(90 days)
The cobas® CT/NG on the cobas® 6800/8800 system 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), clinician-collected vaginal swab specimens, and endocervical 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.
cobas® CT/NG is a new qualitative test performed on the cobas® 6800 System and cobas® 8800 System. cobas® CT/NG enables the detection of CT/NG DNA in endocervical, vaginal, urine and cervical specimens of infected female patients and urine specimens in infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. cobas® CT/NG is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as positive, negative or invalid. Results can be reviewed directly on the system screen, exported, or printed as a report.
Here's a breakdown of the acceptance criteria and study information for the cobas® CT/NG for use on the cobas® 6800/8800 Systems device, extracted from the provided text:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance and reproducibility study results. The device aims for high sensitivity, specificity, and reproducibility.
Table of Acceptance Criteria and Reported Device Performance
| Metric / Test Category | Acceptance Criteria (Implicit from text, generally very high % agreement for validated tests) | Reported Device Performance (Cobas CT/NG) |
|---|---|---|
| Clinical Performance (CT) | ||
| Female Urine | High Sensitivity and Specificity (e.g., >90% and >98%) | SENS: Symptomatic 96.0%, Asymptomatic 95.2%, Overall 95.6% SPEC: Symptomatic 99.8%, Asymptomatic 99.6%, Overall 99.7% |
| Female Clinician-collected Vaginal Swab (VS-C) | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 97.6%, Overall 98.6% SPEC: Symptomatic 99.2%, Asymptomatic 99.0%, Overall 99.1% |
| Female Self-collected Vaginal Swab (VS-S) | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 98.4%, Overall 99.2% SPEC: Symptomatic 98.8%, Asymptomatic 99.2%, Overall 99.0% |
| Female PreservCyt® Cervical Specimens (PC) | High Sensitivity and Specificity | SENS: Symptomatic 95.1%, Asymptomatic 90.3%, Overall 92.5% SPEC: Symptomatic 99.5%, Asymptomatic 99.7%, Overall 99.6% |
| Female Endocervical Swab (ES) | High Sensitivity and Specificity | SENS: Symptomatic 95.9%, Asymptomatic 91.1%, Overall 93.3% SPEC: Symptomatic 99.1%, Asymptomatic 99.5%, Overall 99.4% |
| Male Urine | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 100.0%, Overall 100.0% SPEC: Symptomatic 99.6%, Asymptomatic 99.8%, Overall 99.7% |
| Clinical Performance (NG) | ||
| Female Urine (Prospective & Archived) | High Sensitivity and Specificity | SENS: Prospective Overall 89.5%; Archived Overall 98.7%; Combined Overall 94.8% SPEC: Prospective Overall 99.9%; Archived Overall 100.0%; Combined Overall 99.9% |
| Female Clinician-collected Vaginal Swab (VS-C) | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 100.0%, Overall 100.0% SPEC: Symptomatic 99.7%, Asymptomatic 99.8%, Overall 99.7% |
| Female Self-collected Vaginal Swab (VS-S) | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 100.0%, Overall 100.0% SPEC: Symptomatic 99.7%, Asymptomatic 99.7%, Overall 99.7% |
| Female PreservCyt® Cervical Specimens (PC) | High Sensitivity and Specificity | SENS: Prospective Overall 96.4%; Archived Overall 97.0%; Combined Overall 96.6% SPEC: Prospective Overall 99.9%; Archived Overall 100.0%; Combined Overall 99.9% |
| Female Endocervical Swab (ES) | High Sensitivity and Specificity | SENS: Prospective Overall 94.5%; Archived Overall 100.0%; Combined Overall 97.0% SPEC: Prospective Overall 99.9%; Archived Overall 100.0%; Combined Overall 99.9% |
| Male Urine | High Sensitivity and Specificity | SENS: Symptomatic 100.0%, Asymptomatic 100.0%, Overall 100.0% SPEC: Symptomatic 98.7%, Asymptomatic 99.7%, Overall 99.5% |
| Analytical Performance (Reproducibility) | Lower limit of the 95% exact CI of % correct test results for 1x LoD ≥ 91% | CT: ≥ 97.4% NG: ≥ 95.3% |
| Lower limit of the 95% exact CI of % correct test results for 3x LoD ≥ 98% | CT: 98.3% NG: 98.3% | |
| Analytical Performance (LoD) | Detection in ≥ 95% of replicates | CT (Serovar D): 0.3-0.6 IFU/mL CT (Serovar I): 1.3-2.9 IFU/mL NG (Strain 2948): 0.2-0.4 CFU/mL NG (Strain 891): 0.04-0.08 CFU/mL |
| Analytical Performance (Inclusivity) | 100% positive | 13 additional CT serovars and 43 NG strains were 100% positive at varying concentrations (Tables 3 & 4). |
| Analytical Performance (Analytical Specificity/Cross-reactivity) | No interference or false positives | None of the 149 tested organisms (bacteria, fungi, viruses, non-gonorrhoeae Neisseria) interfered with CT/NG detection or produced false positives. |
| Analytical Performance (Interference) | Tolerance to common OTC/prescription products and endogenous substances | Metronidazole Vaginal Gel, Replens™ Long-Lasting Vaginal Moisturizer, RepHresh™ Odor Eliminating Vaginal Gel, and RepHresh™ Clean Balance produced false negative or invalid results in some replicates. All other tested substances did not interfere. Specific concentrations tolerated for endogenous substances were provided (Table 10), e.g., Whole Blood (10% for endocervical, 5% for PreservCyt® and urine) and Cervical Mucus (0.5% for endocervical, 1.0% for PreservCyt®, 0.5% for urine). |
| Analytical Performance (Competitive Inhibition) | Stable detection of one target in presence of high concentration of other. | When NG was at high concentration, CT was detected at low and moderate levels across all specimen types. When CT was at high concentration, NG was detected at moderate levels across all specimen types; however, NG was not consistently detected at low levels (35-60% detection). |
| Analytical Performance (Cross-contamination/Carryover) | Low cross-contamination rate | Sample-to-sample cross-contamination rate: 0.5% (2/432) (95% CI: 0.1%-1.7%). Run-to-run cross-contamination: 0% (0/282). |
2. Sample Size Used for the Test Set and Data Provenance
Clinical Performance Study:
- Total Subjects Enrolled: 5,197
- Eligible Subjects: 5,105
- Evaluable Subjects (Prospective): 5,053 (3,860 females, 1,193 males)
- Archived Specimens (Female): 371 urogenital samples from 295 female subjects (used for NG detection). These originated from a previous clinical study for cobas® CT/NG v2 test on the cobas® 4800 System.
- Total Samples Tested (across both CT & NG analyses, including prospective and archived): 17,169
Data Provenance:
- Geographic Origin: 9 geographically diverse sites in the US.
- Retrospective/Prospective: Primarily prospective data collection. Some female NG archived specimens were used, which were "archived prospectively collected" from a previous study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The ground truth was established using a Patient Infected Status (PIS) algorithm, which relied on the results of multiple FDA-cleared NAATs (Nucleic Acid Amplification Tests) rather than human expert interpretation of images or clinical findings directly.
- Number of "Experts" (for constructing ground truth):
- For females: A combination of results from 2 commercially available FDA-cleared NAATs.
- For males: A combination of results from 3 commercially available FDA-cleared NAATs.
- Qualifications of "Experts": The "experts" in this context are the FDA-cleared NAATs themselves, which are established diagnostic tests for CT/NG. The text does not mention human experts delineating ground truth for individual cases.
4. Adjudication Method for the Test Set
The adjudication method was a Patient Infected Status (PIS) algorithm based on the concordance of results from multiple FDA-cleared NAATs.
- For females:
- Infected: One or more positive results in each of the two NAATs. A scenario where one NAAT is positive/negative and the other is positive/positive also leads to "Infected".
- Not Infected: Varied combinations of negative results or discordant results between the two NAATs, where the majority are negative.
- Indeterminate: If one or more sample types are invalid for the NAATs, or if there are discordant results with invalid/missing data, the PIS is indeterminate.
- For males:
- Infected/Not Infected: At least 2 out of the 3 test results must be concordant positive or negative, respectively.
- Indeterminate: If one test result is invalid/missing and the other two are discordant, or if 2 or 3 test results are invalid/missing, the PIS is indeterminate.
This method essentially acts as a "majority vote" or expert consensus (of diagnostic tests) ground truth.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly performed or described in the provided text. This study focuses on the diagnostic accuracy of the device compared to a composite reference standard (PIS), not on how human readers' performance might improve with the AI (an in vitro diagnostic device) as an aid.
Effect Size: N/A (since an MRMC study was not described)
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the study describes the standalone performance of the cobas® CT/NG system. The device is referred to as an "automated, qualitative in vitro nucleic acid diagnostic test" that uses real-time PCR. It directly detects CT/NG DNA, and the system software "assigns test results for all tests as positive, negative or invalid." This clearly indicates an algorithm-only standalone performance evaluation.
7. The Type of Ground Truth Used
The type of ground truth used was a composite reference standard known as Patient Infected Status (PIS).
- This PIS was determined by a combination of results from multiple FDA-cleared NAATs.
