(123 days)
ImmunoCard® Toxins A & B is a rapid, qualitative, horizontal-flow enzyme immunoassay (ElA) for detecting Clostridium difficile toxins A and B in human stool. This assay is used as an aid in the diagnosis of C.difficile-associated disease.
ImmunoCard Toxins A & B is distributed as a test kit that includes the following reagents: ImmunoCard Toxins A & B Test Device, Sample Diluent, Positive Control, Enzyme Conjugate, Wash Reagent, and Substrate Reagent. The test device is a chromatography strip membrane pad housed in a plastic frame. The membrane carries immobilized monoclonal anti-Toxin A and goat polyclonal anti-Toxin B at the TEST reaction port and crude C. difficile toxin at the CONTROL reaction port. The Enzyme Conjugate Reagent consists of antibodies to toxins A and B coupled to horseradish peroxidase. The test involves diluting a stool sample with Sample Diluent and Enzyme Conjugate, incubating, adding the mixture to sample ports on the test device, incubating again, washing, adding Substrate Reagent, incubating, and visually reading the result based on the appearance of a blue color in the reaction ports.
Here's a summary of the acceptance criteria and study details for the ImmunoCard® Toxins A & B 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 (e.g., "must achieve X% sensitivity"). Instead, it presents the device's performance characteristics and compares them to predicate devices and the standard ground truth method (cytotoxin assay). The implicit acceptance is that the device's performance metrics are comparable or superior to predicate devices and acceptable for diagnostic aid.
| Performance Metric | Acceptance Criteria (Implicit) | Reported ImmunoCard® Toxins A & B Performance |
|---|---|---|
| Clinical Sensitivity | Comparable to/better than predicate devices and standard method | 95.2% (Overall) |
| Clinical Specificity | Comparable to/better than predicate devices and standard method | 98.5% (Overall) |
| Predictive Value of a Positive Test | Comparable to/better than predicate devices and standard method | 93.5% (Overall, incidence = 1%) |
| Predictive Value of a Negative Test | Comparable to/better than predicate devices and standard method | 99.0% (Overall) |
| Precision/Reproducibility | 100% within and between test sites | 100% |
| Analytical Sensitivity (Limit of Detection) | Not explicitly stated for acceptance, but a target of 3 ng/mL is implied | 3 ng/mL for both Toxin A and Toxin B |
| Cross-reactivity (Microbial) | No interference from common stool microbes (except related C. sordellii) | Only Clostridium sordellii (VPI 9048) caused a false positive |
| Cross-reactivity (Non-Microbial/Drugs) | No significant interference from common drugs/substances in stool | Fecal fat, metronidazole, whole blood, vancomycin, mucin, barium sulfate, Imodium AD®, Kaopectate® Caplets, Pepto Bismol® were tested and did not show significant interference based on the defined criteria (+/- 3 grades from control average). |
| High Dose Hook Effect | None | None observed |
2. Sample Size Used for the Test Set and Data Provenance
- Total Clinical Test Set Sample Size: 591 samples
- Data Provenance: Archival human stool samples collected from symptomatic patients. The study was conducted across three independent clinical laboratories and Meridian Bioscience's Development Laboratory. The data is retrospective, as it uses "archival samples collected from symptomatic patients that had been ungrouped for toxins."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Number of Experts: Not explicitly stated as "experts." However, the "cytotoxin and neutralization" assay served as the gold standard for ground truth. This assay requires specialized laboratory personnel to perform and interpret. The text states: "Meridian's Development Laboratory was responsible for performing all confirmation cytotoxin assays for Site 1 and Site 3." This implies trained laboratory personnel are involved.
- Qualifications of Experts: Not explicitly detailed beyond "Meridian's Development Laboratory." The cytotoxin assay is described as "the most accurate assay overall for the detection of C. difficile."
4. Adjudication Method for the Test Set
- The ground truth was established by the cytotoxin and neutralization assay. This method itself is the gold standard, implying its results were taken as the definitive truth. The text states: "The status of all samples (whether positive or negative by ImmunoCard) was confirmed by cytotoxin and neutralization."
- For samples producing discordant results between ImmunoCard and the cytotoxin assay, some were re-tested (e.g., 3-103, 3-118, 3-241 were "converted to positive on repeat testing at 1:10 dilution" in the cytotoxin assay). However, it's not described as a formal adjudication by an independent panel.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No MRMC comparative effectiveness study was done to assess how much human readers improve with AI vs. without AI assistance. This device is a rapid diagnostic assay, not an AI-assisted diagnostic tool interpreted by human readers.
6. Standalone (Algorithm Only Without Human-in-the-Loop) Performance
- This device is a standalone diagnostic kit (ImmunoCard® Toxins A & B), not an "algorithm." Its performance is evaluated directly in comparison to the gold standard (cytotoxin assay) and predicate devices. There is no human-in-the-loop component in the interpretation of the test device's result beyond visual assessment of color change. The test result (appearance of blue color in the test port) is directly interpreted.
7. Type of Ground Truth Used
- Expert Concensus / Gold Standard Laboratory Method: The primary ground truth used for performance evaluation was the cytotoxin and neutralization assay. This is considered the "standard method" for detecting C. difficile toxins.
8. Sample Size for the Training Set
- The document implies that the study was primarily for validation against a reference standard, not for training a machine learning algorithm. Therefore, there is no "training set" in the context of AI. The performance evaluation was done on a test set of 591 archival samples.
9. How the Ground Truth for the Training Set Was Established
- Not applicable, as there is no mention of a training set for an AI algorithm. The assay is a lateral flow immunoassay where the "ground truth" for its development would be based on biochemical binding and detection principles calibrated against known concentrations of toxins and validated with clinical samples against the gold standard (cytotoxin assay).
§ 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.