(77 days)
The Cepheid Xpert TV Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test for the detection of Trichomonas vaginalis genomic DNA. The test utilizes automated real-time polymerase chain reaction (PCR) to detect Trichomonas vaginalis genomic DNA. The Xpert TV Assay uses female and male urine specimens, endocervical swab specimens, and patient-collected vaginal swab specimens (collected in a clinical setting). The Xpert TV Assay is intended to aid in the diagnosis of trichomoniasis in symptomatic or asymptomatic individuals.
Ancillary Collection Kits:
Xpert Vaginal/Endocervical Specimen Collection Kit
The Cepheid® Xpert® Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.
Xpert Urine Specimen Collection Kit
The Cepheid® Xpert® Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis. Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in first-catch female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.
The Xpert TV Assay is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of genomic DNA from Trichomonas vaginalis. The Xpert TV Assay is intended as an aid in the diagnosis of trichomoniasis.
The Xpert TV Assay is performed on the Cepheid GeneXpert® Instrument Systems (GeneXpert Dx., GeneXpert Infinity-48, GeneXpert Infinity-48s, and GeneXpert Infinity-80 systems). The GeneXpert Instrument System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Instrument Systems require the use of single-use, disposable cartridges (the Xpert TV 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 Xpert TV Assay cartridges contain reagents for the detection of genomic DNA from T. vaginalis for use with the following specimens collected from symptomatic and asymptomatic individuals: female and male urine, endocervical swab and patientcollected vaginal swab (collected in a clinical setting). A Sample Processing Control (SPC), Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are controls utilized by the GeneXpert Instrument System platform. The SPC, SAC, and PCC are controls utilized by the GeneXpert Instrument System platform. The SPC is present to control for adequate processing of the target trichomonads and to monitor the presence of inhibitors in the real-time PCR reaction to reduce the possibility of false negative results. 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, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of genomic DNA from T. vaginalis in 70 minutes or less. The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems and the GeneXpert Infinity Systems, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores', and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
The swab and/or urine specimens are collected from asymptomatic or symptomatic patients and placed into a specimen transport tube containing preservative. The specimen is transferred to the sample chamber of the disposable fluidic cartridge (the Xpert TV cartridge). The user initiates a test from the system user interface and places the cartridge into the GeneXpert instrument platform, which performs hands-off real-time, multiplex PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
The ancillary specimen collection kits for use with the Xpert TV Assay are the Cepheid Xpert Vaginal/Endocervical Specimen Collection Kit and the Cepheid Xpert Urine Specimen Collection Kit.
This document describes the Xpert TV Assay, a qualitative in vitro diagnostic test for the detection of Trichomonas vaginalis genomic DNA, performed on GeneXpert Instrument Systems.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in a dedicated table. However, the study aims to demonstrate "substantial equivalence" to a predicate device (Cepheid Xpert TV Assay [510(k) #K151565]) based on analytical and clinical performance. The reported performance suggests the device aims for high sensitivity and specificity in detecting T. vaginalis.
The following table summarizes the key performance metrics reported from the clinical study:
| Metric | Specimen Type (Symptomatic Status) | Reported Performance (95% CI) |
|---|---|---|
| Sensitivity | Endocervical Swabs (Symptomatic) | 100% (94.9%-100%) |
| Endocervical Swabs (Asymptomatic) | 98.1% (93.4%-99.8%) | |
| Endocervical Swabs (Overall) | 98.9% (96.0%-99.9%) | |
| Patient-Collected Vaginal Swabs (Symptomatic) | 98.6% (92.7%-100%) | |
| Patient-Collected Vaginal Swabs (Asymptomatic) | 95.0% (89.3%-98.1%) | |
| Patient-Collected Vaginal Swabs (Overall) | 96.4% (92.7%-98.5%) | |
| Female Urine (Symptomatic) | 98.6% (92.5%-100%) | |
| Female Urine (Asymptomatic) | 98.2% (93.6%-99.8%) | |
| Female Urine (Overall) | 98.4% (95.3%-99.7%) | |
| Male Urine (Symptomatic) | 87.5% (71.9%-95.0%) | |
| Male Urine (Asymptomatic) | 90.3% (82.6%-94.8%) | |
| Male Urine (Overall) | 89.6% (83.0%-93.8%) | |
| Specificity | Endocervical Swabs (Symptomatic) | 98.5% (97.2%-99.3%) |
| Endocervical Swabs (Asymptomatic) | 99.1% (98.3%-99.6%) | |
| Endocervical Swabs (Overall) | 98.9% (98.3%-99.3%) | |
| Patient-Collected Vaginal Swabs (Symptomatic) | 99.5% (98.6%-99.9%) | |
| Patient-Collected Vaginal Swabs (Asymptomatic) | 99.6% (99.0%-99.9%) | |
| Patient-Collected Vaginal Swabs (Overall) | 99.6% (99.1%-99.8%) | |
| Female Urine (Symptomatic) | 99.8% (99.1%-100%) | |
| Female Urine (Asymptomatic) | 99.6% (99.0%-99.9%) | |
| Female Urine (Overall) | 99.7% (99.3%-99.9%) | |
| Male Urine (Symptomatic) | 99.8% (99.3%-99.9%) | |
| Male Urine (Asymptomatic) | 99.2% (98.8%-99.4%) | |
| Male Urine (Overall) | 99.3% (99.0%-99.5%) | |
| Reproducibility (Agreement with Expected Results) | FS-Neg (Female Swab Negative) | 100% (144/144) (Across 3 sites) |
| FS-Mod Pos (Female Swab Moderate Positive) | 100% (144/144) (Across 3 sites) | |
| FS-LoD (Female Swab LoD) | 95.8% (138/144) (Across 3 sites) | |
| FS-High Neg (Female Swab High Negative) | 76.4% (110/144) (Across 3 sites) | |
