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The Xpert® MRSA/SA Skin and Soft Tissue Infection test (Xpert MRSA/SA SSTI test) performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI test is indicated for use in conjunction with other laboratory tests, such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI test is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g., Gram-negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the limit of detection (LoD) of the test.

The Xpert MRSA/SA SSTI (Xpert MRSA/SA Skin and Soft Tissue Infection) test is an automated in vitro diagnostic DNA test for the qualitative, simultaneous detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from skin and soft tissue specimen swabs. The specimen is collected on a double swab, one of which is placed in a tube containing elution reagent. Following brief vortexing, the eluted material is transferred to a different, uniquely labeled sample chamber of a disposable fluidic cartridge (the Xpert MRSA/SA SSTI cartridge).

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 platform requires the use of singleuse disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The user initiates a test from the system user interface of the GeneXpert® Instrument Systems platform and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of SA and MRSA DNA.

Depending upon the specific instrument, a GeneXpert® instrument system may contain 1–80 modules, each which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests. 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 ICORE® thermocycler for performing real-time PCR and detection.

The Xpert MRSA/SA SSTI test kit includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA SSTI test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The test includes a sample processing control (SPC) to control for 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 MRSA/SA SSTI test performed on the GeneXpert® Instrument Systems provides results in approximately 62 minutes.

The provided text is a 510(k) summary for a medical device called Xpert MRSA/SA SSTI. It describes a diagnostic test for Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs, performed on the GeneXpert Instrument Systems.

The document does not contain information about the design of a study to prove acceptance criteria using a test set of data with expert ground truth, human reader performance, or multi-reader multi-case studies.

Instead, it details a Special 510(k) submission to modify an already cleared and legally marketed device (Xpert MRSA/SA SSTI, K080837). The specific modification is to include the GeneXpert® Infinity System instruments as a compatible platform for the test.

Therefore, the performance data presented is focused on demonstrating that the performance of the test on the new instrument platform (GeneXpert Infinity) is equivalent to its performance on previously cleared platforms (GeneXpert Dx System, GeneXpert System with Touchscreen). This is a bridging study rather than a primary clinical validation or an AI performance study as implied by many of the questions.

Given this, I cannot answer all your questions as the relevant information is not in the provided text. However, I will answer what is available and clarify what is missing.

Acceptance Criteria and Reported Device Performance

The acceptance criteria here refer to demonstrating equivalent performance of the Xpert MRSA/SA SSTI test when run on the new GeneXpert Infinity System compared to the previously cleared GeneXpert Dx System.

Study Details (Based on available information)

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

   • The document mentions "contrived positive (MRSA cells added to negative matrix) and negative (negative matrix only) samples" for functional testing. It does not provide the specific number of samples (sample size) used in these studies.
   • Data Provenance: The data appears to be prospective as it's generated from specific verification studies ("prepared cartridge hold time study and functional testing") conducted for this 510(k) submission. The country of origin is not specified but implicitly North American given the FDA submission.

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

   • This is a molecular diagnostic test, not an AI image analysis device. The "ground truth" for the functional testing would be the known concentration/presence of MRSA/SA cells in the contrived samples. This is established by the assay design and sample preparation, not by expert interpretation.
   • Therefore, this question does not apply to the type of study described.

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

   • Not applicable. This relates to expert consensus in interpreting complex data, which is not the ground truth methodology for this type of molecular test. The measurements (Ct values, presence/absence of signal) are quantitative and objective.

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, an MRMC study was not done. This is a diagnostic device for detecting specific DNA sequences, not an AI-powered device assisting human readers.

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

   • The device itself (Xpert MRSA/SA SSTI test on the GeneXpert Instrument Systems) is a standalone automated diagnostic test. Its "performance" is the detection of specific DNA sequences. The studies assess the instrument's ability to run the test and yield equivalent results. The "functional testing" mentioned is effectively the standalone performance of the assay on the new instrument.

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

   • The ground truth for the functional testing was contrived samples with known positive and negative status (e.g., negative matrix, or MRSA cells added to negative matrix where the concentration of MRSA/SA is known). This allows for direct assessment of sensitivity and specificity against a known standard.

7. The sample size for the training set:

   • This device is based on real-time PCR technology, not machine learning that requires a "training set" in the conventional sense. The test's probes and primers are designed based on biological knowledge of the target sequences.
   • Therefore, this question does not apply.

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

   • Not applicable, as there is no traditional "training set" for this type of diagnostic device.

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The Cepheid Xpert® MRSA NxG Control Panel is intended for use as an external assayed positive and negative quality control to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin-Resistant Staphylococus aureus performed with the Cepheid Xpert® MRSA NxG Assay on the GeneXpert® Instrument System. The controls comprise cultured and inactivated Methicillin-Resistant Staphylococcus aureus as the positive control and Staphylococcus epidermidis as the negative control.

The Cepheid Xpert® MRSA NxG Control Panel is not intended to replace manufacturer controls provided with the Cepheid Xpert® MRSA NxG Assay.

The Cepheid Xpert® MRSA NxG Control Panel is used to monitor the DNA extraction, amplification and detection processes of the Cepheid Xpert® MRSA NxG Assay. The Cepheid Xpert® MRSA NxG Control Panel contains cultured microorganisms inactivated by heat treatments. Each Cepheid Xpert® MRSA NxG 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 Methicillin-Resistant Staphylococcus aureus (MRSA) at arget level that is designed to provide reproducible performance above the limit of detection for each of the genes targeted by the Cepheid Xpert® MRSA NxG Assay: methicillin resistance gene mecA (mec) and the Staphylococcal cassette chromosome (SCC). Each negative contains Staphylococcus epidermidis (MSSE) that is not detected by the Cepheid Xpert® MRSA NxG Assay. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert® MRSA NxG Control Panel, based on the provided text:

Acceptance Criteria and Reported Device Performance

(Note: The provided text doesn't explicitly state the acceptance criteria as separate from the performance, but the 100% agreement achieved suggests this was the expected outcome for a control panel's precision and reproducibility study.)

