Primary Diagnosis Study for Validation of Hamamatsu NanoZoomer S360MD Digital Slide Scanner System

Clinical Validation for Non-Inferiority of Primary Diagnosis by WSI Hamamatsu NanoZoomer S360MD Digital Slide Scanner System Compared to Conventional Determination by Light Microscope

The primary objective of this study is to evaluate the safety and accuracy of the Hamamatsu WSI compared to those of the reference method (conventional light microscope (Glass)) under clinical use conditions as an aid for pathologists to view, review and diagnose digital images of surgical pathology slides.

The primary endpoint is the indicator of major discordance in primary diagnosis between ground truth case diagnosis and case diagnosis by each modality, WSI and Glass, separately.

Study Overview

• Status: Completed
• Conditions: Pathology
• Intervention / Treatment: Diagnostic test: Whole Slide Imaging; Diagnostic test: Light Microscopy

• Study Type: Interventional
• Enrollment (Actual): 2000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • TriCore Reference Laboratories
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210-1063
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cases originating from and that were diagnosed at that local site
• Cases are available in the site's archive
• Cases are at least 1 year old since accessioning
• Cases are selected because their primary diagnosis is consistent with the assigned target categories
• Cases have a set of slides representative of the primary diagnosis for which it has been selected

Slide selection for a given case must meet the following criteria:

• Slide is obtained by surgical pathology and prepared from FFPE human tissue
• Slides must be stained with H&E and accompanying special stains (histochemical and/or immunohistochemical)
• All special stains slides (histochemical and/or immunohistochemical) where the slide and stain is used for diagnosis, not prognosis.
• A chosen slide must demonstrate and be representative of the primary diagnosis; 1 slide selection may suffice for biopsy cases,
• For resection cases, a minimum of 5 slides must be selected, which represent the primary diagnosis. If represented with less than 5 slides, additional slides (primary, secondary, or benign slides) from same case may be used to fulfill minimum number
• Slide is intact, has correct size/thickness, good edges, undamaged coverslip, without pen markings that can't be removed, no air bubbles, tidy labels, and fulfills the quality checks per the general clinical practice

Exclusion Criteria:

• Case does not have relevant slides or if case information necessary for the study is missing
• Case is still active (less than 1 year old) at the local site
• Cases for which the control slides for immunohistochemistry and special stains are not available
• Two cases from same individual
• Gross-only cases that have no slides
• Cases that are frozen section, cytology or hematology or immunofluorescence specimens only
• Case where the only available set of slides have evidence only of secondary or no diagnoses and not the primary diagnosis for which the case is being screened.

Slides for a given case will be excluded if they meet the following criterion:

• Glass slide that is broken, has abnormal size/thickness, beveled edges, poor coverslip (cracks, waviness, scratches), is sticky, has many pen markings or dirt that cannot be removed, contains air bubbles and overhanging labels that can't be corrected, and if stain is severely faded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NanoZoomer Whole Slide Imaging; All cases will be assessed via Whole Slide Imaging using the Hamamatsu NanoZoomer S360MD Digital Slide Scanner System to assess pathological characteristics of scanned slides.	Diagnostic test: Whole Slide Imaging; Scanning of a glass slide to create a digital image that can be viewed on a monitor; Other Names: NanoZoomer Scanning & Imaging
Active Comparator: Glass Slide Light Microscopy; All cases will be assessed via the use of traditional light microscopy to assess pathological characteristics of glass slides.	Diagnostic test: Light Microscopy; Use of traditional light microscopy per institutional standard practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Discordance Rate	Indpendent reads by four Reading Pathologists (RPs) of both imaging modalitites (8 reads/case) were compared to the original diagnosis ("ground truth" or GT) by an independent adjudication process. This resulted in one of four adjudication outcomes for each read: "Match" (read = GT), "Minor" (minor discordance between read & GT), "Major" (major discordance between read & GT), or "Deferred" (read deferred by RP and excluded from the primary endpoint analysis). The outcome measure was the rate at which major discordances occurred for each modality.	1 day

Collaborators and Investigators

• Sponsor: Hamamatsu Photonics K.K.
• Investigators: Principal Investigator: Liron Pantanowitz, University of Pittsburgh Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: June 18, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 19, 2019

Study Record Updates

• Last Update Posted (Actual): December 22, 2022
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HCT-P001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No