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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 Xpert® SA Nasal Complete test performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test designed for detection of Staphylococcus aureus (SA) and methicillin-resistant 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/SA DNA. The Xpert SA Nasal Complete test is intended to aid in the prevention and control of MRSA/SA infections in healthcare settings. The Xpert SA Nasal Complete test is not intended to diagnose, guide or monitor treatment for MRSA/SA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA/SA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The Xpert SA Nasal Complete 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 nasal 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 different, uniquely-labeled chamber of the disposable fluidic cartridge (the Xpert SA Nasal Complete cartridge). The user initiates a test from the user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into the GeneXpert® Instrument System platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of S. aureus (including MRSA) DNA.

In the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx Systems, GeneXpert® System with Touchscreen, and GeneXpert® Infinity Systems), sample preparation, amplification, and real-time detection are all fully-automated and completely integrated. The platform requires 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.

Depending on the specific instrument, the GeneXpert® Instrument Systems may contain 1–80 modules, each of 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 I-CORE thermocycler for performing real-time PCR and detection.

The Xpert SA Nasal Complete test kit includes reagents for the simultaneous detection of SA and MRSA targets. The primers and probes provided in the Xpert SA Nasal Complete test kit detects 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 Xpert SA Nasal Complete cartridge 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 dve stability.

The Xpert SA Nasal Complete test performed on the GeneXpert® Instrument Systems provides results in approximately 65 minutes.

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

Acceptance Criteria and Study Details for Xpert SA Nasal Complete (K243070)

This submission (K243070) seeks to modify the existing Xpert SA Nasal Complete device (K100822) to include the GeneXpert® Infinity Systems instruments in its compatible instrument family. The study described focuses on demonstrating equivalent performance on the new instrument systems.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state quantitative acceptance criteria for clinical performance (e.g., sensitivity, specificity) for this specific 510(k) submission (K243070). This is likely because the core assay and its clinical performance were extensively validated and accepted during the original clearance of K100822, and this submission focuses on adding new compatible instruments while demonstrating equivalent performance.

However, based on the studies conducted, the implicit acceptance criteria relate to demonstrating equivalent performance on the new GeneXpert Infinity Systems compared to the predicate device run on previously cleared GeneXpert systems.

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

The document describes two types of studies impacting the acceptance criteria:

• Prepared Cartridge Hold Time Study:

  • Sample Size: Not explicitly stated. The study involved verifying a maximum acceptable hold time. This would typically involve testing multiple samples at various time points within and beyond the proposed hold time.
  • Data Provenance: Not specified, but likely laboratory-based controlled studies.

• Functional Testing:

  • Sample Size: Not explicitly stated. The study used "both contrived positive (MRSA added to negative matrix) and negative (negative matrix only) samples." It also notes "Each target of the Xpert SA Nasal Complete test was analyzed." This implies a sufficient number of samples to represent positive and negative outcomes for both SA and MRSA targets.
  • Data Provenance: Not specified, but based on the description of "contrived positive" and "negative matrix," it is a retrospective laboratory-based study using controlled samples. The materials used (e.g., negative matrix) would be laboratory-sourced.

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

Not Applicable for this particular submission. The ground truth for the functional testing was established by the nature of the contrived samples:

• Contrived positive samples: MRSA added to negative matrix, meaning the positive status was known and intentionally created.
• Negative samples: Negative matrix only, meaning the negative status was known and intentionally created.

This type of study does not require human expert interpretation to establish the ground truth of the samples.

4. Adjudication Method for the Test Set

Not Applicable. As the ground truth was established by the deliberate creation of contrived positive and negative samples, no adjudication by human experts was required to determine the true status of the samples.

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

No, a MRMC comparative effectiveness study was not done. This submission (K243070) is for a device modification to expand compatible instruments rather than to assess human reader improvement with AI assistance. The device in question is an automated in vitro diagnostic test that provides a qualitative result (positive/negative) directly, without requiring human interpretation for its primary output.

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

Yes, a standalone performance study was effectively done. The Xpert SA Nasal Complete test is an automated nucleic acid amplification test (NAAT). The "functional testing" described assesses the device's ability to correctly identify contrived positive and negative samples when run on the new GeneXpert Infinity Systems instruments, independently determining the presence or absence of the target DNA. This is a standalone performance evaluation of the device itself.

7. The Type of Ground Truth Used

The ground truth used for the functional testing was established by the deliberate creation of contrived samples. This includes:

• Contrived positive samples: MRSA added to a negative matrix, where the presence of the pathogen (MRSA) is known and controlled.
• Negative samples: Negative matrix only, where the absence of the pathogen is known and controlled.

This methods ensures a definitive and known ground truth.

8. The Sample Size for the Training Set

Not applicable/Not explicitly stated. The Xpert SA Nasal Complete test is a PCR-based diagnostic with specific primers and probes for target DNA. It is not typically a machine learning/AI model that undergoes "training" in the traditional sense with a distinct training set. The assay's design (primers, probes, thermocycling protocols) would have been developed and optimized during its initial development, but this isn't referred to as a "training set" in the context of this type of device. The current submission is a modification focusing on instrument compatibility.

