Search Results
Found 100 results
510(k) Data Aggregation
(200 days)
Dimension Vista High-Sensitivity Troponin I (TNIH) Assay
The Dimension Vista® High-Sensitivity Troponin I (TNIH) assay is for in vitro diagnostic use in the quantitative measurement of cardiac troponin I in human plasma using the Dimension Vista system. The assay can be used to aid in the diagnosis of acute myocardial infarction (AMI).
The Dimension Vista® TNIH assay is a homogeneous, sandwich chemiluminescent immunoassay based on LOCI® technology. The LOCI reagents include two synthetic bead reagents and two biotinylated anti-cardiac troponin I monoclonal antibody fragments. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a third anticardiac troponin I monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibodies to form bead-cardiac troponin Ibiotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the cardiac troponin I concentration in the sample. Lithium heparin plasma specimens may be used. The reagent is stored unopened at 2 – 8 °C, is stable sealed on system for 30 days and opened on the system for 7 days. Calibration is performed every 30 days for a reagent lot.
The provided document describes the Siemens Healthcare Diagnostics Dimension Vista High-Sensitivity Troponin I (TNIH) Assay. The following information regarding its acceptance criteria and a study proving its performance is extracted:
Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Detection Limit | ||
| - Limit of Blank (LoB) | 95th percentile of all values, measured using a non-parametric approach. | 1.0 pg/mL |
| - Limit of Detection (LoD) | Non-parametric approach following CLSI EP17-A2. | 2.0 pg/mL (consistent with range of 0.7 - 1.9 pg/mL) |
| Limit of Quantitation (LoQ) | Analyte level with a within-lab CV of ≤ 20.0%. | 3.0 pg/mL (Lot-1: 1.2 pg/mL, Lot-2: 2.4 pg/mL, Lot-3: 2.2 pg/mL) |
| 10% CV Limit | Analyte level with a within-lab CV of ≤ 10.0%. | Consistent with 10.0 pg/mL (Lot-1: 2.7 pg/mL, Lot-2: 5.7 pg/mL, Lot-3: 5.4 pg/mL) |
| Precision | All precision goals were met. (Specific goals for SD and %CV not explicitly detailed but implied by "All precision goals were met" statement). | Repeatability: Plasma 1 (48.9 pg/mL): 1.12 SD, 2.3% CV; Plasma 2 (157.7 pg/mL): 1.55 SD, 1.0% CV; QC (8088.5 pg/mL): 99.54 SD, 1.2% CV. |
| Within-Lab: Plasma 1: 3.05 SD, 6.2% CV; Plasma 2: 2.60 SD, 1.6% CV; QC: 200.36 SD, 2.5% CV. | ||
| Linearity | The p values of nonlinear terms in the quadratic and cubic fit equations are non-significant (p ≤ 0.05). If p-value > 0.05, then allowable bias is ≤ 10% or 3 pg/mL, whichever is greater. | Confirmed linearity from 3.0 - 25,000.0 pg/mL. |
| Interferences | Bias exceeding 10% is considered interference. | Exogenous Compounds: No interference detected from Hemoglobin (400 mg/dL), Bilirubin (conjugated 30 mg/dL, unconjugated 40 mg/dL), Lipemia (3000 mg/dL) at approximately 40 pg/mL and 1350 pg/mL cTnI. |
| Numerous therapeutic/toxic substances: No interference detected at specified low/therapeutic and high/toxic concentrations (details in document for each substance). | ||
| High Dose Hook Effect | Not explicitly stated as a numerical criterion, but implies absence of hook effect. | No hook effect found at 1,000,000 pg/mL troponin. |
| Dilution Recovery | Supported use of diluent for over-range samples. (Specific numerical criteria not explicitly stated). | Testing supported use of the diluent for over-range samples. |
| Calibration Stability | P-value of regression slope ≥ 0.05 OR drift ≤ LoQ OR drift ≤ 10% for values up to 20,000 pg/mL OR drift ≤ 13% for values > 20,000 pg/mL. | Calibration interval measured to be 30 days. |
| Open Well Stability | P-value of regression slope ≥ 0.05 OR drift ≤ LoQ OR drift ≤ 10% for values up to 20,000 pg/mL OR drift ≤ 13% for values > 20,000 pg/mL. | Stability of reagents opened onboard the instrument was 7 days per well set. |
| Sample Stability | Lower bound of the one-sided 95% confidence interval of the regression line must be ≤ -10% AND all individual data points must have a bias of ≤ -20% when compared to time zero. | Separated samples stable for 8 hours at room temperature, 24 hours at 2-8 °C, up to 40 days at or below -20 °C (non-frost free), and up to 1 year at or below -70 °C. |
| Clinical Performance (Sensitivity) | Not explicitly stated as acceptance criteria, but clinical performance is assessed for diagnostic accuracy. | Pooled Gender (58.9 pg/mL 99th percentile): ranged from 79.0% (0-24h). |
| Male (78.5 pg/mL 99th percentile): ranged from 74.0% (0-24h) to 92.5% (0-24h) to 94.4% (0- |
Ask a specific question about this device
(248 days)
Dimension Vista LOCI Total Testosterone Flex reagent cartridge, Dimension Vista Testosterone Calibrator
The Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge is an in vitro diagnostic test for the quantitative measurement of total testosterone in human serum and plasma on the Dimension Vista® System. Measurements of testosterone are used in the diagnosis and treatment of disorders involving the male sex hormones (androgens), including primary and secondary hypogonadism, delayed or precocious puberty, impotence in males, and in females, hirsutism (excessive hair), and virilization (masculinization) due to tumors, polycystic ovaries, and adrenogenital syndromes.
The Dimension Vista® Testosterone Calibrator is an in vitro diagnostic product for the calibration of the Total Testosterone (TTST) assay on the Dimension Vista® System.
The Dimension Vista® LOCI Total Testosterone Flex® Reagent Cartridge (TTST) method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI reagents include two synthetic bead reagents and labeled testosterone antibody. The first bead reagent (Chemibeads) is coated with a testosterone analog and contains a chemiluminescent dye. The second bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. Chemibeads and labeled testosterone antibody are added sequentially to the reaction vessel. Testosterone from the patient sample competes with the testosterone-analog-chemibead for a limited amount of labeled testosterone antibody. Sensibeads are then added and bind to the biotinylated portion of the labeled testosterone antibody to form bead pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of total testosterone in the sample.
Dimension Vista® LOCI Total Testosterone reagents are liquid and contained in reagent wells of a Flex® reagent cartridge. There are twelve (12) wells in each Flex® reagent cartridge. A barcode label on the Flex® reagent cartridge identifies the test method, lot number, expiration date, and fixed number of tests for which the Flex® reagent cartridge can supply reagent. There are eighty (80) tests per Flex® reagent cartridge and four (4) Flex® reagent cartridges per carton.
The Dimension Vista® Testosterone Calibrator (TTST CAL) is a lyophilized human serum based calibrator set containing testosterone and preservatives. Within each set of twelve (12) vials there are two (2) 1.0 mL amber glass vials for each calibrator level. There are six (6) calibrator levels labeled A, B, C, D, E, and F, which span the assay range. Each glass vial is closed with a plug and a color coded plastic cap. Vials are stored at 2-8°C. Lyophilized calibrators are reconstituted with reagent grade water using the steps listed in the instructions for use (IFU).
The provided document describes the Siemens Healthcare Diagnostics Inc. Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge and its associated calibrator, seeking substantial equivalence to predicate devices. The study focuses on the performance characteristics of the new device.
Here's an analysis of the acceptance criteria and study details based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" in a quantitative, pass/fail format for each performance characteristic. Instead, it presents the results of various performance studies and implies that these results demonstrate substantial equivalence to the predicate device. The predicate device itself and recognized CLSI guidelines serve as implicit benchmarks for acceptable performance.
