(142 days)
For the qualitative determination of IgM antibodies in human serum to Epstein Barr (recombinant) Viral Capsid antigen (EBV-VCA) antigen. The EBV-VCA IgM assay should be used in conjunction with other Epstein-Barr serologies (EBV-VCA IgG, EBNA-1 IgG, EA-D IgG, EA-D IgM, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious monomucleosis. The test can be performed either manually or in conjunction with the MAGO PLUS ™ Automated EIA Processor.
The & EBV-VCA IgM ELISA Kit is an enzyme-linked immunosorbent assay (ELISA) for the detection of IgM antibodies to Epstein-Barr Viral Capsid antigen in human serum.
Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
Device Name: EBV-VCA IgM ELISA Kit (also referred to as Is-EBV-VCA IgM Test Kit and 7 VCA IgM ELISA)
| Acceptance Criteria Category | Specific Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|---|
| Clinical Performance | Relative Specificity (Convalescent) | High specificity (specific threshold not explicitly stated but implied by high performance) | 97.0% (95% CI: 91.6-99.4) |
| Relative Sensitivity (Current Infection) | High sensitivity (specific threshold not explicitly stated but implied by high performance) | 95.0% (95% CI: 83.1-99.4) | |
| Relative Specificity (Seronegative) | High specificity (specific threshold not explicitly stated but implied by high performance) | 100% (95% CI: 89.1-100) | |
| Overall Agreement (with predicate/characterized sera) | High agreement (specific threshold not explicitly stated but implied by high performance) | 97.1% (95% CI: 93.4-99.1) | |
| Precision | Intra-assay Precision (CV%) | Low variability (threshold not explicitly stated) | Site #1: Positive sera CV% = 6.07-9.92; Negative sera CV% = 8.51-49.37 (higher for negatives, especially low index ones) |
| Site #2: Positive sera CV% = 3.95-6.35; Negative sera CV% = 7.41-17.42 | |||
| Site #3: Positive sera CV% = 4.15-6.22; Negative sera CV% = 7.16-12.82 | |||
| MAGO Plus: Positive sera CV% = 3.53-9.27; Negative sera CV% = 0.00-22.59 (0.00 for one low negative, likely due to rounding or being below detection) | |||
| Interassay Precision (CV%) | Low variability (threshold not explicitly stated) | Site #1: Positive sera CV% = 12.05-13.69; Negative sera CV% = 22.75-39.31 | |
| Site #2: Positive sera CV% = 6.53-7.34; Negative sera CV% = 9.38-14.80 | |||
| Site #3: Positive sera CV% = 5.08-5.80; Negative sera CV% = 12.70-13.26 | |||
| MAGO Plus: Positive sera CV% = 4.55-8.64; Negative sera CV% = 17.76-0.00 (0.00 for one low negative, likely due to rounding or being below detection) | |||
| Inter-Site Precision (CV%) | Low variability (threshold not explicitly stated) | Positive sera CV% = 11.13-13.43; Negative sera CV% = 20.69-28.77 (NC has 60.11%, likely due to very low index values making CV% highly sensitive) | |
| Cross-Reactivity | Specificity with Potentially Cross-Reactive Sera | Minimal cross-reactivity expected | Some cross-reactivity is suggested: 1/4 anti-VZV IgM positive sera were reactive for anti-VCA IgM; 2/5 anti-CMV IgM positive sera were reactive for anti-VCA IgM. 4/4 anti-HSV positive sera were non-reactive. Results indicate that some specific cross-reactivity should be expected with VZV and CMV. |
| Method Correlation | Manual and MAGO Plus Results Correlation | Strong correlation (specific threshold not explicitly stated but implied by high performance) | Pearson Correlation Coefficient = 0.990 (indicating strong positive correlation) |
Study Details Proving Acceptance Criteria
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Sample Size used for the test set and the data provenance:
- Clinical Sensitivity and Specificity: 176 frozen retrospective sera. The provenance (country of origin) is not explicitly stated, but it's referred to as "sera from one hundred and seventy-six patients" which suggests human samples. The study explicitly states it was a "pre-selected, retrospective, population."
- Precision:
- Intra-assay and Interassay Precision: Four positive and two negative sera (6 unique sera) were assayed 10 times each, in 3 different runs. This was done at 3 different sites.
- Inter-Site Precision: The document mentions n=90 for serum samples A-F (presumably 90 total measurements across sites for each serum type, or 3 sites * 3 runs * 10 replicates = 90 total for each serum type), and n=36 for CAL (Calibrator), n=18 for LPC (Low Positive Control), n=18 for NC (Negative Control).
- Specificity with Potentially Cross-Reactive Sera: 13 sera.
- Correlation of Manual and MAGO Plus Results: 120 serum samples.
- MAGO Plus Precision: Six sera were assayed 10 times each in 3 different runs (similar to the manual precision study).
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For the "Clinical Sensitivity and Specificity Using Characterized Sera" section, the sera were "characterized using commercially available kits for VCA IgM, VCA IgG, EBNA IgG and heterophile antibodies." This implies an established laboratory testing method rather than human expert opinion directly establishing ground truth for individual cases. No human experts are explicitly mentioned for ground truth establishment.
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Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned. The ground truth was established by comparing to results from "commercially available kits" for other EBV serologies.
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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:
- This is not an MRMC study. The device is an ELISA kit, which is an in vitro diagnostic (IVD) test, not an AI-assisted diagnostic tool for human readers. There is no mention of human readers or AI assistance in this context. The comparison is between the new EBV-VCA IgM ELISA Kit and existing commercial kits/methods.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, for the EBV-VCA IgM ELISA Kit, the performance data provided (sensitivity, specificity, precision, cross-reactivity) represents the standalone performance of the diagnostic assay. This assay is a laboratory test, and its results are read and interpreted, but the performance characteristics apply to the kit itself.
- The "Correlation of Manual and MAGO Plus Results" section compares the standalone performance of the kit when processed manually versus using an automated EIA processor (MAGO Plus). Both are "standalone" in the sense of the chemical assay's performance.
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The type of ground truth used:
- Clinical Performance: "EBV Serological Status" derived from other "commercially available kits for VCA IgM, VCA IgG, EBNA IgG and heterophile antibodies." This is a lab result-based ground truth (or predicate method comparison) rather than pathology, clinical outcome, or expert consensus on a subjective measure. The document explicitly states: "There was not an attempt to correlate the assay's results with disease presence or absence."
- Precision: Ground truth for positive/negative samples was pre-established (e.g., "four positive and two negative sera").
- Cross-Reactivity: Sera "reactive for IgM antibodies to varicella zoster, cytomegalovirus and herpes simplex virus by EIA". This is again a lab result-based ground truth to check for specific antibody interference.
- Correlation: Comparison between the manual and MAGO Plus results on the same samples.
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The sample size for the training set:
- The document does not explicitly describe a "training set" in the context of machine learning or AI. This is an in vitro diagnostic (IVD) assay. The development of such assays typically involves research and development where reagents and protocols are optimized. The "Characterized Sera" mentioned in the clinical performance section serves as the test set for the final validation of the device.
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How the ground truth for the training set was established:
- As no "training set" in the AI sense is explicitly mentioned, this question is not fully applicable. For the development and optimization of the ELISA kit itself, ground truth for sample characterization would have been established through well-characterized reference materials, clinical samples with known serological status using predicate methods, or samples from a disease registry. The "Characterized Sera" in the performance study were characterized using "commercially available kits for VCA IgM, VCA IgG, EBNA IgG and heterophile antibodies," which indicates the method used to establish the "ground truth" for those specific samples relative to established serological definitions.
§ 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).