Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)
 

Components of Participating Organizations

National Institute of Neurological Disorders and Stroke (NINDS)
Office of Rare Diseases (ORD)

Funding Opportunity Title

Limited Competition for the Continuation of Rare Diseases Clinical Research Consortia in the Rare Diseases Clinical Research Network (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR-11-187

Companion FOA

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

 93.853 

FOA Purpose

The purpose of this limited competition Funding Opportunity Announcement (FOA) is to provide an opportunity for the NINDS American Recovery and Reinvestment Act (ARRA)-funded consortia to compete for another three years of participation in the Rare Diseases Clinical Research Network (RDCRN).  The RDCRN is a collaborative and coordinated network of Clinical Research Consortia comprised of investigators and patient support groups committed to investigation of rare diseases working in partnership with the Data Management Coordinating Center to enhance communication and sharing of resources in a multidisciplinary approach. The RDCRN is focused on 1) the collection of clinical information to better define disease natural history and to develop biomarkers as well as new approaches to diagnosis, prevention, and treatment of rare diseases, and 2) training of new clinical investigators in rare diseases research. 

Key Dates
Posted Date

March 31, 2011

Letter of Intent Due Date

May 15, 2011

Application Due Date(s)

June 15, 2011  

AIDS Application Due Date(s)

Not applicable

Scientific Merit Review

August, 2011

Advisory Council Review

August, 2011

Earliest Start Date(s)

September, 2011

Expiration Date

June 16, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

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

Research Objectives

The Office of Rare Diseases Research (ORDR) and the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) invite new and renewal applications (U54) for ARRA-funded Rare Diseases Clinical Research Consortia, which are currently part of the Rare Diseases Clinical Research Network (RDCRN). The purpose of this limited competition FOA is to allow the three consortia an opportunity to compete to continue their participation in the RDCRN, which supports 1) collaborative clinical research in rare diseases, including longitudinal studies of individuals with rare diseases, clinical studies, and/or phase I, II and II/III  trials; 2) training of clinical investigators in rare diseases research; 3) pilot and demonstration projects; 4) distributed clinical data management that incorporates novel approaches and technologies for data management, data mining, and data sharing across rare diseases, data types, and platforms; and 5) access to information related to rare diseases for basic and clinical researchers, academic and practicing physicians, patients, and the lay public.

Each Rare Diseases Consortium (RDC) in the network performs collaborative clinical research in rare diseases, trains new investigators in rare diseases research, and provides content for an internet resource site on rare diseases.  Each RDC consists of a group of clinical investigators, institutions, and relevant organizations, including patient support organizations, focused on a subset of rare diseases.  Use of the resources available through a Clinical and Translational Science Award (CTSA) should be incorporated into each RDC if available at the applicants’ institutions.  The focus of each RDC can be on particular disorders, e.g., muscle channelopathies, spinocerebellar ataxias and mitochondrial diseases.  Since rare diseases are diverse, the nature of clinical research that is feasible varies.  The application must describe the group of rare diseases to be included, the rationale for this grouping, and the relevant expertise available in the proposed RDC.  The individual RDCs will be responsible for the design and implementation of their clinical studies.  The Data Management and Coordinating Center (DMCC) will provide the data management and analysis infrastructure and support necessary for the RDCs to function optimally.  The DMCC will work with each RDC to integrate protocols, forms, and research tools into the Network.

Background

Approximately 25 million people in the United States are affected by an estimated 6,000 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.

The Rare Disease Act of 2002 (Public Law 107-280) directed ORD (now Office of Rare Diseases Research, ORDR), 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.

Despite the advances and opportunities for research in rare diseases, difficulties remain in clinical diagnosis and management.  Diagnoses may be straightforward with well-described phenotypes or difficult with poorly defined criteria. There are insufficient characterizations of the courses of many rare diseases.  Treatment can be equally challenging with many questions concerning appropriate and best clinical management.  Rare diseases pose unique challenges to identification and coordination of resources and expertise for small populations dispersed over wide geographic areas.  Rare diseases research 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 resolve controversies concerning current treatment strategies.  Well described patient populations will be important to bring promising therapies to the clinic.

