Search Results

The Xpert Xpress CoV-2/Flu/RSV plus test, performed on the GeneXpert Infinity Systems, is an automated multiplexed real-time reverse transcriptase chain reaction (RT-PCR) test intended for use in viro qualitative detection and differentiation of severe acute respiratory syndrome coronavirus (SARS-CoV-2), influenza B, and/or respiratory syncytial virus (RSV) viral RNA in nasopharyngeal swab specimens collected from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar.

The Xpert Xpress CoV-2/Flu/RSV plus is intended for use in the differential detection of SARS-CoV-2, influenza B and or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza B, and RSV viral RNA are generally detectable in nasopharyngeal swab anterior nasal swab specimens during the acute phase of infection.

Positive results are indicative of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Xpert Xpress COV-2/Flu/RSV plus test may not be the definite cause of disease.

Negative results do not preclude SARS-CoV-2, influenza B, and/or RSV infection. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

The Xpert Xpress CoV-2/Flw/RSV plus test is an automated in vitro diagnostic test for the simultaneous qualitative detection and differentiation of SARS-CoV-2, Flu A, Flu B, and RSV viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals showing signs and symptoms of respiratory viral infection.

The Xpert Xpress CoV-2/Flu/RSV plus test is performed on GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48s and GeneXpert Infinity-80 systems), which consist of an instrument, computer, and preloaded software for running tests and viewing the results. The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time reverse transcription (RT)-polymerase chain reaction (PCR) and PCR assays. Depending on the instrument, the GeneXpert Instrument Systems can have from 1 and up to 80 randomly accessible modules, each capable of performing separate sample preparation and real-time RT-PCR and 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 RT-PCR and PCR as well as detection. The systems require the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are selfcontained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2/Flu/RSV plus test includes reagents for the detection of SARS-CoV-2, Flu A. Flu B and RSV viral RNA from NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2/Flu/RSV plus test are designed to amplify and detect unique sequences in the genes that encode the following proteins: SARS-CoV-2 nucleocapsid (N), SARS-CoV-2 envelope (E), SARS-CoV-2 RNA-dependent RNA polymerase (RdRP), influenza A matrix (M), influenza A basic polymerase (PB2), influenza A acidic protein (PA), influenza B matrix (M), influenza B non-structural protein (NS), and the RSV A and RSV B nucleocapsid. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress CoV-2/Flu/RSV plus test is designed for use with NPS or NS specimens collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM), or eNAT®.

Acceptance Criteria and Study Details for Xpert Xpress CoV-2/Flu/RSV plus

The Xpert Xpress CoV-2/Flu/RSV plus test is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the qualitative detection and differentiation of SARS-CoV-2, Influenza A, Influenza B, and/or Respiratory Syncytial Virus (RSV) viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens.

The performance of the device was evaluated through analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly derived from the observed clinical performance, demonstrating acceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a U.S. FDA-cleared molecular reference method.

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

• Clinical Performance Study:
  • SARS-CoV-2: A total of 5051 specimens (2536 NPS and 2515 NS) yielded valid results and were included in the performance evaluation.
    • NPS: 462 True Positives, 37 False Positives, 2023 True Negatives, 14 False Negatives.
    • NS: 448 True Positives, 24 False Positives, 2035 True Negatives, 8 False Negatives.
  • Flu A/B/RSV: A total of 5954 specimens (3011 NPS and 2943 NS) yielded valid results and were included in the performance evaluation.
    • NPS:
      • Flu A: 191 True Positives, 24 False Positives, 2794 True Negatives, 2 False Negatives.
      • Flu B: 57 True Positives, 0 False Positives, 2952 True Negatives, 2 False Negatives.
      • RSV: 71 True Positives, 0 False Positives, 2939 True Negatives, 1 False Negative.
    • NS:
      • Flu A: 196 True Positives, 18 False Positives, 2725 True Negatives, 4 False Negatives.
      • Flu B: 34 True Positives, 3 False Positives, 2906 True Negatives, 0 False Negatives.
      • RSV: 69 True Positives, 0 False Positives, 2871 True Negatives, 3 False Negatives.
• Data Provenance:
  • Prospective Data: Fresh (98.9%) and frozen (1.1%) specimens (Category I) were prospectively collected and tested in 2022 from 33 geographically diverse sites in the United States.
  • Retrospective Data: Archived prospectively collected frozen clinical specimens (Category II) from the 2016-2017 influenza season were used to supplement the sample size for Flu/RSV. These were primarily collected from the US.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth. Instead, the ground truth was established by comparing the Xpert Xpress CoV-2/Flu/RSV plus test results to results from a U.S. FDA-cleared molecular respiratory panel for SARS-CoV-2 and a U.S. FDA-cleared molecular Flu A/B/RSV assay for their respective targets.

4. Adjudication Method for the Test Set

Discrepant results between the Xpert Xpress CoV-2/Flu/RSV plus test and the comparator method were investigated as follows:

• SARS-CoV-2 target: Discrepant results were investigated using a U.S. FDA EUA SARS-CoV-2 molecular test.
• Flu A/B/RSV targets: Discrepant results were investigated using a U.S. FDA-cleared molecular respiratory panel.

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 explicitly conducted as the device is an in-vitro diagnostic (IVD) test, not an AI-powered diagnostic imaging device involving human readers.

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

Yes, the studies presented are generally standalone performance evaluations of the device (an automated test) without human-in-the-loop adjustment of the result. The device automates sample preparation, nucleic acid extraction, amplification, and detection, and provides results automatically ("algorithm only"). The clinical performance compares the device's output directly to accepted reference methods.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical performance study was established using U.S. FDA-cleared molecular reference methods for viral detection:

• A U.S. FDA-cleared molecular respiratory panel for SARS-CoV-2.
• A U.S. FDA-cleared molecular Flu A/B/RSV assay for Flu A, Flu B, and RSV.
• For discrepant results, additional U.S. FDA EUA SARS-CoV-2 molecular test or U.S. FDA-cleared molecular respiratory panel was used for adjudication.

8. The Sample Size for the Training Set

The document does not specify a distinct "training set" for the clinical performance study as is typical for AI/ML models. For IVD devices like this, the development process (which would involve internal analytical studies and optimization) constitutes the "training" equivalent. The analytical studies describe the evaluation of analytical sensitivity, inclusivity (wet-testing of multiple strains), and exclusivity, which would directly inform the device's design and parameters. For example:

• Analytical sensitivity (LoD) testing involved 2 reagent lots and 20 replicates per virus/lot combination.
• Analytical reactivity (inclusivity wet-testing) involved testing 102 respiratory viral strains (18 SARS-CoV-2, 69 influenza, 15 RSV) at ~3x LoD, with 3 replicates per strain.

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

For the analytical "training" phase:

• Analytical Sensitivity (LoD): Ground truth was established by using known concentrations of inactivated viruses and international standards (e.g., NATtrol SARS-CoV-2, 1st WHO International Standard, cultured Flu A, Flu B, and RSV strains) spiked into negative clinical matrices. The LoD was determined by Probit regression analysis and verified as the lowest concentration yielding 95% positive results.
• Analytical Reactivity (Inclusivity): Ground truth was established by testing known viral strains at specified concentrations (~3x LoD) and expecting a positive detection for the corresponding target.
• Analytical Specificity (Exclusivity): Ground truth was established by testing a panel of known microorganisms and expecting negative results for all targets, thus confirming no cross-reactivity. These were either cultured microorganisms or synthetic RNA/genomic DNA at known concentrations.

Ask a specific question about this device