(272 days)
The ADVIA Centaur EBV-EBNA IgG (EBVnaG) assay is for in vitro diagnostic use in the qualitative detection of IqG antibodies to Epstein-Barr virus (EBV) nuclear antigen (EBNA) in human pediatric (2-21 years old) and adult serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur XP system. When used in conjunction with other EBV markers, this assay is intended for use as an aid in the diagnosis of Epstein-Barr virus infection, such as infectious mononucleosis.
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The provided text describes the performance of the ADVIA Centaur EBV-EBNA IgG assay, an in vitro diagnostic device for the qualitative detection of IgG antibodies to Epstein-Barr virus (EBV) nuclear antigen (EBNA).
Here's an analysis of the acceptance criteria and study data:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the ADVIA Centaur EBV-EBNA IgG assay are primarily demonstrated through its agreement with an FDA-cleared reference EBV EBNA IgG assay. While explicit "acceptance criteria" are not listed with numerical thresholds in a dedicated table, the clinical study results (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA) are implicitly compared against an expectation of substantial equivalence to the predicate device.
For precision and reproducibility, specific targets are mentioned.
| Performance Metric | Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Clinical Study | Substantial Equivalence to Predicate Device (LIAISON EBNA IgG) | Population 1 (Total Study Population - symptomatic individuals) |
- NPA: 92.8% (95% CI: 89.6% - 95.1%)
- PPA: 99.4% (95% CI: 98.8% - 99.7%)
Population 2 (Known EBV EBNA IgG negative individuals)
- NPA: 98.2% (95% CI: 94.9% - 99.4%)
Pediatric Population (Population 1 - symptomatic)
- NPA: 97.3% (95% CI: 94.3% - 98.8%)
- PPA: 98.4% (95% CI: 96.0% - 99.4%)
Pediatric Population (Population 2 - known negative)
- NPA: 100% (95% CI: 94.9% - 100%) |
| Precision | Not explicitly stated as a single value, but individual sample CVs are presented. | Serum Samples: Total Precision CVs range from 4.4% to 13.3%.
Plasma, EDTA Samples: Total Precision CVs range from 4.3% to 9.5%.
Controls: Control 1 (0.32 Index) Total Precision SD 0.014; Control 2 (3.16 Index) Total Precision CV 4.1%. |
| Reproducibility | - Concentration $\le$ 0.80 Index: N/A (for CV) - Concentration > 0.80 Index: $\le$ 20.0% CV | Serum Samples:
- Serum A (0.77 Index): SD 0.048, CV N/A (within $\le$ 0.80 Index)
- Serum B-E (1.07 to 8.85 Index): CVs range from 4.0% to 9.8% (all $\le$ 20.0%)
Plasma, EDTA Samples: - Plasma A (0.78 Index): SD 0.044, CV N/A (within $\le$ 0.80 Index)
- Plasma B-E (1.06 to 8.75 Index): CVs range from 5.0% to 10.7% (all $\le$ 20.0%)
Controls: Control 1 (0.36 Index) SD 0.022, CV N/A; Control 2 (3.31 Index) CV 4.0%. |
| Specimen Equivalency | Regression equation close to y=x, high correlation coefficient (r). | EDTA Plasma vs. Serum: y = 1.00x - 0.01 Index; r = 1.00
Lithium Heparin Plasma vs. Serum: y = 0.98x - 0.01 Index; r = 0.99
Conclusion: EDTA Plasma and Lithium Heparin Plasma are equivalent matrixes to Serum. |
| Interferences | ±10% bias for reactive samples and ±0.10 Index for nonreactive samples. | The listed substances (Hemoglobin, Bilirubin, Lipemia, Biotin, Cholesterol, Protein, etc.) do not interfere at the indicated concentrations. |
| Cross-reactivity | Not explicitly stated as a numerical criterion, but demonstrated by testing against various viral antibodies and disease states. | Data presented for 330 samples across 29 clinical categories, showing agreement or defined discrepancies with the comparative assay. For HCV, Mycoplasma pneumoniae IgG, HSV-1 IgG, and HSV-2 IgG, possible cross-reactivity cannot be excluded for a few discordant samples and should be interpreted clinically. |
| Onboard Stability | 28 days for reagents, 28 days for calibration. | Reagents: 28 days. Calibration: 28 days. |
| Calibrator Stability (Opened Vial) | 60 days when stored at 2-8ºC. | 60 days when stored at 2-8ºC. |
| Unopened Reagents/Calibrators Stability | Until expiration date when stored at 2-8°C. | Until expiration date when stored at 2-8°C. |
2. Sample Size and Data Provenance
Clinical Study (Test Set):
- Total Study Population (Population 1): 1428 leftover samples.
