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The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test for detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridioides 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 GeneXpert® Instrument Systems 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 test is intended as an aid in the diagnosis of CDI. Detection of 027/NAP/Bl strains of C. difficile by the Xpert® C. difficile/Evi test is presumptive and is solely for enidemiological 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 Xpert C. difficile/Epi test is an automated in vitro diagnostic test for qualitative detection of toxin producing Clostridioides difficile (formerly known as Clostridium difficile) directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridioides difficile infection (CDI). The test detects the toxin B gene (tcdB), the binary toxin (CDT) gene, and the single base pair deletion at nucleotide 117 (tcdCΔ117) within the gene encoding TcdC, a negative regulator of toxin production. The combined presence of the genes encoding toxin B and binary toxin and the tcdCA117 deletion has 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 test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System. GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The single-use disposable Xpert C. difficile/Evi cartridge, required by the platform for use, holds the PCR reagents and hosts the PCR process. Because the cartridge is self-contained, cross-contamination between samples is minimized.

The Xpert C. difficile/Epi test includes reagents for the detection of toxigenic C. difficile and the detection of sequences for presumptive identification of 027/NAP 1/BI strains. In addition, the test 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.

The Xpert C. difficile/Evi test system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA. A swab is inserted into the stool specimen and then placed in a tube containing Sample Reagent. Following brief vortexing, the content of the Sample Reagent is transferred to the Sample Chamber of the disposable fluidic cartridge (the Xpert C. difficile/Epi cartridge). The user initiates a test from the system user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time PCR for detection of C. difficile DNA.

Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests for the detection of gene sequences for C. difficile toxin B and binary toxin and the tcdCA117 deletion in less than 45 minutes. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.

The provided document is a 510(k) summary for the Cepheid Xpert C. difficile/Epi test. It details the device's characteristics, intended use, and performance studies conducted to demonstrate substantial equivalence to a predicate device and compliance with special controls.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal acceptance criteria with numerical targets (e.g., minimum sensitivity/specificity percentages). Instead, it summarizes "verification studies" to demonstrate performance and compliance. The key performance indicators mentioned relate to agreement with expected results and accurate identification of strains.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size for Test Set:
  • Prepared Cartridge Hold Time Study: Not explicitly stated how many "contrived positive" and "negative" samples were used, only that they were held for "various times under three (3) hold environments."
  • Functional Testing: Not explicitly stated how many "contrived positive" and "negative" samples were used.
  • Inclusivity Study: 26 C. difficile strains were tested (18 from previous study K110203 and 8 additional strains for K243730).
• Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. The studies mentioned (Hold Time, Functional Testing, Inclusivity) appear to be laboratory-based verification studies, rather than clinical trials with patient samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document does not mention the use of experts to establish ground truth for the test set. The performance studies appear to be analytical verification studies using contrived samples and known bacterial strains, implying that the ground truth for these studies was established by laboratory methods rather than expert consensus on clinical samples.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe any adjudication method for establishing ground truth, as the studies are analytical verification studies using controlled samples with known statuses (contrived positive/negative, specific C. difficile strains).

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. The device is a diagnostic assay (Nucleic Acid Amplification Test) for infectious disease, not an AI-powered image analysis tool requiring human reader interpretation. No mention of AI assistance or human readers is present.

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

Yes, the studies described (Prepared Cartridge Hold Time, Functional Testing, Inclusivity) assess the performance of the Xpert C. difficile/Epi test in a standalone manner. The device is an automated in vitro diagnostic test that performs sample preparation, amplification, and real-time detection without human intervention in the result determination process. It's an "algorithm-only" performance in the sense that the instrument provides a final result based on its internal processes.

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

The ground truth for the verification studies was based on:

• Known status of contrived samples: "contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples" for hold time and functional testing.
• Known bacterial strains: "C. difficile strains selected to broadly represent the majority of C. difficile toxinotypes encountered in practice" for the inclusivity study, where accurate identification of these known strains served as the ground truth.