Study Details

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

   • Sample Size:
     • For Positive Controls: 93 tests (32 at Site 1, 31 at Site 2, 30 at Site 3).
     • For Negative Controls: 92 tests (31 at Site 1, 31 at Site 2, 30 at Site 3).
   • Data Provenance: The study was conducted at three different testing locations (referred to as Site 1, Site 2, and Site 3). The document does not specify the country of origin, but it implies a prospective study since it describes "a precision and reproducibility study was conducted."

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

   • The concept of "ground truth" as established by experts (e.g., radiologists) is not applicable here. This is a study for a quality control material for a diagnostic assay, not an AI diagnostic device evaluating patient data. The "ground truth" for the control material is inherently defined by its composition (e.g., inactivated Methicillin-Resistant Staphylococcus aureus for the positive control, Staphylococcus epidermidis for the negative control) and the known expected results from the Cepheid Xpert® MRSA NxG Assay.

3. Adjudication method for the test set:

   • Not applicable. As this is a study for a quality control material, the results are objective (positive/negative detection) based on the performance of the assay with the control. There's no subjective interpretation requiring adjudication among experts. The study reports raw agreement percentages. Any "ERROR" responses were retested with a new control, indicating a procedural re-evaluation rather than expert adjudication of a result.

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 type of study (MRMC for AI) is not applicable to a quality control panel. This product is a control material for an in-vitro diagnostic assay, not an AI-powered diagnostic device.

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

   • Yes, in essence. The "device performance" refers to the performance of the control panel itself, which is then used by human operators with the GeneXpert® Instrument System and Cepheid Xpert® MRSA NxG Assay. While human operators are involved in running the test, the evaluation of the control material's performance against the assay's expected results is a standalone assessment of the control material's ability to consistently produce those results. This isn't an AI algorithm; rather, it's a quality control for an existing diagnostic system.

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

   • The "ground truth" for the control panel is based on its known composition and the expected analytical performance when run on the target assay. For the positive control, the ground truth is the presence of Methicillin-Resistant Staphylococcus aureus (mec, SCC) at a level detectable by the assay. For the negative control, the ground truth is the presence of Staphylococcus epidermidis which should not be detected by the target assay.

7. The sample size for the training set:

   • Not applicable. This study is for a quality control material, not a machine learning or AI algorithm that requires a training set. The "samples" used are the control materials themselves tested on the assay system.

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

   • Not applicable. As there is no training set for an AI algorithm, this question is not relevant to the described device and study.

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The Cepheid® Xpert® MRSA/SA Blood Culture test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples from BD BACTEC™ Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined by Gram Stain as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC). The Xpert MRSA/SA Blood Culture test is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood culturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture test is not intended to monitor treatment for MRSA/SA infections.

The Cepheid Xpert® MRSA/SA Blood Culture test is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle samples that are detected as positive for microbial growth and shown to contain Gram Positive Cocci by Gram stain. The primers and probes in the Xpert MRSA/SA Blood Culture test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site. The test includes a Sample Processing Control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability. The sample for testing with the Xpert MRSA/SA Blood Culture test consists of an aliguot taken from a positive blood culture bottle. Using one of the disposable fixed 50 µL volume transfer pipettes provided with the test kit, an aliquot of the positive blood culture is transferred into a single-use tube of Elution Reagent, also provided with the kit. The Elution Reagent is briefly vortexed and the entire content is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture cartridge), after which the cartridge is ready to place on the instrument. The assay is performed on the Cepheid GeneXpert Systems, which automate and integrate sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated. The Xpert MRSA/SA Blood Culture test performed on the GeneXpert Instrument Systems provides results in approximately 60 minutes. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and realtime PCR tests. 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.

This document describes the Xpert MRSA/SA Blood Culture test, a qualitative in vitro diagnostic test for detecting Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from positive blood cultures. The submission is a Special 510(k) to modify the assay definition file (ADF).

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

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

The provided document is a 510(k) summary for a Special 510(k) submission, indicating a modification to an existing cleared device (predicate device). For such submissions, the primary "acceptance criterion" is demonstrating substantially equivalent performance to the predicate device, especially considering the specific change made. In this case, the change is to the assay definition file (ADF).

The document explicitly states: "The re-analyses showed the devices were substantially equivalent." This implies that the performance after the ADF update met the previous performance standards or comparable benchmarks. However, the document does not present a table of specific numerical acceptance criteria (e.g., sensitivity, specificity thresholds) or a direct comparison of the reported device performance against those criteria in a quantitative manner for the new device. Instead, it relies on the assertion of substantial equivalence based on re-analysis of existing data.

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 states: "The updated Assay Definition File with rules-based algorithms and release of new GeneXpert software to support this update have been validated by the re-analyses of the original clinical performance data and a subset of the original analytical performance data, including LoD, inclusivity, exclusivity, potential interfering substances, reproducibility, and precision."

• Sample Size: The document does not specify the sample size used for the re-analysis of the clinical performance data or the subset of analytical performance data. It only refers to "original clinical performance data" and "a subset of the original analytical performance data."
• Data Provenance: The document does not provide information on the country of origin of the data or whether the original data was retrospective or prospective. It only mentions "original clinical performance data," implying data collected during the initial clearance of the predicate device (K130894).

