(160 days)
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 | Metric (Clinical Study) | Clinician-collected (CVS) Performance (95% CI) | Self-collected (SVS) Performance (95% CI) |
|---|---|---|---|
| BV | PPA | 92.9% (429/462) (90.1% - 94.9%) | 93.5% (434/464) (90.9% - 95.4%) |
| NPA | 94.5% (719/761) (92.6% - 95.9%) | 93.6% (711/760) (91.6% - 95.1%) | |
| Candida group* | Sensitivity | 98.1% (360/367) (96.1% - 99.1%) | 97.8% (359/367) (95.8% - 98.9%) |
| Specificity | 94.9% (820/864) (93.2% - 96.2%) | 92.9% (804/865) (91.0% - 94.5%) | |
| Candida glab-krus | Sensitivity (Fresh Pros.) | 94.1% (32/34) (80.9% - 98.4%) | 100% (33/33) (89.6% - 100%) |
| Specificity (Fresh Pros.) | 99.8% (1195/1197) (99.4% - 99.9%) | 99.7% (1195/1199) (99.1% - 99.9%) | |
| Sensitivity (Contrived) | 99.0% (98/99) (94.5%-99.8%) | N/A | |
| Specificity (Contrived) | 96.4% (27/28) (82.3%-99.4%) | N/A | |
| TV | PPA (Fresh Pros.) | 98.0% (48/49) (89.3% - 99.6%) | 97.9% (47/48) (89.1% - 99.6%) |
| NPA (Fresh Pros.) | 99.6% (1155/1160) (99.0% - 99.8%) | 99.7% (1159/1162) (99.2% - 99.9%) | |
| PPA (Contrived) | 94.4% (84/89) (87.5%-97.6%) | N/A | |
| NPA (Contrived) | 100% (29/29) (88.3%-100%) | N/A |
*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.
§ 866.3975 Device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis.
(a)
Identification. A device that detects nucleic acid sequences from microorganisms associated with vaginitis and bacterial vaginosis is a qualitative in vitro diagnostic device intended for the detection of microbial nucleic acid sequences in vaginal specimens collected from patients with signs and symptoms of vaginitis or bacterial vaginosis. This device is intended to aid in the diagnosis of vaginitis or bacterial vaginosis when used in conjunction with clinical signs and symptoms and other laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) Documentation with a detailed device description of device components; ancillary reagents required but not provided; and explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(ii) Documentation with information that demonstrates the performance characteristics of the device, including:
(A) Limit of Detection;
(B) Precision (reproductivity);
(C) Analytical specificity;
(D) Analytical reactivity (inclusivity);
(E) Specimen stability; and
(F) Effects of interfering substances.
(iii) Detailed documentation from a prospective clinical study. As appropriate to the intended use, the prospective clinical study must be performed on an appropriate study population, including women of various ages and ethnicities. The prospective clinical study must compare the device performance to results obtained from well-accepted comparator methods.
(iv) Detailed documentation for device software, including software applications and hardware-based devices that incorporate software.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed explanation of the interpretation of results and acceptance criteria;
(ii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, clinical performance stratified by patient demographics such as race, ethnicity, age, and pregnancy status.
(iii) For devices with an intended use that includes detection of nucleic acid sequences from bacteria associated with bacterial vaginosis, a summary of device results in an asymptomatic population with demographic characteristics appropriate to the intended use population.
(iv) For devices with an intended use that includes detection of either Candida species or bacteria associated with bacterial vaginosis, a limitation that
Candida species and bacterial compositions associated with bacterial vaginosis can be present as part of normal vaginal flora and results should be considered in conjunction with available clinical information.