (efficacy) trial.)

Depending on the state of knowledge of the particular diseases, the projects could include strategies for assessing current therapeutic interventions, or new clinical trials. Under current regulations, NCATS will support Phase I or Phase IIa but will not support phase IIb, IIb/III or phase III clinical trials. If proposing such trials contact NIH IC Scientific/Research contacts. (See Section VII. Agency Contacts). Although clinical trials can be supported through RDCRC, clinical trials are NOT a required component of an RDCRC.Each application must include a description and rationale for the planned clinical trials. Strategies for recruitment, retention, assessment, and analysis must be included. Strategies for biomarker discovery studies utilizing specimens from these trials are encouraged.

Each application must include a description and rationale for the planned clinical studies and longitudinal assessment of subjects. Strategies for recruitment, retention, assessment, and analysis must be included. Data supporting recruitment number is recommended.Evidence of the ability to conduct clinical studies as well as demonstration of successfully recruiting and retaining study participants should be provided. Proposed longitudinal studies should be hypothesis-driven with defined quantifiable scientific objectives. Developing a patient registry is not considered a longitudinal study for this program.  

Incorporating the patients’ voice into clinical research studies as outcome measures is widely recognized as essential to fully capture both benefit and harm to the patients, as well as assess their health-related quality of life (HRQoL).  This is especially true for patients with rare diseases.   Applicants are encouraged to explore options for including and initially validating not only existing, but also emerging, patient-reported outcomes (PROs) such as the NIH-funded PROMIS® (www.nihpromis.org) and NeuroQoL (www.neuroqol.org).  Owing to their unique reliance on item-response theory (IRT) and a focus on domains rather than diseases, these new tools may facilitate assessment of symptoms and HRQoL in many, if not most, rare diseases.

A plan for a clinical research project must include provisions for rigorous data management, quality assurance, and safety monitoring. These monitoring activities are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).

For renewal applications: Applicants should outline the scientific accomplishments and discuss the potential impact on the rare disease for each clinical research project (study) completed in the last grant period. Applicants should also describe how they have partnered with the relevant patient advocacy groups and the roles these groups have played in the studies undertaken and engagement with patients.  Any difficulties in achieving the previously proposed specific aims should be addressed.  If a clinical trial(s) or longitudinal/Observational studies have been conducted as a part of a research project in your previous application, a table should be provided listing the following information for each trial: protocol number, protocol title, date trial opened, date trial closed and total number of accrual.  With the exception of the publication list, this information should be incorporated into the Preliminary Studies/Progress Report of each clinical research project. Proposed work can be a combination of: 1) the continuation of ongoing projects, 2) follow-on studies of current projects (eg. a Phase II clinical trial based on a results from a Phase I trial), and/or 3) new projects.

Human Subjects Protections: Provide a general description of a monitoring plan to establish the overall framework for data and safety monitoring. This description should explain the plans for detecting, monitoring, and reporting any adverse event during a clinical study. A copy of a draft or IRB-approved clinical research protocol (Observational/Longitudinal Studies and clinical trials), along with informed consent forms and a specific data and safety monitoring (DSM) plan, should be included in the Human Subjects section if the study is anticipated to begin within the first year of an award. A data and safety monitoring plan is required for all clinical studies. Depending upon the risk of the study, appropriate monitoring could include, for example, the PD/PI and IRB, a study monitoring committee, or an independent data and safety monitoring board (DSMB). NIH policy requires establishment of a DSMB for multi-site clinical trials involving interventions that entail potential risk to the participants. Requirements for monitoring of other types of clinical studies vary by IC; please contact IC Scientific/Review staff for IC-specific policies and guidance (See Section VII. Agency Contacts). See http://grants.nih.gov/grants/policy/hs/data_safety.htm.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modification:

Pilot/Demonstration Clinical Research Projects Program

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

These funds are intended to remain flexible and to support studies of 2 years or less.

The funds for these projects should be utilized for research activities and cannot be used for the purchase of any large equipment.

Budget for Entire Proposed Period of Support (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed.

Biographical Sketch (Pilot/Demonstration Clinical Research Projects Program)

Do not include Biographical Sketches here.  All Biographical Sketches should be included in Overall section.

