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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pathology

Intervention / Treatment
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* Diagnostic Test: Whole Slide Imaging
* Diagnostic Test: Light Microscopy


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Cases are assessed using both glass slide light microscopy and NanoZoomer digital whole slide imaging in a random order
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NanoZoomer Whole Slide Imaging<br>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<br>* Scanning of a glass slide to create a digital image that can be viewed on a monitor<br>* Other names: NanoZoomer Scanning & Imaging;|
| Active Comparator: Glass Slide Light Microscopy<br>All cases will be assessed via the use of traditional light microscopy to assess pathological characteristics of glass slides. | Diagnostic Test: Light Microscopy<br>* Use of traditional light microscopy per institutional standard practice<br>|

What is the study measuring?
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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 |