(199 days)
The Xpert® CT/NG Assay, 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 Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal urogenital disease. The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).
Ancillary Collection Kits Indications for Use:
The Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve and transport patient Chiamydia trachomatis and Neisseria gonorrhoeae DNA in endocervical and vaginal specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.
The Cepheid® Xpert® CT/NG Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis and Neisseria gonorrhoeae DNA in first-catch male and female urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Cepheid Xpert CT/NG Assay.
The Xpert CT/NG Assay is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoege (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The GeneXpert Instrument Systems automate and integrate sample purification, nucleic acid amplification, and detection of the target sequences in simple or complex samples using real-time PCR and RT-PCR assays. The systems consist of an instrument, personal computer, and preloaded software for running the tests on collected samples 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 selfcontained, cross-contamination between cartridges during the testing process is minimized.
The Xpert CT/NG Assay includes reagents for the 5' exonuclease real-time PCR detection and differentiation of CT and NG. Reagents for the detection of a Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included in the cartridge. 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 DNA. The PCC verifies reagent rehydration. PCR tube filling in the cartridge, probe integrity, and dye stability. The primers and probes in the Xpert CT/NG Assay detect chromosomal sequences in the bacteria. One target is detected for CT (CT1) and two different targets are detected for NG (NG2 and NG4). Both NG targets need to be positive for the Xpert CT/NG Assay to return a positive NG result.
The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System 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 svringe 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 Assay are the Cepheid® Xpert® CT/NG Vaginal/Endocervical Specimen Collection Kit and the Cepheid® Xpert® CTNG Urine Specimen Collection Kit.
This response describes the acceptance criteria and the study that proves the device meets the acceptance criteria, as extracted from the provided text.
Acceptance Criteria and Device Performance
The acceptance criteria for the Xpert CT/NG Assay are primarily demonstrated through its analytical sensitivity (Limit of Detection - LoD), analytical specificity (cross-reactivity), and clinical performance (sensitivity and specificity compared to a Patient Infected Status algorithm).
Table of Acceptance Criteria and Reported Device Performance (Clinical Performance - Overall "All" Category):
| Test | Specimen Type | Acceptance Criteria (Implied by achieved performance, generally high sensitivity/specificity) | Reported Sensitivity % (95% CI) | Reported Specificity % (95% CI) |
|---|---|---|---|---|
| Chlamydia trachomatis (CT) | Patient-collected Vaginal Swab | High performance necessary for diagnostic aid | 99.5 (97.3-100) | 99.1 (98.8-99.4) |
| Endocervical Swab | High performance necessary for diagnostic aid | 96.0 (92.3-98.3) | 99.6 (99.3-99.7) | |
| Female Urine | High performance necessary for diagnostic aid | 98.1 (95.2-99.5) | 99.8 (99.6-99.9) | |
| Male Urine | High performance necessary for diagnostic aid | 98.5 (95.6-99.7) | 99.8 (99.6-99.9) | |
| Neisseria gonorrhoeae (NG) | Patient-collected Vaginal Swab | High performance necessary for diagnostic aid | 100 (93.2-100) | 99.9 (99.8-100) |
| Endocervical Swab | High performance necessary for diagnostic aid | 100 (93.2-100) | >99.9 (99.8-100) | |
| Female Urine | High performance necessary for diagnostic aid | 94.4 (84.6-98.8) | >99.9 (99.9-100) | |
| Male Urine | High performance necessary for diagnostic aid | 98.3 (94.1-99.8) | 99.9 (99.7-100) |
Note: The document does not explicitly state pre-defined numerical "acceptance criteria" thresholds for clinical performance. Instead, it presents the achieved performance metrics, which are then assessed for substantial equivalence to predicate devices.
Study Information
1. Sample sizes used for the test set and data provenance:
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Clinical Study:
- Female Subjects: A total of 3767 female subjects were included in the overall clinical performance analysis across various specimen types.
- Patient-Collected Vaginal Swabs (PC-VS) analyzed for CT: 3766 subjects
- Endocervical Swabs (ES) analyzed for CT: 3757 subjects
- Female Urine analyzed for CT: 3767 subjects
- PC-VS analyzed for NG: 3766 subjects
- ES analyzed for NG: 3757 subjects
- Female Urine analyzed for NG: 3767 subjects
- Male Subjects: A total of 3436 male subjects were included in the overall clinical performance analysis.
- Male Urine analyzed for CT: 3436 subjects
- Male Urine analyzed for NG: 3436 subjects
- Data Provenance: The study was a "multi-site prospective investigational study at 36 US and UK institutions". This indicates the data is prospective and collected from multiple countries (United States and United Kingdom).
