(168 days)
ImmunoCard STAT! EHEC is an immunochromatographic rapid test for the qualitative detection of Shiga toxins 1 and 2 (also called Verotoxins) produced by E. coli in cultures derived from clinical stool specimens. ImmunoCard STAT! EHEC is used in conjunction with the patient's clinical symptoms and other laboratory tests to aid in the diagnosis of diseases caused by enterohemorrhagic E. coli (EHEC) infections.
ImmunoCard STAT! EHEC is an immunochromatographic rapid test utilizing monoclonal antibodies labeled with red-colored gold particles. The test device has a circular sample port and an oval-shaped test (Toxin 1, Toxin 2) and control (Control) window. The sample is applied to the chromatography paper via the circular sample port. The sample is absorbed through the pad to the reaction zone containing colloidal, gold-labeled antibodies specific to Shiga toxins. Any Shiga toxin (ST1 and ST2) antigen present complexes with the gold-labeled antibody and migrates through the pad until it encounters the binding zones in the test (Toxin 1, Toxin 2) area. The binding zones (Toxin 1 and Toxin 2) contain another anti-ST1 or -ST2 antibody, which immobilizes any Shiga toxin-antibody complex present. Due to the gold labeling, a distinct red line is then formed. The remainder of the sample continues to migrate to another binding reagent zone within the control zone, and also forms a further distinct red line (positive control). Regardless of whether any Shiga toxin is present or not, a distinct red line should always be formed in the control zone and confirms that the test is working correctly.
Here's a summary of the acceptance criteria and study details for the ImmunoCard STAT! EHEC device, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly derived from the comparative performance against the predicate device, Premier EHEC, and the Duopath Verotoxin GLISA, as well as the observed reproducibility. The document emphasizes "substantial equivalence" as the primary goal. The critical performance metrics are clinical sensitivity and specificity.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate/Study Goals) | ImmunoCard STAT! EHEC Performance (Combined Broths) |
|---|---|---|
| Clinical Sensitivity | Comparable to Premier EHEC (100% reported for predicate) | 90.3% (post-resolution: 94.9%) |
| Clinical Specificity | Comparable to Premier EHEC (97.9% reported for predicate) | 100% (post-resolution: 100.0%) |
| Reproducibility | 100% (as shown by predicate) | 100% |
| Correlation | Comparable to predicate (98.1%) | 98.2% (post-resolution: 99.1%) |
Note on Acceptance Criteria: The document does not explicitly state numerical acceptance criteria in a dedicated section. Instead, the "Substantial Equivalence" determination (K062546) is based on the performance of the new device being comparable to the predicate device and being safe and effective for its intended use. The predicate device's performance characteristics serve as the benchmark for "acceptable" performance. The post-resolution values for sensitivity and correlation are higher and demonstrate improved agreement with the gold standard.
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size: A total of 360 stool samples were evaluated (340 produced growth in GN broth, 344 in Mac broth).
- Data Provenance: The data was collected from clinical samples in the United States, Canada, and Argentina. The study was prospective for collecting clinical samples to validate the product's new intended use with broth cultures. Some samples were tested fresh, while others were evaluated following frozen storage.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number or qualifications of experts used to establish the ground truth. It refers to the cytotoxin assay (CTA) as the method for resolving discrepant results, which implies a laboratory-based gold standard.
4. Adjudication Method for the Test Set
- Adjudication Method: Discrepant results between the ImmunoCard STAT! EHEC and the predicate device (Premier EHEC) were further analyzed using a cytotoxin assay (CTA). This indicates an adjudication process where the CTA served as a tie-breaker or definitive test for discordant outcomes.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not explicitly mentioned or described in the provided text. The device is a rapid immunochromatographic assay with clear positive/negative results (red lines), which typically does not involve human interpretation variability in the same way as imaging studies. The performance metrics focus on the device's accuracy against a reference standard.
6. If a Standalone Study Was Done
- Yes, a standalone study was performed. The "Performance evaluation" section details the evaluation of ImmunoCard STAT! EHEC with clinical samples (broth cultures) and its performance (sensitivity, specificity) was measured independently and then compared to the predicate device.
7. The Type of Ground Truth Used
- Primary Ground Truth: The predicate device (Premier EHEC) was initially used as the reference for comparison in calculating initial sensitivity and specificity. However, for resolving discrepant results, the cytotoxin assay (CTA) was used, which represents a more definitive diagnostic method for Shiga toxins. Therefore, the ground truth for discordant samples was cytotoxin assay (outcomes data/definitive lab test).
8. The Sample Size for the Training Set
- The document does not specify a separate training set size. The study focuses on the performance evaluation of the ImmunoCard STAT! EHEC for its new intended use. Since this is an immunochromatographic assay, typically, extensive machine learning training sets in the modern sense are not applicable. The device's design and reagent selection would have been developed prior to this validation study.
9. How the Ground Truth for the Training Set Was Established
- As no explicit training set is mentioned in the context of machine learning, this question is not applicable in the traditional sense. The "ground truth" for the device's development (e.g., antibody selection, assay parameters) would have been established through a combination of scientific knowledge, laboratory experiments with known positive and negative controls, and optimization trials, rather than a single "training set" with established ground truth from clinical samples.
§ 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.