(519 days)
The Virtuoso system provides automated digital slide creation, management, analysis, and viewing. It is intended for in vitro diagnostic use as an aid to the pathologist in the display, detection, counting, review and classification of tissues and cells of clinical interest based on particular morphology, color, intensity, size, pattern and shape.
The IHC Ki-67 (30-9) Digital Read and Image Analysis applications are intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of Ki-67 protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. Ki-67 results are indicated for use in assessing the proliferative activity of normal and neoplastic breast tissue. When used with Ventana Medical Systems, Inc. CONFIRM™ anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody Assay, it is indicated for use as an aid in the assessment of Ki-67 status in breast cancer patients (but is not the sole basis for treatment).
The Virtuoso™ System is an instrument-plus-software system designed to assist the qualified pathologist in the consistent assessment of protein expression in immunohistochemically stained histologic sections from formalin-fixed, paraffinembedded normal and neoplastic tissues. The system consists of a slide scanner (iScan), computer, monitor, keyboard, mouse, image analysis algorithms for specific immunohistochemical markers, and software with a Windows web browser-based user interface. Virtuoso is a web-based, end-to-end, digital pathology software solution that allows pathology laboratories to acquire, manage, view, analyze, share, and report digital images of pathology specimens. Using the Virtuoso software, the pathologist can view digital images, add annotations, make measurements, perform image analysis, and generate reports.
Hardware: The iScan slide scanning device captures digital images of formalin-fixed. paraffin-embedded tissues that are suitable for storage and viewing. The device includes a digital slide scanner, racks for loading glass slides, computer, scanner software, keyboard, mouse and monitor.
Software: The Virtuoso software is designed to complement the routine workflow of a qualified pathologist in the review of immunohistochemically stained histologic slides. It allows the user to select fields of view (FOVs) in the digital image for analysis and provides quantitative data on these FOVs to assist with interpretation. The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process.
The Ventana Virtuoso™ System for IHC Ki-67 (30-9) was tested for its performance in both digital reading (DR) and image analysis (IA) of Ki-67 stained slides. The overall acceptance criterion for each measurement was 75% overall percent agreement (OPA) with manual microscopic reads.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Overall Percent Agreement) | Reported Device Performance (Overall Percent Agreement) |
|---|---|---|
| Digital Read (DR) vs. Manual Read | ≥ 75% | 90.0% (95% CI: 83.3-94.2) |
| Image Analysis (IA) vs. Manual Read (Overall) | ≥ 75% | 78.0% (95% CI: 69.7-84.5) |
| Image Analysis (IA) vs. Manual Read (Site 1) | ≥ 75% | 86.6% (95% CI: 79.1-91.7) |
| Image Analysis (IA) vs. Manual Read (Site 2) | ≥ 75% | 90.8% (95% CI: 84.2-94.8) |
2. Sample Size and Data Provenance for the Test Set
- Digital Read (DR) Test Set: 120 cases.
- Image Analysis (IA) Test Set: 120 cases.
- Data Provenance: The document does not explicitly state the country of origin. The studies appear to be prospective concordance studies where new data was generated for validation.
3. Number of Experts and Qualifications for Ground Truth Establishment (Test Set)
- Digital Read (DR): "one pathologist at one site" established the manual score (reference result). No specific qualifications are provided beyond "pathologist".
- Image Analysis (IA): "three pathologists at three sites" established the manual score (reference result). No specific qualifications are provided beyond "pathologists".
4. Adjudication Method for the Test Set
The document describes concordance studies where manual scores were compared to device scores. It does not mention any formal adjudication method beyond establishing the "manual score (reference result)" by one or more pathologists. This implies a single expert's opinion served as the ground truth for each case initially, rather than multiple experts with a specific adjudication process.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No formal MRMC comparative effectiveness study is described where human readers' performance with and without AI assistance is directly compared to quantify an effect size. The studies focus on the agreement between the device alone (digital read or image analysis) and manual reads.
6. Standalone (Algorithm Only) Performance
Yes, standalone performance was done for both Digital Read and Image Analysis:
- Digital Read Performance: This section describes the agreement between the digital image reviewed by a pathologist ("Digital Read") and the manual microscopic read. While a pathologist is involved in the "Digital Read," the intent is to show that replacing the physical microscope with a digital image viewer (which is part of the system) does not negatively impact the pathologist's ability to score the cases.
- Image Analysis Performance: This section directly assesses the agreement between the Virtuoso Image Analysis application's output and the manual microscopic read. This represents the algorithm-only performance in providing a quantitative score before any potential human override.
7. Type of Ground Truth Used
The ground truth used for both the Digital Read and Image Analysis studies was expert consensus (specifically, manual microscopic reads) by qualified pathologists. The manual score was explicitly stated as the "reference result" or "true score."
8. Sample Size for the Training Set
The document does not provide any information regarding the sample size used for the training set of the Virtuoso™ System's image analysis algorithms. This information is typically found in the development and validation sections, which are not detailed in this 510(k) summary.
9. How Ground Truth for the Training Set Was Established
The document does not provide any information on how the ground truth for the training set was established.
§ 864.1860 Immunohistochemistry reagents and kits.
(a)
Identification. Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.