- Female Subjects: A total of 3767 female subjects were included in the overall clinical performance analysis across various specimen types.
-
Reproducibility Study (Test Set):
- Panel of 22 specimens (11 in urine matrix, 11 in swab matrix), tested 4 times per day, by 2 operators, for 5 days, across 3 sites.
- Total replicates per panel member: 22 specimens x (4 runs/day * 5 days * 2 operators * 3 sites) = 120 replicates per panel member.
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Instrument System Precision Study (Test Set):
- Panel of 20 specimens (10 in urine matrix, 10 in swab matrix), tested on 12 different days by 2 operators, with each operator conducting 4 runs of each panel specimen per day on each of two instrument systems.
- Total replicates per panel member: 20 specimens x (4 runs/day * 12 days * 2 operators * 2 instrument systems) = Approximately 191-192 total agreement results reported per panel member depending on specific run outcomes (ERROR, INVALID, NO RESULT).
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the clinical study (Patient Infected Status - PIS) was established using an algorithm based on the results from two currently marketed NAAT tests (predicate devices). The document does not specify the number or qualifications of human experts involved in establishing the PIS, as it relies on a composite reference standard from established molecular diagnostic tests (GEN-PROBE® APTIMA® Combo 2 Assay and Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay).
3. Adjudication method for the test set:
- For the clinical study, the PIS algorithm was defined as:
- Infected (I) for CT or NG: If at least one positive result was reported from each of the two reference NAAT tests.
- Equivocal (EQ): If both NAAT tests resulted in equivocal results for both sample types (swab and urine). (No study participants fell into this category).
- Not Infected (NI): Any other combination of results.
- Specific rules were applied for cases where reference urine was positive and swab negative, or vice versa (e.g., for females, positive on both reference urine and negative on both reference swab would be 'infected' for urine and 'not infected' for swab).
- This approach constitutes a composite reference standard using two predicate devices. It's not a typical human expert adjudication method (e.g., 2+1), but rather an algorithmic adjudication based on existing cleared tests.
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 MRMC comparative effectiveness study was performed or described. This device is an automated, qualitative in vitro real-time PCR test, meaning it directly detects and differentiates genomic DNA. It does not involve human readers interpreting results, nor does it incorporate AI for diagnostic assistance in the manner typically described in MRMC studies.
5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the clinical performance study evaluated the Xpert CT/NG Assay as a standalone algorithm (device only) against the Patient Infected Status (PIS) algorithm. The device is designed to be fully automated and provides qualitative results (DETECTED, NOT DETECTED), thus it inherently operates without human interpretation of the primary result.
6. The type of ground truth used:
- The ground truth for the clinical performance study was a Patient Infected Status (PIS) algorithm, which served as a composite reference standard. This PIS was derived from the combined results of two predicate (legally marketed) Nucleic Acid Amplification Tests (NAATs): GEN-PROBE® APTIMA® Combo 2 Assay and Becton Dickenson ProbeTec™ ET Chlamydia trachomatis /Neisseria gonorrhoeae Amplified DNA Assay.
7. The sample size for the training set:
- The document describes pre-market non-clinical (analytical) and clinical validation studies. There is no mention of a separate "training set" in the context of machine learning model development. This device is a real-time PCR assay, not a machine learning or AI-based diagnostic that typically undergoes an explicit training phase with a distinct training dataset. The development of such an assay involves analytical optimization and robust validation rather than AI model training.
8. How the ground truth for the training set was established:
- As the device is a real-time PCR assay and not an AI/ML-based system, an explicit "training set" with ground truth in the AI sense is not applicable. The development cycle would involve designing primers and probes, optimizing reaction conditions, and verifying analytical performance against known standards and cultured organisms to establish the assay's ability to detect target DNA. For the non-clinical analytical studies (e.g., LoD, specificity), the ground truth was established by using purified elementary bodies or cells of known organisms at specified concentrations (e.g., ATCC reference strains) or well-characterized human biological samples confirmed negative for the targets.
§ 866.3390
Neisseria spp. direct serological test reagents.(a)
Identification. Neisseria spp. direct serological test reagents are devices that consist of antigens and antisera used in serological tests to identifyNeisseria spp. from cultured isolates. Additionally, some of these reagents consist ofNeisseria spp. antisera conjugated with a fluorescent dye (immunofluorescent reagents) which may be used to detect the presence ofNeisseria spp. directly from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusNeisseria, such as epidemic cerebrospinal meningitis, meningococcal disease, and gonorrhea, and also provides epidemiological information on diseases caused by these microorganisms. The device does not include products for the detection of gonorrhea in humans by indirect methods, such as detection of antibodies or of oxidase produced by gonococcal organisms.(b)
Classification. Class II (performance standards).