However, based on the provided data, we can infer some targets or observed ranges that indicate acceptable performance. The "Reported Device Performance" column reflects the results of the studies described.
| Performance Characteristic | Implicit Acceptance Criteria (Inferred from CLSI Guidelines & Predicate) | Reported Device Performance (Dimension Vista® LOCI Total Testosterone Flex®) |
|---|---|---|
| Method Comparison (vs. CDC ID/LC-MS/MS) | High correlation (e.g., r > 0.95), slope near 1, y-intercept near 0, 95% Confidence Interval for slope encompassing 1, for intercept encompassing 0. | N=113 samples. Range: 7.3 - 1033 ng/dL (CDC), 8-949 ng/dL (Vista TTST). |
| Slope: 0.93 | ||
| y-intercept: 4.0 | ||
| Correlation coefficient (r): 0.994 | ||
| 95% CI Slope: 0.92 to 0.95 | ||
| 95% CI Intercept: 0.4 to 5.7 | ||
| Precision (Repeatability %CV) | (Based on CLSI EP05-A2 and typical immunoassay performance expectations, generally 0.05 from polynomial regression, high correlation coefficient). | Statistically linear across 8 to 1,000 ng/dL for serum, lithium heparin, sodium heparin, and EDTA plasma. p-values > 0.05. |
| Serum: $0.97x + 0.1$, r=0.999 | ||
| Sodium Heparin: $0.98x + 0.1$, r=0.998 | ||
| Lithium Heparin: $0.98x + 0.0$, r=0.999 | ||
| EDTA: $0.96x + 0.1$, r=0.999 | ||
| Limit of Blank (LoB) | Stated as 4 ng/dL | 4 ng/dL |
| Limit of Detection (LoD) | Stated as 5 ng/dL | 5 ng/dL |
| Limit of Quantitation (LoQ) | Reproducible measurement with total precision ≤20% (as per CLSI EP05-A2). | 8 ng/dL (with total precision ≤20%) |
| Interferences (Hemoglobin, Bilirubin, Lipemia Bias) | Low bias (e.g., 0.95), slope near 1, intercept near 0. | Li Hep Plasma: Slope 0.98, Intercept -1.6 ng/dL, r=0.998 |
| Na Hep Plasma: Slope 0.99, Intercept -1.4 ng/dL, r=0.996 | ||
| K2 EDTA Plasma: Slope 1.00, Intercept -1.1 ng/dL, r=0.995 |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: 120 serum samples were initially measured. After removing 7 samples (6 below range, 1 above range), 113 samples were used for regression analysis.
- Data Provenance: Not explicitly stated but clinical samples were used, likely from a patient population within the US given the submission to the FDA. The study was performed at Siemens Healthcare Diagnostics' Newark, DE site. This is a retrospective analysis in the sense that samples were collected and then tested.
- Precision: Serum pools, a plasma pool, and commercial controls were used.
- Sample Size: Tested in singlicate from two independent cups twice a day for 20 days. This implies 40 measurements per sample type.
- Data Provenance: Not specified, but likely proprietary pools or commercial controls. Study performed at Siemens Healthcare Diagnostics' Newark, DE site.
- Analytical Measuring Range/Linearity: High and low pools for serum, lithium heparin, sodium heparin, and EDTA samples.
- Sample Size: Each level was assayed N=5 replicates. The number of distinct pools (high/low) is not specified for each sample type, but implied to be sufficient to cover the range.
- Data Provenance: Not specified, likely internal laboratory prepared pools. Study performed at Siemens Healthcare Diagnostics' Newark, DE site.
- Limits of Detection and Quantitation: Testosterone free serum samples and low testosterone serum samples.
- Sample Size: Not explicitly stated for LoB/LoD, but LoQ was determined based on precision data (implied 40 measurements).
- Data Provenance: Not specified, likely internal laboratory prepared samples.
- Interferences: Serum samples with various interfering substances spiked in.
- Sample Size: Not specified per substance, typically multiple replicates at each concentration.
- Data Provenance: Not specified, likely internal laboratory prepared samples.
- Heterophilic Antibody Interference: Individual human serum samples with low and high endogenous HAMA.
- Sample Size: Not specified, but implied individual samples were tested.
- Data Provenance: Not specified.
- Cross-reactivity: Spiked test samples.
- Sample Size: Not specified per cross-reactant, typically multiple replicates at each concentration and testosterone level.
- Data Provenance: Not specified, likely internal laboratory prepared samples.
- Serum and Plasma Equivalency: Sixty (60) matched sets of fresh draws.
- Sample Size: 60 matched sets. One sample removed, so 59 sets for regression analysis.
- Data Provenance: Not explicitly stated, but implies prospectively collected clinical samples.
- Expected Values (Reference Interval):
- Adult Males ≤50 years old: 174 samples
- Adult Males >50 years old: 174 samples
- Pre-menopausal females: 174 samples
- Post-menopausal females: 174 samples
- Pediatric (various age/gender/Tanner stages): Ranges from 20 to 125 samples per group.
- Data Provenance: Not specified, but likely from healthy volunteers (prospective) or carefully selected retrospective samples to establish reference ranges for different demographics.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
-
Ground Truth for Method Comparison: The reference method was the CDC Isotope dilution/liquid chromatographic-tandem mass spectrometry (CDC ID/LC-MS/MS). This is a highly accurate and precise analytical method that by its nature serves as its own "expert" or gold standard. It does not rely on human interpretation or consensus for ground truth.
-
Ground Truth for Reference Intervals: The reference intervals were established using the "robust" method or non-parametric methods described in CLSI EP28-A3c, applied to samples from healthy individuals. The "ground truth" here is the biological range observed in these populations, rather than an expert interpretation of the result from a single patient. The selection of "healthy" individuals likely involves criteria established by medical professionals, but this is not detailed as a panel of experts.
4. Adjudication Method for the Test Set
This type of in-vitro diagnostic device (immunoassay for a quantitative measurement) does not typically involve an adjudication method in the way medical imaging AI devices do (e.g., 2+1 radiologist review). The output is a quantitative value. Agreement is assessed statistically against a reference method or through precision studies, not through expert consensus on the device's output for individual cases.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices where human readers interpret results, and the AI system acts as an aid to improve their performance. This document concerns a fully automated in-vitro diagnostic immunoassay which provides a numerical result directly, rather than an image or complex data needing human interpretation.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, the entire submission and the performance studies detailed (Method Comparison, Precision, Linearity, Limits of Detection/Quantitation, Interferences, Cross-reactivity, Serum/Plasma Equivalency, Reference Intervals) effectively describe the standalone performance of the algorithm, as it's an automated device that provides quantitative results without human interpretation in the determination of the final value. The performance evaluation focuses on the analytical performance of the Dimension Vista® LOCI Total Testosterone Flex® reagent cartridge and system itself.
7. Type of Ground Truth Used
- Method Comparison: CDC Isotope dilution/liquid chromatographic-tandem mass spectrometry (CDC ID/LC-MS/MS) (a highly accurate reference analytical method, considered a gold standard).
- Precision, Linearity, LoD/LoQ, Interferences, Cross-reactivity, Serum/Plasma Equivalency: These studies rely on known concentrations (e.g., spiked samples, control materials, or reference method values from the method comparison) to establish the accuracy and reliability of the device's measurements.
- Expected Values (Reference Interval): Data from well-defined populations of healthy individuals, analyzed using statistical methods (non-parametric or "Robust" method).
8. Sample Size for the Training Set
The provided document does not mention a training set in the context of machine learning or AI algorithms as the primary development method for the immunoassay. This device is based on a "homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology" (a biochemical detection method), not a software algorithm that learns from a training dataset in the typical AI sense. The development of such an assay involves extensive biochemical optimization, reagent formulation, and analytical validation.
9. How the Ground Truth for the Training Set Was Established
As no training set (in the AI/ML context) is discussed, this question is not applicable. The "ground truth" for developing this type of immunoassay would involve precise chemical standards and assays to characterize reagent performance and assay kinetics during R&D.
Ask a specific question about this device
(263 days)
Dimension Vista MMB Assay
Dimension Vista® MMB Assay:
The MMB method is an in vitro diagnostic test for the quantitative measurement of mass creatine kinase MB isoenzyme in human serum and plasma on the Dimension Vista® System for confirmation of acute myocardial infarction.
Dimension Vista® 1500 System:
The Siemens Healthcare Diagnostics Dimension Vista® 1500 System is an in vitro diagnostic device intended to duplicate manual analytical procedures such as pipetting, mixing, and measuring spectral intensities to determine a variety of analytes in human body fluids. Dimension Vista® chemical and immunochemical applications use photometric, turbidimetric, chemiluminescence, nephelometric and integrated ion-selective multisensor technology for clinical use.
Dimension Vista® MMB Assay:
The MMB method is a homogeneous sandwich chemiluminescent immunoassay based on LOCI® technology. LOC10 reagents include two synthetic bead reagents and a biotinylated antimass creatine kinase MB isoenzvme monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitive dye. The second bead reagent (Chemibeads) is coated with a second anti-mass creatine kinase MB isoenzyme monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a beadmass creatine kinase MB isoenzyme-biotinylated antibody sandwich. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex by light at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the mass creatine kinase MB isoenzyme concentration in the sample.
