Validation of a suite of ERP and QEEG biomarkers in a pre-competitive, industry-led study in subjects with schizophrenia and healthy volunteers
M Cecchi, M Adachi, A Basile, D L Buhl, H Chadchankar, S Christensen, E Christian, J Doherty, K C Fadem, B Farley, M S Forman, S Honda, J Johannesen, B J Kinon, D Klamer, M J Marino, C Missling, P O'Donnell, T Piser, C B Puryear, M C Quirk, M Rotte, C Sanchez, D G Smith, J M Uslaner, D C Javitt, R S E Keefe, D Mathalon, W Z Potter, D P Walling, L Ereshefsky, M Cecchi, M Adachi, A Basile, D L Buhl, H Chadchankar, S Christensen, E Christian, J Doherty, K C Fadem, B Farley, M S Forman, S Honda, J Johannesen, B J Kinon, D Klamer, M J Marino, C Missling, P O'Donnell, T Piser, C B Puryear, M C Quirk, M Rotte, C Sanchez, D G Smith, J M Uslaner, D C Javitt, R S E Keefe, D Mathalon, W Z Potter, D P Walling, L Ereshefsky
Abstract
Objective: Complexity and lack of standardization have mostly limited the use of event-related potentials (ERPs) and quantitative EEG (QEEG) biomarkers in drug development to small early phase trials. We present results from a clinical study on healthy volunteers (HV) and patients with schizophrenia (SZ) that assessed test-retest, group differences, variance, and correlation with functional assessments for ERP and QEEG measures collected at clinical and commercial trial sites with standardized instrumentation and methods, and analyzed through an automated data analysis pipeline.
Methods: 81 HV and 80 SZ were tested at one of four study sites. Subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40 Hz auditory steady-state response paradigm, an eyes-closed resting state EEG, and an active auditory oddball paradigm. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), Positive and Negative Syndrome Scale (PANSS), and Virtual Reality Functional Capacity Assessment Tool (VRFCAT).
Results: Standardized ERP/EEG instrumentation and methods ensured few test failures. The automated data analysis pipeline allowed for near real-time analysis with no human intervention. Test-retest reliability was fair-to-excellent for most of the outcome measures. SZ subjects showed significant deficits in ERP and QEEG measures consistent with published academic literature. A subset of ERP and QEEG measures correlated with functional assessments administered to the SZ subjects.
Conclusions: With standardized instrumentation and methods, complex ERP/EEG testing sessions can be reliably performed at clinical and commercial trial sites to produce high-quality data in near real-time.
Keywords: Automated data analysis; ERP Biomarker Qualification Consortium; Event related potentials; Quantitative EEG; Schizophrenia; Test-retest reliability.
Conflict of interest statement
Declaration of competing interest M. Cecchi is an employee of Cognision. M. Adachi and S. Honda are employees of Astellas Pharma. A. Basile. M.J. Marino, and J.M. Uslaner are employees of Merck & Co. D.L. Buhl is an employee and shareholder of Takeda Pharmaceuticals. H. Chadchankar and M. Rotte are employees of Novartis. S. Christensen is an employee of Lundbeck. E. Christian is an employee of Gilgamesh Pharmaceuticals. J. Doherty and B. Farley are employees and shareholders of Sage Therapeutics. K.C. Fadem is an employee and shareholder of Cognision. M.S. Forman is an employee of Passage Bio. J. Johannesen, P. O'Donnell, and M.C. Quirk are employees of Sage Therapeutics. B.J. Kinon is an employee of Cyclerion Therapeutics. D. Klamer and C. Missling are employees and shareholders of Anavex Life Sciences Corp. T. Piser is an employee of Onsero Therapeutics; T. Piser has financial interest in the development of NMDA receptor modulators owned by Novartis Pharmaceuticals, and is an inventor on issued patents on some of these compounds. C.B. Puryear is an employee of Praxis Precision Medicines. C. Sanchez and D.G. Smith are employees and shareholders of Alkermes. D.C. Javitt has received consulting payments within the last 2 years from Autifony, Biogen, SK Life Sciences, Boehringer Ingelheim, and Biogen; he holds intellectual property rights for use of NMDA modulators in treatment of neuropsychiatric disorders, for parcel-guided TMS treatment of depression, and for EEG-based diagnosis of neuropsychiatric disorders; he also holds equity in Glytech, AASI, and NeuroRx. R.S.E. Keefe is the owner of VeraSci, a for-profit company that supports clinical trials for over 100 business entities, mostly pharmaceutical companies; VeraSci provided paid support for this study. D.P. Walling has received grant funding from Novartis, Janssen, Intracellular, Lyndra, Rovi, Otsuka, Alkermes, Cerevel, Abbvie, Allergan, Noven, Takeda, Indivior, Avanir, Lundbeck, Roche, Boehringer Ingelheim, Biogen, Sunovion and Acadia; he has served on Advisory Boards for Otsuka, Janssen, Biogen, Boehringer Ingelheim and Lyndra. L. Ereshefsky receives support from CenExel, which conducts research for most pharma, and is a performing site for NIH and Alzheimer's Foundation. Moreover, Follow the Molecule LLC receives consulting compensation from Bioxcel, Blackthorn, Neurocrine, Athira, Ceravance, Digestome, Immune Brain Check, Gilgamesh, and Karuna Therapeutics.
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Source: PubMed