8. The sample size for the training set

The document does not mention a "training set" in the context of machine learning or AI. This is a diagnostic assay, and its development likely involved traditional analytical validation and verification rather than an AI model requiring a training set.

9. How the ground truth for the training set was established

Not applicable, as no training set (in the AI/ML sense) is mentioned or implied for this device.

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The Cepheid Xpert® C. difficile/Epi Control Panel is intended for use as external assayed positive and negative quality controls to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Clostridioides (Clostridium) difficile performed with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The controls comprise cultured and inactivated Clostridioides (Clostridium) difficile 027-NAP1-B1 as the positive control and Clostridium sordellii as the negative control.

The Cepheid Xpert® C. difficile/Epi Control Panel is not intended to replace manufacturer controls provided with the device.

The Cepheid Xpert® C. difficile/Epi Control Panel to monitor DNA extraction, amplification and detection of the Cepheid Xpert® C. difficile/Epi assay. The Cepheid Xpert® C. difficile/Epi Control Panel contains cultured microorqanisms inactivated by heat treatments. Each Cepheid Xpert® C. difficile/Epi Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains cultured and inactivated Clostridioides difficile at a target level that is designed to provide reproducible performance above the limit of detection of the Cepheid Xpert® C. difficile/Epi assay. The positive control swab is expected to produce positive results for each of the genes targeted by the Cepheid Xpert® C. difficile/Epi assay: toxin B (tcdB), binary toxin (CDT) and the variant requlator gene, tcdC. Each negative control swab contains Clostridium sordelli. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

Here's an analysis of the provided text to fulfill your request regarding acceptance criteria and the study proving device performance:

Device Name: Cepheid Xpert C. difficile/Epi Control Panel

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a codified manner for a diagnostic accuracy study (e.g., target sensitivity, specificity). Instead, it presents the results of a precision and reproducibility study to demonstrate the performance of the control panel itself. The implicit acceptance criterion for a control panel is 100% agreement with the expected result (positive controls yield positive results, negative controls yield negative results).

2. Sample Size Used for the Test Set and Data Provenance

• Test Set Sample Size: 91 positive control tests and 91 negative control tests.
  • For the positive control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
  • For the negative control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
• Data Provenance: The document does not specify the country of origin. The study was conducted as a "precision and reproducibility study," which is typically prospective, designed to evaluate product consistency.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

Not applicable. This study evaluates a quality control panel, not a diagnostic device's ability to identify disease in patient samples. The "ground truth" for the test set is established by the known composition of the control panel itself (i.e., the positive control contains C. difficile, and the negative control contains C. sordellii). There are no human experts classifying images or results for ground truth in this context.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the "ground truth" is inherent in the design of the control panel. The performance is assessed against the expected molecular detection profile of the contained microorganisms.

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

Not applicable. This is a study for a quality control panel, not an AI-powered diagnostic device. No human readers or AI assistance are involved in interpreting the results beyond standard laboratory procedures for running the GeneXpert® Dx System.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The study inherently evaluates the "standalone" performance of the control panel in conjunction with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The control panel is a reagent designed to monitor the assay's performance. The results (presence/absence of targets, Ct values) are generated directly by the GeneXpert system without further human interpretation beyond confirming the system's output.

7. The Type of Ground Truth Used

The ground truth is based on the known composition of the manufactured control materials. The positive control contains cultured and inactivated Clostridioides difficile, and the negative control contains Clostridium sordellii. The expected results are therefore known beforehand based on the microbial content.

8. The Sample Size for the Training Set

Not applicable. This device is a quality control panel, not an algorithm or AI system that requires a "training set." The study evaluated the performance of the manufactured controls.

9. How the Ground Truth for the Training Set Was Established

Not applicable (as described in point 8).

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The Cepheid Xpert® C. difficile Assay, performed on the Cepheid GeneXpert® Dx System, is a qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences from unformed (liquid or soft) stool specimens collected from patients suspected of having Clostridium difficile infection (CDI). The test utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert C. difficile Assay is intended as an aid in the diagnosis of CDI. Concomitant culture is necessary only if further typing or organism recovery is required.

