(89 days)
Lyme B. burgdorferi (IgG) MarStripe Test is an immunoblot assay for the in vitro qualitative detection of human IgG antibody to individual proteins of Borrelia burgdorferi in human serum or plasma (K2- EDTA) in samples which have been found positive or equivocal using an EIA or IFA test procedure to provide supportive evidence of infection with B. burgdorferi.
The kit is an immunoblot method to detect IgG antibodies against B. burqdorferi antigens. The test kit contains: Nitrocellulose Test Strips with purified B. burgdorferi antigens (10) and quality control lines (3) present in specific positions, Sample Diluent, Positive Control, Negative Control, Conjugate (Antihuman IgG-HRP Conjugate), TMB Substrate, and PBS Wash Buffer concentrate. To perform the test, serum or plasma is added to individual B. burgdorferi Test Strips. In positive sera antibodies specifically bind to one or more of the test lines on the strips are washed according to the protocol, and then the pre-diuted, ready-to-use Conjugate is added to the test strips. After incubation and wash steps, the ready-to-use Substrate is added to the strips. During a 10 minute (±4 min) incubation, conjugate and substrate binding produces visible blue/purple lines for Serum Addition Control (SAC), Conjugate Addition Control (CAC) and Cut-Off Control lines. If the sample is positive for any of the antigen coated test lines, it will show a reaction more intense than the Cut-Off line. Reactions are read visually and reported as positive or equivocal (comparable to Cut-Off line). Strips which have 5 (or more) of the 10 test lines are considered positive for specific IgG antibody to B. burgdorferi.
Here's a breakdown of the acceptance criteria and study details for the Lyme B. burgdorferi (IgG) MarStripe Test, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating pre-defined acceptance criteria for performance metrics like sensitivity and specificity percentage targets. However, the reported performance against the predicate device and consensus can be considered the de-facto acceptance criteria for equivalence.
| Performance Metric | Acceptance Criteria (Implicit from Predicate Equivalence) | Reported Device Performance (Lyme B. burgdorferi (IgG) MarStripe Test) |
|---|---|---|
| Reproducibility | 100% positive or negative agreement for all specimens across sites and operators | 100% (for overall positive/negative agreement across 8 specimens, 3 sites, 2 operators, 432 readouts) |
| Analytical Specificity | Not explicitly stated, but high specificity is expected, ideally comparable to predicate. | 99.5% (95% CI: 97.1% - 100%) against 219 healthy blood donors |
| Cross-reactivity | Low positive incidence, and positive specimens should be confirmed by predicate device. | 4.4% positive incidence across 136 potentially cross-reactive specimens; all positives confirmed by predicate IgG Western blot. |
| Interference | 100% qualitative agreement with and without interfering agents. | 100% qualitative agreement for all specimens (5 sera spiked with hemoglobin, bilirubin, RF, triglycerides, cholesterol). |
| Serum vs. Plasma Equivalence | 100% qualitative agreement between serum and plasma samples. | 100% qualitative agreement for all 20 pairs of serum/plasma samples. |
| Positive Agreement (vs. Predicate) | High agreement (e.g., >90%) deemed substantially equivalent to predicate. | 92.9% (95% CI: 88.6% - 95.7%) |
| Negative Agreement (vs. Predicate) | High agreement (e.g., >95%) deemed substantially equivalent to predicate. | 97.7% (95% CI: 95.9% - 98.7%) |
| Sensitivity (Clinical Specimens, vs. Predicate) | Similar sensitivity to the predicate device. | 22.3% (21/94) (95% CI: 14.7%-32.3%) - Predicate: 20.2% (19/94) |
| Sensitivity (CDC Panels, vs. Predicate) | Similar specificity to the predicate device. | 16.7% (7/42) - Predicate: 16.7% (7/42) |
2. Sample Size Used for the Test Set and Data Provenance
- Reproducibility Test: 8 specimens (2 low negative, 2 high negative, 2 low positive, 2 moderate positive). Each specimen tested in 4 replicates, 2 runs per day, for a total of 72 tests per specimen at three laboratory sites.
- Analytical Specificity: 219 sera from healthy blood donors.
- Cross-reactivity: 136 potentially cross-reactive specimens from individuals with various other or infectious conditions.
- Interference: 5 sera (2 Lyme IgG negative, 3 Lyme IgG positive).
- Serum vs. Plasma Comparison: 10 pairs of native serum/plasma samples, plus 10 pooled serum/plasma samples (total 20 pairs).
