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The Xpert HCV test, performed on the GeneXpert Xpress System, is an automated in vitro reverse transcription polymerase chain reaction (RT-PCR) test for the qualitative detection of hepatitis C virus (HCV) RNA in human fingerstick K2-EDTA whole blood from adult individuals at risk and/or with signs and symptoms of HCV infection with or without antibody evidence of HCV infection. Detection of HCV RNA indicates that the virus is replicating and therefore is evidence of active infection. Detection of HCV RNA does not discriminate between acute and chronic states of infection.

The Xpert HCV test is not intended for monitoring patients undergoing treatment or for use in screening blood, plasma, or tissue donors.

The Xpert HCV test, is an automated qualitative in vitro reverse transcription polymerase chain reaction (RT-PCR) test. The Xpert HCV test is performed on the GeneXpert Xpress System. With this system an operator can run the test by performing four steps: 1) mix the specimen. 2) transfer the liquid sample to the cartridge with a transfer pipette, 3) run the test on the instrument, and 4) read the results.

The GeneXpert Xpress System (Hub configuration) consists of a GeneXpert IV instrument that conducts the sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the test, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform separate sample preparation and testing. The 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 (Intelligent Cooling/Heating Optical Reaction) thermocycler for performing real-time PCR and RT-PCR and detection.

The Xpert HCV test requires the use of a single-use disposable GeneXpert cartridge that contains all necessary reagents for the detection of HCV RNA. Because the cartridges are self-contained, the risk of cross-contamination between samples is minimized. The Xpert HCV test includes reagents for the detection of HCV RNA in clinical specimens as well as a sample processing control (SPC) and internal control high (IC-H) used to control for adequate processing of the target and to monitor the presence of inhibitor(s) in the RT and PCR reactions. The Probe Check Control (PCC) verifies reagent rehydration. PCR tube filling in the cartridge, probe integrity, and dye stability. The Sample Volume Adequacy (SVA) control ensures the sample was correctly added to the cartridge and verifies that the correct volume of sample has been added to the sample chamber.

The Xpert HCV test is designed for use with human K2-fingerstick EDTA whole blood. The BD Microtainer for capillary whole blood collection was validated for use with the Xpert HCV test. After collecting human fingerstick EDTA whole blood in the BD Microtainer, a 100μl aliquot of the specimen is transferred to the sample chamber of the Xpert HCV cartridge using the transfer pipette supplied in the Xpert HCV kit.

The sample results are interpreted by the GeneXpert Xpress System from measured fluorescent signals and embedded calculation algorithms and are shown in the View Results window. It also reports if the test has encountered an instrument error or produces no result and needs to be repeated.

This document describes the evaluation of the Xpert HCV test for an automatic Class III designation. The test is an automated qualitative reverse transcription polymerase chain reaction (RT-PCR) test for the qualitative detection of hepatitis C virus (HCV) RNA.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Xpert HCV test are implied by the reported performance in both analytical and clinical studies. For analytical performance, the agreement rates for precision and reproducibility are presented. For clinical performance, Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a Patient Infected Status (PIS) algorithm are key metrics.

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

• Precision Study Test Set: The precision study used a total of 60 replicates per panel member (e.g., negative, GT1a 1.5x LoD, etc.). The study was conducted in a blinded and randomized manner.
• Multi-Site Reproducibility Study Test Set: A total of 90 replicates per panel member were tested across three sites. The study was blinded and randomized.
• Clinical Study Test Set: 1,012 fingerstick whole blood (FS) specimens were initially collected. After exclusions due to protocol deviations, unresolved non-determinate results, and non-evaluable comparator test results, 982 FS samples were included in the performance calculations (Table 13, 14).
• Non-Viral Hepatitis Samples Study: 78 FS samples from individuals with non-viral hepatitis were included, with 68 being evaluable for performance comparison (Table 15).
• Data Provenance for Clinical Study: Prospective, all-comers blinded clinical study conducted at 15 CLIA waived sites located in the US.

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

The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. Instead, it states that the "patient infected status (PIS) algorithm based on results from an FDA approved HCV RNA test and an antibody test" served as the comparator/ground truth for the clinical study. This implies that the ground truth was established by the performance of these approved reference tests, rather than by a panel of human experts directly reviewing the samples.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) involving human experts for the test set. The clinical study's ground truth was established by comparing the Xpert HCV test results to the "patient infected status (PIS) algorithm based on results from an FDA approved HCV RNA test and an antibody test." Any discrepancies would likely be resolved by the established reference method rather than expert adjudication of the fingerstick samples themselves. The retesting of "Two (2) specimens (1 false positive and 1 false negative) with suspicion of specimen handling and testing errors" suggests a method for investigating discrepancies, but not a general expert adjudication for all 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 comparing human readers with and without AI assistance was not done. This device is an automated qualitative RT-PCR test, and its output (HCV DETECTED/NOT DETECTED) is a direct result from the instrument, not interpreted by human readers in the traditional sense that an AI would assist. The "operators" mentioned in the analytical studies are those performing the physical test steps, not interpreting diagnostic images or complex medical data.

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

Yes, a standalone performance evaluation was done. The Xpert HCV test is an automated system where the "sample results are interpreted by the GeneXpert Xpress System from measured fluorescent signals and embedded calculation algorithms" and results are "displayed in the View Results window." The clinical study (Section VI.C.3) directly evaluates the performance of this automated system against the patient infected status algorithm. The operators in the study are described as "untrained," further emphasizing the standalone nature of the device's interpretation.

