(220 days)
The Applied Imaging Ariol™ is an automated scanning microscope and image analysis system. It is intended for in vitro diagnostic use as an aid to the pathologist in the detection, classification, and counting of cells of interest based on particular color, intensity, size, pattern, and shape.
This Hersight application is intended for use as an accessory to the HercepTest™ (DAKO USA, Carpinteria, CA) and is intended to provide semi-quantitative immunohistochemical (IHC) results to aid in the determination of HER-2/neu (HER2) over-expression in breast cancer tissues routinely processed for histological evaluation.
When used with DAKO HercepTest, it is indicated for use as an aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered. Note: The actual correlation of the DAKO HercepTest to Herceptin clinical outcome has not been established.
The Ariol system is an adjunctive computer-assisted methodology to assist the reproducibility of a qualified pathologist in the acquisition and measurement of images from microscope slides of breast cancer specimens stained for the presence of HER2 receptor protein. The accuracy of the test result depends upon 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 DakoCytomation HercepTest to assure the validity of the Ariol-assisted HER2 score.
The Applied Imaging Ariol™ is an automated scanning microscope and image analysis system.
The provided document is limited in the detail it provides regarding acceptance criteria and study particulars. However, I can extract the information that is present and indicate where details are missing.
Acceptance Criteria and Device Performance (Limited Information Available)
The document primarily states the device's intended use and substantial equivalence to a predicate device, rather than explicit acceptance criteria and corresponding performance metrics for a de novo marketing authorization. It presents performance in relation to a Human Reader (Pathologist) as an adjunctive computer-assisted methodology.
Based on the information provided, here's a table of what can be inferred/extracted:
| Acceptance Criteria Category | Specific Acceptance Criteria (Inferred/Stated) | Reported Device Performance |
|---|---|---|
| Intended Use | Aid to pathologist in detection, classification, and counting of cells based on color, intensity, size, pattern, and shape. | Intended for use as an accessory to the HercepTest™ to provide semi-quantitative IHC results to aid in determination of HER-2/neu (HER2) overexpression. |
| Accuracy (of HER2 score) | Aid in the assessment of breast cancer patients for whom Herceptin® (Trastuzumab) treatment is being considered. | "The accuracy of the test result depends upon the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist to employ appropriate morphological studies and controls... to assure the validity of the Ariol-assisted HER2 score." (This implies the device's contribution to accuracy is contingent on human pathologist oversight and proper staining, rather than a standalone accuracy claim demonstrated by the device itself.) |
| Reproducibility | Assist the reproducibility of a qualified pathologist in the acquisition and measurement of images. | No specific quantitative reproducibility metric is provided for the device itself; it is stated as assisting human reproducibility. |
Study Information from the Document:
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Sample size used for the test set and the data provenance:
- Test Set Sample Size: Not specified in the provided text.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective/prospective).
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Number of Experts: Not specified.
- Qualifications of Experts: The document refers to the role of a "qualified pathologist," but does not specify the number or specific qualifications (e.g., years of experience) for establishing ground truth in any study for this submission.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not specified.
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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:
- The document describes the Ariol system as an "adjunctive computer-assisted methodology" to "assist the reproducibility of a qualified pathologist." This strongly suggests the device is intended for use with a human-in-the-loop. However, the document does not provide details of an MRMC comparative effectiveness study or any effect size quantifying human improvement with AI assistance. It indicates the device provides "semi-quantitative immunohistochemical (IHC) results."
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- The document implies the device is not standalone. It is an "accessory" and an "adjunctive computer-assisted methodology" that assists a pathologist, and the "accuracy of the test result depends upon the quality of the immunohistochemical staining. It is the responsibility of a qualified pathologist...to assure the validity of the Ariol-assisted HER2 score." This indicates a human-in-the-loop system where the pathologist retains ultimate responsibility and oversight. No standalone performance data is presented.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The document does not explicitly state the type of ground truth used for any studies validating the device. However, given its intended use with HercepTest™ and pathologists, it highly implies that pathological assessment or expert consensus would be the basis for ground truth, but this is not detailed.
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The sample size for the training set:
- Not specified.
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How the ground truth for the training set was established:
- Not specified.
Summary of Missing Information:
The provided document is a 510(k) clearance letter, which typically focuses on demonstrating substantial equivalence to a predicate device rather than providing detailed clinical study reports or comprehensive performance data like a PMA submission would. Much of the specific information requested about acceptance criteria, study design parameters (sample sizes, expert details, adjudication methods), and detailed performance metrics (especially quantifying assist or standalone accuracy) is not present in this document. The emphasis is on the device's role as an aid or accessory to a pathologist, where the pathologist ultimately assures the validity of the score.
§ 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.