(153 days)
The Zeus Scientific Varicella Zoster Virus (VZV) IgM ELISA Test System is intended for the qualitative detection of IgM class antibodies to Varicella Zoster Virus in human serum as an aid in the diagnosis of primary infection or reactivation.
The assay performance in detecting antibodies to VZV in individuals vaccinated with the FDA licensed VZV vaccine is unknown.
The user of this assay is responsible for establishing the performance characteristics with VZV vaccinated individuals.
The assay performance in detecting antibodies to VZV in cord blood and neonates has not been established.
The Zeus Scientific VZV IgM ELISA Test System is an enzyme linked immunosorbent assay intended for the qualitative detection of distict IgM antibody to the Varicella-zoster virus.
The test is designed to detect IgM antibody using inactivated VZV antigen: strain, Ellen.
This submission describes the Zeus Scientific VZV IgM ELISA Test System, an in-vitro diagnostic device. As such, acceptance criteria and performance are typically measured in terms of diagnostic accuracy metrics (sensitivity, specificity, agreement) against a comparator method, rather than effect sizes of human reader improvement or standalone algorithm performance.
Here's a breakdown of the requested information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" as clear numerical thresholds for performance. However, it presents the "Agreement Summary" with a commercially distributed ELISA assay as the primary evidence of performance. The performance metrics are Positive % Agreement and Negative % Agreement.
| Metric | Acceptance Criteria (Not explicitly stated, inferred from results) | Reported Device Performance (Prospective and Retrospective Samples: Combined Sites) |
|---|---|---|
| Positive % Agreement | Sufficiently high agreement with predicate (e.g., >90%) | 97.4% (95% CI: 86.5% to 99.9%) |
| Negative % Agreement | Sufficiently high agreement with predicate (e.g., >90%) | 95.6% (95% CI: 91.8% to 97.1%) |
Note: The reported performance for "Prospective Samples: Combined Sites" also provides similar figures: Positive % Agreement = 100% (95% CI: 54.1% to 100.0%) and Negative % Agreement = 95.6% (95% CI: 92.6% to 97.6%). The table above uses the combined prospective and retrospective data as it represents a larger and more comprehensive dataset for agreement.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Prospective samples: 302
- Retrospective samples: 36
- Total combined samples: 338 (used for the primary agreement summary)
- Data Provenance: Retrospective and Prospective. The document does not specify the country of origin of the data.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- The ground truth for the test set was established by comparison to a "commercially distributed VZV IgM ELISA test system" (predicate device). There is no mention of human experts establishing ground truth for the test set.
4. Adjudication Method for the Test Set
- The document implies a direct comparison method, where the results of the Zeus Scientific VZV IgM ELISA Test System were compared against the results of the "commercially distributed VZV IgM ELISA test system." There is no mention of an adjudication process (like 2+1 or 3+1). The commercial ELISA served as the reference standard.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, and Effect Size of 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 assay (ELISA kit), not an AI-assisted diagnostic tool involving human readers. Therefore, this section is not applicable.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, the performance presented is standalone for the assay. ELISA tests are inherently standalone, as they provide a direct result based on chemical reactions, without human interpretation other than reading the optical density and interpreting it against a cut-off (which is part of the assay's design).
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- Ground Truth Type: Comparison to a predicate commercial ELISA test system. This is a common method for establishing the performance of new in-vitro diagnostic assays, where a well-established and legally marketed assay serves as the reference standard.
8. The Sample Size for the Training Set
- The document mentions smaller sets of samples used for various non-clinical performance aspects:
- Cut-off Establishment: 25 known negative samples and a minimum of 5 known positive samples (total at least 30 samples). These were confirmed by a commercially distributed ELISA assay.
- Interfering Substances: 3 samples (positive, borderline, negative) were tested with various interfering substances.
- Cross-Reactivity: A minimum of 10 samples for each cross-reactive substance (EBV, CMV, Lyme, RF, Mumps, Toxo, Measles, Rubella) were tested (total at least 80 samples). These were confirmed negative for VZV IgM using the predicate device.
- Precision: 6 samples were used, tested at three sites, over three days.
- It's important to note that for IVDs like ELISA kits, the concept of a "training set" as understood in machine learning (where an algorithm learns from data) isn't directly applicable in the same way. These studies are for establishing performance characteristics rather than "training" an algorithm. The samples listed above are used to define the assay's characteristics and validate its function.
9. How the Ground Truth for the Training Set was Established
- For studies like cut-off establishment and cross-reactivity, the ground truth was established by confirmation using a commercially distributed ELISA assay (the predicate device). For other studies like linearity, limits of detection, interfering substances, and precision, the ground truth is inherent to the experimental design (e.g., known dilutions, spiked samples, or reproducibility across replicates/sites).
§ 866.3900 Varicella-zoster virus serological reagents.
(a)
Identification. Varicella-zoster virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to varicella-zoster in serum. The identification aids in the diagnosis of diseases caused by varicella-zoster viruses and provides epidemiological information on these diseases. Varicella (chicken pox) is a mild, highly infectious disease, chiefly of children. Zoster (shingles) is the recurrent form of the disease, occurring in adults who were previously infected with varicella-zoster viruses. Zoster is the response (characterized by a rash) of the partially immune host to a reactivation of varicella viruses present in latent form in the patient's body.(b)
Classification. Class II (performance standards).