(126 days)
The Platelia" Lyme IgG assay is a qualitative test intended for use in the presumptive detection of human IgG antibodies to Borrelia burgdorferi in human serum or plasma (K3 EDTA, sodium heparin or sodium citrate). The EIA test system should be used to test serum or plasma from patients with a history and symptoms of infection with B. burgdorferi. All positive and equivocal specimens should be re-tested with a specific, second-tier test such as Western blot. Positive second-tier results are supportive evidence of infection with B. burgdorferi. The diagnosis of Lyme disease should be made based on history and symptoms (such as erytherna migrans), and other laboratory data, in addition to the presence of antibodies to B. burgdorferi. Negative results (either first or second-tier) should not be used to exclude Lyme disease.
The Platelia" Lyme IgG Assay is a qualitative assay for the detection of human IgG antibodies to Borrelia burgdorferi in human serum or plasma. The PlateliaTM Lyme IgG Assay uses an indirect ELISA immuno-enzymatic method. Inactivated antigens of Borrelia burgdorferi B31 are used for coating the microplate. A monoclonal antibody labeled with peroxidase which is specific for human gamma chains (anti-IgG) is used as the conjugate.
The Bio-Rad Platelia™ Lyme IgG assay is a qualitative test intended for the presumptive detection of human IgG antibodies to Borrelia burgdorferi in human serum or plasma.
Here's an analysis of the acceptance criteria and the studies performed:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for the sensitivity and specificity values. Instead, it presents the performance of the device and a comparative analysis. Here's a summary of the reported performance:
| Performance Metric | Acceptance Criteria (Implicit from comparable device performance and general expectations for diagnostic tests) | Reported Device Performance (Platelia™ Lyme IgG) |
|---|---|---|
| Sensitivity | Demonstrated ability to detect Borrelia burgdorferi IgG antibodies in infected individuals. | - Retrospective Study (Culture-confirmed): |
All Stages: 62.7% (CI [54.5, 69.0]) | ||
Early Stage: 59.2% (CI [50.2, 67.6]) | ||
Disseminated Stage: 60.6% (CI [43.7, 75.3]) | ||
Late Stage: 100.0% (CI [77.2, 100]) | ||
| Specificity | Demonstrated ability to yield negative results in uninfected individuals and those with other conditions. | - Analytical Specificity (Blood Donors): |
Endemic Region: 1.2% positive/equivocal | ||
Non-Endemic Region: 0.0% positive/equivocal | ||
Overall: 0.5% positive/equivocal | ||
| Agreement with Clinical Diagnosis (CDC Panel) | Comparable agreement to a marketed device for various time points from onset and normal samples. | Total: 69.8% (for the Platelia™ Lyme IgG) vs. 63.6% (for Predicate Lyme IgG EIA Assay) |
| Cross-Reactivity | Minimal cross-reactivity with other disease conditions. | 1 out of 161 (0.62%) samples from 16 disease conditions showed cross-reactivity (1 Syphilis sample) |
| Precision | Acceptable intra-assay, inter-assay, and inter-site variability (CV%). | CV% values generally ranged from ~2% to ~18% across various samples and precision types. |
| Matrix Comparison | Results for plasma should be comparable to serum with minimal change in interpretation. | Small variation in positive/equivocal samples, no change in interpretation. Large variation in negative plasma vs. serum, but no change in interpretation. |
| Interfering Substances | Results should not be affected by common interfering substances. | No effect observed from albumin, unconjugated bilirubin, triolein, and hemoglobin within specified concentrations. |
2. Sample Sizes and Data Provenance
- Sensitivity (Retrospective Study):
- Test set size: 166 patient samples.
- Data provenance: Retrospective. The origin country is not explicitly stated, but it's implied to be within relevant geographical regions for Lyme disease based on the nature of the study.
- Sensitivity (CDC Panel):
- Test set size: 43 samples (Platelia™ Lyme IgG) / 44 samples (Predicate Lyme IgG EIA Assay).
- Data provenance: A serum panel obtained from the CDC. The document mentions this panel is "masked, characterized." Implied U.S. origin.