7. The Type of Ground Truth Used

The ground truth used for the clinical study was the Patient Infected Status (PIS) algorithm, which was "based on results from an FDA approved HCV RNA test and an FDA approved HCV antibody test." This constitutes a form of established clinical diagnosis reference standard (or "outcomes data" in a broader sense of established clinical status).

8. The Sample Size for the Training Set

The document does not specify a sample size for a training set. As an RT-PCR diagnostic device, the "training" of the device involves the internal development and calibration of the assay (e.g., primer and probe design, thermal cycling conditions, fluorescent signal thresholds, embedded calculation algorithms) by the manufacturer based on analytical studies and known HCV characteristics, rather than a classical machine learning training phase on a large clinical dataset.

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

Since no explicit training set is mentioned in the context of machine learning, there is no description of how ground truth for a training set was established. The development of the assay likely involved extensive analytical studies (e.g., determining LoD for various genotypes, specificity, interference) using well-characterized HCV strains and clinical samples to establish the assay's performance parameters and the embedded algorithms' decision rules. These characterization efforts would form the basis of the device's "knowledge," but it's not a "training set" in the sense of supervised learning for an AI algorithm that learns from labeled data.

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The Xpert® Xpress MVP test, performed on the GeneXpert® Xpress System, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• Organisms associated with bacterial vaginosis (detected organisms not reported individually) .
  • Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226) O
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) O
  • Megasphaera-1 O
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated) .
• Candida glabrata/Candida krusei (species not differentiated) ●
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. In the CLIA-waived environment, the Xpert Xpress MVP test is performed on the GeneXpert® Xpress System.

The latest Hub configuration of the GeneXpert Xpress System consists of a GeneXpert IV instrument that executes sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the tests, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the test results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform independent sample preparation and testing.

The Xpert Xpress MVP test is a PCR-based Nucleic Acid Amplification Test. Each test requires the use of a single-use disposable GeneXpert cartridge that contains all necessary reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge serving as internal controls. The SPC is present to control for adequate sample processing, to monitor PCR conditions, the presence of potential inhibitor(s) and possible reagent degradation. 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. Because the cartridges are self-contained, the risk of cross- contamination between samples is minimized.

The Xpert Xpress MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The ancillary specimen collection kit for use with the Xpert Xpress MVP test is the Xpert Swab Specimen Collection Kit. The swab and the transport reagent included in the Xpert Swab Specimen Collection Kit are designed to collect and preserve patient specimens to allow transport to the testing site prior to analysis with the Xpert Xpress MVP test.

Here's a summary of the acceptance criteria and study details for the Cepheid Xpert Xpress MVP device based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a numerical, threshold-based format. Instead, it presents the clinical performance results (PPA/NPA, Sensitivity/Specificity) for the Xpert Xpress MVP test. The implication is that these reported performance metrics meet internal or regulatory acceptance thresholds for substantial equivalence.

*Target includes C. albicans, C. tropicalis, C. parapsilosis, and C. dubliniensis

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

• Sample Size:
  • Clinical Study: 1,275 female patients (18 to ≥50 years of age, plus two patients 14-17 years old). A total of 2,544 vaginal swabs were tested (likely one clinician-collected and one self-collected per patient).
• Data Provenance: Retrospective and prospective. The clinical study was conducted at 9 geographically diverse sites in the U.S.

3. Number of Experts Used to Establish Ground Truth and Qualifications:

The document does not specify the number or qualifications of experts used to establish the ground truth for the clinical study. It refers to "reference/comparator methods" for ground truth.

4. Adjudication Method for the Test Set:

• For BV, Candida group, Candida glab-krus, and TV, the performance was determined relative to specific reference/comparator methods (see point 7).
• For discrepant results, "investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT." This indicates a form of discrepancy resolution rather than a multi-expert adjudication on all cases. The exact adjudication method (e.g., 2+1, 3+1) for discrepant cases is not detailed, but it involves re-testing with an FDA-cleared NAAT.

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

No MRMC comparative effectiveness study was mentioned. The device is an in vitro diagnostic test, which typically does not involve human readers interpreting images or data to the same extent as AI-assisted diagnostic tools. Performance is typically compared against reference methods.

6. Standalone (Algorithm Only) Performance:

Yes, the entire clinical study and analytical studies described are standalone performance evaluations of the Xpert Xpress MVP device (an automated qualitative in vitro diagnostic test) without human-in-the-loop assistance in its diagnostic output. Its output is a qualitative detection result (Positive/Negative/Not Detected).

7. Type of Ground Truth Used:

• Bacterial Vaginosis (BV): An FDA-cleared nucleic acid amplification test (NAAT).
• Candida group (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis): Yeast culture followed by mass spectrometry for species identification.
• Candida glabrata/Candida krusei: Yeast culture followed by mass spectrometry for species identification.
• Trichomonas vaginalis (TV): A patient infected status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture.
• Discrepant Results: Re-tested with another FDA-cleared NAAT.

8. Sample Size for the Training Set:

The document does not explicitly mention a "training set" in the context of machine learning model development. This device is a PCR-based NAAT, not an AI/ML-driven diagnostic. Therefore, the concept of a training set for an algorithm is not directly applicable in the same way as for an image-based AI device. Analytical studies (e.g., Limit of Detection, Analytical Reactivity, Analytical Specificity) and reproducibility studies served to characterize the device's performance chemically and biologically.

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

As noted above, the device is a PCR-based NAAT, not an AI/ML system, so a "training set" for an algorithm in the traditional sense is not discussed. The development and optimization of the assay's chemical and molecular components would have been guided by fundamental scientific principles and laboratory testing, rather than an algorithmic training process using labeled data. Benchmarking for analytical characteristics (like LoD) would involve preparing samples with known concentrations of organisms.

