The national blueprint for 21st century data and specimen collection and observational cohort studies: NHLBI State of the Science Workshop on factor VIII inhibitors

Abstract

Introduction A devastating complication of hemophilia A, the congenital deficiency of coagulation factor VIII (FVIII), therapy is the development of inhibitory antibodies (inhibitors) to infused FVIII concentrate affecting up to 30% of people with the most severe form of the disease. Although the number of patients affected by hemophilia A with inhibitors is small, the physical, emotional, financial, and public health impact is overwhelming to the patient, family, and medical system. To best serve this patient population, as well as enhance knowledge around this complication, a robust data and specimen collection strategy must be designed. Aim Working Group 2 (WG2) of the National Heart, Lung, and Blood Institute (NHLBI)‐ sponsored State of the Science (SOS) workshop on factor VIII inhibitors in 2018 was tasked with developing recommendations around the conduct of research, modeling efficient data and specimen collection, developing infrastructure support, establishing partnerships with all stakeholders, including international collaborators, addressing ethical issues, maximizing patient/family engagement and promoting training opportunities. Methods A group with diverse expertise was assembled who reviewed the current state of data and specimen collection in patients with hemophilia and developed recommendations for the future. Results Our results were presented at the SOS Workshop where additional feedback was gained. Conclusion Our charge and recommendations are summarized in this manuscript.

The national blueprint for future factor VIII inhibitor clinical trials: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors

“…The support would enable HTC clinicians to provide care to all patients at HTCs through standard of care protocols approved through single IRBs and with standardized collection of natural history data. HTC investigators would develop hypothesis‐driven protocol concepts informed by national cohort studies, as addressed by Working Group 2, which would be vetted, prioritized and approved by a Steering Committee, developed into trial protocols and submitted to NIH and other research sponsors for review and funding recommendations.…”

Executive summary of the NHLBI State of the Science (SOS) Workshop: Overview and next steps in generating a national blueprint for future research on factor VIII inhibitors

“…The blueprints for future basic, translational and clinical research in FVIII immunogenicity, and in the prevention and eradication of FVIII inhibitors has been detailed in each of the full Working Group reports . This paper will serve to highlight and integrate several key points from each body of work.…”

“…This Working Group focused on the following key areas to identify the best future state for lifespan observational cohorts . This group identified an existing haemophilia data/specimen collection infrastructure on which to build a nationally integrated and coordinated 21st century data and specimen collection network designed to support basic, translational and clinical research (clinical trials and observational cohort studies).…”

“…Such a study could be best accomplished through novel interdisciplinary efforts, and through patient community engagement to overcome the barriers to enrolment. The infrastructure required to support such a cohort and integrate the required mechanistic studies were informed by the deliberations of Working Groups 2 and 3 …”

“…Working Group 2 highlighted key points for strategic implementation that include improvements that build on existing clinical databases; establishment and optimization of automated clinician‐ and patient‐entered data transfer; use of standard measures and PROs across studies for harmonization of clinical phenotypes and outcomes to facilitate data integration; streamlining of protocols, contracting and informed consent processes; and centralized tracking of biorepository specimens and data.…”