(172 days)
The Access Intact PTH assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of intact parathyroid hormone (parathyrin, PTH) levels in human serum and plasma using the Access Immunoassay Systems. It is indicated to aid in the differential diagnosis of hyperparathyroidism, hypoparathyroidism, or hypercalcemia of malignancy and can be used intraoperatively. Assay results should be used in conjunction with other clinical data to assist the clinician in making individual patient management decisions.
The Access Intact PTH assay is a sandwich immunoenzymatic assay. The Access Intact PTH assay consists of the reagent pack and calibrators. Other items needed to run the assay include substrate and wash buffers. The Access intact PTH assay reagent pack, Access intact PTH assay calibrators, along with the Access wash buffer and substrate are designed for use on the Dxl 9000 Access Immunoassay Analyzers in a clinical laboratory setting.
The provided text describes the performance validation of the Beckman Coulter Access Intact PTH assay on the Dxl 9000 Access Immunoassay Analyzer. This is a biomedical measurement device, specifically an in vitro diagnostic (IVD) rather than an AI-powered system as might be initially implied by the format of the request. Therefore, some of the requested information regarding AI-specific criteria (like number of experts for ground truth, adjudication methods, MRMC studies, training set details) is not applicable to this type of device.
Here's an analysis of the acceptance criteria and study results, focusing on the relevant aspects for an IVD device:
Acceptance Criteria and Reported Device Performance
The study primarily focuses on demonstrating the performance characteristics of the Access Intact PTH assay run on the Dxl 9000 system, compared to its predicate device (Access Intact PTH on the Access 2 Immunoassay System). The "acceptance criteria" here are performance targets related to analytical precision, linearity, and detection/quantitation limits, based on standard laboratory guidelines (CLSI documents).
Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria (Design Criteria) | Reported Device Performance (Routine Mode) | Reported Device Performance (Intraoperative Mode) |
|---|---|---|---|
| Imprecision (Within-Laboratory) | ≤ 0.96 pg/mL (0.10 pmol/L) SD at concentrations ≤ 12 pg/mL (1.3 pmol/L) | ||
| ≤ 8.0% CV at concentrations > 12 pg/mL (1.3 pmol/L) | SD: Sample 1: 0.46 pg/mL (0.05 pmol/L) | ||
| %CV: Sample 1: 5.9%, Sample 2: 6.5%, Sample 3: 4.3%, Sample 4: 3.7%, Sample 5: 2.7% | SD: Sample 1: 0.23 pg/mL (0.02 pmol/L) | ||
| %CV: Sample 1: 13.2% (exceeds 8%), Sample 2: 5.0%, Sample 3: 4.8%, Sample 4: 4.2%, Sample 5: 4.0%, Sample 6: 4.3%, Sample 7: 3.3% | |||
| Linearity | (Implicitly: demonstrate linearity across measuring interval) | Demonstrated linearity across measuring interval (1.7 - 3500 pg/mL) | Demonstrated linearity across measuring interval (1.7 - 3500 pg/mL) |
| Limit of Blank (LoB) | ≤ 1.0 pg/mL (≤ 0.11 pmol/L) | 0.5 pg/mL (0.05 pmol/L) | 0.5 pg/mL (0.05 pmol/L) |
| Limit of Detection (LoD) | ≤ 1.0 pg/mL (≤ 0.11 pmol/L) | 0.7 pg/mL (0.08 pmol/L) | 0.8 pg/mL (0.08 pmol/L) |
| Limit of Quantitation (LoQ) (≤ 20% within-lab CV) | ≤ 1.7 pg/mL (≤ 0.18 pmol/L) | 0.7 pg/mL (0.08 pmol/L) | 0.8 pg/mL (0.08 pmol/L) |
| Method Comparison (vs. Predicate) | (Implicitly: demonstrate substantial equivalence with predicate) | ||
| Expected slopes near 1.0 and intercepts near 0, | |||
| high correlation (R near 1.0) | Slope: 0.97 (95% CI: 0.96-0.98) | ||
| Intercept: -0.23 (95% CI: -0.33 to -0.12) | |||
| Correlation (R): 1.00 | Slope: 1.02 (95% CI: 1.00-1.04) | ||
| Intercept: -0.081 (95% CI: -0.36 to 0.20) | |||
| Correlation (R): 0.99 |
Notes on Performance:
- For Imprecision, one sample in the "Intraoperative Mode" (Sample 1, 1.7 pg/mL) shows a %CV of 13.2%, which exceeds the general criteria of "≤ 8.0% CV at concentrations > 12 pg/mL (1.3 pmol/L)" and also "≤ 0.96 pg/mL (0.10 pmol/L) SD at concentrations ≤ 12 pg/mL (1.3 pmol/L)". However, given the actual concentration and the stated SD for this sample (0.23 pg/mL), it might be acceptable for very low concentrations where relative variability can be higher, or it might fall into a specific acceptance sub-criterion not fully detailed here. The SD of 0.23 pg/mL is still well below the 0.96 pg/mL SD target for concentrations ≤ 12 pg/mL.