Organization of the Rare Diseases Clinical Research Network

The Rare Diseases Clinical Research Network (RDCRN) is a cooperative network composed of several Rare Diseases Consortia (RDC) and a single DMCC to facilitate clinical research in rare diseases carried out by the RDCs.  A Steering Committee, composed at a minimum of the Principal Investigator (Director) of each RDC, the Principal Investigator (Director) of the DMCC, and the Office of Rare Diseases Research Program Coordinator will evaluate existing procedures for the RDCRN and develop new procedures as needed, as outlined in section "Steering Committee."   This funding opportunity announcement is open to existing RDCs supported by NINDS using ARRA funds.

The RDC will require cooperation among the ORDR Program Coordinator, the participating NINDS Project Scientists, Directors of the RDC and their collaborators, and the Director of the DMCC to maximize effectiveness.  A number of issues need to be addressed in the cooperative agreement applications including those highlighted in section VI.2 Cooperative Agreement Terms and Conditions.

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, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations, and the submission of a sufficient number of meritorious applications.

Award Budget

The maximum budget to be requested per application is $1,250,000 total costs.

Award Project Period

The maximum period is 3 years.

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

Only currently active NINDS Rare Diseases Consortia are eligible to apply.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

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/Principal Investigator (PD/PI) 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.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.    

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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.     

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 PHS398 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:

Descriptive title of proposed research
Name, address, and telephone number of the PD(s)/PI(s)
Names of other key personnel
Participating institutions
Number and title of this funding opportunity

The letter of intent should be sent to:

Randall R. Stewart, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Neuroscience Center, Room 2135
6001 Executive Blvd.
Bethesda, MD 20892-9523
(For courier delivery:  Rockville, MD 20852)
Telephone: 301-496-1917
E-mail: stewartr@ninds.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:

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

Page Limitations

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Applications should include the following information in the relevant subsections:

Overall Research Plan (limited to 6 pages)

Describe the group of rare diseases to be included, the rationale for this grouping, and the relevant expertise available in the consortium. Each RDC should include a group of at least three diseases.  State the clinical research objectives of the proposed RDC 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.

Each RDC must document access to an adequate 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 RDC must describe how patients will be identified and recruited for study.  The development and maintenance of patient registries may be appropriate and necessary core activities of an RDC in some cases.

Clinical Research Projects for Observational/Longitudinal Studies and/or Clinical Trials (Research Strategy is limited to 12 pages per project and at least two projects are required, one of which must be a longitudinal study)

These projects should be numbered consecutively with use of only integers (i.e., Project 1, Project 2, Project 3, Project 4, etc.); projects 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. 

Describe the research strategy in enough detail so the scientific merit can be judged on the basis of the written application.   Begin each project with a short section that clearly states how that project contributes to the objectives of the RDC as a whole. The budget for each research project should reflect the instructions for Form PHS 398. A detailed budget is required for the first year; budget estimates are required for all subsequent years of support. Explicit and detailed budget justifications must be included for all years. Budget pages must be labeled so that they can be readily associated with the particular projects to which they apply. The project leader should devote at least 1.8 calendar months to the research. The section for human subjects should be labeled according to the project number.

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.  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 to design efficient clinical 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 trial.

Depending on the state of knowledge of the particular diseases, the projects could include strategies for assessing current therapeutic interventions, Phase I, II or Phase II/III clinical trials.  Each application must include a description and rationale for planned clinical trials or longitudinal studies.  Strategies for recruitment, retention, assessment, and analysis must be included.  Evidence of the ability to conduct clinical studies as well as demonstration of successfully recruiting and retaining study participants should be provided.

For all applications: applicants should outline the scientific accomplishments and discuss the potential impact on the rare disease for each clinical research project (study) in progress or completed in the last grant period. Publications should be restricted to those that cite support from the RDC grant. If a clinical trial(s) or longitudinal/observational studies have been conducted as 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. 

Pilot/Demonstration Projects (Research Strategy limited to 12 pages per project)

Include Pilot Project title with Director(s) followed by the project plan

Every RDC application must allocate a significant effort to support pilot/demonstration projects for short term clinical studies that take maximum advantage of new clinical research opportunities in rare diseases.  At least one pilot project is required. Such projects may be collaborative among scientists within one or more RDC, or with scientists outside the RDC environment. The applicant should propose funding pilot projects that generate feasibility data and have the most promising clinical research potential. These funds are intended to remain flexible and to support studies of a limited duration, of 2 years or less. New applicants must include a description of eligible projects.  Pilot projects can 1) include development of novel laboratory assays and clinical instruments and 2) Phase I and Phase II clinical trials. Later phase trials (Phase II/III, Phase III) are not ruled out but may not be feasible for all rare diseases.  At least one pilot/demonstration project must be included in the application.

