(63 days)
The DGTX Flex™ reagent cartridge for the Dimension® clinical chemistry system is an in vitro diagnostic device intended to quantitatively measure digitoxin in human serum and plasma. Measurements of digitoxin are used in the diagnosis and treatment of digitoxin overdose and in monitoring levels of digitoxin to ensure appropriate therapy.
The digitoxin assay uses an immunoassay technique in which free and digitoxin-bound antibody-enzyme species are separated using magnetic particles. Digitoxin in the sample is bound by the F(ab')2-ß-galactosidase in the Antibody Conjugate reagent. Magnetic particles coated with the digitoxin analog ouabain are added to bind free (unbound) antibody-enzyme conjugate. The reaction mixture is then separated magnetically. Following separation, the supernatant containing the digitoxin-antibody-enzyme complex is transferred and mixed with a substrate. The ß-galactosidase (ß-gal) portion of the Digoxin-F(ab')2-βgalactosidase complex catalyzes the hydrolysis of chlorophenol red-β-D galactopyranoside (CPRG) to chlorophenol red (CPR). The change in absorbance at 577 nm due to the formation of CPR is directly proportional to -B-galactosida: e activity. Since ß-galactosidase is not present in serum, its activity is directly proportional to di ¿itoxin in the patient's sample and is measured using a bichromatic (577, 700 nm) rate technique.
Here's an analysis of the provided text regarding the acceptance criteria and the study that proves the device meets those criteria:
Acceptance Criteria and Study Details for DGTX Flex™ Reagent Cartridge
1. Acceptance Criteria and Reported Device Performance
The provided document defines substantial equivalence based on the correlation with a predicate device. The primary acceptance criteria are derived from this comparative study.
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Correlation with Predicate Device (aca® DGTX assay): | Correlation coefficient (r): 0.952 |
| - High correlation coefficient (ideally close to 1) | Slope: 1.06 |
| - Slope ideally close to 1 | Intercept: -0.6 |
| - Intercept ideally close to 0 | |
| Intended Use Equivalence: | The DGTX Flex™ reagent cartridge is intended to quantitatively measure digitoxin (DGTX) in human serum and plasma, which is consistent with the general function of digitoxin test systems. |
| Methodology Equivalence: | While methodology differs (Affinity particle mediated immunoassay vs. Affinity column mediated immunoassay), the study demonstrates equivalent performance, justifying the different approaches. |
| Sample Type Equivalence: | |
| - Serum and/or plasma | The DGTX Flex™ uses serum and plasma, while the predicate used serum. The split sample comparison would have validated performance across the shared sample type (serum) and implicitly indicated acceptable performance for plasma if included in the 93 clinical samples. |
2. Sample Size and Data Provenance
- Sample Size for Test Set: 93 clinical patient samples.
- Data Provenance: The document does not explicitly state the country of origin. However, the submission is to the U.S. FDA, and the product is intended for the U.S. market, suggesting the data is likely relevant to the U.S. patient population if not collected therein. The data is retrospective, as it's a "split sample comparison" using existing clinical patient samples.
3. Number of Experts and Qualifications for Ground Truth
The document does not specify the number of experts used or their qualifications to establish ground truth for the test set.
4. Adjudication Method
The document does not specify an adjudication method. In a split-sample comparison for an analytical device, the "ground truth" is typically the result from the predicate device itself, or a reference method that the predicate device was previously validated against.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic imaging or interpretation devices where human readers provide an assessment. The DGTX Flex™ is an in vitro diagnostic reagent cartridge for quantitative measurement, not a device requiring human interpretation of images or complex data.
6. Standalone Performance Study
Yes, a form of standalone performance was conducted, but it's framed as a comparison to a predicate device, not as an absolute standalone validation against a gold standard that is independent of any existing device. The correlation study directly assesses the performance of the DGTX Flex™ reagent cartridge on the Dimension® clinical chemistry system.
7. Type of Ground Truth Used
The ground truth for the test set was the results obtained from the predicate device, the aca® DGTX assay. This is evident from the "split sample comparison," where both the new device and the predicate device analyzed the same clinical samples, and the predicate's results served as the reference for comparison.
8. Sample Size for Training Set
The document does not specify a training set size. For an IVD reagent, method development typically involves extensive internal validation and optimization, but a distinct "training set" in the context of machine learning (where this term is often used) is not applicable here. The "93 clinical patient samples" refer to the test set used for the substantial equivalence comparison.
9. How Ground Truth for Training Set Was Established
As no specific training set is mentioned in the context of the substantial equivalence claim, the method for establishing its ground truth is not applicable/not provided in this document. During the development of the assay, calibration and internal validation would have been performed using methods established for quantitative assays, likely involving certified reference materials or highly characterized samples.
§ 862.3300 Digitoxin test system.
(a)
Identification. A digitoxin test system is a device intended to measure digitoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digitoxin overdose and in monitoring levels of digitoxin to ensure appropriate therapy.(b)
Classification. Class II.