The Dimension Vista® 1500 System:
The Dimension Vista® 1500 System is a floor model, fully automated, microprocessor-controlled, integrated instrument system that uses prepackaged Flex reagent test cartridges to measure a variety of analytes in human body fluids. The system is a multi-functional analytical tool that processes chemical and immunochemical methodologies, utilizing photometric, turbidimetric, chemiluminescence, nephelometric, and integrated ion selective multisensor detection technologies for clinical use. The Dimension Vista® 1500 System can analyze up to 1500 tests/hour (typical, depending on the method mix) using a variety of analytical detection capabilities. Dimension Vista® 1500 System detection technologies are: Photometric, Turbidimetric, Chemiluminescent, Nephelometric, Multisensor, ion selective technology
The Siemens Healthcare Diagnostics Dimension Vista® MMB Assay is an in vitro diagnostic test for the quantitative measurement of mass creatine kinase MB isoenzyme in human serum and plasma for confirmation of acute myocardial infarction. The K143720 submission describes the modification of the Dimension Vista® 1500 System with a new photomultiplier tube (PMT) and its impact on the MMB assay.
Here's an analysis of the acceptance criteria and study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" in a separate section with pass/fail thresholds. Instead, it presents performance characteristics (method comparison, precision, linearity, LoB, LoD, LoQ) for the modified system and implicitly assumes that these demonstrate substantial equivalence to the predicate device. For this response, I will interpret the performance data provided as the "reported device performance" and infer the implied "acceptance criteria" based on the comparison to the existing predicate and typical performance expectations for such devices.
| Performance Characteristic | Implicit Acceptance Criteria (Inferred) | Reported Device Performance (Modified System) |
|---|---|---|
| Method Comparison | Close agreement with predicate device (slope near 1, intercept near 0, high correlation). | Passing-Bablok Regression: Slope = 0.99 (95% CI: 0.98 - 0.99), Intercept = -0.16 ng/dL (95% CI: -0.20 - -0.10). Linear Regression: Slope = 0.97, Intercept = 0.64, Correlation Coefficient = 0.999. (Range: 1.0 - 274.0 ng/mL) |
| Precision (Repeatability) | Low coefficient of variation (CV) at various concentration levels. | QC1 (8.66 ng/mL): SD = 0.15, %CV = 1.72. QC2 (24.13 ng/mL): SD = 0.36, %CV = 1.50. QC3 (70.73 ng/mL): SD = 0.91, %CV = 1.28. Plasma Pool 1 (3.26 ng/mL): SD = 0.15, %CV = 4.71. Plasma Pool 2 (6.15 ng/mL): SD = 0.15, %CV = 2.45. |
| Precision (Within-Lab) | Low coefficient of variation (CV) at various concentration levels. | QC1 (8.66 ng/mL): SD = 0.22, %CV = 2.59. QC2 (24.13 ng/mL): SD = 0.56, %CV = 2.30. QC3 (70.73 ng/mL): SD = 1.27, %CV = 1.80. Plasma Pool 1 (3.26 ng/mL): SD = 0.19, %CV = 5.99. Plasma Pool 2 (6.15 ng/mL): SD = 0.21, %CV = 3.40. |
| Linearity | Demonstrated linearity across the assay range (slope near 1, intercept near 0, high correlation). | Range: 0 – 313.5 ng/mL. Slope = 1.004, Intercept = 0.170, Correlation Coefficient = 0.999. |
| Limit of Blank (LoB) | Acceptably low. | 0.4 ng/mL. |
| Limit of Detection (LoD) | Acceptably low (proportion of false positives/negatives |
Ask a specific question about this device
(441 days)
Dimension Vista Chemistry 1 Calibrator (CHEM 1 CAL), Dimension Vista Magnesium Flex reagent cartridge
The Dimension Vista® Magnesium Flex® reagent cartridge (MG) method is an in vitro diagnostic test for the quantitative measurement of magnesium in human serum, plasma and urine on the Dimension Vista® System. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia (abnormally low plasma levels of magnesium) and hypermagnesemia (abnormally high plasma levels of magnesium).
The Dimension Vista® Chemistry 1 Calibrator (CHEM 1 CAL) is an in vitro diagnostic product for the calibration of Blood Urea Nitrogen (BUN),Calcium (CA), Cholesterol (CHOL), Creatinine (CRENCRE2), Glucose (GLU), Lactic Acid (LA), Magnesium (MG), Thyroxine (T4), Thyronine Uptake (TU) and Uric Acid (URCA) methods on the Dimension Vista® System.
CHEM 1 CAL is a liquid, frozen multi-analyte, bovine serum albumin based product used to calibrate blood urea nitrogen, calcium, cholesterol, creatinine, glucose, lactic acid, magnesium, thyroxine, thyronine uptake and uric acid. The kit consists of six vials, three vials of Calibrator A and three vials of Calibrator B.
The Dimension Vista® MG Flex® reagent cartridge uses a modified methylthymol blue (MTB) complexometric technique. MTB forms a blue complex with magnesium. Calcium interference is minimized by forming a complex between calcium and Ba-EGTA (chelating agent). The amount of MG-MTB complex formed is proportional to the magnesium concentration and is measured using a bichromatic (600 and 510 nm) endpoint technique.
The provided text describes the performance characteristics of the Dimension Vista® Magnesium Flex® reagent cartridge (MG) and the Dimension Vista® Chemistry 1 Calibrator (CHEM 1 CAL). The focus is on demonstrating substantial equivalence to predicate devices and meeting established clinical laboratory guidelines. However, the information is primarily focused on analytical performance rather than clinical effectiveness or diagnostic accuracy in specific patient populations.
Here's an attempt to extract the requested information, acknowledging that some categories may not be directly applicable or fully detailed given the nature of an in vitro diagnostic device's analytical validation.
1. Table of Acceptance Criteria and Reported Device Performance
Device: Dimension Vista® Magnesium Flex® reagent cartridge (MG) for quantitative measurement of magnesium.
| Performance Characteristic | Acceptance Criteria (Implicit from CLSI Guidelines and Study Design) | Reported Device Performance (MG Assay) |
|---|---|---|
| Method Comparison (Correlation) | High correlation (e.g., r > 0.975) with a legally marketed device; slope close to 1, intercept close to 0. | Serum: Slope: 1.10, Intercept: -0.15 mg/dL, Correlation Coefficient: 1.00 (vs. Beckman AU Magnesium assay) |
| Lithium Heparin Plasma: Slope: 1.05, Intercept: -0.01 mg/dL, Correlation Coefficient: 0.994 (vs. Beckman AU Magnesium assay) | ||
| Urine: Slope: 1.05, Intercept: 0.09 mg/dL, Correlation Coefficient: 0.995 (vs. Beckman AU Magnesium assay) | ||
| Precision (Repeatability & Within-Lab CV%) | Low Coefficient of Variation (CV%) as per CLSI EP05-A2. (Specific numerical criteria are not explicitly stated, but typical ranges for clinical assays are often |
Ask a specific question about this device
(237 days)
DIMENSION VISTA FREE THYROXINE FLEX REAGENT CARTRIDGE, FT4, DIMENSION VISTA THYROID STIMULATING HORMONE
The FT4L method is an in vitro diagnostic test for the quantitative measurement of Free Thyroxine in human serum and plasma on the Dimension® EXL™ integrated chemistry system with LOCI® Module. Measurements of free thyroxine are used in the diagnosis and monitoring of thyroid disease.
The TSH method is an in vitro diagnostic test for the quantitative measurement of Thyroid Stimulating Hormone in human serum and plasma on the Dimension Vista® System. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.
The submission describes the Dimension® Vista Free Thyroxine Flex® reagent cartridge, FT4 and the Dimension Vista® Thyroid Stimulating Hormone Flex® reagent cartridge, TSH. These are in vitro diagnostic tests for the quantitative measurement of Free Thyroxine and Thyroid Stimulating Hormone in human serum and plasma, respectively, on the Dimension Vista® System. The submission is for the inclusion of pediatric reference intervals to the labeling (Package Inserts) of these assays. No changes were made to the reagents, device design, or manufacturing process.
