EXTH-39. BENCH TO BEDSIDE NEURO-ONCOLOGY: ADVOCATING FOR A CLINICALLY RELEVANT STRATEGY

Abstract

Abstract INTRODUCTION Therapeutic successes in neuro-oncology have lagged dramatically behind exciting laboratory discoveries, and successful translation of promising laboratory findings into clinical practice is rare. We hypothesize that one important reason for this discordance is the use of very different paradigms for designing laboratory and clinical trials, and that utilizing clinically relevant procedures could improve laboratory study impact. METHODS We identified all pre-clinical neuro-oncology therapeutic trials published in four high-impact journals between 11/2018 and 4/2019, and assigned a level of evidence (LOE) to each study using the American Academy of Neurology evidence classification system. We also extracted details about statistical techniques, funding, and institutional setting. RESULTS Of the 26 articles identified, 85% had a LOE of IV (highest-I, lowest-IV) and 15% were class III. Factors contributing to the low LOE included lack of randomization (65%) or allocation concealment (100%), absence of masked assessment (96%), and no comparison of treatment and control groups with respect to prognostically relevant characteristics (92%). Effect size and confidence interval reporting, power calculation, correction for multiple hypothesis testing, and multivariate analysis were absent in 92%, 92%, 100%, 88%, and 92% of studies respectively. The “reverse” analysis (starting with successful human trials and analyzing existing pre-clinical support studies) showed significantly more high quality laboratory studies supporting “successful” compared to “unsuccessful” trials (p=0.04). CONCLUSIONS When rigorous human clinical trials criteria are applied to therapeutic laboratory studies, laboratory study LOE is uniformly poor. For laboratory research intended to inform clinical trial design and improve clinical outcomes, this situation dooms most basic science research to fail in the clinical arena. The steps required to solve this problem are challenging but addressable, and costs associated with the solution are dwarfed by the expense of early phase human trials which are destine to failure.