(104 days)
The Gold Standard Diagnostics Borrelia burgdorferi B31 IgG Line Blot Test Kit is intended for the qualitative detection of IgG antibodies to B. burgdorferi sensu stricto (B31) in human serum. This test is intended for use in testing human serum samples which have been found positive or equivocal using an ELISA or IFA test procedure to provide supportive evidence of infection with B. burgdorferi.
The assay requires a total of 70 minutes incubation time. The test uses purified antigens coated on nitrocellulose strips. Serum is added to each strip and incubated for 30 minutes. If Borrelia burgdorferi antibodies are present they will bind to the antigens on the strips. Unbound serum is removed by washing the wells three times. An enzyme-conjugated anti-human IgG is then added to each strip and incubated for 30 minutes. If antibody is present, it will bind to the antibody attached to the antigen on the strip. The wells are again washed three times followed by a DI water wash to remove any unbound conjugate. After unbound conjugate has been removed by a further washing step, a visualization of the antigen-antibody complex is accomplished by the addition of a substrate which forms blue-violet precipitates at each site (antigen bands). The reaction is stopped by washing the nitrocellulose strip with distilled or deionized water. Depending on the observed band pattern one can interpret the presence of specific IgG antibodies to B. burgdorferi infection.
Here's a breakdown of the acceptance criteria and study details for the Gold Standard Diagnostics Borrelia burgdorferi B31 IgG Line Blot Test Kit, based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied by the predicate device comparison and various performance studies. Explicit, quantifiable acceptance criteria are not clearly stated as pass/fail thresholds in this summary but are demonstrated through observed agreement and sensitivity/specificity values compared to a predicate device and clinical classifications.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Reproducibility | Consistent results for band and sample interpretation. | Band Reproducibility: Negative (100%), High Negative (92.8%), Low Positive (97.6%), Moderate Positive (100%). Sample Reproducibility: Negative (100%), High Negative (100%), Low Positive (87.8%), Moderate Positive (100%). _Note: Expected 95% for low positive_ |
| Cross-Reactivity | Minimal or no significant cross-reactivity with common interfering conditions/infections (comparable to predicate). | 3/215 (1.4%) cross-reactivity detected (2 Babesiosis, 1 Tick-borne relapsing fever/Rickettsial Diseases). These also tested positive on the predicate device. |
| Interfering Substances | No change in final interpretation with tested interferents. | No influence on band pattern, small variability in band intensity within normal deviation range. Final interpretation unchanged. |
| Specimen Stability | Consistent results after specified storage conditions. | Consistent results for: 2-8°C for up to 168 hours; Room Temp for up to 8 hours; up to 10 freeze-thaw cycles. |
| Clinical Sensitivity | Comparable to predicate device and clinically expected values. | Early: 7.5% (3/40) [95% CI: 1.6%-20.4%] (Predicate: 7.5%) |
| Disseminated: 60.0% (12/20) [95% CI: 36.1%-80.9%] (Predicate: 60.0%) | ||
| Late: 95.0% (38/40) [95% CI: 83.1%-99.4%] (Predicate: 92.5%) | ||
| Analytical Specificity | High specificity, especially in non-endemic regions. | Endemic: 98.3% (113/115 negative) |
| Non-Endemic: 100% (119/119 negative) | ||
| CDC Reference Panel Agreement | High agreement with CDC reference values, comparable to predicate. | Healthy: 100% (5/5) (Predicate: 100%) |
| Early: 93.3% (14/15) (Predicate: 100%) | ||
| Intermediate: 84.6% (11/13) (Predicate: 76.9%) | ||
| Late: 100% (7/7) (Predicate: 85.7%) | ||
| Method Comparison (PPA/NPA) | High Positive and Negative Percent Agreement with predicate. | Positive Percent Agreement: 99.1% (112/113) [95% CI: 95.2-100%] |
| Negative Percent Agreement: 99.0% (195/197) [95% CI: 96.4-99.9%] |
2. Sample Size and Data Provenance for Test Sets
- Reproducibility: Not explicitly stated as "test set" but 4 samples (negative, high negative, low positive, moderate positive) were tested, generating 30 data points per sample. Data provenance not specified (likely internal laboratory).
- Cross-Reactivity: 215 specimens. Provenance: "known to contain potentially cross reactive antibodies to B. burgdorferi" and "patients with infections and sera from patients with diagnoses that can be confused with the late manifestations of Lyme disease." Retrospective implied.
- Interfering Substances: 6 sera (2 positive, 1 low positive, 1 high negative, 2 negative). Data provenance not specified (likely internal laboratory).
- Specimen Collection and Handling: 3 samples. Data provenance not specified (likely internal laboratory).
