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.