(427 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. CONFIRM™ 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 CONFIRM™ 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.
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.
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 a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
| Metric | Acceptance Criteria (Predetermined) | Reported Device Performance (Digital Read) | Reported Device Performance (Image Analysis) |
|---|---|---|---|
| Positive Percent Agreement (PPA) | 75% | 94.4% (95% CI: 86.6-97.8) | 95.9% (95% CI: 88.7-98.6) |
| Negative Percent Agreement (NPA) | 75% | 97.6% (95% CI: 87.4-99.6) | 97.5% (95% CI: 87.1-99.6) |
| Overall Percent Agreement (OPA) | 75% | 95.6% (95% CI: 90.1-98.1) | 96.5% (95% CI: 91.3-98.6) |
As stated in the document, "The overall agreement between the digital read and the manual read was 95.6%, the overall agreement between image analysis and the manual read was 96.5%, and the predetermined acceptance criterion for each measurement of 75% has been met."
Study Details
2. Sample size used for the test set and the data provenance
- Sample Size: Approximately 120 cases. For the Digital Read analysis, 113 cases were analyzed. For the Image Analysis, 114 cases were analyzed.
- Data Provenance: The document does not explicitly state the country of origin. It was a retrospective study as it compares different assessment methods of already prepared slides.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Number of Experts: One pathologist.
- Qualifications of Experts: The document specifies "one pathologist" but does not explicitly state their experience level (e.g., "10 years of experience"). It implies they are a "qualified pathologist."
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Adjudication Method: Not explicitly stated as a formal adjudication process involving multiple pathologists. The ground truth ("manual score") was established by a single pathologist performing a routine microscopic read.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- MRMC Study: No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not explicitly described. The study involved one pathologist evaluating cases in three different ways (manual, digital read, image analysis).
- Effect Size of Human Improvement with AI: This study does not provide data on the effect size of how much human readers improve with AI assistance. It focuses on the concordance between the digital methods (digital read and image analysis) and the manual read by a single pathologist.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Standalone Performance: Yes, the "Image Analysis Read" data in the table represents the performance of the algorithm as an aid to the pathologist. While the pathologist selected the fields of view, the scores themselves are generated by the software. The document also states "The software makes no independent interpretations of the data and requires competent human intervention for all steps in the analysis process." This implies it's not a purely standalone, fully automated system without human oversight, but the "Image Analysis Read" itself is the algorithmic output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- Type of Ground Truth: Expert individual pathologist's manual microscopic read ("manual score").
8. The sample size for the training set
- Training Set Sample Size: The document does not provide information about the sample size used for the training set of the Virtuoso software. The study described is a clinical validation study, not a development or training study.
9. How the ground truth for the training set was established
- Ground Truth for Training Set: The document does not explain how the ground truth for the training set was established, as it does not detail the training phase of the algorithm.
§ 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.