Resources (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Pilot/Demonstration Clinical Research Projects Program)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: Describle specific aims of Pilot/Demonstration Clinical Research Projects Program.

Research Strategy: Each RDCRC application must propose to support one or more pilot/demonstration projects that take maximum advantage of new clinical research opportunities in rare diseases. Such projects may be collaborative among scientists within one or more RDCRC, or with scientists outside the RDCRC environment. The applicant should propose funding pilot projects that generate feasibility data and have the most promising clinical research potential. All applicants must include a description of eligible projects. Describe and provide rationale for the planned pilot projects. Examples of pilot/demonstration studies include development of novel laboratory assays and clinical instruments, development of tools for drug discovery (e.g. development of bioassays for screening compounds), analysis of extracellular RNAs as biomarkers of disease and/or response to therapeutics, retrospective chart review from different study sites. Depending on the state of knowledge of the particular diseases, the pilot studies could include strategies for assessing current therapeutic interventions, or phase I, I/II, phase II and Phase II/III clinical trials. Under current regulations, NCATS does not support phase IIb and IIb/III trials. If proposing phase IIb or IIb/III trials, contact NIH IC Scientific/Research contacts to adhere to the IC policies. (See Section VII Agency Contacts) Each pilot project should be proposed for a period of no more than two years.

This is a required component of RDCRC, and must be maintained throughout the entire term of the award. The NIH will monitor the activities of RDCRC sponsored pilot/demonstration during non-competitive years to assure that there is adherence to the clinical research intention of the RDCRC program during the term of the award.

Human Subjects Protection: Provide a general description of a monitoring plan to establish the overall framework for data and safety monitoring. This description should explain the plans for detecting, monitoring, and reporting any adverse event during a clinical study. A copy of a draft or IRB-approved clinical research protocol along with informed consent forms and a specific data and safety monitoring (DSM) plan, should be included in the Human Subjects section (Section E) if the trial already is anticipated to begin within the first year of an award. If the trial will be performed during the latter part of the award term, submission of these items to NIH program staff is required prior to the initiation of the trial. A data and safety monitoring plan is required for all clinical studies. Depending upon the risk of the study, appropriate monitoring could include, for example, the PD/PI and IRB, a study monitoring committee, or an independent data and safety monitoring board (DSMB). NIH policy requires establishment of a DSMB for multi-site clinical trials involving interventions that entail potential risk to the participants. Requirements for monitoring of other types of clinical studies vary by IC; please contact IC Scientific/Research contact for IC-specific policies and guidance. (See Section VII. Agency Contacts). http://grants.nih.gov/grants/policy/hs/data_safety.htm

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

Training (Career Development) Component

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (Training (Career Development) Component )

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:  Add name of the Director of Training (Career Development) Component.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Training (Career Development) Component)

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Training (Career Development) Component )

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (Training (Career Development) Component)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

A minimum of $50,000 direct costs per year from the RDCRC budget must be dedicated to this program and be utilized to support the salary and research costs of candidates with outstanding potential. At least two trainees over 5 years must be supported and trained. The RDCRC should spend $250,000 over 5 years for training. Institutional and outside support for this program is encouraged. Each junior level candidate (senior post-doctoral fellows, clinical fellows, and assistant professors/junior faculty) should have a mentor(s) and devote at least 3 calendar months of his/her effort to clinical research.

Budget for Entire Proposed Period of Support (Training (Career Development) Component)

All instructions in the PHS 398 Application Guide must be followed.

Biographical Sketch (Training (Career Development) Component)

Do not include Biographical sketches here.  All Biographical Sketches should be included in Overall section.

Resources (Training (Career Development) Component )

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (Training (Career Development) Component)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: 

Specific Aims:  Describe specific aims of Training(Career Development) Component

Research Strategy: Each application must include a plan for training of new investigator(s) for clinical research in rare diseases within their RDCRC.  Each RDCRC should provide a unique environment for clinical research in rare diseases that can be used to prepare new scientists for careers in this field and provide the opportunity for established scientists to re-orient their research careers toward rare diseases research through relevant courses, mentorship, and participation in clinical research.

