(210 days)
The Curian Shiga Toxin assay, for use with the Curian Analyzer, is a rapid, qualitative, fluorescent immunoassay for the simultaneous detection and differentiation of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in a single test device. It is intended for use with cultures derived from human stool specimens to aid in the diagnosis of disease caused by Shiga toxin producing Escherichia coli (STEC) infections. Test results are to be used in conjunction with the patient's clinical symptoms and history.
The Curian® Shiga Toxin assay is a qualitative in vitro diagnostic test for the detection of Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) in cultures derived from human stool specimens. The Curian® Shiga Toxin assay utilizes fluorescence technology with the cleared Curian® Analyzer (K192817) to detect Stx1 and Stx2 in cultures derived from human stool.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria, but it presents the performance of the Curian Shiga Toxin assay against a reference method (Vero cell Cytotoxin Assay). We can infer the implicit acceptance criteria from the reported performance, which demonstrates high sensitivity and specificity.
| Performance Metric | Acceptance Criteria (Implied by High Performance) | Reported Device Performance (Prospective Specimens) | Reported Device Performance (Archived Specimens) |
|---|---|---|---|
| Stx1 Sensitivity | High (e.g., >90%) | 100.0% (95% CI: 56.6% - 100.0%) | 100.0% (95% CI: 92.3% - 100.0%) |
| Stx1 Specificity | High (e.g., >90%) | 99.4% (95% CI: 98.9% - 99.7%) | 97.8% (95% CI: 92.2% - 99.4%) |
| Stx2 Sensitivity | High (e.g., >90%) | 100.0% (95% CI: 51.0% - 100.0%) | 97.0% (95% CI: 84.7% - 99.5%) |
| Stx2 Specificity | High (e.g., >90%) | 99.5% (95% CI: 99.1% - 99.8%) | 98.0% (95% CI: 93.1% - 99.5%) |
Note: The low end of the 95% CI for sensitivity in prospective specimens (e.g., 56.6% for Stx1) is due to the very small number of positive cases in that cohort (5 for Stx1 and 4 for Stx2). The 100% point estimate, while positive, has a wide confidence interval reflecting this small sample size. The archived cohort provides more robust sensitivity estimates.
2. Sample Size Used for the Test Set and Data Provenance
- Prospective Test Set: 1,627 stool specimens collected from patients suspected of having a Shiga toxin-producing Escherichia coli (STEC) infection.
- Evaluable Prospective Specimens: 1,538
- Data Provenance: Prospective collection from five clinical study sites representing geographically distinct regions throughout the United States.
- Archived Test Set: 140 archived stool samples.
- Evaluable Archived Specimens: 135 (5 excluded due to inconclusive reference results).
- Data Provenance: Retrospective testing of archived samples at all five clinical study sites.
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 qualifications for establishing the ground truth. It mentions that the reference method was the "Vero cell Cytotoxin Assay (with neutralization) performed on the broth culture obtained from the stool specimen." This is a laboratory-based assay, and its interpretation would typically be performed by trained laboratory personnel rather than a panel of clinical experts (e.g., radiologists).
4. Adjudication Method for the Test Set
The document does not describe any adjudication method for the test set. The ground truth was established by the "Vero cell Cytotoxin Assay (with neutralization)."
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not conducted. This device is an in vitro diagnostic (IVD) assay interpreted by an analyzer, not a medical imaging or diagnostic aid that multiple human readers would interpret with and without AI assistance. The Curian Analyzer automates the interpretation of results ("Results interpretation automated by Curian® Analyzer").
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the clinical performance study (both prospective and archived) represents the standalone performance of the device (Curian Shiga Toxin assay and Curian Analyzer). The results are "produced by the Curian Analyzer," indicating an automated, algorithm-only interpretation without a human-in-the-loop performance evaluation in the context of these clinical studies.
7. The Type of Ground Truth Used
The type of ground truth used was a laboratory reference method: the Vero cell Cytotoxin Assay (with neutralization) performed on broth cultures obtained from the stool specimens.
8. The Sample Size for the Training Set
The document does not provide information about the sample size for a training set. This is common for IVD submissions, where the focus is on the analytical and clinical performance of the device itself rather than the development of the underlying algorithms through a specific training set. The device is a "lateral flow fluorescent immunoassay," which is a biochemical detection method, not a machine learning algorithm that typically requires a large training dataset in the same way.
9. How the Ground Truth for the Training Set Was Established
Since no training set information is provided, there is no description of how ground truth for a training set was established.
§ 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.