(47 days)
Method: For the quantitative measurement of myoglobin in human serum and plasma on the Dimension Vista™ System as an aid in the rapid diagnosis of acute myocardial infarction.
Calibrator: For the calibration of the myoglobin (MYO) method on the Dimension Vista™ System.
Method: The MYO method is a homogenous sandwich chemiluminescent immunoassay based on Luminescent Oxygen Channeling Immunoassay (1.OCI™) technology. LOCI™ reagents include two latex bead reagents and a biotinylated anti-myoglobin monoclonal antibody fragment. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with a second anti-myoglobin monoclonal antibody and contains chemiluminescent dye. Sample is incubated with Chemibeads and biotinylated antibody to form a beadmyoglobin-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 Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the myoglobin concentration in the sample.
Calibrator: The Dade Behring MYO Calibrator is a three level (A, B, C), frozen liquid product containing purified human heart myoglobin in a 6% bovine albumin matrix with stabilizers and preservatives. The kit contains 3 vials of each level (A= 2.0 mL. B= 1.0 mL. C= 1.5 mL).
Here's a breakdown of the acceptance criteria and the study details for the Dade Behring Dimension Vista™ MYO reagent cartridge and calibrator, based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" but rather presents a comparison to a predicate device and then reports the performance of the new device. The implied acceptance criteria are that the new device should perform comparably to the predicate device and meet certain analytical performance characteristics.
| Performance Metric | Implied Acceptance Criteria (relative to predicate or analytical standards) | Reported Device Performance (Dimension Vista™ MYO) |
|---|---|---|
| Method Comparison | Slope near 1.00, intercept near 0, high correlation coefficient (e.g., >0.98) | Slope: 1.003, Intercept: 6.98 ng/mL, Correlation Coefficient: 0.998 |
| Analytical Sensitivity | Lower or equal to predicate (1 ng/mL) | 0.5 ng/mL (Improved) |
| Reportable Range | Wider or equal to predicate (1 to 1000 ng/mL) | 0.5 - 1000 ng/mL (Wider) |
| Interferences | No significant interference from common interferents at specified levels | Bilirubin (conj/unconj) up to 60 mg/dL, Hemoglobin up to 1000 mg/dL, Triglycerides up to 3000 mg/dL (Improved for triglycerides compared to predicate) |
| Hook Effect | No high dose effect up to high concentrations | No high dose effect (up to 300,000 ng/mL) |
| Calibration Interval | Stable for a reasonable period | Six levels every 30 days with the same reagent lot |
| Sample Volume | Optimized for efficiency | 2 uL (Reduced from predicate's 20 uL) |
| Serum/Plasma Comparison | Good agreement between sample types (slope near 1.0, high correlation) | Serum vs. lithium heparin: Slope 1.05, Correlation 1.0, Intercept -5.12 ng/mL (n=37) |
| Lithium vs. sodium heparin: Slope 1.00, Correlation 1.0, Intercept -0.54 ng/mL (n=115) | ||
| Reproducibility (Precision) | Acceptable SD and %CV for various myoglobin levels | Pool 1 (110.3 ng/mL): %CV 5.0 |
| Pool 2 (501.5 ng/mL): %CV 3.7 | ||
| Pool 3 (830.8 ng/mL): %CV 3.3 | ||
| Control Level 1 (113.5 ng/mL): %CV 3.6 |
2. Sample Sizes and Data Provenance:
- Method Comparison Test Set: 160 patient samples (serum and heparinized plasma).
- Data Provenance: Not explicitly stated, but typically these samples would be from a clinical laboratory or reference lab, retrospective. The document does not specify country of origin.
- Serum/Plasma Comparison Test Set:
- 37 matched serum and lithium heparin pairs.
- 115 lithium and sodium heparin samples.
- Data Provenance: Not explicitly stated regarding country or retrospective/prospective. Assumed to be from a clinical setting.
- Reproducibility Test Set: Three human serum pools and one commercial cardiac marker control. The number of individual measurements for repeatability and within-lab is not specified, but it states "a single test from two independent cups was analyzed twice per day" according to NCCLS guideline EP5-A2, which typically involves multiple days of testing.
3. Number of Experts and Qualifications for Ground Truth:
- This submission describes an analytical performance study for an in vitro diagnostic (IVD) device, not a clinical study involving interpretation of images or patient outcomes for which human experts would establish a ground truth.
- Therefore, the concept of "experts establishing ground truth" as it applies to image interpretation or clinical diagnosis is not applicable here. The ground truth for such devices is typically the true concentration of the analyte, established by reference methods or validated materials.
4. Adjudication Method for the Test Set:
- Not applicable. This relates to clinical studies where multiple human readers assess a case. For an IVD device, the "adjudication" is inherent in the analytical process, where the instrument measures an analyte and its performance is assessed against a predicate device or established analytical standards.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No. An MRMC study is not relevant for this type of IVD device. This device analytically measures myoglobin concentration, and its performance is compared to a predicate device, not against human readers' diagnostic accuracy, nor is it designed to assist human readers in image interpretation.
6. Standalone Performance Study:
- Yes. The entire submission details the standalone performance of the Dimension Vista™ MYO system (reagent and calibrator) by demonstrating its analytical characteristics (sensitivity, range, interference, precision, method comparison, serum/plasma comparison). The results presented are solely the performance of the algorithm/device itself.
7. Type of Ground Truth Used:
- For the method comparison and serum/plasma comparison, the ground truth is essentially the measurement obtained from the predicate device (Dade Behring Dimension® MYO immunoassay). The goal is to show the new device produces equivalent results.
- For analytical characteristics like sensitivity, range, and reproducibility, the ground truth is established using reference materials, calibrators, and characterized human serum pools with known or assigned myoglobin concentrations.
8. Sample Size for the Training Set:
- The document does not provide information on a "training set" in the context of machine learning. This is an immunoassay device, and while it would have undergone extensive development and optimization (which could be considered analogous to "training" in a broad sense), the specific term "training set" for an algorithm, as used in AI/ML, isn't applicable here and thus no sample size is reported.
9. How Ground Truth for Training Set was Established:
- Not applicable as there is no explicitly defined "training set" as understood in AI/ML for this immunoassay device. The "ground truth" during the development phase would involve using validated reference materials and methods to optimize the reagent formulations and assay parameters.
§ 862.1150 Calibrator.
(a)
Identification. A calibrator is a device intended for medical purposes for use in a test system to establish points of reference that are used in the determination of values in the measurement of substances in human specimens. (See also § 862.2 in this part.)(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.