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

Not applicable. As noted above, the concept of a "training set" and its associated ground truth establishment is not directly relevant to this PCR-based diagnostic device in the context of this submission. The assay's analytical performance and target specificity are inherent to its biochemical design.

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The ARIES® MRSA Assay is an integrated, real-time, polymerase chain reaction (PCR) based qualitative in vitro diagnostic test for the direct detection of methicillinresistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization.

The ARIES® MRSA Assay is intended to aid in the prevention and control of MRSA infections in healthcare settings.

The assay is not intended to guide, diagnose, or monitor treatment for MRSA infections. It is not intended to provide results of susceptibility to oxacillin/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 ARIES® MRSA Assay is indicated for use with ARIES® Systems.

The ARIES® MRSA Assay is a polymerase chain reaction (PCR)-based qualitative in vitro diagnostic test system which consists of the ARIES® System or the ARIES® M1 System with their included ARIES® Software, a sample processing tube, an assay-specific cassette, and an assay-specific protocol file. The ARIES® MRSA Assay cassette is a disposable, single-use cassette containing nucleic acid purification reagents, internal sample process control (SPC), and an assay-specific master mix capable of performing the designated assay on one sample. The ARIES® MRSA Assay cassette directly detects methicillin-resistant Staphylococcus aureus (MRSA) from nasal swabs in patients at risk of nasal colonization. Specifically, the ARIES® MRSA Assay cassette detects the methicillin resistance genes (mecA and mecC), Staphylococcus aureus orfX gene, the SCCmec junction region, and a DNA Sample Processing Control.

Nasal swab specimens are collected using the Liquid Amies Elution Swab (ESwab™) Collection and Transport System, or equivalent. A portion of the sample is transferred to the provided 2 mL ARIES MRSA Sample Processing Tube and vortexed. The processed sample is then transferred to the ARIES® MRSA Assay cassette.

The specimen is lysed and nucleic acid is extracted using an ARIES® instrument. An extractable sample processing control (SPC) target present in the ARIES® MRSA Assay cassette is processed with the specimen. The SPC controls for recovery of extracted nucleic acid, for inhibitory substances and for PCR reagent and instrument integrity. The Ct value of the SPC is designed to verify nucleic acid extraction, to identify PCR inhibition, if any, and verify proper function of the extraction system and real-time instrument.

The extracted nucleic acid and SPC are transferred via magnetic beads through the cassette to the ARIES® MRSA Assay lyophilized PCR reagents in the PCR tube that contain primer pairs and probes specific to mecA/mecC, orfX, SCCmec and the SPC sequence. Each probe is labeled with a distinct fluorophore and detected in a distinct channel of an ARIES® System. PCR amplification is performed and assay fluorescence is monitored. Hybridization of a fluorescently labeled probe to the amplified target results in the release of quenching and generation of fluorescence signal that is indicative of PCR generated amplicon. Following amplification, the reaction is heated to separate the fluorescentlabeled probe from the amplified target, a process that results in a decrease in the fluorescence signal. The reaction fluorescence is measured during this process and the temperature at which the change in fluorescence is the maximum is the Tm of the amplicon. The instrument fluorescence output is analyzed and test results are determined using the ARIES® System software and the ARIES® MRSA Assay protocol and run files. ARIES® MRSA Assay results may be reported from the ARIES® Software or from the optional SYNCT® Software.

Here's a breakdown of the acceptance criteria and study information for the ARIES® MRSA Assay, extracted from the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

Study Information

The provided document describes studies primarily for analytical and clinical performance.

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

   • Analytical Studies (Test Set):

     • Precision/Reproducibility: A blinded panel of 5 samples (2 MRSA strains at 1x LoD and 5x LoD, and 1 negative sample). Each tested in triplicate by 2 operators over 5 days (within-lab) or at 3 sites by 2 operators over 5 days (site-to-site). Total replicates: 30 per condition for within-lab, 90 per condition for site-to-site.
     • Limit of Detection (LoD): 20 replicates for each MRSA strain at suspected LoD concentration.
     • Inclusivity: 55 MRSA strains, each tested in triplicate. Total: 165 replicates.
     • Challenge Study: 16 MRSA strains with high MICs (some retested), 17 MRSA strains with low MICs (one retested), 4 BORSA strains, 16 empty cassette SA variants, 1 MRSE strain. Each tested in triplicate.
     • Cross-Reactivity: 99 organisms, each tested in triplicate with MRSA positive and negative samples.
     • Interfering Substances: 24 substances, each tested in triplicate with MRSA positive and negative samples.
     • Nasal Swab Equivalency: 1 MRSA strain at 3 concentrations, 1 negative sample. Each tested with two swab types, likely in replicates (e.g., 6/6 for MRSA positivity suggests 6 replicates for each condition).
     • Data Provenance: Not explicitly stated for analytical studies, but often performed in-house by the manufacturer. The strains used are from established collections (BEI, ATCC, ARLG, CDC AR Bank, Lyon University), suggesting controlled laboratory conditions.

