Notice Number: NOT-HL-18-652
Key Dates
Release Date: September 05, 2018
Release Date: November 12, 2018
None
Issued by
National Heart, Lung, and Blood Institute (NHLBI)
Purpose
This RFI solicits perspectives and comments from the community on scientific opportunities, critical needs, strategies, and infrastructure that would be conducive to the establishment of a US-based national ante-, peri-, and post-natal resource, to foster research into the pathophysiology underlying alloantibody formation and to improve treatment of patients with the severe Hemophilia A phenotype [Factor VIII (FVIII) activity level of <1% of normal].
Background
Hemophilia is a rare genetic disorder that predisposes an affected individual to the potential for increased spontaneous or post-traumatic hemorrhage. Approximately 15,000 individuals are affected by Hemophilia A, and the current standard of care therapy requires lifelong intravenous infusion of FVIII concentrates derived from recombinant biotechnology or human plasma.
The major complication of FVIII replacement is the development of neutralizing alloantibodies (inhibitors) which can eventually preclude FVIII administration, and render the treatment of bleeding episodes complex and difficult. While some predictors of immunogenicity are known, more research is warranted to fully elucidate the determinants of alloantibody formation.
Advancing our understanding of alloimmunization to optimize treatment strategies for individuals with Hemophilia A will rely heavily on establishing a sharable resource of relevant biospecimens and robust matching contextual and clinical phenotypic data. Scientific priorities for establishment of this resource would include elucidation of the mechanisms of immunogenicity and tolerance to FVIII exposure in severe Hemophilia A patients, as well as the development of prediction tools to 1) identify severe Hemophilia A patients who are at risk for developing inhibitors; 2) mitigate modifiable risk factors; and 3) inform novel inhibitor prevention and treatment strategies.
Information Requested
NHLBI seeks comments on any, or all of the following topics but not limited to:
- Relevant study populations other than the maternal/fetal unit
- Strategies, including those based in electronic health record (EHR) systems, which could be leveraged to identify women who carry a severe Hemophilia A gene mutation and who are either pregnant or considering pregnancy
- Challenges to recruitment, enrollment, and follow-up of pregnant carrier women and their neonate(s) diagnosed with Hemophilia A
- Hemophilia community outreach, engagement and communication strategies and opportunities
- Approaches for focused outreach to underrepresented groups, including ethnic minorities
- Bioethical considerations in subject recruitment, study design and data/biospecimen sharing
- Clinical, socio-contextual, demographic, and patient-reported outcomes data of interest
- Existing sources for clinical, socio-contextual, demographic, and patient-reported outcomes data of interest
- Infrastructure requirements for the collection, verification, standardization, storage, sharing and analysis of data of interest, as well as current infrastructure availability
- The types of maternal, placental, umbilical cord, neonatal, and infancy/early childhood biospecimens most relevant to the evaluation of the pathophysiology underlying inhibitor development and the establishment of a national research resource
- The timing and frequency of sample collection, and sampling strategies that would address the unique challenges of specimen procurement in the neonate and child, and which would be most useful in a longitudinal prospective cohort
- Types of currently available assays, models and associated functional analyses that are amenable to the study of rare diseases, and which would further our understanding of the role of the genome, proteome, microbiome, epigenome, metabolome, and glycome in the development of immunogenicity or tolerance to FVIII in individuals with severe Hemophilia A
- Infrastructure requirements for processing, storage, sharing and analysis of biospecimens and associated quality control metrics, as well as current infrastructure availability
- Long-term stability and feasibility of using archived biospecimens
- Technologies to enable in-home participant biospecimen collection and shipment to a processing facility
- Challenges associated with, and successful models for building lifespan/intergenerational cohorts with rare disorders
- Resources and partners required for successful lifespan/intergenerational cohorts with rare disorders, including unique challenges in sample procurement and banking
- Opportunities for a broader collaboration in maternal/fetal/neonatal science within the narrow scope of this project
Submitting a Response
All responses must be submitted via email to FactorVIII@nhlbi.nih.gov by November 12, 2018. Please include the Notice number NOT-HL-18-652 in the subject line. The submitted information will be reviewed by NIH staff.
Responses to this RFI are voluntary. Please do not include any proprietary, classified, confidential, or sensitive information in your response. NIH will use information submitted in response to this RFI at its discretion and will not provide comments to any responder’s submission. The collected information will be reviewed by NIH staff, may appear in reports, and may be shared publicly on an NIH web site.
The government reserves the right to use any non-proprietary technical information in summaries of the state of the science, and any resultant solicitation(s). The NIH may use information gathered by this RFI to inform development of future funding opportunity announcements.
This RFI is for information and planning purposes only and should not be construed as a solicitation or an obligation on the part of the Federal Government, the National Institutes of Health (NIH), or individual NIH institutes and Centers. NIH does not intend to make any awards based on responses to this RFI or to otherwise pay for preparation of any information submitted or for the Government’s use of such information. No basis for claims against the U.S. Government shall arise as a result of a response or from the Government’s use of such information.
Inquiries
Please direct all inquiries to:
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: FactorVIII@nhlbi.nih.gov
and Human Services (HHS)
