(90 days)
The BioPlex 2200 Lyme Total kit is a multiplex flow immunoassay intended for the qualitative detection of total (lgM/IgG) antibodies to Borrelia burgdorferi in human serum and plasma (EDTA, heparin). This assay should be used to test patients with a history and/ or symptoms of infection with B. burgdorferi. The BioPlex 2200 Lyme Total assay is intended for use with the Bio-Rad BioPlex 2200 System. All reactive and equivocal specimens should be tested with a second tier test such as Lyme IgM and IgG Western blot assays. Positive second tier results are supportive evidence of infection with B. burgdorferi. Diagnosis of Lyme borreliosis should be made based on the presence of B. burgdorferi antibodies, history, symptoms, and other laboratory data. Non-reactive first tier or negative second tier results should not be used to exclude borreliosis.
BioPlex 2200 Lyme Total kit includes the following components:
- One (1) 10 mL vial of Bead Set , containing dyed beads coated with recombinant p58, OspC ● type B (OspCB) and synthetic peptide FVlsE (consisting of FlaB and VlsE sequences), an Internal Standard bead (ISB) and a Serum Verification bead (SVB) in MOPS (3-[N-Morpholino] propane sulfonic acid) buffer containing bovine proteins with protein stabilizers. BND (5-bromo-5-nitro-1,3-dioxan) (≤ 0.1%), ProClin 300 (≤ 0.3%), sodium benzoate (≤ 0.1%) and sodium azide (
The document provided is a 510(k) Summary for the BioPlex 2200 Lyme Total kit, which is an in vitro diagnostic (IVD) device for the qualitative detection of total (IgM/IgG) antibodies to Borrelia burgdorferi. It is not an AI/ML-driven device, nor does it involve human readers interpreting images. Therefore, many of the requested criteria in your prompt (such as human readers, AI assistance, expert consensus for ground truth, adjudication methods, or sample size for training sets) are not applicable to this type of device.
However, I can extract information related to the acceptance criteria and performance study from the provided document as it pertains to an IVD device.
Key takeaway: This document describes a traditional in-vitro diagnostic device, not an AI/ML system for diagnostic imaging. Therefore, concepts like "human readers improve with AI vs without AI assistance" or "standalone (i.e. algorithm only without human-in-the-loop performance)" are irrelevant. The "acceptance criteria" for this IVD device would typically refer to predefined performance specifications agreed upon for regulatory clearance.
Here's the relevant information based on the document provided:
1. Table of Acceptance Criteria and Reported Device Performance
For IVD devices, acceptance criteria are generally established for various performance characteristics like sensitivity, specificity, precision, cross-reactivity, and interference. The document presents the results of these studies, and the implicit acceptance is that these results demonstrate substantial equivalence to the predicate device and are clinically acceptable. The performance is compared against a commercial Lyme IgM/IgG immunoassay or a CDC reference panel.
| Performance Metric | Acceptance Criteria (Implicit from Study Design/Context) | Reported Device Performance (BioPlex 2200 Lyme Total) | Predicate Device / Commercial Assay Performance (for comparison) |
|---|---|---|---|
| Clinical Sensitivity (Prospective Samples) | (Expected to be comparable to or better than predicate) | PPA = 70.1% (68/97) (60.0 - 79.0% CI) | |
| when compared to predicate's positive/equivocal results. | Commercial Lyme IgM/IgG Immunoassay: Pos: 88, Eqv: 9, Neg: 695 | ||
| Clinical Specificity (Prospective Samples) | (Expected to be comparable to or better than predicate) | NPA = 95.1% (661/695) (93.2 - 96.6% CI) | |
| when compared to predicate's negative results. | Commercial Lyme IgM/IgG Immunoassay: Pos: 88, Eqv: 9, Neg: 695 | ||
| Sensitivity by Disease Stage (Archived Samples) | (Expected performance across stages) | Acute: 69.4% (50/72) | |
| Convalescent: 61.5% (16/26) | |||
| Late: 85.7% (6/7) | |||
| Total: 68.6% (72/105) | Commercial Lyme IgM/IgG Immunoassay: | ||
| Acute: 58.3% (42/72) | |||
| Convalescent: 69.2% (18/26) | |||
| Late: 71.4% (5/7) | |||
| Total: 61.9% (65/105) | |||
| Precision (Within Run / Total %CV) | (Low variability expected) | Within Run: 2.7% - 6.1% | |
| Total: 4.0% - 6.8% (for various AI levels) | N/A (Internal study on device's own performance) | ||
| Reproducibility (Total %CV) | (Low variability across sites/days) | Total: 5.1% - 8.1% (for various AI levels) | N/A (Internal study on device's own performance) |
| Analytical Specificity (Asymptomatic Samples) | (High percentage of negatives expected) | Asymptomatic Non-Endemic: 96.4% Negatives | |
| Asymptomatic Endemic: 96.4% Negatives | Commercial Lyme IgM/IgG Immunoassay: | ||
| Non-Endemic: 95.4% Negatives | |||
| Endemic: 94.8% Negatives | |||
| Cross-Reactivity (% Negative Agreement) | (High % Agreement, low false positives with other conditions) | 91% - 100% for various cross-reactants (e.g., EBV: 92%, Syphilis: 98%) | N/A (compared to Commercial Lyme Immunoassay's negative results) |
| Matrix Comparison (Correlation r) | (High correlation between serum and plasma) | K2-EDTA vs. Serum: r=0.960 | |
| K3-EDTA vs. Serum: r=0.951 | |||
| Sodium Heparin vs. Serum: r=0.970 | |||
| Lithium Heparin vs. Serum: r=0.981 | N/A | ||
| CDC Panel Performance | (High agreement with CDC characterized samples) | Clinical Diagnosis Agreement: Acute 84.6%, Convalescent 93.5%, Late 100%, Look-alike 96.7%, Healthy 97.0% | Comparison against another commercial assay also performed and reported. |
2. Sample Sizes Used for the Test Set and Data Provenance
- Clinical Method Comparison Study (Test Set): 792 prospectively collected serum samples from patients submitted for Lyme disease testing.