| UR-Neg (Urine Negative) | 100% (144/144) (Across 3 sites) | |
| UR-Mod Pos (Urine Moderate Positive) | 100% (144/144) (Across 3 sites) | |
| UR-LoD (Urine LoD) | 88.8% (127/143) (Across 3 sites) | |
| UR-High Neg (Urine High Negative) | 70.8% (102/144) (Across 3 sites) | |
| Precision (Agreement with Expected Results) | FS-Neg (Female Swab Negative) | 99.7% (287/288) (Across 3 instruments) |
| FS-Mod Pos (Female Swab Moderate Positive) | 100% (288/288) (Across 3 instruments) | |
| FS-LoD (Female Swab LoD) | 91.7% (264/288) (Across 3 instruments) | |
| FS-High Neg (Female Swab High Negative) | 75.6% (217/287) (Across 3 instruments) | |
| UR-Neg (Urine Negative) | 100% (287/287) (Across 3 instruments) | |
| UR-Mod Pos (Urine Moderate Positive) | 100% (288/288) (Across 3 instruments) | |
| UR-LoD (Urine LoD) | 94.1% (271/288) (Across 3 instruments) | |
| UR-High Neg (Urine High Negative) | 77.8% (224/288) (Across 3 instruments) |
2. Sample Size for Test Set and Data Provenance
- Test Set (Clinical Performance):
- Female Study Participants: 1867 unique individuals. However, the tables break down results by specimen type and symptomatic status, showing total N for each subgroup. For example, Endocervical Swabs (Overall) had 1799 samples, Patient-Collected Vaginal Swabs (Overall) had 1791 samples, and Female Urine (Overall) had 1793 samples. It's implied these are from the 1867 female participants.
- Male Study Participants: 4626 unique individuals, with 4611 urine samples tested (Overall).
- Total Tests Performed: 10,017 (including initial invalid results).
- Data Provenance: Prospective, multi-site investigational study with samples collected from 17 clinical sites in the US.
3. Number of Experts and Qualifications for Ground Truth
The document does not explicitly mention "experts" establishing ground truth in the traditional sense of multiple individual reviewers. Instead, the ground truth (Patient Infected Status - PIS) was established algorithmically based on reference laboratory tests:
- For female specimen types: Culture and a validated FDA-cleared NAAT test.
- For male urine: Culture and validated bidirectional sequencing (primary sequencing).
The qualifications of personnel performing these reference tests are not specified but would typically be laboratory professionals trained in these methods.
4. Adjudication Method for the Test Set
The adjudication method was a "patient infected status (PIS) algorithm" defined as follows:
- A study participant was considered infected by PIS if any one of the two reference test results (culture or NAAT/sequencing) were positive.
- The subject was considered not infected by PIS when both reference test results were negative.
For discrepant results between the Xpert TV Assay and the PIS, validated bi-directional Sanger sequencing was performed, but these results were "footnoted for informational purposes only" and did not change the primary PIS definition.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This study focuses on the performance of the device itself (standalone) against a composite reference standard (PIS), not on how human readers' performance might improve with or without AI assistance from this device. The device is an automated in vitro diagnostic test, not an AI-assisted diagnostic aid for human interpretation.
6. Standalone Performance
Yes, a standalone performance study was done. The entire clinical performance section evaluates the Xpert TV Assay's performance (sensitivity, specificity, PPV, NPV) directly against the Patient Infected Status (PIS) algorithm without human interpretation of the device's output. The device itself produces a "TV DETECTED" or "TV NOT DETECTED" result.
7. Type of Ground Truth Used
The ground truth used was a composite reference standard termed "Patient Infected Status (PIS) algorithm." This PIS was established from a combination of:
- Culture
- Validated bidirectional sequencing (for male urine)
- FDA-cleared NAAT test (for female specimens)
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI development. Since this is an in vitro diagnostic device for nucleic acid detection (real-time PCR), it typically relies on pre-defined primer/probe sets and reaction conditions rather than a machine learning model that requires a distinct training set. The assay's development would involve analytical studies (e.g., LoD, inclusivity, specificity) using spiked samples and isolates, but these are not referred to as a "training set" in the common AI sense.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" in the AI sense is not applicable here. The analytical studies (LoD, inclusivity, specificity) used well-characterized Trichomonas vaginalis strains (e.g., ATCC® 30001™, ATCC® 30238™) and other microorganisms at specific concentrations, often spiked into negative clinical matrices. The ground truth for these analytical studies was established by:
- Known concentrations of characterized organisms for LoD and inclusivity.
- Known presence or absence of specific microorganisms at specified concentrations for analytical specificity/cross-reactivity and competitive interference.
- Visual enumeration by light microscopy for T. vaginalis cell counts.
- CFU/mL, genomes/mL, or TCID50/mL for other microorganisms.
§ 866.3860
Trichomonas vaginalis nucleic acid assay.(a)
Identification. ATrichomonas vaginalis nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens, from women symptomatic for vaginitis, cervicitis, or urethritis and/or to aid in the diagnosis of trichomoniasis in asymptomatic women. The detection of trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused byTrichomonas vaginalis .(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection ofTrichomonas vaginalis; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.