The RDCRC must demonstrate a consistent and significant commitment to a Training (career development) Program in clinical research. Funds from this program may be used to support advanced post-doctoral or clinical fellows, junior faculty (e.g. assistant professor rank, research faculty, instructors), or established investigators who wish to develop or refocus their careers on clinical research in rare diseases. RDCRC Training Programs are not intended for predoctoral candidates or junior level post-doctoral fellows (e.g. fewer than 2 years).

The description of this program should include the policies, criteria, and processes for selecting candidates, including special efforts to recruit individuals from groups underrepresented in the biomedical sciences. The plan should include the number and types of positions (e.g., advanced post-doctoral fellows, junior faculty, and established investigators) that will be made available, the criteria for eligibility and selection of candidates, and a description of the selection process. All applicants should provide a short description of types and qualifications of potential candidates, as well as the qualifications and research activities of mentors.

A Training component, as a required element of a RDCRC, must be maintained throughout the entire term of the award. Funds from the Training Program should be utilized to support clinical research activities, including partial salary support for the candidate, research personnel, supplies, travel, and/or other expenses. Training funds should not be used for the purchase of any large equipment.

For renewal applications: List individuals supported during the last award period, their scientific accomplishments while supported by the RDCRC, and how RDCRC support has advanced their clinical research careers in rare diseases. Provide the number of individuals from groups underrepresented in the biomedical sciences trained and the number of calendar months devoted to clinical research.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

RDCRC Administrative Unit

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.

Face Page (RDCRC Administrative Unit )

All instructions in the PHS 398 Application Guide must be followed.

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (RDCRC Administrative Unit) 

All instructions in the PHS 398 Application Guide must be followed.

Table of Contents (Training (RDCRC Administrative Unit)

All instructions in the PHS 398 Application Guide must be followed.

Detailed Budget for Initial Budget Period (RDCRC Administrative Unit)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

The RDCRC Director (PD/PI of the application) is expected to make a commitment of at least 2.0 months to the overall administration of the program plus 1.2 months as a leader of a RDCRC project (if leading a clinical research project. RDCRC Administrative Unit support personnel may be budgeted at no more than 12 calendar months, which may be divided among one or more positions. This FTE must be fully justified. Note that the RDCRC Director is expected to send two RDCRC participants to three 2-day meetings in the first year in the Washington, D.C. area and biannually thereafter in Bethesda, MD with NIH staff, and should budget for these meetings.

Budget for Entire Proposed Period of Support (RDCRC Administrative Unit)

All instructions in the PHS 398 Application Guide must be followed.

Biographical Sketch (RDCRC Administrative Unit)

Do not include Biographical sketches here.  All Biographical Sketches should be included in Overall section.

Resources (RDCRC Administrative Unit)

All instructions in the PHS 398 Application Guide must be followed.

Research Plan (RDCRC Administrative Unit)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Specific Aims: Describe specific aims of RDCRC Administrative Unit.

Research Strategy: The purpose of a RDCRC is to expedite development and application of new knowledge in clinical research of specific importance to rare diseases. The RDCRC Administrative Unit is responsible for the overall administration of the RDCRC (including policy, procedure, and fund allocation). Describe in detail, and by diagram if appropriate, the chain of responsibility for decision-making and administration. Include to whom the RDCRC Director (PD/PI) reports and the administrative structure as it relates to the investigators responsible for the clinical research projects. If advisory groups will be used, indicate their specific functions, composition and to whom they report. Describe a sound plan for communication (meetings, conference calls etc.) and participation of all personnel within the consortium. The description of the administrative unit of an RDCRC should detail how the activities and contribution of the collaborating investigators and institutions will be coordinated.

The RDCRC Administrative Unit must include a clinical investigator who ensures a mutually supportive interaction between scientists conducting clinical research. The qualifications of the clinical investigator and the plan to promote clinical research should be described.

An Administrative Director should be identified on the application who will be responsible for assisting the RDCRC Director (PD/PI of the application) with the day-to-day administrative details, program coordination, and planning and evaluation of the program, and who would be in charge in the absence of the RDCRC Director. The Administrative Director may be from a different Institution.