   • Clinical Performance Study (Test Set):

     • Total specimens collected: 2254 nasal swab specimens.
     • Specimens meeting eligibility criteria and included in analysis: 1762 unique specimens.
     • Data Provenance: Prospective collection from August 2018 to February 2019 at four (4) geographically distinct clinical sites within the United States.

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

   • Analytical Studies: Ground truth was established by known organism concentrations and characteristics (e.g., specific MRSA strains, non-MRSA organisms, substances). No human experts are typically involved in establishing ground truth for these types of analytical tests.
   • Clinical Study: The "reference method" for ground truth was direct and enriched bacterial culture. This process is laboratory-based and while it involves trained microbiologists, it does not typically involve "experts" in the sense of clinical reviewers or adjudicators for each case. The results of the culture are the ground truth.

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

   • Analytical Studies: No adjudication method described as ground truth is based on known laboratory preparations and characteristics.
   • Clinical Study: No explicit adjudication method for the reference method (bacterial culture) is described. The culture results are presented as the definitive ground truth.

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 MRMC comparative effectiveness study was mentioned. The ARIES® MRSA Assay is a diagnostic molecular assay that directly detects target DNA; it is not an AI-based imaging or interpretive device that assists human readers.

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

   • Yes, the ARIES® MRSA Assay is a standalone diagnostic device. The performance data presented (sensitivity, specificity, agreement) directly reflects the algorithm's performance (the assay and its associated software) compared to the reference method (bacterial culture). There is no "human-in-the-loop" component for interpretation of the assay results, as the software determines whether the result is Positive, Negative, or Invalid based on predefined internal cut-offs.

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

   • Analytical Studies: Ground truth was based on known bacterial strains, concentrations, and characteristics (e.g., presence or absence of specific genes like mecA/mecC, orfX, SCCmec; known categories of non-MRSA organisms or interfering substances).
   • Clinical Study: Ground truth was established by direct and enriched bacterial culture for MRSA.

7. The sample size for the training set:

   • The document implies that an "Initial Assay Protocol File parameters were set during internal optimization and benchmarking studies" and "The final Assay Protocol File parameters were then established during internal verification studies using data from optimization, benchmarking and verification." However, specific sample sizes for these internal training or development phases are not explicitly provided in the 510(k) summary. The listed analytical studies are effectively "test sets" for various performance metrics, not necessarily for training.

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

   • As detailed above, specific training sets and their ground truth establishment methods are not explicitly described in this summary. For molecular diagnostic assays like this, the "training" typically involves empirical testing with known positive and negative controls, spiked samples, and characterized clinical samples during assay development to optimize PCR parameters, probe design, and define interpretation algorithms (Ct cut-offs, Tm windows). The "ground truth" during this development phase would be based on well-characterized strains and samples, similar to the analytical studies described.

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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 cobas® MRSA/SA Test on the cobas® 4800 system, is a qualitative in vitro diagnostic real-time PCR assay, for the direct detection of methicillin-resistant Staphylococus aureus (MRSA) and S.aureus (SA) DNA from nasal swabs to aid in the prevention and control of MRSA and SA infections in healthcare settings. The cobas® MRSA/SA Test is not intended to diagnose, guide or monitor treatment for MRSA or SA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA/SA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiology typing or for further susceptibility testing.

The Roche Molecular Systems (RMS) cobas® MRSA/SA Test utilizes real-time polymerase chain reaction (PCR) for the detection of Methicillin resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) DNA from nasal swab specimens collected in MSwab medium to aid in the prevention and control of MRSA and SA infections in healthcare settings.

The cobas® MRSA/SA Test contains two major processes: (1) automated sample preparation to extract nucleic acids from the nasal swab specimens; (2) PCR amplification of target DNA sequences using MRSA and SA specific primers, and real-time detection of cleaved fluorescentlabeled MRSA and SA specific oligonucleotide detection probes. An Internal Control (IC), containing unrelated randomized DNA sequence, is added to all samples prior to automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.

The MSwab Collection, Transport and Preservation System (Copan Flock Technologies S.r.1.) is used for specimen collection, transportation and storage of specimen for the cobas MRSA/SA Test.

The cobas® MRSA/SA Test utilizes six reagent kits:

1. cobas® 4800 MRSA/SA Amplification/Detection Kit
2. cobas® 4800 MRSA/SA Controls and Cofactor Kit
3. cobas® 4800 System Wash Buffer Kit
4. cobas® 4800 System Lysis Kit 1
5. cobas 4800 System Internal Control Kit 1
6. cobas® 4800 System Sample Preparation Kit

The cobas® 4800 System uses the cobas x 480 Instrument for sample preparation, and the cobas z 480 Analyzer for amplification and detection. Both the cobas x 480 Instrument and the cobas z 480 Analyzer are controlled by a computer workstation running the cobas® 4800 System Software.

Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided text:

Device Name: cobas® MRSA/SA Test

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of acceptance criteria in the sense of predefined thresholds for performance metrics. Instead, it reports the achieved performance from various studies. However, based on the studies conducted, we can infer the performance metrics that were evaluated and for which the device demonstrated acceptable results.

Here's a table summarizing the reported device performance, categorized by the relevant studies:

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

The primary clinical performance evaluation used the following test set:

• Sample Size: 2528 subjects, yielding 2504 evaluable results.
• Data Provenance:
  • Country of Origin: United States. Specimens were collected at six geographically diverse sites across the US.
  • Retrospective or Prospective: Prospective. Specimens were collected prospectively from eligible male and female subjects.

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 ground truth for the clinical test set was established by a reference laboratory that specialized in culture and molecular detection of methicillin-resistant MRSA and SA. However, it does not specify the number of individual experts or their specific qualifications (e.g., "radiologist with 10 years of experience"). It implies that the laboratory's established practices for culture and molecular confirmation (including non-selective direct and enrichment culture, Gram-stain, latex agglutination, Kirby-Bauer cefoxitin disc diffusion for MRSA, and laboratory developed PCR assay for femA and mecA genes) served as the "expert" ground truth.

4. Adjudication Method for the Test Set

The ground truth was established by comparing the cobas® MRSA/SA Test results against a combined direct and enrichment culture (reference method).

• Discrepant Analysis: For samples with discordant results between the cobas® MRSA/SA Test and the combined direct and enrichment culture, a second, FDA-cleared nucleic acid amplification test (NAAT) and a non-selective direct and enrichment culture were used for further analysis.
• Control Samples: A randomly selected subset of samples with concordant results were also included in this discrepant analysis as controls.

This method resembles a 2+1 adjudication model in spirit for discordant cases, where the initial test (cobas® MRSA/SA) results are compared against a reference standard (combined culture), and any discrepancies are resolved by a third, independent method (second NAAT and non-selective culture).

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

No, a MRMC comparative effectiveness study was not done. The device being evaluated is an in vitro diagnostic real-time PCR assay for direct detection of bacterial DNA, not an imaging device that requires human interpretation. Therefore, the concept of "human readers" or "AI assistance" in the context of improving human reader performance is not applicable to this device.

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

Yes, the primary clinical performance study (Section 5.2) and all analytical studies (Section 4) represent standalone algorithm-only performance. The cobas® MRSA/SA Test is an automated diagnostic assay that reports qualitative results (Positive/Negative for MRSA/SA) based on real-time PCR amplification and detection. The interpretation of these results is done by the cobas 4800 System Software, which then reports out the final results (Section 6.1.2). Human involvement is in specimen collection, loading, and result interpretation, but the core detection and qualitative output is automated by the device itself.

7. The Type of Ground Truth Used

The ground truth used for the clinical performance evaluation was a combined microbiological culture method:

• Combined Direct and Enrichment Culture: This involved both direct plating onto selective and differential chromogenic media, and enrichment culture in tryptic soy broth.
• Confirmatory Tests: Suspect isolates from these cultures were further identified by Gram-stain, latex agglutination, and for MRSA, Kirby-Bauer cefoxitin disc diffusion.
• Discrepant Analysis: For discordant results, a second FDA-cleared NAAT and non-selective direct and enrichment culture were used, with identification of isolates confirmed using a laboratory developed PCR assay for femA and mecA genes.

This represents a robust, multi-faceted ground truth derived from established microbiological techniques and molecular confirmation.

8. The Sample Size for the Training Set

The document does not explicitly state the sample size for a "training set."
Medical device submissions for in vitro diagnostics like this PCR assay typically focus on analytical validation (LOD, specificity, precision) and clinical validation with an independent test set. The algorithms for interpreting PCR cycle thresholds are generally fixed and based on scientific principles rather than being "trained" on a large dataset in the same way machine learning models are. However, the analytical studies used various isolates to define parameters and confirm performance:

• Analytical Sensitivity (LOD): 2 MRSA culture isolates and 1 SA culture isolate for initial LOD, and 35 additional MRSA and 5 additional SA culture isolates for genotype LOD verification.
• Geographical Inclusivity: 281 MRSA and 85 SA isolates from diverse geographical locations.
• Precision: 2 MRSA culture isolates and 1 SA culture isolate.
• Analytical Specificity: 43 CoNS/MR-CoNS organisms, 93 non-MRSA/SA microorganisms and human cells, 2 SA isolates, 10 BORSA isolates, and 16 mecA dropouts.

These isolates were used to characterize the device's analytical performance across various conditions and strains, which could be considered akin to "training" or extensive characterization data, but not in the machine learning sense of model optimization.

