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. Author manuscript; available in PMC: 2023 Jan 28.
Published in final edited form as: Haemophilia. 2019 Jul;25(4):581–589. doi: 10.1111/hae.13717

TABLE 5.

Scientific Priorities for Clinical Trials to Prevent and Eradicate Inhibitors

Partner Resource
I. Define resources and partnerships for clinical trials
Industry Contributes licensed drug, novel mechanistic assays and high-risk studies
Foundation Supports HTCs to conduct trials; educate and engage community
Federal Agencies Continue to promote surveillance registries, standardizes assays, procedures
NHLBI Continues to develop mechanisms and resources, and review strategies to support small clinical trials
Community Supports consumer education on research and promote trial participation
Haemophilia Centre Trains staff to educate patients about inhibitors and participation in trials
HTC Physician Engage in clinical trials, participate in writing protocols and enrolling patients
Partner Resource
II. Leverage support for the haemophilia treatment centre research infrastructure
Network Provides for personnel, data collection, assays and statistical consultant
Capacity Incorporates research within HTC, where patients receive medical care
CDC, ATHN Establishes surveillance, uniform data collection and blood sampling/shipping
Partners Community, industry and foundations support HTC research
HTC Trains, educates staff, patients and families on importance of research
HTC Physician Develops and proposes clinical trial concepts with community agreement
Steering Committee Reviews, vets and prioritizes clinical trial concepts and new protocols
Trial Protocols Developed from concept, submitted to and reviewed by NIH/other funding organizations
Goal Specific mechanistic study
III. Embed mechanistic studies into clinical trials
Feasibility Anti-FVIII IgG subclasses
ELISPOT assays on peripheral blood mononuclear cells
FVIII-specific T-cell proliferation assays
FVIII-specific T regulatory cell induction studies
Intracellular cytokine expression assays
Microbiome studies
Implementation Fingerstick sampling for RNA sequencing or qPCR
Validation of assays for small volumes in infants
Epitope mapping and single cell assays
Network Utilization (ITN, CTSA) Existing resources utilized to implement assays
Alternate networks leveraged to help implement trial, serve as data centre
Partner Resource
IV. Optimize public-private partnerships in clinical trials
NHF/HFA Serve as a philanthropic partner to promote research
Educate providers, consumers on importance and commitment to research
Set up a well-crafted Public Relations campaign on research
Encourage providers, consumers to participate in registries, clinical trials
Incorporate clinical trial importance into national, regional meetings
Include clinical trial information on social media, publications and web portal
Industry/foundations Engage in support of clinical trials and in HTC network to conduct trials
Support novel agent assay development and mechanistic assays and studies
CDC Promote surveillance registries to embed in trials
Provide standardized assays and uniform data collection by HTCs
Research networks Provide expertise, immune, mechanistic assays, models and resources
Foundations Help support registries, trial network, HTC community to engage in trials
Resource/Group Goal
V. Engage the patient community in clinical trials
HTC MD/Staff Discusses research with patients at each HTC visit
Evaluates available studies for which patient may be eligible
Reviews risks, benefits and subject protection
Encourages participation in registries and clinical trials
Supports “twinning” of new families with experienced families
Chapter/Community Promote discussion, educate and engage the community
Sponsor educational webinars on trials as part of “culture of care”
Inform the community of importance of clinical trials
Provide information/webinars on registries, novel therapies
Role Training
VI. Embed training opportunities for early stage investigators in haemophilia trials
Mentor (Grant recipient) Incorporates training of young investigators in clinical trials
Provides mentorship for trainees to learn about clinical trial operations
Mentee (Fellow, trainee) Gains clinical trial research skills
Learns how to plan, design and conduct a clinical trial
Gains insight on the development of a clinical trial protocol
Applies human subject protection principles to informed consent process
Understands randomization techniques and intervention arm assignment
Studies principles of analysis of study endpoints
Gains knowledge of implementation of quality control standards
Recognizes roles of safety monitoring and data safety monitoring boards
Learns trial organization: clinical and data coordinating centres
Furthers training through career-building opportunities provided by NIH, Foundations and professional societies

CDC, Center for Disease Control; CTSA, Clinical and Translational Science Awards Program (NIH-sponsored); HFA is Haemophilia Federation of America; HTC, haemophilia Treatment Centre; ITN is immune tolerance network; NHF is National Haemophilia Foundation; NHLBI, National Institutes of Health Heart Lung Blood Institute; qPCR is quantitative polymerase chain reaction; RNA is ribonucleic acid.