(209 days)
The C. DIFF QUIK CHEK COMPLETE™ test is a rapid membrane enzyme immunoassay for the simultaneous detection of Clostridium difficile glutamate dehydrogenase antigen and toxins A and B in a single reaction well. The test detects C. difficile antigen, glutamate dehydrogenase, as a screen for the presence of C. difficile and confirms the presence of toxigenic C. difficile by detecting toxins A and B in fecal specimens from persons suspected of having C. difficile disease. 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 COMPLETE™ test uses antibodies specific for qlutamate dehydrogenase (GDH) and Toxins A and B of C. difficile. The device contains a Reaction Window with two solid lines and a dotted line of immobilized antibodies. The Antigen line ("Ag") contains antibodies against C. difficile GDH. The Toxin line ("Tox") contains antibodies against C. difficile toxins A and B. The dotted line, representing a control line ("C"), contains anti-HRP antibodies. The Conjugate consists of antibodies to GDH, toxin A, and toxin B 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, toxin A or toxin B in the sample binds to the corresponding antibody-peroxidase conjugate. The antigen-antibody complexes migrate through a filter pad to a membrane where they are captured by the immobilized anti-GDH, anti-toxin A or Anti-toxin B antibody in the line. The Reaction Window is subsequently washed with Wash Buffer, followed by the addition of Substrate. After a 10-minute incubation, the "Ag" and "Tox" reaction is examined visually for the appearance of a blue line. A blue line indicates a positive test. A positive "C" reaction, indicated by a blue dotted 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 breakdown of the acceptance criteria and the study details for the C. DIFF QUIK CHEK COMPLETE™ device, based on the provided text:
Acceptance Criteria and Reported Device Performance
The document provides performance metrics rather than explicitly stated "acceptance criteria" in the format of pass/fail thresholds. However, the reported performance data can be interpreted as the device meeting the implicit acceptance criteria by demonstrating adequate clinical accuracy compared to established reference methods.
| Metric (GDH Antigen) | Acceptance Criteria (Implicit) | Reported Device Performance (vs. Bacterial Culture) | Reported Device Performance (vs. Tissue Culture Assay – for positive samples) |
|---|---|---|---|
| Sensitivity | High (demonstrate effective detection of true positives) | 90.5% (95% CI: 85.7 - 93.9) | N/A (compared differently) |
| Specificity | High (demonstrate effective identification of true negatives) | 93.1% (95% CI: 91.2 - 94.7) | N/A (compared differently) |
| Predictive Positive Value | High (ensure positive results are reliable) | 76.4% (95% CI: 70.7 - 81.3) | N/A (compared differently) |
| Predictive Negative Value | High (ensure negative results are reliable) | 97.6% (95% CI: 96.2 - 98.4) | N/A (compared differently) |
| Correlation/Overall Agreement | High (demonstrate strong agreement with reference method) | 92.6% (95% CI: 91.8 - 93.4) | 90.1% (95% CI: 89.0 - 91.1) |
| Percent Positive Agreement | High (demonstrates agreement for positive results, especially against a gold standard for positive detection, like tissue culture for toxigenic C. difficile) | N/A (compared differently) | 98.7% (95% CI: 95.0 - 99.8) |
| Percent Negative Agreement | High (demonstrates agreement for negative results) | N/A (compared differently) | 88.8% (95% CI: 86.6 - 90.6) |
| Metric (Toxins A and B) | Acceptance Criteria (Implicit) | Reported Device Performance (vs. Tissue Culture Assay) |
|---|---|---|
| Sensitivity | High (demonstrate effective detection of true positives) | 87.8% (95% CI: 81.4 - 92.3) |
| Specificity | High (demonstrate effective identification of true negatives) | 99.4% (95% CI: 98.6 - 99.7) |
| Predictive Positive Value | High (ensure positive results are reliable) | 95.8% (95% CI: 90.7 - 98.3) |
| Predictive Negative Value | High (ensure negative results are reliable) | 98.1% (95% CI: 96.9 - 98.8) |
| Correlation | High (demonstrate strong agreement with reference method) | 97.8% (95% CI: 97.6 - 98.0) |
Study Information
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Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: n = 1126 clinical samples.
- Data Provenance: The study was conducted at 3 clinical sites. The document does not specify the country of origin, but given the FDA 510(k) submission, it is highly likely to be within the United States. The nature of comparing with "tissue culture assay" and "bacterial culture" suggests these are prospectively collected clinical samples, though the document does not explicitly state "prospective" or "retrospective." However, the wording "results from all 3 clinical sites are included in the summary" typically indicates a prospective collection for a clinical trial or evaluation.
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Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not provide details on the number or qualifications of experts. However, the ground truth was established by laboratory methods (bacterial culture and tissue culture assay) and further resolved by commercial ELISA tests. These methods are typically performed by trained laboratory personnel. -
Adjudication Method for the Test Set:
- GDH Antigen: Discrepant samples between the C. DIFF QUIK CHEK COMPLETE™ test and bacterial culture were resolved using the C. DIFFICILE CHEK™ - 60 ELISA (which detects GDH antigen).
- Toxins A and B: Discrepant results between the C. DIFF QUIK CHEK COMPLETE™ test and tissue culture assay were analyzed by either the C. DIFFICILE TOX A/B I/™ test or a "second commercially available Toxin A&B test."
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If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, What was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance:
This device is a rapid membrane enzyme immunoassay (a diagnostic test kit), not an AI-powered image analysis or diagnostic system. Therefore, an MRMC comparative effectiveness study involving human readers with/without AI assistance is not applicable to this device. The results are read visually for the appearance of a blue line, which is a direct interpretation of the assay's chemical reaction, not a complex image requiring human expert interpretation in the way AI systems are typically evaluated in MRMC studies. -
If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done:
Yes, a standalone performance was done. The results presented for sensitivity, specificity, predictive values, and agreement are directly comparing the device's output (positive/negative blue line) to the ground truth established by the reference methods (bacterial culture and tissue culture assay). There is no explicit "human-in-the-loop" aspect being evaluated in these performance metrics beyond the visual reading of the test result itself, which is integral to the device's function. -
The Type of Ground Truth Used:
- For GDH antigen:
- Primary reference: Bacterial Culture (for overall presence of C. difficile organism).
- Secondary/Discrepant resolution: C. DIFFICILE CHEK™ - 60 ELISA (an established GDH antigen detection assay).
- A separate comparison was also made against Tissue Culture Assay (presumably for toxigenic C. difficile, as it usually detects toxin production), specifically looking at the GDH antigen portion of the C. DIFF QUIK CHEK COMPLETE™.
- For Toxins A and B:
- Primary reference: Tissue Culture Assay (the gold standard for detecting toxigenic C. difficile).
- Secondary/Discrepant resolution: C. DIFFICILE TOX A/B I/™ test or a "second commercially available Toxin A&B test."
- For GDH antigen:
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The Sample Size for the Training Set:
The document does not specify a separate "training set" size for the clinical accuracy evaluation. The n=1126 samples are referred to as the clinical performance evaluation set. This device is an immunoassay kit, which typically does not involve machine learning or AI algorithms that require distinct training and test sets in the same manner as software devices. Any "training" would have been part of the assay development and optimization phases, not explicitly quantified as a clinical "training set" in this context. -
How the Ground Truth for the Training Set Was Established:
As there's no explicitly defined "training set" in the context of clinical accuracy for this type of device mentioned in the document, this question is not directly applicable. The methods used to establish ground truth for the evaluation set (bacterial culture and tissue culture assay with ELISA for discrepancy resolution) would be the standard reference methods used in the development and validation of similar assays.
§ 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.