NOT-AR-14-014: Notice of Intent to Publish a Funding Opportunity Announcement for Accelerating Medicines Partnership Rheumatoid Arthritis/Lupus Research Sites (UH2/UH3)

Notice of Intent to Publish a Funding Opportunity Announcement for Accelerating Medicines Partnership Rheumatoid Arthritis/Lupus: Research Sites (UH2/UH3)

Notice Number: NOT-AR-14-014

Key Dates
Release Date: February 21, 2014
Estimated Publication Date of Announcement: March 2014
First Estimated Application Due Date: May 2014
Earliest Estimated Award Date: September 2014
Earliest Estimated Start Date: September 2014

Related Announcements
NOT-AR-14-013

Issued by
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

The National Institutes of Health (NIH), pharmaceutical companies and nonprofit organizations have together created the Accelerating Medicines Partnership (AMP) to develop new models for identifying and validating promising biological targets for new diagnostics and drug development. A major goal is to generate pre-competitive, disease-specific data that will be publicly accessible to the broad biomedical community for further research (http://www.nih.gov/science/amp/).

The partners have designed a project plan to address relevant challenges for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (AMP RA/SLE Program). The goal is to ascertain and define shared and disease-specific biological pathways in order to identify relevant drug targets for the treatment of autoimmune diseases. This program will involve an enhanced systems-level understanding of gene expression and signaling in target tissues from affected end organs (synovium for RA, kidney and skin for lupus) and blood cells. The initial focus of research will be on RA and lupus, with the flexibility to expand in the future to related autoimmune diseases contingent on scientific feasibility and availability of resources.

The NIAMS and NIAID, as participating members of the AMP RA/SLE Program, intend to promote these objectives by publishing two Funding Opportunity Announcements (FOAs) to solicit applications for the development of a Leadership Center and Research Sites. The Leadership Center and the Research Sites awardees will work collaboratively within a network structure to implement the AMP RA/SLE program. The resulting network will be developed by NIH in collaboration with industry partners that will co-fund and actively participate in the scientific direction of the project (http://www.niams.nih.gov/Funding/Funded_Research/AMP_RA_Lupus/default.asp).

This new research network will be established using two interrelated FOAs to support (i) the AMP RA/Lupus Leadership Center, and (ii) AMP RA/Lupus Research Sites, which together will form the AMP RA/Lupus Network. The AMP RA/Lupus Network is defined as the consortium of investigators and institutions funded under both FOAs and will provide the framework for the AMP RA/SLE Program. A diagram of the organizational structure and description of research phases can be found at (http://www.niams.nih.gov/Funding/Funded_Research/AMP_RA_Lupus/default.asp).

The intent of this Notice is to provide potential applicants with lead time to start the process of forming teams, building collaborations, and planning responsive applications.

The FOA is expected to be published in March 2014, with an expected application due date in May 2014. This FOA will utilize the Phase Innovation Awards Cooperative Agreement (UH2/UH3) activity code, with separate funding for the exploratory phase (UH2) and the demonstration phase (UH3), to be submitted in a single application. Details of the planned FOA are provided below. The FOA will be open to all qualified domestic and foreign applicant organizations.

Research Initiative Details

This Notice encourages investigators and teams with expertise and insights in the areas of RA, lupus, tissue analytics, and bioinformatics to consider applying for this new FOA to establish the AMP RA/Lupus Research Sites. The Research Sites will: 1) establish infrastructure, design and implement research strategies to enroll patients with RA or lupus and healthy controls to obtain relevant tissue specimens (Clinical Research Sites); or 2) conduct research in emerging technologies and standardize their application to tissues and cells from patients with RA and/or lupus and healthy controls (Technology Research Sites); or both. Successful applicants will become part of the AMP RA/Lupus Network and work collaboratively with investigators in the AMP RA/Lupus Leadership Center, NIH staff and the AMP RA/SLE Steering Committee.

To be responsive to the upcoming FOA, applications must address all the main requirements summarized below.

Clinical Research Sites Applications:

Applications may be submitted by single sites or by investigator consortia or networks.
Projects must focus on lupus and/or RA, and a statement demonstrating capability to extend the approach to a third related autoimmune disease is encouraged. Applicants who wish to propose work in both RA and lupus should indicate a primary focus in one disease.
Demonstrate capability in recruiting large cohorts and obtaining tissue specimens from patient cohorts and relevant controls. Applications to be considered will need to identify and provide the scientific rationale for the selection of patient cohorts and controls that are most advantageous for phase 0, phase I and phase II studies (see http://www.niams.nih.gov/Funding/Funded_Research/AMP_RA_Lupus/default.asp)
Include plans for patient phenotyping. The projects will include a description, rationale and approach for the clinical, laboratory and other parameters that will be determined for each patient population.
Focus on Tissue Acquisition. Provide plans to obtain and compare results of analyses using tissue samples from different sources (e.g., biopsy, surgical, etc.) and in relation to factors such as disease status (e.g., active disease, end-stage disease). Applications will propose specific plans to collect appropriate and scientifically-justified tissue samples from controls and describe samples on hand from patients and controls if available.

