(147 days)
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.
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.