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 provide information on the number or qualifications of experts used to establish the ground truth for the testing. Since this is an in vitro diagnostic test for bacterial detection, the ground truth would typically be established by standard microbiological culture and identification methods, which are considered objective laboratory results rather than expert interpretation in the same way a medical image would be.

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

The document does not specify any adjudication method. This is not typically relevant for in vitro diagnostic tests where ground truth is established through objective laboratory methods (like culture) rather than subjective expert consensus on complex cases.

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 is designed for evaluating situations where human readers (e.g., radiologists, pathologists) interpret cases, and the technology aims to assist or replace their interpretation.

This section is not applicable to the Xpert MRSA/SA Blood Culture test. This device is an automated in vitro diagnostic test that directly detects bacterial DNA from blood cultures. It does not involve human "readers" interpreting results in the same way an imaging AI might.

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

Yes, the device performs as a standalone algorithm (test kit and instrument system) without human-in-the-loop performance for its primary function of detecting MRSA/SA DNA. The device "utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA." The changes described are to the "Assay Definition File" which contains "rules-based algorithms." This indicates a standalone performance where the algorithm generates the result. While a trained technician initiates the test and reviews the output, the diagnostic decision of positive/negative for MRSA/SA is made by the device's automated analysis.

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

The ground truth for such a molecular diagnostic test for bacterial identification is typically established through standard microbiological culture and identification methods, including phenotypic and potentially genotypic characterization of the isolates. This is considered an objective laboratory ground truth, not based on expert consensus, pathology, or outcomes data in the usual sense. The "Indications for Use" mention that "Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing," which points to culture as the gold standard for definitive identification and further characterization.

8. The sample size for the training set

The document is for a modification (Special 510(k)) to an already cleared device ("predicate device," K130894). The modification is to the "assay definition file (ADF) with rules-based algorithms." It explicitly states that this update was validated by "re-analyses of the original clinical performance data" and "a subset of the original analytical performance data."

This implies that the current submission does not involve a new "training set" for developing a new algorithm from scratch. Instead, it seems the "rules-based algorithms" were modified, and their impact was assessed using existing (original) validation data. Therefore, information about a "training set" for the modified algorithm is not provided as it's likely not applicable in the context of this specific type of submission.

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

As inferred above (point 8), a new "training set" for the modified algorithm is not explicitly mentioned. If the "rules-based algorithms" were developed using any data, that process is not described. However, given the nature of the device (molecular detection of bacteria), any "training" or optimization data would have relied on a ground truth established by standard microbiological culture and identification methods, similar to the validation data.

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The Xpert® MRSA NxG Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA-specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The Xpert MRSA NxG Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA NxG Assay is not intended to diagnose, guide, or monitor treatment for MRSA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The Xpert MRSA NxG Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of methicillin-resistant Staphylococcus aureus (MRSA) directly from nasal swab specimens of patients at risk for colonization with MRSA in a healthcare setting. The Xpert MRSA NxG Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection. The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert MRSA NxG cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized. The Xpert MRSA NxG Assay includes reagents for the detection of target MRSA DNA. The primers and probes in the Xpert MRSA NxG Assay detect proprietary sequences for the gene for methicillin/oxacillin resistance (mecA and mecC), and staphylococcal cassette chromosome mec (SCCmec), which is inserted into the SA chromosomal attB site. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The Probe Check Control verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability. The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of genomic DNA from methicillinresistant Staphylococcus aureus (MRSA) in 70 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. 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 RT-PCR and detection. Nasal swab specimens are collected using the Cepheid Sample Collection Device and are transported to the laboratory or designated GeneXpert testing area. The nasal swab specimen is placed in a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using a transfer pipette. For nasal swab specimens that are collected using Copan Liquid Amies Elution Swab (ESwab) collection and transport system, 300 uL of liquid sample is transferred to a tube containing 2 mL of Elution Reagent. Following a brief vortexing of the sample, the entire contents of the Elution Reagent tube are transferred to the sample chamber of the Xpert MRSA NxG cartridge using a transfer pipette. The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.

Here's a breakdown of the acceptance criteria and the study details for the Xpert MRSA NxG device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for the clinical performance in a numerical format that would be directly comparable to the predicate device. Instead, it aims to demonstrate "substantial equivalence" to the predicate device (BD MAX™ MRSA XT assay). The primary performance metrics for this type of in vitro diagnostic test are analytical sensitivity (Limit of Detection), clinical sensitivity, and clinical specificity. I've extracted the relevant performance metrics from the clinical studies to serve as the reported device performance.

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

• Clinical Test Sets:
  • Rayon Swab Study: 1103 eligible nasal swab specimens.
  • ESwab Study: 846 eligible nasal swab specimens.
  • Combined: 1949 total specimens.
• Data Provenance: The clinical studies were prospective, multi-site investigational studies.
  • The Rayon Swab study involved "eight investigational sites within the US and outside of the US."
  • The ESwab study involved "six investigational sites within the US."

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

The ground truth for the clinical test set was established using a reference culture and susceptibility testing method, not expert consensus in the traditional sense of medical image interpretation (e.g., radiologists). The document does not specify the number or qualifications of laboratory personnel performing these culture and susceptibility tests. However, the FDA's acceptance of this method implies that these are standard, qualified laboratory procedures.

4. Adjudication Method (for the test set)

The adjudication method was based on the reference culture and susceptibility testing.