- Therefore, the ground truth is based on a consensus of highly accurate molecular diagnostic tests, which is a form of expert consensus (where the "experts" are established diagnostic technologies). It is not based on pathology reports, simple expert visual review, or patient outcomes data directly.
8. The Sample Size for the Training Set
The document does not provide information regarding a specific "training set" sample size. This is typical for a diagnostic device undergoing FDA clearance, where the focus is on validation against an independent test set rather than reporting on the development (training) phase of an AI or algorithm. The device is a PCR-based test, which generally involves laboratory optimization and locked-down algorithms rather than iterative machine learning training sets in the same way an image-based AI would.
9. How the Ground Truth for the Training Set Was Established
As no specific training set and its associated ground truth establishment were described in this document, this information is not available / not applicable based on the provided text.
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Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. Food & Drug Administration" in blue.
March 21, 2018
Roche Molecular Systems, Inc. Nobuko Nakajima Manager, Regulatory Affairs 4300 Hacienda Drive Pleasanton, California 94588-2722
Re: K173887
Trade/Device Name: cobas CT/NG for use on cobas 6800/8800 systems Regulation Number: 21 CFR 866.3390 Regulation Name: Neisseria spp. direct serological test reagents Regulatory Class: Class II Product Code: LSL, MKZ, OOI Dated: December 20, 2017 Received: December 21, 2017
Dear Nobuko Nakajima:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
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Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Tamara V. Feldblyum -S for
Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K173887
Device Name
cobas® CT/NG for use on the cobas® 6800/8800 Systems
Indications for Use (Describe)
The cobas® CT/NG on the cobas® 6800/8800 system 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 gonorthoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), clinician-collected vaginal swab specimens, and endocervical 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.
Ancillary Collection Kits:
The cobas® PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens.
Note: This kit has been validated for use with the following tests:
· cobas® CT/NG v2.0 Test
- · cobas® CT/NG for use on cobas® 6800/8800 Systems
The cobas® PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens.
Note: This kit has been validated for use with the following tests:
- · cobas® CT/NG v2.0 Test
• cobas® CT/NG for use on cobas® 6800/8800 Systems
· cobas® Cdiff Test for use on the cobas® 4800 System
The cobas® PCR Urine Sample Kit is used to collect and transport urine specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for urine specimens. Use this cobas® CT/NG on cobas® 6800/8800 Systems or the cobas® CT/NG v2.0 Test.
Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
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cobas® CT/NG for use on the cobas® 6800/8800 Systems 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
| Submitter Name | Roche Molecular Systems, Inc. |
|---|---|
| Address | 4300 Hacienda DrivePleasanton, CA, 94588-2722 |
| Contact | Nobuko NakajimaPhone: (925)730-8215FAX: (925)225-0207Email: nobuko.nakajima@roche.com |
| Date Prepared | December 4, 2017 |
| Proprietary Name | cobas® CT/NGfor use on cobas® 6800/8800 systems |
| Common Name | Real-time PCR assay, in vitro nucleic acid amplification test for the quantitativedetection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) |
| Classification Name | Sec. 866.3390 Neisseria spp. direct serological test reagentsSec. 866.3120 Chlamydia serological reagents,Sec. 862.2570 Real Time Nucleic Acid Amplification System |
| Product Codes | LSLMKZOOI |
| Predicate Devices | cobas® CT/NG v2.0 Test (K163184) |
| Establishment Registration | Roche Molecular Systems, Inc. (2243471) |
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1. DEVICE DESCRIPTION
cobas® CT/NG is a new qualitative test performed on the cobas® 6800 System and cobas® 8800 System. cobas® CT/NG enables the detection of CT/NG DNA in endocervical, vaginal, urine and cervical specimens of infected female patients and urine specimens in infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control.
Principles of the procedure 1.1.
cobas® CT/NG is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as positive, negative or invalid. Results can be reviewed directly on the system screen, exported, or printed as a report.
Nucleic acid from patient samples, external controls and added internal control DNA (DNA-IC) molecules is simultaneously extracted. In summary, bacterial nucleic acid is released by addition of proteinase and lysis reagent to the sample. The released nucleic acid binds to the silica surface of the added magnetic glass particles. Unbound substances and impurities, such as denatured protein, cellular debris and potential PCR inhibitors are removed with subsequent wash steps and purified nucleic acid is eluted from the magnetic glass particles with elution buffer at elevated temperature.
Selective amplification of target nucleic acid from the sample is achieved by the use of targetspecific forward and reverse primers which are selected from highly conserved plasmid and genomic regions of CT and NG. A region on the CT cryptic plasmid and the ompA gene (dual target) and two conserved sequences of the NG DR-9 region are amplified by cobas® CT/NG.
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Selective amplification of DNA-IC is achieved by the use of sequence-specific forward and reverse primers which are selected to have no homology with either the CT or NG target regions. A thermostable DNA polymerase enzyme is used for PCR amplification. The target and DNA-IC sequences are amplified simultaneously utilizing a universal PCR amplification profile with predefined temperature steps and number of cycles. The master mix includes deoxyuridine triphosphate (dUTP), instead of deoxythimidine triphosphate (dTTP), which is incorporated into the newly synthesized DNA (amplicon). Any contaminating amplicon from previous PCR runs are eliminated by the AmpErase enzyme, which is included in the PCR master mix, during the first thermal cycling step. However, newly formed amplicons are not eliminated since the AmpErase enzyme is inactivated once exposed to temperatures above 55℃.
The cobas® CT/NG master mix contains two detection probes specific for the CT target sequences, two detection probes specific for the NG target sequences and one for the DNA-IC. The probes are labeled with target specific fluorescent reporter dyes allowing simultaneous detection of CT targets, NG targets and DNA-IC in three different target channels. When not bound to the target sequence, the fluorescent signal of the intact probes is suppressed by a quencher dye. During the PCR amplification step, hybridization of the probes to the specific single-stranded DNA template results in cleavage of the 5' to 3' exonuclease activity of the DNA polymerase resulting in separation of the reporter and quencher dyes and the generation of a fluorescent signal. With each PCR cycle, increasing amounts of cleaved probes are generated and the cumulative signal of the reporter dye increases concomitantly. Real-time detection and discrimination of PCR products is accomplished by measuring the fluorescence of the released reporter dyes for the CT and NG targets and DNA-IC, respectively.
Figure 1: cobas® CT/NG on the cobas® 6800/8800 system
| [IVD] | ||
|---|---|---|
| cobas CT/NG Positive Control Kit | cobas CT/NG | cobas Buffer Negative Control Kit |
| Positive control kit for use on the cobas 6800/8800 Systems | Qualitative nucleic acid test for use on the cobas 6800/8800 Systems | Buffer negative control kit for use on the cobas 6800/8800 Systems |
| cobas | cobas | cobas |
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2. INTENDED USE
The cobas® CT/NG on the cobas® 6800/8800 system 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), clinician-collected vaginal swab specimens, and endocervical 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.
Ancillary Collection Kits 2.1.
The cobas® PCR Media Dual Swab Sample Kit is used to collect and transport endocervical and vaginal swab specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for gynecological specimens.
Note: This kit has been validated for use with the following tests:
- cobas® CT/NG v2.0 Test .
- cobas® CT/NG for use on cobas® 6800/8800 Systems .
The cobas® PCR Media Uni Swab Sample Kit is used to collect and transport human specimens. The cobas® PCR Media serves as a nucleic acid stabilizing transport and storage medium for human specimens.
Note: This kit has been validated for use with the following tests:
- cobas® CT/NG v2.0 Test .
- cobas® CT/NG for use on cobas® 6800/8800 Systems .
- cobas® Cdiff Test for use on the cobas® 4800 System .
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The cobas® PCR Urine Sample Kit is used to collect and transport 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 either cobas® CT/NG on cobas® 6800/8800 Systems or the cobas® CT/NG v2.0 Test.
TECHNOLOGICAL CHARACTERISTICS 3.
The primary technological characteristics and intended use of the RMS cobas® CT/NG for use on the cobas® 6800/8800 systems are substantially equivalent to other legally marketed nucleic acid amplification tests intended for the qualitative detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).
