(142 days)
For the qualitative determination of IgM antibodies in human serum to Epsien Barr Virus (recombinant) Nuclear antigen (EBNA-1) antigen. The 78 EBNA-1 IgM assay should be used in conjunction with other Epstein-Barr serologies (VCA IgM, VCA IgG, EA-D IgG, EBNA-1 IgG and heterophile) as an aid in the diagnosis of infectious mononucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS TM Automated EIA Processor.
The & EBNA-1 IgM ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies to Epstein-Barr Nuclear antigen-1 in human serum.
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
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Clinical Performance | Relative Specificity (Convalescent): High accuracy in identifying individuals who have had a past EBV infection (negative for current infection markers). | 97.0% (95% CI: 91.6-99.4) |
| Relative Sensitivity (Current Infection): High accuracy in identifying individuals with a current (recent) EBV infection (positive for current infection markers). | 59.5% (95% CI: 42.1-75.3) | |
| Relative Specificity (Seronegative): High accuracy in identifying individuals who have never been infected with EBV (negative for all EBV markers). | 100.0% (95% CI: 89.1-100.0) | |
| Overall Agreement: General concordance with the established EBV serological status across all characterized sera. | 89.4% (95% CI: 84.8-94.0) | |
| Precision | Intra-Assay and Interassay Precision (Site #1, 2, 3): Consistent results within a single run and across multiple runs at individual sites for positive and negative sera, indicating reliability and reproducibility of the assay. (Implicitly, CV% values should be within an acceptable range, although specific numerical acceptance criteria are not explicitly stated. The provided CV% values are reported.) | Site #1: Interassay CV% range for positive sera: 4.85-10.00%; negative sera: 16.74-44.75%. Site #2: Interassay CV% range for positive sera: 5.75-6.51%; negative sera: 15.67-34.34%. Site #3: Interassay CV% range for positive sera: 4.43-22.09%; negative sera: 23.91-62.45%. |
| Inter-Site Precision: Consistent results across different testing sites, indicating robustness of the assay across various laboratory environments. (Implicitly, CV% values should be within an acceptable range.) | Inter-site CV% range for positive sera: 6.80-14.33%; negative sera: 10.37-39.85%. | |
| Cross-Reactivity | Specificity with Potentially Cross-Reactive Sera: Minimal false positives when tested against samples known to be positive for other common viral infections (Varicella Zoster, Cytomegalovirus, Herpes Simplex Virus IgM). The expectation is that the EBNA-1 IgM Test Kit should not react with these other antibodies. (Implicitly, a low number of cross-reactive results is desired.) | Some cross-reactivity expected: 2/5 anti-CMV IgM positive sera were non-reactive for anti-EBNA-1 IgM, 4/4 anti-VZV IgM positive sera were non-reactive, and 4/4 anti-HSV positive sera were non-reactive. This phrasing suggests some reactivity with CMV was observed, but the non-reactive counts imply a level of specificity. |
| Automation Equivalence | Correlation of Manual and MAGO Plus Results: Strong positive correlation between results obtained manually and those obtained using the MAGO Plus™ Automated EIA Processor, demonstrating that the automated system provides equivalent results to the manual method. (Implicitly, high Pearson Correlation Coefficient and close agreement.) | Pearson Correlation Coefficient of 0.985 with a linear regression of Y = 0.0186 + 0.9826 X. |
| MAGO Plus Precision: Consistent results (intra-assay and interassay precision) when the assay is performed on the MAGO Plus Automated EIA Processor. (Implicitly, CV% values should be within an acceptable range for automated use). | Interassay CV% range for positive sera: 8.11-10.15%; negative sera: 6.88-66.58%. |
Study Details
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Test Set Sample Size and Data Provenance:
- Sample Size: 176 sera.
- Data Provenance: Frozen retrospective sera from patients.
- Country of Origin: Not specified.
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Experts Used for Ground Truth and Qualifications:
- The text does not specify the number of experts used to establish the ground truth or their qualifications.
- The "ground truth" was established by characterizing the sera using commercially available kits for VCA IgM, VCA IgG, EBNA-1 IgG, and heterophile antibodies, and then classifying them into "convalescent," "current infection," or "seronegative" based on the results of this testing.
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Adjudication Method for the Test Set:
- The text does not describe an adjudication method for the test set. The characterization of sera appears to be based on the results of multiple commercial assays rather than a human consensus process.
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Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic test, and the study evaluated its performance against established serological markers, not against human readers with and without AI assistance.
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Standalone (Algorithm Only) Performance:
- Yes, a standalone performance study was done. The entire clinical performance section evaluates the device (the EBNA-1 IgM ELISA Kit) directly against the characterized sera without human-in-the-loop assistance for the interpretation of the EBNA-1 IgM ELISA results. Human interpretation was part of the "ground truth" establishment using other assays, but the device's output (positive, negative, equivocal) was directly compared.
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Type of Ground Truth Used:
- Expert Consensus (indirectly) / Reference Comparator Assay Results: The ground truth was established by classifying patient sera based on the results of multiple commercially available EBV serology kits (VCA IgM, VCA IgG, EBNA-1 IgG, and heterophile antibodies). This is a form of reference standard based on accepted laboratory diagnostics.
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Training Set Sample Size:
- The document does not specify a training set sample size. This is typical for traditional ELISA kits, where optimization and assay development are performed, but a distinct "training set" for an algorithm in the modern AI sense is not applicable. The device's parameters (e.g., cut-offs) would have been established during its development phase.
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How Ground Truth for Training Set Was Established:
- As there is no distinct "training set" in the AI sense for this device, the concept of establishing ground truth for it is not directly applicable. The development of the assay (e.g., determining optimal concentrations, incubation times, and cut-off values) would have involved extensive experimentation and standardization using characterized samples, similar to how the ground truth for the test set was established using comparator assays.
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).