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

As noted above, there isn't a "training set" in the machine learning context described. The ground truth for the various analytical studies (e.g., sensitivity, specificity, inclusivity) was established through:

• Quantified Culture Isolates: For LOD and precision studies, specific MRSA and SA culture isolates with known concentrations (CFU/swab) were used.
• Characterized Clinical Isolates: For genotype LOD and inclusivity studies, isolates were selected based on known characteristics such as SCCmec type, spa type, PFGE type, MIC values, and geographical origin.
• Established Microbiological Methods: For analytical specificity, cultures of known microorganisms (both targets and non-targets) were used, often from ATCC or other reference collections, and their identity was presumably confirmed by standard microbiological identification techniques.

Essentially, for these analytical studies, the "ground truth" was defined by standard reference strains and well-characterized clinical isolates, obtained and verified through established microbiology laboratory practices.

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The BD MAX™ MRSA XT assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection of methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ MRSA XT assay is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose MRSA infections nor guide or monitor treatment for MRSA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The BD MAX™ System and the BD MAX™ MRSA XT assay are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, extraction reagents, and sample buffer tubes. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, and target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test results. A test result may be called as MRSA NEG, MRSA POS or MRSA UNR (Unresolved)] based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.

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

Acceptance Criteria and Device Performance Study for BD MAX™ MRSA XT Assay

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria for all performance analytical and clinical metrics. However, it presents the results of various studies which implicitly define the performance achieved. For the purpose of this response, I've inferred "acceptance criteria" from the satisfactory performance reported by the manufacturer. The clinical performance is compared against a "Reference Method" (Direct/Enriched Culture).

• Moderate Positive (MP): 100% agreement
• Low Positive (LP): 97.9% agreement
• High Negative (HN): 60.4% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Reproducibility (Site-to-Site) | High agreement for positive/negative samples, reasonable for low positives. | - MP: 100% agreement
• TN: 100% agreement
• LP: 96.7% agreement
• HN: 63.3% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Reproducibility (Lot-to-Lot) | High agreement for positive/negative samples, reasonable for low positives. | - MP: 100% agreement
• TN: 100% agreement
• LP: 96.7% agreement
• HN: 61.1% agreement (No specific acceptance criterion defined for this category, but reported.) |
  | Analytical Sensitivity (LoD) | Detection of MRSA strains at low concentrations. | LoD ranged from 64 to 343 CFU/swab at 95% positivity for various MRSA genotypes. |
  | Analytical Inclusivity | Detection of a wide range of MRSA strains and types. | All 77 MRSA strains (across various MREJ genotypes, SCCmec types, PFGE types, geographic origins, and including VRSA/VISA) were detected at 2-3x LoD. |
  | Analytical Specificity | No detection of non-target organisms (MSSA, CoNS, CoPS, other species, viruses). | - Empty cassette variant MSSA: 15/15 MRSA NEG
• Non-staphylococcal species (57 strains): 57/57 MRSA NEG
• Coagulase-Negative/Positive staphylococcal strains (45 strains): 45/45 MRSA NEG
• MSSA (50 strains): 50/50 MRSA NEG
• Viruses (17 species): 17/17 MRSA NEG |
  | Interfering Substances | No interference from common nasal substances/microorganisms. | No reportable interference from 28/29 tested substances/microorganisms. Tobramycin showed reportable interference at 4.5 x 10^-3 g/swab. |
  | Carryover/Cross-Contamination | Low rate of false positives due to carryover. | 3 false positive results out of 210 expected negative results (1.4%). |
  | Clinical Sensitivity (vs. Reference Method) | High agreement for positive specimens. | 93.1% (95% CI: 88.1%, 96.1%) |
  | Clinical Specificity (vs. Reference Method) | High agreement for negative specimens. | 97.5% (95% CI: 96.8%, 98.1%) |
  | Positive Predictive Value (PPV) (vs. Reference Method) | Reasonable PPV given prevalence. | 73.2% (95% CI: 67.8%, 78.3%) |
  | Negative Predictive Value (NPV) (vs. Reference Method) | High NPV. | 99.5% (95% CI: 99.1%, 99.7%) |
  | Positive Percent Agreement (vs. Direct Culture) | High agreement for positive specimens. | 96.5% (95% CI: 92.0%, 98.5%) |
  | Negative Percent Agreement (vs. Direct Culture) | High agreement for negative specimens. | 96.9% (95% CI: 96.1%, 97.6%) |
  | Unresolved Rate (Initial) | Low initial unresolved rate. | 0.6% (16/2399) |
  | Unresolved Rate (After Repeat) | Very low unresolved rate after repeat. | 0.1% (2/2398) |

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

• Clinical Performance Study:

  • Test Set Size:
    • Reference Method comparison: 2352 compliant specimen results used for sensitivity/specificity calculations. A total of 2451 specimens were initially enrolled, with 94 noncompliant and 5 non-reportable PCR results removed.
    • Direct Culture comparison: 2391 compliant specimen results used for positive/negative percent agreement. A total of 2451 specimens were initially enrolled, with 54 noncompliant and 6 non-reportable PCR results removed.
  • Data Provenance: Multi-site prospective investigational study. Specimens were collected from patients at risk for nasal colonization from three investigational centers (countries not explicitly stated but typically within the regulatory region, e.g., North America for an FDA submission).