A Pilot/Demonstration Project, as a required component of an RDC, must be maintained throughout the entire term of the grant. The NIH will monitor the activities of RDC sponsored Pilot/ Demonstration Projects during non-competitive years to assure that there is adherence to the clinical research intention of the RDC program during the term of the award. Pilot/Demonstration Project funds should be utilized for research activities and cannot be used for the purchase of any large equipment.

For all applications: describe any pilot or demonstration project funded during the last grant period and the outcome of the project relative to the RDC objectives, ongoing pilot and demonstration projects, and short descriptions of other potentially eligible projects.  If a clinical trial(s) has been conducted as a part of a pilot 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.

Training (career development) Strategy (limited to 6 pages)

Each application must include a plan for training of new investigator(s) for clinical research in rare diseases within the RDC.  An RDC 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.

The RDC 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 (who will be independent investigators within the next year), junior faculty, or established investigators who wish to develop or refocus their careers on clinical research in rare diseases. RDC Training Programs are not intended for predoctoral candidates or junior level post-doctoral fellows.

A minimum of $50,000 direct costs per year from the RDC budget must be dedicated to this program and be utilized to support the salary and research costs of candidates with outstanding potential. 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. The description of this program should include the policies, criteria, and processes for selecting candidates, including special efforts to recruit qualified women and minorities. 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. New applicants should provide a list and short descriptions of potential candidates, as well as the names and research activities of mentors. Describe the plan to seek out and include qualified women and minorities for participation in the proposed program

A Training component, as a required element of a RDC, must be maintained throughout the entire term of the grant. 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. At least two trainees should be supported by this program.

For all applications: denote individuals supported during the last grant period, their scientific accomplishments while supported by the RDC, and how RDC support has advanced their clinical research careers in rare diseases. Provide the number of women and minorities trained and the number of calendar months devoted to clinical research.

Website Content Plan (include in Facilities & Other Resources section)

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 links or materials for lay public, patients, basic and clinical researchers, and clinicians. 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 RDC through the Steering Committee. The RDC 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

RDC Administrative Unit Plan (include in Facilities & Other Resources section)

The RDC Administrative Unit is responsible for the overall administration of the RDC. Describe by diagram if appropriate, the chain of responsibility for decision-making and administration. Include to whom the RDC 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 RDC Administrative Unit must include a clinical investigator who ensures a mutually supportive interaction between scientists conducting clinical research and those performing clinical investigation. The qualifications of the clinical investigator and the plan to promote clinical research should be described.

The RDC Director (PD/PI of the cooperative agreement) 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 an RDC project (if leading a clinical research project). RDC Administrative Unit support personnel may be budgeted in 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 RDC Director is expected to send two RDC participants to biannual meetings in the Washington, D.C. area, and should budget for these meetings.

Describe the biostatistical support for the RDC in this section. The biostatistician will provide statistical support for protocol development and assist in study designs. The biostatistician in collaboration with DMCC will also assist in the collection of epidemiologic information, data analysis, and quality assurance for database and statistical analyses of pooled data for the RDC. The description of the administrative unit of an RDC should explain how the activities and contribution of the collaborating investigators and institutions will be coordinated.

An individual should be identified on the application who will be responsible for assisting the RDC 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 RDC Director.  This individual may be from a different Institution.

Collaboration with Patient Advocacy Group Plan (include in Facilities & Other Resources section)

Include a plan to fully incorporate the patient support organizations’ 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 organizations activities should be appropriate for the level of advocacy capabilities.

Collaboration with Data Management Coordinating Center (DMCC) Plan

In the Resource Sharing Plan section, describe the level of collaboration with the DMCC.  At a minimum, an RDC should transfer data to the DMCC monthly and should use the electronic adverse event reporting system developed by the DMCC.

Leveraging Local Research Resources Plan

The applicant should describe in the Facilities and Other Resources section how local clinical research resources such as equipment, space and research staff will relate to the RDC, and, if applicable, how the RDC will integrate CTSA resources.

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 PHS398 Application Guide, with the following modifications:

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 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 PHS398 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, NIH. Applications that are incomplete will not be reviewed.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in subsection 2.A. of Section VI.  "Award Administration Information".

