(108 days)
The TOX A/B QUIK CHEK™ test is a rapid immunoassay for detecting Clostridium difficile 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 and results should be considered in conjunction with the patient history. FOR IN VITRO DIAGNOSTIC USE.
The TOX A/B QUIK CHEK™ test uses antibodies specific for toxins A and B of C. difficile. The device contains a Reaction Window with two lines of immobilized antibodies. The test line ("T") contains antibodies against C. difficile toxins A and B. The other, representing a control line ("C"), contains anti-IgG antibodies. The Conjugate consists of antibodies to toxins A and 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 toxin A and toxin B in the sample bind to anti-toxin antibody-peroxidase conjugate. The toxin-antibody complexes migrate through a filter pad to a membrage where they are captured by the immobilized anti-toxin antibodies in the line. The Reaction Well 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. A blue line indicates a positive test. A positive "C" reaction, indicated by a blue line, onfirms 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.
TOX A/B QUIK CHEK™ 510(k) Summary
This document describes the acceptance criteria and the studies that demonstrate the TOX A/B QUIK CHEK™ device meets these criteria for detecting Clostridium difficile toxins A and B in fecal specimens.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the TOX A/B QUIK CHEK™ device are not explicitly stated as numerical targets in the provided text. However, based on the Summary of Performance Data, the reported device performance is presented as follows, which can be inferred as the criteria the device met for clearance.
| Metric | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Sensitivity | High (for diagnostic aid) | 90.2% (95% CI: 84.1 - 94.2) |
| Specificity | High (for diagnostic aid) | 99.7% (95% CI: 98.8 - 99.9) |
| Predictive Positive Value (PPV) | High (for diagnostic aid) | 98.6% (95% CI: 94.4 - 99.8) |
| Predictive Negative Value (PNV) | High (for diagnostic aid) | 97.9% (95% CI: 96.4 - 98.7) |
| Correlation | High (for diagnostic aid) | 98.0% (95% CI: 97.8 - 98.2) |
| Cross-Reactivity | Minimal with non-C. difficile | Only C. sordellii VPI 9048 reacted among tested common intestinal bacteria and pathogens. No cross-reactivity with tested viruses or interfering substances. |
| Analytical Sensitivity | Ability to detect low concentrations of toxins | Consistently positive at 0.63 ng/mL for toxin A and 1.25 ng/mL for toxin B. |
| Reproducibility | Consistent results across sites and days | 100% agreement with expected results in a 3-site, 3-day study. |
2. Sample Size and Data Provenance for the Test Set
- Sample Size for Test Set: 842 fecal specimens.
- Data Provenance: The study was a "clinical performance" study, including "5 studies (2 in-house studies and 3 on-site studies)". The country of origin is not explicitly stated. The nature of the studies (in-house and on-site) suggests these were prospective or a combination of prospective and retrospective collections for clinical validation. It is not explicitly stated whether the data was retrospective or prospective, but clinical performance studies typically involve prospective data collection or a mix of archived and newly collected specimens.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly state the number of experts used or their specific qualifications (e.g., radiologist with 10 years of experience) for establishing the ground truth.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1, none) for the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. The device is a rapid immunoassay, which typically does not involve human readers interpreting complex images or data in a comparative effectiveness study format.
6. Standalone Performance Study
Yes, a standalone performance study was done. The "Summary of clinical performance" section directly compares the "TOX A/B QUIK CHEK™ test" results against the "tissue culture assay" as the ground truth. This evaluates the algorithm-only performance.
7. Type of Ground Truth Used
The ground truth used for the clinical accuracy evaluation was a tissue culture assay. Specifically, for the comparative performance table, "Tissue culture assay" results were used as the reference standard (Tiss Cult pos/neg).
8. Sample Size for the Training Set
The document does not explicitly state a separate "training set" or its sample size. For an immunoassay, the development and optimization of antibodies and assay conditions (analytical sensitivity, cross-reactivity, interfering substances) would involve internal studies that serve a similar function to a training set in machine learning. The clinical performance data presented here is typically considered the validation or test set for regulatory submission.
9. How the Ground Truth for the Training Set Was Established
As no explicit training set is mentioned in the context of clinical accuracy, the ground truth establishment for a training set is not detailed. However, the comprehensive analytical studies (analytical sensitivity, cross-reactivity, interfering substances) would have relied on established laboratory reference methods and defined concentrations of toxins or specific organisms to characterize the device's behavior during its development phase.
§ 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.