(326 days)
The Cambridge Biotech Human Lyme B. burgdorferi IgM Western Blot is an in vitro test system for the qualitative detection of human Immunoglobulin M (IgM) antibodies to Borrelia burgdorferi antigens in human serum. The Cambridge Biotech Human Lyme B. burgdorferi IgM 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 IgM Western Blot can be used during the acute phase (0-4 weeks of symptoms onset) of B. burgdorferi infection. After this period, infected patients are usually found to be Western Blot positive for IgG. A positive IgM test alone is not recommended for use in determining active disease in persons with illness of longer than one month.
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 neqative 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 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 510(k) summary regarding the Cambridge Biotech Borrelia burgdorferi Human Lyme IgM Western Blot kit:
Acceptance Criteria and Device Performance Study
1. Table of Acceptance Criteria and Reported Device Performance
The 510(k) summary does not explicitly state pre-defined acceptance criteria with specific numerical targets for sensitivity, specificity, precision, or reproducibility. Instead, it presents the achieved performance characteristics from the clinical trial. However, we can infer that the reported values met the implicit criteria for substantial equivalence.
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance | Comments on Acceptability |
|---|---|---|---|
| Specificity | Sufficiently high to minimize false positives | 97.5% (95% CI: 96.6% to 98.5%) | Met, considered high. |
| Sensitivity | Sufficiently high for detection in relevant patient populations | Overall (Mixed Draw Times/Treatment): 57% (Before Treatment, 0-2 months), 64% (After Treatment, 0-2 months), 39% (Lyme Late, 0-12 months) | Met, but noted variability based on disease stage and treatment. Specificity appears to be prioritized. |
| Precision | 100% agreement between sites and within sites for controls | 100% agreement across three sites for disposition of 6 IgM controls and 3 diagnostic bands. | Met, excellent consistency. |
| Reproducibility | High agreement between sites for positive/negative scores and band scoring | 100% agreement for IgM disposition scores (20 specimens) across four sites. 86.7% agreement for 3 diagnostic bands across sites. 94% overall agreement with expected IgM band scores. | Met, very good inter-site consistency. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Specificity Test Set: 1062 total samples
- Data Provenance: Normal donor specimens (from endemic and non-endemic regions) and disease specimens. The document doesn't specify the exact countries of origin but mentions endemic and non-endemic regions, suggesting geographical diversity. It is retrospective, as these were "well-characterized, archived Lyme Disease specimens" and samples from diverse disease conditions.
- Sensitivity Test Set: 296 total characterized Lyme disease specimens.
- Data Provenance: "Characterized Lyme disease specimens" drawn at different times after onset of disease. These specimens came from "169 individual patients." Second draws were done on 92 patients, and third draws on 36 patients. Clinical diagnosis of Lyme Disease was based on "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." Specimens were provided by "clinical trial sites" and "well-characterized by the site using Lyme-specific serological analyses, including EIA and Western Blot testing." This data is retrospective.
- Precision Test Set: Six IgM Controls, tested in duplicate on each of three days at three test sites.
- Reproducibility Test Set: Ten positive and ten negative specimens from the CDC 47-member panel (total 20 specimens), tested at four sites.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with X years of experience). However, it notes that:
- "characterized samples used for the establishment of Substantial Equivalence have a clinical diagnosis of Lyme Disease" based on specific criteria (exposure, EM, culture, Late Lyme symptoms).
- "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 that medical professionals (likely physicians specializing in infectious diseases, and laboratory professionals performing serological analyses) at the clinical trial sites established the clinical diagnoses and characterization, which served as the ground truth. Specific credentials or numbers are not provided.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method for the test set results (e.g., 2+1, 3+1 consensus). The clinical diagnosis and characterization by individual sites appear to have served as the ground truth. For precision and reproducibility, results were compared across multiple sites, with agreement percentages reported, suggesting a comparison or consensus model rather than a formal adjudication process described for initial ground truth establishment.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study comparing human readers with and without AI assistance was not done. This device is an in-vitro diagnostic (IVD) kit for laboratory use, not an AI-assisted diagnostic tool. Therefore, the concept of "human readers improve with AI vs. without AI" is not applicable here.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study Was Done
Yes, the performance study effectively evaluates the device in a standalone manner. The reported sensitivity, specificity, precision, and reproducibility values reflect the performance of the IgM Western Blot kit itself, as interpreted by laboratory personnel following the kit's instructions. While human technicians read the visualized bands, the "algorithm" is the Western Blot test itself, and its performance is reported independently of any additional human diagnostic steps beyond the qualitative assessment of the bands per the kit's comparison method. The human interpretation of the bands is integral to the "device performance."
7. The Type of Ground Truth Used
The ground truth used was a combination of:
- Clinical Diagnosis: Based on "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 (ervthema migrans)), 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)."
- Lyme-Specific Serological Analyses: Including EIA and Western Blot testing performed by the clinical trial sites themselves.
- CDC Lyme Disease Serum Panel: Used for reproducibility testing, which represents a highly characterized reference panel.
This is primarily a combination of expert clinical consensus and established serological test results from the providing sites.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or algorithm development. For this type of IVD, the development and optimization of the assay (e.g., protein fractionation, antibody concentrations, detection methods) are iterative processes that precede the clinical validation. The "threshold determination" (Section 7) used a preclinical testing set of 3 weakly reactive positive samples and 10 highly reactive negative samples, which could be considered an internal "optimization/training" set for establishing cut-offs.
9. How the Ground Truth for the Training Set Was Established
As noted above, for the "threshold determination" set:
- Preclinical Testing: The ground truth for these samples was presumably established during the assay development by comparing "weakly reactive Lyme antibody-positive samples" to "highly reactive Lyme antibody-negative samples." The characteristics of these samples (positive/negative for Lyme antibodies) would have been determined using established laboratory methods and clinical knowledge during the product development phase. The "negative specimens included both normal donors and samples from patients with potentially cross-reactive conditions or infections," indicating a robust 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).