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The Xpert® Xpress GBS test, performed on the GeneXpert® Instrument Systems, is an automated, real-time PCR test for the qualitative detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens collected from pregnant patients for intrapartum testing at term (e.g., >37 weeks) who have unknown or unavailable antepartum GBS screening test results and no additional risk factors that would warrant empiric antibiotic prophylaxis. The Xpert Xpress GBS test performed during intrapartum is intended to aid in the detection of GBS colonization in patients presenting in labor who may be candidates for antibiotic prophylaxis.

The Xpert Xpress GBS test does not provide antimicrobial susceptibility test results. Culture is necessary to obtain isolates to perform susceptibility testing as recommended for penicillin-allergic patients.

This test is conducted using direct specimen without enrichment is recommended to enhance detection of GBS colonization). In contrast to a positive test result, which can indicate colonization, a presumptive negative result cannot exclude the possibility of GBS colonization. A false negative test result at intrapartum carries a potential harm to the infant if it is used in making decisions regarding empiric antibiotic prophylaxis. Providers must use caution and default to known patient risk factors and clinical guidance regarding a role for intrapartum prophylaxis.

The Xpert® Xpress GBS test is an automated in vitro diagnostic test for the qualitative detection of Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens collected from pregnant patients at intrapartum.

The Xpert Xpress GBS test is performed on the Cepheid 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 real-time detection. 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 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 as well as detection. The systems require the use of single-use disposable cartridges that hold the PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self- contained, cross-contamination between cartridges during the testing process is minimized.

The Xpert Xpress GBS test includes reagents for the simultaneous detection of target GBS DNA from vaginal/rectal swab specimens. The primers and probes in the Xpert Xpress GBS test are designed to amplify and detect unique sequence in two conserved chromosomal targets in S. agalactiae: a) a member of the glycosysl transferase gene family, and b) a LysR transcriptional regulator. A Sample Adequacy Control (SAC), Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SAC is a non-target sequence naturally present in the specimen. which is amplified along with the assay target. In the Xpert Xpress GBS test, the SAC detects the presence of the human hydroxymethylbilane synthase (HMBS) gene to ensure that the sample is properly collected and contains adequate human cells from the vaginal/rectal flora. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the 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 GBS test is designed for use with vaginal/rectal swab specimens collected from pregnant patients at intrapartum and placed into a collection device. The ancillary specimen collection kit validated for use with the Xpert Xpress GBS test is the Cepheid Collection Device (Catalog 900-0370). The sample collection device allows dual vaginal/rectal swab specimens from patients to be collected and transported to laboratory prior to analysis with the Xpert Xpress GBS test.

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

1. Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific numeric thresholds for sensitivity, specificity, PPV, and NPV. However, it presents the clinical performance results as compared to enriched bacterial culture + MALDI-TOF MS. The implied acceptance is that the device's performance is deemed "acceptable for its intended use" and "substantially equivalent to the predicate device."

Here are the reported performance metrics from the clinical study:

2. Sample Size and Data Provenance for the Test Set

• Sample Size for Test Set: A total of 899 intrapartum vaginal/rectal specimens were included in the performance analysis. Initially, 912 specimens were enrolled, but 13 were excluded due to non-determinate Xpert Xpress results upon retest or no culture results.
• Data Provenance: The study was conducted at twelve (12) clinical sites from geographically diverse regions within the United States. This indicates the data is prospective and multi-site (US).

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number or qualifications of experts used to establish the ground truth. The ground truth was established by "enriched bacterial culture with species identification via MALDI-TOF MS." This method is considered a laboratory-based gold standard for GBS detection. The interpretation of these results would typically be done by trained laboratory personnel.

4. Adjudication Method

The document mentions that discordant results between the Xpert Xpress GBS test and the comparator method (enriched culture + MALDI-TOF MS) were investigated using an FDA-cleared nucleic acid amplification test (NAAT). However, the exact adjudication method (e.g., 2+1, 3+1, etc.) for resolving these discrepancies to establish a final ground truth is not explicitly described. The text states that the results of the FDA-cleared NAAT are "footnoted in Table 5-8, for informational purposes only," suggesting that the primary "ground truth" remained the enriched culture, and the NAAT was used for further investigation of discrepancies rather than as a tie-breaker in a formal adjudication process.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned. This device is an automated, standalone diagnostic test and does not involve human readers for interpretation in the same way an imaging AI algorithm would.

6. Standalone Performance Study

Yes, a standalone performance study (i.e., algorithm only without human-in-the-loop performance) was performed. The clinical performance characteristics were evaluated by directly comparing the Xpert® Xpress GBS test results to an enriched bacterial culture with species identification via MALDI-TOF MS.

7. Type of Ground Truth Used

The primary ground truth used for the clinical performance study was enriched bacterial culture with species identification via MALDI-TOF MS.

8. Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. The study detailed in the document focuses on the clinical performance evaluation of the finished device.

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

Since no information on the training set is provided, the method for establishing its ground truth is also not detailed in this document. Typically, for PCR-based tests like this, development and training would involve a combination of characterized GBS strains and cultured clinical samples verified by traditional microbiology methods.

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The Xpert® Xpress MVP test, performed on the GeneXpert® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV). Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
  • o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) O
  • o Megasphaera-1
• . Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
• Candida glabrata/Candida krusei (species not differentiated)
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis. Candida species associated with vulyovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems. 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 PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The 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.