Describe the biostatistical support for the RDCRC in this section. The biostatistician from RDCRC will provide statistical support for protocol development and assist in study designs and statistical data analysis. The biostatistician in collaboration with DMCC will also assist in the collection of epidemiologic information and quality assurance for database of pooled data for the RDCRC. The DMCC will work with NIH program staff to register RDCRN studies in dbGaP and will upload data on a regular basis according to the data sharing plan established by the Steering Committee.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix for the Entire Application

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS 398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

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.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Post-Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in

NOT-OD-13-030.

Section V. Application Review Information


1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

For RDCRC applications (U54), peer review of scientific and technical merit will focus on all components of RDCRC.

Overall Impact - Overall

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

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in the determination of scientific 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 RDCRC address an important problem or a critical barrier to progress in the field? If the aims of the RDCRC 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(s)/PI(s), collaborators, and other researchers well suited to the RDCRC? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, 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?

Specific for this FOA

Leadership:

Are the scientific qualifications and involvement of PD/PI (RDCRC Director) and Administrative Director as well as scientific and administrative leadership capabilities and time commitment presented and sufficient for the requirements of the proposed RDCRC?

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 RDCRC? 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 RDCRC 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? 

Specific for this FOA

Rare Diseases Patient Population:

Is access to the proposed rare diseases patients populations for conducting clinical research adequate to ensure likely success of the goals of the program? (For renewal applications, documentation of accomplished clinical research goals, including evidence of human subjects enrollment on clinical research studies during the past funding period should be provided.)

Multidisciplinary Team Involving Patient Advocacy Groups Collaborations:

Is there a plan to fully incorporate the relevant Patient Advocacy Groups within RDCRC structure and interactions (including conference calls and meetings)?

Is Patient Advocacy Group participation described across the planned objectives (e.g. in addressing clinical design, recruitment and education)?

Are proposed activities appropriate for the level of the Patient Advocacy Groups?

Is there evidence of tangible interactions with Patient Advocacy Groups

Is there evidence of tangible interactions with other participating sites?

Are the abilities of the investigators to interact with other participating sites and with the NIH in sharing information, participating in committees, and collaborating on activities of mutual interest evident and sufficient? (For renewal applications, contributions and outcomes from RDCRN meeting, Workshop and other related RDCRC meetings during the term of the award should be provided. Partnership with Patient Advocacy Group in prior funding period should be included)

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? 

Specific for this FOA

Institutional Commitment:

Is there an appropriate description of resources to the included in the web site for education and research in rare diseases?

Are there features in the institutional environment that are relevant to the effective implementation of the proposed program? 

Is there institutional commitment to establishing the RDCRC as an integral part of its overall clinical research environment?

Will the institution align or adjust incentives and rewards to promote the academic mission of collaborative rare diseases research?

Is there commitment from the institutional leadership to protect the time of the investigators to pursue clinical research and mitigate the demands of providing patient care?

Will clinical researchers/trainees be supported for the training program?

Is the institutional leadership committed to this program and its goals in terms of providing assets specifically for the program, such as faculty support, specific equipment, dedicated space, or financial support as a few examples?

Do the plans for integrating the activities of RDCRC clinical research projects with existing institutional resources (e.g., use of safety management systems, biostatistical support, etc.), give confidence and sufficient evidence that such efforts are likely to be effective? 

Scored Review Criteria - Clinical Research Projects

Reviewers will consider each of the review criteria below in the determination of scientific 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 this study address an important problem? If the aims of the application are achieved, will scientific knowledge or clinical practice be advanced? Will these studies affect the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Approach

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 applicant acknowledge potential problem areas and consider alternative approaches? Is the proposed research plan appropriate for the state of knowledge, current capabilities and resources for the rare diseases? Are the questions being asked for the rare disease(s) and objectives outlined most likely to characterize and more completely define the disease(s) and its course? Is the clinical design appropriate to address the objectives of the research plan? Are adequate strategies for recruitment, retention, assessment, and analysis of subjects included?

Innovation

Are the projects original and innovative? Do the projects challenge existing paradigms or clinical practice? Do the projects address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Are there novel methods for recruitment and outreach to health professionals?

Investigators

Are the investigators appropriately trained and well suited to carry out this work? Do they have experience in conducting clinical research? Is the work proposed appropriate to the experience level of the Project Leader and other researchers? Does the investigative team bring complementary and integrated expertise to the project? Are the investigators committed to collaborative and cooperative nature of this program?

