(298 days)
The cobas® CT/NG Test is an in vitro nucleic acid amplification test that utilizes Polymerase Chain Reaction (PCR) and nucleic acid hybridization for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonormoeae (NG) DNA to aid in the diagnosis of chlamydial and gonococcal disease. The test may be used with vaginal swab specimens self-collected in a clinical setting and male urine from both symptomatic and asymptomatic individuals. Specimens to be tested should be collected in cobas® PCR Media.
Ancillary Collection Kits
The cobas® PCR Female Swab Sample Kit is used to collect and transport self-collected vaginal swab specimens in a clinical setting. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens. Use this collection kit only with the cobas CT/NG Test. NOTE: This collection kit should not be used for collection of alternative gynecological specimens.
The cobas® PCR Urine Sample Kit is used to collect and transport male urine specimens.
The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this collection kit only with the cobas® CT/NG Test. NOTE: This collection kit should not be used for collection of female urine specimens.
The Roche Molecular Systems (RMS) cobas® CT/NG Test consists of five reagent kits:
- cobas® 4800 System Sample Preparation Kit .
- cobas® 4800 CT/NG Amplification/Detection Kit .
- cobas® 4800 CT/NG Controls Kit .
- . cobas 4800 System Wash Buffer Kit
- . cobas® 4800 System Control Diluent Kit
Sample Collection Kits to be used for the cobas® CT/NG Test are:
- . cobas® PCR Female Swab Sample Kit
- cobas® PCR Urine Sample Kit .
The cobas® CT/NG Test for Chlamvdia trachomatis (CT) and Neisseria gonorrhoeae (NG) is based on two major processes: (1) automated sample preparation to obtain nucleic acids. including CT and NG DNA; (2) simultaneous PCR amplification of target DNA sequences using both CT and NG specific complementary primer pairs and real-time detection of cleaved fluorescent-labeled CT and NG specific oligonucleotide detection probes. Internal control, containing CT and NG DNA, is added to all samples during automated sample preparation and is amplified and detected simultaneously with each sample to monitor the entire process.
The cobas 4800 System utilizes the cobas x 480 Instrument for automated sample preparation, and the automated cobas z 480 Analyzer for automated amplification and detection. The cobas 4800 system software integrates the sample preparation with nucleic acid amplification and detection to generate test results.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
cobas® CT/NG Test: Acceptance Criteria and Study Details
The cobas® CT/NG Test is an in vitro nucleic acid amplification test for the qualitative detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA.
1. Table of Acceptance Criteria and Reported Device Performance
The document describes both non-clinical performance evaluations (analytical sensitivity, inclusivity, specificity, interference, precision) and clinical performance evaluations (reproducibility and a clinical specimen study). The acceptance criteria for analytical and reproducibility studies are generally indicated by the achieved performance (e.g., ≥ 95% detection for LOD, 100% agreement for negative controls, high positive percent agreement for reproducibility). For clinical performance, the reported sensitivity and specificity serve as the primary metrics.
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Analytical Sensitivity (LOD): Target concentration detectable as positive in ≥ 95% of replicates. | C. trachomatis (CT): |
- Urine: 0.75 IFU/mL
- Vaginal Swabs: 10.00 IFU/mL
N. gonorrhoeae (NG):
- Urine: 2.25 CFU/mL
- Vaginal Swabs: 100.00 CFU/mL |
| Inclusivity: Detection of additional CT serovars/variants and NG strains around LOD levels with high positive hit rates. | CT: Analytical sensitivity for 14 serovars + nvCT ranged from 0.125 IFU/mL to 5.0 IFU/mL (PCR Media + urine) and all showed 100% positive hit rates at 10 IFU/mL in stabilized negative vaginal specimens.