• Analytical Studies (e.g., Sensitivity, Specificity, Inclusivity, Precision, Reproducibility): These studies used prepared samples (simulated nasal matrix, bacterial suspensions) and well-characterized strains from public collections and clinical isolates. The Analytical Inclusivity study explicitly states that 77 MRSA strains were from 27 countries.

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

• The ground truth for the clinical performance study test set was established using a Comparative Reference Method consisting of direct culture complemented by enriched culture.
• The document does not explicitly state the number of experts or their specific qualifications (e.g., microbiologists, lab technologists) involved in performing or interpreting these culture methods at the clinical sites. However, it details the laboratory procedures: presumptive S. aureus colonies on selective media, subculture to Blood Agar, identification confirmation with an agglutination test, and methicillin-resistance confirmation by Cefoxitin disk diffusion susceptibility testing. For enriched culture, TSB 6.5% NaCl broth was used, followed by inoculation of chromogenic medium and BA plates, with MRSA confirmation as described. This implies trained laboratory personnel using standardized microbiological techniques.

4. Adjudication Method for the Test Set

• The document describes a "Reference Method" (Direct/Enriched Culture) as the independent ground truth standard.
• For discordant results between the BD MAX™ MRSA XT assay and the Reference Method in the clinical study, further investigation was performed.
  • "12 of 54 MRSA False Positive BD MAX™ MRSA XT specimens were found to be MRSA POS after repeat of Reference Method."
  • "5 of 11 MRSA False Negative BD MAX™ MRSA XT specimens were found to be MRSA NEG after repeat of Reference Method."
  • This indicates a form of adjudication by repeat testing using the Reference Method (culture) for discordant clinical samples. It is not a 2+1 or 3+1 expert consensus model, but rather re-evaluation using the established gold standard.

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, an MRMC comparative effectiveness study involving human readers/interpreters with and without AI assistance was not done.
• This device is an automated in vitro diagnostic test (NAAT) for direct detection of MRSA DNA. Its results are automatically interpreted by the BD MAX™ System software (MRSA NEG, MRSA POS, MRSA UNR).
• The comparison is between the automated device performance and traditional culture methods, not between human performance with and without AI assistance.

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

• Yes, a standalone performance evaluation was done.
• The entire premise of the analytical and clinical performance studies is to assess the BD MAX™ MRSA XT assay's performance as an automated qualitative in vitro diagnostic test. The device generates "MRSA NEG, MRSA POS or MRSA UNR (Unresolved)" results automatically.
• The "Substantial Equivalence" section explicitly states that the "Interpretation of Test Results" is "Automated (Diagnostic software of BD MAX™ System)."
• The clinical performance section directly compares "BD MAX™ MRSA XT Assay" results to the Reference Method and Direct Culture.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

• Clinical Performance Study: The ground truth for clinical performance was established by a Comparative Reference Method consisting of direct culture complemented by enriched culture. This is a laboratory-based microbiological gold standard.
• Analytical Performance Studies (e.g., LoD, Inclusivity, Specificity): The ground truth was established by known concentrations of characterized bacterial strains (e.g., CFU/swab), often from controlled laboratory settings or public reference collections.

8. The Sample Size for the Training Set

• The document does not provide details about a specific training set size for the BD MAX™ MRSA XT assay's algorithm.
• This is a molecular diagnostic test (PCR), and its performance is determined by the design and optimization of the primers and probes, and the reaction conditions, rather than a machine learning model that requires a "training set" in the conventional sense of AI. The analytical validation experiments (LoD, inclusivity, specificity) are used to characterize the assay's performance across a wide range of relevant targets and non-targets, ensuring its robustness and accuracy.

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

• As noted above, the concept of a "training set" in the context of a machine learning algorithm is not directly applicable here.
• The development and optimization of the PCR assay would involve:
  • Designing primers and probes to target specific MRSA DNA sequences (e.g., MREJ, mecA, mecC).
  • Testing against characterized bacterial strains with known genotypes, SCCmec types, and concentrations to ensure accurate detection and specificity.
  • Optimizing reaction parameters (e.g., temperatures, times, reagent concentrations).
• The ground truth for these developmental and optimization activities would be derived from established molecular biology techniques, bacterial genotyping, sequencing, and quantitative culturing methods to confirm the presence, identity, and concentration of target DNA.

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The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes realtime polymerase chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The BD MAX™ System and the BD MAX™ StaphSR assay are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, extraction reagents, and sample buffer tubes. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, and target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test results. A test result may be called as [SA NEG MRSA NEG (negative)], [SA POS, MRSA POS (MRSA positive)], [SA POS, MRSA NEG (SA positive)] or [SA UNR, MRSA UNR (Unresolved)] based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.