The document describes the establishment of pediatric reference intervals for the Dimension Vista® Free Thyroxine (FT4) and Thyroid Stimulating Hormone (TSH) Flex® reagent cartridges. It does not contain an acceptance criteria table related to the device's performance against specific metrics of accuracy or precision in the traditional sense, but rather focuses on establishing biological reference intervals. The study's primary goal was to define these pediatric reference intervals.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
As noted, the document doesn't provide a table of discrete acceptance criteria for device performance (e.g., sensitivity, specificity, accuracy against a gold standard). Instead, the acceptance in this context relates to the establishment and statistical validation of reference intervals for pediatric populations.
The reported "performance" for the Dimension Vista® FT4 and TSH assays, in the context of this submission, is the established pediatric reference intervals. These are compared against adult reference intervals and the assay's analytical measuring range to demonstrate suitability for pediatric use.
| Reference Interval Category | Dimension Vista® FT4 (ng/dL) | Dimension Vista® TSH (µIU/mL) |
|---|---|---|
| Pediatric Reference Intervals | ||
| Infants (01 - 23 months) | 0.88 - 1.48 | 0.816 - 5.91 |
| Children (02 - 12 years) | 0.81 - 1.35 | 0.662 - 3.90 |
| Adolescents (13 – 20 years) | 0.78 - 1.33 | 0.463 - 3.98 |
| Euthyroid Adults (for comparison) | 0.76 - 1.46 | 0.358 - 3.74 |
| Assay Range (for comparison) | 0.1 - 8.0 | 0.005 - 100 |
Justification of Suitability for Pediatric Use (Acceptance Criteria Implicitly Met):
The document states two key rationales for accepting the pediatric reference intervals, implicitly acting as "acceptance criteria" for the device's application in this population:
- 1. Alignment with Indications for Use: "Testing of pediatric patients is within the established indications for use in the diagnosis and treatment of thyroid disease..."
- 2. Analytical Compatibility: "The newly-established pediatric reference intervals are either within or are above the previously-established reference intervals for euthyroid (normal thyroid) adult populations and they are within the analytical measuring ranges of the Dimension Vista® FT4 and TSH assays. Therefore, the Dimension Vista® FT4 and TSH assays have appropriate analytical performance to test pediatric patients."
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: A total of 421 patients were analyzed to establish the pediatric reference intervals:
- Infants (01 - 23 months): 82
- Children (02 - 12 years): 191
- Adolescents (13 – 20 years): 148
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. It implies the samples were collected specifically for this study ("Data from a total of 421 patients... were analyzed to establish..."). Given the context of establishing reference intervals, it is likely prospective collection from healthy individuals within the specified age groups, though this is not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable to this study. The "ground truth" here is the biological variation of FT4 and TSH levels in healthy pediatric populations. Reference intervals are established statistically from a cohort of presumably healthy individuals, not through expert consensus on individual cases.
4. Adjudication Method for the Test Set
This is not applicable. There was no need for adjudication as the study focused on quantitative measurements and statistical analysis of those measurements to define reference ranges.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This is not applicable. The device is an in-vitro diagnostic test for quantitative measurement, not an imaging device or a diagnostic aid requiring human interpretation that benefits from AI assistance. Therefore, an MRMC study and effect size for human improvement are not relevant.
6. Standalone Performance
Yes, this study inherently focuses on the standalone performance of the Dimension Vista® FT4 and TSH assays. The goal was to determine the measured analyte levels in a specific population (pediatrics) using the device alone, to establish reference intervals. There is no human-in-the-loop component for the determination of the numeric values.
7. Type of Ground Truth Used
The ground truth used to establish the reference intervals is biological reference data from a population of presumably healthy subjects within specified age groups. This involves statistical methods (non-parametric for children/adolescents, robust symmetric for infants, sometimes after log transformation for skewed data) to determine the central 95% of values.
8. Sample Size for the Training Set
This study is not framed in terms of a "training set" for an algorithm. The samples of 421 pediatric patients (82 infants, 191 children, 148 adolescents) directly served as the dataset from which the reference intervals were derived using statistical methods, which could be considered the "training" for the reference interval definition.
9. How the Ground Truth for the Training Set Was Established
The "ground truth" (i.e., the reference intervals) for the pediatric populations was established through statistical analysis of quantitative measurements of FT4 and TSH in serum/plasma samples from the 421 pediatric subjects.
- CLSI C28-A3c Guideline: The study followed the "Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline -- Third Edition (CLSI C28-A3c)" standard.
- Non-parametric approach: Used for children and adolescents, where the 2.5th and 97.5th percentiles of the distribution of values were calculated. This technique is typically used when the sample size is sufficient (usually >120).
- Robust symmetrical method (Horn and Pesce, CLSI EP28-A3c): Used for infants due to a sample size of less than 120 (82 patients).
- Log transformation: For the TSH assay in infants, the data was highly positively skewed, so a natural log transformation was applied to achieve a normal distribution before applying the robust symmetric method.
- Confirmation with Simulated Reference Intervals: Both methods were confirmed with two simulated reference intervals (non-parametric and robust symmetric) estimated as the means of the 95% upper and lower bounds from 1000 data sets.
Ask a specific question about this device
(49 days)
DIMENSION VISTA CREATININE (CRE2) FLEX REAGENT CARTRIDGE
The CRE2 method is an in vitro diagnostic test for the quantitative measurement of creatinine in human serum, plasma, and urine on the Dimension Vista® System. Creatinine measurements are used in the diagnosis and treatment of certain renal disease, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
The Dimension Vista® Creatinine (CRE2) Flex® reagent cartridge uses a modified kinetic Jaffe technique. In the presence of a strong base such as sodium hydroxide, picrate reacts with creatinine to form a red chromophore. The rate of increasing absorbance at 510 nm due to the formation of this chromophore is directly proportional to the creatinine concentration in the sample and is measured using a bichromatic (510, 577 nm) rate technique.
Here's a breakdown of the acceptance criteria and study information for the Dimension Vista® System Creatinine (CRE2) Flex® reagent cartridge, based on the provided text:
Acceptance Criteria and Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Method Comparison (Serum) | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 when compared to predicate device (Vista CREA Assay) | Vista CREA Assay (Serum): Range 0.38 – 18.93 mg/dL, Slope = 1.02, Intercept = -0.11 mg/dL, Correlation Coefficient = 1.000 (n=140) |
| Method Comparison (Urine) | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 when compared to predicate device (Vista CREA Assay) | Vista CREA Assay (Urine): Range 8.39 – 299.60 mg/dL, Slope = 1.05, Intercept = -4.29 mg/dL, Correlation Coefficient = 0.999 (n=112) |
| Method Comparison (IDMS) | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 when compared to IDMS Reference Method | IDMS Reference Method (Serum): Range 0.18–6.32 mg/dL, Slope = 1.06, Intercept = -0.03 mg/dL, Correlation Coefficient = 0.997 (n=48) |
| Serum Plasma Equivalency | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 for matched serum vs. lithium heparin plasma samples | Slope = 1.03, Intercept = -0.002, Correlation Coefficient (r) = 0.998 (Range 0.418 - 17.9, n=56) |
| Precision | Within-Lab %CV values for various serum and urine pools and control materials. (Implicitly, these should be within acceptable limits for a diagnostic test, though specific numerical criteria for acceptance are not explicitly stated as a single value) | Reported %CVs: Serum Pool 1 (2.7%), Serum Pool 2 (0.7%), BioRad Multiqual Level 1 (4.0%), Level 2 (2.5%), Level 3 (1.1%), Urine Pool 1 (3.6%), Urine Pool 2 (1.0%), BioRad Liquicheck Level 1 (2.2%), Level 2 (2.0%). (All values are low, indicating good precision.) |
| Limit of Blank (LoB) | Consistent with claim of 0.05 mg/dL (serum), 1.0 mg/dL (urine) | LoB (Serum): 0.030 mg/dL (consistent with 0.05 mg/dL claim) |
