(163 days)
The Immunoscan CCPlus® test kit is an enzyme-linked immunosorbent assay (ELISA) for qualitative and semi-quantitative determination of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. The analysis should be performed by trained laboratory professionals. "For in vitro diagnostic use".
The Immunoscan CCPlus® test kit is a modification of the Immunoscan RA anti-CCP Test kit, K052133. It is an enzyme-linked immunosorbent assay (ELISA) for qualitative and semi-quantitative determination of IgG antibodies to Cyclic Citrullinated Peptides (CCP) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Rheumatoid Arthritis (RA), in conjunction with other laboratory and clinical findings. The analysis should be performed by trained laboratory professionals. "For in vitro diagnostic use".
The wells are coated with Cyclic Citrullinated Peptides. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.
The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase labelled antibodies to human IgG binds to the antibodies in the wells in this second incubation.
After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the colour intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units.
Here's a breakdown of the acceptance criteria and study information for the Immunoscan CCPlus® device, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance
The Immunoscan CCPlus® device is a modification of the Immunoscan RA anti-CCP Test kit and its performance is compared to this predicate device. The acceptance criteria are implicitly set by demonstrating substantial equivalence to the predicate device, implying that the modified device's performance characteristics should be similar to or better than the predicate's.
| Metric | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (Immunoscan CCPlus®) |
|---|---|---|
| Clinical Sensitivity | ~75.1% | 77.4% |
| Clinical Specificity | Between 94.1% - 100% | Between 94.1% - 100% |
| Intra-assay Precision (low %C.V.) | Anti-CCP: 34 - 1007 U/mL %C.V.: 4.3-12.8 | Anti-CCP: 28 - 2685 U/mL %C.V.: 1.0-7.6 |
| Inter-assay Precision (low %C.V.) | Anti-CCP: 33 - 1106 U/mL %C.V.: 6.0-17.7 | Anti-CCP: 28 - 2696 U/mL %C.V.: 2.1-12.2 |
| Lot to lot Precision (low %C.V.) | Anti-CCP: 29 - 1117 U/mL %C.V.: 3.8-12.2 | Anti-CCP: 60 - 2896 U/mL %C.V.: 6.9-17.0 |
| Detection Limit | Not explicitly stated for predicate in summary | 1.6 U/mL |
| Positive Percent Agreement | Not explicitly stated for predicate in summary | 99.3% (compared to predicate) |
| Negative Percent Agreement | Not explicitly stated for predicate in summary | 98.6% (compared to predicate) |
| Overall Percent Agreement | Not explicitly stated for predicate in summary | 98.9% (compared to predicate) |
Study Information
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Sample size used for the test set and the data provenance:
- Comparative Agreement Study (Immunoscan CCPlus® vs. Predicate):
- Sample Size: 628 frozen retrospective sera.
- Data Provenance: 368 samples from RA patients, 260 samples from apparently healthy blood donors. The country of origin is not specified but is likely Sweden, given the manufacturer's location. The data is retrospective.
- Clinical Sensitivity and Specificity Study (Immunoscan CCPlus®):
- Sample Size: 1180 frozen retrospective sera.
- Data Provenance: The origin of these samples is not specified beyond being "frozen retrospective sera with clinical characterisation." The distribution includes 399 patients with clinically defined RA and various control and disease groups. Country of origin not specified; data is retrospective.
- Comparative Agreement Study (Immunoscan CCPlus® vs. Predicate):
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document describes the use of "clinically defined RA" for the ground truth of RA patients and "apparently healthy blood donors" or "non-RA diseased patients" for controls.
- It does not specify the number of experts, their qualifications, or the process by which "clinical characterisation" or "clinically defined RA" was established. This suggests that the ground truth was based on pre-existing clinical diagnoses rather than a panel of experts reviewing the cases specifically for this study.
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Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned or implied for establishing the ground truth of the clinical samples. The "clinically defined RA" and control groups appear to have pre-determined diagnoses.
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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:
- No. This device is an in vitro diagnostic (ELISA) assay that directly measures antibodies. It does not involve human readers interpreting images or data alongside an AI, so an MRMC study is not applicable. The device provides a quantitative or semi-quantitative result directly.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device in the sense that the test results are generated by the assay without real-time human interpretation affecting the output. The assay produces a direct quantitative or semi-quantitative result for anti-CCP antibodies. The results are then used by trained laboratory professionals in conjunction with other clinical findings.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth for the clinical sensitivity and specificity study was based on clinical characterization/diagnosis, specifically "clinically defined RA" for the RA group and various diagnosed control groups (e.g., SLE, IBD, blood donors, etc.) for the non-RA groups. This implies a combination of clinical symptoms, other laboratory findings, and possibly imaging, leading to a physician's diagnosis. It is not explicitly stated to be expert consensus, nor pathology or direct outcomes data, but rather an established clinic diagnosis.
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The sample size for the training set:
- The document does not specify a training set. This is typical for traditional in-vitro diagnostic assays, which are usually developed using analytical methods and then validated with clinical samples, rather than "trained" in the machine learning sense. The information provided pertains solely to the validation/test sets.
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How the ground truth for the training set was established:
- Since no training set is mentioned for an algorithm, this question is not applicable. For an ELISA kit, development involves optimizing reagents and protocols against known positive and negative samples, but this isn't typically referred to as "training" in the same way as AI/ML.
§ 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).