Abstract WP310: PRIMED Preclinical Evidence Scoring Tool to Assess Readiness for Translation of Neuroprotection Therapies

Abstract

Introduction: Multiple neuroprotective therapies (NPT’s) for treatment of acute ischemic stroke have failed in translation to human studies, indicating a need for more rigorous quality assessment of all the cumulative preclinical evidence supporting an NPT prior to conducting human trials. There is a need for an updated translational readiness assessment tool to assess candidate therapies that combines desirable elements of existing instruments (STAIR 2.0, CAMARADES, RoB2) and include additional important elements. Methods: Candidate items for the intervention translational readiness scale, based on prior instruments, were rated by importance, reliability, and feasibility. For illustrative purposes, the assessment tool was applied to four NPT in current development, including two pharmacologic agents [uric acid (UA) and trans sodium crocetinate (TSC)] and two neuromodulatory device interventions [cathodal direct current stimulation (C-DCS) of ischemic hemisphere and fastigial nucleus stimulation (FSN)]. Results: The final Preclinical evidence of Readiness In stroke Models Evaluating Drugs/Devices (PRIMED) assessment tool rates evidence available from all reported animal studies in 10 domains (Fig1). Among the four assessed candidate NPT’s, the scores for two pharmacologic NPT’s indicated high translational readiness (UA and TSC 17) and the two neuromodulatory NPT’s had intermediate readiness-for-translation (C-DCS 12, FNS 8). Conclusion: The PRIMED assessment tool is an updated, multidimensional tool that provides a detailed assessment of multiple important readiness features across all preclinical experiments testing an NPT to assess readiness for translation, applicable to both pharmocologic and device therapies for acute stroke, providing both qualitative profiling of agent strengths and weaknesses and a quantitative summary score. Based on this tool, translational readiness is high for UA and TSC and intermediate for C-DCS and FNS.