- Provenance: Collected over a contiguous time period from individuals for whom an EBV test was ordered. The document does not specify the country of origin but implies a clinical setting ("symptoms and signs for whom an EBV antibody test was ordered"). It is a retrospective collection of leftover samples.
- Known EBV EBNA IgG Negative Population (Population 2): 167 samples.
- Provenance: Samples with a known EBV EBNA IgG negative result, used to supplement numbers for negative EBV EBNA IgG. Retrospective.
- Pediatric Population: Subsets of Population 1 (479 samples including 84 unclassified serostatus individuals) and Population 2 (72 samples including 6 unclassified serostatus individuals).
- Cross-reactivity Study: 330 samples across various clinical categories.
- Specimen Equivalency Study: 97-98 sets of matched samples (SST, EDTA plasma, lithium heparin plasma).
- Provenance: Commercial sources.
3. Number of Experts and Qualifications for Ground Truth
The document explicitly states that the ground truth for the clinical study was established by an "FDA cleared EBV EBNA IgG reference assay."
It also states: "Equivocal reference assay results were resolved by 2 other comparative assays."
- Number of 'Experts' (resolving assays): 2 (for equivocal cases from the primary reference assay).
- "Qualifications" of these 'experts': These were "comparative assays" rather than human experts. The document does not specify if these were other FDA-cleared assays or the nature of their qualification, but the implication is that they served as a consensus mechanism to resolve indeterminate results from the primary reference assay.
4. Adjudication Method for the Test Set
The adjudication method for equivocal results from the primary reference assay was by "2 other comparative assays." This is a form of 2+0 or 1+2 (primary reference + 2 comparative). If the two comparative assays agreed, that likely established the reconciled ground truth for the equivocal samples. The document does not describe what happened if the two comparative assays disagreed.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic assay, which typically does not involve human readers interpreting images or data alongside AI. The device is evaluated for its analytical and clinical performance against a reference method. Therefore, there is no information on how much human readers improve with AI vs. without AI assistance.
6. Standalone (Algorithm only without human-in-the loop performance)
Yes, a standalone performance study was done. The entire clinical study, precision, reproducibility, specimen equivalency, and interference studies evaluate the performance of the ADVIA Centaur EBV-EBNA IgG assay as a standalone device (algorithm/assay only) against a reference method or predetermined analytical specifications. There is no human-in-the-loop component described for its primary intended use and evaluation.
7. Type of Ground Truth Used
The ground truth used for the clinical study was based on an FDA-cleared EBV EBNA IgG reference assay, with equivocal results resolved by 2 other comparative assays. This indicates a reference method or comparative assay-based ground truth.
8. Sample Size for the Training Set
The document is a 510(k) summary for an in vitro diagnostic assay. It does not provide information regarding a "training set" in the context of machine learning or AI models.
The samples mentioned are for performance evaluation (clinical study, precision, etc.) and are analogous to test or validation sets. For IVD devices, a "training set" might refer to samples used during the development and optimization of the assay's reagents and parameters, but this information is not typically disclosed in a 510(k) summary in this format.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" described in the context of an AI/ML model for this IVD assay according to the provided document, this information is not applicable and not available.
§ 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).