• A specimen was considered positive for MRSA if the presence of MRSA was confirmed in either direct culture on MRSA selective chromogenic medium or via an enriched culture (Trypticase Soy Broth (TSB) with 6.5% Sodium Chloride followed by subculture on Blood Agar (BA) and MRSA selective chromogenic medium).
• Identification of presumptive S. aureus colonies was confirmed with Gram stain, catalase, and coagulase testing.
• MRSA confirmation was done by susceptibility testing with a Cefoxitin disk (30µg).
• For discrepancies (e.g., false positives/negatives by the device), repeat subculture of the enrichment broth was performed, as noted in the footnotes to Tables 8-7 and 8-8. This acts as a form of "adjudication" for discrepant results.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This device is an automated, standalone diagnostic assay (real-time PCR) for detecting MRSA DNA. It does not involve human "readers" in the interpretation of results in a way that would be typical for image-based AI tools. Therefore, there's no "human improvement with AI vs without AI assistance" to report.

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

Yes, a standalone performance evaluation was conducted. The Xpert MRSA NxG Assay is an automated qualitative in vitro diagnostic test, and its performance (sensitivity, specificity) was directly compared against the reference method without human interpretation of the assay's output itself. The device itself performs sample preparation, amplification, and real-time detection, automatically generating results.

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

The ground truth used was laboratory culture and susceptibility testing, specifically:

• Direct culture on MRSA selective chromogenic medium.
• Enriched culture (TSB with 6.5% NaCl, followed by subculture on BA and MRSA selective chromogenic medium).
• Confirmation of S. aureus by Gram stain, catalase, and coagulase testing.
• Confirmation of MRSA by Cefoxitin disk susceptibility testing.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning model development. This is an in vitro diagnostic device based on PCR technology, which typically does not involve machine learning training in the same way an AI imaging model would. The "training" here would refer to the development and optimization of the PCR primers and probes, and the cartridge and instrument system, which is part of the product development process rather than a distinct "training set" for an algorithm.

However, if we consider "training" in the sense of analytical development, the following data points could be relevant to the development and optimization of the assay's internal logic and performance parameters:

• Analytical Sensitivity (LoD) Study: Used 13 individual MRSA strains (representing various SCCmec types).
• Analytical Specificity (Cross-reactivity) Study: Tested 152 potentially cross-reactive microorganisms and human cells.
• Analytical Reactivity (Inclusivity) Study: Evaluated 196 methicillin-resistant Staphylococcus aureus strains.

These studies technically inform and confirm the performance of the developed assay, which is analogous to a validation set in traditional software, but not a training set for an AI/ML algorithm.

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

As noted in point 8, the concept of a "training set" in the context of an AI/ML algorithm, along with its ground truth, is not applicable here. The assay's analytical parameters (e.g., LoD, specificity, inclusivity) were established through rigorous laboratory testing using well-characterized microbial strains and samples, where the "ground truth" for each analytical study (e.g., presence/absence of a specific MRSA strain, concentration, presence of interfering substance) was defined by standard microbiological and chemical methods.

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The Cepheid® Xpert® MRSA/SA Blood Culture Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture samples from BD BACTEC™ Plus Aerobic/F, BacT/ALERT® SA (Standard Aerobic) or VersaTREK REDOX 1® (aerobic) blood culture bottles that are determined by Gram Stain as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC). The Xpert MRSA/SA Blood Culture Assay is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from positive blood cultures. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert MRSA/SA Blood Culture Assay is not intended to monitor treatment for MRSA/SA infections.

The Cepheid Xpert® MRSA/SA Blood Culture Assay (Xpert MRSA/SA Blood Culture Assay) is a rapid, automated DNA test for the simultaneous qualitative detection of MRSA and SA DNA directly from blood culture bottle specimens that are detected as positive for microbial growth and shown to contain Gram Positive Cocci by Gram stain. The primers and probes in the Xpert MRSA/SA Assay detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The test includes a Sample Processing Control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The specimen for testing with the Xpert MRSA/SA Blood Culture Assay consists of an aliquot taken from a positive blood culture bottle. Using one of the disposable fixed 50 µL volume transfer pipettes provided with the test kit, an aliquot of the positive blood culture is transferred into a single-use tube of Elution Reagent, also provided with the kit. The Elution Reagent is briefly vortexed and the entire content is transferred to the "S" chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture Assay cartridge), after which the cartridge is ready to place on the instrument.

The assay is performed on the Cepheid GeneXpert Instrument Systems, which automate and integrate sample purification, nucleic acid amplification of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, crosscontamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fully-automated and completely integrated. The Xpert MRSA/SA Blood Culture Assay performed on the GeneXpert Instrument Systems provides results in approximately 60 minutes.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR tests. 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.

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert® MRSA/SA Blood Culture Assay:

Acceptance Criteria and Reported Device Performance

Study Details

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

   • Sample Size: A total of 792 specimens were tested for MRSA and SA.
   • Data Provenance: The data was collected from a multi-site prospective study at eight US 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 explicitly state the number of experts or their specific qualifications for establishing ground truth within the clinical comparison study.
   • The ground truth was established by reference culture results and susceptibility testing, which are standard laboratory practices and would generally involve trained microbiologists or laboratory technicians rather than individual "experts" in the context of interpretation. Susceptibility testing was performed in accordance with CLSI documents M2-A11 and M100-S22, using cefoxitin disc as a surrogate for methicillin/oxacillin resistance, indicating reliance on established guidelines.