The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System 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 PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the 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 MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert Xpress MVP device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on demonstrating equivalence between a "new design" and an "original design" of the Xpert Xpress MVP, rather than establishing de novo acceptance criteria against a clinical reference standard in this specific submission. The acceptance criteria for the analytical sensitivity equivalency study were defined internally for comparison between the two designs:

1. Both original and new design report 19/20 or 20/20 POSITIVE/DETECTED results at LoD/Near Cut-off concentrations.
2. Statistical analysis (two-sample t-test) comparing mean Ct values shows no statistically significant difference (p-value > 0.05) with a marginal difference of 1.0 Ct value. | Met:

• All targets (Atopobium vaginae, Megasphaera-1, BVAB2, Candida albicans, Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Candida glabrata, Candida krusei, Trichomonas vaginalis) consistently showed 19/20 or 20/20 positive/detected results at LoD.
• All BV targets showed 19/20 or 20/20 positive/detected (BV positive) results at near cut-off concentrations.
• For all targets and conditions (SVM/VS matrix), the difference in mean Cts between the two designs was within 1.0 Ct, and the t-test p-values were consistently > 0.05 (most were >0.9), indicating no statistically significant difference in analytical sensitivity. |
  | Clinical Specimen Equivalency (PPA/NPA) | The PPA (Positive Percent Agreement) and NPA (Negative Percent Agreement) of the new design relative to the original design for Bacterial Vaginosis (BV), Candida group, Candida glabrata/Candida krusei, and Trichomonas vaginalis (TV) targets should demonstrate equivalence. (No specific numerical thresholds provided in this summary, but the implication is "high agreement"). | Met:
• BV: PPA 98.3% (56/57), NPA 99.1% (112/113)
• Candida group: PPA 97.4% (38/39), NPA 98.5% (129/131)
• Candida glab-krus: Overall PPA 100% (31/31), NPA 100% (159/159). (Fresh PPA 100% (11/11), Contrived PPA 100% (20/20))
• TV: Overall PPA 100% (32/32), NPA 100% (158/158). (Fresh PPA 100% (12/12), Contrived PPA 100% (20/20))
• Discordant results were investigated and attributed to samples near LoD or sub-LoD levels, supporting overall equivalence. |
  | Non-Determinate Rate | Implicitly, the non-determinate rates for both designs should be low and acceptable. | Met:
• Overall non-determinate rate for original design: 0.42% (1/236)
• Overall non-determinate rate for new design: 1.4% (3/220)
  These rates are considered acceptable. |
  | Interfering Substances | No clinically significant inhibitory effects from substances encountered in vaginal specimens, except where a limitation is appropriate. | Met:
• No clinically significant inhibitory effects observed for new design, with the exception of 5.5% v/v mucin (same as original design). At 4.0% mucin, no interference was observed. A limitation for ≥5.5% mucin is included in the instructions. |

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

• Analytical Sensitivity Equivalency Study (LoD & Near Cut-off):

  • Sample Size: 20 replicates for each target at LoD/near cut-off concentration for both the original and new designs. This included testing in Simulated Vaginal Matrix (SVM) and Pooled Negative Natural Clinical Vaginal Swab Matrix (VS) for some targets.
  • Data Provenance: Not explicitly stated, but these are analytical studies meaning they used prepared samples (cultures, specific concentrations) rather than clinical patient samples.

• Equivalency Study using Clinical Specimens:

  • Sample Size:
    • Initial Enrollment: 174 participants (174 clinician-collected vaginal swabs).
    • Included in Final Analysis: 170 prospectively collected ("fresh") clinician-collected vaginal swab specimens.
    • Additional Contrived Specimens: 20 contrived C. glabrata and C. krusei specimens, and 20 contrived T. vaginalis specimens.
  • Data Provenance:
    • Country of Origin: United States (three sites).
    • Retrospective or Prospective: Prospectively collected. Clinician-collected vaginal swabs were taken from symptomatic female patients ≥ 14 years of age. All testing was performed at Cepheid (Sunnyvale, CA).

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

This submission is about demonstrating equivalence between two versions of the same diagnostic device, not evaluating the device against a clinical reference standard with expert interpretation for ground truth. Therefore, experts were not used to establish the "ground truth" for the test set in the traditional sense of clinical diagnosis.

Instead, the "ground truth" in the clinical equivalency study was the result produced by the predicate device (original design of Xpert Xpress MVP).

4. Adjudication Method for the Test Set

No adjudication method using human experts was described for the clinical equivalency study. The comparison was directly between the test results of the new device and the predicate device. Discordant results were investigated by retesting with both designs if enough sample volume remained, but these retest results were for information only and not used for adjudication in the primary data analysis.

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

• No, an MRMC comparative effectiveness study was NOT done. This document describes the analytical and clinical performance equivalence of a device modification to its predicate, not a study evaluating human reader performance with or without AI assistance.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, this is essentially a standalone (algorithm only) performance study. The Xpert Xpress MVP system is an automated in vitro diagnostic test that provides a qualitative result. While human operators are involved in sample preparation and loading, the "performance" described here (detection of DNA targets) is that of the automated system and its reagents/software, acting as an algorithm-only device in the context of its defined output. There isn't a human-in-the-loop component being evaluated in these studies.

7. Type of Ground Truth Used

• Analytical Sensitivity Study: The ground truth was based on known concentrations of target organisms (CFU/mL or copies/mL) spiked into matrices.
• Clinical Specimen Equivalency Study: The "ground truth" for comparison was the results obtained from the predicate device (original Xpert Xpress MVP K212213). The study aimed to show agreement with the predicate device, not with an external clinical gold standard.

8. Sample Size for the Training Set

No information about a training set is provided. This document describes validation studies for a device, not the development or training of an AI algorithm. If there were internal machine learning components in the original device, their training data would have been part of the original K212213 submission.

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

As no training set is mentioned, this information is not applicable to the provided document.

