(40 days)
The SeraQuest EBV EA-D IgG test is for the qualitative detection of human IgG antibodies to Epstein-Barr virus early antigen diffuse (EA-D) in human serum by enzyme immunoassay. This assay uses a 28 kd E. coli expressed recombinant Epstein-Barr virus early antigen. When performed in conjunction with other EBV serological tests, this assay can be used as an aid in the laboratory diagnosis of EBV infectious mononucleosis in patients with signs and symptoms of EBV infectious mononucleosis. For In Vitro Diagnostic Use Only.
The SeraQuest EBV EA-D IgG Test is a solid-phase enzyme immunoassay (EIA), which is performed in microwells, at room temperature, in three thirty minute incubations. It has been developed to detect IgG antibodies which are directed against EBV Early Antigen D (EA-D), in human serum.
The document describes the SeraQuest EBV EA-D IgG Test, a solid-phase enzyme immunoassay (EIA) designed for the qualitative detection of human IgG antibodies to Epstein-Barr virus early antigen diffuse (EA-D) in human serum. This assay aids in the laboratory diagnosis of EBV infectious mononucleosis when used with other EBV serological tests.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds (e.g., "Positive Agreement must be >X%"). Instead, it presents various performance metrics derived from its clinical evaluation, which are then compared to a legally marketed predicate device. The implicit acceptance criterion appears to be "substantial equivalence" to the predicate device in terms of performance characteristics for diagnostic aid in EBV infectious mononucleosis.
The performance is reported in terms of percent agreement and associated confidence intervals, categorized by EBV serological status.
| EBV Serological Status | Performance Metric (SeraQuest EBV EA-D IgG Test) | Reported Value (Prospectively Collected & Tested) | 95% Confidence Interval (Prospectively Collected & Tested) | Reported Value (Retrospectively Tested) | 95% Confidence Interval (Retrospectively Tested) |
|---|---|---|---|---|---|
| Acute Infection | Positive Agreement | 54.8% (17/31) | 36.0-72.7% | 70.0% (35/50) | 55.4-82.1% |
| EBV Seronegative | Negative Agreement | 78.3% (47/60) | 65.8-87.9% | 86.7% (13/15) | 59.5-98.3% |
| Past Infection | Negative Agreement | 60.1% (187/311) | 54.7-65.6% | Not applicable (0 retrospectively tested past infection samples) | Not applicable |
Note: For comparison, the predicate device (Comparator EBV EA-D IgG Test) achieved:
- Acute Infection Positive Agreement: 41.9% (13/31) with CI 24.5-60.9% (prospectively tested)
- Acute Infection Positive Agreement: 64.0% (32/50) with CI 49.2-77.1% (retrospectively tested)
- EBV Seronegative Negative Agreement: 78.3% (47/60) with CI 65.8-87.9% (prospectively tested)
- No Infection Negative Agreement: 73.3% (11/15) with CI 44.9-92.2% (retrospectively tested)
- Past Infection Negative Agreement: 62.7% (195/311) with CI 57.3-68.1% (prospectively tested)
2. Sample Size Used for the Test Set and Data Provenance
- Total Test Set Sample Size: 542 serum samples.
- Prospectively Collected and Prospectively Tested: 477 samples.
- Prospectively Collected but Retrospectively Tested: 65 samples (50 acute specimens, 15 EBV seronegative).
- Data Provenance:
- Country of Origin: 3 U.S. clinical testing sites.
- Nature of Data: Mixed; primarily prospective (477 samples) with a supplementary retrospective component (65 samples that were prospectively collected but retrospectively tested). The study notes that the 65 specimens were retrospectively tested to "supplement the prospective study data."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document states that specimens were classified into EBV serological states (Acute, EBV seronegative, Past Infection, Indeterminate) "as determined by other EBV serological reagents" and "reference EBV serology assays for EBV VCA IgG, EBV VCA IgM, and EBV EBNA-1 IgG." It does not mention the use of human "experts" or their qualifications to establish the ground truth for the test set. The ground truth was established by the results of established reference serological assays.
4. Adjudication Method for the Test Set
The document does not describe an "adjudication method" in the traditional sense involving human review of discrepancies. Instead, it details how equivocal results from both the SeraQuest test and the comparator test were handled for percent agreement calculations:
- "SeraQuest EBV EA-D IgG test equivocal results were assigned to the opposite test result interpretation than that of the corresponding comparative test results."
- "Likewise, the comparative test equivocal results were assigned to the opposite test result interpretation than that of the corresponding SeraQuest EBV EA-D IgG Test results."
This is a statistical adjustment for calculation rather than clinical adjudication by experts.
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 section is not applicable to this device. The SeraQuest EBV EA-D IgG Test is an in vitro diagnostic (IVD) immunoassay, not an AI-assisted diagnostic imaging or interpretation device that would involve human "readers" or "AI assistance." The "comparator" in this study refers to another commercially available EBV EA-D IgG ELISA test, not human readers or an AI system.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This section is applicable as the SeraQuest EBV EA-D IgG Test is an immunoassay that operates independently to produce a result. Its performance was evaluated in a standalone manner by comparing its output (positive, negative, equivocal) to the serological classification derived from reference EBV serology assays. The results presented in Tables 6 and 7 directly reflect the standalone performance of the SeraQuest test relative to the established EBV serological classification.
7. The Type of Ground Truth Used
The ground truth for classifying specimens into EBV serological states (Acute, EBV seronegative, Past Infection, Indeterminate) was established using a combination of results from reference EBV serology assays: EBV VCA IgG, EBV VCA IgM, and EBV EBNA-1 IgG. This can be categorized as serological reference assay data. The document explicitly states: "The EBV EA-D IgG result generated by the commercially available comparator EBV EA-D IgG ELISA test was not considered for purposes of characterizing the EBV serological state of the specimen."
8. The Sample Size for the Training Set
The document does not mention a "training set." This device is an immunoassay kit, not a machine learning or AI algorithm that requires a training set in the typical sense. The studies described are for clinical performance validation, not for training a model.
9. How the Ground Truth for the Training Set Was Established
Since there is no mention of a "training set" in the context of this immunoassay, this question is not applicable. The "ground truth" for the performance evaluation (test set) was established using reference EBV serology assays, as described in point 7.
§ 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).