(134 days)
The Viral Capsid Antigen (VCA) IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to VCA antigen. The Clark anti-VCA IgG assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgM, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis in a adult population.
The Epstein-Barr Viral Capsid Antigen (VCA) IgG kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to VCA antigen. The Clark anti-VCA IgG assay may be used in conjunction with other Epstein-Barr serologies (EA-D IgG, VCA IgM, EBNA-1 IgG, EBNA-1 IgM and heterophile) as an aid in the diagnosis of infectious mononucleosis. For In Vitro Diagnostic Use Only. The VCA IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Epstein-Barr Viral Capsid Antigen. Purified recombinant VCA antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
Here's a breakdown of the acceptance criteria and study details for the VCA IgG ELISA Test Kit, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the different performance metrics. However, we can infer the reported performance as the outcome of the evaluation.
| Performance Characteristic | Reported Device Performance |
|---|---|
| Sensitivity | |
| Relative Sensitivity (Acute) | 58.8% (95% CI: 41.9%-75.7%) |
| Relative Sensitivity (Seropositive) | 95.0% (95% CI: 90.5%-99.4%) |
| Specificity | |
| Relative Specificity (Seronegative) | 100% (95% CI: 89.0%-100%) |
| Agreement | |
| Relative Agreement | 87.5% (95% CI: 82.3%-92.7%) |
| Precision | (Coefficient of Variation (CV) |
| Serum 1 | 7.80% |
| Serum 2 | 11.33% |
| Serum 3 | 8.33% |
| Serum 4 | 13.32% |
| Serum 5 | 23.48% |
| Serum 6 | 26.16% |
| HP (High Positive) | 9.19% |
| Cal (Calibrator) | 5.99% |
| LP (Low Positive) | 13.92% |
| NC (Negative Control) | 105.88% |
| Cross-Reactivity | No cross-reactivity observed with Herpes Simplex Virus I & II, Cytomegalovirus, and Varicella Zoster Virus IgG antibodies (all VCA IgG results ≤ 0.61 for these sera, with negative threshold ≤ 0.90). |
2. Sample size used for the test set and the data provenance
- Sample Size (Sensitivity and Specificity study): 166 selected serum samples.
- 39 samples characterized as Acute
- 99 samples characterized as Seropositive
- 28 samples characterized as Seronegative
- Data Provenance: The serums were "tested at a clinical lab." The origin country is not specified, but the context of the submission to the FDA suggests the data is likely from the United States or intended for the US market. The study is retrospective, as the serum samples were "selected" and "characterized" prior to testing with the VCA IgG ELISA kit.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The ground truth was established by "characteriz[ing]" the serum samples as "seronegative," "acute," or "seropositive" based on other Epstein-Barr virus (EBV) serologies (VCA IgM, EBNA IgG, heterophile antibody).
- Number of experts: Not explicitly stated. The characterization appears to be based on the results of other EBV serology tests, rather than direct expert interpretation of the VCA IgG ELISA results themselves. It's implied that clinical laboratory professionals would interpret these other serology results to categorize the samples.
- Qualifications of experts: Not specified, but implied to be individuals competent in interpreting EBV serology results, such as clinical laboratory scientists or physicians.
4. Adjudication method for the test set
The document does not describe an adjudication method for the test set. The categorization of serum samples into "acute," "seropositive," and "seronegative" was based on a panel of other EBV serology tests, and then the VCA IgG ELISA test result was compared to this established classification. Equivocal results from the VCA IgG ELISA were not retested or adjudicated; they were simply excluded from the sensitivity and specificity calculations.
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
- No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) ELISA test kit, not an AI-powered image analysis or diagnostic tool that involves human "readers" in the context of interpretation. Therefore, a study on human reader improvement with AI assistance is not applicable.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, a standalone performance study was done. The entire performance characteristic section (sensitivity, specificity, precision, cross-reactivity) evaluates the VCA IgG ELISA device on its own, independent of human interpretation or assistance beyond the standard laboratory procedures for running the assay and reading the photometric results. The "human-in-the-loop" here is the lab technician conducting the test and reading the quantifiable outcome, not interpreting complex images or clinical scenarios that would typically involve an AI algorithm.
7. The type of ground truth used
The ground truth used was "serological characterization" based on a panel of established EBV serology tests (VCA IgM, EBNA IgG, heterophile antibody). This is a form of reference standard test result.
8. The sample size for the training set
- Not applicable. The provided text describes a traditional ELISA diagnostic kit. There is no mention of a "training set" as would be used for machine learning or AI models. The development of such a kit typically involves assay optimization and validation during its development, but not in the sense of a machine learning training set.
9. How the ground truth for the training set was established
- Not applicable, as there is no training set for this type of device.
§ 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).