Regulatory and Funding Strategies to Develop a Safety Study of an Auditory Brainstem Implant in Young Children Who Are Deaf

Abstract

Background: In the US, a child born deaf with abnormal inner ear anatomy and for whom a cochlear implant fails to provide benefit has no approved surgical treatment options. The auditory brainstem implant (ABI) was developed in the US for patients with Neurofibromatosis 2. A European surgical team has advanced ABI use in young children, with promising outcomes. Clinical teams face a number of challenges, from regulatory issues to funding. The strategic decisions leading to the safety and early efficacy protocol of the ABI for young children with congenital deafness are described. Methods: A sponsor-investigator pre–Investigational Device Exemption (IDE) was significantly altered in discussion with the Food and Drug Administration (FDA), followed by approval of a revised protocol. A critical step involved securing external funding through an NIH U01 clinical trial grant, and enrollment began in 2014. Early Results: The protocol focused on strict inclusion criteria, clear stopping rules, and rigorous interim safety data review before proceeding with enrollment. To date, 4 of the 7 enrolled subjects met criteria for implantation. A single expected serious adverse event occurred, which resolved completely without sequela. Conclusions: Promising innovative treatments face a number of obstacles along the pathway to full commercialization. A strategy that included early conversations with the FDA and the device manufacturer, and successfully obtaining external funding, resulted in an approved IDE protocol. Early results indicated that the risks, though not minimal, can be successfully mitigated. These young children appear to benefit audiologically from the ABI.

Early Communication Development of Children with Auditory Brainstem Implants

“…Commencing in 2012, several FDA-sponsored Phase I trials were initiated in the United States to investigate the safety and feasibility of the Nucleus ABI in young non-NF2 children (Fisher et al, 2015;Puram et al, 2016;Teagle, Henderson, He, Ewend, & Buchman, 2018;Wilkinson et al, 2017). We recently described one such trial and presented 1-year results for four children and 3-month results for one child with the ABI (Wilkinson et al, 2017).…”