- Method Comparison (Clinical Tests): 753 prospectively collected consecutive specimens, all initially positive on an FDA-cleared first-step EIA.
- Sensitivity (Clinical Specimens): 94 well-characterized Lyme disease clinical specimens (from the 753 specimens in Method Comparison).
- CDC Panels: 42 specimens from CDC (Lyme Disease Validation Panel n=10, Lyme Disease Basic Research Panel n=32).
Data Provenance:
- Healthy Blood Donors (Analytical Specificity): Representing endemic geographic regions of the United States.
- Clinical Specimens (Method Comparison & Sensitivity): Prospectively collected consecutive specimens tested at three sites. No further country of origin or specific demographic details are provided.
- CDC Panels: From the Center for Disease Control and Prevention.
Retrospective or Prospective:
- Method Comparison (Clinical Specimens): Explicitly stated as "prospectively collected consecutive specimens." The other studies do not explicitly state but generally, these types of validation studies are prospective or involve carefully selected retrospective samples to meet specific criteria.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
There is no mention of external human experts establishing the ground truth for the test set in the conventional sense of, for example, radiologists interpreting images.
- Reproducibility: Results were read by 2 human operators at each of the 3 sites. No specific qualifications (e.g., years of experience) are provided for these operators, who are presumably laboratory personnel following a protocol.
- Method Comparison: The ground truth for comparing the device primarily relies on the predicate device (MarDx B. burgdorferi IgG MarBlot Strip Test System).
- Discrepant Analysis: For the 29 discrepant specimens, two additional commercially available B. burgdorferi IgG Western blot methods were used as comparators to establish a "consensus result." This implies laboratory methods rather than expert human interpretation.
- CDC Panels: Ground truth is established by the CDC's characterization of the panels.
4. Adjudication Method for the Test Set
- Reproducibility: No formal adjudication method like "2+1" is mentioned for individual band interpretation. The "Final positive or negative agreement was 100% for all specimens" suggests direct agreement between operators or that any differences were resolved internally to reach a unified result for each specimen.
- Discrepant Analysis (Method Comparison): A "2/3 comparator" consensus was used where the Lyme B. burgdorferi (IgG) MarStripe Test result was compared to results from two additional commercially available B. burgdorferi IgG Western blot methods.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done in the context of human readers improving with AI vs. without AI assistance. This device is a diagnostic test kit (immunoblot assay) and not an AI-powered image analysis system that would typically involve human-in-the-loop performance evaluation. The "human operators" mentioned in reproducibility are interpreting the results of the kit, not an AI output.
6. Standalone Performance Study
- Yes, a standalone performance study was done. The entire set of non-clinical and clinical tests (reproducibility batch, analytical specificity, cross-reactivity, interference, serum vs. plasma testing, and the initial method comparison against the predicate) represents the standalone performance of the device/kit itself. The "algorithm" here refers to the immunodetection process and interpretation rules inherent to the diagnostic kit, not a separate AI algorithm.
7. Type of Ground Truth Used
- Reproducibility: Based on prior FDA-cleared B. burgdorferi ELISA results (categorizing samples as low/high negative, low/moderate positive).
- Analytical Specificity: Healthy blood donors (presumed negative for Lyme).
- Cross-reactivity: Individuals with other infectious or autoimmune conditions (used to challenge specificity).
- Interference: Artificially spiked samples.
- Serum vs. Plasma Comparison: Comparison to results from an FDA-cleared Lyme EIA assay and subsequent Western blot IgG positivity/negativity.
- Method Comparison (Clinical Tests): The primary ground truth was the predicate device's result. For discrepant samples, a consensus of two additional commercial IgG Western blot methods served as the ground truth.
- Sensitivity (Clinical Specimens): "Well characterized Lyme disease clinical specimens" from the clinical study, with characterization across disease stages (early, early disseminated, late).
- CDC Panels: Characterized reference panels provided by the Center for Disease Control and Prevention.
8. Sample Size for the Training Set
No training set is explicitly mentioned or applicable in the context of this device. This is a diagnostic test kit that functions based on established biochemical reactions and interpretation algorithms, not a machine learning or AI model that requires a separate training phase. The described studies are validation studies for the finished product.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned for an AI/ML model, this question is not applicable. The device's "ground truth" (i.e., its intended performance characteristics) is established through the development and analytical/clinical validation studies presented.
§ 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).