(161 days)
The Calcium Gen.2 assay is an in vitro diagnostics reagent system intended for the quantitative determination of calcium in human serum, plasma, and urine on Roche/Hitachi cobas c systems. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease, and tetany.
The Calcium Gen. 2 test system employs a photometric test method where calcium ions react with a calcium specific polyamino carboxylic acid under alkaline conditions to form a complex. This complex reacts in the second step with EDTA. The calcium concentration is directly proportional to the change in absorbance which is measured photometrically.
Here's an analysis of the provided text regarding the Calcium Generation 2 Assay, focusing on acceptance criteria and study details.
Note: This document is a 510(k) summary, which typically presents performance data to demonstrate substantial equivalence to a predicate device, rather than explicitly stating pre-defined "acceptance criteria" and then proving them met in the same way a clinical trial protocol would. The acceptance criteria are implied by the comparisons made to the predicate device and the typical performance expectations for such assays. The "study" described is the performance characterization of the new device.
Acceptance Criteria and Device Performance
The "acceptance criteria" are implicitly set by the performance of the predicate device and general expectations for clinical chemistry assays, particularly in terms of precision and measuring range. The submission demonstrates that the Calcium Gen. 2 assay performs comparably or better than the predicate device in key areas.
| Performance Metric | Implied Acceptance Criteria (Based on Predicate/Clinical Norms) | Reported Device Performance (Calcium Gen. 2) | Meets Criteria? |
|---|---|---|---|
| Measuring Range (Serum/Plasma) | Similar to predicate (0.2 – 20 mg/dL) and clinically appropriate. | 0.8 – 20.1 mg/dL | Yes |
| Measuring Range (Urine) | Similar to predicate (0.48 – 48 mg/dL) and clinically appropriate. | 0.8 – 30.1 mg/dL | Yes |
| Lower Limits of Measure (Serum/Plasma) | Clinically relevant LoB, LoD, LoQ would be established. | **LoB: 0.4 mg/dL | |
| LoD: 0.8 mg/dL | |||
| LoQ: 0.8 mg/dL** | N/A (Predicate had "Not Established") | ||
| Lower Limits of Measure (Urine) | Clinically relevant LoB, LoD, LoQ would be established. | **LoB: 0.4 mg/dL | |
| LoD: 0.8 mg/dL | |||
| LoQ: 0.8 mg/dL** | N/A (Predicate had "Not Established") | ||
| Precision (Serum/Plasma) | Comparable or better than predicate, generally low CVs. Predicate example (Human serum): Repeatability 0.9%, Intermediate precision 1.6% (implied from data layout). | Human serum 1 (2.4 mg/dL): Repeatability CV 2.0%, Intermediate precision CV 2.5% | |
| Human serum 2 (10.2 mg/dL): Repeatability CV 0.8%, Intermediate precision CV 0.9% | |||
| Human serum 3 (17.9 mg/dL): Repeatability CV 0.8%, Intermediate precision CV 0.9% | |||
| Precinorm U (9.0 mg/dL): Repeatability CV 0.8%, Intermediate precision CV 0.8% | |||
| Precipath U (14.1 mg/dL): Repeatability CV 0.8%, Intermediate precision CV 0.9% | Yes | ||
| Precision (Urine) | Comparable or better than predicate, generally low CVs. Predicate example (Human urine): Repeatability 0.8%, Intermediate precision 1.4% (implied from data layout). | Human urine 1 (2.3 mg/dL): Repeatability CV 3.0%, Intermediate precision CV 3.1% | |
| Human urine 2 (15.7 mg/dL): Repeatability CV 1.1%, Intermediate precision CV 1.2% | |||
| Human urine 3 (20.8 mg/dL): Repeatability CV 0.9%, Intermediate precision CV 1.1% | |||
| Human urine 4 (24.4 mg/dL): Repeatability CV 1.3%, Intermediate precision CV 1.3% | |||
| Control Level 1 (7.4 mg/dL): Repeatability CV 1.3%, Intermediate precision CV 1.5% | |||
| Control Level 2 (10.9 mg/dL): Repeatability CV 1.1%, Intermediate precision CV 1.3% | Yes | ||
| Interference (Serum/Plasma) | No significant interference up to established thresholds for icterus, hemolysis, lipemia. Known drug interferences should be identified. | Icterus: no significant interference up to an I index of 60. | |
| Hemolysis: no significant interference up to an H index of 1000. | |||
| Lipemia: no significant interference up to an L index of 1000. | |||
| MRI contrast media (Omniscan®, Optimark®): No interference at therapeutic concentration for Omniscan®, interference at higher concentrations. Optimark® showed interference at therapeutic and higher concentrations. | |||
| Gammopathy: In very rare cases, type IgM may cause unreliable results. | Yes (comparable or expanded) | ||
| Interference (Urine) | No significant interference up to established thresholds. Known drug interferences should be identified. | Icterus: no significant interference up to a conjugated bilirubin concentration of 60 mg/dL. | |
| Hemolysis: no significant interference up to a hemoglobin concentration of 1000 mg/dL. | |||
| Magnesium: no significant interference up to a concentration of 60 mmol/L. | |||
| Drugs: No interference found at therapeutic concentrations using common drug panels. | |||
| MRI contrast media (Omniscan®, Optimark®): No interference at therapeutic concentration for Omniscan®, but at higher concentrations. Optimark® showed interference at therapeutic and higher concentrations. | Yes (expanded upon predicate's limited urine interference data) | ||
| Reagent Stability | Comparable to predicate (e.g., on-board stability). | Unopened: 2-8°C until expiration date. | |
| On-board in use: 42 days. | Yes |
Study Details
The provided document describes the performance characteristics of the Calcium Gen. 2 assay to demonstrate its substantial equivalence to a legally marketed predicate device (Calcium, K921661). This means the "study" is primarily a standalone performance characterization of the new assay.
