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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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