(315 days)
The iDart™ Lyme IgG ImmunoBlot Kit is an immunoblot assay intended for the in vitro qualitative detection of IgG antibodies to Borrelia burgdorferi in human serum. The iDart Lyme IgG ImmunoBlot Kit is intended to detect antibodies to LSA and multiple other B. burgdorferi antigens following a modified two-tier test methodology. Positive results from the iDart Lyme IgG ImmunoBlot Kit are supportive evidence for the presence of antibodies and exposure to B. burgdorferi. Negative results do not preclude infection with B. burgdorferi. iDart™ Lyme IgG ImmunoBlot Kit is intended to aid in the diagnosis of Lyme disease and the test kit should only be used on samples from patients with clinical history, signs and symptoms consistent with Lyme disease. The iDart Lyme IgG Immunoblot Kit is not intended as a screen for asymptomatic patients.
Test results are to be used in conjunction with information obtained from the patient's clinical evaluation and other diagnostic procedures.
For in vitro diagnostic use only
For professional use only
For prescription use only
The iDart™ Lyme IgG ImmunoBlot tests are line immunoblot assays. Antigenic proteins specific for Borrelia species that cause Lyme Disease are produced by recombinant DNA technology in Escherichia coli. The purified proteins are then applied as discrete lines on a nitrocellulose membrane along with two control proteins.
The iDart™ Lyme IgG ImmunoBlot Kit contains IgG ImmunoBlot strips and the proteins are applied in the following order: C1 (lgG/lgM - conjugate control), C2 (Protein L - calibrator/serum control), P93, P41, P39, P23, P31, P66, P58, P45, P34, P30, P28, P18 and LSA (a chimeric VISE peptide termed the Lyme Screen Antigen).
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the iDart™ Lyme IgG ImmunoBlot Kit are primarily demonstrated through its analytical performance (reproducibility, analytical specificity, cross-reactivity, interference) and clinical performance (method comparison with STTT, clinical sensitivity/specificity using a CDC panel).
| Acceptance Criteria Category | Specific Metric / Evaluation | Acceptance Threshold (Implied/Explicit) | Reported Device Performance (as stated) |
|---|---|---|---|
| Analytical Performance | |||
| Reproducibility | Agreement across sites, operators, runs, days | 100% agreement expected | 100% agreement of all bands among all runs, all days and across 3 sites for negative, moderate negative, high negative, moderate positive, and high positive samples (Table 1). |
| Analytical Specificity (Endemic) | Specificity in healthy individuals from endemic areas | High specificity | 99.36% (2 false positives out of 313 samples from CDC and Bay Area Lyme Foundation) (Table 2). |
| Analytical Specificity (Non-Endemic) | Specificity in healthy individuals from non-endemic areas | High specificity | 100% (0 false positives out of 112 samples from CDC and CA) (Table 3). |
| Cross-Reactivity | False positivity with various conditions | Low/no cross-reactivity | 100% specificity for LSA, 98.67% specificity for ≥2 bands, and 100% specificity for IgG Positive across 376 potentially cross-reactive samples from various disease states and infections (Table 4). Minor false positives (5 for ≥2 bands) were noted but resulted in 0% IgG positive or only a single band out of the two required for positivity. |
| Interference | Effect of endogenous analytes | No interference | No interference observed for bilirubin, albumin, cholesterol, triglycerides, and hemoglobin at specified low and high concentrations on positive, low positive, and negative Borrelia IgG samples (Table 5). |
| Clinical Performance | |||
| Method Comparison (STTT) | Positive Percent Agreement (PPA) with STTT | High PPA and NPA | Bay Area Lyme Foundation (n=290): PPA: 95.00% (95% CI: 76.39% – 99.11%), NPA: 86.67% (95% CI: 82.09% – 90.21%) (Table 7) |
| IGeneX Inc. Cohort 2 (n=248): PPA: 95.00% (95% CI: 89.52% – 97.69%), NPA: 90.63% (95% CI: 84.33% - 94.56%) (Table 8) | |||
| IGeneX Inc. Cohort 3 (n=230): PPA: 90.91% (95% CI: 62.27% – 98.38%), NPA: 96.80% (95% CI: 93.55% – 98.44%) (Table 9) | |||
| Clinical Sensitivity | Performance against CDC Reference Panel | High sensitivity for later stages | Stage I: 58.33% (higher than STTT at 30.00%) |
| Stage II: 90.00% (equal to STTT) | |||
| Stage III: 100% (equal to STTT) | |||
| Overall: 71.11% (higher than STTT at 52.22%) (Table 10). | |||
| Clinical Specificity | Performance against CDC Reference Panel | High specificity | Healthy controls: 100% (equal to STTT) |
| Disease Controls: 100% (equal to STTT) (Table 10). | |||
| Fresh and Frozen Sample Comparability | Consistent results between fresh and frozen samples | Consistent results | All IgG positive samples remained positive and all negative samples remained negative after freezing (Table 11). |
| Antibody Class Specificity | Specificity of anti-human IgG conjugate | Specific to IgG | All positive samples tested without treatment or with human IgM remained positive, and all negative samples remained negative. When treated with human IgG, all positive samples became negative, confirming specificity (Table 12). |
2. Sample Size Used for the Test Set and Data Provenance
- Reproducibility: 90 samples for each of the 6 sample types (High Positive, Moderate Positive, Negative-1, Negative-2, Negative-3, Low Positive). Total of 540 tests performed across 3 sites, 2 operators, 5 days, 2 runs/day. Data provenance is not explicitly stated beyond "blinded and coded samples."
