(251 days)
The VIDAS Lyme IgM (LYM) assay is an automated qualitative enzyme immunoassay intended for use on the instruments of the VIDAS family in the presumptive detection of human IgM 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 IgM positive and equivocal specimens should be further tested with a Western Blot IgM assay to obtain supportive evidence of infection with B. burgdorferi.
The VIDAS Lyme IgM assay principle combines a 2-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA) (see User's Manual).
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 antibodies to B. burgdorferi present in the specimen will bind to the B. burgdorferi specific recombinant proteins coating the interior of the SPR.
Unbound sample components are washed away. Anti-human IgM 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 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. burgdorferi IgM antibody present in the sample.
At the end of the VIDAS Lyme IgM assay, results are automatically calculated by the instrument. A test value is generated and a report is printed.
The provided text describes the 510(k) summary for the VIDAS® Lyme IgM Assay. Here's a breakdown of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly present a table of acceptance criteria for performance metrics. Instead, it presents the device's performance results, which are then compared to a predicate device and established Lyme disease testing methodologies. The "acceptance" can be inferred from the statement in Section I, "Conclusion," which states that the results "demonstrate that the VIDAS® Lyme IgM is substantially equivalent to the predicate device."
However, we can extract the key performance metrics reported in relation to the predicate and other ground truth methods:
| Performance Metric | Acceptance Criteria (Implied / Comparator) | Reported Device Performance (VIDAS Lyme IgM) | Study/Section |
|---|---|---|---|
| Sensitivity (Stage I Lyme Disease) | Compared to Predicate (Platelia™ Lyme IgM) | 52.1% (62/119) | Clinical Testing - Sensitivity |
| Sensitivity (Stage II Lyme Disease) | Compared to Predicate (Platelia™ Lyme IgM) | 91.9% (57/62) | Clinical Testing - Sensitivity |
| Sensitivity (Stage III Lyme Disease) | Compared to Predicate (Platelia™ Lyme IgM) | 76.2% (16/21) | Clinical Testing - Sensitivity |
| Overall Sensitivity (All Stages) | Compared to Predicate (Platelia™ Lyme IgM) | 66.8% (135/202) | Clinical Testing - Sensitivity |
| First Tier Positive % Agreement (PPA) | Compared to Predicate Lyme IgM | 51.0% (107/210) | Clinical Testing - Method Comparison |
| Negative % Agreement (NPA) | Compared to Predicate Lyme IgM | 88.6% (678/765) | Clinical Testing - Method Comparison |
| Second Tier Positive % Agreement (PPA) | Compared to Predicate Lyme IgM + Western Blot IgM | 80.8% (84/104) | Clinical Testing - Second-Tier Testing |
| Concordance with IgM Western Blot | Not explicitly stated as a target, but reported for comparison. | 49.0% (95/194) | Clinical Testing - Second-Tier Testing |
| Cross-Reactivity (Overall Range) | Not explicitly stated, but reported for various infections/diagnoses. | Ranges from 4.34% (Mumps) to 35.00% (HIV) | Clinical Testing - Cross-Reactivity |
| Precision (Total CV%) | Not explicitly stated, but clinical data provided | Sample 1: 5.2%; Sample 2: 9.1%; Sample 3: 4.7%; Sample 4: 6.9%; Positive Control: 10.1%; Negative Control: 0.0% | Nonclinical Tests - Precision |
| Reproducibility (Total CV%) | Not explicitly stated, but clinical data provided | Sample 1: 6.3%; Sample 2: 7.8%; Sample 3: 6.2%; Sample 4: 9.4%; Positive Control: 12.1%; Negative Control: 0.0% | Nonclinical Tests - Reproducibility |
2. Sample Size for the Test Set and Data Provenance
Sensitivity Testing (Retrospective):
- Sample Size: 202 retrospective samples.
- Data Provenance: Samples were from patients meeting a case definition of Lyme Disease (LD) and confirmed positive for B. burgdorferi infection. The country of origin is not specified but implied to be regions with LD prevalence due to the context of "clinical testing." These were clearly retrospective samples.
Method Comparison (Prospective):
- Sample Size: 975 fresh or frozen prospectively collected sera.
- Data Provenance: Samples were submitted for routine Lyme disease testing from an endemic area of the United States. These were prospective samples.