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The Xpert GBS LB XC test, performed on the GeneXpert® Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens, using real- time polymerase chain reaction (PCR).

Xpert GBS LB XC testing is indicated as an aid in determining the GBS colonization status of antepartum women.

· The Xpert GBS LB XC test is intended for antepartum testing on enriched Lim broth cultures of vaginal/rectal swabs after 18-24 hours of incubation

· The Xpert GBS LB XC test does not provide antimicrobial susceptibility test results. Culture is necessary to obtain isolates to perform susceptibility testing as recommended for penicillin-allergic women

The Xpert GBS LB XC test is an automated in vitro diagnostic test for qualitative detection of DNA from Group B Streptococcus (GBS) from vaginal-rectal swab specimens obtained from pregnant women that are transported to the laboratory following enrichment in Lim broth.

The primers and probes in the Xpert GBS LB XC test are designed to simultaneously amplify and detect two unique GBS chromosomal targets: the first is a target within a coding region for a glycosyl transferase family protein and the second is within a coding region for a LysR family transcriptional regulator of Streptococcus agalactiae DNA.

The Xpert GBS LB XC test includes reagents for the detection of DNA from GBS in Lim broth-enriched vaginal/rectal swabs. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate extraction and processing of the target sequences and to monitor for the presence of inhibitors in the PCR reaction. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dve stability.

The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of GBS genomic DNA in as little as 27 minutes with high titer specimens; GBS negative specimens generate results in approximated 43 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 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.

The Xpert GBS LB XC test 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 systems consist of an instrument, computer, and preloaded software for running tests and viewing the results.

The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert GBS LB XC 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.

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

Acceptance Criteria and Reported Device Performance

The document describes the performance of the Xpert GBS LB XC test, a qualitative in vitro diagnostic test for the detection of Group B Streptococcus (GBS) DNA. The acceptance criteria are implicitly derived from the reported performance characteristics.

Study Details

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

   • Test Set Sample Size: 621 specimens were included in the Xpert GBS LB XC versus Composite Comparator analysis.
   • Data Provenance: The study was a multi-site clinical study conducted in the United States. It used vaginal/rectal swab specimens collected from pregnant females as part of routine care. The nature of the specimen collection ("as a part of routine care") suggests it was likely a prospective collection for this study, though it might have utilized leftover samples. The text specifies "aliquots of leftover Lim broth samples were obtained for testing."

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

   • The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth was established using a "composite comparator method" which involved enriched bacterial culture and an FDA cleared NAAT. For the culture component, species identification was performed via Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectroscopy (MALDI-TOF MS). While MALDI-TOF MS requires skilled lab personnel, the term "expert" in the sense of a medical professional making a diagnostic determination is not used for this ground truth establishment.

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

   • The adjudication method for the test set was: "a specimen was considered positive if either enriched bacterial culture or the FDA cleared NAAT was positive and negative when both enriched bacterial culture and the FDA cleared NAAT were negative." This is a rule-based composite comparator rather than an expert adjudication method like 2+1.

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 focusing on human readers improving with AI assistance was not done. This device is an automated in vitro diagnostic test (NAAT) for detecting GBS DNA. It does not involve human "readers" in the diagnostic process beyond laboratory technicians operating the equipment and interpreting the automated qualitative results.

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

   • Yes, the clinical "Performance of Xpert GBS LB XC v Composite Comparator" (Table 9) is a standalone performance assessment. The Xpert GBS LB XC test is an automated qualitative test where the instrument system performs sample preparation, amplification, and real-time detection, with the software running tests and viewing results. This is inherently an "algorithm only" performance, as the final output is a qualitative (Positive/Negative) result generated by the device itself.

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

   • A composite comparator method was used as the ground truth. This method combined:
     • Enriched bacterial culture with species identification via Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectroscopy (MALDI-TOF MS).
     • An FDA cleared Nucleic Acid Amplification Test (NAAT).

7. The sample size for the training set:

   • The document describes a clinical validation study for regulatory submission. It does not provide information about the sample size used for the training set of the algorithm or device. Regulatory submissions typically focus on validation performance rather than development/training data.

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

   • Since information on the training set (including its sample size) is not provided, the method for establishing its ground truth is also not detailed in this document.

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The Xpert Xpress MVP test, performed on the GeneXpert Instrument Systems, is an automated qualitative in vitro diagnostic test for the detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis (BV), Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis. The Xpert Xpress MVP test uses clinician-collected and self-collected vaginal swabs (collected in a clinical setting) from patients who are symptomatic for vaginitis/vaginosis. The Xpert Xpress MVP test utilizes real-time polymerase chain reaction (PCR) for the amplification of specific DNA targets and utilizes fluorogenic target-specific hybridization probes to detect and differentiate DNA from:

• . Organisms associated with bacterial vaginosis (detected organisms not reported individually)
  • o Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226)
  • Bacterial Vaginosis-Associated Bacterium 2 (BVAB2) o
  • Megasphaera-1 o
• Candida spp. (C. albicans, C. tropicalis, C. parapsilosis, C. dubliniensis, species not differentiated)
• Candida glabrata/Candida krusei (species not differentiated)
• . Trichomonas vaginalis

The Xpert Xpress MVP test is intended to aid in the diagnosis of vaginal infections in women with a clinical presentation consistent with bacterial vaginosis, vulvovaginal candidiasis, or trichomoniasis.

The Xpert® Xpress MVP test is an automated in vitro diagnostic test for qualitative detection of DNA targets from anaerobic bacteria associated with bacterial vaginosis, Candida species associated with vulvovaginal candidiasis, and Trichomonas vaginalis, the agent of trichomoniasis. The Xpert Xpress MVP test is performed on GeneXpert Instrument Systems.

