(160 days)
The VIDAS Lyme IgG (LYG) assay is an automated qualitative enzyme immunoassay intended for use on the instruments of the VIDAS family in the presumptive detection of human IgG antibodies to Borrelia burgdorferi in human serum (plain or separation gel) or plasma (sodium heparin or lithium heparin). It should be used to test patients with a history and/or symptoms of infection with B. burgdorferi. All VIDAS Lyme IgG positive specimens should be further tested with a Western Blot IgG assay to obtain supportive evidence of infection with B. burgdorferi.
The VIDAS Lyme IgG assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device for the assay. Reagents for the assay are ready-to-use and predispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.
After a preliminary wash step and a sample dilution step, the sample is cycled in and out of the SPR. Antibodies to B. burgdorferi present in the specimen will bind to the B. burgdorferi antigen coating the interior of the SPR. Unbound sample components are washed away. Anti-human IgG antibodies conjugated with alkaline phosphatase will attach to the immunocomplex bound to the SPR wall. A final wash step removes unbound conjugate.
During the final detection step, the substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence is proportional to the quantity of anti-B. burgdorfen IgG antibodies present in the sample. At the end of the assay, results are automatically calculated by the instrument. A test value is generated and a report is printed for each test.
Here's a breakdown of the acceptance criteria and the study details for the VIDAS® Lyme IgG Assay, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for sensitivity, specificity, or agreement rates. Instead, the study reports the performance of the VIDAS Lyme IgG assay and compares it to a predicate device, aiming to demonstrate substantial equivalence rather than meeting specific numerical thresholds set forth as acceptance criteria. However, we can infer performance targets based on the documented results and competitive performance against the predicate.
For the purpose of this exercise, I will present the reported performance, and where applicable, indicate an implicit "acceptance" based on comparison to the predicate device or a recognized standard (like the CDC panel).
| Performance Metric | Acceptance Criteria (Inferred/Implicit) | Reported Device Performance (VIDAS Lyme IgG) | Supporting Study Section |
|---|---|---|---|
| Sensitivity (Clinical) | At least comparable to predicate device | Overall: 64.40% (95% CI [57.3% – 71.0%]) | H. Clinical Testing - Sensitivity testing |
| Stage I (1-30 days) | 49.60% | ||
| Stage II (1-30 days) | 83.60% | ||
| Stage III (late) | 90.90% | ||
| Positive % Agreement (PPA) | Not explicitly stated | 74.0 % (94/127) [95% CI; 65.5% - 81.4%] | H. Clinical Testing - Method Comparison |
| Negative % Agreement (NPA) | Not explicitly stated | 95.8 % (812/848) [95% CI; 94.2% - 97.0%] | H. Clinical Testing - Method Comparison |
| Analytical Specificity (Endemic) | Not explicitly stated | 3.0% Positivity, 97.0% Negativity | H. Clinical Testing - Analytical Specificity |
| Analytical Specificity (Non-Endemic) | Not explicitly stated | 0.0% Positivity, 100.0% Negativity | H. Clinical Testing - Analytical Specificity |
| CDC Reference Panel (Agreement with Clinical Status) | Demonstrated performance with characterized panel (no specific %) | Overall: 66.6% (26/39) | H. Clinical Testing - CDC Reference Panel |
| Normals | 100.0 % (5/5) | ||
| 1 year | 100.0 % (7/7) | ||
| Precision | Acceptable within-run, within-day, between-days variability | See detailed table in section G. | G. Nonclinical Tests - Precision |
| Reproducibility | Acceptable within-run, within-day, between-days, and between-site variability | See detailed table in section G. | G. Nonclinical Tests - Reproducibility |
| Interfering Substances | No significant influence from specified substances | None identified for listed substances | G. Nonclinical Tests - Interfering Substances |
| Cross-Reactivity | Low cross-reactivity for listed conditions | Small numbers of positive results for some conditions (e.g., Anti Nuclear Antibodies 8.33%, Systemic Lupus Erythematosus 7.14%) | H. Clinical Testing - Cross-Reactivity |
2. Sample Size Used for the Test Set and Data Provenance
- Sensitivity Testing: 202 retrospective samples
- Data Provenance: Not explicitly stated (implied clinical samples from patients meeting case definition).
- Method Comparison (PPA/NPA): 975 fresh or frozen prospectively collected sera
- Data Provenance: Endemic area of the United States (prospectively collected).