| LoB (Urine): 0.438 mg/dL (consistent with 1.0 mg/dL claim) | ||
| Limit of Detection (LoD) | Consistent with claim of 0.1 mg/dL (serum), 2.0 mg/dL (urine) | LoD (Serum): 0.056 mg/dL (consistent with 0.1 mg/dL claim) |
| LoD (Urine): 0.828 mg/dL (consistent with 2.0 mg/dL claim) | ||
| Limit of Quantitation (LoQ) Serum/Plasma | Allowable total error for creatinine published by CLIA, CAP, AAB, NYS, and WSLH is +/- 0.3 mg/dL or +/- 15%. (LoQ should meet these recommendations). | LoQ (Serum/Plasma): 0.15 mg/dL based on allowable total error of 0.15 mg/dL. This meets the recommendations. |
| Limit of Quantitation (LoQ) Urine | No recognized allowable total error limit for urine creatinine measurements. (Implicit acceptance is that the determined LoQ is appropriate and justified). | LoQ (Urine): 5.00 mg/dL based on allowable total error of 3.00 mg/dL. |
| Linearity (Serum) | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 across the assay range | Linearity (Serum): Range 0.00 – 21.9 mg/dL, Slope = 0.996, Intercept = -0.05, Correlation Coefficient = 1.0 (N=12) |
| Linearity (Urine) | Slope close to 1, Intercept close to 0, Correlation Coefficient close to 1 across the assay range | Linearity (Urine): Range 1.71 – 338 mg/dL, Slope = 0.995, Intercept = 0.47, Correlation Coefficient = 1.0 (N=12) |
| Interfering Substances | Bias exceeding 10% is considered interference. Dilution studies determine the level at which spiked substances no longer display significant interference. | Demonstrated concentrations where various substances cause 10% bias, the concentration at which interference is no longer significant through dilution. For example, Acetone interferes at 150 mg/dL (18% bias) but not at 75 mg/dL (9% bias). Bilirubin (unconjugated) at 40mg/dL shows -29.6% bias at low creatinine, but 20mg/dL shows -0.2% bias. |
| HIL Interference | Bias exceeding 10% is considered interference. | Intralipid 20% interferes at 2000 mg/dL and 1500 mg/dL (at low creatinine concentration) (15.5% and 15.1% bias, respectively), but not at 1500 mg/dL (at high creatinine concentration) (9.5% bias) or 1000 mg/dL (7.0% bias). Hemoglobin shows no significant interference at 1000 mg/dL (~7% and 3% bias). Bilirubin (unconjugated) at 40 mg/dL shows -29.6% interference at low creatinine levels. Bilirubin (conjugated) shows 16.1% interference at 40 mg/dL at low creatinine levels. |
| Expected Values (Serum & Plasma) | ≤10% of samples within the study should fall outside of established range. | Males: 5 (9.4%) out of 53 samples outside range (meets ≤10%). |
| Females: 2 (5.0%) out of 40 samples outside range (meets ≤10%). (Supports published ranges). | ||
| Expected Values (Urine) | ≤10% of samples within the study should fall outside of established range. | Males: 2 (9.1%) out of 22 samples outside range (meets ≤10%). |
| Females: 1 (5.0%) out of 20 samples outside range (meets ≤10%). (Supports published ranges). | ||
| Reportable Range Dilution (Serum) | Mean percent recovery of 90-110% for autodiluted samples. | Mean of N=5 reps: 16.5 µL (normal volume) = 16.5; 6.6 µL (auto-dilute volume) = 16.0; % Bias = -3.0%. (Implicitly meets recovery criteria, as bias is very low). Supports extended range to 40.0 mg/dL. |
| Reportable Range Dilution (Urine) | Mean percent recovery of 90-110% for autodiluted samples. | Mean of N=5 reps: undiluted (normal) = 268; auto-dilute 3x with water = 245; % Bias = -8.6%. (Implicitly meets recovery criteria, as bias is very low). Supports extended range to 900 mg/dL. |
Study Details
-
Sample sizes used for the test set and the data provenance:
- Method Comparison (Predicate Device):
- Serum: 140 patient samples. Remnant de-identified serum samples. No patient history. Inclusion/exclusion criteria not applicable. Both native and spiked samples.
- Urine: 112 patient samples. Remnant de-identified urine samples (implied). No patient history. Inclusion/exclusion criteria not applicable.
- Method Comparison (IDMS Reference Method):
- Serum: 48 patient samples. Remnant de-identified serum samples. No patient history. Inclusion/exclusion criteria not applicable. All native samples.
- Serum Plasma Equivalency: 56 matched serum and lithium heparin plasma samples. All samples fresh and never frozen. 8 spiked sample sets.
- Precision: Not a direct "test set" in the sense of patient samples, but testing involved: 2 serum pools, 3 levels of BioRad Multiqual material, 2 levels of BioRad Liquicheck material, and 2 urine pools. Each tested multiple times (over 20 days, 2 runs, 2 samples per run).
- Limit of Blank/Detection (Serum): 4 samples with no analyte (N=5 reps for 3 days), 4 low patient serum samples (N=5 reps for 3 days).
- Limit of Blank/Detection (Urine): 4 samples with no analyte (N=5 reps for 3 days), 4 low patient urine samples (N=5 reps for 3 days).
- Linearity: 12 equally spaced samples for serum, 12 for urine.
- Analytical Specificity (Interference): Low (~1.5 mg/dL) and High (~5.0 mg/dL) creatinine serum pools; Low (~40 mg/dL) and High (~175 mg/dL) creatinine urine pools. Number of individual samples/tests per interferent is not explicitly stated but implied to be sufficient for creating means and controls.
- Expected Values:
- Serum and Plasma: 53 male donors, 40 female donors (all normal healthy adults).
- Urine: 22 male donors, 20 female donors (all normal healthy adults).
- Reportable Range Dilution: N=5 replicates for each dilution study (serum and urine).
Data Provenance: The studies were conducted internally by Siemens Healthcare Diagnostic Inc. R&D organization personnel. Remnant de-identified samples were used for method comparison studies, implying retrospective or archived samples. Patient history was not obtained. The origin of the patient samples (e.g., country) is not specified, but the internal R&D location would presumably be Newark, DE, USA based on the applicant's address.
- Method Comparison (Predicate Device):
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not mention the use of experts to establish ground truth for the test set in the context of clinical interpretation. For method comparison, the "ground truth" for the new device was established by comparison to a legally marketed predicate device (Dimension Vista® Creatinine (CREA) Flex® reagent cartridge) and the IDMS reference method. These are analytical "gold standards" rather than expert interpretation. -
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable. The reported studies are analytical performance evaluations of a quantitative laboratory test, not diagnostic interpretations requiring adjudication. -
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 a quantitative in vitro diagnostic test for creatinine, not an imaging or interpretive device that would typically involve human readers or AI assistance in the way an MRMC study would assess. -
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, these are all standalone (algorithm only) performance studies. The device itself performs the quantitative measurement of creatinine from samples without human interpretation in the loop of the measurement. -
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For Method Comparison studies: The ground truth was established by two primary methods:
- Comparison to a predicate device (Dimension Vista® Creatinine (CREA) Flex® reagent cartridge).
- Comparison to the IDMS reference method (Isotope Dilution Mass Spectrometry), which is a highly accurate and precise analytical method often considered a "gold standard" for creatinine measurements.
- For Expected Values studies: Published reference ranges in scientific literature (e.g., Tietz 1999, Clin Chem 54:3 (2008), Clin Chem Acta 344 (2004) 137-148) served as the basis for validating the established ranges for the new device.
- For LoQ validation: Allowable total error limits published by regulatory and accreditation bodies (CLIA, CAP, AAB, NYS, WSLH) were used. The reference values are traceable to IDMS.
- For Method Comparison studies: The ground truth was established by two primary methods:
-
The sample size for the training set:
Not applicable in the context of typical AI/machine learning studies. This device is a reagent cartridge for an automated clinical chemistry system, not an AI or machine learning algorithm that undergoes 'training' in the conventional sense with labeled data. The development and internal refinement of the reagent formulation and measurement parameters would be analogous to "training" but is not quantified in terms of a discrete sample set size like this. -
How the ground truth for the training set was established:
Not applicable for the same reasons as above. The "ground truth" for developing such a system would involve rigorous analytical chemistry principles, extensive experimentation, and calibration using traceable standards (e.g., NIST SRM 914a (IDMS assigned crystalline creatinine standard)).
Ask a specific question about this device
(22 days)
DIMENSION VISTA PROGESTERONE CALIBRATOR (PROG CAL)
The PROG CAL is an in vitro diagnostic product for the calibration of the Progesterone (PROG) assay on the Dimension Vista® System.
