Validation of a Suite of ERP and QEEG Biomarkers in a Pre-Competitive, Industry-Led Study in Subjects with Schizophrenia and Healthy Volunteers

24 Pages Posted: 16 Sep 2022

See all articles by Marco Cecchi

Marco Cecchi

Cognision

Megumi Adachi

Astellas Pharma

Anthony Basile

Merck & Co., Inc.

Derek Buhl

Takeda Pharmaceuticals

Heramb Chadchankar

Novartis

Søren Christensen

Lundbeck

Edward Christian

Gilgamesh Pharmaceuticals

Jim Doherty

Sage Therapeutics

KC Fadem

Cognision

Brandon Farley

Sage Therapeutics

Mark Forman

Passage Bio

Sokichi Honda

Astellas Pharma

Jason Johannesen

Sage Therapeutics

Bruce Kinon

Cyclerion Therapeutics

Daniel Klamer

Anavex Life Sciences Corp.

Marino Michael

Merck & Co., Inc.

Christopher Missling

Anavex Life Sciences Corp.

Patricio O'Donnell

University of Maryland - Department of Psychiatry

Timothy Piser

Onsero Therapeutics

Corey Puryear

Praxis Precision Medicines

Michael Quirk

Sage Therapeutics

Michael Rotte

Novartis

Connie Sanchez

Alkermes

Daniel Smith

Alkermes

Jason M. Uslaner

Merck & Co Inc

Daniel Javitt

Columbia University School of Medicine

Richard SE Keefe

VeraSci

Daniel H. Mathalon

University of California, San Francisco (UCSF)

William Potter

Alkermes

David P. Walling

CenExel - CNS

Larry Ereshefsky

CenExel Research; The University of Texas

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 group differences, variance, and correlation with functional assessments for ERP and QEEG parameters collected at commercial and clinical trial sites with standardized methods and analyzed through an automated data analysis pipeline.

Methods: 81 HV and 80 SZ were tested at one of four study sites. Study subjects were administered two ERP/EEG testing sessions on separate visits. Sessions included a mismatch negativity paradigm, a 40Hz auditory steady state response, an eyes-closed resting state EEG, and an active auditory oddball task. SZ subjects were also tested on the Brief Assessment of Cognition (BAC), the Positive and Negative Syndrome Scale (PANSS), and the Virtual Reality Functional Capacity Assessment Tool (VRFCAT).

Results: Standardized ERP/EEG testing equipment and protocols ensured a low number of test failures. The automated data analysis pipeline allowed for near real-time assessment of results. Test-retest reliability was fair-to-excellent for most of the measures collected. SZ subjects showed significant deficits in ERP and QEEG parameters that were consistent with the published academic literature. A subset of ERP and QEEG parameters correlated with functional assessments administered to the SZ subjects.

Conclusions: With standardized equipment and methods, complex ERP/EEG testing sessions can be reliably performed at commercial and clinical study sites to produce high-quality data in near real-time.

Note:
Clinical Trial Registration Details: ClinicalTrials.gov number NCT04025502.

Funding Information: This research was funded by the ERP Biomarker Qualification Consortium.

Declaration of Interests: None.

Ethics Approval Statement: The study was approved by institutional review boards for each site. Written informed consent was obtained from each study participant, after which subjects were screened for eligibility.

Keywords: ERP Biomarker Qualification Consortium, Event Related Potentials, Quantitative EEG, schizophrenia, Test-Retest Reliability, Automated Data Analysis.

Suggested Citation

Cecchi, Marco and Adachi, Megumi and Basile, Anthony and Buhl, Derek and Chadchankar, Heramb and Christensen, Søren and Christian, Edward and Doherty, Jim and Fadem, KC and Farley, Brandon and Forman, Mark and Honda, Sokichi and Johannesen, Jason and Kinon, Bruce and Klamer, Daniel and Michael, Marino and Missling, Christopher and O'Donnell, Patricio and Piser, Timothy and Puryear, Corey and Quirk, Michael and Rotte, Michael and Sanchez, Connie and Smith, Daniel and Uslaner, Jason M. and Javitt, Daniel and Keefe, Richard SE and Mathalon, Daniel H. and Potter, William and Walling, David P. and Ereshefsky, Larry, Validation of a Suite of ERP and QEEG Biomarkers in a Pre-Competitive, Industry-Led Study in Subjects with Schizophrenia and Healthy Volunteers. Available at SSRN: https://ssrn.com/abstract=4188821

Megumi Adachi

Astellas Pharma ( email )

Anthony Basile

Merck & Co., Inc. ( email )

Derek Buhl

Takeda Pharmaceuticals ( email )

Heramb Chadchankar

Novartis ( email )

Søren Christensen

Lundbeck ( email )

Edward Christian

Gilgamesh Pharmaceuticals ( email )

Jim Doherty

Sage Therapeutics ( email )

KC Fadem

Cognision ( email )

Brandon Farley

Sage Therapeutics

Mark Forman

Passage Bio ( email )

Sokichi Honda

Astellas Pharma ( email )

Jason Johannesen

Sage Therapeutics ( email )

Bruce Kinon

Cyclerion Therapeutics ( email )

Daniel Klamer

Anavex Life Sciences Corp. ( email )

Marino Michael

Merck & Co., Inc. ( email )

Christopher Missling

Anavex Life Sciences Corp. ( email )

Patricio O'Donnell

University of Maryland - Department of Psychiatry ( email )

110 South Paca Street
Baltimore, MD 21201
United States

Timothy Piser

Onsero Therapeutics ( email )

Corey Puryear

Praxis Precision Medicines ( email )

Michael Quirk

Sage Therapeutics ( email )

Michael Rotte

Novartis ( email )

Connie Sanchez

Alkermes ( email )

Daniel Smith

Alkermes ( email )

Jason M. Uslaner

Merck & Co Inc ( email )

Daniel Javitt

Columbia University School of Medicine ( email )

3022 Broadway
New York, NY 10027
United States

Richard SE Keefe

VeraSci ( email )

Daniel H. Mathalon

University of California, San Francisco (UCSF) ( email )

San Francisco, CA
United States

William Potter

Alkermes ( email )

David P. Walling

CenExel - CNS ( email )

12772 Valley View St. Ste 3
Garden Grove, CA CA 92845
United States
7147997799 (Phone)
92845 (Fax)

Larry Ereshefsky

CenExel Research ( email )

12772 Valley View St. Ste 3
Garden Grove, CA CA 92845
United States

The University of Texas ( email )

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