3. Adjudication method for the test set:

   • The document does not specify an explicit adjudication method (like 2+1 or 3+1). The ground truth was determined by comparing the device's results to "reference culture results and susceptibility testing (the current standard of care)." This implies a direct comparison to established laboratory methods, rather than an expert consensus process for adjudication of conflicting results between readers.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a Nucleic Acid Amplification Test (NAAT), which is an automated molecular diagnostic test producing a definitive positive/negative result, not an imaging-based AI system that would assist human readers in interpretation. Therefore, the concept of human readers improving with or without AI assistance is not applicable here.

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

   • Yes, a standalone performance study was done. The entire clinical comparison study (792 specimens) directly evaluated the performance of the Xpert MRSA/SA Blood Culture Assay (an automated DNA test) against reference culture methods. The device's output is a definitive positive or negative result for MRSA and SA, generated automatically by the instrument system without human interpretive input for each individual test result.

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

   • The ground truth used was reference culture results and susceptibility testing. This represents established laboratory diagnostic methods considered the "standard of care" for identifying and characterizing Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.

7. The sample size for the training set:

   • The document focuses on the validation or test set performance rather than detailing a specific "training set" in the context of machine learning. The device is a NAAT, meaning its "learning" or development process involved analytical studies (inclusivity, LoD, specificity, etc.) and wet-lab experiments during its development, rather than observational data-driven machine learning.
   • For analytical inclusivity (reactivity), 250 SA strains (47 MSSA and 203 MRSA) from multiple sources were tested. This could be considered part of the development/training of the assay's target detection capabilities, but it's not a "training set" in the common AI/ML sense.

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

   • As noted above, a "training set" in the machine learning sense is not directly applicable. For the analytical studies that inform the assay's design and performance claims:
     • Analytical Inclusivity (Reactivity): Strains were characterized by methods like pulsed-field gel electrophoresis (PFGE) to confirm their USA types and classifications (e.g., USA100, USA300, USA400). The document also mentions a SA strain (LGA251) with a novel mecA gene (SCCmec type XI) which was incorrectly identified, implying that the ground truth for these strains was established through advanced genomic and microbiological characterization.
     • Limit of Detection (LoD): Ground truth was established by precise quantification of bacterial cells (CFU/mL, then CFU/test) using plate counts in triplicate.
     • Analytical Specificity (Exclusivity): Organisms were identified as Gram positive, Gram negative, or yeast, and specifically classified (e.g., methicillin-sensitive, coagulase negative Staphylococcus) based on standard microbiological techniques and sourced from reputable culture collections (ATCC, CCUG, NCTC, NARSA).

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The Cepheid Xpert™ MRSA/SA Blood Culture Assay performed on the GeneXpert® Dx System™ is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from patient positive blood cultures. The assay utilizes automated real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture specimens using BD BACTEC™ Plus Aerobic/F blood culture bottles that are determined as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC) by Gram stain. The Xpert MRSA/SA Blood Culture Assay is indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from patient positive blood cultures. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing. The Cepheid Xpert™ MRSA/SA Blood Culture Assay is not intended to monitor treatment for MRSA/SA infections.

When an MRSA negative/SA positive result is obtained, the result should be interpreted as "MRSA indeterminate/SA Positive, antimicrobial susceptibility testing pending". Further testing should be performed using an FDA-cleared, phenotypic antimicrobial susceptibility testing method on isolated colonies recovered from the blood culture bottle. MRSA positive results should be reported as such.

The Cepheid Xpert® MRSA/SA Blood Culture Assay (Xpert MRSA/SA Blood Culture Assay) is a rapid, automated DNA test for simultaneously detecting MRSA and SA directly from positive blood culture specimens. The assay is performed on the Cepheid GeneXpert Dx System.

This summary is based on the provided text, which refers to a 510(k) submission for a device modification rather than a new study. Therefore, the information typically associated with a new study's acceptance criteria and performance data is not fully present. The document explicitly states that the device is "substantially equivalent" to a previously cleared predicate device and that "the only changes that have been made to the new device are to the package insert, as directed by the agency." This means there wasn't a new clinical study to establish performance against acceptance criteria for this specific submission.

However, I can extract the relevant information regarding the equivalence claim and the device itself.

1. Table of Acceptance Criteria and Reported Device Performance

Since this 510(k) is for a modification (package insert changes) to an already cleared device, there are no new acceptance criteria or device performance metrics presented in this document. The device's performance is implicit in its substantial equivalence to the predicate device, which would have undergone its own performance evaluation.

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

Not applicable for this 510(k) submission as no new performance study was conducted. The document focuses on the substantial equivalence of the modified device to its predicate, primarily due to labeling changes.

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

Not applicable for this 510(k) submission as no new performance study was conducted.

4. Adjudication Method for the Test Set

Not applicable for this 510(k) submission as no new performance study was conducted.

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

No, an MRMC comparative effectiveness study was not done for this 510(k) submission. The document explicitly states that the changes are related to the package insert, and the device is substantially equivalent to a predicate.

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

The device itself is an automated DNA test ("Nucleic Acid Amplification Test, DNA, Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA), qualitative") performed on the Cepheid GeneXpert Dx System. Therefore, it inherently operates in a standalone manner (algorithm only) to detect MRSA/SA DNA. However, this specific 510(k) is not presenting a new standalone performance study, but rather confirming the substantial equivalence of a modified version of an already cleared standalone device. The device's intended use also states that it's "indicated for use in conjunction with other laboratory tests, such as culture, and clinical data available to the clinician." This implies that while the algorithm provides a result, clinical interpretation involves other human-generated data.

