(125 days)
The C. DIFF QUIK CHEK™ test is a rapid membrane enzyme immunoassay for use as a screening test to detect Clostridium difficile antigen, glutamate dehydrogenase, in fecal specimens from persons suspected of having C. difficile disease. The test does not distinguish toxigenic from nontoxigenic 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 disease. As with other C. difficile tests, results should be considered in conjunction with the patient history. FOR IN VITRO DIAGNOSTIC USE.
The C. DIFF QUIK CHEK™ test uses antibodies specific for glutamate dehydrogenase (GDH) of C. difficile. The device contains a Reaction Window with two lines of immobilized antibodies. The test line ("T") contains antibodies against C. difficile GDH. The other, representing a control line ("C"), contains anti-IgG antibodies. The Conjugate consists of antibody to GDH coupled to horseradish peroxidase. To perform the test, the fecal specimen is diluted with Diluent, and Conjugate is added to the diluted sample. The diluted sample conjugate mixture is added to the Sample Well and the device is allowed to incubate at room temperature for 15 minutes. During the incubation, any GDH in the sample binds to antibodyperoxidase conjugate. The antigen-antibody complexes migrate through a filter pad to a membrane where they are captured by the immobilized anti-GDH antibody in the line. The Reaction Window is subsequently washed with Wash Buffer, followed by the addition of Substrate. After up to a 10-minute incubation, the "T" reaction is examined visually for the appearance of a blue line indicates a positive test. A positive "C" reaction, indicated by a blue line, confirms that sample and all reagents were added in proper sequence and volume, that reagents were active at the time of performing the assay, and that proper sample migration occurred.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device: C. DIFF QUIK CHEK™ test
Intended Use: A rapid membrane enzyme immunoassay for use as a screening test to detect Clostridium difficile antigen, glutamate dehydrogenase, in fecal specimens from persons suspected of having C. difficile disease. The test does not distinguish toxigenic from nontoxigenic 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 disease. Results should be considered in conjunction with the patient history.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document. However, the study aims to demonstrate substantial equivalence to previously cleared devices and clinical correlation. Based on the "Clinical Performance Comparing C. DIFF QUIK CHEK™ Test to Presumptive Bacterial Culture" table and the "Clinical Performance of C. DIFF QUIK CHEK™ Test versus Bacterial Culture Assay after Resolution by another GDH Test" table, the implied acceptance range would be within the 95% Confidence Limits of the reported performance metrics.
| Performance Metric | Acceptance Criteria (Implied/Expected) | Reported Device Performance (vs. initial culture) | Reported Device Performance (vs. resolved culture) |
|---|---|---|---|
| Clinical Performance | |||
| Sensitivity | High sensitivity (e.g., >88%) | 92.8% (95% CI: 88.3% - 95.7%) | N/A (not directly reported post-resolution) |
| Specificity | High specificity (e.g., >90%) | 92.6% (95% CI: 90.4% - 94.3%) | N/A (not directly reported post-resolution) |
| Predictive Negative Value | High PVN (e.g., >96%) | 97.8% (95% CI: 96.3% - 98.7%) | 99.6% (95% CI: 98.7% - 99.9%) |
| Correlation | High correlation (e.g., >90%) | 92.6% (95% CI: 91.7% - 93.4%) | 96.9% (95% CI: 96.5% - 97.2%) |
| Analytical Sensitivity | Detect at low GDH concentration | Consistently positive at 0.4 ng/mL for GDH | Not applicable |
| Cross-Reactivity | No false positives with common organisms | No reactivity with listed organisms and viruses | Not applicable |
| Interfering Substances | No interference | No effect with listed substances | Not applicable |
| Reproducibility | High consistency (e.g., 100%) | 100% correlation across 3 labs | Not applicable |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 979 fecal specimens.
- Data Provenance: The document states that "Results from 3 studies are included in the summary," and the protocols are in Appendix A and D. It does not specify the country of origin of the data or whether it was retrospective or prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The document does not explicitly state the number or qualifications of experts used to establish initial ground truth. The primary comparator was "Presumptive Bacterial Culture."
4. Adjudication Method for the Test Set
The document describes an adjudication method for discrepant samples:
- "The discrepant samples generated from the C. DIFF QUIK CHEK™ test and the presumptive bacterial culture assay were resolved using a PCR assay, an ELISA for the antigen, or a membrane test for the antigen, as described in the individual studies."
- This indicates a "discrepant analysis" approach, where discrepancies between the index test (C. DIFF QUIK CHEK) and the initial comparator (presumptive bacterial culture) were sent for re-evaluation using one or more additional, often more sensitive or specific, methods (PCR, ELISA, membrane test).
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
No, a multi-reader, multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic test (a rapid membrane enzyme immunoassay) and not an AI-assisted diagnostic tool designed to aid human readers in interpreting images or other complex data. Therefore, the concept of human readers improving with AI assistance does not apply.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done. The C. DIFF QUIK CHEK™ test is presented as a standalone diagnostic device, where the visual interpretation of a distinct blue line (or lack thereof) is the final output. The performance metrics (sensitivity, specificity, etc.) presented are for the device operating independently.
7. The Type of Ground Truth Used
The primary initial ground truth was presumptive bacterial culture (Clostridium difficile Culture media such as cycloserine cefoxitin fructose agar (CCFA)).
For discrepant results, the refined ground truth was established using consensus or advanced methods including:
- PCR assay
- ELISA for the antigen
- Another membrane test for the antigen
This is a form of resolved gold standard, where a more definitive test is used to resolve disagreements between the index test and the initial comparator.
8. The Sample Size for the Training Set
The document does not provide information regarding a specific "training set" or its sample size. This type of regulatory submission (510(k)) for an in-vitro diagnostic typically focuses on clinical validation of the final device, rather than the developmental or training phases that might involve machine learning algorithms. The development of an immunoassay involves laboratory optimization and verification, but not typically a "training set" in the context of AI.
9. How the Ground Truth for the Training Set was Established
As no specific training set information is provided, how its ground truth was established is not applicable and not described in this document.
§ 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.