(54 days)
The SYNCHRON® Systems Digoxin (DIGN) Reagent, when used in conjunction with Beckman SYNCHRON® Systems and SYNCHRON® Systems Drug Calibrator 2 set, is intended for the quantitative determination of total digoxin in human serum or plasma on SYNCHRON® Systems.
The SYNCHRON® Systems Drug Calibrator 2, used in conjunction with SYNCHRON® Digoxin reagent, is intended for use on Beckman's SYNCHRON Systems for the calibration of Digoxin test systems.
The SYNCHRON System Digoxin (DIGN) Reagent is designed for optimal performance on the SYNCHRON CX and LX Systems. It is intended for use in the quantitative determination of Digoxin in human serum or plasma.
The provided text describes a 510(k) premarket notification for the SYNCHRON® Systems Digoxin (DIGN) Reagent. This is an in-vitro diagnostic device, and the information requested (acceptance criteria, study design, etc.) is typically applied to medical devices that assist in diagnosis or treatment. The performance data provided for this diagnostic reagent focuses on method comparison and imprecision against a predicate device, which is standard for IVDs to establish substantial equivalence.
Based on the provided document, here's an analysis of the acceptance criteria and study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance
For in-vitro diagnostic devices, "acceptance criteria" against a predicate device typically involve demonstrating comparable performance in terms of method comparison (correlation coefficient, slope, intercept) and precision. The document doesn't explicitly state numerical acceptance criteria, but substantial equivalence is implied if the results are "equivalent" to the predicate. The reported device performance is:
| Performance Metric | SYNCHRON CX System (Serum) | SYNCHRON LX System (Serum) |
|---|---|---|
| Method Comparison (vs. Abbott TDx Digoxin II) | ||
| Slope | 1.053 | 1.054 |
| Intercept (ng/mL) | -0.03 | -0.06 |
| Correlation Coefficient (r) | 0.991 | 0.990 |
| Number of Samples (n) | 113 | 112 |
| Estimated Within-Run Imprecision | ||
| CX System | ||
| Level 1 (0.74 ng/mL) | 6.96% CV | |
| Level 2 (1.73 ng/mL) | 3.29% CV | |
| Level 3 (2.48 ng/mL) | 1.80% CV | |
| LX System | ||
| Level 1 (0.80 ng/mL) | 6.06% CV | |
| Level 2 (1.78 ng/mL) | 1.78% CV | |
| Level 3 (2.49 ng/mL) | 2.62% CV |
Implicit Acceptance Criteria (inferred from common IVD submission practices and the results reported):
- Method Comparison: A high correlation coefficient (typically >0.97 or 0.98), a slope close to 1 (e.g., between 0.95 and 1.05), and an intercept close to 0 (e.g., within a clinically acceptable range for the analyte) compared to the predicate device. The reported values of r=0.991 and 0.990, slopes of 1.053 and 1.054, and intercepts of -0.03 and -0.06 strongly suggest these criteria were met.
- Imprecision: Within-run Coefficient of Variation (CV) values that are deemed acceptable for the assay and analyte, and ideally comparable to or better than the predicate. The reported CVs (1.80% - 6.96%) are generally considered good for a quantitative immunoassay.
2. Sample sized used for the test set and the data provenance
- Sample Size for Test Set:
- Method Comparison: 113 samples for the SYNCHRON CX System and 112 samples for the SYNCHRON LX System. These samples were human serum.
- Imprecision (for each level): 80 samples each for Levels 1, 2, and 3 on both CX and LX systems, totaling 240 samples per system for imprecision assessment.
- Data Provenance: The document does not specify the country of origin of the data or whether it was retrospective or prospective. It only states the samples were "human serum" or "human serum or plasma" in the intended use.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This question is not directly applicable in the typical sense for an in-vitro diagnostic reagent like this. The "ground truth" for a quantitative analyte such as Digoxin is established by a reference method or a predicate device that is already FDA-cleared and considered accurate.
- In this case, the predicate device, Abbott TDx Digoxin II, served as the comparative method against which the new device's measurements were compared. The "ground truth" measurements for the method comparison were obtained using this predicate device. This is a common approach for demonstrating substantial equivalence for IVDs.
- No human experts were used to "establish ground truth" in the way one might for image interpretation or disease diagnosis.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set
Not applicable. This is not a study involving human interpretation or subjective assessment that would require an adjudication method. The comparison is between two quantitative analytical instruments.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This is an in-vitro diagnostic device, not an AI-powered diagnostic imaging or interpretation system. There are no "human readers" in the context of this submission, nor is there AI assistance involved.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, in the context of an IVD, the "standalone performance" is precisely what was evaluated. The SYNCHRON Digoxin Reagent, when run on the SYNCHRON CX and LX Systems, generates a quantitative result without direct human interpretation of the measurement itself (though a human interprets the quantitative value in a clinical context). The method comparison and imprecision studies demonstrate the performance of the device itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the test set was effectively established by the predicate device, the Abbott TDx Digoxin II system. The new device's performance was evaluated against the measurements obtained from this legally marketed and accepted predicate method.
8. The sample size for the training set
The document does not specify a "training set" sample size. For an IVD reagent, method development involves internal studies and optimization, but the 510(k) submission generally focuses on the validation (test set) data demonstrating equivalence to a predicate. The reported sample sizes (112-113 for method comparison, 80 per level for imprecision) are for the validation/test studies.
9. How the ground truth for the training set was established
Not explicitly stated or applicable in the sense of a machine learning "training set" with ground truth labels. For the development of the reagent, the "ground truth" for optimizing its performance would have been established through internal validation using reference methods, established standards, or comparisons to existing assays during the development phase. The 510(k) focuses on the final performance validation against a predicate.
§ 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.