(391 days)
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:
| Metric | Reported Device Performance (%) (95% CI) |
|---|---|
| Sensitivity | 93.5% (85.7 – 97.2) |
| Specificity | 95.5% (93.9 – 96.7) |
| PPV | 66.1% (56.8 – 74.3) |
| NPV | 99.4% (98.5 – 99.7) |
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.
§ 866.3740
Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.