(87 days)
The Xpert® CT/NG test, 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 Chlamvdia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal disease in the urogenital tract and extragenital sites (pharynx and rectum). The assay may be used to test the following specimens from asymptomatic and symptomatic individuals: female and male urine, patient-collected vaginal swabs (collected in a clinical setting), clinician-collected endocervical swabs, and female and male pharyngeal and rectal swabs.
The Xpert CT/NG test is an automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG). The test is performed on the Cepheid GeneXpert Instrument Systems. The Xpert CT/NG test on the GeneXpert Instrument System automates and integrates sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The system consists of an instrument, personal computer, and preloaded software for running the tests 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 self-contained, crosscontamination between samples is minimized.
The Xpert CT/NG test includes reagents for the detection and differentiation of CT and NG. A Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included. 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 cells. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.
The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System. GeneXpert Infinity-48s. 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 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 detection.
The ancillary specimen collection kits for use with the Xpert CT/NG test are the Xpert Vaginal/Endocervical Specimen Collection Kit, Xpert Swab Specimen Collection kit and the Xpert Urine Specimen Collection kit.
This looks like a 510(k) summary for the Cepheid Xpert CT/NG test. The document provides information on analytical and clinical performance studies.
Here's a breakdown of the requested information based on the provided text:
1. Table of acceptance criteria and the reported device performance:
The document doesn't explicitly state "acceptance criteria" with numerical targets for clinical performance (sensitivity, specificity) in the same way it defines LoD for analytical sensitivity. However, based on the presentation and context, the reported sensitivities and specificities from the clinical performance study appear to be the performance demonstrated to justify substantial equivalence.
Since the submission is for a 510(k), the implied "acceptance criteria" for clinical performance is that the device's performance is substantially equivalent to a predicate device. The document states "the Xpert CT/NG test performance is equivalent to the predicate" in the conclusions.
Here's a table summarizing the reported clinical performance:
| Specimen Type | Target Organism | Performance Metric | % (95% CI) |
|---|---|---|---|
| Pharyngeal Swab | CT | Sensitivity | 95.9% (86.3-98.9) |
| Pharyngeal Swab | CT | Specificity | 99.7% (99.4-99.8) |
| Rectal Swab | CT | Sensitivity | 86.0% (80.9-89.9) |
| Rectal Swab | CT | Specificity | 99.4% (98.9-99.6) |
| Pharyngeal Swab | NG | Sensitivity | 94.7% (90.7-97.0) |
| Pharyngeal Swab | NG | Specificity | 98.8% (98.3-99.2) |
| Rectal Swab | NG | Sensitivity | 91.2% (86.6-94.4) |
| Rectal Swab | NG | Specificity | 99.6% (99.3-99.8) |
Analytical Sensitivity (LoD) - (Example of explicit acceptance criteria and performance)
- Acceptance Criteria for LoD: The lowest concentration at which 95% of at least 20 replicates are positive.
- Reported Device Performance (LoD - Pharyngeal Swab Matrix):
- CT ATCC vr885 serovar D: 161 EB/mL
- CT ATCC vr879 serovar H: 225 EB/mL
- NG ATCC 19424: 7.1 CFU/mL
- NG ATCC 49226: 6.4 CFU/mL
- Reported Device Performance (LoD - Rectal Swab Matrix):
- CT ATCC vr885 serovar D: 88 EB/mL
- CT ATCC vr879 serovar H: 161 EB/mL
- NG ATCC 19424: 4.9 CFU/mL
- NG ATCC 49226: 5.3 CFU/mL
2. Sample size used for the test set and the data provenance:
- Sample Size for Test Set:
- Pharyngeal Swabs: 2577 specimens (eligible for inclusion in data analyses)
- Rectal Swabs: 2538 specimens (eligible for inclusion in data analyses)
- Data Provenance:
- Country of Origin: United States ("multi-site prospective investigational study at 9 US institutions").
- Retrospective or Prospective: Prospective ("multi-site prospective investigational study").
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that the ground truth was established using an "anatomic site infected status (ASIS) algorithm based on combined results from two NAAT tests, with a tiebreaker NAAT test if applicable." This suggests a reliance on laboratory test results rather than human expert interpretation of raw data.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
The adjudication method used for establishing the ASIS (ground truth) was a form of 2+1 rule:
- The anatomic site was considered infected if both primary reference NAAT test results were positive.