As indicated in Table 1, the cobas® CT/NG for use on the cobas® 6800/8800 systems is substantially equivalent to significant characteristics of the identified predicate device, the currently cleared cobas® CT/NG v2.0 Test (K163184).
| Predicate Device:cobas® CT/NG v2.0 Test(K163184) | Submitted Devicecobas® CT/NG for use on thecobas® 6800/8800 systems | |
|---|---|---|
| Intended Use | The cobas® CT/NG v2.0 Test is anautomated, in vitro nucleic acid amplificationtest for the qualitative detection ofChlamydia trachomatis (CT) and/orNeisseria gonorrhoeae (NG) DNA inurogenital specimens. The Test utilizes thePolymerase Chain Reaction (PCR) for thedetection of Chlamydia trachomatis andNeisseria gonorrhoeae DNA in male andfemale urine, self-collected vaginal swabspecimens (collected in a clinical setting),clinician-collected vaginal swab specimens,and endocervical swab specimens, allcollected in cobas® PCR Media (RocheMolecular Systems, Inc.), and cervicalspecimens collected in PreservCyt® solution.This test is intended as an aid in thediagnosis of chlamydial and gonococcaldisease in both symptomatic andasymptomatic individuals. | The cobas® CT/NG on the cobas® 6800/8800system is an automated, qualitative in vitronucleic acid diagnostic test, that utilizes real-timepolymerase chain reaction (PCR), for the directdetection of Chlamydia trachomatis (CT) and/orNeisseria gonorrhoeae (NG) DNA in male andfemale urine, clinician instructed self-collectedvaginal swab specimens (collected in a clinicalsetting), clinician-collected vaginal swabspecimens, and endocervical swab specimens,all collected in cobas® PCR Media (RocheMolecular Systems, Inc.), and cervicalspecimens collected in PreservCyt® solution.This test is intended as an aid in the diagnosis ofchlamydial and gonococcal disease in bothsymptomatic and asymptomatic individuals. |
| Predicate Device:cobas® CT/NG v2.0 Test(K163184) | Submitted Devicecobas® CT/NG for use on thecobas® 6800/8800 systems | |
| Ancillary Collection Kits: | Ancillary Collection Kits: | |
| The cobas® PCR Media Dual Swab SampleKit is used to collect and transportendocervical and vaginal swab specimens.The cobas® PCR Media serves as a nucleicacid stabilizing transport and storagemedium for gynecological specimens. Usethis collection kit only with the cobas®CT/NG v2.0 Test. | The cobas® PCR Media Dual Swab Sample Kitis used to collect and transport endocervical andvaginal swab specimens. The cobas® PCRMedia serves as a nucleic acid stabilizingtransport and storage medium for gynecologicalspecimens. Note: This kit has been validated foruse with the following tests: cobas® CT/NG v2.0Test cobas® CT/NG for use oncobas® 6800/8800 Systems. | |
| Intended Use,cont. | The cobas® PCR Media Uni Swab SampleKit is used to collect and transport humanspecimens. The cobas® PCR Media servesas a nucleic acid stabilizing transport andstorage medium for human specimens. Usethis collection kit with cobas® CT/NG v2.0Test and cobas® Cdiff Tests. | The cobas® PCR Media Uni Swab Sample Kit isused to collect and transport human specimens.The cobas® PCR Media serves as a nucleic acidstabilizing transport and storage medium forhuman specimens Note: This kit has beenvalidated for use with the following tests:cobas® CT/NG v2.0 Test cobas® CT/NG for useon cobas® 6800/8800 Systems cobas® CdiffTest for use on the cobas® 4800 System |
| The cobas® PCR Urine Sample Kit is usedto collect and transport urine specimens.The cobas® PCR Media serves as a nucleicacid stabilizing transport and storagemedium for urine specimens. Use thiscollection kit only with the cobas® CT/NGv2.0 Test. | The cobas® PCR Urine Sample Kit is used tocollect and transport urine specimens. Thecobas® PCR Media serves as a nucleic acidstabilizing transport and storage medium forurine specimens Use this collection kit only witheither cobas® CT/NG on cobas® 6800/8800Systems or the cobas® CT/NG v2.0 Test. | |
| Sample Types | • Male and female urine,• Self-collected/clinician-collectedvaginal swab specimens incobas® PCR Media,• Endocervical swab specimens incobas® PCR Media,• Cervical specimens in PreservCyt®solution | Same |
| Subject Status | Asymptomatic and symptomatic | Same |
| Sample CollectionDevices | cobas® PCR Media Dual Swab Sample Kitcobas® PCR Media Uni Swab Sample Kitcobas® PCR Urine Sample Kit | Same |
| CT Analyte targets | CT cryptic plasmid DNACT ompA gene | Same |
| NG Analyte targets | NG genomic DNA | Same |
| Predicate Device:cobas® CT/NG v2.0 Test(K163184) | Submitted Devicecobas® CT/NG for use on thecobas® 6800/8800 systems | |
| SamplePreparationProcedure | Semi-automated | Automated |
| AmplificationTechnology | Real-time PCR | Same |
| DetectionChemistry | Paired reporter and quencher fluorescencelabeled probes (TaqMan Technology) usingfluorescence resonance energy transfer(FRET) | Same |
| Result Analysis | Based on PCR cycle threshold analysis | Same |
| Analyzer | cobas® 4800 System | cobas® 6800/8800 systems |
Comparison of the cobas® CT/NG for use on the cobas® 6800/8800 systems with Table 1: the Predicate Device
{9}------------------------------------------------
{10}------------------------------------------------
4. NON-CLINICAL PERFORMANCE EVALUATION
4.1. Limit of Detection (LoD)
Analytical sensitivity (Limit of Detection or LoD) was determined by analyzing a dilution series of quantified cultures of Chlamydia trachomatis (serovars D and I) and Neisseria gonorrhoeae isolates 2948 (ATCC 19424) and 891. CT and NG cultures were diluted into a matrix of pooled negative specimens of each sample type and 70-78 replicates were tested for each level in each specimen type. All levels were analyzed across 3 unique lots of reagents. LoD for each specimen type is shown in Table 2 as the target concentration which can be detected in ≥ 95% of the replicates for all lots.
| Specimen Types | C. trachomatis | N. gonorrhoeae | ||||||
|---|---|---|---|---|---|---|---|---|
| Serovar D | Serovar I | Strain 2948 | Strain 891 | |||||
| LOD(IFU/mL) | MeanCtValue | LOD(IFU/mL) | MeanCtValue | LOD(CFU/mL) | MeanCtValue | LOD(CFU/mL) | MeanCtValue | |
| Endocervical Swabin cobas® PCR | 0.3 | 36.6 | 1.4 | 37.1 | 0.4 | 36.3 | 0.08 | 37.5 |
| Vaginal Swab in | 0.3 | 37.3 | 1.4 | 37.0 | 0.4 | 36.3 | 0.08 | 37.0 |
| cobas® PCR | 0.2 | 37.8 | 1.3 | 37.1 | 0.2 | 36.3 | 0.04 | 38.3 |
| Table 2: Analytical sensitivity (Limit of Detection) |
|---|
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| Cervical Samplescollected intoPreservCyt®Solution | 0.6 | 37.4 | 2.9 | 37.4 | 0.2 | 36.7 | 0.08 | 37 |
|---|---|---|---|---|---|---|---|---|
| --------------------------------------------------------------- | ----- | ------ | ----- | ------ | ----- | ------ | ------ | ---- |
IFU = Inclusion Forming Unit; quantification of the same C. trachomatis culture using DFA method equates 1 IFU to 6.6 signal generating units (SGU) for Serovar D, and 13.9 SGU for serovar I, where SGU includes Elementary Bodies as well as Reticulate Bodies of C. trachomatis
CFU = Colony Forming Units
4.2. Inclusivity
Inclusivity testing was performed for 13 additional CT serovars, the Swedish new variant strain (nvCT) and an additional 43 independently isolated strains of NG using one lot of reagents. Testing was performed using CT and NG cultures diluted into pools of negative specimens. Results are shown in Table 3 and Table 4 for CT serovars and NG strains, respectively. Twenty replicates per dilution level were tested for each strain in each specimen type.
| Swab* Specimens | Urine Specimens | PreservCyt Specimens | |||||
|---|---|---|---|---|---|---|---|
| Serovar Type or Variant | IFU/mL | % Pos | IFU/mL | % Pos | IFU/mL | % Pos | |
| A | 1.4 | 100 | 0.7 | 100 | 1.4 | 100 | |
| B | 5.9 | 100 | 2.9 | 100 | 5.9 | 100 | |
| Ba | 18.3 | 100 | 9.1 | 100 | 18.3 | 100 | |
| C | 0.6 | 100 | 0.3 | 100 | 0.6 | 100 | |
| E | 6.4 | 100 | 3.2 | 100 | 6.4 | 100 | |
| F | 3.2 | 100 | 1.6 | 100 | 3.2 | 100 | |
| G | 2.9 | 100 | 1.5 | 100 | 2.9 | 100 | |
| H | 9.7 | 100 | 4.8 | 100 | 9.7 | 100 | |
| J | 1.4 | 100 | 0.7 | 100 | 1.4 | 100 | |
| K | 2.0 | 100 | 1.0 | 100 | 2.0 | 100 | |
| LGV Type 1 | 5.9 | 100 | 3.0 | 100 | 5.9 | 100 | |
| LGV Type 2 | 12.8 | 100 | 6.4 | 100 | 12.8 | 100 | |
| LGV Type 3 | 0.7 | 100 | 0.4 | 100 | 0.7 | 100 | |
| nyCT | 0.7 | 100 | 0.3 | 100 | 0.7 | 100 |
Inclusivity Testing for CT Serovars Table 3:
- Vaginal swab samples were used as a representative swab sample type for vaginal and endocervical swab specimens.
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| Numbers of NG Strains | Swab* Specimens | |
|---|---|---|
| CFU/mL | % Pos | |
| 39 | 0.4 | ≥ 95 |
| 4 | 1.0 | ≥ 95 |
| Total = 43 | ||
| Numbers of NG Strains | Urine Specimens | |
| CFU/mL | % Pos | |
| 41 | 0.2 | ≥ 95 |
| 2 | 0.5 | 100 |
| Total = 43 | ||
| Numbers of NG Strains | PreservCyt Specimens | |
| CFU/mL | % Pos | |
| 42 | 0.4 | ≥ 95 |
| 1 | 1.0 | 100 |
| Total = 43 |
Table 4: Inclusivity Testing for NG strains
- Vaginal swab samples were used as a representative swab sample type for vaginal and endocervical swab specimens.
