(347 days)
The A-LYTE® Integrated Multisensor (IMT Na K Cl) is for in vitro diagnostic use in the quantitative determination of sodium, potassium, and chloride (Na, K, Cl) in human serum, plasma (lithium heparin) and urine using the Atellica® Cl Analyzer. Measurements of sodium obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of arge amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance. Measurements of potassium obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of disease conditions characterized by low or high blood potassium levels. Chloride measurements are used in the diagnosis and treatment of electrolyte and metabolic disorders such as cystic fibrosis and diabetic acidosis.
The A-LYTE Na, K, and Cl assays use indirect Integrated Multisensor Technology (IMT). There are four electrodes used to measure electrolytes. Three of these electrodes are ionselective for sodium, potassium and chloride. A reference is also incorporated in the multisensor.
A diluted sample (1:10 with A-LYTE IMT Diluent)) is positioned in the sensor and Na+. K+ or Cl- ions establish equilibrium with the electrode surface. A potential is generated proportional to the logarithm of the analyte activity in the sample. The electrical potential generated on a sample is compared to the electrical potential generated on a standard solution, and the concentration of the desired ions is calculated by use of the Nernst equation.
This document describes the performance characteristics of the A-LYTE® Integrated Multisensor (IMT Na K Cl) device, which is used for the quantitative determination of sodium, potassium, and chloride in human serum, plasma, and urine. The information provided outlines the acceptance criteria for various performance metrics and the study results demonstrating that the device meets these criteria.
Here's a breakdown of the requested information:
1. A table of acceptance criteria and the reported device performance:
The document doesn't explicitly list "acceptance criteria" in a separate table, but rather describes the design goals or target performance for each characteristic, followed by the obtained results. I will present these as acceptance criteria and reported performance.
Table 1: Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Analyte | Sample Type | Acceptance Criteria (Design Goal) | Reported Device Performance |
|---|---|---|---|---|
| Detection Capability | Na | Serum & Plasma | LoQ ≤ 50 mmol/L with ≤ 20% total error | LoQ = 43.4 mmol/L, with ≤ 20% total error (calculated using Westgard model) |
| Na | Urine | LoQ ≤ 10 mmol/L with ≤ 30% total error | LoQ = 6.12 mmol/L, with ≤ 30% total error | |
| K | Serum & Plasma | LoQ ≤ 1 mmol/L with ≤ 20% total error | LoQ = 0.606 mmol/L, with ≤ 20% total error | |
| K | Urine | LoQ ≤ 2 mmol/L with ≤ 30% total error | LoQ = 1.22 mmol/L, with ≤ 30% total error | |
| Cl | Serum & Plasma | LoQ ≤ 50 mmol/L with ≤ 20% total error | LoQ = 40.4 mmol/L, with ≤ 20% total error | |
| Cl | Urine | LoQ ≤ 20 mmol/L with ≤ 30% total error | LoQ = 8.70 mmol/L, with ≤ 30% total error | |
| Linearity | Na | Serum | Linear range 50–200 mmol/L (demonstrated linearity of claimed measuring range) | $y=0.9858x - 0.53$ (demonstrated linearity) |
| K | Serum | Linear range 1–10 mmol/L (demonstrated linearity of claimed measuring range) | $y=0.98229x - 0.0085$ (demonstrated linearity) | |
| Cl | Serum | Linear range 50–200 mmol/L (demonstrated linearity of claimed measuring range) | $y=1.00040x + 0.037$ (demonstrated linearity) | |
| Na | Urine | Linear range 10–300 mmol/L (demonstrated linearity of claimed measuring range) | $y=0.9505x - 5.556$ (demonstrated linearity) | |
| K | Urine | Linear range 2–300 mmol/L (demonstrated linearity of claimed measuring range) | $y=0.9668x - 0.020$ (demonstrated linearity) | |
| Cl | Urine | Linear range 20–330 mmol/L (demonstrated linearity of claimed measuring range) | $y=1.00429x - 2.135$ (demonstrated linearity) | |
| Precision | Na | Serum/Urine | Detailed precision criteria not explicitly defined as "acceptance criteria", but results are presented. | See detailed tables in the document (within-laboratory precision, repeatability). |
| K | Serum/Urine | See detailed tables in the document. | ||
| Cl | Serum/Urine | See detailed tables in the document. | ||
| Assay Comparison | Na | Serum/Urine | Correlation coefficient ≥ 0.980, slope for Na 1.00 ± 0.05 | Serum: r=0.998, y=1.00x-2.69; Urine: r=0.999, y=1.02x-4.47 |
| K | Serum | Correlation coefficient ≥ 0.980, slope for K 1.00 ± 0.07 | Serum: r=1.000, y=0.97x+0.0353 | |
| K | Urine | Correlation coefficient ≥ 0.980, slope for K 1.00 ± 0.05 | Urine: r=0.999, y=1.02x-0.209 | |
| Cl | Serum/Urine | Correlation coefficient ≥ 0.980, slope for Cl 1.00 ± 0.05 | Serum: r=0.999, y=0.99x+0.161; Urine: r=0.991, y=0.99x-0.582 | |
| Reproducibility | Na/K/Cl | Serum/Urine | Detailed reproducibility criteria not explicitly defined as "acceptance criteria", but results are presented. | See detailed tables in the document (repeatability, between-day/-lot/-instrument, total reproducibility). |
| Specimen Equivalency | Na/K/Cl | Plasma vs Serum | Not explicitly defined as acceptance criteria, but correlation coefficient and regression equations are provided. | Na: r=0.994; K: r=0.983; Cl: r=0.998 |
| Interferences | Na/K/Cl | Serum/Urine | Bias ≤ 10% (for specific interferents at specified concentrations), except for hemoglobin/Na (-6% bias) and hemoglobin/Cl (-7% to -9% bias) at 1000 mg/dL, and urine Na/heme (-9% bias) at 500 mg/dL. | See detailed tables in the document. No bias > 10% reported for HIL, except for a few instances that are specifically called out as not needing correction. |
| Non-Interfering Substances | Na/K/Cl | Serum/Urine | Bias ≤ 10% at specified concentrations (except Salicylate with bias ≤ 15% for Cl). | All substances tested shown to have bias ≤ 10% (except Salicylate for Cl, which is ≤ 15% and noted as such). |
2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):
-
Test Set Sample Sizes:
- Detection Capability (LoQ): 180 determinations for each analyte (Na, K, Cl) in both serum/plasma and urine.
