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The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is an automated, qualitative in vitro diagnostic test, that uses real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridioides difficile (C.difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile Infection (CDI). The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.

The cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System (cobas® Cdiff) is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of C. difficile DNA in human stool specimens. The cobas® Liat® is for in vitro diagnostic use. The system is designed to identify and/or measure presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real-time detection, and result interpretation in a rapid manner. The cobas® Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Cdiff assay tube, no reagent preparation or additional steps are required. The cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR process specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas® Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas® Liat® Analyzer software controls and coordinated these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Cdiff assay tube, thereby eliminating the potential for cross-contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer.

The document provided does not contain the level of detail required to answer all aspects of your request. Specifically, it is a 510(k) summary for a change in shelf life for an existing device, the cobas® Cdiff Nucleic Acid Test. Therefore, it focuses on demonstrating that this change does not negatively impact performance, rather than providing all the original study details for the device's initial clearance.

Here's an analysis of the provided text in relation to your questions:

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

The document does not explicitly state specific numerical acceptance criteria for the initial device performance. It focuses on demonstrating that the performance of the device with the new shelf life is equivalent to the currently cleared device.

However, it does mention a new stability study was performed with "modified stability testing approach and acceptance criteria." It then states the result:

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

The document mentions a "new stability study" was performed to verify the shelf life. It does not provide:

• Sample size: No explicit number of samples or runs for this stability study is provided.
• Data Provenance: Not mentioned (e.g., country of origin).
• Retrospective/Prospective: Implied to be prospective for the shelf-life stability study, as it's a "new stability study." However, for the original clearance of the device itself, this information is not provided.

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).

This device is an in vitro diagnostic (IVD) test for detecting a bacterial gene (Clostridioides difficile toxin B gene). The "ground truth" for such a test would typically be established by:

• Reference methods: E.g., bacterial culture, toxigenic culture, or a highly sensitive and specific laboratory reference PCR assay.
• Clinical diagnosis: Based on patient symptoms, other lab tests, and clinical assessment.

This document does not mention the use of human experts (like radiologists) for ground truth establishment. For an IVD, the "experts" are the laboratory and clinical staff following established protocols to provide the comparator data. The document does not specify details about these "experts" or their qualifications.

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

Not applicable or not mentioned. Adjudication methods like 2+1 or 3+1 are typically used in image analysis studies where human readers interpret images. For an IVD, the comparison is usually against a pre-defined "gold standard" or reference method.

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 an IVD test, not an AI-powered diagnostic imaging device that assists human readers.

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

Yes, by its nature, an IVD test like the cobas® Cdiff Nucleic Acid Test on the cobas® Liat® System is a standalone device. The "algorithm" here refers to the pre-programmed steps of nucleic acid extraction, amplification, and real-time detection performed by the automated system, leading to a qualitative result (positive/negative). The document states: "The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples... The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer." This indicates standalone performance.

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

The document implies the ground truth for establishing initial performance would have been comparison to a reference method, likely a combination of toxigenic C. difficile culture and a highly reliable molecular method, or clinical diagnosis supported by confirmatory lab tests in the original clearance (K171770). For the current shelf-life stability study, the ground truth appears to be the expectation that the device continues to perform according to its established analytical specifications when tested at different time points after manufacturing. It refers to "assay performance and claims."

8. The sample size for the training set.

Not applicable/Not mentioned. As an IVD test, there isn't a "training set" in the machine learning sense. The device's performance is established through analytical and clinical validation studies with defined sample sizes. The document doesn't provide these sizes for the original device, nor for any "training" in the context of this specific 510(k) which is for a shelf-life change.

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

Not applicable/Not mentioned for the same reasons as #8. For an IVD, the "ground truth" for validation studies (analogous to a test set in ML) would be established by reference methods or clinical diagnosis.

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The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is an automated, qualitative in vitro diagnostic test that uses real-time polymerase chain reaction (PCR) for the detection of the toxin B (tcdB) gene of toxigenic Clostridioides difficile (C.difficile) in unformed (liquid or soft) stool specimens obtained from patients suspected of having C. difficile infection (CDI). The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.

The cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System (cobas® Cdiff) is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of C. difficile DNA in human stool specimens. The cobas® Liat® is for in vitro diagnostic use. The system is designed to identify and/or measure presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real-time detection, and result interpretation in a rapid manner. The cobas® Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Cdiff assay tube, no reagent preparation or additional steps are required. The cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR process specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas® Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas® Liat® Analyzer software controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Cdiff assay tube, thereby eliminating the potential for cross-contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer.

The provided text is a 510(k) summary for the cobas® Cdiff Nucleic Acid Test for use on the cobas® Liat® System. The purpose of this submission is to demonstrate substantial equivalence to a previously cleared device (K171770), specifically addressing a software update (Liat® Analyzer Software 3.3).