The BD MAX™ StaphSR assay is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs. The performance of the device was evaluated in both analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the BD MAX™ StaphSR assay are primarily based on achieving certain levels of sensitivity and specificity when compared against a reference method (direct culture complemented by enriched culture). The document details the reported performance for MRSA and SA detection.

Acceptance Criteria and Reported Performance for BD MAX™ StaphSR Assay

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

For the clinical performance studies, a total of 2451 specimens were enrolled. After excluding non-compliant specimens, 2354 specimen results were used to determine the clinical performance against the Reference Method, and 2393 specimen results were used for comparison against Direct Culture.

The data provenance for the clinical study is prospective, collected from three geographically diverse investigational centers. The specific countries of origin for these centers are not explicitly stated.

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

The document does not explicitly state the number of experts used to establish the ground truth or their specific qualifications (e.g., radiologist with X years of experience). However, the ground truth was established using laboratory methods rather than expert interpretation of images or clinical assessments.

4. Adjudication Method for the Test Set

The adjudication method for the clinical test set involved a Comparative Reference Method consisting of direct culture complemented by enriched culture.

• For specimens negative for MRSA or SA by direct culture, enriched culture analysis was performed.
• Presumptive S. aureus colonies on chromogenic medium were subcultured onto Blood Agar (BA) for identification confirmation with an agglutination test.
• Methicillin resistance was confirmed by Cefoxitin disk (30 µg) diffusion susceptibility testing.
• Enrichment in Trypticase Soy Broth with 6.5% NaCl was carried out if MRSA or SA was not confirmed by initial direct culture.
• Turbid TSB 6.5% NaCl broth was used to inoculate additional chromogenic medium and BA plates, and MRSA confirmation followed the same procedure.
• Further investigation was performed on specimens with discordant results between the Reference Method and the BD MAX™ StaphSR assay. For MRSA, 12 of 54 false positive and 5 of 11 false negative BD MAX™ StaphSR specimens were re-evaluated by the Reference Method. For SA, 28 of 118 false positive and 23 of 52 false negative BD MAX™ StaphSR specimens were re-evaluated by the Reference Method.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, What was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

This information is not applicable as the BD MAX™ StaphSR assay is an automated in vitro diagnostic test (molecular assay) for direct detection of DNA. It does not involve "human readers" or AI assistance in the interpretation of results in the context of an MRMC study. The device provides an automated interpretation of results.

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

Yes, a standalone performance study was done. The BD MAX™ StaphSR assay is an automated instrument-based test that directly provides a qualitative result ([SA NEG MRSA NEG], [SA POS, MRSA POS], [SA POS, MRSA NEG], or [SA UNR, MRSA UNR]). The clinical performance data presented in Tables 10-17 directly reflect the standalone performance of the assay compared to the reference microbiological methods.

7. The Type of Ground Truth Used

The ground truth used for both the analytical and clinical studies was based on microbiological culture methods:

• Direct culture complemented by enriched culture for clinical performance evaluation.
• Cultured bacterial suspensions and well-characterized clinical isolates for analytical studies (e.g., LoD, inclusivity, specificity, competitive inhibitory effect).

8. The Sample Size for the Training Set

The document describes premarket studies for a diagnostic device. For such devices, there isn't typically a "training set" in the machine learning sense. Instead, development and optimization are performed using various analytical samples and potentially some initial clinical samples, followed by a robust validation (clinical performance) on an independent set. The details of any specific samples used for internal development or optimization (analogous to a training set) are not provided in this 510(k) summary. The provided sample sizes relate to the analytical validation and the final clinical validation dataset.

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

Given that this is a molecular diagnostic assay and not an AI/ML-based image interpretation product, the concept of a "training set" with ground truth established in that context is not directly applicable. If one were to consider the samples used for assay development and optimization as a "training set," their ground truth would have been established through known bacterial cultures (characterized strains, quantified suspensions) and potentially well-characterized clinical isolates with confirmed microbiological status (e.g., through traditional culture, biochemical tests, and susceptibility testing). However, specific details of such "pre-validation" ground truth establishment are not provided in this regulatory summary.

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MRSA/SA ELITe MGB® is a qualitative in vitro diagnostic test for the direct detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) using DNA purified from nasal swabs. MRSA/SA ELITe MGB® is intended to aid in the prevention and control of MRSA infections in healthcare settings. It is not intended to diagnose, guide or monitor MRSA infections, or provide results of susceptibility to oxacillin/methicilliin. A negative result does not preclude MRSA/SA (Staphylococcus aureus) nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

Special conditions for use statement(s): Prescription Use Only.