PROG CAL is a single analyte, liquid, frozen, product containing progesterone and preservatives in a human serum base, for in vitro diagnostic use. Contains human source material. Each donor unit used in the preparation of this product was tested by FDA-approved methods for the presence of antibodies to Human Immunodeficiency Virus Type 1 (HIV-1) and Type 2 (HIV-2), as well as for Hepatitis B surface Antigen and antibody to Hepatitis C Virus (HCV), and found to be negative (not repeatedly reactive). Because no testing can offer complete assurance that these or other infectious agents are absent, this material should be handled using good laboratory practice to avoid skin contact and ingestion. The kit consists of ten vials, two each of five levels containing 1 mL per vial.
The provided text describes a 510(k) submission for a medical device (Siemens Healthcare Diagnostics Dimension Vista® Progesterone Calibrator) and focuses on demonstrating substantial equivalence to a predicate device. It does not contain information about the acceptance criteria or a study proving the device meets those criteria, as typically found in clinical performance studies. The document primarily details the device's technical specifications, intended use, and a comparison to a similar, already-marketed device for the purpose of regulatory clearance.
Therefore, many of the requested details, such as sample size, data provenance, expert qualifications, adjudication methods, MRMC studies, standalone performance, and ground truth for training sets, are not applicable or not mentioned in this regulatory submission for a calibrator.
However, I can extract the information that is present:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state quantitative acceptance criteria in a table format for device performance in the way a clinical study would. The primary "performance" discussed relates to stability and value assignment, which are confirmed to meet "defined acceptance criteria" without specifying the exact criteria or the numerical results of those criteria in detail.
| Acceptance Criteria Category | Reported Device Performance |
|---|---|
| Stability (Frozen: -15C to -25C) | Real-time calibrator shelf life determined by comparing results of calibrator levels stored at -15C and -25C with control calibrators stored at -70C. Recovery versus time monitored, and percent change over time determined. "Defined acceptance criteria were met at all conditions." |
| Stability (Opened/Thawed: 2-8°C) | Real-time testing after thawing at 2-8°C for 15 days. "Defined acceptance criteria were met at all conditions." Assigned values are stable for 15 days when recapped immediately and stored at 2-8°C. Assigned values are stable for 15 days when stored on board the Dimension Vista System after vial puncture. |
| Value Assignment | Values for each level of calibrator assigned using multiple Dimension Vista instruments and multiple reagent lots. Traceable to the Progesterone reference method (ID/GC/MS). The bottle value for each level is the mean of 45 replicates. "Defined acceptance criteria were met at all conditions." |
2. Sample Size for Test Set and Data Provenance:
- Sample Size for Test Set: Not explicitly stated as a separate "test set" in the context of clinical performance. For value assignment, "45 replicates" were used for each calibrator level to determine the mean bottle value. For stability, multiple calibrator levels were tested over time.
- Data Provenance: Not specified. Likely internal laboratory data from Siemens Healthcare Diagnostics. Given it's a calibrator, the "data" would be analytical measurements rather than patient data.
- Retrospective/Prospective: Not explicitly stated. Stability studies generally imply a prospective monitoring over time.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications:
- Not applicable in the context of calibrator performance. Ground truth for progesterone concentration is established through a reference method (ID/GC/MS), not expert consensus.
4. Adjudication Method for the Test Set:
- Not applicable. The ground truth is based on an analytical reference method (ID/GC/MS) rather than subjective interpretation requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. This is a calibrator, not an AI-assisted diagnostic device that would involve human readers interpreting images or results. Therefore, an MRMC study is not relevant.
6. Standalone Performance Study:
- Yes, indirectly. The stability testing and value assignment studies describe the performance of the calibrator itself (algorithm/device only in this context) to ensure it performs as expected over time and accurately assigns progesterone values. These studies confirm its analytical performance in a standalone capacity.
7. Type of Ground Truth Used:
- Reference Method Traceability: The "ground truth" for the progesterone concentrations in the calibrator levels is established through traceability to the Isotope Dilution Gas Chromatography Mass Spectrometry (ID/GC/MS) reference measurement procedure.
8. Sample Size for the Training Set:
- Not applicable. This is a calibrator, not a machine learning algorithm that requires a "training set" in the conventional sense. Its values are assigned based on measurements, not learning from data.
9. How the Ground Truth for the Training Set Was Established:
- Not applicable, as there is no "training set" for a calibrator. The accuracy of the calibrator's assigned values is rooted in its traceability to the ID/GC/MS reference method.
Ask a specific question about this device
(97 days)
DIMENSION VISTA; AMMONIA FLEX REAGENT CARTRIDGE (AMM), CHEMISTRY 3 CALIBRATOR (CHEM 3 CAL)
The AMM method is an in vitro diagnostic test for the quantitative measurement of ammonia in human plasma on the Dimension Vista® System. Ammonia measurements are used in the diagnosis and treatment of severe liver disorders such as cirrhosis, hepatitis and Reye's syndrome.
The CHEM 3 CAL is an in vitro diagnostic product for the calibration of Ammonia (AMM), Carbon Dioxide (CO2) and Ethyl Alcohol (ETOH) methods on the Dimension Vista" System.
The Dimension Vista® Ammonia assay (AMM) is an enzymatic method that uses glutamate dehydrogenase (GLDH) and a stabilized NADPH analog. Ammonia reacts with a-ketoglutarate and reduced cofactor to form L-glutamate and the cofactor. The reaction is catalyzed by glutamate dehydrogenase. The decrease in absorbance due to the oxidation of the reduced cofactor is monitored at 340/700 nm and is proportional to the ammonia concentration.
The Dimension Vista® Ammonia (AMM) Flex® reagent cartridge is an in vitro diagnostic device that consists of prepackaged reagents in a plastic cartridge for use on the Dimension Vista® System.
The Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) is a two level, liquid calibrator. It is packaged as a kit of six vials with 2.5 mL per vial. The product is a multi-analyte, aqueous product containing ammonium bicarbonate, sodium carbonate and ethyl alcohol.
The provided document describes the Siemens Dimension Vista® Ammonia Flex® reagent cartridge (AMM) and Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) and their performance characteristics. As a laboratory assay and calibrator, the concept of "acceptance criteria" and "device performance" relates to analytical performance metrics rather than diagnostic accuracy as would be the case for an AI medical device. Similarly, concepts like "sample size used for the test set," "data provenance," "number of experts," "adjudication method," "MRMC comparative effectiveness study," "standalone performance," and "ground truth" are not directly applicable in the context of validating an in vitro diagnostic reagent and calibrator kit.
However, I can extract the relevant analytical performance characteristics and compare them to accepted standards (often implied by the CLSI guidelines referenced).
Here's an interpretation of the requested information, adapted to the context of an in vitro diagnostic (IVD) reagent and calibrator:
Acceptance Criteria and Study to Prove Device Meets Criteria
The studies conducted for the Siemens Dimension Vista® Ammonia Flex® reagent cartridge (AMM) and Dimension Vista® Chemistry 3 Calibrator (CHEM 3 CAL) evaluate their analytical performance against established guidelines (primarily CLSI standards). The 'acceptance criteria' are generally understood to be meeting these established analytical performance benchmarks to demonstrate substantial equivalence to predicate devices and ensure reliable test results.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied by CLSI Guidelines & Predicate Equivalence) | Reported Device Performance (AMM Assay) |
|---|---|---|
| Method Comparison | High correlation (r > 0.975), acceptable slope (0.95-1.05), and intercept against predicate device. | Correlation: r = 0.993 (AMM vs. Dimension® AMON) |
| Slope: 1.03 | ||
| Intercept: 13.6 µg/dL [8.0 µmol/L] | ||
| Plasma Equivalency | High correlation (r > 0.975), acceptable slope (0.95-1.05), and intercept between different plasma types. | Correlation: r = 1.00 (Lithium Heparin vs. EDTA) |
| Slope: 0.96 | ||
| Intercept: 3.3 µg/dL [2.0 µmol/L] | ||
| Reference Interval | Validation of existing reference interval by transference or establishment of new interval. | Validated transference of 19 - 54 µg/dL [11 - 32 µmol/L] from predicate. |
| Precision | Acceptable %CV for repeatability and within-lab variability across different analyte levels. | Repeatability %CV: Level 1 (6.1), Level 2 (1.2), Level 3 (0.6) |
| Within-Lab %CV: Level 1 (7.5), Level 2 (1.7), Level 3 (0.9) | ||
| Linearity (Analytical Measurement Range) | Demonstrated linear response over the claimed range. | 17 - 1277 µg/dL [10 - 750 µmol/L] |
| Interference | Bias due to interfering substances 10% bias at specific concentrations for some ammonia levels. Further analysis showed no significant interference for certain endogenous interferents at specific analyte level based on recovery within 10% of expected value. | |
| Limit of Blank (LoB) | LoB value that supports the claimed analytical range. | 4 µg/dL [2 µmol/L] (Claimed LoB: 9 µg/dL [5 µmol/L]) |
| Limit of Detection (LoD) | LoD value that supports the claimed analytical range. | 15 µg/dL [9 µmol/L] (Claimed LoD: 17 µg/dL [10 µmol/L]) |
| Limit of Quantitation (LoQ) | LoQ value that supports the claimed analytical range. | 17 µg/dL [10 µmol/L] (Claimed LoQ: 17 µg/dL [10 µmol/L]) |
2. Sample Size Used for the Test Set and the Data Provenance
- Method Comparison: 100 patient samples. Provenance is not explicitly stated (e.g., country of origin) but inferred to be clinical laboratory samples. Data type is prospective, as fresh samples were tested.