4.3. Precision
In-house precision was examined using a panel composed of CT and NG cultures diluted into a pool of negative endocervical swab specimen matrix collected in cobas® PCR Media, a pool of negative urine matrix plus cobas® PCR Media and a pool of negative cervical specimen matrix collected in PreservCyt® Solution. Endocervical swabs were intended to represent all swab samples collected in cobas® PCR Media (endocervical and vaginal). Four levels were tested using CT serovar D and NG strain 2948 (ATCC 19424) as the target organisms.
The precision panel was designed to include members with high negative, low and moderate concentrations of CT and NG for each panel matrix, corresponding to ~0.3x, ~1x and ~3x LoD. Testing was performed with three lots of cobas® CT/NG reagents and two instruments for a total of 24 runs. A description of the precision panels and the study performance hit rate is shown in Table 5. All negative panel members tested negative throughout the study. Analysis of standard deviation and percent coefficient of variation of the Ct values from valid tests performed on
{13}------------------------------------------------
positive panel members (see Table 6 and Table 7) yielded overall CV (%) ranges from 1.62% to 4.05% for CT and from 1.17% to 3.55% for NG. Testing occurred over 12 days, using 2 instruments, with 2 runs per day. Each run consisted of 3 replicates of each sample.
| Level | N Tested | N positive CT | N positive NG | Hit Rate | 95% CI CT | 95% CI NG | |||
|---|---|---|---|---|---|---|---|---|---|
| CT | NG | LL | UL | LL | UL | ||||
| Endocervical Swab in cobas® PCR Media | |||||||||
| Negative | 72 | 0 | 0 | 0% | 0% | 0.0 | 5.0 | 0.0 | 5.0 |
| High Negative | 72 | 51 | 32 | 71% | 44% | 59 | 81 | 33 | 57 |
| Low | 72 | 69 | 68 | 96% | 94% | 88 | 99 | 86 | 98 |
| Moderate | 72 | 72 | 72 | 100% | 100% | 95 | 100 | 95 | 100 |
| Cervical samples collected into PreservCyt® Solution | |||||||||
| Negative | 72 | 0 | 0 | 0% | 0% | 0.0 | 5.0 | 0.0 | 5.0 |
| High Negative | 72 | 38 | 47 | 53% | 65% | 41 | 65 | 53 | 76 |
| Low | 72 | 72 | 69 | 100% | 96% | 95 | 100 | 88 | 99 |
| Moderate | 72 | 72 | 72 | 100% | 100% | 95 | 100 | 95 | 100 |
| cobas® PCR Media with Urine | |||||||||
| Negative | 72 | 0 | 0 | 0% | 0% | 0.0 | 5.0 | 0.0 | 5.0 |
| High Negative | 72 | 56 | 56 | 78% | 78% | 66 | 87 | 66 | 87 |
| Low | 72 | 71 | 72 | 99% | 100% | 92 | 100 | 95 | 100 |
| Moderate | 72 | 72 | 72 | 100% | 100% | 95 | 100 | 95 | 100 |
Table 5: Summary of within-laboratory precision
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| Level(Hit Rate) | Mean Ct | Betweeninstrument | Betweenlot | Within run | Betweenrun | Betweenday | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | ||
| Endocervical Swab in cobas® PCR Media | |||||||||||||
| HighNegative(71%) | 39.7 | 0.0 | 0.0 | 0.0 | 0.0 | 1.2 | 3.21 | 0.0 | 0.00 | 0.3 | 0.8 | 1.3 | 3.3 |
| Low(96%) | 38.5 | 0.0 | 0.0 | 0.0 | 0.1 | 1.1 | 2.96 | 0.0 | 0.00 | 0.4 | 1.2 | 1.2 | 3.2 |
| Moderate(100%) | 36.9 | 0.0 | 0.0 | 0.2 | 0.6 | 0.5 | 1.45 | 0.0 | 0.18 | 0.0 | 0.0 | 0.6 | 1.6 |
| Cervical Samples collected into PreservCyt® Solution | |||||||||||||
| HighNegative(53%) | 38.3 | 0.6 | 1.5 | 0.5 | 1.3 | 1.1 | 2.92 | 0.0 | 0.00 | 0.0 | 0.0 | 1.3 | 3.5 |
| Low(100%) | 36.9 | 0.2 | 0.5 | 0.2 | 0.7 | 0.6 | 1.85 | 0.0 | 0.00 | 0.0 | 0.0 | 0.7 | 2.0 |
| Moderate(100%) | 35.6 | 0.0 | 0.0 | 0.2 | 0.5 | 0.5 | 1.46 | 0.0 | 0.24 | 0.0 | 0.0 | 0.5 | 1.5 |
| cobas® PCR Media with Urine | |||||||||||||
| HighNegative(78%) | 38.9 | 0.0 | 0.0 | 0.1 | 0.3 | 1.2 | 3.22 | 0.3 | 1.01 | 0.0 | 0.0 | 1.3 | 3.3 |
| Low(99%) | 38.3 | 0.1 | 0.2 | 0.0 | 0.0 | 1.5 | 3.97 | 0.0 | 0.00 | 0.2 | 0.7 | 1.5 | 4.0 |
| Moderate(100%) | 37.1 | 0.0 | 0.0 | 0.0 | 0.0 | 1.0 | 2.84 | 0.0 | 0.00 | 0.2 | 0.7 | 1.0 | 2.9 |
Table 6: Overall mean, standard deviations and coefficients of variation (%) for cycle threshold, CT positive panel members
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| Level(Hit Rate) | Mean Ct | Betweeninstrument | Betweenlot | Within run | Betweenrun | Betweenday | Total | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | SD | CV% | ||
| Endocervical Swab in cobas® PCR Media | |||||||||||||
| HighNegative(44% ) | 39.1 | 0.00 | 0.00 | 0.31 | 0.79 | 0.84 | 2.14 | 0.72 | 1.85 | 0.57 | 1.46 | 1.28 | 3.28 |
| Low (94%) | 38.1 | 0.00 | 0.00 | 0.00 | 0.00 | 1.27 | 3.34 | 0.00 | 0.00 | 0.00 | 0.00 | 1.27 | 3.34 |
| Moderate(100%) | 36.5 | 0.00 | 0.00 | 0.24 | 0.67 | 0.69 | 1.89 | 0.00 | 0.00 | 0.15 | 0.40 | 0.74 | 2.04 |
| Cervical Samples collected into PreservCyt® Solution | |||||||||||||
| HighNegative(65%) | 39.0 | 0.34 | 0.87 | 0.00 | 0.00 | 1.11 | 2.85 | 0.08 | 0.20 | 0.45 | 1.16 | 1.25 | 3.21 |
| Low (96%) | 38.0 | 0.00 | 0.00 | 0.00 | 0.00 | 1.25 | 3.28 | 0.00 | 0.00 | 0.00 | 0.00 | 1.25 | 3.28 |
| Moderate(100%) | 35.8 | 0.00 | 0.00 | 0.28 | 0.78 | 0.76 | 2.13 | 0.00 | 0.00 | 0.00 | 0.00 | 0.81 | 2.27 |
| cobas® PCR Media with Urine | |||||||||||||
| HighNegative(78%) | 39.1 | 0.00 | 0.00 | 0.26 | 0.66 | 1.35 | 3.46 | 0.00 | 0.00 | 0.18 | 0.45 | 1.39 | 3.55 |
| Low(100%) | 36.7 | 0.14 | 0.38 | 0.16 | 0.42 | 0.71 | 1.92 | 0.00 | 0.00 | 0.00 | 0.00 | 0.74 | 2.00 |
| Moderate(100%) | 34.9 | 0.00 | 0.00 | 0.16 | 0.47 | 0.37 | 1.06 | 0.06 | 0.18 | 0.00 | 0.00 | 0.41 | 1.17 |
Table 7: Overall mean, standard deviations and coefficients of variation (%) for cycle threshold, NG positive panel members
Analytical specificity/Cross-reactivity 4.4.
A panel of 149 bacteria, fungi and viruses, including those commonly found in the male and female urogenital tract, 20 representatives of non-gonorrhoeae Neisseria strains and other phylogenetically unrelated organisms, were tested with cobas®CT/NG to assess analytical specificity. The organisms listed in Table 8 were spiked at concentrations of approximately 1 x 106 units*/mL for bacteria and approximately 1 x 105 units*/mL for viruses into pools of negative vaginal swab specimens in cobas® PCR Media, urine stabilized in cobas® PCR Media
{16}------------------------------------------------
and cervical specimens in PreservCyt® Solution. Testing was performed with each potential interfering organism alone as well as with each organism mixed with CT and NG cultures at ~3x LoD. Results indicated that none of these organisms interfered with the detection of CT and NG or produced false positive results in the CT/NG negative matrices. (N=3 across the tested specimen types).
