(439 days)
MRL Diagnostics' Lyme Disease B. burgdorferi Genogroup 1 Western Blot IgG test is intended for the qualitative detection of IgG class antibodies, in human serum, to the genogroup 1 (Borrelia burgdorferi sensu stricto) of B. burgdorferi sensu lato. The MRL Diagnostics Lyme Disease B. burgdorferi Western Blot IgG test is intended to provide supportive evidence of infection with B. burgdorferi, the causative agent of Lyme disease as an aid in the diagnosis of Lyme disease, using serum samples which have been found positive or equivocal by a B. burgdorferi screening method (e.g., IFA or ELISA). The MRL Diagnostics Lyme Disease B. burgdorferi Western Blot IgG can be used at any time following onset of symptoms provided the IFA or ELISA is positive or equivocal. Also, it should be used for follow up when: 1) only IgM antibodies were originally detected, 2) IgG antibodies were detected, but were not considered significant by Western blot, or 3) previously seronegative patients subsequently test positive by IFA or ELISA.
MRL Diagnostics separates B. burgdorferi proteins by polyacrylamide gel electrophoresis and electrophoretically transfers the fractionated proteins from the gel to a nitrocellulose membrane. The nitrocellulose membrane is dried and cut into strips. The antigen strips are numbered and packaged. The MRL Diagnostics Lyme Disease B. burgdorferi Genogroup 1 Western Blot IgG test is a two stage procedure. In the first stage, the patient sera is diluted and incubated with individual antigen strips. If antibodies to B. burgdorferi are present in the sera, they will bind to the Borrelia antigens immobilized on the nitrocellulose membranes. In the second stage, visualization of the bound antibodies is accomplished by incubating the blots with alkaline phosphatase-conjugated goat anti-human IgG, (Fc fragment specific) followed by the addition of substrate (BCIP/NBT) which forms a colored precipitate at each site (antigen band) where the anti-human conjugate has bound. The resulting pattern of band reactivity is then interpreted.
Response to Request for Information on Device Acceptance Criteria and Study Details:
This document is a 510(k) Safety and Effectiveness Summary for the MRL Diagnostics Lyme Disease B. burgdorferi Genogroup 1 Western Blot IgG device. It describes the device, its intended use, and performance data.
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state formal "acceptance criteria" with numerical targets for sensitivity, specificity, and reproducibility. Instead, it presents the results of studies demonstrating the device's performance across various populations and conditions. The implied acceptance, given the 510(k) clearance, is that the demonstrated performance is considered substantially equivalent to a predicate device and adequate for its intended use as an aid in diagnosing Lyme disease.
Here's a table summarizing the reported device performance:
| Performance Metric | Reported Device Performance (MRL Diagnostics Lyme Disease B. burgdorferi Genogroup 1 Western Blot IgG) |
|---|---|
| Sensitivity (Overall) | 46% (83/179) (95% CI: 39-54%) (Across three investigational sites) |
| Specificity (Normals) | 100% (0/82 for endemic normals; 0/244 for non-endemic normals) |
| Specificity (Cross-reactives) | Generally 0%, with some exceptions: Arthritis (7%), Arthralgia (9%), Misc. Neurologic (4%) |
| Reproducibility (Intra-lab) | 90% for interpretation, 90-100% for individual bands |
| Reproducibility (Inter-lot) | 90% for interpretation, 90-100% for individual bands |
| Reproducibility (Inter-reader) | 94% for interpretation, 90-98% for individual bands |
| Reproducibility (Inter-site) | 88% for interpretation, 73-97% for individual bands |
Note: The sensitivity values are provided for different timeframes post-infection as well, indicating varying performance throughout the course of the disease. The document highlights that "weakly reactive (borderline) specimens decrease the kit's reproducibility."
2. Sample Sizes Used for the Test Set and Data Provenance:
Sensitivity Study (Lyme Disease Population):
- Total Sample Size: 184 well-characterized Lyme disease positive patient sera from 158 patients.
- Data Provenance: Retrospective.
- Investigational Sites 1 and 2 used samples from their "own well-characterized serum banks."
