(174 days)
The QualiCode™ B. burgdorferi IgM Western Blot Kit is an in vitro qualitative assay for the detection of human IgM antibodies reactive with Borrelia burgdorferi antigens present on a membrane strip. The QualiCode™ B. burgdorferi IgM Western Blot Kit is intended for supplemental testing of human serum specimens which yield positive or equivocal results on B. burgdorferi ELISA or IFA screening assays. QualiCode test results can provide additional, more specific evidence of infection with B. burgdorferi which may be useful in the diagnosis of Lyme disease.
The QualiCode™ B. burgdorferi IgM Western Blot Kit can be used to test human sera for IgM antibodies during the acute phase of disease, within one month of infection, in accordance with CDC/ASTPHLD guidelines. During this period, patients may not yet have developed a detectable IgG response. Beyond one month from infection, an IgG Western Blot test is recommended. Patients should not be tested solely for IgM antibodies at this stage due to the higher probability of false-positive results. Symptomatic patients showing IgM but not IgG antibodies at an early stage in infection should be re-tested for IgG antibodies 2-4 weeks later.
The device is a Western Blot assay. Proteins and other antigenic components of the Borrelia spirochete are fractionated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The separated proteins are electrophoretically transferred from the gel to nitrocellulose membranes. which are subsequently blocked to minimize non-specific binding and cut into strips. These nitrocellulose strips with resolved Borrelia burgdorferi antigens are then reacted with diluted serum and controls (positive and negative sera of defined reactivity).
During the incubation period, human antibodies specific to the B, burgdorferi antigens, if present in the sample or control, will bind to the antigen to which they have affinity. Unbound serum and non-specific antibodies are washed from the strip. Detection of bound IgM antibodies is accomplished by reacting and incubating the strips with a solution containing anti-human IgM antibodies conjugated with alkaline phosphatase. Unbound conjugate antibodies are removed by washing. The qualitative assessment of the detected IgM antibodies is then accomplished by the reaction of the alkaline phosphatase with a chemical substrate, which is cleaved into a colored, insoluble product that can be visualized. The determination of the reactivity of each unknown specimen is accomplished by comparison of the identified, visualized bands to the Band Identifying and Band Intensity Controls.
Here's an analysis of the provided text to extract the requested information about device acceptance criteria and studies:
Immunetics QualiCode™ B. burgdorferi IgM Western Blot Kit (K991062)
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria (e.g., "The device must achieve X% sensitivity and Y% specificity"). Instead, it presents the performance characteristics found during the clinical trials. We can infer the expected performance based on these reported values.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Specificity | High specificity across normal and cross-reactive populations | Normal - Overall: 96% (95% CI: 93-97%) |
| Normal - Endemic Region: 95% (95% CI: 92-97%) | ||
| Normal - Non-Endemic Region: 96% (95% CI: 92-98%) | ||
| Cross-Reactive Panel: 87% (95% CI: 88-96%) | ||
| Sensitivity | High sensitivity particularly in the early acute phase (12 months:** 47% (95% CI: 25-72%) | |
| Inter-Lot Reproducibility | High agreement between different kit lots | 80% Interpretation Agreement |
| Inter-Run Reproducibility | High agreement between different runs | 85% Interpretation Agreement (overall, averaged over 3 sites) |
| Inter-Reader Reproducibility | High agreement between different readers | 93% Interpretation Agreement (overall, averaged over 3 sites) |
2. Sample Sizes and Data Provenance for the Test Set
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Specificity Test Set:
- Normal Population: n=430 (279 from Lyme disease endemic regions, 151 from non-endemic regions).
- Cross-Reactive Panel: n=172 (samples from patients with diseases other than Lyme disease that may be cross-reactive).
- Total Specificity Samples: 602
- Provenance: Not explicitly stated by country, but regional (endemic/non-endemic) and from clinical trial sites. The data is retrospective, as these were "well-characterized, archived Lyme Disease specimens" and other pre-existing panels.
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Sensitivity Test Set:
- Lyme Disease Panel: n=186 (samples from patients with a clinical diagnosis of Lyme disease).
- Provenance: Not explicitly stated by country, but from clinical trial sites. The data is retrospective, consisting of "well-characterized, archived Lyme Disease specimens." These samples were drawn at different times after onset of disease.
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Reproducibility Test Set:
- Panel: n=20 specimens (including positive, weakly reactive, and negative sera).
- Provenance: Not specified, but likely internal or from the clinical trial sites.
3. Number of Experts and their Qualifications for Ground Truth
The document does not explicitly state the number of experts or their specific qualifications for establishing the ground truth for the test set. However, it does refer to:
- "Clinical diagnosis of Lyme Disease in accordance with the CDC case definition, i.e. based on the presence of EM (erythema migrans) or the presentation of late Lyme clinical manifestations (e.g., arthritic, cardiac, or neurological symptoms)." This implies diagnosis by clinicians.
- "Infection was confirmed by culture of Borrelia from biopsies in many examples."
- "Specimens selected for the trial were required to have tested positive or indeterminate on a B. burgdorferi screening assay, typically an ELISA, in accordance with the two-tier testing protocol recommended by CDC/ASTPHLD." This indicates that initial characterization involved standard serological testing overseen by labs or clinicians.
- The "Lyme Disease Serum Panel" from the Centers for Disease Control (CDC) was also used, which would have its own established ground truth.
For the reproducibility studies, "two independent readers" were used for inter-reader reproducibility, but their qualifications are not specified.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (like 2+1 or 3+1) for establishing the ground truth of the test set specifically for this study. Instead, the samples were "well-characterized" based on clinical diagnosis, culture confirmation, and pre-existing serological testing (two-tier protocol) under CDC/ASTPHLD guidelines. The CDC Lyme Disease Serum Panel also likely has its ground truth externally defined and accepted.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not reported. The study focuses on the standalone performance of the device and its reproducibility characteristics (inter-lot, inter-run, and inter-reader agreement), not on comparing human readers with and without AI assistance.
6. Standalone Performance Study (Algorithm Only)
Yes, a standalone performance study was done. The entire "Summary of Performance" section describes the device's performance (sensitivity, specificity, reproducibility) on various sample panels without human interpretation assistance for the core performance metrics. The result interpretations from the device were compared against the established ground truth of the samples.
7. Type of Ground Truth Used for the Test Set
The ground truth for the test set was a combination of:
- Clinical Diagnosis: Based on CDC case definition (erythema migrans or late Lyme clinical manifestations).
- Pathology/Culture Confirmation: Infection confirmed by culture of Borrelia from biopsies in many examples.
- Established Serological Testing: Initial positive or indeterminate results on B. burgdorferi screening assays (ELISA/IFA) following CDC/ASTPHLD two-tier testing protocol.
- Reference Panels: Utilization of the Centers for Disease Control Lyme Disease Serum Panel, which comes with its own established reference status.
8. Sample Size for the Training Set
The document does not provide information on a specific training set or its sample size. The description of "clinical trials" and "characterized samples" refers to the general methodology for assessing the device's performance, but there is no explicit mention of data used to "train" the assay itself in the context of machine learning or AI. This is a traditional in-vitro diagnostic (IVD) device, not an AI/ML-based device.
9. How Ground Truth for the Training Set Was Established
Since there's no mention of a dedicated training set in the context of an AI/ML algorithm, this question is not applicable. The "training" of a traditional IVD device like this is typically through its design, reagent selection, and optimization during development, rather than a data-driven training set used for machine learning. The clinical performance data presented here serves to validate the final device's performance against established ground truths.
§ 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).