- The correlation coefficients (R) of 1.00 and 0.99 for method comparison indicate excellent agreement with the predicate device. The slopes and intercepts also demonstrate good agreement, supporting the claim of substantial equivalence.
Study Details:
As this is a 510(k) submission for an in vitro diagnostic immunoassay system, the concept of AI-driven image analysis or clinical decision support is not applicable. Therefore, many of the questions related to AI-specific validation (e.g., number of experts, adjudication, MRMC studies, AI training sets) are not relevant to this document. The "ground truth" for an IVD refers to the true concentration of an analyte as measured by a reference method or established through rigorous characterization of control materials.
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Sample sizes used for the test set and data provenance:
- Imprecision Study:
- Routine Mode: 86 replicates for most samples (one sample with 84 replicates).
- Intraoperative Mode: 88 replicates for all samples.
- Data Provenance: Not explicitly stated, but typically these studies are conducted in a controlled laboratory setting (prospective data collection from prepared samples/controls). No country of origin for the data is specified, but given the manufacturer (Beckman Coulter, Inc., Chaska, MN, USA), it's highly likely to be US-based or from their global R&D facilities.
- Method Comparison Study:
- Routine Mode: N=144 patient samples.
- Intraoperative Mode: N=116 patient samples.
- Data Provenance: Not explicitly stated regarding country of origin or retrospective/prospective. These are typically patient plasma/serum samples collected prospectively for the study or from biobanks.
- Imprecision Study:
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable. This is an immunoassay device for quantitative determination of a hormone. The "ground truth" for these tests is based on the chemical measurement itself, validated against reference materials or established methods, not subjective expert interpretation of images or clinical data.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not Applicable. See point 2.
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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 is an automated immunoassay system, not an AI-assisted diagnostic tool requiring human reader interpretation studies.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This entire validation represents the "standalone" performance of the analytical instrument and assay kit. The Dxl 9000 Access Immunoassay Analyzer functions largely as an automated "algorithm" in that it processes samples and produces quantitative results without direct human interpretive input during the measurement process. Human oversight and quality control are part of its real-world use.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for this immunoassay is likely established through:
- Reference Materials/Calibrators: These are materials with precisely known concentrations of intact PTH, used to calibrate the instrument and verify accuracy.
- Predicate Device Comparison: The "Method Comparison" study uses the results from the legally marketed predicate device (Access Intact PTH on the Access 2 Immunoassay System) as the comparative reference, implicitly relying on the established accuracy of that predicate.
- Analytical Standards: Performance metrics (LoB, LoD, LoQ, linearity) are assessed against internationally recognized analytical standards, such as those from CLSI (Clinical and Laboratory Standards Institute), which define the statistical and experimental methods for confirming these basic analytical performance parameters.
- The "ground truth" for this immunoassay is likely established through:
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The sample size for the training set:
- Not Applicable. This is an immunoassay device, not an AI/machine learning model that requires a "training set" in the conventional sense. The "training" of the device involves calibration using specified calibrator materials and internal quality control procedures.
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How the ground truth for the training set was established:
- Not Applicable. See point 7.
§ 862.1545 Parathyroid hormone test system.
(a)
Identification. A parathyroid hormone test system is a device intended to measure the levels of parathyroid hormone in serum and plasma. Measurements of parathyroid hormone levels are used in the differential diagnosis of hypercalcemia (abnormally high levels of calcium in the blood) and hypocalcemia (abnormally low levels of calcium in the blood) resulting from disorders of calcium metabolism.(b)
Classification. Class II.