- The anatomic site was considered not infected if both primary reference NAAT test results were negative.
- If there was discordance between the two primary reference tests, an additional (tiebreaker) NAAT was performed. In this case, agreement of 2 out of 3 (two primary reference tests + tiebreaker) determined the ASIS result.
5. 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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study is an analytical and clinical performance evaluation of an in vitro diagnostic (IVD) nucleic acid amplification test (NAAT), not an AI-assisted diagnostic imaging or interpretation device that would involve human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, a standalone performance study was done. The study directly compares the results of the Xpert CT/NG test (algorithm only) to the established ASIS ground truth for each specimen. There is no human-in-the-loop component mentioned for the interpretation of the Xpert CT/NG results themselves.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth used was Anatomic Site Infected Status (ASIS), which was determined by a composite reference method involving multiple nucleic acid amplification tests (NAATs). This is a type of laboratory-based diagnostic ground truth, not pathology, expert consensus on images, or long-term outcomes data.
8. The sample size for the training set:
The document does not provide information on the sample size for a training set. This is typical for traditional in vitro diagnostic (IVD) submissions like this one, as the assay development and validation generally don't utilize "training sets" in the same way machine learning algorithms do. The studies described are for validation of the final device.
9. How the ground truth for the training set was established:
Not applicable, as a distinct training set and its ground truth establishment are not discussed in this document, which focuses on the validation of the Xpert CT/NG assay.
§ 866.3393 Device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s).
(a)
Identification. A device to detect nucleic acids from non-viral microorganism(s) causing sexually transmitted infections and associated resistance marker(s) is an in vitro diagnostic device intended for the detection and identification of nucleic acids from non-viral microorganism(s) and their associated resistance markers in clinical specimens collected from patients suspected of sexually transmitted infections. The device is intended to aid in the diagnosis of non-viral sexually transmitted infections in conjunction with other clinical and laboratory data. These devices do not provide confirmation of antibiotic susceptibility since mechanisms of resistance may exist that are not detected by the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use for the labeling required under § 809.10 of this chapter must include a detailed description of targets the device detects, the results provided to the user, the clinical indications appropriate for test use, and the specific population(s) for which the device is intended.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed discussion of the performance characteristics of the device for all claimed specimen types based on analytical studies, including Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate;
(iii) Detailed descriptions of the test procedure, the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) Limiting statements indicating that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) Reliable results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(D) If appropriate (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer reviewed research), that the clinical performance is inferior in a specific clinical subpopulation or for a specific claimed specimen type; and(v) If the device is intended to detect antimicrobial resistance markers, limiting statements, as appropriate, indicating that:
(A) Negative results for claimed resistance markers do not indicate susceptibility of detected microorganisms, as resistance markers not measured by the assay or other potential mechanisms of antibiotic resistance may be present;
(B) Detection of resistance markers cannot be definitively linked to specific microorganisms and the source of a detected resistance marker may be an organism not detected by the assay, including colonizing flora;
(C) Detection of antibiotic resistance markers may not correlate with phenotypic gene expression; and
(D) Therapeutic failure or success cannot be determined based on the assay results, since nucleic acid may persist following appropriate antimicrobial therapy.
(4) Design verification and validation must include:
(i) Detailed device description documentation, including methodology from obtaining sample to result, design of primer/probe sequences, rationale for target sequence selection, and computational path from collected raw data to reported result (
e.g., how collected raw signals are converted into a reported result).(ii) Detailed documentation of analytical studies, including, Limit of Detection, inclusivity, cross-reactivity, microbial interference, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, within lab precision, and reproducibility, as appropriate.
(iii) Detailed documentation and performance results from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, when determined to be appropriate by FDA, additional characterized clinical samples. The study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained from FDA accepted comparator methods. Documentation from the clinical studies must include the clinical study protocol (including a predefined statistical analysis plan) study report, testing results, and results of all statistical analyses.
(iv) A detailed description of the impact of any software, including software applications and hardware-based devices that incorporate software, on the device's functions.