Key Dates

NOT-AR-21-014 - Notice of Intent to Publish a Funding Opportunity Announcement for Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases: Technology and Analytic Cores (TACs) and Research Management Unit (RMU) (UC2) (Clinical Trials Not Allowed)

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

National Institute of Allergy and Infectious Diseases (NIAID)

National Institute of Dental and Craniofacial Research (NIDCR)

All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Research on Women's Health (ORWH)

This Notice is to inform the research community that the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Allergy and Infectious Disease (NIAID), National Institute of Dental and Craniofacial Research (NIDCR), and Office of Research on Women's Health (ORWH) intend to issue a Funding Opportunity Announcement (FOA) for the Accelerating Medicines Partnership Autoimmune and Immune-Mediated Diseases: Disease Teams for Rheumatoid Arthritis, Lupus, Psoriatic Spectrum Diseases and Sjogren’s Syndrome (UC2 Clinical Trial Optional). This FOA will use the UC2 (High Impact Research and Research Infrastructure Cooperative Agreement Programs) grant mechanism.

This Notice of Intent to Publish (NOITP) is being provided to allow potential eligible applicants sufficient time to assemble teams and develop competitive and responsive projects.

The FOA is expected to be published in March 2021. Details of the planned FOA are provided below.

The purpose of this Funding Opportunity Announcement (FOA) is to invite UC2 applications to continue and expand the clinical infrastructure of the AMP RA/SLE Program as part of the planned AMP Autoimmune and Immune Mediated Diseases (AMP AIM) Program.

The NIH, pharmaceutical companies and nonprofit organizations 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. Over the last 6 years, the Accelerating Medicines Partnership rheumatoid arthritis and systemic lupus erythematosus (AMP RA/SLE) program has brought together public and private communities to make unprecedented progress in understanding the cell populations, pathways and potential novel drug targets that drive these diseases.

AMP AIM will extend the concept of disease deconstruction that was established by the AMP RA/SLE Program to psoriatic spectrum diseases (PSD) and Sjogren’s syndrome (SS). The AMP AIM Program will also pioneer the concept of disease reconstruction by bringing in novel multi-modal analytics to elucidate how innate and adaptive cells of the immune system and tissue-resident cells network with each other to cause inflammation, abnormal function, tissue injury, and clinical disease. The goal of the program is to develop a comprehensive and integrated understanding of disease pathways to identify targets for intervention.

The AMP AIM Program will be carried out by a research infrastructure to be established using two interrelated FOAs that will support research teams which will form the AMP AIM Network. The Network is defined as the consortium of investigators and institutions funded under both FOAs. A diagram of the organizational structure can be found on the NIAMS website.

Teams supported by this FOA will work together and with the Technology and Analytics Cores (TACs) (as described in the companion notice NOT-AR-21-014) to analyze tissue and specimens from patients with RA, Lupus, PSD, or SS. The Disease Teams and Cores will probe and resolve the structural, functional and molecular complexities of tissue at the single-cell level. Following a short planning and harmonization period, teams will conduct initial, pilot, exploratory projects with existing tissue samples to demonstrate the feasibility of scaling up new interrogation methods. Large-scale analytic pipelines will be implemented once samples become available. An NIH-designated Knowledge Portal (KP) will provide the infrastructure, resources and management for sharing data, network models, and analytical tools, as well as the data integration activities for the AMP AIM Program. This FOA is intended to support only human studies; applications that include animal or model systems are not responsive.

The AMP AIM Network will be made up of four distinct, highly interactive Research Components with complementary roles as follows:

1. Disease Teams (DTs). Each DT will lead the development of the research agenda and research priorities for one disease (RA, Lupus, PSD, or SS). The teams will identify critical opportunities and, select, recruit and deep phenotype the most informative patient populations to implement disease de- and reconstruction strategies of the AMP AIM program. They will establish cross-sectional and longitudinal cohorts and collect biopsy tissue and biosamples for research projects.

2. Technology and Analytics Cores (TACs). TACs will test, optimize and apply innovative technologies to interrogate and analyze human biopsy tissue and biosamples (e.g. single cell metabolomics and lipidomics). The TACs include the specialized Tissue Repository and Systems Biology Cores. All TACs will be aligned to work collaboratively to support Network-wide activities and priorities.

