(23 days)
For in vitro diagnostic use only. VITROS urCR DT Slides quantitatively measure creatinine concentration in urine on the DT60/DT60 II analyzer.
Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
For in vitro diagnostic use only. VITROS Chemistry Products DT Calibrator Kit is specially formulated for use as calibrators for ALB, ALKP, ALT, AMYL, AST, TBIL, NBIL, BUN/UREA, Ca, CHOL, CK, Cl, CO2, CREA, CRSC, Fe, GGT, GLU, HDLC, K+, LAC, LDH, LIPA, Mg, Na+, NH3, PHOS, TP, TRIG, urCR, and URIC on VITROS DT Chemistry Systems.
The VITROS urCR assay is performed using the VITROS Chemistry Products urCR DT Slides, and the VITROS Chemistry Products DT Calibrator Kit on VITROS DT60/DT60II Chemistry Systems.
The VITROS urCR Slide is a multilayered, analytical element coated on a polyester support.
A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Creatinine diffuses to the reagent layer, where it is hydrolyzed to creatine in the rate-determining step. The creatine is converted to sarcosine and urea by creatine amidinohydrolase. The sarcosine, in the presence of sarcosine oxidase, is oxidized to glycine, formaldehyde, and hydrogen peroxide. The final reaction involves the peroxidase-catalyzed oxidation of a leuco dye to produce a colored product.
Following addition of the sample, the slide is incubated. During the initial reaction phase, endogenous creatine in the sample is oxidized. The resulting rate of change in reflection density is proportional to the concentration of creatinine in the sample
Once a calibration has been performed for each slide lot, creatinine concentration in unknown samples can be determined using the software-resident rate math model and the change in reflectance calculated for each unknown test slide.
VITROS DT Calibrator Kit contains four levels of lyophilized standards with corresponding diluents. The standards are prepared from processed bovine serum to which organic analytes, electrolytes, stabilizers, and preservatives have been added. The diluents are prepared from processed water to which inorganic salts have been added. Once reconstituted, the appropriate standards are used to calibrate VITROS DT60/DT60 II Chemistry Systems for the quantitative measurement of creatinine in urine.
Calibration of the VITROS urCR assay requires the use of bottles 1, 2 and 4 of the VITROS DT Calibrator Kit.
Here's an analysis of the provided text to extract information about the device's acceptance criteria and the supporting study:
Device: VITROS Chemistry Products urCR DT Slides (modified device) and VITROS Chemistry Products DT Calibrator Kit.
Intended Use (urCR DT Slides): Quantitatively measure creatinine concentration in urine for diagnosis and treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes the modified device's performance characteristics and compares them to a predicate device. While explicit "acceptance criteria" for quantitative metrics aren't stated as pass/fail thresholds, the comparison table implies what was considered acceptable for substantial equivalence. The key performance aspects are the analytical range and calibration traceability.
| Acceptance Criteria / Characteristic | Modified Device (VITROS urCR assay) Reported Performance | Predicate Device (VITROS urCR assay original) Reported Performance |
|---|---|---|
| Intended Use | No change (Matches predicate) | For in vitro diagnostic use only. Quantitatively measure creatinine concentration in urine. |
| Calibration Traceability | Traceable to Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) method¹ and NIST SRM®914, creatinine standard reference material. | Traceable to Certified NIST Reference Material SRM® 914a. |
| Reference Interval (Urine) | Males: 1000 – 2000 mg/day² Females: 800 – 1800 mg/day² | 800 – 2800 mg/day |
| Reportable Range (Urine) | 1.0 – 339.2 mg/dL* (*After multiplying by a dilution factor of 21) | 2.1 – 346.5 mg/dL* (*After multiplying by a dilution factor of 21) |
| Sample Type | No change (Matches predicate) | Urine |
| Basic Principle | No change (Matches predicate) | Colorimetric rate |
| Instrumentation | No change (Matches predicate) | VITROS DTSC/DTSCII Module (presumably VITROS DT60/DT60II Chemistry Systems as stated in device description) |
Conclusion on Acceptance: The document primarily focuses on demonstrating substantial equivalence to the predicate device. The "acceptance criteria" are therefore inferred to be that the modified device's characteristics (intended use, calibration, reportable range, etc.) are equivalent to, or demonstrate comparable performance to, the predicate device. The changes noted (e.g., specific traceability methods, slightly refined reference intervals, and a minor adjustment in the lower boundary of the reportable range) were deemed acceptable as they did not impact the substantial equivalence based on the rationale provided.
2. Sample Size Used for the Test Set and Data Provenance
The document states: "Equivalence was demonstrated using manufactured reagents along with quality control fluids, proficiency samples, and human urine with measured creatinine values spanning the assay range."
- Sample Size for Test Set: Not explicitly stated. The specific number of "human urine" samples is not provided, nor are the quantities of quality control fluids or proficiency samples.
- Data Provenance: The data comes from tests on "human urine," "quality control fluids," and "proficiency samples." The geographic origin (country) is not specified. The study is implied to be prospective in nature, as it's demonstrating the performance of a newly "modified device" and its manufactured reagents.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This is a chemical assay, not an imaging device requiring expert interpretation. The "ground truth" for creatinine concentration would be established by reference methods or validated laboratory measurements.
- Number of Experts: Not applicable in the traditional sense of human readers/interpreters.
- Qualifications of Experts: Not applicable. Ground truth for chemical analytes is established by highly accurate and precise analytical methods. The document mentions traceability to:
- Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) method
- NIST SRM®914, creatinine standard reference material (National Institute of Standards and Technology Standard Reference Material). These describe the methodology and reference standards for establishing ground truth, not human experts.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. This is a chemical assay, not involving human interpretation that would require adjudication. The performance is assessed by comparing results from the device to established reference methods/ground truth, and potentially by comparing the modified device's performance to the predicate device's performance.
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
- MRMC Comparative Effectiveness Study: No. This is a chemical assay device, not an AI-assisted diagnostic imaging or interpretation system involving human readers.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- Standalone Performance: Yes, implicitly. The device itself (VITROS urCR assay) operates as an automated system measuring creatinine. The performance evaluation described (using various samples and demonstrating equivalence) represents the "standalone" performance of the assay system without human intervention in the measurement process itself, beyond sample loading and calibration. The result is quantitative and objective, not subject to human interpretation in the way, for example, a radiological image would be.
7. The Type of Ground Truth Used
- Type of Ground Truth: The ground truth for creatinine concentration was established through reference methods and certified reference materials. Specifically:
- Gas Chromatography Isotope Dilution Mass Spectrometry (GC/IDMS) method.
- NIST SRM®914 (National Institute of Standards and Technology Standard Reference Material) for creatinine.
8. The Sample Size for the Training Set
- Sample Size for Training Set: Not applicable/Not specified. This document describes a modification to an existing chemical assay, which typically involves analytical validation rather than machine learning "training sets." While there would have been extensive development and optimization work, the concept of a "training set" in the context of an AI/ML algorithm is not relevant here. The device's calibration process involves known standards, but this is a calibration, not an algorithmic training process as understood in AI/ML.
9. How the Ground Truth for the Training Set was Established
- How Ground Truth for Training Set was Established: Not applicable. As noted above, typical machine learning training sets are not relevant to this type of chemical assay device. The ground truth for the calibrators is established by traceability to GC/IDMS and NIST SRM®914, as described in point 7.
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.