(153 days)
The cobas® CT/NG for use on the cobas® 6800/8800 Systems is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), and clinician-collected vaginal swab specimens, endocervical swab specimens, oropharyngeal (throat) swab specimens and anorectal swab specimens all collected in cobas® PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt® Solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals.
The cobas® CT/NG for use on the cobas® 6800/8800 systems is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA. The current submission is a device modification for the claim extension to include oropharyngeal (throat) and anorectal swab specimens to cleared clinical specimen types. The assay’s principle relies on polymerase chain reaction (PCR) for amplification and a paired reporter and quencher fluorescence-labeled probes (TaqMan Technology) using fluorescence resonance energy transfer (FRET) for detection. Results are analyzed based on PCR cycle threshold analysis.
Here's a summary of the acceptance criteria and study details for the cobas CT/NG device, extracted from the provided FDA 510(k) clearance letter:
1. Table of Acceptance Criteria (Implicit) and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate table, but the clinical performance results serve as the evidence to meet the implied criteria for sensitivity and specificity in the new specimen types.
| Metric | Target (Implicit Acceptance Criteria) | Reported Device Performance (CT - Anorectal) | Reported Device Performance (CT - Oropharyngeal) | Reported Device Performance (NG - Anorectal) | Reported Device Performance (NG - Oropharyngeal) |
|---|---|---|---|---|---|
| Sensitivity | High (e.g., typically >90% for diagnostic tests) | 95.1% (90.2%, 97.6%) | 100.0% (87.9%, 100.0%) | 99.0% (94.6%, 99.8%) | 100.0% (96.2%, 100.0%) |
| Specificity | High (e.g., typically >95-99% for diagnostic tests) | 99.2% (98.8%, 99.5%) | 99.8% (99.6%, 99.9%) | 99.3% (98.9%, 99.6%) | 98.9% (98.4%, 99.2%) |
Note: The confidence intervals (CIs) are provided as ranges for the reported performance.
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Subjects Enrolled: 2,390 (2,439 subjects were consented, but 49 excluded).
- Anorectal Specimens Tested: 2,365
- Oropharyngeal Specimens Tested: 2,382
- Total Samples: 4,747 (2,365 anorectal + 2,382 oropharyngeal)
- Data Provenance: Multi-site, prospective collection study from 8 geographically diverse clinic sites (STD, HIV, Family Planning, and STD Research). The country of origin is not explicitly stated but is implied to be the US given the FDA clearance.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth was established by a composite reference method using three commercially available CT/NG NAATs. There's no mention of human experts defining the ground truth for individual cases.
4. Adjudication Method for the Test Set
The adjudication method used for establishing the "Infection Status (IS)" (ground truth) was a 2-out-of-3 concordance rule involving three comparator NAAT assays:
- A positive IS was derived when at least 2 of the 3 comparator reference assays were positive.
- If one of the comparator assays was Uninterpretable/Invalid/Failed, the two remaining assays had to be concordant to define the IS as Positive (+) or Negative (-).
- Any other combination of Uninterpretable/Invalid/Failed and valid results were excluded from the analyses.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not conducted. This study focused on the standalone performance of the cobas CT/NG system against a composite reference standard, not on comparing human reader performance with and without AI assistance.
6. If a Standalone Study Was Done
Yes, a standalone study was done. The clinical performance evaluation directly tested the cobas CT/NG system against the established Infection Status (ground truth) for each specimen type. The results are presented as the device's sensitivity and specificity.
7. The Type of Ground Truth Used
The ground truth used was an expert consensus of commercially available NAATs, forming a "Infection Status (IS)" algorithm. It is a composite reference standard.
8. The Sample Size for the Training Set
The document does not provide information on the sample size used for the training set. The 510(k) pertains to a "device change" (claim extension) for an already cleared device (K173887). The training would have occurred during the development of the original cleared device. This submission focuses on the validation for new specimen types.
9. How the Ground Truth for the Training Set Was Established
The document does not provide information on how the ground truth for the training set was established. Similar to the training set size, this information would likely be part of the original K173887 submission for the device development. This current submission focuses on evaluating the device's performance for expanded claims.
§ 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.