Environment

Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support? Is there active participation of relevant Patient Advocacy Groups? Will the proposed administrative plan, infrastructure, and resources provide appropriate support for the clinical research to be undertaken by the RDCRC?

Scored Review Criteria - Pilot/Demonstration Projects Program

Reviewers will consider each of the review criteria below in the determination of scientific 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.

Innovation

Does the proposed plan address attracting new ideas and pilot studies within RDCRC institutions?

Approach

Does the proposed plan address continuously reviewing and funding a spectrum of pilot projects with clinical research potential in rare diseases?

Will the proposed plan support pilot/demonstration projects that take maximum advantage of new clinical research opportunities in rare diseases?

Scored Review Criteria - Training (Career Development) Component

Reviewers will consider each of the review criteria below in the determination of scientific 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.

Innovation

Does the proposed plan for the training describe how promising candidates for clinical research in rare diseases will be identified and selected?

Environment

Is the training plan adequate and the environments within the proposed center appropriate for supporting the training of new investigators?

Does the proposed plan address the recruitment and inclusion of individuals from groups underrepresented in the biomedical sciences? (For renewal applications, provide current status and clinical research activities of individuals who have been supported by the training program). This may include continuing support and integration of successful trainees as research project co-investigators.

Scored Review Criteria -  RDCRC Administrative Unit

Reviewers will consider each of the review criteria below in the determination of scientific 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.

Approach

Are the plan(s) for overall administration of RDCRC, coordination of clinical research and collaborations presented and sufficient for the requirements of the proposed RDCRC?

Is the plan for communication and participation of all personnel within the consortium well described?

Does the RDCRC provide appropriate biostatistical support?

Is it clear how the activities and contribution of the collaborating investigators and institutions will be coordinated and is the plan appropriate?

Additional Review Criteria - Overall

As applicable for the RDCRC proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, 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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children 

When the proposed RDCRC 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. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Resubmissions

 Not Applicable

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

Not Applicable

Additional Review Considerations - Overall

As applicable for the RDCRCt proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Plan for Streamlining the Protocol Approval Process

Applications from Foreign Organizations

Not Applicable

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; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s)convened by the NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

Appeals of initial peer review will not be accepted for applications submitted response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information


1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.      

Any application awarded in response to this FOA will be subject to the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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 The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) 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.

The PD(s)/PI(s) will have the primary responsibility for:
The Principal Investigator of the RDCRC will have the primary responsibility for defining the details of the project within the guidelines of the RFA-TR-13-002 and for performing the scientific activity, and agrees to accept close coordination, cooperation, and participation of the NIH staff in those aspects of the scientific and technical management of the project described below. Specifically, awardees have primary responsibility as described below.

RDCRC Director and the DMCC Director

The Rare Diseases Clinical Research Consortium Directors (RDCRC Directors) with the assistance of the Data Management and Coordinating Center Director (DMCC Director) are responsible for the overall management of their RDCRC (Consortium) and coordination with the other Consortia. The relationship between the Consortia and the Data Management and Coordinating Center (DMCC) should be one of equal partners in the Rare Disease Clinical Research Network (Network).

Collaboration and Coordination

The collaboration of investigators between Consortia is highly encouraged based on shared interests and complementary talents. The planned collaborating sites within the Consortium must be ongoing and active. Plans for evaluating and removing or replacing non-productive sites of a Consortium must be in place for each Consortium.

Network Steering Committee Membership and Meeting Attendance

Each Consortium Principal Investigator will be designated the Consortium Director. Each Consortium Director will be a voting member of the Network Steering Committee and participate in all Committee activities and decisions including, but not limited to, conference calls and special subcommittees as may be necessary. The Steering Committee shall be responsible for determining the frequency of meetings and scheduling the time and location. The Steering committee will establish the procedures for the function of the Consortia network, as outlined in section 2.A.3 "Network Steering Committee."