Technology Research Sites Applications:

Focus on one or more cutting-edge experimental techniques. Examples include 1) deep RNA-seq of multiple distinct immune cell subsets from blood and tissue, 2) single cell RNA sequencing of tissue-resident cells from biopsies, 3) evaluation of epigenetic changes including methylation, histone modifications, DNAse hypersensitivity in specific cell subsets of interest, 4) multiparameter cell phenotyping and phospho-flow analysis using mass cytometry approaches (CyTOF), 5) global phosphoproteome analysis of selected cell types, 6) immunoglobulin repertoire analysis by application of single cell RNA-seq from circulating plasmablasts, 7) serum/urine proteomics and metabolomics, and 8) analysis of the microbiome.
Preliminary Data. Suitable technologies or assays to be proposed for development/adaptation must be based on a working prototype (for new technologies) or an existing technology (which will serve as basis for adaptation) demonstrating a general feasibility of the proposed approaches. Data demonstrating applicability to RA and lupus are not a prerequisite for applying. The application will describe plans for standardization and validation. In phase 0 and phase I (UH2), a variety of tissue/cell types, collection methods and analytic techniques can be applied and compared.
Describe approaches to ensure quality of data and consistency of the experimental techniques, data management, statistical plans, and the proposed analyses.

Combined Clinical and Technology Research Sites:

Applications will need to meet all requirements listed above for Clinical Research Sites and for Technology Research Sites; additionally, preliminary data demonstrating the feasibility of obtaining relevant samples and the technologies proposed must be included.
These sites are also appropriate when there is a requirement to conduct tissue analytics experiments at a site nearby or within the facility of tissue acquisition.

All applications should:

Describe Research Phase 0 and Phase I activities (conducted during the UH2 period) to establish the feasibility of Phase II projects (conducted during the UH3 period) (see http://www.niams.nih.gov/Funding/Funded_Research/AMP_RA_Lupus/default.asp).
Include a Concept for a Pilot and Feasibility Project that may either (i) require additional resources to be provided by the AMP RA/Lupus Network (e.g., systems analysis), (ii) be at a very early stage of development, or (iii) represent an alternative to the approach proposed for the main activities of the UH2 funding period.
Propose Phase II studies (Phase II/UH3). All the projects must include plans, including budget, for an appropriate clinical study in a defined relevant cohort that will be conducted collaboratively with AMP RA/Lupus Network investigators. Focus of the UH3 scaled up phase will be on larger (50-200 patients), well defined informative cohorts (e.g., patients starting anti-TNF therapy subject to a repeat biopsy, early RA cohorts, new onset lupus nephritis, etc.). Patient stratification is expected for comparison within a disease (e.g., RA: treatment responder vs. non-responder, early vs. established RA, comparison among disease-modifying anti-rheumatic drugs (DMARD) treated groups; lupus: before treatment vs. after treatment, comparison among types of kidney disease, etc.). Technology Research Sites will propose projects to study the proposed tissue analytic/technology in one or more of the large cohorts obtained by the Network.
Describe the availability of a Central IRB service at the institution and/or the willingness to use a commercial or Central IRB for these studies.
Propose milestones to measure progress and go/no-go criteria to transition between project phases.

This FOA will utilize cooperative agreements with the UH2/UH3 activity code with separate funding for the exploratory phase (UH2) and the demonstration phase (UH3), to be submitted in a single application. Initial milestone-driven, cooperative agreement awards of up to two years will be granted for an exploratory (UH2) phase to establish the infrastructure, plan and demonstrate technical functionality and tissue acquisition capabilities in RA and lupus (Phase 0) and initiate the systems-level analysis of disease-specific pathways to identify differences between disease and control (Phase I). The most promising, milestone-meeting projects will transition to the Phase II (UH3) period of the award (for up to three additional years). The primary focus of the UH3 phase is to scale up the analysis to gain an understanding of key pathways that drive disease progression, severity or response to therapies in RA and/or lupus with the goal of delineating pathways that differ between subsets of patients within each disease.

APPLICATIONS ARE NOT BEING SOLICITED AT THIS TIME.

Inquiries

Please direct all inquiries to:

Su-Yau Mao, Ph.D.
Yan Wang, M.D., Ph.D.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-594-5032
Email: [email protected]
Website: http://www.niams.nih.gov/Funding/Funded_Research/AMP_RA_Lupus/default.asp