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. 2023 Mar;16(sup1):55-70.
doi: 10.1080/17474086.2023.2175661.

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for ultra-rare inherited bleeding disorders

Diane Nugent  1   2 , Suchitra S Acharya  3 , Kimberly J Baumann  4 , Camille Bedrosian  5 , Rebecca Bialas  6 , Kai Brown  7 , Deya Corzo  8 , Amar Haidar  9 , Catherine P M Hayward  10   11 , Peter Marks  12 , Marzia Menegatti  13 , Margaret E Miller  14 , Kate Nammacher  7 , Roberta Palla  13   15 , Skye Peltier  4 , Rajiv K Pruthi  16 , Michael Recht  17   18 , Benny Sørensen  19 , Michael Tarantino  20 , Alisa S Wolberg  21   22 , Amy D Shapiro  23
Affiliations

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities for ultra-rare inherited bleeding disorders

Diane Nugent et al. Expert Rev Hematol. 2023 Mar.

Abstract

Background: Ultra-rare inherited bleeding disorders (BDs) present important challenges for generating a strong evidence foundation for optimal diagnosis and management. Without disorder-appropriate treatment, affected individuals potentially face life-threatening bleeding, delayed diagnosis, suboptimal management of invasive procedures, psychosocial distress, pain, and decreased quality-of-life.

Research design and methods: The National Hemophilia Foundation (NHF) and the American Thrombosis and Hemostasis Network identified the priorities of people with inherited BDs and their caregivers, through extensive inclusive community consultations, to inform a blueprint for future decades of research. Multidisciplinary expert Working Group (WG) 3 distilled highly feasible transformative ultra-rare inherited BD research opportunities from the community-identified priorities.

Results: WG3 identified three focus areas with the potential to advance the needs of all people with ultra-rare inherited BDs and scored the feasibility, impact, and risk of priority initiatives, including 13 in systems biology and mechanistic science; 2 in clinical research, data collection, and research infrastructure; and 5 in the regulatory process for novel therapeutics and required data collection.

Conclusions: Centralization and expansion of expertise and resources, flexible innovative research and regulatory approaches, and inclusion of all people with ultra-rare inherited BDs and their health care professionals will be essential to capitalize on the opportunities outlined herein.

Keywords: Inherited bleeding disorder; National Hemophilia Foundation; knowledge gaps; patient-centered; research; therapeutic gaps; ultra-rare disorders.

Plain language summary

Living with an ultra-rare inherited bleeding disorder is challenging. Patients can feel alone and unsure of where to find support because their disorder is so rare. In this paper, a group of ultra-rare bleeding disorder experts, including doctors, researchers, regulators, patient advocates, and patients, identify the research that could best improve the lives of people with these disorders. They propose a national network of specialists who can help doctors, who may never have seen these disorders before, to find the right diagnosis faster. A centralized laboratory specialized in ultra-rare bleeding disorders could also improve diagnosis and do research studies. This would help us learn, for example, how symptoms change throughout a patient’s life, how effective different treatments are, and what it is like for patients to live with these disorders. A second research priority is to better understand each individual disorder so that the best treatments can be chosen or developed. A pathway showing doctors which treatment options to try, in which order, would help them help their patients. The third research priority is to make it easier to study new treatments for ultra-rare bleeding disorders. This requires designing studies with very small numbers of participants, identifying meaningful outcomes to measure, and convincing pharmaceutical companies to invest in these studies. International agreement on these requirements would allow more patients to participate and benefit from the research. These top-priority research goals should greatly improve knowledge about, and diagnosis and treatment of, ultra-rare inherited bleeding disorders.

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Conflict of interest statement

Declaration of interests

The authors are integrated members of the inherited bleeding disorders community: people with inherited bleeding disorders, their family members, health care providers and researchers (including physicians, nurses, physical therapists, pharmacists, social workers/psychologists, geneticists/genetic counselors, etc.), industry partners, government officials/regulators, local community organization representatives and others.

Figures

Figure 1.
Figure 1.
Working Group 3 Research Priorities for Ultra-rare Inherited Bleeding Disorders schematic of community-identified areas for priority research framework POC: point of care
Figure 2.
Figure 2.
Questions and elements/modalities considered by the WG3 subgroup to address community priorities in diagnostics, systems biology, and mechanistic science of ultra-rare inherited bleeding disorders. DNA: deoxyribonucleic acid, WG: working group
Figure 3.
Figure 3.
Questions and elements/modalities considered by WG3 to address clinical, data collection, and research infrastructure community priorities for ultra-rare inherited bleeding disorders. DNA: deoxyribonucleic acid, IRB: institutional review board, QoL: quality-of-life
Figure 4.
Figure 4.
Questions and elements/modalities considered by WG3 to address community priorities in regulatory processes for novel therapeutics and required data collection for ultra-rare inherited bleeding disorders. FDA: U.S. Food and Drug Administration
Figure 5.
Figure 5.
Plot of feasibility, impact, and risk scores of the questions evaluated by the three WG3 subgroups. *Diagnostics, Systems Biology, Mechanistic Science questions were not scored for risk Label numbers correspond to those in Table 3, note that some data points have identical coordinates and, therefore, overlap.
See this image and copyright information in PMC

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