*All bacteria were quantified as Colony Forming Units (CFU) except Chlamydophila pneumonia and Chlamydophila psittaci which were quantified as Elementary Bodies (EB). All viruses were quantified as units/mL as determined by TCID50 Endpoint Dilution Assay. Trichomonas vaginalis and HPV16 were quantified as cells/mL.
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| Achromobacter xerosis | Gemella haemolysans | Neisseria subflava |
|---|---|---|
| Acinetobacter calcoaceticus | Haemophilus ducreyi | Neisseria weaverii |
| Acinetobacter Iwoffi | Haemophilus influenzae | Pantoea agglomerans |
| Actinomyces israelii | Helicobacter pylori | Paracoccus denitrificans |
| Aerococcus viridans | Herpes simplex virus I | Peptostreptococcus anaerobius |
| Aeromonas hydrophila | Herpes simplex virus II** | Peptostreptococcusasaccharolyticus |
| Alcaligenes faecalis | HPV16* | Peptostreptococcus magnus |
| Atopobium vaginae | Kingella dentrificans | Plesiomonas shigelloides |
| Bacillus subtilis | Kingella kingae | Propionibacterium acnes |
| Bacteriodes fragilis | Klebsiella oxytoca | Proteus mirabilis |
| Bacteroides caccae | Klebsiella pneumoniae | Proteus penneri |
| Bacteroides ureolyticus | Lactobacillus acidophillus | Proteus vulgaris |
| Bergeriella denitrificans | Lactobacillus brevis | Providencia rettgeri |
| Bifidobacterium adolescentis | Lactobacillus crispatus | Providencia stuartii |
| Bifidobacterium breve | Lactobacillus jensenii | Pseudomonas aeruginosa |
| Bifidobacterium longum | Lactobacillus lactis | Pseudomonas fluorescens |
| Blautia product | Lactobacillus leichmannii | Pseudomonas putida |
| Branhamella catarrhalis | Lactobacillus oris | Rahnella aquatilis |
| Brevibacterium linens | Lactobacillus parabuchnerri | Rhizobium radiobacter |
| Campylobacter coli | Lactobacillus reuteri | Rhodospirillum rubrum |
| Campylobacter jejuni | Lactobacillus vaginalis | Saccharomyces cerevisiae |
| Candida albicans | Lactococcus lactis cremoris | Salmonella choleraesuis |
| Candida glabrata | Legionella pneumophila | Salmonella minnesota |
| Candida parapsilosis | Leuconostoc paramesenteroides | Salmonella typhimurium |
| Candida tropicalis | Listeria monocytogenes | Serratia denitrificans |
| Chlamydophila pneumoniae | Micrococcus luteus | Serratia marcescens |
| Chlamydophila psittaci | Moraxella lacunata | Shigella dysenteriae |
| Chromobacter violaceum | Moraxella osloensis | Staphylococcus aureus |
| Citrobacter freundii | Morganella morganii | Staphylococcus epidermidis |
| Clostridium difficile | Mycobacterium smegmatis | Staphylococcus saprophyticus |
| Clostridium perfringens | Mycoplasma genitalium*** | Streptococcus agalactiae |
| Corynebacterium genitalium | Mycoplasma hominis | Streptococcus anginosus |
| Corynebacterium xerosis | Neisseria cinerea | Streptococcus bovis |
| Cryptococcus neoformans | Neisseria elongata subsp. elongata | Streptococcus dysgalactiae |
| Cytomegalovirus** | Neisseria elongata subsp. nitroreducens | Streptococcus equinis |
| Deinococcus radiodurans | Neisseria flava | Streptococcus mitis |
| Derxia gummosa | Neisseria flavescens | Streptococcus mutans |
| Eikenella corrodens | Neisseria kochi | Streptococcus pneumoniae |
| Enterobacter aerogenes | Neisseria lactamica | Streptococcus pyogenes |
| Enterobacter cloacae | Neisseria macacae | Streptococcus salivarius |
| Enterococcus avium | Neisseria meningitidis Serogroup A | Streptococcus sanguis |
| Enterococcus casseliflavus | Neisseria meningitidis Serogroup B | Streptomyces griseinus |
| Enterococcus faecalis | Neisseria meningitidis Serogroup C | Trichomonas vaginalis |
| Enterococcus faecium | Neisseria meningitidis Serogroup D | Trueperella pyogenes |
| Erysipelothrix rhusiopathiae | Neisseria meningitidis Serogroup W135 | Ureaplasma urealyticum |
| Escherichia coli | Neisseria meningitidis Serogroup Y | Veillonela parvula |
| Escherichia fergusonii | Neisseria mucosa | Vibrio cholerae |
| Flavobacterium meningosepticum | Neisseria perflava | Vibrio parahaemolyticus |
| Fusobacterium nucleatum | Neisseria polysaccharea | Yersinia enterocolitica |
| Gardnerella vaginalis | Neisseria sicca | - |
Table 8: Microorganisms tested for analytical specificity/cross reactivity
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HPV16 was tested as CaSki cells.
** Organism was tested at a concentration of 1 x 104 Units/mL.
***Organism was tested at a concentration of 1 x 105 CFU/mL.
4.5. Interference
The effects of over-the-counter or prescription products that may be present in urogenital specimens (Table 9), were evaluated. Testing was done using pooled clinical specimens (vaginal swab, urine and PreservCyt® specimens) with spiking of potential interferents at levels expected from normal patient usage. Interferents were tested in CT/NG negative specimen pools as well as in specimen pools with CT/NG at ~3x LoD. CT serovars D and I and NG strains 2948 (ATCC 19424) and 891 were used in this study. Five replicates each of CT/NG negative and CT/NG positive samples were tested with each product in each specimen type, except for RepHresh™ Odor Eliminating Vaginal Gel and RepHresh™ Clean Balance Gel, which were tested with 2 replicates each to verify interference that had been observed with Replens™ Long-Lasting Vaginal Moisturizer, a product with a similar formulation.
Of the over-the-counter (OTC) and prescription products tested, Metronidazole Vaginal Gel, Replens™ Long-Lasting Vaginal Moisturizer, RepHresh™ Odor Eliminating Vaginal Gel and RepHresh™ Clean Balance produced false negative or invalid results in at least one replicate of the samples tested.
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| Product Name | VaginalSwabs | Urine | PreservCytSolution |
|---|---|---|---|
| mg/mL | mg/mL | mg/mL | |
| Clindamycin Phosphate Vaginal Cream | 7.1 | 3.4 | 1.6 |
| Equate tioconazole 1 | 3.7 | 1.7 | 0.8 |
| Equate Vagicaine Anti-Itch Cream | 4.1 | 2.0 | 0.9 |
| Estrace | 3.8 | 2.0 | 1.0 |
| K-YTM Ultra Gel | 5.7 | 2.7 | 1.2 |
| Metronidazole Vaginal Gel | 0.1* | 0.1* | 0.2* |
| Monistat 3 Vaginal Antifungal Combination Pack | 3.7 | 1.7 | 0.7 |
| Monistat® Complete Care Itch Relief Cream | 3.7 | 1.8 | 0.9 |
| 7 Day Vaginal Cream | 3.9 | 1.8 | 0.8 |
| Norforms Suppositories | 3.4 | 1.7 | 0.7 |
| Premarin | 6.1 | 3.1 | 1.4 |
| ReplensTM Long-Lasting Vaginal Moisturizer | 0.05* | 0.05* | 0.2* |
| Summer's Eve Feminine Deodorant Spray | 6.4 | 3.1 | 2.0 |
| VCF - Vaginal Contraceptive Foam | 2.1 | 1.0 | 0.4 |
| Yeast Gard Advanced | 3.7 | 1.7 | 1.0 |
| Azo Standard (urine only) | N/A | 0.1 | N/A |
| RepHreshTM Odor Eliminating Vaginal Gel | ‡ | ‡ | ‡ |
| RepHreshTM Clean Balance Gel | ‡ | ‡ | ‡ |
| * Concentrations above this level may cause interference in clinical samples |
Table 9: List of substances with concentrations tested that do not interference with test performance in urogenital specimens
RepHresh™ products were tested using simulated swab specimen. Concentrations of product that did not interfere with test performance were not determined
Endogenous substances that may be present in urogenital specimens were tested for interference. Testing was done using pooled clinical specimens (endocervical swab, urine and PreservCyt® specimens) with spiking of potential endogenous interferents were tested in CT/NG negative specimen pools as well as in the presence of CT/NG at ~3x LoD. CT serovars D and I and NG strains 2948 (ATCC 19424) and 891 were used in this study. Five replicates each of CT/NG negative and CT/NG positive samples were tested with each substance in each specimen type.
