Search Results

The Cepheid Xpert® C. difficile/Epi Assay is a qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridium difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having C. difficile infection (CDI). Presumptive identification of 027/NAP1/BI strains of C. difficile is by detection of binary toxin (CDT) gene sequences and the single base pair deletion at nucleotide 117 in the tcdC gene. The tcdC gene encodes for a negative regulator in C. difficile toxin production. The test is performed on the Cepheid GeneXpert® Dx System and utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert C. difficile/Epi Assay is intended as an aid in the diagnosis of CDI. Detection of 027/NAP1/BI strains of C. difficile by the Xpert C. difficile/Epi Assay is presumptive and is solely for epidemiological purposes and is not intended to guide or monitor treatment for C. difficile infections. Concomitant culture is necessary only if further typing or organism recovery is required.

The Cepheid Xpert C. difficile/Epi Assay is a rapid, automated in vitro diagnostic test for qualitative detection of toxin producing Clostridium difficile directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridium difficile infection (CDI). The assay detects the toxin B gene (tcdB), the binary toxin gene (CDT), and the single base pair deletion at nucleotide 117 within the gene encoding a negative regulator of toxin production (tcdCA117). The combined presence of the genes encoding toxin B and binary toxin and the tcdCA117 deletion have been associated with a hypervirulent C. difficile strain known as 027/NAP1/BI, which has been associated with severe disease outbreaks in healthcare facilities worldwide. The assay is performed on the Cepheid GeneXpert Dx System. The Xpert C. difficile/Epi Assay system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA. The GeneXpert Dx System consists of a GeneXpert® instrument, personal computer, and disposable fluidic cartridges. Each instrument contains 1-16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests for detection of C. difficile toxin B and binary toxin gene sequences, and the tcdCA117 deletion, in less than 45 minutes. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and I-CORE® thermocycler for performing real-time PCR and detection. A swab is inserted into the stool specimen and then is placed in a tube containing elution reagent. Following brief vortexing, the eluted material and two single-use reagents (Reagent 1 and Reagent 2) that are provided with the Assay are transferred to different, uniquely-labeled chambers of the disposable fluidic cartridge (the Xpert C. difficile/Epi cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert Dx System instrument platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated. The Xpert C. difficile/Epi Assay includes reagents for the detection of toxigenic C. difficile and the presumptive detection of sequences found in 027/NAP1/B1 strains. In addition, the assay reagents include an internal sample processing control (SPC) to ensure adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR Assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The acceptance criteria are implied by the performance metrics reported in the clinical comparison study against reference methods. The device's performance is reported relative to these established methods.

Study Details

1. Sample size used for the test set and the data provenance:

   • Sample Size: 2293 specimens were tested in the overall clinical comparison study.
   • Data Provenance: Multi-site prospective investigation study at seven US and Canadian institutions.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • The document does not specify the number or qualifications of experts directly used for ground truth establishment.
   • The ground truth methods involved "reference culture followed by cell cytotoxicity testing on the isolates and strain typing on the toxigenic strains by restriction endonuclease analysis (REA), pulsed-field gel electrophoresis (PFGE), and PCR ribotyping methods."
   • "Following central culture testing, the toxigenic C. difficile positive isolates were sent to a second set of central laboratories for strain identification by REA, PFGE and PCR ribotyping." This suggests specialized laboratory personnel, but their specific qualifications are not detailed.

3. Adjudication method for the test set:

   • The document does not explicitly describe an adjudication method for conflicting results if multiple experts were involved beyond the described laboratory processes. The ground truth seems to be established through a hierarchical laboratory workflow (initial culture, then cytotoxin B testing, then specific strain typing methods in central labs).

4. 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:

   • No, this was not an MRMC study. This device is an automated in vitro diagnostic test (a nucleic acid amplification test), not an imaging-based AI system that assists human readers.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • Yes, the clinical comparison study evaluates the Xpert C. difficile/Epi Assay as a standalone algorithm. The assay is fully automated, as described: "In this platform, additional sample preparation, amplification, and real-time detection are all fully-automated and completely integrated." Its performance is directly compared against the established reference laboratory methods.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • The ground truth was established through a combination of microbiological culture, cell cytotoxicity testing, and molecular strain typing methods (REA, PFGE, PCR ribotyping) performed in central laboratories. This is a robust laboratory-based ground truth for identifying toxigenic C. difficile and specific hypervirulent strains.

7. The sample size for the training set:

   • The document does not mention a specific training set size. The device is a PCR-based assay, not a machine learning algorithm that typically requires a distinct training set in the same way. The analytical studies (inclusivity, sensitivity, specificity, linearity, interfering substances) would have been used during development and validation, but these don't constitute a "training set" in the machine learning sense.

8. How the ground truth for the training set was established:

   • As no specific "training set" in the machine learning sense is described, there's no mention of how its ground truth would have been established. The analytical studies used well-characterized C. difficile strains and other microorganisms with known genetic profiles (which serves a similar purpose to "ground truth" for analytical validation).

Ask a specific question about this device