(63 days)
Diazyme Lithium Enzymatic Assay Kit is for quantitative in vitro determination of lithium in human serum and plasma. Measurements of lithium are carried out essentially to ensure that proper drug dosage is administered in the treatment of patient suffering from bipolar disorder and to avoid toxicity.
Diazyme's lithium enzymatic assay is a spectrophotometric method, which can be adapted to most automated clinical chemistry analyzers. In Diazyme's lithium enzymatic assay, Lithium is determined spectrophotometrically through a kinetic coupling assay system involving a Diazyme's proprietary phosphatase whose activity is sensitive to lithium concentration (IC50=0.1mM). Through enzymatic coupling, the phosphatase substrate, adenosine biphosphate (PAP) is converted to hypoxanthine by a series of enzymatic reactions to generate uric acid and hydrogen peroxide (H2O2). H2O2 generated reacts with N-Ethyl-N-(2-hydroxy-3-sulfopropyl)-3-m-toluidine (EHSPT) and 4-aminoantipyrine (4-AA) in the presence of peroxidase (POD) to form a quinone dye which has maximal absorbance at 556nm. The rate of the quinine dye formation is inversely proportion to the concentration of lithium in serum samples.
The provided document (K033360) describes the Diazyme Lithium Enzymatic Assay Kit, a device for quantitative in vitro determination of lithium in human serum and plasma. The document is a 510(k) premarket notification, which seeks to demonstrate substantial equivalence to a legally marketed predicate device.
Here's an analysis of the acceptance criteria and study data based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in a quantitative manner as "pass/fail" thresholds. Instead, the document presents performance characteristics and asserts that they demonstrate excellent accuracy and safety/effectiveness. The comparison is primarily against a predicate device and existing methods.
| Performance Metric | Implicit Acceptance Criteria (based on predicate comparison/general clinical needs) | Reported Device Performance |
|---|---|---|
| Precision | Low coefficient of variation (CV%) indicating good reproducibility. | 1.0mM Li+: Within Precision CV%=4.7%, Total Precision CV%=6.9% |
| 2.4mM Li+: Within Precision CV%=3.3%, Total Precision CV%=5.5% | ||
| Measuring Range | Clinically relevant range for lithium therapy monitoring (typically 0.6-1.2 mM for maintenance, up to 1.5mM for acute treatment, toxicity > 1.5mM). | 0 to 3 mmol/L |
| Correlation with Predicate Device (Trace colorimetric method) | Strong positive correlation (e.g., correlation coefficient > 0.95) | Correlation coefficient of 0.97 |
| Correlation with Reference Method (ISE method) | Strong positive correlation (e.g., correlation coefficient > 0.95) | Correlation coefficient of 0.97 |
| Interference | Minimal or no significant interference from common biological substances and medications. | Little interference found at indicated concentrations for various substances (NH4Cl, KPi, CaCl2, NaCl, KCl, CuCl2, FeCl3, ZnCl2, Triglyceride, Ascorbic Acid, Bilirubin). |
| Accuracy / Substantial Equivalence | No significant deviation compared to the predicate device and good agreement with reference methods. | "excellent accuracy and is safe and effective." |
| "No significant deviation between the results obtained by Diazyme's Lithium Enzymatic assay and legally marketed predicate Trace Lithium Reagent when testing clinical patient serum samples." |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document mentions "clinical patient serum samples" for the comparison analysis with the predicate device but does not specify the exact number of samples used in the test set.
- Data Provenance: The document does not explicitly state the country of origin. The studies appear to be retrospective as they involve testing existing clinical patient serum samples and comparing them to established methods.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is generally not applicable to an in vitro diagnostic (IVD) assay for a quantitative analyte like lithium. The "ground truth" for lithium concentration would be established by established analytical methods (e.g., ISE, atomic absorption spectrophotometry, predicate device) or reference materials, not by expert consensus on interpretation. Therefore, there were no experts in the sense of clinicians or radiologists used to establish ground truth.
4. Adjudication Method for the Test Set
Not applicable. As noted above, the "ground truth" is analytical, not interpretive.
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 is an in vitro diagnostic assay for quantifying a chemical analyte (lithium), not an imaging device or AI-driven diagnostic that involves human reader interpretation. Therefore, MRMC studies and "human reader improvement with AI" are not relevant to this device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This statement applies to the Diazyme Lithium Enzymatic Assay as it is a standalone assay. It provides a quantitative result for lithium concentration based solely on the enzymatic reaction and spectrophotometric measurement, without human intervention for interpretation beyond standard laboratory procedures (e.g., sample handling, instrument operation). The "algorithm" here is the chemical reaction and measurement protocol that generates the result.
7. The Type of Ground Truth Used
The ground truth was established by:
- Comparison to Legally Marketed Predicate Device: Trace Lithium Reagent (K003583).
- Comparison to Established Analytical Methods: Ion-selective electrode (ISE) method.
- Reference Materials/Spiking Studies: For linearity (implied by "wide measuring range") and interference studies, where samples were spiked with known concentrations of lithium or interfering substances.
- Known Concentrations: For precision studies (1.0mM Li+ and 2.4mM Li+).
8. The Sample Size for the Training Set
The document does not specify a training set size. For an enzymatic assay like this, "training set" is not typically a concept used in the same way as for machine learning algorithms. The assay development would involve optimizing reagents and conditions, which is analogous to "training" but doesn't involve a distinct, quantified "training set" of patient samples in the way an AI model would have.
9. How the Ground Truth for the Training Set Was Established
As explained above, a traditional "training set" with established ground truth in the context of an AI/machine learning model is not directly applicable. The "ground truth" for optimizing the assay would come from:
- Chemical principles and known reactions: The design of the enzymatic coupling system.
- Known concentrations of lithium: To establish the dose-response curve and sensitivity.
- Reference materials: For calibration and verification of the assay's performance during development.
- Comparison to existing methods: During the development and optimization phase to ensure the new assay aligns with established ways of measuring lithium.
§ 862.3560 Lithium test system.
(a)
Identification. A lithium test system is a device intended to measure lithium (from the drug lithium carbonate) in serum or plasma. Measurements of lithium are used to assure that the proper drug dosage is administered in the treatment of patients with mental disturbances, such as manic-depressive illness (bipolar disorder).(b)
Classification. Class II.