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Interference was noted with whole blood at 10% for urine and PreservCyt® specimens and with cervical mucus at 1% in endocervical specimens when at least one replicate of the samples tested produced false negative or invalid results . Levels of endogenous substances tolerated by the assay for all specimen types are shown in Table 10.
| Interferent | Endocervical Swab | PreservCyt® | Urine |
|---|---|---|---|
| Albumin (% w/v) | N/A | N/A | 5% |
| Bilirubin (% w/v) | N/A | N/A | 0.5% |
| Mucus (% w/v) | 0.5% | 1.0% | 0.5% |
| Glucose (% w/v) | N/A | N/A | 1.0% |
| Peripheral Blood Mononuclear Cells(PBMCs as cells/mL) | 1.0E+06 | 1.0E+06 | 1.0E+06 |
| pH (acidic and alkaline) | N/A | N/A | pH 4 and pH 9 |
| Semen (% w/v) | 1.5% | 1.5% | N/A |
| Whole Blood (% v/v) | 10% | 5% | 5% |
Table 10: Summary of endogenous substance concentrations that do not show interference
4.6. Competitive Inhibition
To assess competitive inhibition between CT and NG, samples of vaginal swab, urine and PreservCyt® specimens were tested with low and moderate concentrations of one target mixed with very high concentrations of the opposite target. Low and moderate concentrations were defined as ~1x LoD and ~3x LoD, respectively, and high concentrations (≥103 IFU/mL for CT and ≥104 CFU/mL for NG) were defined as generating a signal greater than observed in 95% of target positive clinical specimens. Testing results indicated that when NG was present at a high concentration, CT was detected in all specimen types, at both low (~1x LoD) and moderate (~3x LoD) levels. Results also indicated that when CT was present at a high concentration, NG was detected in all specimen types at moderate (~3x LoD) levels, however, NG was not consistently detected at low levels (Expanded testing indicated detection in 35% (7/20) of the samples at 0.4 CFU/ml and 60% (12/20) of the samples at 0.65 CFU/ml).
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Cross contamination/Carryover 4.7.
Studies were performed to evaluate potential cross-contamination on the cobas® 6800/8800 Systems using cobas® CT/NG. Cross-contamination can cause false positive results. In this performance study the sample-to-sample cross-contamination rate of cobas® CT/NG has been determined to be 0.5% (2/432), (95% CI: 0.1%-1.7%) when alternating very high positive and negative samples were tested over nine runs. Run-to-run cross-contamination has not been observed (0/282). Testing was done using samples prepared with cobas® PCR Media and with PreservCyt® Solution and with urine stabilized in cobas® PCR Media. High positive samples (≥103 IFU/mL for CT and ≥104 CFU/mL for NG) in the study were prepared to generate a Ct value that was lower than that obtained with 95% or more of the specimens of infected patients in the intended use population. Cross contamination rates in clinical settings depend on the proportion of high positive samples and prevalence of the disease. Routine clinical crosscontamination rates are expected to be lower than what was observed in this study and need to be assessed in user's settings.
CLINICAL PERFORMANCE EVALUATION 5.
Clinical Performance 5.1.
5.1.1. Study Design
The clinical utility and performance of cobas® CT/NG was established in a multi-site, prospective collection study by comparing the results to a Patient Infected Status (PIS) that used a combination of FDA-cleared NAATs for urogenital specimens. Female and male urogenital specimens were collected at 9 geographically diverse sites in the US with testing performed at 4 laboratory testing sites (3 external and 1 internal).
Prospectively enrolled female subjects provided the following urogenital specimens: first-void urine, 3 vaginal swabs, 1 endocervical swab in cobas® PCR Media, and 1 cervical sample in PreservCyt® Solution. If the female was in the clinician-collected vaginal swab arm of the study, 2 of the vaginal swabs were placed in the respective manufacturers' collection device and 1 in cobas® PCR Media. If the female subject was in the self-collected vaginal swab self-collection arm of the study, then 1 vaginal swab was self-collected first and placed into cobas® PCR Media
{22}------------------------------------------------
and then followed by the 2 clinician-collected vaginal swabs and placed in the 2 respective manufacturers' collection devices.
Prospectively enrolled male subjects provided a urine specimen that was aliquoted into the respective manufacturers' collection device and cobas® PCR Media.
Subjects were classified as symptomatic if they self-reported symptoms indicative of a CT or NG infection as listed below:
- Dysuria (pain during urination) .
- Coital pain, difficulty or bleeding .
- Pelvic pain .
- Abnormal vaginal discharge .
- Pelvic, uterine or ovarian pain .
- Urethral discharge .
- Testicular pain .
- Scrotal pain or swelling .
Prospectively enrolled subjects were classified as asymptomatic if they did not report any of the above symptoms.
Specimens were tested for CT and NG using cobas® CT/NG and commercially available FDAcleared NAATs. All tests were run according to the respective manufacturers' Instructions For Use.
The clinical performance of cobas® CT/NG was evaluated by comparing the results from collected specimen types to a pre-specified PIS (Patient Infected Status) algorithm as determined by the combined results from 2 commercially available NAATs for females and 3 commercially available NAATs for males. The PIS algorithms for Female and Male subjects are shown in Table 11 and Table 12, respectively.
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For NG, archived prospectively collected female urine, cervical specimens in PreservCyt®, and endocervical swabs were obtained from the clinical study for cobas® CT/NG v2 test on the cobas® 4800 System. The PIS of these specimens were already determined from the clinical study for cobas® CT/NG v2 test on the cobas® 4800 System..
| NAAT1Urine/Vaginal | NAAT2Urine/Vaginal | Patient Infected Status (PIS)b |
|---|---|---|
| +/+ | +/+ | Infected |
| +/+ | +/- or -/+ | Infected |
| +/- or -/+ | +/+ | Infected |
| +/- | -/+ | Infected |
| -/+ | +/- or -/+ | Infected |
| +/- | +/- | Infected (Urine)Non-Infected (Vaginal) |
| +/- or -/+ | -/- | Not Infected |
| +/+ | -/- | Not Infected |
| -/- | +/+ | Not Infected |
| -/- | +/- or -/+ | Not Infected |
| -/- | -/- | Not Infected |
Table 11: Determination of female Patient Infected Status (PIS) for urogenital specimensª
ª One or more positives in each NAAT (NAAT1 and NAAT2) designates the PIS as Infected. Any other combination of results defines the PIS as Not Infected.
b In the scenario where one or more of the sample types are invalid, the remaining sample types with valid results from NAAT1 and NAAT2 must have concordant positive or concordant negative results to determine the PIS as Infected or Not Infected, respectively. For all other cases where one or more of the sample types are invalid, the PIS is indeterminate.
{24}------------------------------------------------
| NAAT1Urine | NAAT2Urine | NAAT3Urine | Patient Infected Status(PIS)a |
|---|---|---|---|
| + | + | + | Infected |
| + | + | - | Infected |
| + | - | + | Infected |
| - | + | + | Infected |
| - | - | + | Not Infected |
| - | + | - | Not Infected |
| + | - | - | Not Infected |
| - | - | - | Not Infected |
Table 12: Determination of male Patient Infected Status (PIS) for urine specimens
ª If at least 2 out of the 3 test results are concordant positive then the PIS can be considered as Infected or Not Infected, respectively. If one test result is invalid/missing and the other two test results are discordant then the PIS is indeterminate. If 2 or 3 test results are invalid/missing, then the PIS is indeterminate.
Sensitivity (SENS), specificity (SPEC), positive predictive value (PPV), and negative predictive value (NPV) of cobas® CT/NG were calculated separately for the detection of CT or NG using the PIS as the composite reference standard and evaluated by gender, sample type, and symptom status. In addition, the predictive values were calculated based on overall sensitivity and specificity (with all data combined for males and females) for a range of hypothetical prevalence values.
5.1.2. Results
A total of 5.197 subjects were prospectively enrolled, of which 5.105 were eligible for inclusion. Of the 5,105 eligible subjects contributing prospective specimens, 5,053 (99.0%) (3,860 females and 1,193 males) were evaluable and were included in the data analyses. A total of 52 subjects (1.0%) were classified as non-evaluable and excluded from all statistical analyses. There were a total of 371 archived prospectively collected female urogenital samples (urine, cervical specimens in PreservCyt, and endocervical swabs) tested in this clinical study from 295 female subjects. Among the 17.169 samples tested in this study, 19 samples exhibited invalid results on the first run (invalid rate of 0.11% (95%CI: 0.07% ; 0.17%)). Upon repeat testing, 3 samples exhibited valid results.
{25}------------------------------------------------
Table 13 and Table 14 summarize the results from symptomatic and asymptomatic, prospectively enrolled subjects designated as infected or non-infected with CT (females and males, respectively) according to the PIS algorithm. A total of 271 females and 118 males were infected with CT. Symptoms were reported in 45.8% (124/271) of infected and 36.7% (1318/3589) of non-infected females. Symptoms were reported in 53.4% (63/118) of infected and 22.5% (242/1074) of non-infected males.
