(14 days)
The DiaSorin ETI-EA-G kit uses Enzyme Linked Immunosorbent Assay (ELISA) technology for the qualitative and/or semi-quantitative detection of IgG antibodies to the EBV Early Antigen Diffuse. The assay is designed for human serum. The presence of EA antibodies is used as an aid in the diagnosis of EBV associated infectious mononucleosis when used in conjunction with other EBV serologies in pediatric, adult, transplant donor and transplant recipient populations. When evaluating properly paired sera, the results of these assays are used to demonstrate seroconversion or significant change in antibody titer as evidence of recent infection. Both specimens should be tested simultaneously.
The method for the determination of specific anti-EA (D) IgG utilizes the enzyme-linked immunosorbent assay (ELISA) technique. Polystyrene microtiter wells are coated with recombinant EA (D) antigen. Diluted patient serum is incubated with the purified antigen bound to the solid surface of a microtiter well. The EA (D) IgG antibodies present in a patient's serum will be captured by the solid phase. After washing, affinity purified polyclonal goat anti-human IgG (Fc) antibodies coniugated to horseradish peroxidase are added to the well. After this incubation, chromogen containing tetramethylbenzidine is added. Enzyme action on the chromogen results in a color reaction. The color can be detected with a photometer at a wavelength of 450 nm. The measured enzyme activity is directly proportional to the concentration of specific anti-EA (D) IgG bound to the solid phase.
This document describes the performance data for the DiaSorin ETI-EA-G Epstein-Barr Viral Early Antigen Diffuse EA (D) IgG ELISA Immunoassay.
1. Table of Acceptance Criteria and Reported Device Performance
For the purpose of this analysis, the "acceptance criteria" are inferred from the Expected Prevalence and the desire for high Sensitivity, Specificity, and Agreement with the predicate device.
| Performance Metric | Expected Pattern (Adult Population) | Adult Population (Reported) | Expected Pattern (Pediatric Population) | Pediatric Population (Reported) |
|---|---|---|---|---|
| Primary Disease State | ||||
| Sensitivity | High (not explicitly defined, but close to 100% ideal) | 97.8% (95% CI: 88.5 - 99.9%) | High (not explicitly defined) | 89.7% (95% CI: 72.6 – 97.8%) |
| Specificity | N/A (not applicable for positive pattern) | N/A | N/A | N/A |
| Agreement | High (not explicitly defined) | 97.8% | High (not explicitly defined) | 89.7% |
| Prevalence ELISA | In range (80-100%) | 97.8% | In range (80-100%) | 89.7% |
| Prevalence IFA (Predicate) | In range (80-100%) | 100% | In range (80-100%) | 100% |
| Seronegative Population | ||||
| Sensitivity | N/A | N/A | N/A | N/A |
| Specificity | High (not explicitly defined, but close to 100% ideal) | 100.0% (95% CI: 59.0 - 100.0%) | High (not explicitly defined) | 96.0% (95% CI: 86.3 - 99.5%) |
| Agreement | High (not explicitly defined) | 100.0% | High (not explicitly defined) | 96.0% |
| Prevalence ELISA | In range (0%) | 0.0% | In range (0%) | 4.0% |
| Prevalence IFA (Predicate) | In range (0%) | 0.0% | In range (0%) | 0.0% |
| Reactivated Population | ||||
| Sensitivity | High (not explicitly defined, but close to 100% ideal) | 96.8% (95% CI: 83.3-99.9%) | High (not explicitly defined) | 100.0% (95% CI: 39.8 - 100.0%) |
| Specificity | N/A | N/A | N/A | N/A |
| Agreement | High (not explicitly defined) | 96.8% | High (not explicitly defined) | 100.0% |
| Prevalence ELISA | In range (90-100%) | 96.8% | In range (90-100%) | 100.0% |
| Prevalence IFA (Predicate) | In range (90-100%) | 100% | In range (90-100%) | 100% |
| Past Infection Population | ||||
| Sensitivity | Varies (36.4% and 66.7% are reported) | 36.4% (95% CI: 20.4 - 54.9%) | Varies | 66.7% (95% CI: 9.0 - 99.9%) |
| Specificity | Varies (75.0% and N/A are reported) | 75.0% (95% CI: 19.4-99.4) | Varies | N/A |
| Agreement | Varies (40.5% and 66.7% are reported) | 40.5% | Varies | 66.7% |
| Prevalence ELISA | In range (10-40%) | 32.4% | In range (10-40%) | 66.7% |
| Prevalence IFA (Predicate) | In range (10-40%) | 89.2% | In range (10-40%) | 100% |
| Transplant Recipient Population | ||||
| Sensitivity | Varies (47.6% and N/A are reported) | 47.6% (95% CI: 25.7 - 70.2%) | Varies | N/A |
| Specificity | Varies (33.3% and 85.7% are reported) | 33.3% (95% CI: 0.8% - 90.6%) | Varies | 85.7% (95% CI: 42.1 - 99.6%) |
| Agreement | Varies (45.8% and 75.0% are reported) | 45.8% | Varies | 75.0% |
| Prevalence ELISA | Not explicitly defined as expected | 50.0% | Not explicitly defined as expected | 12.5% |
| Prevalence IFA (Predicate) | Not explicitly defined as expected | 87.5% | Not explicitly defined as expected | 12.5% |
Summary of Acceptance:
The document states: "The ETI-EA-G ELISA demonstrates good sensitivity and specificity in Primary, Seronegative and Reactivated populations. The prevalence rates were within the expected range for each of these populations." It also provides explanations for the observed differences in Past Infection and Transplant Recipient populations, attributing them to the difference in antigen detection between the predicate and the new device, and concluding that "The results support the Transplant claim in the Intended Use."
