(146 days)
The LIAISON® HSV-2 Type Specific IgG assay is a chemiluminescent immunoassay to be used with the LIAISON® Analyzer for the qualitative determination of type specific IgG antibodies to Herpes simplex virus Type 2 (HSV-2) in human serum. The assay is indicated for testing sexually active adults or expectant mothers to aid in the presumptive diagnosis of HSV-2 infection.
The LIAISON® HSV-2 Type Specific IgG assay has not been established for use in the pediatrics population, for neonatal screening, or for testing immunocompromised patients. The assay is neither FDA cleared nor approved for testing blood or plasma donors.
The LIAISON® Control HSV-2 (negative and positive) are intended for use as assayed quality control samples to monitor the performance of the LIAISON® HSV-2 Type Specific IgG assay.
The method for qualitative determination of specific IgG to HSV-2 is an indirect chemiluminescence immunoassay (CLIA). HSV-2 gG2 recombinant antigen is used for coating magnetic particles (solid phase) and a mouse monoclonal antibody is linked to an isoluminol derivative (isoluminolantibody conjugate), During the first incubation, HSV-2 antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with HSV-2 IgG already bound to the solid phase. After each incubation, the 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 HSV-2 IgG concentration present in calibrators, samples or controls.
The information provided details the performance study for the LIAISON® HSV-2 Type Specific IgG assay, but it does not explicitly state pre-defined acceptance criteria for sensitivity and specificity that the device must meet. Instead, it presents the performance data and then concludes that the device performed equivalently to an FDA-cleared comparison method.
However, based on the provided data, we can infer the reported performance metrics.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance:
As mentioned, no explicit "acceptance criteria" are given in terms of numerical thresholds for sensitivity and specificity. The study aims to demonstrate "equivalent performance" to the predicate device. Therefore, the table below will list the reported performance values.
| Performance Metric | Acceptance Criteria (Inferred from "equivalent performance") | Reported Device Performance (LIAISON® HSV-2 Type Specific IgG) |
|---|---|---|
| Sexually Active Adults (n=401) | ||
| Sensitivity | Equivalent to predicate device | 98.1% (95% CI: 95.6 - 99.9%) |
| Specificity | Equivalent to predicate device | 98.0% (95% CI: 96.0 - 99.1%) |
| Expectant Mothers (n=430) | ||
| Sensitivity | Equivalent to predicate device | 94.8% (95% CI: 89.4 - 97.9%) |
| Specificity | Equivalent to predicate device | 97.3% (95% CI: 95.3 - 98.6%) |
| Low Prevalence Population (n=120) | ||
| Sensitivity | Equivalent to predicate device | 100% (95% CI: 86.1 - 100.0%) |
| Specificity | Equivalent to predicate device | 100% (95% CI: 97.0 - 100.0%) |
| CDC Panel (n=100) | ||
| Total Agreement with Positive | Equivalent to predicate device | 100% (52/52) |
| Total Agreement with Negative | Equivalent to predicate device | 100% (48/48) |
2. Sample size used for the test set and the data provenance:
- Total Test Set Sample Size: 951 samples for comparison against the FDA-cleared Immunoblot.
- 401 samples from Sexually Active Adults
- 430 samples from Expectant Mothers
- 120 samples from a "Low Prevalence" population
- Additionally, a 100-sample CDC panel (52% positive, 48% negative) was used for further performance assessment.
- Data Provenance:
- Country of Origin: Northeastern United States for the 951 samples. The CDC panel provenance is not specified beyond being from the Centers for Disease Control and Prevention.
- Retrospective or Prospective: Not explicitly stated, but the description "samples collected" and "samples obtained" suggests a retrospective collection of existing samples, rather than prospective enrollment for the purpose of this study.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The ground truth was primarily established using an FDA-cleared Immunoblot (Predicate Device: Focus Diagnostics HerpeSelect® 1 and 2 Immunoblot IgG, K000238). For equivocal samples on the predicate device, Western Blot testing was performed by a Reference Laboratory in the Pacific Northwest.
- Number of Experts: Not applicable in the context of human expert review for independent ground truth. The initial ground truth was established by another diagnostic device (the predicate Immunoblot).
- Qualifications of Experts: Not applicable, as the primary ground truth was instrument-based. The "Reference Laboratory" for Western Blotting implies trained laboratory personnel, but specific qualifications are not mentioned.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Adjudication Method: Not applicable in the traditional sense of multiple human readers adjudicating results. The ground truth was established by a predicate device, and for equivocal results from the predicate, a Western Blot was used for resolution. This acts as a form of reference method adjudication for indeterminate cases from the predicate.
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:
- MRMC Study: No, this was not a multi-reader multi-case comparative effectiveness study. This study compares the performance of a new in vitro diagnostic device (LIAISON® HSV-2 Type Specific IgG assay) against a legally marketed predicate device (FDA cleared Immunoblot). It does not involve human readers' interpretation of results that are enhanced or assisted by AI.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Standalone Performance: Yes, the study evaluated the LIAISON® HSV-2 Type Specific IgG assay as a standalone diagnostic device. It is an automated chemiluminescent immunoassay (CLIA) and its performance is measured independently against the predicate device and Western Blot as reference methods. It does not involve a human in the loop for interpreting the assay's primary output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Ground Truth Type: A combination of a legally marketed predicate device (FDA-cleared Immunoblot) and a reference laboratory method (Western Blot) for resolving equivocal results from the predicate device. This is a common approach for establishing ground truth in diagnostic device comparisons. The CDC panel serves as an external, well-characterized control for further validation.
8. The sample size for the training set:
- Training Set Sample Size: Not explicitly stated or provided in the document. The document describes a "comparative clinical trial" and "reproducibility study" for performance validation, not the development or training of the assay itself. The LIAISON® HSV-2 Type Specific IgG assay is an immunoassay, the "training" aspect is related to the assay's development and optimization, for which specific sample sizes are not typically released in 510(k) summaries for such devices.
9. How the ground truth for the training set was established:
- Ground Truth for Training Set: Not specified. As an immunoassay, its "training" involves optimizing reagents, concentrations, and reaction conditions during its development phase. The ground truth for this optimization would typically involve well-characterized positive and negative serum samples, likely confirmed by established reference methods (e.g., Western Blot, clinical diagnosis, culture), but these details are not part of the provided 510(k) summary focused on validation.
§ 866.3305 Herpes simplex virus serological assays.
(a)
Identification. Herpes simplex virus serological assays are devices that consist of antigens and antisera used in various serological tests to identify antibodies to herpes simplex virus in serum. Additionally, some of the assays consist of herpes simplex virus antisera conjugated with a fluorescent dye (immunofluorescent assays) used to identify herpes simplex virus directly from clinical specimens or tissue culture isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by herpes simplex viruses and provides epidemiological information on these diseases. Herpes simplex viral infections range from common and mild lesions of the skin and mucous membranes to a severe form of encephalitis (inflammation of the brain). Neonatal herpes virus infections range from a mild infection to a severe generalized disease with a fatal outcome.(b)
Classification. Class II (special controls). The device is classified as class II (special controls). The special control for the device is FDA's revised guidance document entitled “Class II Special Controls Guidance Document: Herpes Simplex Virus Types 1 and 2 Serological Assays.” For availability of the guidance revised document, see § 866.1(e).