(123 days)
For the qualitative and semi-quantitative detection of IgG antibodies to Varicella-Zoster Virus (VZV) in human serum by indirect immunoassay to determine a prior exposure to VZV and, when evaluating paired sera, to aid in the determination of acute or convalescent stage of VZV infection. These reagents can be used either manually or in conjunction with the MAGO® Plus Automated EIA Processor.
The Is-VZV IgG Test System is an enzyme immunoassay (EIA) for the detection and semi-quantitation of IgG antibodies to VZV antigen in human serum
The Diamedix Is-VZV IgG Test System is an enzyme immunoassay (EIA) intended for the qualitative and semi-quantitative detection of IgG antibodies to VZV antigen in human serum. Its purpose is to determine prior exposure to VZV and, when evaluating paired sera, to assist in identifying the acute or convalescent stage of VZV infection. The device can be used manually or with the MAGO Plus Automated EIA Processor.
Here's an analysis of the acceptance criteria and study proving its performance:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Is-VZV IgG Test System are implicitly demonstrated through its "relative" performance compared to other commercially available EIA test kits. While explicit numerical acceptance targets are not stated, the study demonstrates satisfactory performance within specific ranges for sensitivity, specificity, and agreement. The table below summarizes the reported performance for each site and method.
| Performance Metric | Site #1 (Manual) - Is-VZV IgG vs. Other EIA | Site #2 (Manual) - Is-VZV IgG vs. Other EIA | Site #3 (Manual) - Is-VZV IgG vs. Other EIA | Site #3 (MAGO Plus) - Is-VZV IgG vs. Other EIA |
|---|---|---|---|---|
| Relative Sensitivity | 99.4% (95% CI: 96.8-100.0) | 97.6% (95% CI: 94.0-99.3) | 98.3% (95% CI: 95.0-99.6) | 99.4% (95% CI: 96.8-100.0) |
| Relative Specificity | 100.0% (95% CI: 85.2-100.0) | 100.0% (95% CI: 82.4-100.0) | 97.1% (95% CI: 90.1-99.7) | 93.1% (95% CI: 84.5-97.7) |
| Overall Agreement | 99.5% (95% CI: 97.2-100.0) | 97.9% (95% CI: 94.6-99.4) | 97.9% (95% CI: 95.2-99.3) | 97.6% (95% CI: 94.8-99.1) |
Additional Performance Metrics:
- Correlation of Manual and MAGO Plus Results:
- Correlation Coefficient (r): 0.972 (demonstrating good correlation between manual and automated methods for 253 serum samples).
- Linearity/Dynamic Range:
- R values for serial dilutions: 0.972 to 0.999.
- Reportable range: 20-100 EU/ml.
- Semi-Quantitative Data (Ratios for Dilutions):
- Overall mean ratio for 4-fold dilutions: 3.13 (SD 0.35).
- Overall mean ratio for 2-fold dilutions: 1.77 (SD 0.15).
- Estimated ratio for significant increase: 2.8-fold or greater (mean ratio minus 1 SD).
- Cross-Reactivity: No cross-reactivity observed with IgG antibodies to HSV, Measles, Rubella, or CMV in samples negative for VZV.
- Precision (Interassay CV%):
- Site #1 (Manual): Range from 2.20% (Serum F) to 12.50% (Negative Control).
- Site #2 (Manual): Range from 5.45% (Calibrator) to 28.89% (Negative Control).
- Site #3 (Manual): Range from 4.40% (Positive Control) to 12.35% (Negative Control).
- Site #3 (MAGO Plus): Range from 7.03% (Serum F) to 45.93% (Negative Control).
- Inter-Site Precision (Manual): Range from 2.67% (Calibrator) to 20.00% (Negative).
2. Sample Size Used for the Test Set and Data Provenance
A total of 652 sera were tested across three independent sites:
- Site #1 (Miami, FL): 200 sera (all frozen). Samples obtained from the S. Florida area.
- Site #2 (Salt Lake City, Utah): 198 sera (all fresh). Samples obtained from the Mid-West region.
- Site #3 (Diamedix Corp., Miami FL): 254 samples (all frozen) tested manually, and 253 of these samples tested using the MAGO Plus. Samples were selected, with 74 specifically chosen for negative or near-cutoff values, and the remainder from the normal S. Florida blood donor population.
The data provenance is retrospective, as existing serum samples were used. The country of origin for the data is the United States (S. Florida area, Mid-West region).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The study does not specify the number or qualifications of experts used to establish a ground truth. Instead, the performance of the Diamedix Is-VZV IgG Test Kit is compared to "another commercially available EIA test kit" (referred to as "Other EIA"). Referee EIA methods were used for discordant samples. The document explicitly states: "There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease." This indicates that the "ground truth" was essentially the result of a comparative reference assay rather than clinical expert consensus or pathology.
4. Adjudication Method for the Test Set
The adjudication method involved testing discordant samples with a "referee EIA method."
- For Site #1, the single discordant sample was equivocal by the referee EIA.
- For Site #2, discordant sera were not available for further resolution.
- For Site #3 (manual testing), two samples positive by Is-VZV IgG and negative by the other EIA were negative by the referee EIA. For three samples negative by Is-VZV IgG and positive by the other EIA, one was negative, one equivocal, and one positive by the referee method.
- For Site #3 (MAGO Plus testing), five samples positive by Is-VZV IgG and negative by the other EIA were negative by the referee EIA. The one sample negative by Is-VZV IgG and positive by the other EIA was negative by the referee EIA.
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 is not applicable. The device is an automated in vitro diagnostic (IVD) test for detecting antibodies in human serum. It is not an AI-assisted diagnostic device that would involve human readers or image interpretation. Therefore, an MRMC study with human readers and AI assistance was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The primary performance studies (comparison testing) evaluate the Is-VZV IgG Test System in a standalone capacity (i.e., the performance of the test kit itself) against another commercially available EIA. The manual method and the MAGO Plus Automated EIA Processor are both standalone in terms of the test's output. There is no "human-in-the-loop" interaction for interpretation or further decision-making as would be seen with an AI diagnostic. The studies compare the device's results to a reference method's results.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The ground truth used was the result obtained from "another commercially available EIA test kit" and, for discordant samples, a "referee EIA method." There is no mention of expert consensus, pathology, or outcomes data being used to establish a definitive ground truth for VZV infection status. The studies are explicitly described as "relative" comparisons to other assays, not correlations with disease presence or absence.
8. The Sample Size for the Training Set
This information is not provided. The document describes a performance evaluation of a medical device (an IVD kit), not a machine learning or AI algorithm that would typically involve a separate training set. The comparison testing utilized the described 652 sera as a test set for performance validation.
9. How the Ground Truth for the Training Set Was Established
This information is not provided and is not applicable given that this is a performance evaluation of an IVD kit, not an AI or machine learning model that requires a distinct training set with established ground truth.
§ 866.3900 Varicella-zoster virus serological reagents.
(a)
Identification. Varicella-zoster virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to varicella-zoster in serum. The identification aids in the diagnosis of diseases caused by varicella-zoster viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild, highly infectious disease, chiefly of children. Zoster (shingles) is the recurrent form of the disease, occurring in adults who were previously infected with varicella-zoster viruses. Zoster is the response (characterized by a rash) of the partially immune host to a reactivation of varicella viruses present in latent form in the patient's body.(b)
Classification. Class II (performance standards).