(210 days)
The Access Ostase assay is a paramagnetic particle, chemiluminescent immunoassay for use with the Access Immunoassay Systems for the quantitative measurement of bone alkaline phosphatase (BAP), an indicator of osteoblastic activity, in human serum and plasma. This device is intended to be used as an aid in the management of postmenopausal osteoporosis and Paget's disease.
The Access Ostase assay is a one-step sandwich immunoenzymatic assay. The Access Ostase assay consists of the reagent pack, calibrators and QCs. Other items needed to run the assay include substrate and wash buffer. The Access Ostase assay reagent pack, Access Ostase assay calibrators, Access Ostase QCs, along with the UniCel Dxl Wash Buffer II are designed for use with the Dxl 9000 Access Immunoassay Analyzer in a clinical laboratory setting.
The provided text describes the performance of the Beckman Coulter Access Ostase assay on the Dxl 9000 Access Immunoassay Analyzer, comparing it to the predicate device (Access Ostase on Access 2 Immunoassay System).
Here's an analysis of the acceptance criteria and the studies performed, structured as requested:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" for each performance characteristic in a separate, clear table format. However, it does outline the assay's design goals for imprecision and then presents the results. For other parameters like linearity and detection limits, it states the claimed values or that linearity was demonstrated. I will infer the acceptance criteria for imprecision from the "designed to have" statement and present the reported performance.
| Parameter | Acceptance Criteria | Reported Device Performance (Access Ostase on Dxl 9000) |
|---|---|---|
| Method Comparison | Implicit: Close statistical agreement (slope near 1, intercept near 0, high correlation) with the predicate device (Access Ostase on Access 2 Immunoassay System). While not explicitly stated as an "acceptance criteria," the results indicate substantial equivalence. | N: 163 samples |
| Concentration Range: 0.34 - 108 µg/L | ||
| Slope: 0.95 (95% CI: 0.93 - 0.98) | ||
| Intercept: 0.53 (95% CI: 0.32 - 0.75) | ||
| Correlation Coefficient (R): 1.00 | ||
| Imprecision | ≤ 0.2 µg/L SD at concentrations ≤ 3 µg/L | |
| ≤ 7.0% CV at concentrations > 3 µg/L (within-laboratory imprecision) | Sample 1 (Mean 1.8 µg/L): SD 0.1, %CV 4.7 | |
| Sample 2 (Mean 9.1 µg/L): SD 0.4, %CV 4.1 | ||
| Sample 3 (Mean 25 µg/L): SD 1.1, %CV 4.4 | ||
| Sample 4 (Mean 38 µg/L): SD 1.6, %CV 4.3 | ||
| Sample 5 (Mean 98 µg/L): SD 4.1, %CV 4.2 | ||
| All reported within-laboratory %CVs are ≤ 7.0% and the SD for Sample 1 (1.8 µg/L) is 0.1 µg/L, meeting the criteria. | ||
| Linearity | Implicit: Demonstrate linearity across the measuring interval. | Demonstrated linearity across the measuring interval. |
| Limit of Blank (LoB) | Claimed LoB of 0.1 µg/L. | Claimed LoB for Access Ostase assay is 0.1 µg/L on Dxl 9000 Access Immunoassay Analyzer. |
| Limit of Detection (LoD) | Claimed LoD of 0.1 µg/L. | Claimed LoD for Access Ostase assay is 0.1 µg/L on Dxl 9000 Access Immunoassay Analyzer. |
| Limit of Quantitation (LoQ) | Claimed LoQ of 0.3 µg/L. | Claimed LoQ for Access Ostase assay is 0.3 µg/L on Dxl 9000 Access Immunoassay Analyzer. |
2. Sample size used for the test set and the data provenance:
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Method Comparison Test Set:
- Sample Size: 163
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the study involved comparing results from two different immunoassay systems (Access 2 and Dxl 9000) using patient samples, implying real-world or simulated clinical samples.
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Imprecision Test Set:
- Sample Size: 80 for each of the 5 samples tested (total of 400 individual measurements of samples).
- Data Provenance: Not explicitly stated. The study involved testing "multiple samples in duplicate in 2 runs per day for a minimum of 20 days," which suggests a controlled laboratory setting.
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Linearity, LoB, LoD, LoQ: The sample sizes for these studies are not explicitly mentioned, nor is their specific provenance beyond being performed "on the Dxl 9000 Access Immunoassay Analyzer."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This information is not applicable to an in vitro diagnostic (IVD) assay that measures quantitative analytes like bone alkaline phosphatase. The "ground truth" for such devices is typically established through reference methods, certified reference materials, or statistical comparison to a legally marketed predicate device (as done here). There are no "experts" in the human perception or diagnostic interpretation sense used to establish ground truth for this type of test.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies involving human interpretation (e.g., radiology reads) where discrepancies between experts need to be resolved to establish ground truth. This is a quantitative immunoassay.
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 device is an in vitro diagnostic immunoassay, not an AI-assisted diagnostic tool for human readers. No MRMC study was performed.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
This device is an automated immunoassay system that provides quantitative results. The performance studies described (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) inherently represent the standalone performance of the device (including its reagents and analyzer software) in generating these quantitative results. It operates without direct human-in-the-loop interpretation of the primary measurement signal for the reported value. A human reviews the final numerical result, but the device itself generates that result primarily through an automated process.
7. The type of ground truth used:
- Method Comparison: The ground truth was established by comparison to the predicate device (Access Ostase on Access 2 Immunoassay System). This assumes the predicate device's measurements represent a valid "truth" for substantial equivalence purposes. Patient samples were used, and their values from one system were compared to the other.
- Imprecision: The ground truth for evaluating imprecision is the inherent variability of the measurement process itself, determined by repeated measurements of samples with known (or established) concentrations.
- Linearity, LoB, LoD, LoQ: These are determined using samples of known concentrations (dilutions, blank samples, low-concentration samples) and statistical methods based on CLSI guidelines.
8. The sample size for the training set:
Not applicable. This device is a quantitative immunoassay system, not a machine learning or AI model that requires a "training set" in the conventional sense. The development of such assays involves extensive research, development, and optimization of reagents and protocols, but this is distinct from "training data" for an algorithm.
9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" in the context of an AI/ML algorithm.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.