- Investigational Site 3 used a "retrospective well characterized serum panel supplied by the CDC."
- Country of Origin: Not explicitly stated but implied to be United States given the CDC involvement.
Specificity Study (Normal and Cross-reactive Populations):
- Total Sample Size: 606 sera.
- Normal Population: 326 serum samples (from endemic and non-endemic areas).
- Cross-reactive Disease Samples: 286 disease state serum samples.
- Data Provenance: Retrospective.
- Normal samples from persons with "no known history of Lyme disease."
- Cross-reactive samples from patients with "potentially cross-reactive diseases."
- Country of Origin: Not explicitly stated but implied to be United States given the context of general public health data and CDC involvement.
Reproducibility Studies:
- Intra-laboratory and Inter-lot Reproducibility: 10 serum samples (of varying reactivity).
- Inter-reader and Inter-site Reproducibility: 18 patient sera.
- Data Provenance: Retrospective, as these were established serum samples used for testing.
- Country of Origin: Not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not explicitly state the number of individual experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth for the test sets.
However, it describes the ground truth for the Lyme Disease population as:
- Patients with EM (Erythema migrans), a late stage symptom per the CDC case definition.
- B. burgdorferi seropositive.
- B. burgdorferi culture positive.
For the CDC panel, it describes "well-characterized" and "masked, characterized serum panel." This implies that the CDC (Centers for Disease Control and Prevention), a leading public health institution in the US, established the characterization, which would involve expert consensus and established diagnostic criteria for Lyme disease.
For normal and cross-reactive populations, the ground truth was based on "persons with no known history of Lyme disease" and "patients with potentially cross-reactive conditions or infections," respectively. This suggests clinical diagnosis by healthcare professionals rather than a specially convened expert panel for the study.
4. Adjudication Method for the Test Set:
The document does not describe a formal adjudication method (e.g., 2+1, 3+1) for establishing the ground truth of the test set. The ground truth appears to have been established prior to the study using existing clinical and laboratory diagnostics, often leveraging CDC definitions and characterized serum banks.
For reproducibility studies, two readers at each site performed the inter-reader and inter-site assessments, but no formal adjudication of discrepancies is described, only the percentage of identical interpretations and band readings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
A formal MRMC comparative effectiveness study comparing human readers with and without AI assistance was not conducted. The device described is a diagnostic test (Western Blot IgG), not an AI-powered image analysis tool that assists human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, the studies conducted are standalone evaluations of the diagnostic device. The device itself is a laboratory assay (Western Blot) that produces a pattern of bands. Interpretation of these bands is inherent to the use of the device, but the performance metrics provided (sensitivity, specificity) reflect the output of the device and its interpretation rules, rather than the performance of an AI algorithm assisting a human. The reproducibility studies evaluate the consistency of interpretation by human readers, but this is part of the device's operational performance, not an AI assisting human performance.
7. The Type of Ground Truth Used:
The ground truth used for the test sets was a combination of:
- Clinical Definition/Case Definition: For Lyme Disease patients, the CDC case definition (presence of EM, late-stage symptoms) was used.
- Laboratory Confirmation: B. burgdorferi seropositivity or culture positivity was used for Lyme disease patients.
- Historical Data/Clinical Diagnosis: For normal individuals, a lack of known history or symptoms of Lyme disease. For cross-reactive conditions, the clinical diagnosis of those specific conditions.
- Well-Characterized Serum Panels: The CDC supplied a "masked, characterized serum panel" for one of the investigational sites. This typically implies a rigorous, expert-driven characterization process.
8. The Sample Size for the Training Set:
The document does not mention a "training set" in the context of an algorithm or AI. This is a traditional diagnostic assay (Western Blot), not a machine learning model that requires a distinct training phase. The populations described (Lyme disease, Normal, Cross-reactive) are test sets used to evaluate the assay's performance.
9. How the Ground Truth for the Training Set Was Established:
As there is no "training set" for an algorithm in this context, this question is not applicable. The device relies on biochemical reactions and a predefined interpretive criteria for bands rather than a trained algorithm.
§ 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).