Search Results
Found 1 results
510(k) Data Aggregation
(309 days)
The IMMULITE 2000 Anti-CCP IgG assay is an in vitro diagnostic immunoassay for the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum (including Serum Separator Tubes) or plasma (EDTA or lithium heparin) on the IMMULITE 2000 system. Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criteria diagnostic process, encompassing both clinical and laboratory-based assessments.
The IMMULITE 2000 Anti-CCP IgG Calibration Verification Material (CVM) is for in vitro diagnostic use, as a control for calibration verification of the IMMULITE 2000 Anti-CCP IgG assay on the IMMULITE 2000 system.
The IMMULITE 2000 Anti-CCP IgG assay consists of the following components:
- Anti-CCP IgG bead pack coated with cyclic citrullinated peptide . (CCP) antigen
- Anti-CCP IgG reagent wedge containing bovine calf intestine . conjugated to a monoclonal murine anti-human IgG antibody
- Anti-CCP IgG adjustors, low and high, containing lyophilized . human serum with IgG reactive to CCP
- Anti-CCP IgG controls, negative and positive, containing human . serum
- . Autoantibody sample diluent containing protein/buffer matrix
The IMMULITE Anti-CCP IgG Calibration Verification Material consists of one set of four vials, containing low, intermediate and high levels of lyophilized human serum with IgG reactive to cyclic citrullinated peptide (CCP), in buffer with preservative, plus an anti-CCP-free sample.
The IMMULITE® 2000 Anti-CCP IgG Assay is an in vitro diagnostic immunoassay for the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP). It is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information.
Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state acceptance criteria in a single, consolidated table. However, performance characteristics are reported, which implicitly define what the manufacturer considers acceptable for their device to perform as intended and to demonstrate substantial equivalence to the predicate device. Based on the performance characteristics presented, the following can be inferred as the "acceptance criteria" through the demonstrated results.
| Performance Characteristic | Acceptance Criteria (Implicit from Results) | Reported Device Performance |
|---|---|---|
| Precision (Total CV%) | Generally, Coefficients of Variation (CV%) for diagnostic assays should be within acceptable limits (e.g., <10-15% for clinically relevant concentrations). | Ranged from 4.3% to 14.8% for SERP2 (lowest conc.) across different samples and statistical breakdowns (Within-Run to Total Within-Lot). This is generally acceptable for immunoassay precision. |
| Specifically, lower concentrations tend to have higher CVs. | Examples: | |
| - LPIC2 (47.4 U/mL): Total CV 4.3% | ||
| - SERP2 (2.1-1.94 U/mL): Total CV 13.6% (20-Day) / 14.8% (Reproducibility) | ||
| - SERP6 (144.0-139.18 U/mL): Total CV 4.8% (20-Day) / 5.1% (Reproducibility) | ||
| Linearity/Reportable Range | Demonstrating linearity across the specified reportable range (1.50 - 200 U/mL) with acceptable recovery. | Percent recovery generally within ±10% range (e.g., 77.4% to 104.3%). Most samples are above 90%. Exception: P13 (2.64 U/mL) at 77.4% recovery. |
| Detection Limit (LoD) | LoD should be sufficiently low for clinical utility. | LoD determined to be 1.46 U/mL. LoB 0.26 U/mL. |
| Analytical Specificity (Interference) | Mean interference of common endogenous substances should be less than a certain threshold (e.g., ±10%). | Mean interference for all tested substances (Albumin, Triglycerides, Hemoglobin, Bilirubin, Rheumatoid Factor) was less than 10%. |
| Method Comparison (vs. Predicate) | High positive and negative agreement with the predicate device. | Reagent Lot 1: Positive Agreement 86.9%; Negative Agreement 46.2%; Total Agreement 82.2% |
| Reagent Lot 2: Positive Agreement 86.1%; Negative Agreement 42.3%; Total Agreement 81.6% | ||
| Clinical Sensitivity & Specificity | Demonstrating acceptable diagnostic performance (sensitivity and specificity) for aid in RA diagnosis. | Sensitivity: 63.6%; Specificity: 97.0% |
| Matrix Comparison | High correlation and minimal bias between different sample types (serum, plasma). | Correlation Coefficient: 1.000 for all comparisons (Lithium Heparin, SST Serum, EDTA Plasma vs. Serum). Slopes near 1, intercepts near 0. |
2. Sample Sizes Used for the Test Set and Data Provenance
The document describes several studies, each with its own sample size and data provenance:
- Precision/Reproducibility Study:
- 20-Day Imprecision: 11 samples over 20 days, 2 instruments, 2 reagent lots, 2 runs/day, 2 replicates/sample. Total N for calculations is 320 for each sample. Data provenance not specified, but likely internal (manufacturer's lab).
- Reproducibility (Multi-site): Serum donor panels from precision study, 2 different reagent lots, run over 10 days, 2 runs/day, 4 replicates/run. Tested at three external testing sites. N=244 to 246 for each sample for Reagent Lot 201, and N=228 to 240 for Reagent Lot 202. Data provenance suggests multi-site, potentially from different geographical regions but not explicitly stated. Retrospective.
- Linearity Study: A dilution series (11 dilutions) prepared from a reactive and non-reactive serum pool. Run in triplicate on one IMMULITE® 2000 instrument. Data provenance likely internal.
- Detection Limit Study:
- LoB: Non-reactive donor sample tested on 3 instruments over 5 days, twice daily, 2 lots of reagent, 2 replicates/run. NB = 732 blank measurements. Data provenance not specified, likely internal.
- LoD: Five Anti-CCP serum samples (0.26 to 2.5 U/mL) assayed in replicates of 6 using 2 reagent kit lots, run for 5 days with 2 runs/day. Two instruments and 2 operators, generating 960 observations. Data provenance not specified, likely internal.
