Ethics Approval and Consent to Participate
This study was conducted in accordance with this protocol and the applicable requirements outlined in ICH E6 Good Clinical Practices and Title 21 CFR Part 54 (Financial Disclosure), Part 56 (IRB), Part 809 (Labeling), Part 814 (Premarket) and Part 820 (Quality System Regulations). The study was also conducted in conformance with the Declaration of Helsinki and all applicable local laws and regulations.
Protocols, consent form, Case Report Forms (CRFs, as applicable), and recruitment materials were reviewed and approved by specific sites’ Institutional Review Board (IRB) or a central IRB (listed below). Once the IRB provided written/dated approval of the materials and the Sponsor confirmed approval, the site could enroll applicable subjects. Written informed consent was obtained from all individual participants included in the study.
The Principal Investigator(s) (PIs) at each site were responsible for complying with reporting requirements and review requirements of the local IRB (21CFR56). When changes to the protocol, consent forms, or recruitment materials were required, the Sponsor notified the PI who informed the local IRB and obtained necessary approvals. Approval was required prior to implementation of any change.
List of Institutional Review Boards:
Geisinger Institutional Review Board – Danville, PA
The University of Tennessee Health Science Center College of Medicine Institutional Review Board – Chattanooga, TN
University of Texas Medical Branch Institutional Review Board – Galveston, TX
Virtua General Institutional Review Board – Mt. Laurel, NJ
Western Institutional Review Board – Puyallup, WA
Indiana University Intuitional Review Board – Indianapolis, IN
University of Utah Intuitional Review Board – Salt Lake City, UT
University of North Carolina Intuitional Review Board – Chapel Hill, NC
Duke University Intuitional Review Board – Durham, NC
University of Mississippi Medical Center Intuitional Review Board – Jackson, MS
University of Colorado Intuitional Review Board – Denver, CO
Johns Hopkins Medicine Intuitional Review Board – Baltimore, MD
University of Alabama Intuitional Review Board – Birmingham, AL
University of Texas Health Science Center Intuitional Review Board – Houston, TX
Yale University Intuitional Review Board – New Haven, CT
TriHealth Intuitional Review Board – Cincinnati, OH
The Washington University in St. Louis Intuitional Review Board – St. Louis, MO
Medical College of Wisconsin Intuitional Review Board – Milwaukee, WI
Aspire Intuitional Review Board – Santee, CA
Availability of Data
The datasets used and/or analyzed during the current study are not publicly available due to proprietary reasons but are available from the corresponding author on reasonable request.
Sources of Funding
The project, including study design, sample collection, analysis and interpretation of data was supported by funds from Progenity Inc, San Diego, CA.
Consent for Publication
Not Applicable
Disclosures & Conflicts of Interest:
Drs. Mazloom, Abbasi, Lockton, Singh, Del Mastro, Uren, Hendershot, Oberoi and Cooper are or were, at the time of this work, employees of Progenity. Drs. Robinson and Sibai have been paid consultants for Progenity. Dr. Paglia reports no conflict of interest.
Authors’ Contribution
ARM, SL, MA, JH, and CR drafted the manuscript. MJP contributed to critical aspects of the conduct of this research including assessment of subject recruitment and monitoring. All the authors provided a significant intellectual contribution to the drafting and revision of this manuscript with regard to scientific content and form and approved the final manuscript as submitted. ARM led the algorithm development, and the biomarker discovery efforts, MA and SL developed the algorithm and performed statistical analyses. PU led the software development efforts and the analytical Quality Control algorithm development. RDM contributed to the biomarker discovery. JH worked on the assay development and was involved in the sample testing. PO led the assay development activities and critically reviewed all the statistical analyses. SS contributed to the assay troubleshooting and optimization. MC was the executive sponsor of the program and provided strategic guidance on the design of the test including the target population selection which informed the algorithm design.
Acknowledgements
We would to like to extend our appreciation to Emad Samani, Laura Fortier, Jim Del Propostro, Christina Settler, Lara Bagby, Lyndal Hesterberg, Lisa Freedman, Peter Stiegler, Rowena Mittal, and Stephen Thomas, without whose efforts this manuscript and the research behind it would not have been possible. Their support during this research extends to a variety of aspects including but not limited to assay development, instrumentation, programming, statistical analysis and review, sample management and manuscript review.