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510(k) Data Aggregation
(113 days)
The Zeus Scientific, Inc AtheNA Multi-Lyte Borrelia VISE-1/ pepC10 Plus Test System is a multiplexed sandwich immunoassay for the qualitative detection of IgG class antibody to recombinant VISE-1 and the IgM class of antibody to synthetic pepC10 in human serum. The AtheNA Multi-lyte Borrelia VISE-1/pepC10 Plus Test System is intended for use with the Luminex® 200 IS and the AtheNA Multi-Lyte data management package in testing serum samples from symptomatic patients or those with a history of Lyme Borreliosis. All positive specimens should be tested with a second-tier test such as Western Blot which if positive, is supportive evidence of infection with B.burgdorferi. Diagnosis of Borreliosis should be made based on the presence of 8.burgdorferi antibodies, history, symptoms and other laboratory data. Negative first or second tier results should not be used to exclude Borreliosis.
The AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System is a micro particle immunoassay intended for the qualitative detection of distinct IgG class antibody to VlsE-1 and distinct IgM antibody to pepC10. The assay is a multiplexed immunoassay designed to simultaneously detect, distinguish and identify IgG reactivity to recombinant VISE-1 antigen and IgM reactivity to synthetic pepC10 antigen. The test system is comprised of the AtheNA Multi-Lyte test kit and the Luminex Corp instrument model number Luminex™ 200 IS and software version 3.
Here's an analysis of the acceptance criteria and the studies performed for the Zeus Scientific Inc. AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System, based on the provided text:
Important Note: The provided document is a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device. It does not explicitly state "acceptance criteria" in the format of a predefined performance target, but rather presents the results of various validation studies, which imply what would be considered acceptable performance for a diagnostic device in its class. For the purpose of this analysis, I will infer relevant performance metrics from the study results.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Metric Category | Implied Acceptance Criteria (Inferred from context and typical IVD requirements) | Reported Device Performance (AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System) | Relevant Section(s) |
|---|---|---|---|
| Linearity (R-squared) | R-squared value ≥ 0.90 | Demonstrated dilutions recovered within acceptance criteria (implies R-squared ≥ 0.90) | 7A: Linearity |
| Analytical Specificity (Interfering Substances - Signal Change) | Signal change < 20% in the presence of interfering substances (for most cases) | - VlsE-1: Most samples showed <20% change. Borderline VlsE-1 showed 32% (high bilirubin) and 27% (high cholesterol) increase. Negative VlsE-1 showed 36% reduction (high hemoglobin), 23% (low bilirubin), 27% (high bilirubin), 25% (low cholesterol), 45% (high cholesterol), 45% (low and high triglycerides). - pepC10: Most samples showed <20% change. Borderline pepC10 showed 24% reduction (high hemoglobin) and 28% increase (low triglyceride). Crucially, these changes in negative samples did not change the qualitative outcome (remained negative), suggesting acceptable specificity despite some signal shifts. | 7B: Analytical Specificity-Interfering Substances |
| Cross-Reactivity | 0% cross-reactivity with common interfering antibodies/conditions | 0/90 samples showed cross-reactivity with EBV VCA IgG, ANA, Syphilis, CMV IgG, CMV IgM, Rubella IgG, Toxo IgG, VZV IgM, RF. | 7C: Cross Reactivity |
| Performance with Characterized Acute Samples (Agreement with Clinical Diagnosis) | High agreement (e.g., >85%) | 100% (21/21) (95% CI: 86.7%-100%) | Table 1 (Study 1) |
| Performance with Characterized Convalescent Samples (Agreement with Clinical Diagnosis) | High agreement (e.g., >85%) | 94% (47/50) (95% CI: 83.5%-98.8%) | Table 1 (Study 1) |
| Performance with Culture Positive Early Acute Samples (Agreement with Clinical Diagnosis) | Moderate agreement given early stage (no explicit target, but a clear improvement over random) | 51.9% (41/79) (95% CI: 40.4%-63.3%) | Table 1 (Study 1) |
| Performance with Early Convalescent Samples (Agreement with Clinical Diagnosis) | High agreement (e.g., >70%) | 78.5% (62/79) (95% CI: 67.8%-86.9%) | Table 1 (Study 1) |
| Overall Performance with Characterized Samples (Agreement with Clinical Diagnosis) | High overall agreement | 74.7% (171/229) (95% CI: 68.5%-80.2%) | Table 1 (Study 1) |
| Prospective Study (Positive Percent Agreement - PPA) | High PPA compared to predicate ELISA (no explicit target, but expectation is substantial equivalence) | 81.4% (162/199) (95% CI: 75.3-86.6) | Table 2 (Study 2) |
| Prospective Study (Negative Percent Agreement - NPA) | High NPA compared to predicate ELISA (no explicit target) | 91.4% (509/557) (95% CI: 88.7-93.6) | Table 2 (Study 2) |
| Retrospective Study (PPA) | High PPA compared to predicate ELISA | 80% (180/225) (95% CI: 74.2-85.0) | Table 3 (Study 3) |
| Reproducibility (Total %CV) | Acceptable coefficient of variation (typically <20%, lower for higher concentrations) | VlsE-1: 13.5% (Near Cut-off) to 5.3% (High Positive). pepC10: 11.1% (Negative) to 6.2% (High Positive). | Table 6 (Section 9A) |
| Repeatability (Total %CV) | Acceptable coefficient of variation (typically ≤10-15%) | VlsE-1: 11.4% (High Negative) to 6.9% (High Positive). Note: VIsE-1 Negative 1 is 29.7%, which is high, but these values represent iAU performance, and as noted in Analytical Specificity, large iAU shifts for negative samples did not change qualitative outcome. pepC10: 13.1% (Negative 1) to 5.4% (High Positive). | Table 7 (Section 9A) |
| Analytical Specificity (Non-endemic population positivity) | Low positivity rate in a non-endemic population | 9.8% (39/400) | Table 5 (Study 5) |
2. Sample Sizes Used for the Test Set and Data Provenance
The document describes multiple studies with different test sets:
- Characterized Samples (Study 1): 229 human serum samples.
