(29 days)
For in vitro diagnostic use only
The UREA test within the VITROS XT Chemistry Products UREA-CREA Slides quantitatively measures urea concentration, reported either as urea nitrogen or as urea (UREA), in serum, plasma, and urine using the VITROS XT 7600 Integrated System. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases
The CREA test within the VITROS XT Chemistry Products UREA-CREA Slides quantitatively measures creatinine (CREA) concentration in serum, plasma, and urine using the VITROS XT 7600 Integrated System. Creatinine measurements are used in the diagnosis and treatment of renal dialysis, and as a calculation basis for measuring other urine analytes.
Special conditions for use statement: For prescription use only.
The new device, the VITROS XT Chemistry Products UREA-CREA Slide is a single device that contains both a UREA test and a CREA test multilayered, analytical element coated on a polyester support separated by a plastic barrier sealed within a single slide frame. In this format, individual reactions occur and test results are generated for each analyte independently of the other analyte.
To perform the UREA test, a drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Water and nonproteinaceous components then travel to the underlying reagent layer, where the urease reaction generates ammonia. The semipermeable membrane allows only ammonia to pass through to the colorforming layer, where it reacts with the indicator to form a dye. The reflection density of the dye is measured and is proportional to the concentration of urea in the sample.
To perform the CREA test, 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 change in reflection density is measured at 2 time points. The difference in reflection density is proportional to the concentration of creatinine present in the sample.
This document describes the analytical performance of the VITROS XT Chemistry Products UREA-CREA Slides for quantitatively measuring urea and creatinine concentrations. The information provided is for an in-vitro diagnostic device and does not involve AI assistance, human readers, or image analysis, thus many of the requested elements are not applicable.
1. Table of Acceptance Criteria and Reported Device Performance
The device performance is primarily assessed through method comparison (against predicate devices), precision, detection limits, and linearity. The "acceptance criteria" are implied by the measured performance demonstrating substantial equivalence to the predicate devices and meeting clinical laboratory standards for accuracy and precision.
| Test Parameter | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Method Comparison | High correlation (e.g., r > 0.975) and acceptable bias compared to predicate. | UREA Serum: N=124, Slope=1.04, Intercept=0.00, Corr. Coeff.=0.999 (Test Range 3-106 mg/dL, Measuring Range 2.0-120.0 mg/dL) |
| UREA Urine: N=128, Slope=1.05, Intercept=-13.21, Corr. Coeff.=0.999 (Test Range 105-2451 mg/dL, Measuring Range 67-2520 mg/dL) | ||
| CREA Serum: N=130, Slope=1.00, Intercept=-0.01, Corr. Coeff.=1.000 (Test Range 0.20-13.49 mg/dL, Measuring Range 0.15-14.0 mg/dL) | ||
| CREA Urine: N=116, Slope=1.01, Intercept=-0.93, Corr. Coeff.=0.998 (Test Range 13.0-336.6 mg/dL, Measuring Range 3.2-346.5 mg/dL) | ||
| Precision | Demonstrated repeatability, within-day, and within-lab precision within acceptable CV% and SD limits for various concentration levels. | Detailed tables provided showing SD and CV% for Repeatability, Within Day, and Within Lab precision for multiple pools/controls across Urea Serum, Urea Urine, CREA Serum, and CREA Urine. E.g., UREA Serum Pool 1: Repeatability SD 0.1, CV% 4.0; Within Lab SD 0.2, CV% 8.7. CREA Serum Pool 1: Repeatability SD 0.007, CV% 1.1; Within Lab SD 0.011, CV% 1.7. All measured values are generally low, indicating good precision. |
| Detection Limits (LoQ) | Measured LoQ values no greater than claimed LoQ, with Total Error goal met. | UREA Serum: LoQ 1.7 mg/dL (Claimed 2.0 mg/dL); Total Error goal ≤ 1.2 mg/dL |
| UREA Urine: LoQ 41 mg/dL (Claimed 67 mg/dL); Total Error goal ≤ 21 mg/dL Urea N | ||
| CREA Serum: LoQ 0.11 mg/dL (Claimed 0.15 mg/dL); Total Error goal ≤ 0.06 mg/dL | ||
| CREA Urine: LoQ 2.3 mg/dL (Claimed 3.2 mg/dL); Total Error goal ≤ 1.2 mg/dL | ||
| Linearity | Linear range supporting the claimed measuring range. | UREA Serum: Linear Range 1.93-148.79 mg/dL (Claimed Measuring Range 2.0-120.0 mg/dL) |
| UREA Urine: Linear Range 62.46-3198.85 mg/dL (Claimed Measuring Range 67-2520 mg/dL) | ||
| CREA Serum: Linear Range 0.04-14.86 mg/dL (Claimed Measuring Range 0.15-14.0 mg/dL) | ||
| CREA Urine: Linear Range 1.1-418.3 mg/dL (Claimed Measuring Range 3.2-346.5 mg/dL) |
2. Sample Size and Data Provenance
- Method Comparison Test Set:
- UREA Serum: 124 samples
- UREA Urine: 128 samples
- CREA Serum: 130 samples
- CREA Urine: 116 samples
- Precision Test Set: Not specified as a separate patient sample set, but rather "patient pools and quality control materials." Each precision study included "a minimum of 80 observations (2 replicates per run, 2 runs per day over 20 days)" for serum and urine pools/controls.
