(118 days)
REMEL's Xpect™ Clostridium difficile Toxin A/B is a rapid in vitro immunochromatographic test for the direct, qualitative detection of Clostridium difficile Toxin A and/or B in human fecal specimens from patients suspected of having Clostridium difficile-associated disease (CDAD). The test is intended for use as an aid in diagnosis of CDAD. The test can also be used for confirmation of toxigenic Clostridium difficile from Brain Heart Infusion (BHI) broth culture.
The Xpect™ Clostridium difficile Toxin A/B test is a qualitative immunochromatographic assay that detects C. difficile Toxin A and Toxin B in stool specimens or cultures of toxigenic C. difficile. In performing the test, a specimen is first diluted with Specimen Diluent to help solubilize the toxins. A portion of the diluted sample is then mixed with a volume of Conjugate 1 containing antibodies to Toxin A and Toxin B coupled to colored microparticles, plus a volume of Conjugate 2 containing biotinylated antibodies to Toxin A and Toxin B. A volume of this mixture is transferred to a test device having immobilized streptavidin as a test line and goat antiimmunoqlobulin antibody a as a control line. Immunocomplexes of toxin and conjugated antibodies form a visible band as they flow across the test line. Excess colored particle conjugates form a visible band at the control line to document that the test is functioning properly.
Here is a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as distinct numerical targets in the provided text. However, they can be inferred from the reported performance results and the comparison to the predicate device and other commercially available assays. The primary implied acceptance criteria revolve around achieving competitive or superior sensitivity, specificity, and agreement compared to established methods for diagnosing C. difficile-associated disease (CDAD).
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Xpect™ C. difficile Toxin A/B) |
|---|---|---|
| Clinical Accuracy | ||
| Sensitivity | Comparable to or better than predicate/other methods (e.g., CTA) | 86.3% (95% CI = 79.8-91.3%) |
| Specificity | Comparable to or better than predicate/other methods (e.g., CTA) | 96.2% (95% CI = 94.5-97.5%) |
| Positive Predictive Value | Not explicitly defined, but good | 84.1% (95% CI = 77.4-89.4%) |
| Negative Predictive Value | Not explicitly defined, but good | 96.8% (95% CI = 95.2=98.0%) |
| % Correlation (Agreement) | Comparable to or better than predicate/other methods (e.g., CTA) | 94.4% (95% CI = 92.5-95.8%) |
| BHI Broth Culture Performance | High agreement with expected values of known strains | 94.7% (54/57) agreement with expected values |
| Analytical Sensitivity | Detection of Toxins A and B at low concentrations | Toxin A: ≥ 6.25 ng/ml; Toxin B: ≥ 40.0 ng/ml |
| Cross-Reactivity | No cross-reactivity with common microorganisms | No cross-reactivity observed with 54 microorganisms |
| Interfering Substances | No interference from common substances found in fecal specimens | No interference observed from 10 tested substances |
| Reproducibility | High consistency of results across sites and samples | 98.6% (71/72) of samples produced expected result |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Accuracy): A total of 815 specimens were tested.
- Data Provenance: The study was conducted at four geographically diverse regions of the United States, suggesting a prospective collection or at least a multi-site prospective analysis of collected samples. The text does not explicitly state if the samples were collected retrospectively or prospectively, but the term "evaluated at" suggests prospective evaluation over a period of time.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth for the clinical accuracy study was established using the cytotoxin assay (CTA). This is a laboratory-based assay and does not involve human experts in the same way, for example, a radiologist reads images. Therefore, the concept of "number of experts" and "qualifications of experts" does not directly apply to the primary ground truth method used here. The CTA is considered a gold standard for C. difficile toxin detection.
For discordant results, further investigation involved "toxigenic culture and microwell enzyme immunoassay." Again, these are laboratory methods, not expert human review.
4. Adjudication Method for the Test Set
There was a form of adjudication for discordant results.
- "Discordant results were further investigated by toxigenic culture and microwell enzyme immunoassay that detects both Toxin A and B."
- This suggests that when the Xpect™ test result and the CTA result did not agree, additional, more definitive laboratory tests (toxigenic culture and a different EIA) were used to ascertain the true status of the sample. This acts as an "adjudication" in a laboratory context, where a more definitive test is used to resolve discrepancies between the index test and the primary reference standard.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This is not applicable to this device. The Xpect™ Clostridium difficile Toxin A/B test is an in-vitro diagnostic (IVD) assay, not an AI-powered image analysis or diagnostic support tool for human readers. It directly detects bacterial toxins in a specimen. Therefore, there are no "human readers" in the context of interpreting the device's output, nor is there any AI assistance involved.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
This is not applicable to this device. As an IVD assay, the Xpect™ test inherently operates in a "standalone" fashion in terms of its direct detection mechanism (immunochromatography). It produces a visible line without requiring human interpretation other than observing the presence or absence of the line. The performance data presented (sensitivity, specificity) reflects this standalone performance.
7. The Type of Ground Truth Used
The primary ground truth for the clinical accuracy study was the Cytotoxin Assay (CTA). For discordant results, Toxigenic Culture and Microwell Enzyme Immunoassay (EIA) were used as further confirmatory ground truth methods.
8. The Sample Size for the Training Set
The document does not explicitly mention a distinct "training set" for the clinical accuracy study in the traditional sense of machine learning. For traditional IVD assays, optimization and initial validation (which could be considered analogous to training/development) would occur internally during product development, prior to the formal clinical performance study described. The clinical performance study (n=815) serves as the primary validation of the device's performance against the established ground truth.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" is identified, this question is not directly applicable. However, the ground truth for any internal development or optimization would likely have been established using the same (or similar) gold standard methods as the clinical validation, i.e., Cytotoxin Assay and/or Toxigenic Culture.
§ 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.