Therefore, the primary study discussed is a performance evaluation to demonstrate that the software update does not negatively impact the device's performance, thereby maintaining substantial equivalence to the predicate device.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of "acceptance criteria" with numerically reported performance metrics for sensitivity, specificity, accuracy, etc., as typically seen in initial device clearance studies. Instead, it states that the performance of the modified device was evaluated and that the overall cobas® Cdiff assay performance and claims were not impacted by the software changes. This implies that the acceptance criterion was essentially "no significant change in performance" compared to the predicate device, which had already met its own performance criteria.

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

The document does not provide details on the sample size or data provenance (e.g., country of origin, retrospective/prospective) for the performance evaluation related to the software update. It only discusses the evaluation of the software's impact on the assay. The original predicate device clearance (K171770) would contain this information for the initial performance claims.

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

This information is not provided in the context of this software update evaluation. The ground truth for the test set of the original device was likely established during its initial clearance (K171770), and this document focuses on confirming that the software change doesn't alter that established performance.

4. Adjudication Method for the Test Set

This information is not provided in this document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study is not applicable here. This device is an automated in vitro diagnostic test (nucleic acid amplification test), not an imaging device or a system that involves human readers interpreting results in a comparative effectiveness study setting. The device is designed to provide a qualitative result (detection of the toxin B gene).

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

Yes, implicitly. The evaluation focuses on the performance of the cobas® Cdiff assay with the updated software on the cobas® Liat® System. This is a standalone performance assessment of the automated diagnostic device (algorithm and hardware combined) without human interpretation impacting the primary result itself. The result is "automatically analyzed and...displayed" (page 5).

7. The Type of Ground Truth Used

The document does not explicitly state the type of ground truth used for this specific software update evaluation. For the initial clearance of a diagnostic test like this, ground truth for clinical performance studies would typically involve:

• Culture confirmation (e.g., toxigenic C. difficile culture)
• An FDA-cleared reference method or composite reference method (CRM) utilizing multiple tests and/or expert clinical judgment.

This document assumes that the established ground truth methodology for the predicate device remains valid and that the software update does not affect the device's ability to correlate with that ground truth.

8. The Sample Size for the Training Set

The document does not provide information on the sample size for the training set for the software (algorithm) itself. Given that this is a software update for an already cleared diagnostic system, "training set" in the context of machine learning (if applicable for some internal functions) is not detailed. The test uses established PCR principles and validated oligonucleotide sequences.

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

This information is not provided and is likely not relevant as this is an update to an analytical testing platform rather than a de novo AI/ML algorithm requiring a specific "training set" with ground truth in the traditional sense. The assay's core principles (oligonucleotide sequences, PCR) are described as unchanged from the predicate, which would have undergone its own rigorous analytical and clinical validation.

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The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is an automated, qualitative in vitro diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the detection of the toxin B (tcdB) gene of toxigenic Clostridium difficile in unformed (liquid or soft) stool specimens suspected of having C. difficile infection (CDI). The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System is intended for use as an aid in the diagnosis of CDI in humans in conjunction with clinical and epidemiological risk factors.

The cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System (cobas® Cdiff ) is a rapid, automated in vitro diagnostic test for the qualitative detection of C. difficile DNA in human stool specimens. The cobas® Liat® System is for in vitro diagnostic use. The system is designed to identify and/or measure the presence of genetic material in a biological sample. The system automates all nucleic acid amplification test (NAAT) processes, including reagent preparation, target enrichment, inhibitor removal, nucleic acid extraction, amplification, real-time detection, and result interpretation in a rapid manner. The cobas® Cdiff test uses silica magnetic particle-based nucleic acid extraction and TaqMan probe-based real-time PCR amplification and detection. The cobas® Liat® Analyzer automates and integrates sample purification, nucleic acid amplification and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Cdiff assay tube, no reagent preparation or additional steps are required. The cobas® Liat® System consists of an cobas® Liat® Analyzer with integrated software for running tests and analyzing the results, and a single-use disposable cobas® Cdiff assay tube that holds all of the sample purification and PCR reagents and hosts the sample preparation and PCR processes specific for the Cdiff analyte. The test uses the assay tube as both the sample and reaction vessel. The assay tube comprises flexible tubing containing all required unit dose reagents pre-packed in tube segments, separated by pressure-sensitive seals, in the order of reagent use. During the testing process, multiple sample processing actuators of the analyzer compress the cobas® Cdiff assay tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction conditions such as reaction volume, temperature, pressure, and incubation time. Precise control of all these parameters provides optimal conditions for assay reactions, allowing the test to achieve high performance similar to or better than that of currently available molecular assays. The cobas® Liat® Analyzer software controls and coordinated these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Cdiff assay tube, thereby eliminating the potential for cross-contamination between samples. The collected data are automatically analyzed and the result is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer.