The Cepheid Xpert C. difficile Assay is a rapid, automated in vitro diagnostic test for qualitative detection of 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), and is performed on the Cepheid GeneXpert Dx System.

The Xpert C. difficile 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 gene sequences 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 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 realtime, 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 Assay includes reagents for the detection of toxin B gene (tcdB). 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 summary of the acceptance criteria and the study details for the Cepheid Xpert C. difficile Assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" with numerical thresholds in a dedicated table format. Instead, it describes the performance observed in various studies. Based on the "Overall Results" and "Performance vs. Reference Culture" sections of the clinical study, the following can be inferred as the key performance metrics evaluated and achieved:

2. Sample Size Used for the Test Set and Data Provenance:

• Sample Size for the Clinical Study (Test Set): A total of 2296 specimens were tested.
• Data Provenance: The study was a "multisite prospective investigation study at seven US and Canadian institutions." This indicates a prospective design with data collected from multiple locations across the US and Canada.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:

The document describes the ground truth for the clinical study as "reference culture followed by cell cytotoxicity testing on the isolates." It does not explicitly mention the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") involved in performing and interpreting these reference methods. The reference culture and cytotoxin B isolate testing would typically be performed and interpreted by trained laboratory personnel or microbiologists.

4. Adjudication Method for the Test Set:

The document does not describe a formal "adjudication method" involving multiple expert readers for the ground truth. The ground truth was established by the "reference culture method followed by cell cytotoxicity testing on the isolates." This implies a definitive laboratory result rather than a subjective interpretation requiring adjudication among human readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study compared the device (Xpert C. difficile Assay) directly against a laboratory reference standard (culture and cytotoxicity testing), not against human readers with and without AI assistance.

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

Yes, the studies described are standalone performance evaluations of the Xpert C. difficile Assay. The device is a "qualitative in vitro diagnostic test for rapid detection of toxin B gene sequences... The test utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences." The results presented (sensitivity, specificity, LoD, etc.) reflect the performance of the automated algorithm and system without human interpretation as part of the primary diagnostic output. Human involvement is limited to specimen collection, preparation (swab elution, reagent transfer), and initiating the test on the GeneXpert Dx System.

7. The Type of Ground Truth Used:

The primary ground truth used for the clinical comparison study was:

• Reference culture method followed by cell cytotoxicity testing on the isolates.

Specifically:

• Stool specimens were inoculated onto CCFA-D and CCMB-TAL.
• If C. difficile was isolated from CCFA-D and positive by cell cytotoxicity assay, it was classified as "toxigenic C. difficile positive."
• If not, further analysis was done on CCFA-E (subcultured from CCMB-TAL).
• If CCFA-E was positive for C. difficile and the isolate positive for cell cytotoxicity assay, it was classified as "toxigenic C. difficile positive."
• Otherwise, it was reported as "negative."

8. The Sample Size for the Training Set:

The document does not explicitly mention a separate "training set" or its sample size. The focus is on the analytical and clinical validation of the device. Diagnostic PCR assays typically do not have a "training set" in the same way machine learning algorithms do. Instead, they are developed and optimized (which could be considered analogous to training) using various strains and concentrations during the research and development phase. The analytical inclusivity, sensitivity (LoD), and specificity studies describe the validation of the device's ability to detect different strains and concentrations.

9. How the Ground Truth for the Training Set was Established:

As there is no explicitly defined "training set" in the context of this document, there's no description of how its ground truth was established. For the analytical studies, the ground truth was established by:

• Known characteristics of bacterial strains: Analytical inclusivity used 13 C. difficile strains of different toxinotypes, with their toxinotype status being the known ground truth.
• Known concentrations: Analytical sensitivity (LoD) involved preparing C. difficile at known CFU concentrations in a fecal matrix, with these known concentrations serving as the ground truth.
• Confirmed identity of microorganisms: Analytical specificity used 55 strains (including non-toxigenic C. difficile and other Clostridium species) whose identities were confirmed from reputable culture collections or institutions, acting as the ground truth for their presence or absence.

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