(492 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 Virtuoso™ System for IHC PR (1E2) is for digital read and image analysis applications. This particular Virtuoso system is intended for use as an aid to the pathologist in the detection and semi-quantitative measurement of progesterone receptor (PR) protein in formalin-fixed, paraffin-embedded normal and neoplastic tissue. This device is an accessory to Ventana Medical Systems, Inc. CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay. The CONFIRM™ anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody assay is indicated for use as an aid in the assessment of breast cancer patients for whom endocrine treatment is being considered (but is not the sole basis for treatment).
Note: The IHC PR (1E2) Digital Read and Image Analysis applications are adjunctive computer-assisted methodologies for the qualified pathologist in the acquisition and measurement of images from microscope glass slides of breast cancer specimens stained for the presence of PR protein. The pathologist should verify agreement with the Image Analysis software application score. The accuracy of the test results depends on the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls as specified in the instructions for the CONFIRMTM anti-Progesterone Receptor (PR) (1E2) Rabbit Monoclonal Primary Antibody used to assure the validity of the Virtuoso System for IHC PR Digital Read and Image Analysis scores. The actual correlation of CONFIRM™ anti-PR antibody to clinical outcome has not been established.
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.
Here's an analysis of the acceptance criteria and study details based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Metric | Acceptance Criteria (Pre-determined) | Reported Device Performance (Digital Read) | Reported Device Performance (Image Analysis) |
|---|---|---|---|
| Overall Percent Agreement (OPA) | 75% | 95.6% (90.1-98.1% CI) | 96.5% (91.3-98.6% CI) |
| Positive Percent Agreement (PPA)* | Not explicitly stated (implied >75%) | 94.4% (86.6-97.8% CI) | 95.9% (88.7-98.6% CI) |
| Negative Percent Agreement (NPA)* | Not explicitly stated (implied >75%) | 97.6% (87.4-99.6% CI) | 97.5% (87.1-99.6% CI) |
Note: While PPA and NPA thresholds are not explicitly stated, the context of the 75% OPA suggests that these individual agreement metrics would also be expected to be above this threshold for the overall agreement to be met. The reported performance far exceeds this implied threshold.
2. Sample Size and Data Provenance
- Test Set Sample Size: Approximately 120 cases. The specific numbers reported in the tables are 113 for Digital Read and 114 for Image Analysis, likely due to a slight difference in cases included in the analysis after exclusions or variations in how certain cases were processed.
- Data Provenance: The document does not explicitly state the country of origin. It indicates the study was conducted "at one site." It was a retrospective study since the cases were "evaluated three ways" after staining.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts: One pathologist.
- Qualifications: "one pathologist" – no further specific qualifications (e.g., years of experience, sub-specialty) are provided in this document.
4. Adjudication Method for the Test Set
- Adjudication Method: "The manual score (reference result) was compared to both the digital read result and the image analysis result." This indicates a single-reader manual interpretation served as the ground truth against which both digital read and image analysis were compared. There was no explicit multi-reader adjudication process mentioned for establishing the "manual score" ground truth itself.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- Was an MRMC study done? No, an MRMC comparative effectiveness study, which typically compares human readers with and without AI assistance across multiple readers and cases to quantify improvement, was not explicitly described.
- Effect Size of Human Readers' Improvement with AI: Not applicable, as an MRMC study was not described. The study compared the device (digital read and image analysis) directly to the pathologist's manual read.
6. Standalone (Algorithm Only) Performance
- Was a standalone performance study done? Yes, the "Image Analysis" arm of the study specifically assessed the performance of the algorithm without direct human input beyond selecting fields of view. The results demonstrated a 96.5% Overall Percent Agreement with the manual read. The "Digital Read" arm assesses the pathologist's interpretation using the digital image, which is also a form of standalone performance of the digital viewing system, but with human-in-the-loop.
7. Type of Ground Truth Used
- Type of Ground Truth: Expert consensus, specifically a "manual score (reference result)" established by "one pathologist." This manual score was determined using a routine microscope.
8. Sample Size for the Training Set
- The document does not provide any information regarding the sample size of the training set. The clinical validation section focuses solely on the performance evaluation of the final device.
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.