- Linearity: 5 replicates per level for at least nine levels, implying a minimum of 45 measurements per analyte and sample type.
- Precision: N ≥ 80 for each sample type (serum and urine) for each analyte (Na, K, Cl).
- Assay Comparison:
- Na (Serum): 123 samples
- Na (Urine): 117 samples
- K (Serum): 119 samples
- K (Urine): 117 samples
- Cl (Serum): 123 samples
- Cl (Urine): 127 samples
- Reproducibility: N=225 results for each sample type (serum QC, human serum, human urine) per analyte (Na, K, Cl), with n=5 assays in 1 run for 5 days using 3 instruments and 3 sensor lots.
- Specimen Equivalency:
- Na (Lithium heparin plasma vs Serum): 138 samples
- K (Lithium heparin plasma vs Serum): 56 samples
- Cl (Lithium heparin plasma vs Serum): 136 samples
- Interferences: Not explicitly stated as a single "sample size," but implied from the number of test concentrations and conditions evaluated (e.g., specific concentrations of hemoglobin, bilirubin, lipemia).
- Non-Interfering Substances: Not explicitly stated as a single "sample size," but implied from the number of test concentrations and conditions evaluated.
-
Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given it's a 510(k) submission for an in vitro diagnostic device, these studies are typically prospective validation studies conducted at the manufacturer's R&D facilities or contracted labs, adhering to CLSI guidelines.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This device is an in vitro diagnostic (IVD) for quantitative determination of electrolytes. The "ground truth" (or reference values) for these types of devices is established through:
- Reference Methods: Comparison against established, well-characterized reference methods or instruments (e.g., the predicate device in the assay comparison, or other highly accurate laboratory methods). In this case, "Atellica CH Na/K/Cl on Atellica CH Analyzer" served as the comparative assay, which itself would have been validated against reference standards.
- Certified Reference Materials: Use of calibrated standards and controls with known analyte concentrations derived from definitive methods.
Therefore, the concept of "experts" (like radiologists interpreting images) establishing ground truth does not directly apply here. Instead, ground truth is based on physical/chemical measurements and their traceability to metrological standards. There are no human experts involved in adjudicating the "truth" of an electrolyte concentration in a sample as there would be in image interpretation.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable. As explained in point 3, the ground truth for this type of quantitative IVD assay is established through comparison to reference methods, not human adjudication of a qualitative or semi-quantitative outcome.
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 automated laboratory analyzer, specifically an Integrated Multisensor for electrolyte measurement. It is not an imaging AI device that assists human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the performance data presented (Detection Capability, Linearity, Precision, Reproducibility, Interferences) represent the standalone performance of the A-LYTE® Integrated Multisensor (IMT Na K Cl) on the Atellica® CI Analyzer. These are direct measurements of the device's analytical precision, accuracy, and interference profiles under controlled laboratory conditions, without human interpretation influencing the quantitative results. The Assay Comparison also represents the device's performance against another automated laboratory system (the predicate device).
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth for this device's performance studies is based on:
- Reference Standards/Methods: Calibrated reference materials and comparison to a legally marketed predicate device (TD-LYTE Integrated Multisensor on Trinidad CH System, now Atellica CH System). This ensures that the measured concentrations are accurately determined against established analytical benchmarks.
- Known Concentrations: For linearity, precision, and interference studies, samples are often spiked or diluted to known concentrations, or quality control materials with certified values are used.
8. The sample size for the training set:
Not applicable. This device is a measurement instrument based on established potentiometric technology (Ion-Selective Electrodes). It does not employ machine learning or AI models that require a separate "training set" in the conventional sense. The development and calibration of such devices rely on comprehensive analytical chemistry and engineering principles, using calibration standards, quality control materials, and extensive internal testing during the development phase. The data presented here are for the validation of the finalized device, not for its iterative training.
9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" for an AI model. For the development and calibration of the IMT, the ground truth would be established through a combination of:
- Primary Reference Materials: Use of highly pure chemical standards with accurately known concentrations.
- Secondary Reference Standards: Calibrated solutions traceable to primary standards.
- Reference Measurement Procedures: Highly accurate and precise analytical methods (e.g., flame photometry, coulometry, or isotope dilution mass spectrometry for elemental analysis) used to assign values to control materials and calibrators.
- Internal R&D and Optimization: Extensive testing and refinement of the sensor and instrument performance using these traceable standards during the development process.
§ 862.1665 Sodium test system.
(a)
Identification. A sodium test system is a device intended to measure sodium in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of aldosteronism (excessive secretion of the hormone aldosterone), diabetes insipidus (chronic excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance.(b)
Classification. Class II.