- Detection Limits (LoQ) Test Set: 72 determinations for serum (UREA and CREA) and 64 for urine (CREA). 72 for urine (UREA).
- Linearity Test Set: Twenty proportionally related admixtures of low and high test fluids, each tested in quadruplicate. Specific number of patient samples not stated, as it uses contrived samples.
- Specificity (Interference) Test Set: Not explicitly stated how many patient samples were used, but rather "96 test substances" and "88 test substances" were spiked into serum samples, and "two substances" and "nineteen test substances" for urine.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the studies used standard clinical laboratory protocols (e.g., CLSI EP09-A3, EP05-A3, EP17-A2, EP06-A) which typically involve fresh or appropriately preserved clinical samples. The reference interval studies mention "an internal study of 3160 apparently healthy adults" and "an external study" (for UREA) or "an external study of apparently healthy adults (serum: 180 males and 180 females)" and "a separate external study" (for CREA).
3. Number of Experts and Qualifications for Ground Truth
- This is an in-vitro diagnostic device (chemistry analyzer) measuring chemical concentrations. The "ground truth" is established by the reference methodology (predicate devices on a different system) and gravimetric/analytical preparation of calibrators and quality controls. It does not involve human expert interpretation of images or other subjective assessments. Therefore, the concept of "experts establishing ground truth" in the context of radiology or pathology (e.g., radiologists interpreting images) is not applicable here.
4. Adjudication Method for the Test Set
- Not applicable. This is not a study involving human reader interpretation requiring adjudication. Performance is assessed analytically against quantitative measurements.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done
- No, an MRMC study was not done. This device is an automated in-vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Yes, this study represents a standalone analytical performance evaluation of the device's ability to accurately measure urea and creatinine concentrations. "Algorithm" in this context refers to the chemical reactions and measurement principles of the assay, not a software algorithm that processes medical images or data for interpretation. The performance metrics (method comparison, precision, detection limits, linearity, specificity) directly quantify the device's analytical capabilities without human intervention in the measurement process itself.
7. The type of ground truth used
- The ground truth is established through:
- Reference Methods/Predicate Devices: For method comparison, the results generated by the predicate devices (VITROS BUN/UREA Slides and VITROS CREA Slides on the VITROS 5600 Integrated System) serve as the comparative ground truth.
- Analytically Prepared Materials: For precision, detection limits, and linearity, the "ground truth" concentrations of control materials, patient pools, and serially diluted samples are established through precise gravimetric and volumetric preparations, often traceable to certified reference materials.
- Clinical Laboratory Standards (CLSI Protocols): The studies adhered to widely accepted CLSI guidelines for analytical performance evaluation, implying that the methodologies used to establish "ground truth" for each parameter meet industry standards for accuracy and rigor in a clinical lab setting.
8. The Sample Size for the Training Set
- This is not an AI/machine learning study that involves "training sets" in the conventional sense. The device's performance is based on the inherent chemical and optical principles of the dry-slide technology. There's no AI model being trained with data.
9. How the ground truth for the training set was established
- Not applicable, as there is no AI training set.
§ 862.1770 Urea nitrogen test system.
(a)
Identification. A urea nitrogen test system is a device intended to measure urea nitrogen (an end-product of nitrogen metabolism) in whole blood, serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of certain renal and metabolic diseases.(b)
Classification. Class II.