- Plasma Equivalency: 49 fresh matched lithium heparin and EDTA plasma samples. Provenance is not explicitly stated. Data type is prospective.
- Precision: Not explicitly stated as "sample size" in the context of unique patient samples, but testing involved "three levels of Liquicheck™ Ethanol/Ammonia control" tested over 20 days, two separate runs with two test samples for each test material (effectively 3 levels * 20 days * 2 runs * 2 replicates = 240 measurements for each level during repeatability and within-lab assessment).
- Linearity, LoB, LoD, LoQ: The number of unique patient samples is not specified. Studies utilized specific control materials and diluted samples tested across multiple days, runs, and replicates (e.g., for LoB, 4 blank samples tested for 3 days, 1 run/day, 2 replicates/run).
- Interference: Tested with specific concentrations of interfering substances (e.g., 75 mg/dL Hemoglobin) and tested at two analyte concentrations (85 µg/dL and 426 µg/dL). The number of unique patient samples for interference testing is not explicitly stated for all tests, but for certain endogenous interferents which exceeded 10% bias, an aliquot of a patient sample containing the potential interferent was mixed with a plasma pool.
Data provenance is from laboratory studies performed at Siemens Healthcare Diagnostics, Inc. on Dimension Vista® 1500 System, implying a retrospective analysis of collected lab data or controlled prospective lab studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This concept is not applicable to the validation of an IVD reagent and calibrator. The "ground truth" for analytical performance studies is typically established by:
- The results from a legally marketed predicate device (for method comparison).
- Defined reference materials (e.g., control solutions, calibrators).
- Known concentrations in spiked samples.
- Established clinical laboratory reference intervals.
4. Adjudication Method for the Test Set
Not applicable. This concept relates to expert consensus in interpreting complex data (e.g., images) to establish a "ground truth" for a diagnostic model, which is not relevant for analytical performance studies of a laboratory reagent.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
Not applicable. MRMC studies are used for diagnostic devices that involve human interpretation of results (e.g., radiology images). This document describes an automated laboratory assay. The closest equivalent is the "Method Comparison" study, which compares the new device's analytical results to those of an established predicate device.
- Effect size of human readers improvement with AI vs. without AI assistance: Not applicable, as no human-in-the-loop AI component is demonstrated.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was Done
Yes, the studies presented are all "standalone" in the sense that they evaluate the analytical performance of the assay and calibrator on the Dimension Vista® System without direct human judgment influencing the output of the measurement. The results reported (e.g., correlation, precision, linearity) represent the performance of the device itself.
7. The Type of Ground Truth Used
- Method Comparison: The predicate device, Dimension® Ammonia (AMON) assay (K863840), served as the reference or "ground truth" for comparison.
- Plasma Equivalency: Matched samples of different plasma types were compared, with one type serving as a reference point.
- Precision: Standardized control materials (Liquicheck™ Ethanol/Ammonia control) with known or expected ranges.
- Linearity, LoB, LoD, LoQ: Serial dilutions of samples with known concentrations or blank samples, evaluated against expected analytical behavior.
- Interference: Control samples without interferent compared to test samples with known concentrations of potential interferents.
- Reference Interval: Transference of reference interval from widely accepted literature (Textbook of Clinical Chemistry by NW Tietz) and validated through CLSI C28-A3 guidelines.
8. The Sample Size for the Training Set
Not applicable. This device is an IVD reagent and calibrator, not an AI/ML algorithm that requires a "training set" in the computational sense. The development of such reagents involves chemical and enzymatic research, formulation, and optimization rather than data-driven machine learning training.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an AI/ML algorithm. The "ground truth" for performance evaluations (as described in point 7) is based on established analytical chemistry principles, predicate device performance, and reference materials.
Ask a specific question about this device
(147 days)
DIMENSION VISTA VITAMIN B12 (VB12) FLEX REAGENT CARTRIDGE, DIMENSION VISTA LOCI 4 CALIBRATOR
The VB12 method is an in vitro diagnostic test for the quantitative measurement of vitamin B12 in human serum and plasma on the Dimension Vista® System. Measurements of vitamin B12 are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.
The LOCI 4 CAL is an in vitro diagnostic product for the calibration of LOCI Ferritin (FERR), LOCI Folate (FOL), and LOCI Vitamin B12 (VB12) methods on the Dimension Vista® System.
The LOCI vitamin B12 method is a homogeneous, competitive chemiluminescent immunoassay based on LOCI® technology. LOCI® reagents include two synthetic bead reagents and biotinylated intrinsic factor (IF). The first bead reagent (Chemibead) is coated with a B12 derivative and contains a chemiluminescent dye. The second bead reagent (Sensibead) is coated with streptavidin and contains photosensitive dye. The patient sample is pretreated with sodium hydroxide (NaOH) and dithioerythritol (DTE) to release the serum B12 from its carrier proteins. Potassium cyanide (KCN) is added to convert all the forms of B12 into a single, cyanocobalamin form, and dicyanocobinamide is added to keep the B12 from rebinding with the carrier proteins. After the sample pretreatment, the biotinylated IF and chemibead reagents are added sequentially to the reaction vessel. Vitamin B12 from the sample competes with the B12-chemibead for a limited amount of biotinylated IF. Sensibead reagent is then added and binds to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from the Sensibeads which diffuses to the Chemibeads triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the concentration of vitamin B12 in the sample.
LOCI 4 CAL is a multi-analyte liquid, frozen, product containing Ferritin from human liver, Folate, and Vitamin B12. CAL A is a HEPES buffer solution whereas CAL B - E are prepared in a bovine serum albumin base.
The kit consists of ten vials, two each of five levels containing 2 mL per vial. Description of the manufacturing, value assignment and stability testing processes are provided.
The provided text describes the Siemens Healthcare Diagnostics Dimension Vista® LOCI Vitamin B12 Flex reagent cartridge and Dimension Vista® LOCI 4 CAL and their performance in a study to establish substantial equivalence to predicate devices.
Here's the breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes performance for the Vitamin B12 method. While explicit acceptance criteria values (e.g., "r > 0.95" as a specific target) are not definitively stated, the study's aim is to demonstrate "substantial equivalence" to a predicate device. The reported performance for precision and method comparison serves to support this claim, aligning with typical performance expectations for such diagnostic assays.
Vitamin B12 Assay Performance
| Performance Metric | Acceptance Criteria (Implied for Substantial Equivalence) | Reported Device Performance (Dimension Vista® VB12 Flex) |
|---|---|---|
| Reproducibility (Precision) | Generally high precision (low %CV) expected. | |
| QC L1 (275 pg/mL) | - | Repeatability SD: 11.0, %CV: 4.0; Within-Lab SD: 19.2, %CV: 7.0 |
| QC L2 (518 pg/mL) | - | Repeatability SD: 8.2, %CV: 1.6; Within-Lab SD: 20.3, %CV: 3.9 |
| QC L3 (682 pg/mL) | - | Repeatability SD: 16.3, %CV: 2.4; Within-Lab SD: 20.1, %CV: 3.0 |
| Serum Pool 1 (238 pg/mL) | - | Repeatability SD: 8.4, %CV: 3.5; Within-Lab SD: 18.0, %CV: 7.6 |
| Li Heparin Plasma Pool (365 pg/mL) | - | Repeatability SD: 8.9, %CV: 2.4; Within-Lab SD: 12.3, %CV: 3.4 |
| Serum Pool 2 (1007 pg/mL) | - | Repeatability SD: 14.4, %CV: 1.4; Within-Lab SD: 21.0, %CV: 2.1 |
| Serum Pool 3 (1716 pg/mL) | - | Repeatability SD: 20.6, %CV: 1.2; Within-Lab SD: 32.7, %CV: 1.9 |
| Sample Type Equivalence (vs. Serum) | Correlation Coefficient (r) generally expected > 0.975-0.99 for strong equivalence; Slope near 1.0; Intercept near 0.0. | |
| Lithium Heparin Plasma | - | Slope: 0.993; Intercept: -3.2 pg/mL; r: 0.999 |
| Sodium Heparin Plasma | - | Slope: 0.995; Intercept: -3.3 pg/mL; r: 0.999 |
| EDTA Plasma | - | Slope: 0.999; Intercept: -14.4 pg/mL; r: 0.998 |
| Method Comparison (vs. Predicate) | High correlation (r) and agreement (slope near 1, intercept near 0) with predicate device. | |
| Roche Elecsys B12 System (n=162) | - | Passing-Bablok Constant: -7.64; Proportional: 0.985; Least Squares Regression R: 0.993 |
Note: The acceptance criteria are implicitly met by demonstrating "substantial equivalence" based on these performance characteristics, which show good agreement and precision comparable to typical diagnostic assays.
