(379 days)
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EliA RF IgM is intended for the in vitro quantitative measurement of IgM class rheumatoid factor antibodies in human serum and plasma (Li-heparin, EDTA; citrate ) to aid in the diagnosis of rheumatoid arthritis in conjunction with other laboratory and clinical findings. EliA RF IgM uses the EliA IgM method on the instruments Phadia 100 and Phadia 250.
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EliA RF IgA is intended for the in vitro quantitative measurement of IgA class rheumatoid factor antibodies in human serum and plasma (Li-heparin, EDTA, citrate) to aid in the diagnosis of rheumatoid arthritis in conjunction with other laboratory and clinical findings. EliA RF IgA uses the EliA IgA method on the instruments Phadia 100 and Phadia 250.
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EliA RF Positive Control 100 is intended for laboratory use in monitoring the performance of in vitro measurement of rheumatoid factor (RF) with Phadia 100 using the EliA IgM or IgA method.
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EliA RF Positive Control 250 is intended for laboratory use in monitoring the performance of in vitro measurement of rheumatoid factor (RF) with Phadia 250 using the EliA IgM or lgA method.
The new devices belong to a fully integrated and automated system for immunodiagnostic testing. It comprises a Fluorescence-Immunoassay test system using EliA single wells as the solid phase and is intended to be performed on the instruments Phadia 100 and Phadia 250.
The conjugate for the EliA IgM method is mouse anti-human IgM beta-galactosidase, which uses 4-Methylumbellifery1-BD-Galactoside as substrate.
The conjugate for the EliA IgA method is mouse anti-human IgA beta-galactosidase, which uses 4-Methylumbelliferyl-BD-Galactoside as substrate.
The total IgM and IgA calibration is based on a set of six WHO-standardized IgM and IgA Calibrators, respectively, derived from human serum. They are used to establish an initial calibration curve, which may be used for up to 28 days on additional assays and can be stored by the instrument. Each additional assay includes calibrator (curve) controls that have to recover in defined ranges to ensure that the stored calibration curve is still valid. The Fluorescence-Immunoassay test system includes test-, method-specific and general reagents that are packaged as separate units.
The provided document describes the EliA™ RF IgM Immunoassay and EliA™ RF IgA Immunoassay, along with their respective positive controls, for aiding in the diagnosis of rheumatoid arthritis. The study provided focuses on establishing laboratory equivalence to a predicate device, rather than defining specific acceptance criteria for diagnostic performance metrics like sensitivity or specificity against a clinical ground truth.
Here's an analysis based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state numerical acceptance criteria in terms of diagnostic performance metrics (e.g., sensitivity, specificity, accuracy) that the device must meet against a predefined standard of truth. Instead, the study's goal was to demonstrate laboratory equivalence to existing predicate devices.
The "reported device performance" is summarized conceptually as:
| Criterion Type | Acceptance Criterion (Implicit) | Reported Device Performance |
|---|---|---|
| Laboratory Equivalence to Predicate Device | The new devices (EliA™ RF IgM and EliA™ RF IgA) should demonstrate comparable performance to their respective predicate devices (Quanta Lite Rf IgM Elisa and Quanta Lite Rf IgA Elisa) across various sample types (comparison study, clinically defined sera, healthy subjects). This implies similar quantitative results and clinical interpretations. | "In summary, all available data support that the new devices are substantially equivalent to the predicate devices." (No specific numerical metrics are provided in this summary section.) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document mentions "a comparison study between new and predicate device," "results obtained for clinically defined sera," and "results obtained for samples from apparently healthy subjects (normal population)." However, the exact numerical sample sizes for these test sets are not provided.
- Data Provenance: The document does not specify the country of origin for the data. The study appears to be retrospective, as it involves comparing results from existing serum and plasma samples with the new devices against predicate devices.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not describe the establishment of a "ground truth" for the test set in the traditional sense of expert consensus on patient diagnosis. Instead, the study aims to establish equivalence to predicate devices. The "clinically defined sera" used would have implicit ground truth based on their clinical diagnosis of rheumatoid arthritis, but the process of establishing this clinical diagnosis (e.g., how many experts, their qualifications) is not detailed. It's likely these were pre-diagnosed samples.
4. Adjudication Method for the Test Set
Since the study focuses on laboratory equivalence to predicate devices and not on establishing a new diagnostic ground truth by expert review, an adjudication method (like 2+1 or 3+1) for diagnosing patients within the test set is not applicable and not mentioned.
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
This section is not applicable to this device. The EliA™ RF immunoassays are in vitro diagnostic devices that measure specific antibodies in patient samples. They are not AI-powered devices that assist human readers (e.g., radiologists) in interpreting medical images or other complex data. Therefore, an MRMC study and the concept of "human readers improving with AI assistance" are outside the scope of this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The EliA™ RF immunoassays are standalone devices in the sense that they provide quantitative measurements of RF IgM and IgA levels directly. The "algorithm" here is the biochemical assay and the instrument's software for calculating results from fluorescence measurements. Their performance is evaluated independently of human interpretation of the raw assay signal (though a clinician then interprets the final quantitative result). The study described focuses on this standalone performance in comparison to predicate devices.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The primary "ground truth" for the comparison study is the results obtained from the legally marketed predicate devices. For the "clinically defined sera," the ground truth would be the clinical diagnosis of Rheumatoid Arthritis established by treating physicians using a combination of clinical findings and other laboratory tests. For "samples from apparently healthy subjects," the ground truth is the absence of Rheumatoid Arthritis. The method by which these clinical diagnoses were originally established (e.g., based on ACR/EULAR criteria, pathology, long-term outcomes) is not specified in this document.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" sample size. For immunoassay development, "training" typically refers to the development and optimization of the assay itself, selection of reagents, and establishment of calibration curves. The document mentions that the total IgM and IgA calibration is based on a set of six WHO-standardized IgM and IgA Calibrators, but this is for calibration, not a "training set" in the context of machine learning.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" in the machine learning sense is described, the question of how its ground truth was established is not applicable. The "ground truth" for the instrument's calibration is based on WHO-standardized IgM and IgA Calibrators, which are reference materials with known concentrations.
§ 866.5775 Rheumatoid factor immunological test system.
(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).