2. Sample Size Used for the Test Set and Data Provenance
The provided text only discusses the "clinical trials" which represent the "test set" in this context. There is no mention of a separate training set.
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Sample Size for Test Set:
- Primary Disease State (Adult): 46 samples (+)
- Primary Disease State (Pediatric): 29 samples (+)
- Seronegative (Adult): 7 samples (-)
- Seronegative (Pediatric): 50 samples (-)
- Reactivated (Adult): 31 samples (+)
- Reactivated (Pediatric): 4 samples (+)
- Past Infection (Adult): 37 samples (-/+) (33 were IFA positive, 4 IFA negative)
- Past Infection (Pediatric): 3 samples (-/+) (3 were IFA positive)
- Transplant Recipient (Adult): 24 samples (21 were IFA positive, 3 IFA negative)
- Transplant Recipient (Pediatric): 8 samples (1 was IFA positive, 7 IFA negative)
- Total Samples (unique cases are not explicit): 235 samples across all categories.
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Data Provenance: The samples were "patients from the disease states defined below" and "screened" from a clinical laboratory. The data's geographical origin (country) is not explicitly stated. The study is described as "clinical trials," suggesting it was conducted to evaluate the performance of the ETI-EA-G, making it seem prospective for the device's evaluation, although the samples themselves might have been collected retrospectively from existing patient cohorts.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the "number of experts" or their specific "qualifications" (e.g., radiologist with X years of experience).
- Method of Ground Truth Establishment (Primary): The ground truth was established by comparing the DiaSorin ETI-EA-G against a "predicate device," the Gull Laboratories, Inc. EA IgG IFA test.
- Method of Ground Truth Establishment (Secondary/Confirmation): Patient samples were "excluded if they failed to fit a recognized EBV marker pattern determined by EBV VCA (IgG, IgM) and EBNA testing." This implies that the initial classification into disease states (Primary, Seronegative, Reactivated, Past Infection) was done based on a combination of EBV serologies (VCA IgG, IgM, and EBNA testing), which would likely have been interpreted by laboratory professionals or clinicians, effectively acting as "experts" in serology.
4. Adjudication Method for the Test Set
The document does not describe an explicit "adjudication method" in the sense of multiple experts reviewing cases and resolving disagreements. The ground truth appears to be based on the results of the predicate IFA test and other established EBV serologies, which function as objective reference standards within the study design.
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 question is not applicable as the device is an immunoassay (ELISA) for detecting antibodies, not an AI-powered diagnostic imaging or analytical tool that involves human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study is inherently a standalone performance evaluation. The DiaSorin ETI-EA-G ELISA kit is a laboratory test, and its results are generated directly by the assay without human "reading" in the context of interpretation beyond standard laboratory procedures and result reporting. Its performance (sensitivity, specificity, agreement) is reported for the device itself, comparing its output to a predicate standard.
7. The Type of Ground Truth Used
The primary ground truth for comparison was the Gull Laboratories, Inc. EA IgG IFA test. Additionally, the classification into different disease states (Primary, Seronegative, Reactivated, Past Infection, Transplant Recipient) was based on "a recognized EBV marker pattern determined by EBV VCA (IgG, IgM) and EBNA testing." This indicates a combination of a predicate diagnostic test and clinical/serological consensus based on established EBV marker patterns, representing a form of expert consensus derived from widely accepted EBV serology interpretation guidelines.
8. The Sample Size for the Training Set
The document does not mention a separate training set. The samples described were used for "clinical trials" to evaluate the performance of ETI-EA-G. For immunoassay development, "training" often refers to the optimization phase, which is generally not documented in the same way as clinical validation.
9. How the Ground Truth for the Training Set Was Established
As no separate training set is mentioned, this question is not applicable.
§ 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).