Follow the instructions in PHS 398 application kit.  Additional instructions and recommended formats for providing the information requested for this FOA are described below. 

PHS 398 is required for all U54 applications. Each budget unit per project should be written in the style and within the page limitation described in the PHS 398 instruction kit. To assist in developing RDC grant applications and aid in the review of these applications, the applicant should assemble the component units following the format described below.

I. Abstract Page: Description, Performance Sites, Key Personnel (PHS 398 Form, page 2)

Describe the overall proposed clinical research program of the RDC indicating the goals and objectives of the individual clinical research projects.

II. Table of Contents (PHS 398 Form, page 3)

Discard this page from Form PHS 398 and create a Table of Contents appropriate for the RDC grant 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.

III. Budgets and Supporting Form (PHS 398 Form, pages 4 and 5)

Justify and document all costs for current and future years throughout at the level of the individual component budgets.

The overall Consortium budget, "Summary RDC Budget," is to be presented first using PHS Form 398 page 4 entitled "Detailed Budget for First 12-Month Period” 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.

Page 5 of PHS Form 398, "Budget Estimates for All Years of Support Requested Direct Costs Only", should then follow, 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.

Both first 12 month and 3 year individual budgets should be included in the sections for each project. Details and justifications for all budget items must be part of the individual budgets. Read carefully pages 10 - 14 of the Instructions for PHS 398 on how to prepare budget pages and justifications.

Note that this grant mechanism is not intended for the acquisition of costly equipment which should be funded through other sources. Under unusual circumstances, where costly items of equipment are requested, the application must document available equipment within the institution and provide clear justification.

IV. Biographical Sketches

Biographical sketches are required for all professional level personnel who are listed with a measurable effort (including consultants) in the RDC application. The forms found in Form PHS 398 should be used. After the budget pages, put the biographical sketches for all PD/PIs first, followed by the other individual biographical sketches in alphabetical order. These pages should not be duplicated in other components, projects, etc. 

The personal statement section should be used to describe the qualifications, expertise and role of the RDC leadership (PD/PIs. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

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.

Overall Impact - Overall

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the consortium 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 consortium 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 consortium that by its nature is not innovative may be essential to advance a field.

Significance

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

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the consortium? 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?  

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 consortium? 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 consortium involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?   

Environment

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

Additional Review Criteria - Overall

As applicable for the consortium proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Training (Career Development) Component

 

Pilot/Demonstration Projects Program

RDC Administrative Unit:

Overall Clinical Research Program Organization and Capability

·       Leadership:  

·       Rare Diseases Patient Population:  

·       Institutional Commitment:

·       Multidisciplinary Team Involving Patient Support Organizations Collaborations:

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed consortium 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 Human Subjects Protection and Inclusion Guidelines.

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 Renewal applications, reviewers will consider the following:

Revisions

Not applicable.

Additional Review Considerations - Overall

As applicable for the consortium 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/priority score.

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.

Scored Review Criteria for Clinical Research Projects

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for each clinical research project 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 project proposed).

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, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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 tactics? Is the proposed research plan appropriate for the state of knowledge, current capabilities and resources for the rare diseases or group of diseases? Are the questions being asked for the rare disease(s) and objectives outlined most likely to advance knowledge in rare disease(s)? Is the clinical design appropriate to address the objectives of the research plan? 

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; 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 principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project (if applicable)? 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 support organizations? Will the proposed administrative plan, infrastructure, and resources provide appropriate support for the clinical research to be undertaken by the RDC?

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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 . 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:

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 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, CCR 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 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:

            RDC Director and the DMCC Director

            Collaboration and Coordination

            Steering Committee Membership and Meeting Attendance

            Data Coordination, Management and Sharing

            Publication and Presentation of Study Findings

            Federally Mandated Regulatory Requirements

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

            Steering Committee Membership and Meeting Attendance

            Monitoring Performance

            Publication and Presentation of Clinical Studies Findings

            Program Stewardship

Areas of Joint Responsibility include:

            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 Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 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) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Scientific/Research Contact(s)

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

Peer Review Contact(s)

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: (301) 496-9223
E-mail: nindsreview.nih.gov@mail.nih.gov

Financial/Grants Management Contact(s)

Tijuanna E. DeCoster, MPA
National Institute of Neurological Disorders and Stroke  (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.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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