3. Research Management Unit (RMU). The RMU will provide centralized management and operational support to the network including providing and/or overseeing clinical monitoring for the entire AMP AIM program.

4. Knowledge Portal (KP). The KP will provide an interface for storage, analysis aggregation and visualization of all data generated by the DTs and TACs.

It is anticipated that the AMP AIM Program research goals and objectives will be fulfilled through a series of prioritized projects to be implemented collaboratively by the Network following a short planning period. Activities may include, but not limited to:

Planning:

• DTs and TACs collaboratively establish disease research priorities and analytic pipelines.
• Collaboratively define shared priorities across diseases.
• Design analytic pipelines.
• Establish common, harmonized clinical protocols and studies.
• Obtain regulatory approvals.

Pilot:

• Enroll a small number of patients.
• Assess quality of phenotype data and biopsy protocols at each site.
• Optimize and validate tissue processing and interrogation methods.
• Optimize next generation assays.
• Conduct small scale proof of concept studies to determine if clinical and analytic pipelines are robust.
• Refine analytic pipeline design.

Scale-Up Pipelines:

• Implement analytic pipelines in large cohorts.
• Periodically update and release data and tools to facilitate analysis.
• Develop meta-analysis plans and strategies, develop and deploy tools that researchers can use to interrogate the data, promote the identification of potential druggable targets based on new omics type data.
• Make data available via open or controlled access depending on the data type and data source and as determined by the informed consent documents for each study guided by the designated IRB.

Pilot and Scale-Up pipeline projects will be conducted collaboratively.

NIH expects that studies proposed in the applications will be a starting point for discussions regarding the research to be undertaken to achieve the AMP AIM program objectives. It is unlikely that any study proposed in the application will be undertaken exactly as planned, or at an individual site.

FOA Considerations

The FOA is not intended to support hypothesis-driven research but will support discovery.

Each application submitted to this anticipated FOA will be required to address only one disease. Applicants may also submit applications for TACs and RMU under the anticipated companion FOA.

Disease Teams

DTs will lead the disease research efforts. Each DT will define the most significant opportunities based on next-generation tissue interrogation technologies within the context of AMP AIM disease de- and re-construction. They will identify key questions, the most informative patient populations, and work with the TACs to prioritize disease-specific strategies to inform data collection, data analysis and contribute biologic and clinical insights and analysis to interpret findings that emerge from analysis of molecular data.

Key activities include:

• Define the criteria for patients to be recruited, the clinical parameters to be monitored, design the phenotyping approach and analyze and integrate disease specific clinical data.
• Work collaboratively with other DTs and TACs to develop disease specific and shared priorities analytic pipelines and projects.
• Work collaboratively with other Disease and Core Teams to develop standardized, harmonized common data elements and synergies to optimize tissue processing and analytic pipelines.
• Identify patient populations and biosamples from existing, available cohorts and/or registries.
• Recruit, enroll, and phenotype relevant patient populations.
• Obtain all clinical, and other patient data and specimens including biopsy tissue for research purposes.

Each application should be focused on one disease RA, lupus, psoriatic spectrum diseases (PSD), or Sjogren’s syndrome. Applicants will be expected to self-organize into multidisciplinary teams including disease experts (e.g., rheumatologists, nephrologists, dermatologists, dentists), imaging specialists, pathologists, radiologists, clinical nurses and coordinators, statisticians, and outcomes data analysis experts.

Applicant teams should have documented experience and capacity with patient recruitment and safely obtaining biopsies such as kidney/skin/synovial/salivary gland for clinical and/or research purposes. The primary objective of early planning period will be to demonstrate that the site can recruit participants and obtain high-quality research biopsies, while ensuring safety, minimizing risk and conforming to the highest ethical, research and clinical standards followed by continued recruitment into successively larger cohort studies.

As part of the AMP AIM Network, the DTs will work collaboratively with the TACs and the RMU to process, evaluate and visualize data. All data will be submitted to the KP for analysis by the AMP investigators, and as appropriate, the broader scientific community.

Applications are not being solicited at this time.

Please direct all inquiries to:

[email protected]