2. Sample Size Used for the Test Set and Data Provenance
- Reproducibility (Precision) Test: A "single test from two independent cups was analyzed twice per day for 20 days" for each of the 7 materials (3 QC levels, 4 serum/plasma pools). This totals 2 (cups) * 2 (tests/day) * 20 (days) = 80 measurements per material. The exact number of unique patient samples for the serum/plasma pools is not specified, but they are described as "Serum Pool" or "Plasma Pool," implying pooled samples.
- Sample Type Equivalence Test: Seventy-one (71) matched serum, lithium heparin plasma, sodium heparin, and EDTA plasma samples.
- Method Comparison Test: One hundred sixty-two (162) native serum samples.
- Data Provenance: The document does not explicitly state the country of origin or if the data was retrospective or prospective. Given the nature of a 510(k) submission for an in vitro diagnostic device by a major diagnostics company, it's highly probable the studies were conducted prospectively with samples collected for research purposes, likely within a regulated environment (e.g., US or EU).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The device is a quantitative immunoassay for Vitamin B12. The ground truth for such assays is typically established by the analytical method itself or by comparison to an established, validated method (the predicate device in this case) and traceable calibrators.
- Number of Experts: Not applicable in the traditional sense of expert consensus on qualitative data. The "ground truth" for the method comparison is the measurement obtained from the predicate device (Roche Elecsys Vitamin B12 Test System). For precision studies, the 'truth' is inherent to the statistical analysis of repetitive measurements.
- Qualifications of Experts: Not relevant for this type of analytical assay validation.
4. Adjudication Method for the Test Set
Not applicable. As a quantitative assay, the results are numerical measurements from the instruments. Adjudication methods (like 2+1 or 3+1 consensus) are typically used for qualitative or subjective assessments (e.g., image interpretation).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices where human interpretation (e.g., by radiologists, pathologists) is involved, and the AI's role is to assist human readers. This device is an automated, quantitative immunoassay.
- Effect Size of Human Readers with vs. Without AI: Not applicable.
6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the studies presented are all standalone (algorithm only) performance assessments. The device is an automated immunoassay system that provides quantitative results without human interpretation in the loop for the measurement itself. The "method comparison" directly compares the new device's standalone performance to a predicate device's standalone performance.
7. The Type of Ground Truth Used
- For Method Comparison: The ground truth was the measurements obtained from the predicate device, the Roche Elecsys® Vitamin B12 System. This represents a comparative "ground truth" for demonstrating equivalence.
- For Traceability: The calibrators are traceable to United States Pharmacopeia (USP) Grade vitamin B12, which is a form of recognized reference standard. This establishes the metrological ground truth for the measurements.
- For Precision: The ground truth is statistical, derived from repeated measurements of the same sample, indicating the variability of the device itself.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI algorithms. This device is a traditional immunoassay, not an AI/ML-based diagnostic. Its performance characteristics are established through analytical validation studies rather than learning from a training dataset. The development of the assay itself would involve optimization and characterization using various analytical samples, but this is not referred to as a "training set" in the sense of AI/ML.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the AI/ML context for this traditional immunoassay device. The assay design and calibration are based on chemical and biological principles, validated against reference materials and predicate devices.
Ask a specific question about this device
(27 days)
DIMENSION VISTA ALKALINE PHOSPHATASE (ALPI) FLEX REAGENT CARTRIDGE DIMENSION VISTA ALKALINE PHOSPHATASE
The ALPI method is an in vitro diagnostic test for the quantitative measurement of alkaline phosphatase in human serum and plasma on the Dimension Vista® System. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.
ALPI CAL is an in vitro diagnostic product for the calibration of alkaline phosphatase (ALPI) method on the Dimension Vista® System.
The ALPI method employs alkaline phosphatase that catalyzes the transphosphorylation of pnitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) in the presence of the transphosphorylating buffer, 2 amino-2-methyl-1-propanol (AMP). The reaction is enhanced through the use of magnesium and zinc ions. The change in absorbance at 405 nm due to the formation of p-NP is directly proportional to the ALP activity, since other reactants are present in non-rate limiting quantities and is measured using a bichromatic (405, 510 nm) rate technique.
p-NPP + AMP -> p-NP + AMP + PO4 (reaction conditions: pH 10.25, Mg/Zn)
The ALPI CAL is a one (1) level, liquid calibrator. It is packaged as a kit of three vials of Calibrator A (Level 2) with 1.0 mL per vial. The product matrix is a human serum albumin based product containing alkaline phosphatase from porcine kidney. Level 1 is a zero level (system water). Level 2 contains alkaline phosphatase at 1000 U/L.
This product is sold separately from the Flex® reagent cartridge. Values are assigned to new lots from a Masterpool that is from an International Federation of Clinical Chemistry (IFCC) reference.
Here's a breakdown of the acceptance criteria and study information for the Dimension Vista® Alkaline Phosphatase Flex® reagent cartridge (ALPI) and Calibrator (ALPI CAL), based on the provided 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implied by Predicate/Guideline) | Reported Device Performance (Dimension Vista® ALPI) |
|---|---|---|
| Method Comparison | Demonstrated substantial equivalence to predicate device (ADVIA® Chemistry Alkaline Phosphatase AMP assay) with acceptable correlation statistics (slope near 1, intercept near 0, high correlation coefficient). While specific numerical acceptance criteria for slope, intercept, and 'r' aren't explicitly stated as "acceptance criteria," the predicate comparison aims to show the new device performs similarly. | Slope: 1.05 |
| Serum/Plasma Comparison | Demonstrated equivalency between serum and lithium heparin plasma with acceptable linear regression statistics (slope near 1, intercept near 0, high correlation coefficient). | Slope: 1.02 |
| Reference Interval | Establishment of a clinically appropriate reference interval for healthy adults. | 45-117 U/L [0.75 – 1.95 µkat/L] |
| Precision | Consistent and reproducible results across various levels, as evaluated by CLSI EP5-A2 with acceptable repeatability and within-lab standard deviation (SD) and coefficient of variation (%CV). No explicit numerical acceptance criteria for %CV or SD are provided, but the presented data demonstrates good precision with low CVs. | Repeatability: |
- Level 1: 1.0 U/L (2.9% CV)
- Level 2: 1.9 U/L (1.2% CV)
- Level 3: 4.0 U/L (1.3% CV)
- Serum Pool 1: 1.3 U/L (1.7% CV)
- Serum Pool 2: 13.6 U/L (1.6% CV)
Within-Lab: - Level 1: 1.4 U/L (4.1% CV)
- Level 2: 3.1 U/L (2.0% CV)
- Level 3: 4.6 U/L (Not legible in original doc)
- Serum Pool 1: 1.5 U/L (1.9% CV)
- Serum Pool 2: 15.0 U/L (1.8% CV) |
| Linearity/Measuring Range | Established linear range according to CLSI EP-6A, ensuring accurate measurements within the stated range. The curve fit (R-squared) should show high linearity. | 10 - 1000 U/L
Linearity Assessment: y = 1.010x + 3.461, R-squared = 0.999 |
| Analytical Specificity/Interferences | Bias due to interferents (hemoglobin, bilirubin, lipemia) should be less than 10%. | Bias
Ask a specific question about this device
Page 1 of 10