- Analytical Specificity (Interference) Study: One control sample and five (5) different sample pools with differing Anti-CCP concentrations (range 2.0 U/mL to 205 U/mL) were used. Each substance spiked separately. Data provenance not specified, likely internal.
- Assay Cut-off Determination: 388 samples: 212 apparently healthy samples, 106 RA positive samples, 70 anti-CCP positive samples (as determined by a 3rd party method). Data provenance not specified (country of origin), but implies external patient samples. Retrospective.
- Method Comparison with Predicate Device:
- Reagent Lot 1: 255 unaltered patient serum samples.
- Reagent Lot 2: 256 unaltered patient serum samples.
- Data provenance not specified (country of origin), but implies external patient samples. Retrospective.
- Matrix Comparison: 39 matched serum and plasma samples (serum clot, Lithium Heparin, SST, EDTA plasma tubes). 21 of these were spiked. Data provenance not specified, likely internal or from a single collection site.
- Clinical Sensitivity and Specificity Study: 1512 patient serum samples. 1048 RA positive (classified by ACR criteria) and 464 non-RA (with potentially cross-reactive diseases). Data provenance not specified (country of origin), but implies external patient samples. Retrospective.
- Expected Values/Reference Range Study: 200 serum samples from presumed healthy male and female donors. Data provenance not specified (country of origin). Retrospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications
The document does not specify the number of experts used or their qualifications for establishing the ground truth for any of the test sets.
- For the Assay Cut-off Determination and Method Comparison studies, "RA positive samples" and "anti-CCP positive samples, as determined by a 3rd party method" are mentioned, suggesting a clinical diagnosis or another validated assay served as the reference, but reviewer expertise is not detailed.
- For the Clinical Sensitivity and Specificity Study, "RA positive patients were classified according to the ACR criteria." The American College of Rheumatology (ACR) criteria are a widely accepted standard for RA diagnosis, implying that these classifications were made by qualified clinicians (rheumatologists or physicians trained in RA diagnosis). However, the number of such experts and their specific qualifications are not provided.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1, none) for the test sets.
- For the Clinical Sensitivity and Specificity Study, the RA positive patient classification "according to the ACR criteria" is a standardized diagnostic approach, which implicitly involves clinical assessment. However, how consistency or discrepancies in these classifications were handled (e.g., by multiple clinicians, consensus panels) is not described.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) immunoassay, which generates quantitative or semi-quantitative results rather than images requiring human interpretation. Therefore, the concept of "human readers improving with AI vs. without AI assistance" is not applicable in this context. The comparison is primarily between the device's output and clinical reference standards or predicate IVD devices.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies conducted are inherently "standalone" in the sense that they evaluate the performance of the IMMULITE® 2000 Anti-CCP IgG Assay directly, without a human-in-the-loop component for result generation. The assay produces a numerical result (U/mL) which is then interpreted against a clinical cut-off. Performance characteristics like precision, linearity, detection limit, analytical specificity, and clinical sensitivity/specificity assess the algorithm's (assay's) performance. While the interpretation of the results by clinicians for actual patient diagnosis involves human judgment, the device itself provides an objective measurement.
7. The Type of Ground Truth Used
Different types of ground truth were used depending on the study:
- Clinical Sensitivity and Specificity: Patients classified as RA positive "according to the ACR criteria" (American College of Rheumatology criteria). This represents expert consensus clinical diagnosis based on established medical guidelines.
- Assay Cut-off Determination: "RA positive samples" and "anti-CCP positive samples, as determined by a 3rd party method." This implies either clinical diagnosis (for RA positive) or results from a legally marketed predicate/reference assay (for anti-CCP positive).
- Method Comparison with Predicate Device: The predicate device, DIASTAT™ Anti-Cyclic Citrullinated Peptide (anti-CCP) ELISA, results were used as the comparator for agreement analyses. This represents comparison to an existing, validated diagnostic method.
- Laboratory Performance (Precision, Linearity, LoD, Interference): Ground truth is typically established by the inherent properties of the prepared samples (e.g., spiked concentrations, known non-reactive samples) or statistical calculations from repeated measurements.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI algorithms as the device is an immunoassay. However, if "training set" refers to samples used for developing and optimizing the assay's parameters (e.g., cut-off determination), the primary studies mentioned include:
- Assay Cut-off determination: 388 samples were used (212 healthy, 106 RA positive, 70 anti-CCP positive from a 3rd party method) for ROC analysis to establish the cut-off. This set played a role analogous to a "training/optimization set" for the cut-off value.
- Adjustors and Controls: "prepared in house and arbitrary units are assigned during the development process," suggesting internal work to define these.
- Reference Calibrators: "A lot of reference calibrators was prepared by diluting the positive unit with negative normal human serum." These calibrators were "value-assigned by the dilution factor," and this internal standard is used for traceability.
9. How the Ground Truth for the Training Set Was Established
As noted above, for an immunoassay, the concept of a "training set" and its "ground truth" differs from typical AI/ML contexts.
- Assay Cut-off Determination: The ground truth for the 388 samples used in ROC analysis for cut-off determination was established by:
- Clinical diagnosis: for "RA positive samples" and "healthy samples."
- Results from a 3rd party method: for "anti-CCP positive samples."
- Reference Calibrators and Controls: These are established through internal arbitrary assignment, dilution factors, and extensive validation (e.g., precision, stability, value assignment across multiple lots and instruments) against an internal master batch (internal standard). This ensures consistency and reproducibility of the assay's quantitative output.
Ask a specific question about this device
Page 1 of 1