Electrophysiology Based Biomarkers as Outcome Measures, Demonstrate Signal Detection and Reliability in a Simulated Clinical Trial at an Experienced Clinical Research Center Evaluating Study Drug (Ketamine) and Placebo
Larry Ereshefsky1, Marco Cecchi2, Elan Cohen3, K. C. Fadem2, Daniel Javitt4, Daniel Mathalon5, Brett English6, William Potter7 1CenExel Research & Follow the Molecule, 2Cognision, 3CenExel-Hassman Research Institute, 4Columbia University, 5University of California, San Francisco, 6Formerly at CenExel, 7Neuoscience Steering Committee, FNIH
Introduction: We present study results sponsored by the ERP Biomarker Qualification Consortium (https://erpbiomarkers.org). Our study is designed to simulate a randomized placebo (Pbo) controlled clinical trial to detect differences in standardized Event Related Potential (ERP)/Quantitative (Q)EEG measures between study drug (Ketamine) and Pbo in healthy volunteers at an experienced early phase clinical research unit. Low ICCs are a critical limiting factor for the use of ERP/QEEG as biomarkers reducing, confidence in the results. For reliable study results ICCs≥ 0.5 (moderate) and preferably ICCs≥ 0.6 are used in many clinical trials. We report results for a study that tested participants twice under Ketamine administration vs placebo. The study had 3 main objectives:
- Measure the effect size (Cohen’s d) of Ketamine‐induced changes on ERP and QEEG measure collected and analyzed with standardized equipment and methods.
- Quantify the variability of the Ketamine effect on ERP and QEEG measures across two dosing [Intraclass correlation coefficient (ICC)]
- Investigate a possible “disordinal effect” of Ketamine on ERP and QEEG feature parameters, where the direction and magnitude of Ketamine‐induced changes could be predicted by the baseline value.
Read more here: 2023 Nov 21 final ACNP ERP Consortium Ereshefsky