- Prospective Study:
- Test set size: 439 samples.
- Data provenance: Prospective, collected at two different sites in an endemic region in the United States.
- Analytical Specificity:
- Test set size: 183 blood donor samples.
- Data provenance: 83 samples from endemic regions (northeastern US) and 100 samples from non-endemic regions (Nevada, Oregon, and Louisiana) in the United States.
- Cross-Reactivity:
- Test set size: 161 samples.
- Data provenance: Serums from individuals in the United States with disease conditions other than Lyme disease.
- Matrix Comparison Study:
- Test set size: 25 samples (12 negative, 13 positive or equivocal).
- Data provenance: Not specified, but likely from a lab setting where different matrices were prepared or collected.
3. Number of Experts to Establish Ground Truth and Qualifications
The document does not explicitly state the number or qualifications of experts used to establish ground truth for the test sets.
- Retrospective Study: Ground truth was "confirmed positive for Borrelia burgdorferi infection by culture." This suggests a gold standard method, not expert-based consensus.
- CDC Panel: The panel is described as "masked, characterized," implying that the clinical diagnoses were established by recognized authorities (CDC) using a combination of clinical information and laboratory results, but the specific expert count or qualifications aren't detailed.
- Prospective Study: The comparative method used was the "two-tier protocol recommended by the CDC (samples found positive or equivocal on ELISA are retested by Western Blot)." This is a standardized diagnostic workflow, not expert consensus for each individual case.
- Analytical Specificity and Cross-Reactivity: Ground truth appears to be based on the established clinical status of the blood donors (healthy) or patients with specific non-Lyme diseases, likely confirmed through standard diagnostic methods for those conditions.
4. Adjudication Method
No explicit adjudication method (e.g., 2+1, 3+1) is mentioned for the establishment of ground truth in the document for any of the studies. The ground truth was primarily based on objective laboratory findings (culture, Western blot) or established clinical diagnoses rather than subjective expert review requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study involving human readers with and without AI assistance was done. This device is an in vitro diagnostic (IVD) immunoassay, not an AI-powered image analysis or diagnostic decision support tool intended to be used by human readers in that capacity.
6. Standalone (Algorithm Only) Performance
The studies presented describe the standalone performance of the Platelia™ Lyme IgG assay. As an immunoassay, its performance is inherently "standalone" in the sense of being an algorithmic/mechanical process that yields a result without direct human interpretation in achieving that result (though human interpretation is needed for clinical application of the result). The sensitivity, specificity, and agreement data directly reflect this standalone performance.
7. Type of Ground Truth Used
- Retrospective Study: Borrelia burgdorferi infection confirmed by culture. This is a strong and direct form of ground truth.
- CDC Panel: "Clinical diagnosis" and a "characterized serum panel," implying a combination of clinical presentation and other diagnostic results (which often include Western blot for Lyme).
- Prospective Study: The CDC two-tier protocol (ELISA followed by Western Blot for positives/equivocals) was used as the reference method. This is the accepted diagnostic pathway for Lyme disease.
- Analytical Specificity: Healthy blood donors (implied absence of Lyme disease) and individuals from non-endemic regions.
- Cross-Reactivity: Individuals with specific other disease conditions (e.g., Syphilis, CMV, ANA).
8. Sample Size for the Training Set
The document does not provide information about a separate "training set" in the context of device development. Immunoassays like the Platelia™ Lyme IgG are typically developed and validated using a structured approach that includes characterization of reagents, optimization of the assay protocol, and then performance evaluation using clinical samples. Unlike machine learning algorithms, there isn't a distinct "training set" in the same sense. The reported data pertains to the final validated performance of the device.
9. How the Ground Truth for the Training Set Was Established
Since there is no explicit mention of a "training set" in the context of machine learning, ground truth establishment for such a set is not applicable to this immunoassay. The development and validation process would have involved internal studies and characterization using various types of samples, but these are not typically categorized as a "training set" with ground truth established in the same manner as for AI/ML models.
§ 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).