Data Coordination and Management and Sharing

The awardees will have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS and NIH policies. The DMCC will develop a data management system with the input of the Steering Committee. All Consortia will place their data at the DMCC. For complete roles and responsibilities of DMCC see companion FOA. The intention of the NIH is that the data collected within this Network will become a resource for the Rare Disease Community and be made available to the scientific community through an ORDR-governed data repository. Criteria and mechanisms for data sharing among investigators within the Network and with the scientific community will be developed by the Steering Committee. The DMCC will also coordinate with NIH program staff including registration with and data uploading of appropriate RDCRN studies to ORDR-governed data repository (through dbGaP, a database for genotypes and phenotypes, National Library of Medicine). Data transfer to dbGaP is expected to occur on regular basis according to the data sharing policy for RDCRN established by the Steering Committee and as approved by NIH staff.

Publication and Presentation of Study Findings

Timely publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of the Rare Disease Clinical Research Network, ORDR, NCATS, and NIH ICs support. The Steering Committee will establish unifying procedures and criteria for presentation and publication of data developed within the Rare Disease Clinical Research Network so that these procedures and criteria are consistent across the Network.

Federally Mandated Regulatory Requirements

Each institution participating in the Rare Diseases Clinical Research Network is required to meet DHHS regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include:

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.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

An NIH Project Scientist from each participating IC will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. For IC specific roles and responsibilities of Project Scientists contact the appropriate NIH IC Program Official listed in Section VII. Agency Contact.

One representative from ORDR, NCATS will be designated to serve as the Program Coordinator for this cooperative agreement program (RDCRN). The ORDR, NCATS Program Coordinator for RDCRN and one Project Scientist from each participating IC will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for awards.

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

Network Steering Committee Membership and Meeting Attendance

The NIH Program Coordinator from ORDR, NCATS and the Project Scientists from the participating ICs will serve on the Steering Committee and will participate in all Committee activities, including, but not limited to, meetings, conference calls, subcommittees, and special committees. They will assist in development of operating policies, quality control procedures, and policies that require cooperative action. While the ORDR Program Coordinator and participating IC Project Scientist will attend Steering Committee Meetings, their cumulative votes may never exceed 40 percent.

Monitoring Performance

The ORDR, NCATS Program Coordinator and IC Project Scientists will assist the Steering Committee in the development of procedures for monitoring the performance of the clinical studies. This includes participation in periodic on-site monitoring with respect to compliance with protocol specifications, quality control and accuracy of data recording, and accrual.

Publication and Presentation of Clinical Studies Findings

The NIH staff may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the clinical studies to the investigator community and other interested scientific and lay organizations. Co-authorship by the NIH staff will be subject to approval in accordance with the NIH policies regarding staff authorship of publications resulting from extramural awards.

The Government, via the ORDR, NCATS Program Coordinator, IC Project Scientists and Program Officials, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. Information obtained from the data may be used by NIH staff for the preparation of internal reports on the activities of the clinical studies. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Program Stewardship

The assigned Program Official from participating NIH ICs will be responsible for normal programmatic stewardship and monitoring of this award and approval of new pilot studies. The Program Official will not serve as the substantively involved IC Project Scientist. They may receive input and recommendations from other NIH staff in monitoring the awards. 

Areas of Joint Responsibilities include:
All responsibilities are divided between awardees and NIH staff as described above

All investigators within each Consortium and the DMCC must be willing to work cooperatively and collaboratively both within their Consortium and with other Consortia. Each Consortium is expected to send two Consortium participants to three 2-day meetings in the first year in the Washington, D.C. area and biannually thereafter.

Network Steering Committee

A Steering Committee will be established to serve as the main governing body of the cooperative network. At a minimum, the Steering Committee will be composed of one representative from each of the Consortium, one representative from the DMCC, the chairperson of Coalition of Patient Advocay Group (CPAG),  the NIH Program Coordinator from ORDR, NCATS, and other participating IC Project Scientists. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 40 percent.

The Chairperson of the Steering Committee will be selected by the Steering Committee from among the non-Federal members during one of the early meetings of the Committee to be convened by the NIH Program Coordinator from ORDR, NCATS. All major decisions will be made by the Steering Committee. The Committee will meet at least three times during the first 12 months of the program and at least semi-annually thereafter. As needed, the Steering Committee may establish subcommittees for special purposes. It is expected that most of the work of the Steering Committee will be performed in these subcommittees. All Consortia and DMCC must abide by decisions of the Steering Committee.