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 PCR assays. The systems consist of an instrument, computer, and preloaded software for running tests and viewing the results. The 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.

The Xpert Xpress MVP test includes reagents for the detection of DNA from BV organisms, Candida species, and Trichomonas vaginalis from vaginal swab samples. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert System 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 PCR reaction. The SPC also ensures that the PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the 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 MVP test is designed for use with the following specimens collected from symptomatic individuals: self-collected vaginal swabs (collected in a clinical setting) and clinician-collected vaginal swabs. The swab transport reagent included in the Xpert Swab Specimen Collection Kit is designed to collect and preserve patient specimens to allow transport to the laboratory prior to analysis with the Xpert Xpress MVP test.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets for sensitivity, specificity, and agreement rates in the provided document. However, the performance outcomes of the Xpert Xpress MVP test are presented and can be interpreted as the device meeting the performance standards considered acceptable for its intended use, especially given the FDA's 510(k) clearance based on "substantial equivalence." The document compares the device's performance to an FDA-cleared predicate device.

For the purpose of this table, "Acceptance Criteria" will be inferred from the reported performance, as it highlights what the device achieved and what was deemed sufficient for clearance.

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

• Sample Size (Clinical Study/Test Set):
  • Patients: 1,478 female patients (14 to ≥ 50 years of age).
  • Vaginal Swabs Tested: 2,947 (one self-collected vaginal swab (SVS) and five clinician-collected vaginal swab (CVS) specimens per patient).
• Data Provenance:
  • Country of Origin of the Data: United States (multi-site clinical study with 12 sites from geographically diverse locations in the U.S.).
  • Retrospective or Prospective: Prospective observational, method comparison clinical study.

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

The document does not specify the number or qualifications of experts (e.g., radiologists, pathologists) used to establish the ground truth for the clinical test set. The ground truth for the clinical study was established by comparator methods (FDA-cleared NAATs, yeast culture followed by mass spectrometry, and a PIS algorithm). These methods are analytical laboratory tests, not dependent on expert visual review.

4. Adjudication Method for the Test Set

• The document states: "When applicable, investigation of discrepant results was performed by testing specimens with another FDA-cleared NAAT."
• This indicates a form of adjudication for discrepant results, where a third, independent, FDA-cleared NAAT was used to resolve disagreements between the Xpert Xpress MVP test and the initial comparator method. The specific rule (e.g., 2 out of 3 agreement) for this discrepancy resolution is not detailed, but the use of an independent NAAT as a tie-breaker or confirming tool is implied.

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

• No, an MRMC comparative effectiveness study was not done.
• This study evaluates an in vitro diagnostic (IVD) device that detects nucleic acid sequences from microorganisms using real-time PCR. It is not an imaging-based AI device that would typically involve human readers interpreting images. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply to this type of device.

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

• Yes, the primary performance evaluation of the Xpert Xpress MVP test in the clinical study was standalone.
• The device is an automated, qualitative in vitro diagnostic test that performs sample preparation, nucleic acid extraction and amplification, and detection, and provides results "within 60 minutes." The clinical performance tables (Table 5-13) represent the direct output of the device compared to reference methods, without human interpretation of the device's signal directly impacting the final result reported by the device itself.
• Human involvement is in specimen collection, loading the cartridge, and reviewing the system's final reported result for the pathogen. The device's diagnostic output for a given sample is fully automated.

7. The Type of Ground Truth Used

The ground truth varied by the target organism:

• Bacterial Vaginosis (BV): An FDA-cleared nucleic acid amplification test (NAAT).
• Candida group and Candida glabrata/krusei: Yeast culture followed by mass spectrometry for species identification. For Candida glabrata/krusei, there was also a "contrived" study, meaning the ground truth was based on known concentrations of the organisms.
• Trichomonas vaginalis (TV): A Patient Infected Status (PIS) algorithm that included results from an FDA-cleared NAAT and TV culture.
• Discrepancy Resolution: For all targets, a second FDA-cleared NAAT was used for investigation of discrepant results, effectively serving as an adjudication method to establish the clinical ground truth for those specific samples.

8. The Sample Size for the Training Set

The document describes the clinical study as a "performance evaluation" and "method comparison clinical study" used to demonstrate substantial equivalence. It does not explicitly reference or describe a separate "training set" for the device's algorithm in the context of machine learning, because this is a molecular diagnostic test based on PCR, not an adaptable AI algorithm that is trained on data in the traditional sense. The development of such a device involves assay design and optimization rather than machine learning training sets.

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

Since there is no explicit mention of a "training set" in the context of an AI/ML algorithm for this PCR-based diagnostic device, the concept of establishing ground truth for a training set as typically described for AI/ML devices doesn't apply. The development and validation of the device would have involved extensive laboratory (non-clinical) studies, including analytical sensitivity (LoD), analytical reactivity (inclusivity), analytical specificity (exclusivity), microbial interference, competitive interference, interfering substances, and carry-over contamination studies (as described in Section 5.4), where the "ground truth" for these studies would be precisely controlled laboratory-prepared samples with known concentrations of target organisms and potential interferents.