Here's an analysis of the acceptance criteria and study details based on the provided text:

Acceptance Criteria and Device Performance for cobas® Cdiff Nucleic acid test for use on the cobas® Liat® System

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" in a separate section with numerical targets like a typical clinical trial report for an AI device. Instead, the performance metrics are presented as the results of the studies conducted. I will infer the acceptance criteria from the reported performance, implying that the reported values met the internal standards set by the manufacturer for substantial equivalence.

2. Sample size used for the test set and the data provenance

• Analytical Sensitivity (LOD): Not specified as a per-sample-size, but replicates of each 5-member test panel were tested with 2 different lots of assay tubes. Additional replicates were tested for confirmation.
• Inclusivity: 3 replicates per strain (37 toxigenic strains) were tested.
• Analytical Specificity (Cross-reactivity): Not specified as a per-sample-size, but 149 non-toxigenic organisms/cells were tested.
• Interference: Not specified as a per-sample-size, but 38 commonly used medications, fecal fat, whole blood, and mucin were tested.
• Reproducibility: 818 total tests were performed, with 798 valid for analysis across 3 panel members (Negative, ~1xLOD, ~3xLOD). 3 replicates per panel member, run on 5 nonconsecutive days by 2 operators at 3 sites for 3 reagent lots.
• Clinical Performance: 1,013 evaluable fresh remnant stool specimens were prospectively collected.
  • Data Provenance:
    • Country of Origin: Not explicitly stated, but "Nine (9) study sites from geographically diverse locations participated in this study." This suggests a multi-center study, likely within a single country (such as the US, given the FDA submission) or potentially across a few countries, but a specific list is not provided.
    • Retrospective/Prospective: The clinical performance study was prospective. "Evaluable fresh remnant specimens were prospectively collected from 1,013 patients."

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

• Analytical (LOD, Inclusivity, Specificity, Interference): Not applicable for these studies as the "ground truth" is based on engineered samples (known concentrations of specific strains, or presence/absence of interfering substances).
• Reproducibility: Not applicable, as this assessed the consistency of the device's own results, not against an external ground truth.
• Clinical Performance:
  • Number of experts: Not explicitly stated.
  • Qualifications of experts: Not explicitly stated. The "ground truth" was established by "combined results of direct and enriched toxigenic culture using leftover, deidentified, unformed stool samples" performed at a "reference laboratory." The document mentions "Nineteen (19) operators distributed across these study sites performed testing with the cobas® Cdiff test," but these are operators, not necessarily the adjudicating experts for the ground truth. For microbiological culture, laboratory personnel with specific training in microbiology would establish the ground truth.

4. Adjudication method for the test set

• Analytical, Reproducibility: Not applicable.
• Clinical Performance:
  • Initial Ground Truth: "Combined results of direct and enriched toxigenic culture" served as the primary comparative method.
  • Discrepant Analysis: "All evaluable discordant specimens and an equal number of randomly selected and representative concordant samples were used for discrepant testing by an FDA-cleared comparator NAAT. Testing was performed at an external lab that was preselected and qualified by RMS." This implies a form of 2-method consensus with a third method for discrepancies. If direct and enrichment culture disagreed, or if the cobas test disagreed with the combined culture, a third (comparator NAAT) test was used for "discrepant analysis." However, the final clinical performance tables still directly compare the cobas test to the combined culture results, with the discrepant analysis results discussed qualitatively ("Of the 23 specimens with false-negative cobas® Cdiff test results relative to combined direct culture and enrichment culture, 19 were negative. 3 were positive and 1 was invalid by the second NAAT method.").

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test, not an imaging AI device that relies on human-in-the-loop interpretation. The clinical study compares the device's output to laboratory culture results, not to human readers' interpretations with or without AI assistance.

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

• Yes, the performance presented is purely standalone (algorithm/device only). The cobas® Cdiff Nucleic acid test is an automated, qualitative in vitro diagnostic test. The device provides "result interpretation" directly on its integrated LCD touch screen (page 5). The clinical performance data reflects the device's ability to detect the target gene independently, compared against culture methods.

7. The type of ground truth used

• Analytical Studies (LOD, Inclusivity, Specificity, Interference): Lab-prepared spiked samples with known concentrations/compositions.
• Clinical Performance: Microbiological culture results. Specifically, "combined results of direct and enriched toxigenic culture." A "second NAAT method" was used for discrepant analysis.

8. The sample size for the training set

• Not applicable / Not explicitly stated. This is a molecular diagnostic test for Clostridium difficile, not a machine learning or AI algorithm in the typical sense that requires explicit "training data" for a model to learn from. The assay uses predefined primers and probes for real-time PCR detection (page 4). While the assay design and optimization would involve extensive internal development and testing, this is not characterized as a "training set" in the context of typical AI algorithm development.

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

• Not applicable / Not explicitly stated. As mentioned above, this is not an AI/ML device that uses a "training set" in the conventional sense. The "ground truth" for developing the test was based on well-characterized isolates of C. difficile and other microorganisms to design and validate the specificity and sensitivity of the primers and probes.

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