- Sensitivity Testing: 100 clinically characterized samples. Provenance: obtained from Allen C. Steere, MD at the Massachusetts General Hospital, United States. Retrospective (clinically characterized samples).
- Analytical Specificity: 234 asymptomatic samples (blood donors). Provenance: "from both endemic and non-endemic regions" (of Lyme disease), implied United States. Retrospective.
- CDC Reference Panel: 40 samples (5 Healthy, 15 Early, 13 Intermediate, 7 Late). Provenance: Provided by the CDC, United States.
- Method Comparison: Not explicitly stated as a single number for the "test set" but based on the 2x2 table, it's 310 samples (112+2+1+195). Provenance: Prospective clinical study at three different geographic sites in the U.S. (Pennsylvania, North Carolina, and California).
3. Number of Experts and Qualifications for Ground Truth - Test Set
- Reproducibility, Cross-Reactivity, Interfering Substances, Specimen Collection & Handling: No information provided regarding experts for ground truth. Interpretation of bands for these studies was likely performed by qualified lab personnel.
- Sensitivity Testing: "100 clinically characterized samples obtained from Allen C. Steere, MD at the Massachusetts General Hospital." Allen C. Steere is a highly renowned expert in Lyme disease, a physician and rheumatologist, so his clinical characterization would be considered expert ground truth. The exact number of additional experts or their qualifications is not specified, but the source implies high-level clinical expertise.
- Analytical Specificity: Ground truth is implied by the samples being "asymptomatic samples (blood donors)" and their origin from endemic/non-endemic regions for Lyme disease. No explicit experts mentioned, but the nature of the samples serves as the de facto ground truth (healthy/uninfected).
- CDC Reference Panel: Ground truth is established by the CDC, meaning these panels are meticulously characterized and broadly accepted as reference standards. No individual experts are named beyond the CDC institution itself.
- Method Comparison: Ground truth is implied by the comparison to a "commercially available B. burgdorferi IgG Blot test" (the predicate device) after initial screening by ELISA. The study also mentions discrepant samples were tested on "a second commercially available assay." This suggests a comparative approach rather than a single expert adjudication for ground truth.
4. Adjudication Method for the Test Set
- For studies where an adjudication method might be relevant (e.g., Method Comparison), the document implies a comparison to a predicate device and a secondary assay for discrepant results, rather than a formal expert adjudication method like 2+1 or 3+1. For instance, in the method comparison: "The discrepant samples were tested on a second commercially available assay." This suggests a chain of evidence but not a formal consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly done. This study focuses on the standalone performance of the device against a predicate and clinical classifications, not on how human readers' performance improves with or without AI assistance. The device is a laboratory diagnostic test, not an AI-assisted diagnostic tool for image interpretation by human readers.
6. Standalone Performance
- Yes, a standalone performance study was done extensively. The entire submission details the performance of the Gold Standard Diagnostics Borrelia burgdorferi B31 IgG Line Blot Test Kit on its own, through various non-clinical and clinical tests (reproducibility, cross-reactivity, interfering substances, specimen stability, sensitivity, analytical specificity, CDC panel agreement, and method comparison with a predicate device). This is the primary focus of the 510(k) submission.
7. Type of Ground Truth Used
The ground truth varied depending on the study:
- Reproducibility, Interfering Substances, Specimen Stability: Likely internal lab characterization and known properties of samples.
- Cross-Reactivity: Clinical diagnosis of other infections/conditions.
- Sensitivity Testing: Expert clinical characterization by Allen C. Steere, MD (Massachusetts General Hospital). This represents high-level clinical ground truth.
- Analytical Specificity: Implied by the source of samples (asymptomatic blood donors from endemic/non-endemic regions), representing clinically healthy/uninfected individuals.
- CDC Reference Panel: CDC-established reference values/characterization for known Lyme disease stages and healthy controls.
- Method Comparison: Initial screening by ELISA, followed by comparison to a legally marketed predicate device and a "second commercially available assay" for discrepant results. This is a comparative ground truth against established methods.
8. Sample Size for the Training Set
- Information on a specific "training set" is not provided in this 510(k) summary. This type of regulatory submission for a diagnostic kit typically focuses on the validation of the finalized product rather than the development and training phases of an algorithm. For a traditional laboratory assay like a line blot, "training set" doesn't apply in the same way it would for a machine learning algorithm. The development process likely involved internal optimization and testing, but these are not disclosed as formal "training sets."
9. How the Ground Truth for the Training Set Was Established
- As a "training set" is not explicitly mentioned or applicable in the context of this traditional line blot assay as described in the 510(k), the method for establishing its ground truth is not applicable/not provided.
§ 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).