- Provenance: Northeastern state Department of Health Laboratory. Implies a mix of acute, convalescent, and culture-proven Lyme disease patients, likely collected prospectively or retrospectively for diagnostic purposes.
- Prospective Population (Study 2): 756 unselected samples from patients with an order for a Lyme antibody test.
- Provenance: Samples collected from four sites in the US: a hospital laboratory in the Mid-Atlantic (103 samples), a hospital laboratory in upper Connecticut (100 samples), a hospital laboratory in lower Connecticut (107 samples), and a state Department of Health Lab in the northeast (446 samples). All samples were submitted for Lyme antibody testing and were sequentially numbered, de-identified and archived.
- Retrospective Samples (Study 3): 242 samples (124 from Connecticut, 118 from Pennsylvania).
- Provenance: Believed to have screened positive for Borrelia burgdorferi antibodies, tested at a hospital facility in Connecticut and a Pennsylvania hospital laboratory.
- CDC Characterized Lyme Panel (Study 4): 40 samples (5 normal blood donors, 35 Borreliosis patients).
- Provenance: Acquired from the CDC.
- Analytical Specificity / Endemic & Non-Endemic Controls (Study 5): 700 samples (300 endemic from New England, 400 non-endemic from New Mexico).
- Provenance: Blood donors from New England (endemic) and blood donors/individuals undergoing routine non-infectious testing from New Mexico (non-endemic).
- Reproducibility: 5 internal samples (levels: negative, near cut-off, low positive, moderate and high positive).*
- Repeatability: 6 internal samples (levels: negative, high negative, near cut-off, low positive, moderate and high positive).*
*For reproducibility and repeatability, reference samples are typically prepared internally or sourced commercially with known characteristics, not representative of general patient populations for diagnostic accuracy evaluation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The document does not explicitly state the "number of experts" or their specific "qualifications" for establishing ground truth. However, implicitly:
- Clinical Diagnosis: For the "Characterized Samples" (Study 1) and "CDC Characterized Lyme Panel" (Study 4): The ground truth is based on "clinical diagnosis," "history of Borreliosis," "culture proven, early acute Lyme disease," or "patients diagnosed with Borreliosis." This implies a consensus among medical professionals (physicians, infectious disease specialists) using clinical criteria, possibly supported by existing laboratory results.
- Western Blot: For discrepant results in prospective and retrospective studies, Western Blot methodology was used to confirm reactivity. Western Blot interpretation is a specialized skill typically performed and verified by laboratory professionals experienced in serology.
- Predicate Device: For comparative studies, the predicate ELISA test system was used as a reference assay. The "ground truth" here is the result of the predicate device, which itself would have been FDA cleared based on its own validation by medical laboratory experts.
4. Adjudication Method for the Test Set
The document describes adjudication for discrepancies:
- Prospective Samples (Study 2): "If available, western blot testing was performed on the discrepant results."
- Retrospective Samples (Study 3): "Western blot testing was done on discrepant results."
This indicates a form of discrepancy resolution using a higher-tier test (Western Blot), which acts as a secondary adjudication method. The document does not specify if multiple readers were involved in the Western Blot interpretation or what consensus rule was applied (e.g., 2+1).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly conducted or described in the provided text for evaluating human reader performance with and without AI assistance. This device is an in vitro diagnostic test system (an assay), not an AI-powered image analysis tool that assists human interpretation of images. The comparison is between the new assay system and a predicate ELISA assay, not human readers.
6. Standalone Performance
Yes, standalone performance was done. The entire document describes the performance of the "AtheNA Multi-Lyte Borrelia VlsE-1/pepC10 Plus Test System" as a standalone algorithm (a fully automated assay, without human-in-the-loop performance in terms of interpretative decision-making). The results presented are directly from the device's output. Clinical studies compare its performance against clinical diagnoses, recognized reference standards (Western Blot), and a predicate device.
7. Type of Ground Truth Used
The ground truth for the various studies includes:
- Clinical Diagnosis: For characterized samples (e.g., acute, convalescent patients with history of Borreliosis, culture-proven early acute Lyme disease, patients diagnosed with Borreliosis).
- Predicate ELISA: For comparison studies (Prospective, Retrospective) where samples were categorized as "reference assay positive" or "reference assay negative" based on the predicate ELISA.
- Western Blot: Used as a confirmatory test for discrepant results between the investigational device and the predicate device. For the "Characterized Samples" table, Western Blot results are presented as another comparator for agreement with clinical diagnosis.
- CDC Characterized Lyme Panel: Samples from the CDC with established reactivity profiles.
- Normal Blood Donors/Non-infectious Individuals: Used to assess specificity/low prevalence.
8. Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning or AI algorithm development. This is an immunoassay, not typically developed using machine learning with distinct training and test sets in the same way an AI diagnostic algorithm would be. The studies described are validation studies for the device's performance, not for training stages.
9. How the Ground Truth for the Training Set Was Established
Since no explicit "training set" for an AI algorithm is mentioned (as the device is an immunoassay), the method for establishing ground truth for a training set is not applicable here. The focus is on the validation of the assay's performance using established methods of clinical and analytical evaluation.
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