Analytical Specificity:
- Sample Size: 100 sera from apparently healthy subjects from an endemic population (New York) and 100 sera from a non-endemic population (Texas).
- Data Provenance: Healthy subjects from New York (endemic) and Texas (non-endemic). These are likely retrospective collections of healthy individuals.
CDC Reference Panel:
- Sample Size: 39 samples (5 Normals, 5 1 year).
- Data Provenance: A serum panel obtained from the CDC. The origin of the individual samples within the panel is not detailed but is typically well-characterized retrospective samples.
Cross-Reactivity Testing:
- Sample Size: Varied per infection/diagnosis, ranging from 20 (HIV) to 270 (Syphilis). Total samples across all categories would be the sum (e.g., 60 ANA, 61 CRP, etc.).
- Data Provenance: Samples from patients negative for Lyme but positive for various other conditions. The country of origin is not specified but implies diverse patient populations to cover various diseases. These are likely retrospective collections.
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 (e.g., "radiologist with 10 years of experience") used to establish the ground truth for the test set.
However, the ground truth for the Sensitivity Testing refers to "patients meeting a case definition of LD and confirmed positive for B. Burgdorferi infection." This implies a clinical diagnosis, potentially relying on multiple factors and clinical judgment.
For the Second-Tier Testing, the ground truth for confirmation was a "commercially available Lyme IgM Western Blot method." While Western Blot itself is a laboratory test, its interpretation often involves expertise. The document doesn't specify if expert consensus was used for Western Blot interpretation in this study.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method (like 2+1 or 3+1 consensus) for establishing the ground truth or resolving discrepancies between readers/tests.
For the sensitivity and method comparison studies, the performance of the VIDAS assay was compared to either a "case definition" (for sensitivity) or a "predicate Lyme IgM EIA method" and subsequently "Western Blot IgM assay" for confirmation. The document implies that the results of these comparator methods, particularly Western Blot for the second tier, served as the reference standard without detailing a multi-expert adjudication process.
For both the VIDAS Lyme IgM and the predicate test in the sensitivity study, "equivocal results were considered as positive for the evaluation." This is a defined rule for handling equivocal results rather than an adjudication process.
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. The study focuses on evaluating the performance of an automated laboratory assay (VIDAS Lyme IgM) against a predicate device and established diagnostic algorithms (e.g., 2-tier testing with Western Blot), not on the comparative effectiveness of human readers with and without AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance evaluation was done. The VIDAS® Lyme IgM assay is an automated qualitative enzyme immunoassay. The studies (precision, reproducibility, sensitivity, method comparison, analytical specificity, cross-reactivity, CDC reference panel) evaluate the performance of this assay as a device in itself, producing results automatically by the instrument, without a human-in-the-loop component for result generation or primary interpretation in the context of these evaluations. The output is a numerical index and a qualitative result (positive, equivocal, negative).
7. The Type of Ground Truth Used
The types of ground truth used include:
- Clinical Case Definition/Confirmed Infection: For the sensitivity study, samples were from "patients meeting a case definition of LD and confirmed positive for B. Burgdorferi infection." This implies a combination of clinical symptoms and other diagnostic evidence.
- Predicate Device/Western Blot IgM Assay: For the method comparison and second-tier testing, the predicate Platelia™ Lyme IgM assay and a "commercially available Lyme IgM Western Blot method" were used as reference standards for comparison and confirmation, respectively.
- Known Health Status/Other Infection: For analytical specificity and cross-reactivity, subjects were either "apparently healthy" or known to be infected with other specific pathogens/conditions while being negative for Lyme disease.
- CDC Characterized Serum Panel: A masked serum panel from the CDC, which is typically characterized through extensive clinical and laboratory data, served as another reference.
8. The Sample Size for the Training Set
The document does not provide any information regarding a training set size. This is typical for a 510(k) summary for an immunoassay, which does not employ machine learning or AI models that require specific training sets in the same way. The device's underlying "algorithm" (ELFA technique) is based on biochemical reactions, not data-driven machine learning.
9. How the Ground Truth for the Training Set was Established
Since no training set is mentioned (as the device is not an AI/ML system), the establishment of ground truth for a training set is not applicable to this device.
§ 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).