7. The Type of Ground Truth Used

Not explicitly stated in this document for this specific submission as no new performance testing was conducted. For the predicate device, the ground truth for detecting MRSA/SA from positive blood cultures would typically be established through microbiology culture and subsequent identification and susceptibility testing (e.g., phenotypic methods) of the isolated organisms.

8. The Sample Size for the Training Set

Not applicable for this 510(k) submission as no new training was performed for a device modification involving only package insert changes.

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

Not applicable for this 510(k) submission as no new training was performed.

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The Cepheid Xpert™ MRSA/SA Blood Culture Assay performed on the GeneXpert® Dx System™ is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA directly from patient positive blood cultures. The assay utilizes automated realtime polymerase chain reaction (PCR) for the amplification of MRSA/SA specific DNA targets and fluorogenic target-specific hybridization probes for the real-time detection of the amplified DNA. The assay is performed directly on positive blood culture specimens using BD BACTEC™ Plus Aerobic/F blood culture bottles that are determined as Gram Positive Cocci in Clusters (GPCC) or as Gram Positive Cocci in singles (GPC) by Gram stain. The Cepheid Xpert™ MRSA/SA Blood Culture Assay is not intended to monitor treatment for MRSA/SA infections. Subculturing of positive blood cultures is necessary to recover organisms for susceptibility testing or for epidemiological typing.

The Cepheid Xpert™ MRSA/SA Blood Culture Assay (Xpert MRSA/SA Blood Culture Assay) is a rapid, automated DNA test for simultaneously detecting MRSA and SA Alber) I a rapids, and culture specimens. The specimens. The specimen consists of an aliquot taken from a positive blood culture bottle for testing with the Xpert MRSA/SA Blood Culture Assay. Using one of the small disposable transfer pipettes provided with the test kit, a single drop of the positive blood culture aliquot (approximately 50 µL) is transferred into the Elution Reagent. The Elution Reagent is vortexed for 10 seconds and the entire contents are transferred to "S" chamber of the disposable fluidic cartridge (the Xpert MRSA/SA Blood Culture Assay cartridge). The two single-use reagents (Reagent 1 and Reagent 2) that are provided with the assay are transferred to different, uniquelylabeled chambers of the Xpert MRSA/SA 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 fully-automated and completely integrated.

The GeneXpert Dx System consists of a GeneXpert instrument, personal computer, and the multi-chambered fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of MRSA and SA in approximately 50 minutes. Each system has 2 to 16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert MRSA/SA Assay includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA Assay detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The test includes a Sample Processing Control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The acceptance criteria and study proving the device meets them are detailed below for the Cepheid Xpert™ MRSA/SA Blood Culture Assay.

1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly defines acceptance criteria based on the performance observed in the predicate device and the clinical study results. The clinical study results serve as the primary demonstration of meeting these criteria.

Note: The predicate device's performance is listed as "Positive % Agreement" and "Negative % Agreement," which are equivalent to sensitivity and specificity in this context. The implicit acceptance criteria for the new device are to perform at least comparably to the predicate and the "standard of care" (reference culture results and susceptibility testing).

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

• Sample Size for Clinical Test Set: 249 specimens.
• Data Provenance: Multi-site prospective investigation study at three US institutions. The data is prospective, collected from subjects whose routine care included blood culture testing.

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

The document does not explicitly state the number of experts or their specific qualifications (e.g., years of experience as a radiologist) used to establish the ground truth for the clinical test set. It mentions "reference culture results and susceptibility testing, the current standard of care" and that susceptibility testing was performed "in accordance with the CLSI documents M2-A9 and M100-S17." This implies that qualified laboratory personnel, following established clinical microbiology guidelines, performed these reference methods.

4. Adjudication Method for the Test Set:

The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1). The ground truth was established by "reference culture results and susceptibility testing, the current standard of care." This suggests a direct comparison against the established laboratory gold standard, rather than a consensus among multiple human readers.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly done in the context of comparing human readers with and without AI assistance. The study compares the device's performance directly against "reference culture results and susceptibility testing," which is the established standard of care for identifying bacterial infections. The device is an automated nucleic acid amplification test, not an AI assistance tool for human interpretation.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone performance study was conducted. The Cepheid Xpert™ MRSA/SA Blood Culture Assay is an automated device that performs sample preparation, amplification, and real-time detection without human intervention once the sample is loaded. The "Overall Results" section (Page 12) directly reports the device's performance in identifying MRSA and SA specimens relative to culture. This refers to the algorithm's performance without a human in the loop for interpretation.

7. The Type of Ground Truth Used:

The ground truth used for the clinical study was based on:

• Reference Culture Results: This involves standard microbiological culture techniques to isolate and identify organisms.
• Susceptibility Testing: Performed in accordance with CLSI documents (M2-A9 and M100-S17) to determine methicillin/oxacillin resistance, using cefoxitin as a surrogate.

This represents established microbiological laboratory standards, often considered the "gold standard" for pathogen identification and antimicrobial susceptibility.

8. The Sample Size for the Training Set:

The document does not explicitly state a separate "training set" for the clinical validation studies in the way one might for a machine learning algorithm. For analytical studies, various strains were tested:

• Analytical Inclusivity Study on CDC Staphylococcus aureus Specimens: 25 Staphylococcus aureus strains.
• Analytical Inclusivity Study on Expanded Panel of Staphylococcus aureus Specimens: 121 additional Staphylococcus aureus strains.
• "Empty Cassette Variants" Study: 22 Staphylococcus aureus isolates.
• Analytical Limit of Detection: Replicates of 20 for 6 MRSA isolates and 3 MSSA isolates.
• Cross-reactivity Study: 105 strains (98 ATCC, 7 NARSA).