{26}------------------------------------------------
| NAAT1 | NAAT2 | cobas® CT/NG | SymptomStatusa | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total | |
| Infected | + | + | + | + | + | + | + | + | 104 | 108 | 212 | |
| Infected | - | + | + | + | + | + | + | + | 2 | 7 | 9 | |
| Infected | + | + | + | + | + | + | - | + | 1 | 5 | 6 | |
| Infected | + | + | + | + | + | + | + | + | 2 | 4 | 6 | |
| Infected | + | + | + | + | + | + | - | - | 1 | 4 | 5 | |
| Infected | + | + | + | + | + | + | + | - | 1 | 3 | 4 | |
| Infected | - | + | + | + | - | + | + | + | 1 | 3 | 4 | |
| Infected | - | + | - | + | - | + | + | + | 2 | 2 | 4 | |
| Infected | - | + | - | + | + | + | + | + | 2 | 1 | 3 | |
| Infected | + | - | + | + | + | + | - | - | 1 | 1 | 2 | |
| Infected | + | + | + | + | + | + | Failed | + | 0 | 1 | 1 | |
| Infected | + | + | + | + | + | + | + | Failed | 1 | 0 | 1 | |
| Infected | - | + | + | + | + | + | + | + | 0 | 1 | 1 | |
| Infected | - | + | + | + | + | + | + | - | 0 | 1 | 1 | |
| Infected | - | + | + | + | + | + | - | + | 1 | 0 | 1 | |
| Infected | - | + | + | + | + | + | - | - | 0 | 1 | 1 | |
| Infected | - | + | + | + | - | + | - | - | 1 | 0 | 1 | |
| Infected | - | + | - | + | + | + | + | - | 0 | 1 | 1 | |
| Infected | - | + | - | + | - | + | - | + | 0 | 1 | 1 | |
| Infected | + | - | + | + | + | + | + | + | 1 | 0 | 1 | |
| Infected | + | - | + | + | + | - | - | - | 0 | 1 | 1 | |
| Infected | + | - | - | + | - | + | - | - | 1 | 0 | 1 | |
| Infected | + | - | - | + | - | + | 0 | 1 | 1 | |||
| Infectedb | + | - | + | - | + | + | - | + | 1 | 0 | 1 | |
| Infectedb | + | - | + | - | + | + | - | - | 1 | 0 | 1 | |
| Infectedb | + | - | + | - | + | - | - | - | 0 | 1 | 1 | |
| Total | 124 | 147 | 271 | |||||||||
| Non-Infected | - | - | - | - | - | - | - | - | 1252 | 2165 | 3417 | |
| Non-Infected | - | - | - | + | - | - | - | - | 6 | 12 | 18 | |
| Non-Infected | - | Invalid | - | - | - | - | - | - | 7 | 5 | 12 | |
| Non-Infected | - | - | - | - | - | Invalid | - | 6 | 4 | 10 | ||
| Non-Infected | - | - | - | - | - | + | - | - | 1 | 9 | 10 | |
| NAAT1 | NAAT2 | cobas® CT/NG | SymptomStatusª | |||||||||
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total | |
| Non-Infected | - | - | + | - | - | - | - | - | 2 | 7 | 9 | |
| Non-Infected | - | - | - | - | - | - | - | + | 5 | 4 | 9 | |
| Non-Infected | - | - | NA | - | - | - | - | - | 2 | 7 | 9 | |
| Non-Infected | - | - | Invalid | - | - | - | - | - | 0 | 9 | 9 | |
| Non-Infected | - | - | - | - | - | - | - | NA | 3 | 5 | 8 | |
| Non-Infected | + | - | - | - | - | - | - | - | 3 | 3 | 6 | |
| Non-Infected | - | - | - | - | + | - | - | - | 1 | 5 | 6 | |
| Non-Infected | - | + | - | - | - | - | - | - | 2 | 2 | 4 | |
| Non-Infected | - | - | - | - | - | - | + | - | 1 | 3 | 4 | |
| Non-Infected | - | - | - | - | - | NA | - | - | 1 | 3 | 4 | |
| Non-Infected | - | NA | - | - | - | - | - | - | 0 | 4 | 4 | |
| Non-Infected | - | - | - | - | - | - | NA | NA | 0 | 3 | 3 | |
| Non-Infected | - | - | - | NA | - | - | - | - | 1 | 2 | 3 | |
| Non-Infected | NA | - | - | - | - | - | - | - | 0 | 3 | 3 | |
| Non-Infected | Invalid | - | - | - | - | - | - | - | 2 | 1 | 3 | |
| Non-Infected | - | + | - | - | - | + | - | - | 2 | 0 | 2 | |
| Non-Infected | - | - | - | + | - | + | + | + | 0 | 2 | 2 | |
| Non-Infected | - | - | - | + | - | + | + | - | 2 | 0 | 2 | |
| Non-Infected | - | - | - | + | - | + | - | + | 1 | 1 | 2 | |
| Non-Infected | - | - | - | + | - | + | - | - | 0 | 2 | 2 | |
| Non-Infected | - | - | - | - | - | + | + | + | 2 | 0 | 2 | |
| Non-Infected | - | - | - | - | - | - | - | Invalid | 2 | 0 | 2 | |
| Non-Infected | - | - | - | Invalid | - | - | - | - | 1 | 1 | 2 | |
| Non-Infected | - | - | + | + | - | + | - | - | 0 | 1 | 1 | |
| Non-Infected | - | - | + | - | + | - | - | - | 0 | 1 | 1 | |
| Non-Infected | - | - | + | - | - | + | - | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | + | + | + | + | + | 0 | 1 | 1 | |
| Non-Infected | - | - | - | + | - | - | + | + | 1 | 0 | 1 | |
| Non-Infected | - | - | - | + | + | + | - | + | 0 | 1 | 1 | |
| Non-Infected | - | - | - | + | - | - | - | + | 0 | 1 | 1 | |
| Non-Infected | - | - | - | + | + | + | - | - | 0 | 1 | 1 | |
| Non-Infected | - | - | - | - | - | - | NA | - | 0 | 1 | 1 | |
| Non-Infected | - | - | - | - | - | Invalid | Invalid | Invalid | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | - | Invalid | Invalid | 1 | 0 | 1 | |
| NAAT1 | NAAT2 | cobas® CT/NG | SymptomStatusa | |||||||||
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total | |
| Non-Infected | - | - | - | - | - | NA | Invalid | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | - | Invalid | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | + | + | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | - | - | Failed | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | + | - | - | + | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | + | - | + | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | Failed | - | - | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | - | - | Failed | - | - | 1 | 0 | 1 | |
| Non-Infected | - | - | - | Invalid | - | + | + | + | 0 | 1 | 1 | |
| Non-Infected | - | - | NA | + | - | + | - | - | 0 | 1 | 1 | |
| Non-Infected | - | Invalid | - | - | - | Invalid | - | - | 1 | 0 | 1 | |
| Total | 1318 | 2271 | 3589 |
Table 13: CT positive/negative analyses for female Patient Infected Status
{27}------------------------------------------------
{28}------------------------------------------------
ª Symp = symptomatic, Asymp = asymptomatic.
b Infected (Urine), Non-Infected (Swabs).
Note: In the scenario where one or more of the sample types are invalidinot available (NA), for female subjects, the remaining sample types with valid results from NAAT2 must have concordant positive or concordant negative results to determine the PIS as Infected or Not Infected, respectively. For all other cases where one or more of the sample types are invalid/not available (NA), the PIS is indeterminate.
Note: Female subjects with designated infection status (Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table.
Note: + denotes Positive, - denotes Negative, NA denotes Not Available.
Note: UR = urine, VS = vaginal swab, PC = PreservCyt®, ES = endocervical swab.
Note: cobas Invalid are the sum of instrument amplification errors and samples excluded due to protocol deviations
Note: cobas Failed are hardware, software or operator errors causing no result reported
{29}------------------------------------------------
| NAAT1 | NAAT2 | NAAT3 | cobas®CT/NG | Symptom Statusa | |||
|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | UR | UR | UR | Symp | Asymp | Total |
| Infected | + | + | + | + | 60 | 55 | 115 |
| Infected | - | + | + | + | 1 | 0 | 1 |
| Infected | + | Invalid | + | + | 1 | 0 | 1 |
| Infected | + | - | + | + | 1 | 0 | 1 |
| Total Infected | 63 | 55 | 118 | ||||
| Non-Infected | - | - | - | - | 238 | 819 | 1057 |
| Non-Infected | - | Invalid | - | - | 2 | 2 | 4 |
| Non-Infected | Invalid | - | - | - | 0 | 3 | 3 |
| Non-Infected | - | - | Invalid | - | 0 | 3 | 3 |
| Non-Infected | NA | - | - | - | 1 | 1 | 2 |
| Non-Infected | - | - | - | + | 0 | 2 | 2 |
| Non-Infected | - | - | + | - | 0 | 1 | 1 |
| Non-Infected | - | + | - | + | 1 | 0 | 1 |
| Non-Infected | + | - | - | - | 0 | 1 | 1 |
| Total Non-Infected | 242 | 832 | 1074* |
Table 14: CT positive/negative analysis for male Patient Infected Status
a Symp = symptomatic, Asymp = asymptomatic.
*One subject was missing symptom status and is not presented in this table.
Note: If at least 2 out of the 3 test results, for male subjects, are concordant positive or negative then the PIS can be considered as infected or non-infected, respectively. If one test result is invalid/not available (NA) and the other two test results are discordant then the PIS is indeterminate. If 2 or 3 test results are invalid/not available, then the PIS is indeterminate.
Note: Male subjects with designated patient infection status (Infected or Non-Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table.
Note: cobas Invalid are the sum of instrument amplification errors and samples excluded due to protocol deviationsNote: + denotes Positive, - denotes Negative, NA denotes Not Available.
Note: UR = urine.