- Analytical Specificity (Healthy Individuals):
- 313 samples from endemic areas (CDC, Bay Area Lyme Foundation - NY, MA, WI).
- 112 samples from non-endemic areas (CDC, CA).
- Cross-Reactivity Study: 376 samples from various disease states/infections (CDC, IGeneX (CA), New York Biological (NY), BEI, Kamineni Life Sciences Pvt. Ltd, Hydrabad (India), Warde Medical Laboratory (MI)).
- Interference Study: One positive, one low positive, and one negative Borrelia IgG sample were used for each interference agent and concentration, tested in singlicate.
- Clinical Studies (Method Comparison with STTT): A total of 768 serum samples.
- Site 1: 290 clinical serum samples from Bay Area Lyme Foundation.
- Site 2: 37 clinical serum samples (Cohort 2) + 230 clinical serum samples (Cohort 3) from IGeneX Inc.
- Site 3: 211 clinical serum samples (Cohort 2) from IGeneX Inc.
- Data provenance: "procured from two vendors" (Bay Area Lyme Foundation and IGeneX Inc.). Samples were "prospective banked samples" or "clinical serum samples."
- Clinical Sensitivity/Specificity (CDC Serum Panel): 280 serum samples from CDC (patients with Lyme disease at different stages, look-alike conditions, healthy controls from endemic and non-endemic regions).
- Fresh and Frozen Samples Comparison Study: 72 decoded left-over patient serum samples.
- Antibody Class Specificity: 10 previously tested patient samples (6 negatives, 4 positives).
All clinical samples were "blinded, re-coded."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state that experts were used to establish ground truth for the test set derived from clinical samples. Instead, the ground truth for these clinical performance studies appears to be based on:
- STTT (Standard Two-Tier Test Methodology): This is a laboratory-based diagnostic algorithm involving an EIA/IFA screen followed by an immunoblot. Its results serve as the comparator (ground truth) for the method comparison study.
- CDC Reference Panel: For the clinical sensitivity/specificity, the CDC reference panel implicitly has established diagnoses for Lyme disease stages and other conditions. The process by which CDC established these diagnoses (e.g., expert consensus, other gold standards) is not detailed here.
For the reproducibility study, the samples were "blinded and coded" with "expected result" (e.g., High Positive, Negative). It's not specified how these initial categorizations were established.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method involving multiple experts resolving discrepancies for the test set results. The evaluations are primarily against established comparators like STTT or reference panels (CDC). For the reproducibility study, the agreement was 100%, so no adjudication would have been required for discrepancies.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The performance studies focus on the device's standalone accuracy against existing diagnostic methods/reference panels, rather than how human readers' performance might improve with or without AI assistance. The device is an ImmunoBlot Kit, not an AI-assisted diagnostic imaging or interpretation system.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, the studies reflect the standalone performance of the iDart™ Lyme IgG ImmunoBlot Kit. The "Principle of procedures" describes manual interpretation ("A strip reading guide included in each test kit shows the location of specific antigens in the test strip. ... Any band found having a visual intensity equal to or greater than the C2 control band intensity is considered as a significant (positive) band. Depending on the observed bands pattern, one can interpret the presence or absence of Lyme specific IgG antibodies in the patient serum."). The "Result Generation" for the device is listed as "Manual reading" in the comparison table. This indicates the studies assess the kit's performance as a laboratory test, interpreted by a human, but without a "human-in-the-loop" AI system.
7. The Type of Ground Truth Used
- Clinical Performance (Method Comparison): The "ground truth" was established by Standard Two-Tier Test Methodology (STTT), which involves FDA-cleared EIA and immunoblot tests, performed by laboratory personnel.
- Clinical Sensitivity/Specificity: The "ground truth" was established by the CDC Reference Panel, which represents diagnosed cases of Lyme disease at various stages, look-alike conditions, and healthy controls. The methods for establishing these CDC diagnoses are not detailed but likely involve a combination of clinical assessment and established laboratory criteria.
- Analytical Specificity / Cross-reactivity: Ground truth for these samples was "known to contain potentially cross-reactive antibodies to Lyme infection" or "healthy individuals" or specific disease states, implying prior clinical diagnoses or sample characterization.
- Reproducibility: Samples were initially characterized as "High Positive," "Negative," etc., which served as the expected result for comparison. The method for this initial characterization is not specified.
- Fresh/Frozen & Antibody Class Specificity: Ground truth was based on "previously tested patient samples" with known IgG status.
8. The Sample Size for the Training Set
The document does not describe a "training set" in the context of machine learning or AI. The iDart™ Lyme IgG ImmunoBlot Kit is an immunoassay kit, not an AI-based device that requires model training. Therefore, this question is not applicable to the information provided.
9. How the Ground Truth for the Training Set Was Established
As the device is not an AI/ML product, there is no "training set" or corresponding ground truth establishment process described in the document.
§ 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).