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

For the analytical "training" (or rather, validation) sets mentioned above, the ground truth was established through:

• Bacterial strain identification, PFGE type, and SCCmec type determined by the CDC (for CDC specimens).
• Catalase, tube coagulase, and Gram stain for characterizing discordants in the expanded panel study.
• Methicillin susceptibility assessed by disk diffusion using a cefoxitin disk.
• Known characteristics and genetic information of the cultured strains (e.g., MRSA, SA, Cfu/test).

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The Cepheid Xpert MRSA/SA Skin and Soft Tissues Infection Assay (Xpert MRSA/SA SSTI Assay) performed in the GeneXpert® Dx System is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI Assay is indicated for use in conjunction with other laboratory tests such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI Assay is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g. Gram negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the LoD of the assay.

The Cepheid Xpert MRSA/SA Skin and Soft Tissue Infection Assay (Xpert MRSA/SA SSTI Assay) is a rapid, automated DNA test for simultaneously detecting MRSA and SA directly from skin and soft tissue specimen is collected on a double swab, which is placed in a tube containing elution reagent. Following brief vortexing, the eluted matcrial 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 MRSA/SA 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 fully-automated and completely integrated. The GeneXpert® System consists of a GeneXpert instrument, personal computer, and the multi-chambered fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of MRSA and SA in approximately 50 minutes. Each system has 1 to 16 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection. The Xpert MRSA/SA Assay includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA Assay detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for MecA-Mediated Oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site. The test includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. 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 study details for the Cepheid Xpert MRSA/SA SSTI Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" numerical targets in a table format. Instead, it presents performance data (Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA)) in comparison to a reference culture method. These performance metrics implicitly serve as the acceptance criteria for regulatory approval.

Implicit Acceptance Criteria (Performance Targets) and Reported Device Performance

Note: The document states "The test results showed the Xpert MRSA/SA SSTI to be substantially equivalent to the current standard of care" and explicitly lists performance data, which are interpreted as meeting implicit acceptance criteria for regulatory clearance.

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

• Clinical Test Set Sample Size: A total of 848 specimens were collected from patients.
  • No Antibiotic Use (within 3 weeks): 441 subjects
  • Unknown Antibiotic Use (within 3 weeks): 200 subjects
  • Known Antibiotic Use (within 3 weeks): 207 subjects
• Data Provenance: The study was a multi-site prospective investigation conducted at four US institutions. This means the data was collected specifically for this study in a forward-looking manner, and from within the United States.

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

The document states that the reference culture method involved "confirmation of presumptive positive colonies was performed with catalase, tube coagulase, and Gram stain. MecA-Mediated Oxacillin resistance was tested by disk diffusion test using a 30 µg cefoxitin disk and cutoff of 21/22 mm." This implies standard microbiology laboratory procedures were followed by trained laboratory personnel.

• Number of Experts: Not explicitly stated as a specific number of individual "experts."
• Qualifications of Experts: Implied to be trained microbiologists or clinical laboratory technologists experienced in performing and interpreting standard microbiology culture, identification (catalase, coagulase, Gram stain), and susceptibility testing (cefoxitin disk diffusion). The reference culture was performed at a "centralized laboratory," suggesting specialized expertise.

4. Adjudication Method for the Test Set

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the ground truth of the clinical test set. The "reference culture" is treated as the definitive ground truth, performed at a centralized laboratory following established protocols. Implicitly, any discrepancies would be resolved by the standard operating procedures of that centralized laboratory, but a multi-reader adjudication process is not detailed.

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

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an automated in vitro diagnostic test (Nucleic Acid Amplification Test) performed on a GeneXpert Dx System, designed to provide results directly without requiring human interpretation of complex images or data that AI might otherwise augment for human readers. Its comparison is against a reference culture method.

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

Yes, a standalone performance study was done. The Xpert MRSA/SA SSTI Assay is an automated system (algorithm only without human interpretation in the loop beyond sample preparation and loading). The "Performance Characteristics" and "Clinical Performance" sections detail the direct comparison of the Xpert MRSA/SA SSTI Assay's results against the reference culture method, making it a standalone evaluation.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical performance study was reference microbiology culture and susceptibility testing. This involved:

• Enrichment in trypticase soy broth.
• Streaking onto plates with and without cefoxitin.
• Sub-culturing presumptive colonies onto blood agar.
• Confirmation of positive colonies with catalase, tube coagulase, and Gram stain for Staphylococcus aureus (SA) identification.
• MecA-Mediated Oxacillin resistance tested by disk diffusion using a 30 µg cefoxitin disk and a cutoff of 21/22 mm for MRSA identification.

8. The Sample Size for the Training Set

The document does not explicitly state a sample size for a "training set" in the context of machine learning (AI). This device is a real-time PCR assay, which is a molecular diagnostic method based on known biological reactions, not typically developed using machine learning algorithms that require distinct training sets.

However, if "training set" is interpreted more broadly as data used for analytical development and optimization, the document mentions extensive analytical studies:

• Analytical Inclusivity Study on CDC Staphylococcus aureus Specimens: 21 MRSA strains and 3 MSSA strains (total 24 strains).
• Analytical Inclusivity Study on Expanded Panel of Staphylococcus aureus Specimens: 121 additional Staphylococcus aureus strains (78 MRSA, 43 SA).
• Evaluation of Empty Cassette Variants: 22 isolates.
• Limit of Detection Studies: Multiple individual isolates (6 MRSA, 3 SA) each tested with 20 replicates at various concentrations.
• Linearity Studies: SA and MRSA isolates tested across ten-fold serial dilutions.
• Cross-reactivity Study: 105 strains (various bacteria and yeast).
• Evaluation of BORSA Strains: 7 BORSA strains.

