(72 days)
The CEDIA Digoxin II homogeneous enzyme immunoassay is for the quantitation of digoxin in human serum or plasma using automated clinical chemistry analyzers. Measurements are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure proper therapy.
The CEDIA® Digoxin II Assay is based on the bacterial enzyme ßgalactosidase, which has been genetically engineered into two inactive fragments. These fragments spontaneously reassociate to form fully active enzyme that, in the assay format, cleaves a substrate, generating a color change that can be measured spectrophotometrically. In the assay, digoxin in the sample competes with analyte conjugated to one inactive fragment of B-galactosidase for antibody binding site. If analyte is present in the sample, it binds to antibody, leaving the inactive enzyme fragments free to form active enzyme. If analyte is not present in the sample, antibody binds to analyte conjugated on the inactive fragment, inhibiting the reassociation of inactive ß-galactosidase fragments, and no active enzyme is formed.
The presented document is a 510(k) Summary for the CEDIA® Digoxin II Assay. It describes the device, its intended use, and compares its performance characteristics to a predicate device, the Abbott TDx® Digoxin II Assay.
Here's an analysis of the acceptance criteria and study information based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct acceptance thresholds (i.e., "the device must achieve X performance"). Instead, the performance of the CEDIA® Digoxin II Assay is compared directly to the predicate device, the Abbott TDx® Digoxin II Assay, implying that substantial equivalence to the predicate's performance is the overarching acceptance criterion.
| Feature | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (CEDIA® Digoxin II) |
|---|---|---|
| Precision | Modified NCCLS (ng/mL): | |
| Level 1 | Within run %CV: 5.75, Total %CV: 7.67 | Within run %CV: 4.25, Total %CV: 5.44 |
| Level 2 | Within run %CV: 3.15, Total %CV: 3.98 | Within run %CV: 2.22, Total %CV: 3.58 |
| Level 3 | Within run %CV: 1.87, Total %CV: 1.91 | Within run %CV: 1.56, Total %CV: 2.34 |
| Lower Detection Limit | 0.2 ng/mL | 0.15 ng/mL |
| Linearity Range | 0.0 - 4.0 ng/mL | 0.15 - 4 ng/mL |
| Method Comparison | ||
| vs Abbott TDx Digoxin | (Implied high correlation) | y = 0.94x + 0.08, r = 0.962 (N=200) |
| vs Baxter Dade Stratus | (Implied high correlation) | y = 0.98x - 0.12, r = 0.955 (N=99) |
| Deming's: y = 1.02x - 0.17, r = 0.955 (N=99) | ||
| Interfering Substances | No interference at (within ±10% of baseline): | |
| Bilirubin | 20 mg/dL | 66 mg/dL |
| Hemoglobin | 1000 mg/dL | 1000 mg/dL |
| Triglyceride Lipemia | 2500 mg/dL | 100 mg/dL |
| Total Protein | N/A (not provided for predicate) | 10 g/dL |
| Rheumatoid Factor | N/A (not provided for predicate) | 100 IU/mL |
| Specificity (% Cross-reactivity) | ||
| Digoxigenin | up to 200 | 60.5 |
| β-Acetyldigoxin | not tested | 77.0 |
| α-Acetyldigoxin | not tested | 75.3 |
| Gitalin | not tested | 2.1 |
| Digoxingenin-Mono-Digitoxiside | up to 200 | 102.5 |
| Digitoxin-Bis-Digitoxiside | up to 200 | 86.3 |
| Digitoxin | up to 200 | 1.5 |
| β-Methyldigoxin | 4.8 | 76.3 |
| 3-Epe-Digoxigenin | not tested | 37.6 |
| 3-Dehydrodigoxigenin | not tested | 82.6 |
| Epi-Digoxigenin-Glucuronide | not tested | 42.9 |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Test Set N: 120 for each of 3 levels (Level 1, Level 2, Level 3). (Total 360 individual measurements for precision, but N refers to the number of individual tests run for each level.)
- Method Comparison Test Set N:
- Vs Abbott TDx Digoxin: N=200
- Vs Baxter Dade Stratus: N=99
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective or prospective). The samples are referred to as "human serum and plasma."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
There is no mention of experts being used to establish ground truth for this diagnostic assay. The "ground truth" for quantitative assays like this is typically established by comparative analysis against established, often reference, methods or instruments.
4. Adjudication Method for the Test Set
Not applicable. As this is an in vitro diagnostic (IVD) assay for quantitative determination, there is no mention of adjudication by human readers/experts for the test results. The device's output is a quantitative value, not subject to interpretation needing adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This document describes an in vitro diagnostic (IVD) assay, not an imaging device or AI algorithm intended for human-in-the-loop interpretation that would typically involve an MRMC study.
6. Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance)
Yes, the performance characteristics presented (precision, linearity, detection limit, method comparison, interfering substances, specificity) represent the standalone performance of the CEDIA® Digoxin II Assay. There is no human-in-the-loop component mentioned in its operation for these performance metrics.
7. Type of Ground Truth Used
The "ground truth" for the performance studies appears to be based on:
- Reference Methods/Predicate Devices: For method comparison, the results of the CEDIA® assay were compared against the Abbott TDx® Digoxin II Assay and the Baxter Dade Stratus, which serve as reference or predicate methods.
- Standard Spiked Samples: For parameters like precision, linearity, and detection limit, it is implied that samples with known concentrations of digoxin were used, or that the "levels" described were standardized reference materials.
- Known Concentrations of Interfering Substances: For interference and specificity studies, substances were tested at known concentrations.
8. Sample Size for the Training Set
The document does not specify a separate "training set" or its size. This is common for traditional in vitro diagnostic assays that are developed using biochemical principles rather than machine learning algorithms requiring explicit training data. The development and optimization process itself serves a similar function to "training," but it doesn't involve a distinct, quantifiable training set in the machine learning sense.
9. How the Ground Truth for the Training Set Was Established
As there is no explicit "training set" mentioned in the context of machine learning, this question is not directly applicable. The device's underlying principles are based on enzyme immunoassay chemistry, where performance is optimized through reagent formulation and assay design, not by training on a labeled dataset.
§ 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.