- Analytical Specificity: 100 sera from an endemic population (New York) and 100 sera from a non-endemic population (Texas).
- Data Provenance: New York (endemic), Texas (non-endemic).
- CDC Reference Panel: 39 serum samples
- Data Provenance: Obtained from the CDC.
- Cross-Reactivity: Varies for each infection/diagnosis, ranging from 19 to 256 samples.
- Data Provenance: Not explicitly stated for each group.
- Nonclinical Tests (Precision & Reproducibility): 4 serum samples tested multiple times (80 for precision, 240 for reproducibility) and controls.
- Data Provenance: Not specified, likely internally prepared or sourced.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish ground truth for the clinical samples.
- For the Sensitivity Testing, samples were from "patients meeting a case definition of LD and confirmed positive for B. burgdorferi infection." This implies clinical diagnosis and/or confirmatory testing (which often involves expert interpretation), but direct expert counting or qualifications are not provided.
- For the Method Comparison, samples were "submitted for routine Lyme disease testing." Ground truth was established by comparison with a predicate device and then confirmed with a commercially available Lyme IgG Western Blot method, following CDC recommendations for two-tier testing. This indicates a multi-methodological approach to ground truth, but not direct expert consensus on each case.
- For the CDC Reference Panel, the samples are described as a "masked, characterized serum panel." This implies the CDC (as an expert body) established the clinical status, but the specific process (e.g., number of experts, qualifications) is not detailed.
- For Cross-Reactivity, samples were "negative with the test being evaluated and positive for the potentially interfering disease." This indicates known positivity for other infections, likely established by standard diagnostic methods.
4. Adjudication Method for the Test Set
- Clinical Sensitivity/Method Comparison: The primary adjudication method for positive cases appears to be second-tier testing with a Western Blot IgG assay, in accordance with CDC recommendations. The document states: "All VIDAS Lyme IgG positive specimens should be further tested with a Western Blot IgG assay to obtain supportive evidence of infection with B. burgdorferi" and "the VIDAS Lyme IgG positive results and the predicate Lyme IgG positive and equivocal results were confirmed using a commercially available Lyme IgG Western Blot method." This suggests a hierarchical adjudication process where initial positives are subjected to a confirmatory test.
- For the initial comparison between VIDAS and the predicate (prior to Western Blot), "equivocal results [from the predicate] were considered as positive for the evaluation."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not conducted. This device is an automated in vitro diagnostic assay, not an AI-assisted diagnostic tool that interprets images or signals requiring human reader input or comparison.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes, the studies presented are standalone performance evaluations of the VIDAS Lyme IgG assay. As an automated enzyme immunoassay, its performance is assessed independently, without human interaction in the analytical process itself, beyond sample loading and results interpretation. The assay generates a quantitative result which is then interpreted qualitatively (positive/negative) by the instrument.
7. The Type of Ground Truth Used
The ground truth used in the studies varies by context:
- Clinical Sensitivity: "Patients meeting a case definition of LD and confirmed positive for B. burgdorferi infection" - implies a combination of clinical diagnosis and potentially laboratory confirmation (though specific methods for confirmation aren't exhaustively detailed for this set).
- Method Comparison: Western Blot IgG results served as the confirmatory ground truth for positive and equivocal first-tier results, following CDC recommendations. The initial comparison was against a predicate EIA (Platelia™ Lyme IgG).
- Analytical Specificity: Clinical categorization as "apparently healthy subjects from an endemic population" or "non-endemic population with no known history of Lyme disease" for negative cases, and diagnosed "infection or diagnosis" for cross-reactivity panels.
- CDC Reference Panel: The CDC provided a "masked, characterized serum panel," indicating ground truth established by the CDC, likely based on clinical status and expert characterization.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of device development or algorithm training. This is expected for an in vitro diagnostic assay of this type, where performance is derived from biochemical reactions rather than machine learning algorithms trained on data. The studies described are validation and verification studies for the manufactured product.
9. How the Ground Truth for the Training Set was Established
Since no explicit training set is mentioned as part of the assay's development or a machine learning approach, the concept of establishing ground truth for a training set is not applicable here. The assay's "training" in a broad sense would be in its initial design, optimization, and calibration based on known positive and negative samples, but these are not described in the same way as a machine learning training dataset.
§ 866.3830
Treponema pallidum treponemal test reagents.(a)
Identification. Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).