These analytical tests provide the data and parameters for the assay's design and demonstrate its performance characteristics, which is analogous to the role of a training set for algorithm development, even though it's a traditional molecular test.

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

For the analytical studies (which can be considered analogous to a training/development phase for a molecular assay), the ground truth was established through:

• Confirmed Identification: Using CDC-reported strains, phylogenetically characterized strains, ATCC cultures, and NARSA strains.
• Phenotypic Testing: Catalase, tube coagulase, Gram stain, and cefoxitin disk diffusion (for oxacillin resistance) were used to characterize discrepant results and confirm the identity and resistance profile of isolates.
• Genetic Characterization: PFGE for USA types and SCCmec typing for MRSA strains provided detailed genetic ground truth.
• Known Concentrations: For LoD and linearity studies, bacterial concentrations were carefully quantified (CFU/sample) to establish precise analytical ground truth.

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The Cepheid® Xpert MRSA Assay performed on the GeneXpert® Dx System (Xpert MRSA) is a qualitative in vitro diagnostic test designed for rapid detection of methicillinresistant Staphylococcus aureus (MRSA) from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA DNA. The Xpert MRSA Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. The Xpert MRSA Assay is not intended to diagnose MRSA nor to guide or monitor treatment for MRSA infections. Concomitant cultures are necessary only to recover organisms for epidemiological typing or for further susceptibility testing.

The Cepheid Xpert methicillin-resistant Staphylococcus aureus (MRSA) Assay is a rapid, automated DNA test for detecting MRSA directly from nasal swab specimens of patients in a healthcare setting. The Xpert MRSA performs real-time, multiplex polymerase chain reaction (PCR) for detection of DNA after an initial manual sample elution step. In this platform, additional sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The system includes a GeneXpert® System, which consists of an instrument, personal computer, and disposable fluidic cartridges that are designed to complete sample preparation and real-time PCR for detection of MRSA in about 75 minutes. Each instrument contains 2-4 randomly accessible modules that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert MRSA Assay includes reagents for the detection of the target MRSA. The primers and probes in the Xpert MRSA Assay detect the presence of the staphylococcal cassette chromosome (SCC) inserted into the SA chromosomal attB site.

The test includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. 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 study details for the Cepheid Xpert MRSA Assay, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the comparison to the reference culture method and the predicate device. The primary performance metrics are Sensitivity and Specificity.

Note: The predicate device (IDI-MRSA™ Assay) had a reported sensitivity of 83.3% and specificity of 94.4% in the same Cepheid Clinical study using the same reference method. Its package insert (using a different enriched culture method) reported 92.5% sensitivity and 96.4% specificity. The Xpert MRSA Assay met the implicit criterion of performing as well as or better than the predicate in the comparative study.

Study Details

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

   • Test Set Sample Size: 1077 eligible subjects (patients).
   • Data Provenance: A multi-center prospective investigation study at seven institutions. The document does not explicitly state the country of origin, but given the submission is to the FDA, it is highly likely the study was conducted within the United States.

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

   • The ground truth was established by a centralized laboratory culture testing, which is a laboratory method, not directly dependent on expert interpretation in the same way as, for example, a medical imaging study. The document does not specify the number of laboratory personnel or their specific qualifications, but it implies standard microbiological laboratory practices were followed.

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

   • None in the context of human reader adjudication. The ground truth was established by laboratory culture methods (enriched culture method, and for secondary comparison, direct culture method). Presumptive positive colonies from culture methods were confirmed with a tube coagulase test and Gram stain, which are standard laboratory confirmation procedures.

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 comparative effectiveness study involving human readers with and without AI assistance. This study evaluated an automated diagnostic assay (Xpert MRSA) against a reference culture method and a predicate device (IDI-MRSA™). It assesses the performance of the device itself, not an AI assisting human readers.

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

   • Yes, this was essentially a standalone performance study. The Xpert MRSA Assay is an "automated DNA test" where "additional sample preparation, amplification, and real-time detection are all fully automated and completely integrated." The reported performance characteristics (Sensitivity, Specificity, PPV, NPV) are for the assay's output directly compared to the reference standard. While laboratory personnel operate the system, the diagnostic result itself is generated by the instrument/algorithm without human interpretative input beyond loading the sample and reading the final result.

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

   • The primary ground truth used was the enriched culture method performed at a centralized laboratory, which is considered the "most sensitive culture method" for detecting MRSA from nasal swabs. A secondary comparison was made against a "direct culture method." This is a laboratory-based gold standard.

7. The sample size for the training set:

   • The document describes a clinical study for validation, not explicitly a separate training set. For analytical sensitivity (Limit of Detection), a study was performed with MRSA cells at seven concentrations (0, 5, 10, 20, 40, 60, and 80 CFU/swab) to determine the LoD. This is an analytical experiment, not a clinical training set in the sense of machine learning algorithms. The commercial assay itself is not described as involving a machine learning model that requires a distinct "training set" of clinical data for its development in the way an AI diagnostic often does.

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

   • This question is less applicable as the device is a nucleic acid amplification test (NAAT) and not a machine learning-based AI device that typically requires a large "training set" of labeled clinical data. The analytical sensitivity (LoD) was established using controlled dilutions of MRSA type II cells to define the assay's detection limit, not a clinical ground truth for a training set.

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