(148 days)
The SHIGA TOXIN QUIK CHEK test is a rapid membrane enzyme immunoassay for the simultaneous qualitative detection and differentiation of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in a single test device. It is intended for use with human fecal samples from patients with gastrointestinal symptoms to aid in the diagnosis of disease caused by Shiga toxin producing Escherichia coli (STEC). It may be used with fecal specimens, or broth or plate cultures derived from fecal specimens. The test results should be considered in conjunction with the patient history.
FOR IN VITRO DIAGNOSTIC USE.
The SHIGA TOXIN QUIK CHEK test utilizes specific antibodies against Stx1 and Stx2. The Membrane Device contains a Reaction Window with three vertical lines of immobilized antibodies. The "1" test line contains monoclonal antibodies against Stx1. The control line ("C") is a dotted line that contains anti-horseradish peroxidase (HRP) antibodies. The "2" test line contains monoclonal antibodies against Stx2. The Conjugate consists of antibodies to Stx1 and Stx2 coupled to horseradish peroxidase. To perform the test, the sample is added to a tube containing a mixture of Diluent and Conjugate. The diluted sample-coniugate mixture is added to the Sample Well and the device is allowed to incubate at room temperature for 15 minutes. During the incubation, any Stx1 and/or Stx2 present in the sample binds to the antibodyperoxidase conjugates. The toxin-antibody-peroxidase complexes migrate through a filter pad to a membrane where they are captured by the immobilized Stx1 and Stx2 specific monoclonal antibodies in the test lines. The Reaction Window is subsequently washed with Wash Buffer, followed by the addition of Substrate. After a 10 minute incubation period, the Reaction Window is examined visually for the appearance of vertical blue lines on the "1" and "2" sides of the Reaction Window. A blue line on the "1" side of the Reaction Window is a positive result indicating the presence of Stx1. A blue line on the "2" side of the Reaction Window is a positive result indicating the presence of Stx2. A positive "C" reaction, indicated by a vertical dotted blue line under the "C" portion of the Reaction Window, confirms that the test is working properly, the procedure was followed, and the results are valid.
Here's a summary of the acceptance criteria and study details for the SHIGA TOXIN QUIK CHEK device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific percentages for sensitivity, specificity, and correlation for the clinical performance. Instead, it presents the achieved performance metrics as the outcome of the clinical study. However, the study's findings indicate the device's acceptable performance for its intended use. For the analytical sensitivity, the cutoff points are explicitly defined as the acceptance criteria.
| Metric (Stx1 - Direct Fecal) | Acceptance Criteria (Implicit from Results) | Reported Device Performance |
|---|---|---|
| Sensitivity | High sensitivity to detect Stx1 | 98.0% (87.8 - 99.9% CI) |
| Specificity | High specificity to rule out Stx1 | 99.8% (99.0 - 99.9% CI) |
| Correlation | High overall agreement with Gold Standard | 99.7% (99.7 - 99.7% CI) |
| Metric (Stx2 - Direct Fecal) | Acceptance Criteria (Implicit from Results) | Reported Device Performance |
|---|---|---|
| Sensitivity | High sensitivity to detect Stx2 | 98.0% (87.8 - 99.9% CI) |
| Specificity | High specificity to rule out Stx2 | 100% (99.4 - 99.9% CI) |
| Correlation | High overall agreement with Gold Standard | 99.9% (100 - 100% CI) |
| Metric (Stx1 - Broth Cultures) | Acceptance Criteria (Implicit from Results) | Reported Device Performance |
|---|---|---|
| Sensitivity | High sensitivity to detect Stx1 | 100% (89.6 - 100% CI) |
| Specificity | High specificity to rule out Stx1 | 99.5% (98.5 - 99.8% CI) |
| Correlation | High overall agreement with Gold Standard | 99.5% (99.5 - 99.5% CI) |
| Metric (Stx2 - Broth Cultures) | Acceptance Criteria (Implicit from Results) | Reported Device Performance |
|---|---|---|
| Sensitivity | High sensitivity to detect Stx2 | 95.7% (84.3-99.3% CI) |
| Specificity | High specificity to rule out Stx2 | 99.9% (99.1 - 100% CI) |
| Correlation | High overall agreement with Gold Standard | 99.6% (99.6 - 99.6% CI) |
| Metric (Analytical Sensitivity) | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Stx1 Cutoff (Direct Fecal) | Concentration yielding positive results 95% of the time, negative 5% of time | 0.04 ng/mL (found empirically at 0.042 ng/mL) |
| Stx2 Cutoff (Direct Fecal) | Concentration yielding positive results 95% of the time, negative 5% of time | 0.04 ng/mL (found empirically at 0.039 ng/mL) |
| Stx1 Cutoff (Broth Cultures) | Concentration yielding positive results 95% of the time, negative 5% of time | 0.04 ng/mL (found empirically at 0.042 ng/mL) |
| Stx2 Cutoff (Broth Cultures) | Concentration yielding positive results 95% of the time, negative 5% of time | 0.04 ng/mL (found empirically at 0.039 ng/mL) |
2. Sample Size Used for the Test Set and Data Provenance
- Direct Fecal Testing:
- Sample Size: 887 specimens (873 fresh, 14 frozen).
- Data Provenance: Not explicitly stated, but the study was conducted at 3 independent sites, implying clinical samples collected from patients. It does not specify country of origin or whether samples were prospective or retrospective, only that age and sex information was available for 878 patients.
- Broth Cultures Testing:
- Sample Size: 770 specimens (overnight broth cultures from fecal specimens).
- Data Provenance: Not explicitly stated, but derived from fecal specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications (e.g., number of years of experience).
4. Adjudication Method for the Test Set
The document does not describe an adjudication method for disagreements. The comparison was made against a single "gold standard" reference method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not mentioned. This device is an in vitro diagnostic device for lab use, not an AI-assisted diagnostic tool for human readers.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the clinical performance study compares the SHIGA TOXIN QUIK CHEK device directly against the gold standard (Vero Cell Cytotoxin Assay), indicating a standalone assessment of the device's performance. The results are based solely on the device's output.
7. The Type of Ground Truth Used
The ground truth used for establishing clinical performance was the Vero Cell Cytotoxin Assay (with neutralization), which is referred to as the "clinical reference standard (gold standard)".
8. The Sample Size for the Training Set
The document describes the device's validation but does not mention a separate "training set" in the context of machine learning or AI models. This is an in vitro diagnostic test, and its development typically involves internal analytical studies rather than a distinct training/test set split as seen in AI algorithms.
9. How the Ground Truth for the Training Set Was Established
As there's no mention of a "training set" for an AI model, this question is not applicable in the context of this traditional in vitro diagnostic device. The device's analytical setup (e.g., cutoff points for LOD) was established empirically using purified toxins and negative fecal/broth pools, following established protocols (EP17A).
§ 866.3255
Escherichia coli serological reagents.(a)
Identification. Escherichia coli serological reagents are devices that consist of antigens and antisera used in serological tests to identifyEscherichia coli from cultured isolates derived from clinical specimens. Additionally, some of these reagents consist ofEscherichia coli antisera conjugated with a fluorescent dye used to identifyEscherichia coli directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium belonging to the genusEscherichia, and provides epidemiological information on diseases caused by this microorganism. AlthoughEscherichia coli constitutes the greater part of the microorganisms found in the intestinal tract in humans and is usually nonpathogenic, those strains which are pathogenic may cause urinary tract infections or epidemic diarrheal disease, especially in children.(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 the limitations in § 866.9.