(326 days)
The Cambridge Biotech Human Lyme B. burgdorferi IgG Western Blot is intended for use in testing human serum samples which have demonstrated positive or equivocal responses using EIA or IFA test procedures to provide supportive evidence of infection with Borrelia burgdorferi.
The Cambridge Biotech Human Lyme B. burgdorferi IgG Western Blot can be used at any time following onset of symptoms. It should also be used for follow up when (1) only IgM antibodies were originally detected, (2) lgG antibodies were detected but were not considered significant, or (3) previously tested seronegative individuals are shown to develop antibodies by EIA or IFA test procedures.
The assay is not intended for use as a screening assay, nor should it be used for analysis of serum from patients who have not demonstrated symptoms of Lyme Disease.
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 Dodecylsulfate. 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 Borrelia burgdorferi antigens are then reacted with diluted serum and controls (positive and negative sera of defined reactivity) during an incubation period.
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 anti-human IgG antibodies conjugated with alkaline containing 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.
This document describes the Cambridge Biotech Human Lyme Borrelia burgdorferi IgG Western Blot kit. Here's an analysis of its acceptance criteria and the study that proves it meets those criteria:
Acceptance Criteria and Reported Device Performance
| Criterion | Acceptance Criteria (Implicit) | Reported Device Performance |
|---|---|---|
| Specificity | High percentage agreement for negative controls and non-Lyme disease samples. | 100% (95% CI: 99.8%-100.0%) from 1062 total normal donor and disease specimens. |
| Sensitivity (Overall) | Adequate detection of Lyme disease in well-characterized samples, particularly in later stages. | Varies by disease presentation and draw time. Overall from 287 specimens: |
- Before Treatment (X%") are not directly stated but are inferred from the reported results being deemed acceptable for 510(k) clearance.
Study Information
2. Sample Size Used for the Test Set and Data Provenance:
- Specificity Test Set: 1062 samples. These included "normal donor (from endemic and non-endemic regions) and disease specimens." The specific types of disease specimens (other than Lyme) are not detailed, but they are implied to be non-Lyme conditions to assess specificity.
- Sensitivity Test Set: 287 "characterized Lyme disease specimens." These specimens were collected at different times after disease onset. The specimens were from 169 individual patients, with second draws on 92 and third draws on 36.
- Precision Test Set: Six IgG Controls, tested in duplicate on each of three days at three test sites (18 replicates per control).
- Reproducibility Test Set: 10 positive and negative specimens from the CDC 47-member panel (total 20 specimens, likely 10 positive, 10 negative, or 10 unique, tested for both).
- Data Provenance: The document states that "Each of the clinical trial sites provided specimens that were well-characterized by the site." There is no explicit mention of the country of origin, but the "CDC 47-member panel" suggests U.S. data. The studies appear to be prospective for some data collection (e.g., "draw time from disease onset") and retrospective for the use of "archived Lyme Disease specimens" and the CDC panel.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
- Number of Experts: Not explicitly stated.
- Qualifications of Experts: Not explicitly stated. However, ground truth was established by "clinical diagnosis of Lyme Disease based on the probability of exposure/infection (tick bite and/or patient presence in potential tick habitats in an endemic region within 30 days prior to the onset of EM), Borrelia isolation by culture (where possible), or, for non-EM patients, the presentation of Late Lyme clinical manifestations (e.g., cardiac, joint-involvement, or neurological symptoms)." Additionally, "Each of the clinical trial sites provided specimens that were well-characterized by the site using Lyme-specific serological analyses, including EIA and Western Blot testing." This implies clinical specialists and laboratory experts were involved in establishing the ground truth.
4. Adjudication Method for the Test Set:
- Adjudication Method: Not explicitly described. The reliance on "clinical diagnosis" and "well-characterized by the site" suggests that the site's standard diagnostic procedures, likely involving consensus among clinicians or adherence to established guidelines, served as the adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
- No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is a diagnostic kit (Western Blot assay) for detecting antibodies, not an AI-powered image analysis or diagnostic aid that would assist human readers in interpreting complex data.
6. If a Standalone Study (i.e., algorithm only without human-in-the-loop performance) Was Done:
- Yes, this was a standalone study. The performance characteristics of the Western Blot kit were evaluated directly, without human interpretation being the primary variable. The "reading" of the bands is part of the test procedure itself, and while human interpretation is involved, the study assesses the kit's ability to produce those bands accurately and reproducibly. The "scoring" of bands in the reproducibility study is an assessment of consistency of interpretation, rather than human performance with or without AI assistance.
7. The Type of Ground Truth Used:
- Combined Clinical, Laboratory, and Outcome Data:
- Clinical Diagnosis: Based on exposure, EM presentation, or Late Lyme clinical manifestations (cardiac, joint, neurological symptoms).
- Microbiological Evidence: Borrelia isolation by culture (where possible).
- Laboratory Serology: Lyme-specific serological analyses (EIA and Western Blot testing) at the clinical trial sites.
- Reference Panels: Centers for Disease Control Lyme Disease Serum Panel.
- Outcomes Data: Implied by "After Treatment" and categorization of "Lyme Late" presentations, suggesting assessment based on disease progression and response to treatment.
8. The Sample Size for the Training Set:
- The document describes performance evaluation (test sets) rather than a distinct "training set" for an algorithm. This is a traditional diagnostic assay, not a machine learning algorithm. Therefore, the concept of a separate training set as understood in AI/ML is not directly applicable. The "characterized samples used for the establishment of Substantial Equivalence" and the "well-characterized, archived Lyme Disease specimens" served as the basis for demonstrating performance, which is analogous to a validation set in traditional diagnostic development.
9. How the Ground Truth for the Training Set Was Established:
- As noted above, there isn't a "training set" in the AI/ML sense. The ground truth for the specimens used to establish performance (analogous to a validation set) was established through:
- Clinical Diagnosis: As detailed in point 7, based on patient history, symptoms, and clinical presentation.
- Borrelia Isolation by Culture: Direct microbiological confirmation where feasible.
- Lyme-specific Serological Analyses by Clinical Sites: EIA and Western Blot testing performed by the trial sites as part of their standard diagnostic procedures.
- Reference Panel Consensus: The CDC Lyme Disease Serum Panel specimens likely have established ground truth based on extensive characterization.
§ 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).