(174 days)
The QualiCode™ B. burgdorferi IgG Western Blot Kit is an in vitro qualitative assay for the detection of human IgG antibodies reactive with Borrelia burgdorferi antigens present on a membrane strip. The QualiCode™ B. burgdorferi IgG 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, specific evidence of infection with B. burgdorferi which may be useful in the diagnosis of Lyme disease. The OualiCode™ B, burgdorferi IgG Western Blot Kit can be used to test human sera at any time following onset of symptoms, and when (1) only IgM antibodies were originally detected: (2) IgG antibodies were detected previously, but were not considered significant by Western Blot; or (3) previously seronegative patients become positive by ELISA or IFA screening tests.
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 dodecvl 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 IgG antibodies is accomplished by reacting and incubating the strips with a solution containing anti-human IgG antibodies conjugated with alkaline phosphatase. Unbound conjugate antibodies are removed by washing. The qualitative assessment of the detected IgG 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 fulfill your request:
Acceptance Criteria and Study to Prove Device Meets Criteria:
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state pre-defined acceptance criteria for the device's performance metrics (sensitivity, specificity, reproducibility). Instead, it presents the "Summary of Performance" as the observed outcomes from the clinical trials. Given this, the table below reflects the reported performance as if they were the benchmarks the device met.
| Metric | Acceptance Criteria (Implied by Study Results) | Reported Device Performance |
|---|---|---|
| Specificity | ||
| Normal - endemic region | ≥ 95% Negative | 97% Negative (95-99% CI) |
| Normal - non-endemic region | ≥ 92% Negative | 96% Negative (92-98% CI) |
| Normal - overall | ≥ 95% Negative | 97% Negative (95-98% CI) |
| Cross-reactive Panel | ≥ 88% Negative | 93% Negative (88-96% CI) |
| Sensitivity | ||
| Unknown Draw Time | ≥ 69% Positive | 81% Positive (69-91% CI) |
| 12 Months Draw Time | ≥ 17% Positive | 39% Positive (17-63% CI) |
| Reproducibility | ||
| Inter-lot Agreement | ≥ 90% | 90% |
| Inter-run Agreement | ≥ 92% | 92% |
| Inter-reader Agreement | ≥ 97% | 97% |
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Sizes:
- Specificity (Normal Control): 430 samples (279 from endemic regions, 151 from non-endemic regions).
- Specificity (Cross-Reactive Panel): 172 samples.
- Sensitivity (Lyme Disease Panel): 199 samples (further categorized by draw time).
- Reproducibility (Panel): 20 specimens.
- CDC Lyme Disease Serum Panel: Used for "Substantial Equivalence" but specific sample size for this panel within the clinical trials is not explicitly stated.
- Data Provenance:
- The samples were obtained from patients with a clinical diagnosis of Lyme Disease and from normal donors from endemic and non-endemic regions.
- "Each of the clinical trial sites provided specimens that were well characterized by the site." This implies data was collected from multiple clinical trial sites.
- The data appears to be retrospective, as it refers to "archived Lyme Disease specimens" and samples that "had been drawn at different times after onset of disease."
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- The document does not explicitly state the number of experts used to establish ground truth for the test set.
- Qualifications of Experts: Not specified. However, the ground truth for "clinical diagnosis of Lyme Disease" was based on a "clinical diagnosis… in accordance with the CDC case definition," and some infections were "confirmed by culture of Borrelia from biopsies." This suggests that medical professionals (e.g., physicians, pathologists) were involved in the initial diagnosis and characterization of these samples.
4. Adjudication Method for the Test Set:
- The document does not explicitly mention an adjudication method (e.g., 2+1, 3+1).
- For Inter-reader reproducibility, it states, "each strip interpreted by two independent readers." While this involves multiple readers, it describes a reproducibility assessment rather than a consensus for establishing a definitive ground truth for individual cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a MRMC comparative effectiveness study comparing human readers with and without AI assistance was NOT done. This device is a diagnostic kit (Western Blot assay), not an AI-powered image analysis or decision support system that would assist human readers in interpretation. The "Inter-reader reproducibility" section assesses consistency between human readers interpreting the device's results, not the impact of an AI on human performance.
6. Standalone Performance Study:
- Yes, a standalone performance study was done. The entire "Summary of Performance" section details the direct performance of the QualiCode™ B. burgdorferi IgG Western Blot Kit (an "algorithm" in a broader sense of a diagnostic protocol) in detecting IgG antibodies against a defined ground truth (Lyme disease diagnosis, normal controls, cross-reactive conditions). The performance metrics (sensitivity, specificity, reproducibility) are reported for the device itself.
7. Type of Ground Truth Used:
- Clinical Diagnosis: For the Lyme disease panel, the ground truth was "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)."
- Pathology/Culture: Infection was "confirmed by culture of Borrelia from biopsies in many examples." This provides a strong, direct form of ground truth for a subset of the Lyme disease cases.
- Screening Assay Results: Specimens were "required to have tested positive or indeterminate on a B. burgdorferi screening assay, typically an ELISA." This indicates a level of pre-screening was used to select the Lyme disease panel.
- Normal Donor Status: For the specificity studies, ground truth was based on samples from "Normal population" (from endemic and non-endemic regions) and "samples from patients with diseases other than Lyme disease that may be cross - reactive." The assumption here is that these samples are truly negative for Lyme disease.
8. Sample Size for the Training Set:
- The document does not explicitly mention a separate "training set" for the device. As a Western Blot kit, it's a biochemical assay rather than a machine learning model that typically requires a distinct training phase. The "clinical trials" described here are designed for validation and performance evaluation of the developed assay, not for training it.
9. How Ground Truth for the Training Set Was Established:
- Since a separate training set is not indicated in the context of this type of device, this question is not applicable. The device's components (antigens, reagents) are developed based on scientific understanding of B. burgdorferi and immunology, not through a data-driven training process with a specific ground truth dataset like an AI model.
§ 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).