(90 days)
- VITROS Chemistry Products CRBM Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products CRBM Slides quantitatively measure carbamazepine (CRBM) concentration in serum and plasma using VITROS 250/350/950/5.1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements obtained are used in monitoring levels of carbamazepine to help ensure appropriate therapy.
- VITROS Chemistry Products CREA Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Product CREA Slides quantitatively measure creatinine (CREA) concentration in serum, plasma, and urine using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. 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.
- VITROS Chemistry Products TBIL Slides: Rx Only. For in vitro diagnostic use only. VITROS Chemistry Products TBIL Slides quantitatively measure total bilirubin (TBIL) concentration in serum and plasma using VITROS 250/350/950/5,1 FS and 4600 Chemistry Systems and the VITROS 5600/ XT 7600 Integrated System. Measurements of the levels of bilirubin are used in the diagnosis and treatment of liver, hematological and metabolic disorders, including hepatitis and gall bladder block.
- VITROS XT 7600 Integrated System: Rx Only. For in vitro diagnostic use only. The VITROS XT 7600 Integrated System is intended for use in the measurement of a variety of analytes of clinical interest.
The VITROS XT 7600 Integrated System is a fully automated, computer controlled, clinical chemistry and immunodiagnostic analyzer intended for the in vitro determination of a variety of general chemistries, therapeutic drugs, drugs of abuse, proteins, infectious diseases, as well as cardiac, metabolic, thyroid, anemia, and oncology markers in biological fluids such as serum, plasma, urine and cerebral spinal fluid. The System operates in conjunction with reagents, calibrators and controls designed for use with the System in the MicroSlide, MicroTip or MicroWell format.
The VITROS Chemistry MicroSlide range of products (in this case VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, and VITROS Chemistry Products TBIL Slides), are combined with the VITROS XT 7600 Integrated System to perform the VITROS CRBM, CREA, and TBIL assays.
The document describes the performance of the VITROS Chemistry Products CRBM Slides, VITROS Chemistry Products CREA Slides, VITROS Chemistry Products TBIL Slides, and the VITROS XT 7600 Integrated System. The main purpose of the study is to demonstrate substantial equivalence to legally marketed predicate devices.
Here's an analysis of the acceptance criteria and study details:
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state acceptance criteria in a dedicated table format for each performance metric, but rather describes how results were evaluated in the "Specificity" section and implies acceptance based on the comparison to predicate devices and established guidelines. For the method comparison, precision, linearity, and detection limits, the "reported device performance" is the direct result of the testing.
Given the nature of the submission (510(k) for substantial equivalence in an in-vitro diagnostic device), the acceptance criteria would typically revolve around demonstrating comparable performance to the predicate devices and adherence to established clinical laboratory standards (CLSI guidelines).
Below is a table summarizing the reported performance, with implied acceptance criteria based on standard practices for demonstrating substantial equivalence for in-vitro diagnostic devices.
Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Implied Acceptance Criteria (Based on Substantial Equivalence and CLSI Guidelines) | Reported Device Performance (VITROS XT 7600 Integrated System with corresponding slides) |
|---|---|---|
| Method Comparison | Device results should show substantial agreement with the predicate device (e.g., slopes near 1, intercepts near 0, demonstrating agreement across the measuring range). | CRBM Serum: N=118, Deming Regression, Slope=1.00, Intercept=0.12, Test range 3.1-17.8 µg/mL. CREA Serum: N=116, Passing Bablock, Slope=0.99, Intercept=0.00, Test range 0.25-13.4 mg/dL. CREA Urine: N=122, Passing Bablock, Slope=0.99, Intercept=-0.45, Test range 3.7-331.0 mg/dL. TBIL Serum: N=125, Passing Bablock, Slope=0.99, Intercept=0.01, Test range 0.14-23.65 mg/dL. |
| Precision | Within-lab precision (Total %CV and SD) should be acceptable for clinical use and comparable to predicate device specifications (though explicit predicate precision isn't stated here, it's an implied comparison). Lower %CV indicates higher precision. | CRBM (Serum): Within Lab (Total) %CV ranges from 2.41% to 3.98% across 6 concentration levels (3.9 to 17.6 µg/mL). |
| CREA (Serum): Within Lab (Total) %CV ranges from 1.40% to 1.85% across 6 concentration levels (0.82 to 12.65 mg/dL). | ||
| CREA (Urine): Within Lab (Total) %CV ranges from 1.55% to 2.23% across 6 concentration levels (55.6 to 320.9 mg/dL). | ||
| TBIL (Serum): Within Lab (Total) %CV ranges from 1.40% to 6.72% across 5 concentration levels (0.3 to 21.6 mg/dL). | ||
| Linearity | The device should demonstrate linearity across its claimed measuring range. | The linearity studies support the claimed measuring ranges for the VITROS CRBM, VITROS CREA, and VITROS TBIL assays. |
| Detection Limits (LoB, LoD, LoQ) | Calculated detection limits should be at or below the claimed LoQ and support the low end of the claimed measuring range. Acceptance typically involves comparing these values to the claimed LoQ. | CRBM: LoB = 0.6108 µg/mL; LoD = 0.6821 µg/mL; LoQ = 2.6860 µg/mL. Claimed LoQ = 3.0 µg/mL. |
| TBIL: LoB = 0.0378 mg/dL; LoD = 0.0722 mg/dL; LoQ = 0.0616 mg/dL. Claimed LoQ = 0.10 mg/dL. | ||
| Creatinine (Serum/Plasma): LoB = 0.0933 mg/dL; LoD = 0.0991 mg/dL; LoQ = 0.1119 mg/dL. Claimed LoQ = 0.15 mg/dL. | ||
| Creatinine (Urine): LoB = 1.9973 mg/dL; LoD = 2.1986 mg/dL; LoQ = 2.0060 mg/dL. Claimed LoQ = 3.2 mg/dL. | ||
| In all cases, the calculated LoQ is at or below the claimed LoQ, supporting the claimed assay range. | ||
| Specificity (Interference) | Observed bias due to interferents should be within predetermined Maximum Allowable Interference (MAI) or within the 95% Confidence Limit if exceeding Claimed Bias, demonstrating comparable performance to the predicate for known and potential interferents. | Results demonstrate acceptable bias on the VITROS XT 7600 versus the VITROS 5600 for currently claimed interferents. Two previously untested analyte/interferent levels (3.0 ug/mL CRBM/ 20 mg/dL Bilirubin and 3.0 ug/mL CRBM/ 3.0 mg/dL Ethamsylate on CRBM MicroSlides) yielded new information. One new interfering substance, Tolazamide, was identified for CREA(s) MicroSlides. The bias profiles for these demonstrated equivalent magnitudes to the VITROS 5600. The IFU for CRBM and CREA have been updated to claim the additional interfering levels and the new interfering substance. |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Method Comparison Test Set:
- CRBM: 118 human serum samples.
