(146 days)
The Cepheid Xpert GBS performed on the GeneXpert is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens, using fully automated real-time polymerase chain reaction (PCR) with fluorogenic detection of the amplified DNA. Xpert GBS Assay testing is indicated for rapid identification of antepartum and intrapartum GBS colonization.
- . The use of the Xpert GBS for intrapartum screening should not preclude the use of other strategies (e.g., antepartum testing). Intrapartum Xpert GBS results are useful to identify candidates for intrapartum antibiotic prophylaxis when administration of intravenous antibiotics is not delayed pending results.
- . The Xpert GBS assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
The Xpert GBS™ is a rapid, fully-automated DNA test for detecting GBS directly from vaginal/rectal swab specimens from pregnant women. A swab containing the specimen is inserted into an individual single-use multi-chambered cartridge (the Xpert GBSTM cartridge) along with the specified single-use reagents (Reagent 1 and Reagent 2) that are provided with the assay. The user initiates a test from the system user interface, the instrument signals the user where to place the cartridge by flashing a green light, and the cartridge is placed into the indicated module in the GeneXpert Dx System instrument. The GeneXpert Dx System has 1 to 4 randomly accessible modules, each of which can process one sample. The instrument moves the sample and reagents to and from different chambers within the Xpert GBS™ cartridge for sample preparation, hydrates dry reagent beads containing critical components, fills the reaction tube with the final reaction mixture, and performs optical probe checks to ensure proper tube fill and presence of probes. The reaction mixture is then subjected to PCR thermal cycling and real-time detection of DNA. The Xpert GBS™ completes sample preparation and real-time PCR for GBS in approximately 75 minutes.
Here's an analysis of the provided text to extract the acceptance criteria and study details for the Xpert GBS™ device:
Acceptance Criteria and Device Performance for Xpert GBS™
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance characteristics presented relative to the CDC-recommended culture technique. Given that the submission is for substantial equivalence to a predicate device, the performance of the Xpert GBS™ is primarily compared to the predicate device and the gold standard culture method. Explicit, pre-defined numerical acceptance criteria are not presented in a formal "acceptance criteria" section but are evident from the reported sensitivity and specificity values.
| Performance Metric | Acceptance Criteria (Implied by Predicate/Gold Standard Comparison) | Xpert GBS™ Reported Performance (Overall) | Xpert GBS™ Reported Performance (Intrapartum) | Xpert GBS™ Reported Performance (Antepartum) |
|---|---|---|---|---|
| Sensitivity | Substantially equivalent to predicate, and sufficiently high compared to CDC culture for GBS detection. (Predicate: 82.4%) | 91.1% (95% CI = 86.1-94.7%) | 94.6% (95% CI = 87.9–98.2%) | 87.6% (95% CI = 79.4-93.4%) |
| Specificity | Substantially equivalent to predicate, and sufficiently high compared to CDC culture for GBS detection. (Predicate: 94.8%) | 96.0% (95% CI = 94.0-97.4%) | 94.8% (95% CI = 91.8–96.9%) | 97.4% (95% CI = 94.7-98.9%) |
| Reproducibility | High agreement across sites and days for varying GBS concentrations. | 100% agreement across 3 sites, 10 days, 4 specimen types (Negative, Weak Positive, Positive, Strong Positive) | 100% agreement across 3 sites, 10 days, 4 specimen types (Negative, Weak Positive, Positive, Strong Positive) | 100% agreement across 3 sites, 10 days, 4 specimen types (Negative, Weak Positive, Positive, Strong Positive) |
| Analytical Sensitivity (LoD) | Clear limit of detection for target organism. | 25 genome copies per reaction (~4-8 CFU per reaction) | N/A | N/A |
| Analytical Specificity | No cross-reactivity with common vaginal/anal flora or phylogenetically related species. | No positive results for 28 non-GBS Streptococcal isolates. Weakly positive in 1/6 replicates for 4 out of 73 other strains (Enterococcus gallinarium, Staphylococcus simulans, Micrococcus luteus, Propionibacterium acnes). | N/A | N/A |
2. Sample Sizes Used for the Test Set and Data Provenance
- Clinical Study Test Set Sample Size: 784 maternity patients
- 366 antepartum subjects
- 418 intrapartum subjects
- Data Provenance: Prospective investigational study conducted at six institutions with maternity services in the United States.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
- The document does not specify the number of experts or their qualifications for establishing the ground truth. The ground truth was established by a culture technique recommended by the Centers for Disease Control and Prevention (CDC). This implies standard laboratory personnel performing the culture, rather than a panel of clinical experts adjudicating cases.
4. Adjudication Method for the Test Set
- None, in the sense of expert review or consensus. The ground truth was determined solely by the CDC-recommended culture method, which is a laboratory standard rather than an adjudicated clinical finding.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is a standalone diagnostic assay (Nucleic Acid Amplification Assay System) and not an AI-assisted diagnostic tool for human interpretation. The comparison was between the new assay (Xpert GBS™), a predicate assay (IDI-Strep B™ Assay), and a standard culture method.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, the clinical study evaluated the Xpert GBS™ Assay as a standalone diagnostic device. Its performance was measured directly against the CDC-recommended culture technique. It is a "fully-automated DNA test" where the instrument completes "sample preparation and real-time PCR for GBS in approximately 75 minutes," and provides "result interpretation."
7. The Type of Ground Truth Used
- Expert Consensus Pathology / Clinical Outcomes Data: The ground truth for the clinical study was established by a culture technique recommended by the Centers for Disease Control and Prevention (CDC). This involved:
- Microbiological culture in selective broth medium (LIM broth).
- Overnight incubation.
- Subculture onto solid blood agar medium.
- Specific identification of colonies suggestive of GBS with slide agglutination tests.
8. The Sample Size for the Training Set
- The document does not explicitly state a separate training set size for the Xpert GBS™ assay. This is typical for PCR-based diagnostic assays, where a "training set" in the machine learning sense isn't used. Instead, assay development involves analytical studies (specificity, sensitivity/LoD) and then validation with clinical samples. The "multi-center study (Protocol 101, Rev. 5)" using 784 patients serves as the primary clinical validation (test) set.
9. How the Ground Truth for the Training Set Was Established
- As mentioned above, a "training set" in the machine learning context is not applicable here. For the analytical studies (specificity, LoD), the ground truth was established by:
- Analytical Specificity: Using known genomic DNA from 101 identified strains (28 Streptococci, 73 other species including microflora and human DNA) at controlled concentrations. The "ground truth" here is the known identity of the organisms.
- Analytical Sensitivity (LoD): Using 11 Streptococcus agalactiae strains representing nine known serotypes, with quantitated culture and purified genomic DNA. The "ground truth" here is the known presence and concentration of GBS.
§ 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.