(265 days)
The LIAISON® EA IgG assay and LIAISON® EA IgG Controls use chemiluniescent immunoassay (CLIA) technology on the LIAISON Analyzer for the qualitative determination of IgG antibodies to Epstein-Barr virus early antigen-diffuse [EA(D)] in human serum. This assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM).
The method for qualititative determination of specific IgG to Epstein-Barr virus early antigen-diffuse (EA(D) recombinant polypeptide] is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Analyzer. The principal components of the test are magnetic particles (solid phase) coated with EA(D) recombinant polypeptide and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, EA(D) antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with EA(D) antibodies that are already bound to the solid phase. After each incubation, unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of the presence of EA(D) IgG antibodies present in calibrators, samples or controls.
Here's a breakdown of the acceptance criteria and study information for the DiaSorin LIAISON® EA IgG assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined "acceptance criteria" as a separate set of pass/fail thresholds. Instead, it presents the performance results of the device and concludes that these results demonstrate "equivalent performance to the corresponding FDA-cleared assay" and "agreement with the comparison method higher then 92% among prospectively collected samples and 100% agreement among retrospective selected samples."
Therefore, the performance of the predicate device (DiaSorin ETI-EA-G ELISA Kit) effectively serves as the benchmark for acceptance.
Inferred Acceptance Criteria (based on predicate device performance and stated conclusions):
| Performance Metric | Acceptance Criteria (Inferred from Predicate Equivalence) | Reported Device Performance (LIAISON® EA IgG) |
|---|---|---|
| Prospective Samples: | ||
| Positive Agreement | Comparable to predicate (DiaSorin ETI-EA-G) | 90.3% (297/329) [Exact 95% CI: 86.6 – 93.3%] |
| Negative Agreement | Comparable to predicate (DiaSorin ETI-EA-G) | 93.5% (462/494) [Exact 95% CI: 91.0 – 95.5%] |
| Overall Agreement | Comparable to predicate (DiaSorin ETI-EA-G) | 92.2% (759/823) [Exact 95% CI: 90.2 – 94.0%] |
| Retrospective Samples (VCA IgM-positive): | ||
| Positive Agreement | Comparable to predicate (DiaSorin ETI-EA-G) | 100.0% (70/70) [Exact 95% CI: 94.9 - 100.0%] |
| Negative Agreement | N/A (no negative samples in this subset) | N.C.* (0/0) |
| Overall Agreement | Comparable to predicate (DiaSorin ETI-EA-G) | 100.0% (70/70) [Exact 95% CI: 94.9 - 100.0%] |
| Reproducibility (Overall %CV) | (Not explicitly stated, but generally expected to be low for diagnostic assays) | Ranged from 9.43% to 15.36% across 9 samples |
| Interference | No significant effect from common interferents | No effect at specified levels of hemoglobin, triglycerides, bilirubin |
| Cross-Reactivity | Limited cross-reactivity with other common infections and autoantibodies | 15/183 specimens showed positive/equivocal results, particularly with Toxoplasma gondii and rubella virus. Conclusion attributes this to performance differences between test methods. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Prospective Samples:
- Sample Size: 823 samples
- Data Provenance: Subjects sent to the laboratory for EBV testing in the US (specifically from two external US laboratories and DiaSorin). The samples were collected prospectively.
- Retrospective Samples:
- Sample Size: 70 samples
- Data Provenance: VCA IgM-positive samples, implying a pre-selected cohort. No specific country of origin is mentioned beyond the US clinical trial sites, but it's likely from the same geographical region. These were retrospective samples from a repository.
- Reproducibility Panel: 9 frozen repository serum samples.
- Interference Samples: Not specified, but involved controlled studies with substances at given concentrations.
- Cross-Reactivity Panel: 183 specimens from various organism/condition categories.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The study uses a comparison assay (DiaSorin ETI-EA-G ELISA Kit) as the "ground truth" or reference method for the clinical trials. This is a common practice for 510(k) submissions of in-vitro diagnostic devices where an existing FDA-cleared predicate device serves as the a reference.
Therefore, there were no human experts establishing ground truth in the way a radiologist might read images. Instead, the ground truth was established by the results of the already-cleared predicate device.
4. Adjudication Method for the Test Set
Since the ground truth was established by a comparison assay (DiaSorin ETI-EA-G ELISA Kit), there was no explicit mention of a human expert adjudication method (like 2+1 or 3+1) for the clinical trial results presented. The results of the LIAISON® EA IgG assay were compared directly against the results of the predicate device.
For the cross-reactivity study, some equivocal results were noted, and the document states, "...Since it was not possible to acquire follow-up samples collected one to two weeks later as recommended." This suggests that for discordant or equivocal results, a follow-up sample might typically be used for adjudication or clarification, but this was not feasible in all cases during the cross-reactivity testing.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on the performance of an automated immunoassay device compared to another automated immunoassay device (predicate), not on human reader performance with or without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, this study is a standalone performance evaluation of the DiaSorin LIAISON® EA IgG immunoassay. It measures the device's ability to qualitatively detect specific IgG antibodies to EBV EA(D) in human serum without human intervention in the result interpretation, beyond standard laboratory quality control and reporting procedures. The "algorithm" here refers to the immunoassay's reagents and the LIAISON® Analyzer's automated processing and signal interpretation to yield a positive, equivocal, or negative result.
7. The Type of Ground Truth Used
The primary ground truth used for the comparative clinical trials was the results obtained from an FDA-cleared predicate device, the DiaSorin ETI-EA-G ELISA Kit. This is a form of "reference standard" based on another established diagnostic method.
8. The Sample Size for the Training Set
The document does not provide information on a specific training set for the DiaSorin LIAISON® EA IgG assay. Immunoassays, particularly those developed before the widespread adoption of machine learning in diagnostics, typically do not involve a distinct "training set" in the same way a machine learning algorithm would. The development process would involve reagent optimization, calibration curve establishment, and analytical validation (e.g., specificity, sensitivity, reproducibility) using panels of known samples, but these are not usually referred to as "training sets" in the context of this type of device.
9. How the Ground Truth for the Training Set Was Established
As noted above, there is no explicit mention of a "training set" in the provided text. Therefore, the method for establishing ground truth for a training set is not applicable or not described in this 510(k) submission.
§ 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).