- CREA: 116 human serum samples and 122 human urine samples.
- TBIL: 125 human serum samples.
- Data Provenance: The document states "human serum samples" and "human urine samples," implying these are clinical samples. The country of origin and whether the data is retrospective or prospective is not specified.
-
Precision Test Set: For each assay (CRBM, CREA serum, CREA urine, TBIL), the study involved:
- 80 replicates (N=80) for each of the multiple fluid levels (e.g., 6 for CRBM, 6 for CREA serum, 6 for CREA urine, 5 for TBIL). The total number of analyses is much higher (e.g., 80 replicates x 6 levels = 480 for CRBM).
- The samples used were Quality Control fluids and human-based precision fluids.
- Data Provenance: Not specified.
-
Linearity Test Set: A series of eleven proportionally related admixtures of low and high test fluids. Each sample was tested in triplicate.
- Data Provenance: Not specified.
-
Detection Limits (LoB, LoD, LoQ) Test Set:
- LoB: 4 blank samples, tested in replicates of 6 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 216 observations (72 results per reagent lot).
- LoD: 4 pools of human samples with analyte concentrations close to the expected detection limit, tested in replicates of 6 over 3 days, using 3 lots of reagents, with the 4 human sample pools every day, for a total of 216 observations (72 results per reagent lot).
- LoQ: 4 pools of low level samples, tested in replicates of 4 over 3 days, using 3 lots of reagents, 4 samples every day, for a total of 144 observations (48 results per reagent lot).
- Data Provenance: The LoD and LoQ studies used "human samples." The country of origin and whether the data is retrospective or prospective is not specified.
-
Specificity (Interference) Test Set: Chemical interferents, common chemical substances, and claimed non-interferents, including hemoglobin, bilirubin, and intralipid. Testing employed "paired-difference" assessment at a minimum of two analyte levels.
- Data Provenance: Not specified.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
This device measures quantitative concentrations of specific analytes (Carbamazepine, Creatinine, Total Bilirubin). Ground truth for these types of in vitro diagnostic devices usually refers to the reference method (predicate device in this case) or a highly accurate reference standard rather than expert interpretation in the way it applies to image analysis or clinical diagnosis. The document does not mention human experts establishing ground truth in the context of radiologists or similar clinical diagnosticians. The ground truth for the method comparison study was established by the predicate device, VITROS 5600 Integrated System.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
None mentioned. Adjudication methods are typically used when there's a subjective element to ground truth establishment, often involving multiple human readers for diagnostic image interpretation. For quantitative measurements in clinical chemistry, the "truth" is established by reference methods, precision, and linearity studies, not by human adjudication of results.
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
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation, particularly in radiology or pathology, and often involves AI assistance. This document describes an automated in-vitro diagnostic device for quantitative chemical measurements, where human interpretation of results is direct measurement rather than subjective assessment. Therefore, the concept of "human readers improving with AI assistance" is not applicable here.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies described are, in essence, standalone performance evaluations of the VITROS XT 7600 Integrated System itself, with the VITROS Chemistry Products slides, operating automatically without continuous human intervention during the measurement process. The system performs the tests, generates results, and its performance (method comparison, precision, linearity, detection limits, specificity) is evaluated. The comparison is against a predicate device, which is also an automated system.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth for the test set, especially for the method comparison, was established by comparison to the legally marketed predicate device (VITROS 5600 Integrated System), which itself would have been previously cleared based on demonstrating accuracy against established reference methods or accepted gold standards for each analyte. For precision, linearity, and detection limits, the ground truth is established by the known characteristics of reference materials and statistical analysis.
8. The sample size for the training set
The document does not mention a training set. This is because the device described is not an AI/ML-based diagnostic algorithm that learns from data. It is a traditional in-vitro diagnostic instrument with chemical reagent slides. The studies are validation studies for the performance of the integrated system, not for training an algorithm.
9. How the ground truth for the training set was established
Since there is no training set mentioned or used for this type of device, this question is not applicable.
§ 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.