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The Xpert Xpress Strep A test, performed on the GeneXpert Xpress System, is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A B-hemolytic Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Xpert Xpress Strep A test can be used as an aid in the diagnosis of Group A Streptococcal pharvngitis. The assay is not intended to monitor treatment for Group A Streptococus infections.

The Xpert Xpress Strep A test is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of Streptococcus pyogenes from throat swab specimens from patients with signs and symptoms of pharyngitis.

The Xpert Xpress Strep A test is performed on the Cepheid GeneXpert® Xpress System. The GeneXpert Xpress System platform automates sample preparation, amplification and real-time detection.

The GeneXpert Xpress System requires the use of single-use, disposable cartridges (the Xpert Xpress Strep A 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 Xpress Strep A test includes primers and probes for the detection of a targeted sequence of the S. pyogenes genome allowing detection of Strep A directly from throat swab specimens collected from patients with signs and symptoms of pharyngitis. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Xpress 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 S. pyogenes in ~24 minutes or less. The GeneXpert Xpress System, comprised of the GeneXpert Xpress II and GeneXpert Xpress IV, is capable of performing separate sample preparation and realtime 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.

Throat swab specimens are collected using the ESwab collection device and transported to the GeneXpert area and prepared according to package insert instructions. After mixing the specimen, the liquid sample is transferred to the Xpert Xpress Strep A cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert Xpress 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 Cepheid Xpert Xpress Strep A device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined "acceptance criteria" in a bulleted or numbered list with pass/fail thresholds. Instead, it presents the results of various studies and concludes substantial equivalence to a predicate device. For the purpose of this request, I will infer the acceptance criteria from the reported performance of the predicate device and the general regulatory expectations for such assays, then juxtapose it with the Xpert Xpress Strep A's performance.

2. Sample Size and Data Provenance

• Clinical Study Test Set Sample Size: 618 specimens were included in the final analysis (initially 666, with 43 excluded).
• Data Provenance: The clinical study was a prospective, multi-center investigational study conducted at nine clinical sites in geographically diverse regions within the United States between January 2017 and May 2017.

3. Number of Experts and Qualifications for Ground Truth (Clinical Study)

The document specifies that the Xpert Xpress Strep A clinical performance was established relative to culture and latex agglutination for Strep A typing. It also mentions "an alternative PCR/bidirectional sequencing assay" used to investigate discordant results.

• Number of Experts: Not explicitly stated for establishing the primary ground truth (culture and latex agglutination). These methods are standard laboratory procedures typically performed by trained medical technologists or microbiologists.
• Qualifications of Experts: Not explicitly described. However, the use of standard microbiology lab techniques implies performance by qualified laboratory personnel. The "alternative PCR/bidirectional sequencing assay" would also be performed by trained molecular diagnosticians or researchers.

4. Adjudication Method (Clinical Study)

• Primary Adjudication: The primary ground truth for the clinical study was established by culture and latex agglutination for Strep A typing. This acts as the "gold standard" against which the device was compared.
• Discordant Analysis: For specimens where the Xpert Xpress Strep A result differed from the culture result, an "alternative PCR/bidirectional sequencing assay" was used to investigate the discrepancy. This serves as a secondary adjudication method to verify the true status of discordant samples.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, an MRMC comparative effectiveness study was not done. The Xpert Xpress Strep A is an automated in vitro diagnostic (IVD) test, not an AI system designed to assist human readers in image interpretation or similar tasks. Its performance is evaluated independently against a reference method (culture).

6. Standalone Performance

• Yes, a standalone performance study was done. The entire clinical study, analytical sensitivity, specificity, interference, and reproducibility studies assess the performance of the algorithm and instrument (Xpert Xpress Strep A test on the GeneXpert Xpress System) directly against various reference standards and controlled conditions, without human interpretation of the final result. The device provides a "Strep A DETECTED" or "Strep A NOT DETECTED" result automatically.

7. Type of Ground Truth Used (Clinical Study)

• The primary ground truth used for the clinical study was bacterial culture and latex agglutination for Strep A typing.
• For discordant sample resolution, an alternative PCR/bidirectional sequencing assay was used.

8. Sample Size for the Training Set

The document describes pre-market validation studies typically conducted for IVD devices, not machine learning model development. Therefore, there is no explicit "training set" sample size mentioned as would be the case for an AI/ML device. The device's underlying PCR assay design and algorithm are developed based on established scientific principles and analytical verification, rather than being "trained" on a large dataset in the AI sense.

9. How Ground Truth for the Training Set Was Established

As mentioned above, the concept of a "training set" and its "ground truth" in the AI/ML context is not directly applicable here. The device is a PCR assay with a defined molecular target and detection algorithm. The closest analogue to "ground truth establishment" during development would be:

• Analytical Validation: Extensive analytical studies (e.g., Limit of Detection, Inclusivity, Exclusivity, Interference) using well-characterized bacterial strains, spiked samples, and clinical matrices to ensure the assay correctly identifies the target organism and differentiates it from non-targets under various conditions. These studies confirm the assay's fundamental ability to detect S. pyogenes DNA.
• Assay Design and Optimization: The design of the primers and probes for the S. pyogenes genome target would be based on known genetic sequences, and optimized empirically to ensure specificity and sensitivity.