- Data Provenance: "various geographically distinct locations in the U.S." (retrospective or prospective is not explicitly stated for this part, but implies prospective collection for "patients submitted for Lyme disease testing"). The samples were evaluated at "three (3) U.S. clinical testing sites."
- Sensitivity Study (Test Set): 105 clinically characterized samples from an archived collection.
- Data Provenance: Not specified for geographical origin beyond "archived collection."
- Analytical Specificity Study (Test Set): 836 samples from asymptomatic individuals from endemic regions (416 asymptomatic non-endemic, 420 asymptomatic endemic). These were "obtained from an asymptomatic population and excluded pre-screened blood donors."
- Data Provenance: Not explicitly stated (e.g., country of origin), implies collected from relevant populations.
- Cross-Reactivity Study (Test Set): Varies per cross-reactant, e.g., 13 samples for ANA, 49 for EBV, 48 for Syphilis, etc. (Total N for this section is sum of all individual cross-reactant groups). Samples were "known to be positive for each cross-reactant" and "pre-tested by a commercially available Lyme assay and only those that tested negative by the commercially available assay were further tested."
- Precision Study: 80 replicates per panel member (6 panel members evaluated).
- Reproducibility Study: 120 total replicates per panel member (5 panel members evaluated), tested at 3 clinical trial sites.
- Matrix Comparison: Minimum of 40 sets of paired serum and plasma samples, total N for comparison ranged from 74 to 78 pairs.
- CDC Panel: 280 positive and negative specimens from the Centers for Disease Control and Prevention (CDC).
- Data Provenance: CDC (implies U.S. origin).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
Not Applicable / Not Provided for this IVD device. The device measures antibodies. The "ground truth" for clinical studies is based on patient clinical history, symptoms, and other laboratory data, or classification by a reference panel (like the CDC panel) or comparison to an already cleared predicate device. There is no mention of "experts" in the context of image interpretation or similar tasks requiring human consensus.
4. Adjudication Method for the Test Set
Not Applicable / Not Provided for this IVD device. Adjudication methods like "2+1, 3+1" are typically used for interpreting ambiguous cases or discordances in human reader studies, often in the context of imaging. For this IVD device, results are quantitative (Antibody Index) and then categorized into discrete "Reactive," "Equivocal," or "Non-Reactive" bins based on defined cut-offs. Discords between the new device and the predicate or clinical diagnosis are reported, but there's no mention of an adjudication process by human experts to resolve these, rather they are statistical comparisons. For equivocal results, the assay states they "should be tested with a second tier test such as Lyme IgM and IgG Western blot assays."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not Applicable. This document describes an IVD antibody detection kit, not an AI-assisted imaging device or a device involving human readers.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
The BioPlex 2200 Lyme Total kit is a standalone device in the sense that it performs the assay and provides quantitative results (Antibody Index) which are then categorized. There isn't a "human-in-the-loop" performing the primary measurement or interpretation in the way one would for an AI-assisted diagnostic imaging system. The device itself produces the raw data and converts it into the final qualitative result (Reactive, Equivocal, Non-Reactive) based on internal algorithms and calibrated cutoffs. Thus, all the performance data presented (sensitivity, specificity, precision, etc.) represents its standalone performance as an automated IVD assay.
7. The Type of Ground Truth Used
The "ground truth" for this IVD device's performance studies varies:
- Clinical Diagnosis: For the "Sensitivity Study" and "CDC Panel," samples were "clinically characterized" by disease stage (e.g., Acute, Convalescent, Late Lyme) or defined categories (e.g., look-alike diseases, healthy controls).
- Predicate Device Comparison: In the "Method Comparison Study," the new device's qualitative results were compared against an existing "Commercial Lyme IgM/IgG Immunoassay" (the predicate device). This serves as a reference for substantial equivalence.
- Second-Tier Testing (Western Blot): For reactive and equivocal results from both the new device and predicate, a "FDA-cleared IgG and IgM Western blot assays" was used as a confirmatory "second tier test." This provides a more definitive ground truth for those specific samples implicated as positive or equivocal by initial screening assays.
- Archived Collections/Known Status: For the precision, reproducibility, analytical specificity, interfering substances, and cross-reactivity studies, samples with pre-defined characteristics (e.g., specific concentrations, known disease states, known absence of target analyte) were used.
8. The Sample Size for the Training Set
Not Applicable / Not Provided. This document does not describe the development of an AI/ML algorithm that requires a specific training set. The device is a traditional immunoassay kit. The "assay cut-off" (similar to a classification threshold in ML) was determined using "1,372 normal sera" and was "retrospectively selected around the 98th percentile." This cohort was used to define the operational cut-off rather than "training" an algorithm in the AI/ML sense.
9. How the Ground Truth for the Training Set Was Established
Not Applicable. As above, there is no AI/ML training set. The assay cut-off was established using 1,372 normal sera, identifying a relative fluorescence intensity (RFI) corresponding to the 98th percentile to set the 1.0 AI cut-off. This was then "subsequently evaluated for performance against clinically diagnosed samples."
§ 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).