(100 days)
VIDAS® C. difficile GDH (GDH) is an automated test based on the Enzyme Linked Fluorescent Assay technique (ELFA), for use on the VIDAS family instruments. The VIDAS C. difficile GDH (glutamate dehydrogenase) assay is a qualitative test that detects the C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile in fecal specimens from persons suspected of having C. difficile infection (CDI). The test does not distinguish toxigenic from non-toxigenic strains of C. difficile. With the use of additional tests that detect C. difficile toxins, the test is to be used as an aid in the diagnosis of C. difficile infection. As with other C. difficile tests, results should be considered in conjunction with the patient history.
The VIDAS® C. difficile GDH assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR®) serves as the solid phase as well as the pipetting device. Reagents for the assay are ready-to-use and are pre-dispensed in the sealed reagent strips. All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times. Each step is followed by a wash cycle which eliminates unbound components. Specific binding of GDH present in the sample with mouse monoclonal anti-GDH antibody coated on the interior of the SPR. Binding between GDH and mouse monoclonal anti-GDH antibody conjugated with alkaline phosphatase (ALP). Detection: alkaline phosphatase catalyzes the hydrolysis of the substrate (4-Methylumbellifery! phosphate) into a fluorescent product (4-Methy-umbelliferone) the fluorescence of which is measured at 450 nm. The intensity of the fluorescence increases according to the quantity of GDH in the sample. When the VIDAS C. difficile GDH test is completed, the results are analyzed automatically by the instrument, a test value is generated, and a result is printed for each sample.
The provided document describes the VIDAS® C. difficile GDH assay, intended for the detection of C. difficile antigen glutamate dehydrogenase in fecal specimens.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria for clinical performance (sensitivity and specificity) in a pass/fail format. However, it presents the results of clinical studies against two different reference methods. The "Performance" rows in the tables below can be considered the reported device performance.
Against CCFA Bacterial Culture (Reference Standard)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Sensitivity | 95.6% (95% CI: 92.6 - 97.6%) |
| Specificity | 90.1% (95% CI: 88.5 - 91.5%) |
| Negative Predictive Value (NPV) | 99.1% (95% CI: 98.5 - 99.5%) |
Against C. difficile Chromogenic Media Bacterial Culture (Reference Standard)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Positive Percent Agreement (PPA) | 92.6% (95% CI: 89.3 - 95.2%) |
| Negative Percent Agreement (NPA) | 91.8% (95% CI: 90.3 - 93.1%) |
Against a Commercially Available C. difficile GDH Assay (Comparison Study)
| Performance Metric | Reported Device Performance (Total, All Sites combined) |
|---|---|
| Positive Percent Agreement | 97.3% (95% CI: 95.0 – 98.7%) |
| Negative Percent Agreement | 94.4% (95% CI: 93.1 – 95.5%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 1904 stool samples (1891 prospective and 13 retrospective).
- Data Provenance: The samples were collected from patients suspected of having C. difficile infection (CDI) at three sites across the USA and Europe.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not specify the exact number of experts involved in establishing the ground truth or their specific qualifications (e.g., radiologist with X years of experience). The ground truth was established by bacterial culture tests (CCFA and C. difficile chromogenic media) performed "according to the instructions for use." This implies standard laboratory practices would have been followed, likely by trained laboratory personnel.
4. Adjudication Method for the Test Set
The document does not mention any adjudication method for resolving discordant results between the device and the ground truth. It presents the raw comparison data against the reference methods.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is for a diagnostic assay, and the studies described are evaluations of the assay's performance against reference methods and another commercially available assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, a standalone performance study was done. The VIDAS® C. difficile GDH assay is an automated test, and the reported clinical sensitivity, specificity, and agreement data reflect the performance of the algorithm only (the automated instrument) without additional human interpretation or intervention in the diagnostic decision once the test is run. The instrument generates a test value and prints a result for each sample automatically.
7. The Type of Ground Truth Used
The primary ground truth used for the clinical performance evaluation was bacterial culture:
- CCFA bacterial culture test
- C. difficile chromogenic medium bacterial culture test
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" or its size. This is common for diagnostic assays where the development process typically involves internal optimization and validation, and then external clinical validation (the "test set" described) against a gold standard. The clinical study described served as the validation (test) set.
9. How the Ground Truth for the Training Set Was Established
As no specific training set is outlined in the document, there's no information on how its ground truth might have been established. However, for diagnostic assays, internal development and optimization would generally rely on well-characterized samples with confirmed positive and negative status, likely through similar gold standard methods like bacterial culture, to establish parameters like cut-off values.
§ 866.2660 Microorganism differentiation and identification device.
(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.