(588 days)
For in vitro diagnostic use in the quantitative determination of digoxin in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur® XP systems.
Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.
The ADVIA Centaur Digoxin assay reagents come in the following configurations:
5 ReadyPack primary reagent packs containing ADVIA Centaur DIG Lite Reagent and Solid Phase, ADVIA Centaur DIG Master Curve card (250 Tests)
1 ReadyPack primary reagent pack containing ADVIA Centaur DIG Lite Reagent and Solid Phase, ADVIA Centaur DIG Master Curve card (50 Tests)
The ReadyPack consists of the following:
ADVIA Centaur DIG ReadyPack® primary reagent pack; Lite Reagent: 2.5 ml/reagent pack monoclonal mouse anti-digoxin antibody (~26.4 ng/mL) labeled with acridinium ester in protein buffered saline with sodium azide (0.11%) and preservatives.
ADVIA Centaur DIG ReadyPack primary reagent pack; Solid Phase Reagent: 12.5 mL/reagent pack digitoxin (~2 ng/mL) covalently coupled to paramagnetic particles in protein buffered saline with sodium azide (0.11%) and preservatives.
The provided document pertains to the 510(k) summary for the ADVIA Centaur Digoxin assay, specifically regarding the addition of plasma sample types (EDTA and lithium heparin) to its indications for use. It's a submission for an in vitro diagnostic (IVD) device, not an AI/ML-based medical device that relies on complex image analysis or similar algorithms. Therefore, many of the requested details about acceptance criteria, test sets, expert ground truth, MRMC studies, standalone performance, and training sets are not applicable to this type of device and its regulatory submission.
The "acceptance criteria" for this device are demonstrated through analytical performance studies, specifically specimen equivalency and interference studies, to confirm that adding plasma as a sample type does not negatively impact the assay's performance compared to the previously cleared serum sample type.
Here’s an attempt to structure the available information relevant to your request, while highlighting the parts that are not applicable to this specific device (as it's an IVD test, not an AI/ML diagnostic system):
Device: ADVIA Centaur® Digoxin assay
Purpose of Study: To demonstrate substantial equivalence for the addition of plasma (EDTA and lithium heparin) as a valid sample type for the ADVIA Centaur® Digoxin assay.
1. Table of Acceptance Criteria and Reported Device Performance
For an IVD assay like the ADVIA Centaur Digoxin assay, "acceptance criteria" are typically defined by precision, accuracy (often assessed through method comparison/equivalent methods), interference, linearity, and analytical sensitivity. The provided document focuses on demonstrating specimen equivalency and interference for the new sample types.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Specimen Equivalency | Regression statistics indicating strong agreement with serum (e.g., slope near 1.0, intercept near 0, high correlation coefficient). | Dipotassium EDTA plasma vs. Serum: |
| Regression Equation: y = 1.02x - 0.02 ng/mL | ||
| Correlation Coefficient (r): 0.996 |
Lithium heparin plasma vs. Serum:
Regression Equation: y = 1.06x - 0.03 ng/mL
Correlation Coefficient (r): 0.990 |
| Interference | Clinically insignificant bias (e.g., less than a certain percentage) when interfering substances are present at relevant concentrations. | Canrenone: 2.7% (at 1.11 ng/mL Digoxin), -0.5% (at 2.12 ng/mL Digoxin)
Dipotassium EDTA: -0.4% (at 0.91 ng/mL Digoxin), -1.1% (at 3.12 ng/mL Digoxin)
Heparin: 8.9% (at 0.61 ng/mL Digoxin), -1.7% (at 3.66 ng/mL Digoxin)
Potassium Canrenoate: 2.8%, -1.0%
Spironolactone: 1.0%, 2.5% |
Note: The document implies that the observed regression statistics and low bias values are acceptable for demonstrating substantial equivalence.
2. Sample Sizes Used for the Test Set and Data Provenance
- Dipotassium EDTA plasma: 51 samples
- Lithium heparin plasma: 50 samples
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Typically, such analytical validation studies for IVDs are prospective and conducted in a controlled lab environment.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
N/A. This is an IVD assay measuring a chemical concentration. "Ground truth" is established by the analytical method itself and comparison to a reference method or validated primary sample type (serum in this case). It does not involve expert interpretation of images or clinical data in the way an AI diagnostic would require. The "experts" are the analytical chemists and lab professionals performing and validating the assay.
4. Adjudication Method for the Test Set
N/A. Adjudication methods (like 2+1, 3+1) are common in clinical trials or studies where human interpretation or consensus is required to establish ground truth from ambiguous or complex data (e.g., radiology images). For an IVD assay, the comparison is against an established analytical method (serum) or reference standard; there's no need for adjudication of readings.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
N/A. MRMC studies are used to assess the effectiveness of diagnostic tools, particularly imaging, by comparing the performance of multiple human readers across multiple cases, often with and without AI assistance. This is not applicable to a quantitative biochemical assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done
The entire test (ADVIA Centaur Digoxin assay) is a standalone system for measuring digoxin concentration. Its performance is measured directly (e.g., accuracy, precision). There is no "human-in-the-loop" performance in the sense of clinical decision support from an AI. The device directly produces a numerical result.
7. The Type of Ground Truth Used
The "ground truth" for specimen equivalency was the measurement of digoxin in serum samples using the predicate ADVIA Centaur Digoxin assay (which was already cleared). The new plasma results were compared against these serum results. For interference, the ground truth is the known concentration of digoxin in the spiked samples.
8. The Sample Size for the Training Set
N/A. This is an IVD assay, not an AI/ML model that requires training data. The assay's reagents and methodology are developed through R&D, not trained on a dataset.
9. How the Ground Truth for the Training Set was Established
N/A. (See point 8).
Conclusion from the Document:
The study concludes that the modified ADVIA Centaur® Digoxin assay, with the addition of plasma sample types, is substantially equivalent in principle and performance to the Predicate Device (ADVIA Centaur® Digoxin assay cleared under 510(k) K931213). This equivalence is based on the analytical performance data, specifically the specimen equivalency and interference studies.
§ 862.3320 Digoxin test system.
(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.