Notice of Intent to Publish a Funding Opportunity Announcement for Generate an Intergenerational Precision Medicine Resource for the Study of Factor VIII Immunogenicity in Severe Hemophilia A: Biospecimen and Data Resource Center (U24)

Notice Number: NOT-HL-19-727

Key Dates

Release Date: November 19, 2019
Estimated Publication Date of Funding Opportunity Announcement: March 02, 2020
First Estimated Application Due Date: June 25, 2020
Earliest Estimated Award Date: January 05, 2021
Earliest Estimated Start Date: January 05, 2021

Related Announcements

NOT-HL-19-726

Issued by
National Heart, Lung, and Blood Institute (NHLBI)

Purpose

The Division of Blood Diseases and Resources within the National Heart, Lung, and Blood Institute (NHLBI) intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for the following: Generate an Intergenerational Precision Medicine Resource for the Study of Factor VIII Immunogenicity in Severe Hemophilia A: Biospecimen and Data Resource Center, (U24 Resource-Related Research Projects - Cooperative Agreement).

This Notice of Intent to Publish (NOITP) is being provided to allow potential eligible applicants sufficient time to develop competitive and responsive milestone-driven scientific projects and thus prepare applicants for the timely submission of an application.

The anticipated FOA will utilize the U24 Resource-Related Research Projects - Cooperative Agreement activity code to issue a single award for up to seven years for the Biospecimen and Data Resource Center that will provide data management, laboratory, and biospecimen support necessary to establish the anticipated FOA, “An Intergenerational Precision Medicine Resource for the Study of Factor VIII Immunogenicity in Severe Hemophilia A”. The role of the Biospecimen and Data Resource Center is to provide overall project coordination, administration, data and biospecimen management, biostatistics/data analytics support, as well as laboratory (including multi-omics) and biorepository expertise for development of this unique resource. The companion award for the Clinical Coordinating Center (UG3/UH3)(see NOT-19-HL-726) is anticipated to be made in parallel with the Biospecimen and Data Resource Center to allow for the establishment of this unique biospecimen resource. The Clinical Coordinating Center FOA will provide investigators with the opportunity to propose the design of a unique Intergenerational Precision Medicine Resource, derived from a de novo antenatal/ neonatal /pediatric cohort with severe hemophilia A and annotated with robust intergenerational clinical and demographic data, for the purpose of enabling future mechanistic and translational studies of factor VIII immunogenicity and tolerance.

A key characteristic of the Biospecimen and Data Resource Center application will be completion of core milestones. A core milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be performance-based to achieve completion of the Intergenerational Precision Medicine Resource on time and on budget and must be established to align with the bi-phasic mechanism of the Clinical Coordinating Center award. Milestones must be established for both the first three years (coinciding with the UG3 phase of the Clinical Coordinating Center award) and subsequent four years (coinciding with the UH3 phase of the Clinical Coordinating Center award) of the project. Satisfactory completion of the milestones for the first three years will be assessed administratively by NHLBI to determine eligibility to continue the award. Due to the collaborative and parallel nature of these FOAs, NHLBI will enter into negotiation with the Biospecimen and Data Resource Center to achieve early phase-out of the award if Clinical Coordinating Center and/or Biospecimen and Data Resource Center progress is deemed inadequate upon NHLBI administrative review.

Details of the planned FOA are provided below.

Research Initiative Details

The planned Funding Opportunity Announcement (FOA) will support applications for a Biospecimen and Data Resource Center that will support the development of an Intergenerational Precision Medicine Resource for the study of factor VIII immunogenicity in hemophilia A by providing expertise in relevant laboratory (including multi-omics) methodology, biorepository science, data science, bioinformatics, complex statistical (including trans-omics) analysis, project management, and administrative support. The Biospecimen and Data Resource Center applications will be expected to demonstrate the required scientific and laboratory expertise and response capability to lead and coordinate rapid collection, quality control (QC), as well as implementation of scientifically-prioritized tissue and blood biospecimen acquisition protocols and storage and distribution procedures. Responsive applications will emphasize on-site and/or collaborative scientific and laboratory expertise in multi-omics, immunology, microbiology and coagulation science; expertise in biorepository science (collection, processing, shipping, storage of all types of liquid and tissue biospecimens); expertise in the management and microtechnological assay of small volume specimens derived from neonates and children; and the capability to dispatch and oversee expert specimen collection as well as timely processing in the field.