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Genex® Bone Graft Substitute injectable paste provides a bone graft substitute that resorbs and is replaced with bone during the healing process.
• Genex® Bone Graft Substitute is indicated only for bony voids or defects/gaps that are not intrinsic to the stability of the bony structure
• Genex® Bone Graft Substitute is indicated to be gently packed into voids or defects of the skeletal system (i.e long bones, extremities, posterolateral spine and pelvis)
• Genex® Bone Graft Substitute resultant paste can be injected, digitally packed into the bone in situ or moulded into solid implants that are to be gently packed into the defect
• The bony defects or cavities may be surgically created or the result of traumatic injury. Genex® Bone Graft Substitute provides a bone graft substitute that resorbs and is replaced with bone during the healing process

Genex® Bone Graft Substitute is a simple to use synthetic resorbable material designed to promote regeneration of bone in osseous defects. It degrades into component elements normally found in the body and is highly biocompatible. The kit contains a powder and mixing solution which, when combined, provides a mouldable cohesive paste. When injected the mixture sets to form Genex® Bone Graft substitute, a hard but resorbable matrix. Genex® Bone Graft Substitute is supplied sterile.
Genex® Bone Graft Substitute, accessories and packaging are not made from natural rubber latex.

The provided text is a 510(k) summary for the Genex® Bone Graft Substitute. It does not contain information about acceptance criteria or a study proving the device meets specific performance metrics in terms of effectiveness or outcomes.

The document primarily focuses on demonstrating substantial equivalence to a predicate device (Genex® K082381) based on:

• Intended Use / Indications for Use: These are stated to be the same as the predicate device.
• Technological Differences: The subject device is presented as a closed mixing system with differences in the number of syringes and mixing method, but these are claimed not to raise safety and effectiveness concerns.
• Non-Clinical Testing: This includes "Biocompatibility testing, Shelf-Life validation studies and Porosity testing." The summary states that these tests demonstrate substantial equivalence and do not raise new safety or effectiveness concerns.

Therefore, I cannot provide the requested information regarding acceptance criteria and studies proving the device meets them because this information is not present in the provided text. The document is concerned with regulatory clearance via substantial equivalence, not with presenting a efficacy study.

Here's a breakdown of why each requested point cannot be answered:

1. A table of acceptance criteria and the reported device performance: Not provided. The document mentions "non-clinical testing" like biocompatibility, shelf-life, and porosity, but it doesn't list specific acceptance criteria (e.g., a certain percentage of bone growth, time to resorption) or performance outcomes from these tests.
2. Sample size used for the test set and the data provenance: Not provided. No efficacy or outcome study is described.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. No human interpretation of results for an efficacy study is described.
4. Adjudication method for the test set: Not applicable.
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: Not applicable. This device is a bone graft substitute, not an AI-powered diagnostic tool.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done: Not applicable.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.): Not provided. No efficacy or outcome study is described.
8. The sample size for the training set: Not applicable. This device is a medical product, not an AI algorithm requiring a training set.
9. How the ground truth for the training set was established: Not applicable.

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The Xpert BCR-ABL Ultra test is an in vitro diagnostic test for the quantitation of BCR-ABL1 and ABL1 mRNA transcripts in peripheral blood specimens of diagnosed t(9;22) positive Chronic Myeloid Leukemia (CML) patients expressing BCR-ABLI fusion transcripts type e13a2 and/or e14a2. The test utilizes automated, quantitative, real-time reverse transcription polymerase chain reaction (RT-qPCR). The Xpert BCR-ABL Ultra test is intended to measure BCR-ABL1 to ABL1 percent ratios on the International Scale (IS), and also expressed as a log molecular reduction (MR value) from a baseline of 100% (IS), in t(9;22) positive CML patients during of treatment with Tyrosine Kinase Inhibitors (TKIs).

The test does not differentiate between e13a2/b2a2 or e14a2/b3a2 fusion transcripts and does not monitor other rare fusion transcripts resulting from t(9;22). This test is not intended for the diagnosis of CML.

The Xpert BCR-ABL Ultra test is intended for use only on the Cepheid GeneXpert® Dx System and the GeneXpert Infinity System.

The Xpert BCR-ABL Ultra test is an automated in vitro diagnostic test for quantifying the amount of BCR-ABLI (BCR-ABL, hereafter) mRNA transcript as a ratio of BCR-ABL/ABL per the International Scale (IS).

The test is performed on the Cepheid GeneXpert® Dx System and GeneXpert Infinity System (referred to as the GeneXpert systems). The GeneXpert 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 and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized. The GeneXpert 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), and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.

The Xpert BCR-ABL Ultra test includes reagents to detect BCR-ABL fusion genes resulting from two major breakpoints, translocation e13a2/b2a2 and e14a2/b3a2 and the ABL transcript as an endogenous control in peripheral blood specimens. The amount of BCR-ABL transcript in the patient sample is reported as a percent ratio of BCR-ABL/ABL on the International Scale (IS), and also expressed as a log molecular reduction (MR value) from a baseline of 100% (IS), using the GeneXpert software.

There are two controls included in each Xpert BCR-ABL Ultra test, which are the ABL Endogenous Control and the Probe Check Control (PCC). The ABL Endogenous Control normalizes the BCR-ABL target and ensures that sufficient sample is used in the test. The PCC verifies reagent rehydration. PCR tube filling, and that all reaction components, including probes and dyes, are present and functional in the cartridge.

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

Acceptance Criteria and Device Performance for Xpert® BCR-ABL Ultra

Note: The provided document is a 510(k) Summary, which typically focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating pre-defined "acceptance criteria" in a quantitative, pass/fail manner. For this analysis, I will infer relevant performance metrics from the non-clinical and clinical studies presented as evidence of substantial equivalence. The "Acceptance Criteria" column will represent the demonstrated performance that FDA found acceptable for classification, and the "Reported Device Performance" will be the specific results from the studies.