MRSA/SA ELITe MGB® is a real-time, multiplex polymerase chain reaction (PCR) assay for the in vitro qualitative detection of MRSA and SA DNA extracted from human nasal swab samples. In this system, sample preparation and amplification/real-time detection are completed on separate instruments. Sample processing is completed on the bioMérieux NucliSENS® easyMAG® instrument with bioMérieux NucliSENS Nucleic Acid Extraction Reagents according to the manufacturer's instructions. Following processing, the extracted sample is placed in the well of a 96 well plate to which "monoreagent" is added. The monoreagent contains the primers and probes for the genes of interest and the internal control combined with master mix. The assay is performed on an Applied Biosystems 7500 FAST Dx System that consists of the 7500 FAST Dx instrument, a personal computer, 96-well plates and seals. The total system run time is 150 minutes consisting of 60 minutes for sample processing and about 90 minutes for the real time amplification and detection steps. The instrument never comes into contact with any fluids within the 96-well plate. Each disposable plate is intended to test up to 96 samples, controls or any mixture thereof. The 96-well plates are not re-usable and are specific to the system. The kit contains enough reagents for 100 reactions. One positive and one negative control are required for each PCR run; a Negative Processing Control and a Positive Processing Control are recommended to be run in each extraction run. The design of the assay includes systems to identify both the gene responsible for methicillin resistance and for a conserved portion of a gene unique to S. aureus. Thus, for a true "MRSA," both targets will be identified in roughly equal proportions. Results are determined by using an algorithm that compares output. Cq, from the cycler (called Ct in the output from the cvcler.) The algorithm is implemented for automatic results determination by analyzing the output Cq with ELITe MGB® software.

The provided text describes the acceptance criteria and the study that proves the performance of the MRSA/SA ELITe MGB® Software, which is a software component of the overall MRSA/SA ELITe MGB® test system. It's important to note that this 510(k) submission (K132468) is specifically for the software that automates the calling algorithm, not the entire diagnostic test kit, which was previously cleared under K112937. Therefore, most performance studies (analytical sensitivity, reactivity, detection limit, reproducibility, carry-over/cross-contamination, clinical studies) are referenced back to the original K112937 submission as they are not affected by the software change.

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

1. Table of Acceptance Criteria and Reported Device Performance

For this specific 510(k) (K132468), the primary acceptance criterion is the concordance of results generated by the new automated software with the results generated by the previously cleared manual calling algorithm.

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

The document states, "In accordance with guidance received from FDA in Q120176, the original data from K112937 was recalculated using ELITe MGB software."

• Sample Size for Test Set: The specific sample size used for the recalculation is not explicitly stated in this document but is referred to as "the original data from K112937." To determine the exact sample size, one would need to review the K112937 submission.
• Data Provenance: The data is "original data from K112937," implying it was generated during the studies for the initial clearance of the MRSA/SA ELITe MGB® assay. The document doesn't specify the country of origin of the data or whether it was retrospective or prospective, though diagnostic assay validation studies typically involve prospective collection of samples or a combination of prospective and banked (retrospective) samples.

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

This specific submission (K132468) is evaluating the concordance of software interpretation with a manual interpretation algorithm from K112937, rather than establishing a new ground truth against a clinical "gold standard." Therefore, the concept of "experts establishing ground truth" in the traditional sense doesn't directly apply here. The manual calling algorithm itself represents the established interpretation logic from the previous clearance.

4. Adjudication Method for the Test Set

Not applicable for this type of software validation study. The study involved a direct comparison of algorithmic output with the output of a previously defined manual algorithm. There was no "adjudication" between different human interpretations or human and AI interpretations in this specific study.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done for this software submission. The purpose of this submission was to validate the automated software's agreement with the manual algorithm, not to compare human performance with or without AI assistance.

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

Yes, this study is inherently a standalone performance evaluation of the algorithm. The software (algorithm) processes the raw data and determines results automatically. The evaluation compares these automated results directly against the results that would have been obtained by applying the manual algorithm from the predicate device's labeling to the same raw data. There is no human "in the loop" performing interpretation for this part of the study; the software automates the interpretation step.

7. The Type of Ground Truth Used

The "ground truth" for this software validation study is the results derived from the manual calling algorithm as described in the labeling of the predicate device (K112937). It's a comparison to an established interpretation method, not directly to pathology, outcomes data, or expert consensus in the typical sense.

8. The Sample Size for the Training Set

The document states, "The development of the software is in compliance with the requirements of the Guidance. The performance of the software has been validated." However, it does not explicitly mention a separate "training set" size for the ELITe MGB® software development. Software for diagnostic devices generally undergoes rigorous development and verification, which might involve internal testing with various data, but the specific size of such an internal training set is not provided here. The critical performance evaluation (concordance) was done on the original data from K112937.

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

Given that a specific "training set" size is not detailed for this software validation, the method for establishing its ground truth is also not elaborated. For the underlying MRSA/SA ELITe MGB® assay (K112937), the ground truth for clinical performance would have been established through methods like confirmatory microbiology cultures, potentially with additional molecular or phenotypic characterization for MRSA distinction, which are standard for such diagnostic tests. The software's "training" (development) would have been guided by the established rules of the manual calling algorithm.

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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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