The Biospecimen and Data Resource Center will also provide centralized, facilitated approaches to complex data management and integration, QC procedures, data integrity and security, and the necessary statistical support to ensure the conduct of well-designed precision medicine studies and timely large data (including trans-omics) analysis. The data collection overseen by the Biospecimen and Data Resource Center will be expected to adhere to FAIR (Findable, Accessible, Interoperable, Reusable) principles to ensure transparency, reproducibility, and reusability (Wilkinson MD, et al., Scientific Data 2016), to use standard protocols supported through the NIH PhenX toolkit (https://www.phenxtoolkit.org), and to incorporate appropriate well-validated patient-reported outcome (PRO) measures supported through, or comparable to those supported through the NIH Toolbox (http://www.healthmeasures.net/explore-measurement-systems/nih-toolbox).

Responsive applications must therefore demonstrate the requisite data science, bioinformatics, analytic (including integrative omics analytics) and epidemiological expertise, as well as experience in coordinating the conduct of multiple multicenter studies in maternal/fetal, neonatal and/or pediatric populations. Responsive applications must also demonstrate relevant biostatistical expertise and experience in the design of intergenerational studies, and experience in the integrative analyses of large datasets that include multi-omics data; project management expertise in coordinating and managing large multicenter studies in the target populations; laboratory and biorepository science expertise; the requisite IT expertise and support for complex big data and biospecimen tracking and management; and the capacity for development and maintenance of a study coordination web site.

The Biospecimen and Data Resource Center will be supported in parallel with a companion Clinical Coordinating Center (see NOT-19-HL-726 for specific goals to be achieved through the establishment of this Intergenerational Precision Medicine Resource).

Applicants will be expected to propose milestone-driven activities that support, in collaboration with the Clinical Coordinating Center:

  1. The initial three-year phase of the project including, but not limited to:
    1. The scientific and operational Intergenerational Severe Hemophilia A Precision Medicine Resource protocol development;
    2. The development and implementation of the Resource’s Operating Procedures, data and biospecimen management and tracking systems, and a study coordination web site;
    3. The conduct of laboratory pilot studies;
    4. The development of manual of procedures and didactic preparation of sites to implement feasible scientific and operational procedures for data collection and quality control;
    5. The development of manuals of procedures and didactic preparation materials to implement feasible scientific and operational procedures for biospecimen collection, processing, testing, shipping, and storage;
    6. Development and implementation all procedures to provide data, laboratory, and biospecimen management support to clinical sites that will be enrolling and following participants during this three-year phase.
  1. The second four-year phase of the project to include, but not limited to:
    1. Full implementation of all procedures to provide data, laboratory and biospecimen management support to clinical sites that will be enrolling and following participants;
    2. Complete collection of the protocol data and biospecimens for the final build of a sharable fully annotated biorepository;
    3. Data analysis and dissemination of findings;
    4. Submission of the public-use data and biospecimens to the NIH repository resources.

Funding Information

Estimated Total Funding $1,343,000 total costs
Expected Number of Awards 1
Estimated Award Ceiling $872,000 direct costs
Primary CFDA Numbers 93.839

Anticipated Eligible Organizations

Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Small Business
For-Profit Organization (Other than Small Business)
State Government
Indian/Native American Tribal Government (Federally Recognized)
County governments
Independent school districts
Public housing authorities/Indian housing authorities
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Regional Organization

Applications are not being solicited at this time. 

Inquiries

Please direct all inquiries to:

Iman K. Martin, PhD, MPH, MS
National Heart, Lung, and Blood Institute (NHLBI)
301-435-0065
FactorVIII@DBDR.NIH.NHLBI.gov