(108 days)
The illumigene C. difficile DNA amplification assay, performed on the illumipro-10, is a qualitative in vitro diagnostic test for the direct detection of toxigenic C. difficile in human stool specients suspected of having Clostridium difficile associated disease (CDAD).
The illumigene C. difficile assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect the pathogenicity locus (PaLoc) of toxigenic Clostridium difficile PaLoc is a gene segment present in all known toxigenic C. difficile strains. The C. difficile PaLoc codes for both the Toxin A gene (tcdA) and the Toxin B gene (tcdB), has conserved border regions, and is found at the same site on the C. difficile genome for all toxigenic strains . The illumigene C. difficile assay detects the PaLoc by targeting a partial DNA fragment on the Toxin A gene. The tcdA target region was selected as an intact region remaining in all known A+B+ and A-B+ toxinotypes.
illumigene C. difficile is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
The illumigene Molecular Diagnostic Test System is comprised of the illuminene C. difficite DNA Ampification Test Kit. the illumigene C. difficile External Control Kit and the illumipro-10 Automated Isothermal Amplification and Detection System. The illumigene C. difficile DNA amplification assay utilizes loop-mediated isothermal ampification (LAMP) technology to detect the presence of toxigenic C. difficile in patients suspected of having C. difficile associated disease (CDAD). Each illumiaene C. difficile assay is combleted using an illuminene Sample Preparation Apparatus. Illumicene Reaction Buffer, illumigene C. difficile Test Device, Sample Collection Brush, and illumigene Extraction Tube. Samples are prepared using the Sample Collection Brush and the illumigene Sample Collection Apparatus, target DNA is heat extracted in the Extraction Tube and DNA amplification occurs in the illumigene C. difficile Test Device.
The illumipro-10 heats each illumigene C. difficile Test Device containing prepared samples, facilitation of target DNA. When toxigenic C. difficile is present in the patient specific sequence is amplified and Magnesium pyrophosphate is formed. Magnesium pyrophosphate in the reaction mixture. The Illumioro-10 detects the change in light transmission mixture created by the precipitating Magnesium pyrophosphate. Sample results are reported as Positive based on the detected change in transmission.
The illumigene C. difficile External Control Kit consists of a Positive Control Reagent. External Control reagents are provided to aid the user in deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. The illumigene C. difficile External Control Kit is required for routine Quality Control.
The provided document describes the illumigene™ C. difficile DNA Amplification Assay, illumipro-10™ Automated Isothermal Amplification and Detection System, and illumigene™ C. difficile External Control Kit. This system is designed for the direct detection of toxigenic C. difficile in human stool samples to diagnose Clostridium difficile-associated disease (CDAD).
Here's an analysis of the acceptance criteria and the study that proves the device meets these criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in numerical thresholds (e.g., "sensitivity must be >90%"). Instead, the document presents the device's performance characteristics from a clinical study, implying these demonstrated values are acceptable for market clearance. The comparison is made against cytotoxic bacterial culture as the reference comparator.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance (Clinical Study) |
|---|---|---|
| Sensitivity | High | 95.2% (95% CI: 89.2% - 97.9%) |
| Specificity | High | 95.3% (95% CI: 93.2% - 96.7%) |
| Correlation | High | 95.3% (95% CI: 93.4% - 96.6%) |
| Invalid Rate | Low | 2.9% (Overall) |
| Analytical Sensitivity (LoD) | Defined for various strains | 4-64 CFU/test for different strains |
| Non-interference | Demonstrated for common substances & microorganisms | No interference from specified drugs, fecal components, white blood cells, whole blood, and a range of bacteria/viruses at tested concentrations. |
| Reproducibility | High agreement across sites and lots | 100% for negative and positive samples at various test levels, 91% for high negative. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Study (Test Set): 697 qualified patient samples. Of these, 677 samples were used for the overall performance data (Table 1), likely due to invalids or samples not meeting all inclusion criteria for the final analysis.
- Data Provenance: Clinical trials were conducted in 2010 across four independent clinical test sites and the manufacturer located in the Midwestern and Southern regions of the United States. The study involved prospective collection of samples (patient samples collected from individuals suspected of having CDAD).
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 test set was established by cytotoxic bacterial culture, which is a laboratory method, not human expert consensus. Therefore, the concept of "number of experts" or their qualifications for establishing the ground truth is not applicable in this context.
4. Adjudication Method for the Test Set
Not applicable. The ground truth was established by laboratory culture (cytotoxic bacterial culture), not by human interpretation requiring an adjudication process.
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
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is a molecular diagnostic assay, not an imaging-based AI system that would involve human readers interpreting AI results. The comparison is between the automated system and a laboratory reference standard.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done. The clinical performance data (Sensitivity, Specificity, Correlation) presented in "Performance Comparison, Clinical Tests" and "Table 1. Overall performance data" represents the performance of the illumigene C. difficile assay (algorithm/device only) in detecting toxigenic C. difficile directly from patient stool samples, as compared to cytotoxic bacterial culture. The system is designed for automated amplification and detection.
7. The Type of Ground Truth Used
The primary ground truth used for the clinical performance evaluation was cytotoxic bacterial culture.
8. The Sample Size for the Training Set
The document does not specify a separate training set size for the illumigene C. difficile assay's development. This is common for molecular diagnostic assays that are designed based on known genetic targets and biological principles, rather than machine learning algorithms requiring explicit training data. The "Performance Comparison, Clinical Tests" section describes a clinical validation or test set.
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 directly applicable. For the development and initial validation of the assay's ability to detect the pathogenicity locus (PaLoc), the ground truth for targeted sequences would have been established through well-characterized bacterial strains and genetic sequencing data specific to toxigenic C. difficile. The analytical sensitivity section describes testing against various known C. difficile strains with established toxinotypes and phenotypes to determine the limit of detection.
§ 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.