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The Xpert Xpress Strep A Assay, performed on the GeneXpert Instrument Systems, is a rapid, qualitative in vitro diagnostic test for the detection of Streptoccus pyogenes (Group A beta-hemolytic Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis.

The Xpert Xpress Strep A Assay utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA.

The Xpert Xpress Strep A Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of Streptococcus pyogenes from throat swab specimens from patients with signs and symptoms of pharyngitis.

The Xpert Xpress Strep A Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx, 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 Xpress Strep A 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 Xpress Strep A Assay includes primers and probes for the simultaneous detection and differentiation of a targeted sequence of the S. pyogenes genome allowing detection of Strep A directly from throat swab specimens collected from patients with signs and symptoms of pharyngitis. 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 S. pyogenes in ~24 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.

Throat swab specimens are collected using the ESwab collection device and transported to the GeneXpert area and prepared according to package insert instructions. After mixing the specimen, the liquid sample is transferred to the Xpert Xpress Strep A Assay cartridge. 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 an analysis of the provided text to extract the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for performance are not explicitly stated in a dedicated section with pre-defined numerical targets. However, based on the clinical study results and comparisons to the predicate, we can infer the demonstrated performance. The key performance metrics are Sensitivity, Specificity, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) relative to culture and latex agglutination.

Inferred Acceptance Criteria (Based on demonstrating substantial equivalence to predicate) and Reported Device Performance (Combined First and Second Swab Data):

Study Proving Acceptance Criteria (Clinical Performance):

• Study Design: A multi-site clinical study that collected throat ESwab specimens from patients with signs and symptoms of pharyngitis. The study combined data from two approaches:
  • One study collected a second prospective throat swab after a standard of care (SOC) swab.
  • Another study used leftover excess SOC throat swab specimens.

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

• Initial Enrolled Specimens: 844
• Excluded Specimens: 261 (due to inclusion criteria failure, reference culture procedural error, delay in reference culture inoculation, delay in shipment, or labeling error).
• Specimens Included in Performance Analysis (Test Set): 583
  • Successful on initial test: 565/583 (96.9%)
  • Valid results after retest (overall): 577/583 (99.0%)
• Data Provenance: Geographically diverse regions within the United States. The study was conducted between December 2016 and March 2017, suggesting it was a prospective or mixed (prospective and retrospective for leftover samples) collection. The text states "one study enrolled consented subjects from whom a second prospective throat swab specimen was collected" and "another study tested specimens from subjects for which leftover excess standard of care (SOC) throat swab specimens were available."

3. Number of Experts and Qualifications for Ground Truth for the Test Set:

• The document does not specify the number of experts or their qualifications for establishing the initial ground truth (culture and latex agglutination). These are standard laboratory procedures, but details about expert reviewers for discordant results are mentioned.

4. Adjudication Method for the Test Set:

• Discordant results between the Xpert Xpress Strep A Assay and the reference method (culture) were investigated.
• Method: An alternative PCR/bidirectional sequencing assay was used for adjudication. The results of this alternative PCR were footnoted in the performance tables (e.g., for 26 discrepant samples in Table 8-7, 21 were confirmed positive by alternative PCR, 4 negative, and 1 not tested). This indicates an independent molecular method was used to resolve discrepancies.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

• No, a MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay, not an imaging device or one that involves human "readers" interpreting results in a variable way that MRMC studies are designed for. Its performance is evaluated biochemically against a reference standard.

6. Standalone Performance Study (Algorithm only without human-in-the-loop):

• Yes, a standalone study was performed. The clinical performance data presented (Sensitivity, Specificity, PPV, NPV) represents the performance of the Xpert Xpress Strep A Assay (the "algorithm/device") functioning independently relative to a microbiological reference method (culture). The results are automatically generated by the GeneXpert Instrument Systems.

7. Type of Ground Truth Used:

• For the clinical performance study (test set), the primary ground truth reference method was culture and latex agglutination for Strep A typing.
• For resolving discordant results, an alternative PCR/bidirectional sequencing assay was used.

8. Sample Size for the Training Set:

• The document does not specify the sample size for a "training set" in the context of an algorithm. For IVDs, the development process typically involves various internal testing and optimization (which could be considered analogous to training) but not usually a distinct "training set" of patient specimens in the same way an AI model would have. The document focuses on analytical and clinical validation studies.

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

• As a training set is not explicitly defined in the context of this IVD device's approval process in this document, the method for establishing its ground truth is not applicable/not provided. The analytical and clinical validation studies use established reference methods as ground truth.

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