NG: Analytical sensitivity for 44 strains ranged from 3.0 CFU/mL to 20 CFU/mL (PCR Media) and was 3.75 CFU/mL (PCR Media + urine). All showed 100% hit rates at 100 CFU/mL in stabilized negative vaginal specimens. |
| Analytical Specificity: No interference with CT/NG detection or false positives from various microorganisms. | No interference with CT/NG detection or false positive results were observed from 184 bacteria, fungi, and viruses, including those commonly found in urogenital tracts. |
| Interference: No or minimal interference from common OTC products and endogenous substances. | - Replens® vaginal moisturizer produced invalid/false negative results in urine panels, but no interference in vaginal swab specimens. - Maximum allowable concentrations of whole blood (> 0.35% v/v in urine, none in vaginal), PBMC cells (> 1 x 10^5 cells/mL), and routine levels of cervical mucus showed no interference. |
| Precision: Anticipated hit rates (e.g., 100% for positive and 0% for negative at LOD levels) and low CVs for Ct values. | CT & NG (PCR Media & PCR Media + Urine): - Negative levels: 0% hit rate
- 1x LOD / Neg: 100% hit rate (CT & NG)
- 1x LOD / 2.5x LOD: 100% hit rate (CT & NG)
- 2.5x LOD / 1x LOD: 100% hit rate (CT & NG)
- Overall CV (%) for Ct values: 1.1% to 1.5% (urine panel, CT); 1.6% to 1.8% (swab panel, CT); 1.2% to 1.5% (urine panel, NG); 1.4% to 1.9% (swab panel, NG). |
| Reproducibility: High percent agreement across lot, site, operator, run, and day. | CT (Urine & Swab Panels): - Negative Percent Agreement (NPA): 100%
- Positive Percent Agreement (PPA): 100%
NG (Urine & Swab Panels): - NPA: 100%
- PPA: Lowest overall was 99.52%. |
| Clinical Sensitivity (Overall): | CT: 95.7% (246/257) (95% CI: 92.5%, 97.6%)
NG: 99.0% (103/104) (95% CI: 94.8%, 99.8%) |
| Clinical Specificity (Overall): | CT: 99.7% (2585/2594) (95% CI: 99.3%, 99.8%)
NG: 99.9% (2744/2747) (95% CI: 99.7%, 100.0%) |
| Clinical Positive Predictive Value (PPV) at study prevalence: | CT: 96.5%
NG: 97.2% |
| Clinical Negative Predictive Value (NPV) at study prevalence: | CT: 99.6%
NG: 100.0% |
2. Sample size used for the test set and the data provenance
- Clinical Specimen Study:
- Sample Size: A total of 2,851 evaluable male and female subjects were enrolled for the clinical specimen study.
- Data Provenance: The study was a multi-center clinical investigation conducted in the United States. Specimens were collected at 12 geographically diverse sites, including OB-GYN practices, public and private STD clinics, and family planning centers. The study was prospective in nature, as subjects were enrolled, and specimens were collected and tested.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The ground truth ("Patient Infected Status") was established using a combination of two commercially available nucleic acid amplification tests (NAATs) for CT and NG, as reference assays. The number and qualifications of experts involved in the interpretation of these reference assays or in establishing a consensus based on them are not explicitly stated in the provided document. The ground truth was primarily based on the concordance of these reference NAAT results.
4. Adjudication method for the test set
The adjudication method for determining "Patient Infected Status" (PIS) was based on the combined results from two reference NAATs.
- A subject was categorized as infected for CT or NG if a minimum of two positive results (at least one from each reference NAAT) was reported across relevant specimen types (e.g., endocervical swab/urethral swab and/or urine specimen).
- Specific rules were applied for certain situations, such as females being categorized as non-infected for swab specimens if reference swab and PreservCyt were negative, but urine specimens were positive.
- A subject was classified as non-infected if at least one of the reference NAATs reported negative results for all sample types.
- If PIS could not be determined due to missing and/or indeterminate results from the reference tests, the subject was excluded from the analysis. This method implies a form of "consensus" or "composite reference standard" based on the agreement of the two predicate devices, rather than a direct expert panel adjudication in the typical sense of 2+1 or 3+1 for imaging.
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 performed. This device is a fully automated in vitro diagnostic test (nucleic acid amplification test) and does not involve human readers interpreting results. Therefore, there is no AI assistance or effect size on human reader performance to report. The comparison is between the new device and established reference assays.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the primary clinical performance evaluation is a standalone (algorithm only) performance study. The cobas® CT/NG Test is an automated system for sample preparation, amplification, and real-time detection, generating results without human interpretive input. The reported sensitivity, specificity, and predictive values are for the device operating as a standalone diagnostic system.
7. The type of ground truth used
The ground truth used was a composite reference standard (CRS) or "patient infected status" (PIS). PIS was determined based on the combined results from two different, commercially available nucleic acid amplification tests (NAATs) which served as reference assays. A subject was considered infected if at least two positive results were obtained, with at least one from each reference NAAT, across various relevant specimen types.
8. The sample size for the training set
The document does not explicitly describe a separate training set for the clinical performance evaluation in the context of machine learning or AI. Diagnostic devices like the cobas® CT/NG Test typically undergo analytical validation (e.g., LOD, inclusivity, specificity) and then clinical validation with a distinct set of clinical samples. The "training" for such devices is inherent in their design and optimization prior to the formal validation studies, and not usually characterized by a distinct "training set" of patient data in the way an AI model would have. The data described (analytical and clinical) are primarily for performance evaluation and validation.
9. How the ground truth for the training set was established
As noted above, a distinct "training set" in the AI sense is not described. For the general development of the assay, the "ground truth" would be established through highly characterized reference materials (quantified cultures of CT and NG), which were used extensively in the analytical performance studies (LOD, inclusivity, analytical specificity).
§ 866.3120 Chlamydia serological reagents.
(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).