1. Table of Acceptance Criteria and Reported Device Performance

• Linear regression R² for e13a2/b2a2 breakpoint.
• Linear regression R² for e14a2/b3a2 breakpoint.
• Maximum Standard Deviation (SD) within reportable range. | - e13a2/b2a2: R² = 0.98304
• e14a2/b3a2: R² = 0.9788
• Maximum SD = 0.26 (within reportable range of MR0.26 to MR4.52) |
  | Analytical Sensitivity (LoD):
• LoD for e13a2/b2a2 breakpoint (target 95% positivity).
• LoD for e14a2/b3a2 breakpoint (target 95% positivity).
• Overall LoD claimed for both breakpoints. | - e13a2/b2a2: 0.0030% (IS)/MR4.52 (95.74% positivity at this level)
• e14a2/b3a2: 0.0029% (IS)/MR4.55 (96.04% positivity at this level)
• Overall LoD: 0.0030% (IS)/MR4.52 |
  | Analytical Sensitivity (LoQ):
• Equivalence to LoD.
• MR Standard Deviation for e13a2/b2a2 and e14a2/b3a2 within defined limits (e.g.,

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The Xpert® CT/NG test, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamvdia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease in the urogenital tract and extragenital sites (pharynx and rectum). The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, patient-collected vaginal swabs (collected in a clinical setting), clinician-collected endocervical swabs, and female and male pharyngeal and rectal swabs.

The Xpert CT/NG test is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG). The test is performed on the Cepheid GeneXpert Instrument Systems. The Xpert CT/NG test on the GeneXpert Instrument System automates and integrates sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The system consists of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The system requires 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.

The Xpert CT/NG test includes reagents for the detection and differentiation of CT and NG. A Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the PCR reaction. The SAC reagents detect the presence of a single copy human gene and monitor whether the specimen contains human cells. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System. GeneXpert Infinity-48s. and the GeneXpert Infinity-80 System, 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.

The ancillary specimen collection kits for use with the Xpert CT/NG test are the Xpert Vaginal/Endocervical Specimen Collection Kit, Xpert Swab Specimen Collection kit and the Xpert Urine Specimen Collection kit.

This looks like a 510(k) summary for the Cepheid Xpert CT/NG test. The document provides information on analytical and clinical performance studies.

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

1. Table of acceptance criteria and the reported device performance:

The document doesn't explicitly state "acceptance criteria" with numerical targets for clinical performance (sensitivity, specificity) in the same way it defines LoD for analytical sensitivity. However, based on the presentation and context, the reported sensitivities and specificities from the clinical performance study appear to be the performance demonstrated to justify substantial equivalence.

Since the submission is for a 510(k), the implied "acceptance criteria" for clinical performance is that the device's performance is substantially equivalent to a predicate device. The document states "the Xpert CT/NG test performance is equivalent to the predicate" in the conclusions.

Here's a table summarizing the reported clinical performance:

Analytical Sensitivity (LoD) - (Example of explicit acceptance criteria and performance)

• Acceptance Criteria for LoD: The lowest concentration at which 95% of at least 20 replicates are positive.
• Reported Device Performance (LoD - Pharyngeal Swab Matrix):
  • CT ATCC vr885 serovar D: 161 EB/mL
  • CT ATCC vr879 serovar H: 225 EB/mL
  • NG ATCC 19424: 7.1 CFU/mL
  • NG ATCC 49226: 6.4 CFU/mL
• Reported Device Performance (LoD - Rectal Swab Matrix):
  • CT ATCC vr885 serovar D: 88 EB/mL
  • CT ATCC vr879 serovar H: 161 EB/mL
  • NG ATCC 19424: 4.9 CFU/mL
  • NG ATCC 49226: 5.3 CFU/mL

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

• Sample Size for Test Set:
  • Pharyngeal Swabs: 2577 specimens (eligible for inclusion in data analyses)
  • Rectal Swabs: 2538 specimens (eligible for inclusion in data analyses)
• Data Provenance:
  • Country of Origin: United States ("multi-site prospective investigational study at 9 US institutions").
  • Retrospective or Prospective: Prospective ("multi-site prospective investigational study").

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

The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that the ground truth was established using an "anatomic site infected status (ASIS) algorithm based on combined results from two NAAT tests, with a tiebreaker NAAT test if applicable." This suggests a reliance on laboratory test results rather than human expert interpretation of raw data.

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

The adjudication method used for establishing the ASIS (ground truth) was a form of 2+1 rule:

• The anatomic site was considered infected if both primary reference NAAT test results were positive.
• The anatomic site was considered not infected if both primary reference NAAT test results were negative.
• If there was discordance between the two primary reference tests, an additional (tiebreaker) NAAT was performed. In this case, agreement of 2 out of 3 (two primary reference tests + tiebreaker) determined the ASIS result.

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 done. This study is an analytical and clinical performance evaluation of an in vitro diagnostic (IVD) nucleic acid amplification test (NAAT), not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.

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

Yes, a standalone performance study was done. The study directly compares the results of the Xpert CT/NG test (algorithm only) to the established ASIS ground truth for each specimen. There is no human-in-the-loop component mentioned for the interpretation of the Xpert CT/NG results themselves.

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

The ground truth used was Anatomic Site Infected Status (ASIS), which was determined by a composite reference method involving multiple nucleic acid amplification tests (NAATs). This is a type of laboratory-based diagnostic ground truth, not pathology, expert consensus on images, or long-term outcomes data.

8. The sample size for the training set:

The document does not provide information on the sample size for a training set. This is typical for traditional in vitro diagnostic (IVD) submissions like this one, as the assay development and validation generally don't utilize "training sets" in the same way machine learning algorithms do. The studies described are for validation of the final device.

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

Not applicable, as a distinct training set and its ground truth establishment are not discussed in this document, which focuses on the validation of the Xpert CT/NG assay.

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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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