New Approaches to Clinical Trials for Rare Diseases: Decentralized Trial Design for Neurofibromatosis Type 1 and Schwannomatosis

Background: In decentralized clinical trials, some or all activities occur outside of traditional sites, which may reduce time away from school/work and decrease participation burden for patients and their parents/caregivers. This methodology may improve recruitment and retention in studies, which is important for rare diseases like neurofibromatosis type 1 (NF1) and schwannomatosis (SWN). Published guidance exists for the general conduct of decentralized trials, but specific considerations for clinical trial design and endpoints in NF1/SWN have not yet been explored. Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration is a group of researchers, clinicians, and people affected by NF1 and SWN whose shared goal is to advance clinical trial methodology for NF1/SWN. In December 2023, REiNS members met to discuss the opportunities and challenges of conducting NF1/SWN decentralized trials. Results: Endpoints that are promising for use in NF1/SWN decentralized trials include visual acuity (as tested by the computerized amblyopia treatment study HOTV testing algorithm); electronic versions of REiNS-recommended patient reported outcome measures; digital health technologies for functional outcomes; radiography and computed tomography scans for imaging outcomes; remote photography to assess cutaneous neurofibromas; “e-centralized” evaluations of neurocognitive functioning; and remote biomarkers collected with analyte stabilizing tubes and self-collection devices. Conclusions: Further research is necessary to validate endpoints for decentralized trials for NF1/SWN and evaluate their feasibility. However, trial designs that incorporate decentralized elements hold considerable promise for rare diseases like NF1/SWN where patients encounter significant barriers to traditional clinical trial participation.