-
Sample size used for the test set and the data provenance:
- Precision: The precision study used multiple samples, including "Human serum" (3 levels) and "Human urine" (4 levels), plus "Precinorm U" and "Precipath U" controls for serum, and "Control Level 1" and "Control Level 2" for urine. The exact number of replicates or individual patient samples per level is not specified beyond "Mean" and "CV Repeatability/Intermediate precision," which typically imply multiple measurements (e.g., n=20, n=40 etc. as per CLSI guidelines) over several days.
- Interference: Various samples spiked with interferents (icterus, hemolysis, lipemia, magnesium, specific drugs, MRI contrast media) were used. The number of samples for each interference test is not specified, but the results (e.g., "no significant interference up to an X index") indicate a panel of concentrations was tested.
- Data Provenance: Not explicitly stated but clinical chemistry assay validation studies are typically conducted by the manufacturer in a controlled laboratory setting. The origin (e.g., country) of the specific samples (human serum/urine) or controls used is not provided, but it's reasonable to assume they are representative of patient populations where the assay would be used. The studies are retrospective in the sense that they are laboratory characterizations rather than prospective patient follow-up studies.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This question is not applicable to this type of device and study. For a quantitative in vitro diagnostic assay, the "ground truth" is typically established by the reference method (e.g., an established highly accurate chemical method) or by the established concentration of a control material. There are no "experts" interpreting images or clinical data to establish ground truth in this context.
-
Adjudication method for the test set:
- Not applicable. Adjudication methods (like 2+1 or 3+1) are relevant for studies where human interpretation of data (e.g., imaging, pathology slides) contributes to ground truth determination. For an automated quantitative assay, the result is a numerical value, and "adjudication" is not a concept used.
-
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:
- No, this device is a laboratory reagent system, not an AI-powered diagnostic imaging or interpretation tool. Therefore, an MRMC study and effects on human reader performance are not relevant.
-
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, this is a standalone performance study. The Calcium Gen. 2 assay is an in vitro diagnostic reagent system used on an automated analyzer (Roche/Hitachi cobas c systems). The performance data presented (precision, measuring range, interference) directly reflects the algorithm/assay's performance. Human interaction is limited to operating the instrument, performing quality control, and interpreting the numerical result, not in generating the result itself.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For precision, the ground truth is the "true" concentration of calcium in the control materials or pooled human samples, as determined by a reference method or validated assignment, which is then measured repeatedly by the device.
- For measuring range (LoB, LoD, LoQ), the ground truth is the analytical performance characteristics empirically determined through dilution series and statistical analysis around the lowest measurable concentrations.
- For interference, the ground truth is the known concentration of calcium in samples, both with and without the interferent, often compared against a reference method or the predicate device, to see if the interferent causes a clinically significant deviation in the measured calcium value.
-
The sample size for the training set:
- Not explicitly mentioned, and likely not applicable in the context of this device. This is a chemical assay, not a machine learning algorithm that requires a "training set" in the conventional sense. The "training" for such a system would be the R&D and optimization process of the chemical reagents and instrument parameters, based on extensive pre-clinical testing, rather than a distinct "training set" of patient data as might be used for AI/ML models.
-
How the ground truth for the training set was established:
- Not applicable as there isn't a "training set" in the AI/ML sense. The development of the assay would involve iterative testing and optimization against known calcium standards and samples with established reference values to ensure accuracy and precision across the intended measuring range.
§ 862.1145 Calcium test system.
(a)
Identification. A calcium test system is a device intended to measure the total calcium level in serum. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms).(b)
Classification. Class II.