The Steering Committee will have responsibility of facilitating the conduct of the clinical studies, promoting trans-Consortium collaboration, establishing and updating the content of the web resource site, and establishing procedures for reporting results of Consortium studies. 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.

Dispute Resolution:

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 Network 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 dispute resolution procedure does not alter 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

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement..

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: commons@od.nih.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY: 301-451-5936
Email: GrantsInfo@nih.gov

 
Scientific/Research Contact(s)

 Elizabeth Read-Connole, Ph.D.
National Cancer Institute
Telephone: 240-276-6226
Email:  bconnole@mail.nih.gov

Grace L Shen, Ph.D.
National Eye Institute (NEI)
Telephone: 301-451-2020
Email: sheng@mail.nih.gov

National Heart, Lung, and Blood Institute (NHLBI)

For rare heart diseases:

Michelle Olive, PH.D. 
National Heart, Lung and Blood Institute
Telephone: 301-435-0550
Email: olivem@nhlbi.nih.gov

For rare lung diseases:

Susan Banks-Schlegel, Ph.D.
National Heart, Lung, and Blood Institute
Telephone: 301-435-0202
Email: schleges@nih.gov

For rare blood diseases:

Andrei L. Kindzelski, M.D., Ph.D.
National Heart, Lung, and Blood Institute
Telephone: 301-435-0070
Email: kindzelskial@nhlbi.nih.gov

Linda M. Griffith, MD, PhD
National Institute of Allergy and Infectious Diseases
Telephone: 301-496-7104
Email: LGriffith@niaid.nih.gov

James Witter MD, PhD
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-1963
Email: witterj@mail.nih.gov

Mary Lou Oster-Granite, Ph. D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-435-6866
Email: mo96o@nih.gov

Jane C. Atkinson, D.D.S.
National Institute of Dental and Craniofacial Research
Telephone: 301-435-7908
Email: jatkinso@mail.nih.gov

Ellen Leschek, MD
National Institute of Diabetes and Digestive and Kidney Diseases 
Telephone: 301-402-8291
Email: lescheke@extra.niddk.nih.gov

Laura A. Mamounas, Ph.D.
National Institute of Neurological Disorders and Stroke
Telephone: 301-496-5745
Email: mamounal@ninds.nih.gov

Randall R. Stewart, Ph.D.
National Institute of Neurological Disorders and Stroke
Telephone: 301-496-1917
Email: stewartr@ninds.nih.gov

Kathryn Camp, M.S., R.D., CSP
Office of Dietary Supplements
Telephone: 301-435-3608
Email: campkm@od.nih.gov

Issues that remain after consultation with NIH IC program staff that are not addressed in this FOA may be addressed to:
Rashmi Gopal-Srivastava, Ph.D.
Office of Rare Diseases Research, NCATS
Telephone: 301-402–4336
Email: gopalr@mail.nih.gov

Peer Review Contact(s)

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences
Telephone: 301-435-0814
Email: lambert@mail.nih.gov

Financial/Grants Management Contact(s)

Ms. Ruthann Rand
National Center for Advancing Translational Sciences
Telephone: 301-451-4238
Email: randrudy@mail.nih.gov

Mr. Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
Email: woodwars@mail.nih.gov

William W. Darby
National Eye Institute
Telephone: 301-451-2020
Email: darbyw@nei.nih.gov

Ron Caulder
National Heart, Lung, and Blood Institute
Telephone: 301-435-0166
Email: caulderr@nhlbi.nih.gov

Vandhana Khurana
National Institute of Allergy and Infectious Diseases
Telephone: 301-451-7380
Email: khuranav@niaid.nih.gov

Melinda Nelson
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-435-5278
Email: MN23Z@NIH.GOV

Bryan S. Clark, M. B. A.
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Telephone: 301-435-6971
Email: clarkb1@mail.nih.gov

Mary Daley
National Institute of Dental and Craniofacial Research
Telephone: 301-594-4808
Email: Daleym@mail.nih.gov

Craig E. Bagdon 
National Institute of Diabetes and Digestive and Kidney Diseases
Telephone: 301-594-2115
Email: BagdonC@mail.nih.gov

Tijuanna Decoster
National Institute of Neurological Disorders and Stroke
Telephone:  301-496-9231
Email: td18k@nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.


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