Sensitivity, specificity, and predictive values of cobas® CT/NG for CT as defined by PIS are presented by gender, sample type, and symptom status in Table 15.
{30}------------------------------------------------
| SampleTypeª | SymptomStatusb | Total(n) | SENS | 95% ScoreCI | SPEC | 95% ScoreCI | PREV(%) | PPV(%) | NPV(%) |
|---|---|---|---|---|---|---|---|---|---|
| Female | |||||||||
| UR | Symp | 1441 | 96.0%(119/124) | (90.9%,98.3%) | 99.8%(1315/1317) | (99.4%,100.0%) | 8.6 | 98.3 | 99.6 |
| Asymp | 2418 | 95.2%(140/147) | (90.5%,97.7%) | 99.6%(2262/2271) | (99.2%,99.8%) | 6.1 | 94.0 | 99.7 | |
| Overall | 3859 | 95.6%(259/271)c | (92.4%,97.4%) | 99.7%(3577/3588) | (99.5%,99.8%) | 7.0 | 95.9 | 99.7 | |
| VS-C | Symp | 711 | 100.0%(63/63) | (94.3%,100.0%) | 99.2%(643/648) | (98.2%,99.7%) | 8.9 | 92.6 | 100.0 |
| Asymp | 1225 | 97.6%(83/85) | (91.8%,99.4%) | 99.0%(1129/1140) | (98.3%,99.5%) | 6.9 | 88.3 | 99.8 | |
| Overall | 1936 | 98.6%(146/148) | (95.2%,99.6%) | 99.1%(1772/1788) | (98.6%,99.4%) | 7.6 | 90.1 | 99.9 | |
| VS-S | Symp | 720 | 100.0%(59/59) | (93.9%,100.0%) | 98.8%(653/661) | (97.6%,99.4%) | 8.2 | 88.1 | 100.0 |
| Asymp | 1186 | 98.4%(60/61) | (91.3%,99.7%) | 99.2%(1116/1125) | (98.5%,99.6%) | 5.1 | 87.0 | 99.9 | |
| Overall | 1906 | 99.2%(119/120) | (95.4%,99.9%) | 99.0%(1769/1786) | (98.5%,99.4%) | 6.3 | 87.5 | 99.9 | |
| РС | Symp | 1438 | 95.1%(116/122) | (89.7%,97.7%) | 99.5%(1309/1316) | (98.9%,99.7%) | 8.5 | 94.3 | 99.5 |
| Asymp | 2413 | 90.3%(131/145) | (84.4%,94.2%) | 99.7%(2261/2268) | (99.4%,99.9%) | 6.0 | 94.9 | 99.4 | |
| Overall | 3851 | 92.5%(247/267) | (88.7%,95.1%) | 99.6%(3570/3584) | (99.3%,99.8%) | 6.9 | 94.6 | 99.4 | |
| ES | Symp | 1433 | 95.9%(116/121) | (90.7%,98.2%) | 99.1%(1300/1312) | (98.4%,99.5%) | 8.4 | 90.6 | 99.6 |
| Asymp | 2410 | 91.1%(133/146) | (85.4%,94.7%) | 99.5%(2253/2264) | (99.1%,99.7%) | 6.1 | 92.4 | 99.4 | |
| Overall | 3843 | 93.3%(249/267) | (89.6%,95.7%) | 99.4%(3553/3576) | (99.0%,99.6%) | 6.9 | 91.5 | 99.5 | |
| Male | |||||||||
| UR | Symp | 305 | 100.0%(63/63) | (94.3%,100.0%) | 99.6%(241/242) | (97.7%,99.9%) | 20.7 | 98.4 | 100.0 |
| Asymp | 887 | 100.0%(55/55) | (93.5%,100.0%) | 99.8%(830/832) | (99.1%,99.9%) | 6.2 | 96.5 | 100.0 | |
| Overall | 1192* | 100.0%(118/118) | (96.8%,100.0%) | 99.7%(1071/1074) | (99.2%,99.9%) | 9.9 | 97.5 | 100.0 |
Table 15: CT clinical performance compared with Patient Infected Status by gender, sample type, and symptom status
{31}------------------------------------------------
| SampleTypea | SymptomStatusb | Total(n) | SENS | 95% ScoreCI | SPEC | 95% ScoreCI | PREV(%) | PPV(%) | NPV(%) |
|---|---|---|---|---|---|---|---|---|---|
| ----------------- | -------------------- | -------------- | ------ | ----------------- | ------ | ----------------- | ------------- | ------------ | ------------ |
a UR = urine, VS-C = clinician-collected vaginal swab, VS-S = self-collected vaginal swab, PC = PreservCyt®, ES = endocervical swab.
b Symp = symptomatic, Asymp = asymptomatic.
^ Five CT PIS infected females had a CT negative urine specimen with NAAT1 while they had a CT positive vaginal swab with NAAT1 and NAAT2.
- One subject was missing symptom status and is not presented in this table.
Note: In the scenario where one or more of the sample types are invalid/not available, for female subjects, the remaining sample types with valid results from NAAT2 must have concordant positive or concordant negative results to determine the PIS as Infected, respectively. For all other cases where one or more of the sample types are invalid/not available, the PIS is indeterminate.
Note: If at least 2 out of the 3 test results, for male subjects, are concordant positive or negative then the PIS can be considered as infected or non-infected, respectively. If one test result is invalid/not available and the other two test results are discordant then the PIS is indeterminate. If 2 or 3 test results are invalid/not available, then the PIS is indeterminate.
Note: Subjects with designated patient infection status (Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table. An evaluable subject may not have all available sample types or valid test results.
Note: Cl = confidence interval, PREV = prevalence, SENS = sensitivity, SPEC = specificity, PPV = positive predictive value, NPV = negative predictive value.
Table 16 and Table 17 summarize the results from symptomatic and asymptomatic subjects
designated as infected or non-infected with NG (females and males, respectively) according to
the PIS algorithm. A total of 57 females and 87 males were infected with NG. Symptoms were
reported in 45.6% (26/57) of infected and 37.2% (1416/3803) of non-infected females.
Symptoms were reported in 94.3% (82/87) of infected and 20.2% (223/1105) of non-infected males.
{32}------------------------------------------------
| NAAT1 | NAAT2 | cobas® CT/NG | Symptom Statusa | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total |
| Infected | + | + | + | + | + | + | + | + | 20 | 23 | 43 |
| Infected | - | + | - | + | - | + | + | + | 2 | 3 | 5 |
| Infected | + | + | - | + | + | + | + | + | 0 | 2 | 2 |
| Infected | - | + | - | + | + | + | + | + | 2 | 0 | 2 |
| Infected | + | + | + | + | + | + | + | Failed | 1 | 0 | 1 |
| Infected | + | + | + | + | + | + | - | - | 0 | 1 | 1 |
| Infected | + | + | - | + | - | + | - | - | 0 | 1 | 1 |
| Infected | - | + | NA | + | + | + | + | - | 0 | 1 | 1 |
| Infectedb | + | - | + | - | + | - | - | - | 1 | 0 | 1 |
| Total | 26 | 31 | 57 |
Table 16: NG positive/negative analysis for female Patient Infected Status (prospective specimens)
| NAAT1 | NAAT2 | cobas® CT/NG | Symptom Statusa | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total | |
| Non-Infected | - | - | - | - | - | - | - | - | 1368 | 2315 | 3683 | |
| Non-Infected | - | + | - | - | - | - | - | - | 4 | 11 | 15 | |
| Non-Infected | + | - | - | - | - | - | - | - | 5 | 7 | 12 | |
| Non-Infected | - | - | NA | - | - | - | - | - | 2 | 7 | 9 | |
| Non-Infected | - | Invalid | - | - | - | - | - | - | 5 | 4 | 9 | |
| Non-Infected | - | - | - | - | - | Invalid | - | - | 5 | 3 | 8 | |
| Non-Infected | - | - | - | - | - | - | - | NA | 3 | 5 | 8 | |
| Non-Infected | - | - | Invalid | - | - | - | - | - | 0 | 8 | 8 | |
| Non-Infected | - | - | - | - | - | + | - | - | 2 | 4 | 6 | |
| Non-Infected | - | - | - | - | - | NA | - | - | 1 | 3 | 4 | |
| Non-Infected | - | NA | - | - | - | - | - | - | 0 | 4 | 4 | |
| Non-Infected | - | - | - | - | - | - | NA | NA | 0 | 3 | 3 | |
| Non-Infected | - | - | - | NA | - | - | - | - | 1 | 2 | 3 | |
| Non-Infected | NA | - | - | - | - | - | - | - | 0 | 3 | 3 | |
| Non-Infected | Invalid | - | - | - | - | - | - | - | 2 | 1 | 3 | |
| Non-Infected | + | + | - | - | - | + | - | - | 0 | 2 | 2 | |
| Non-Infected | - | - | - | - | + | - | - | - | 2 | 0 | 2 | |
| Non-Infected | - | - | - | - | - | - | - | Invalid | 2 | 0 | 2 |
{33}------------------------------------------------
| NAAT1 | NAAT2 | cobas® CT/NG | Symptom Statusa | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | VS | UR | VS | UR | VS | PC | ES | Symp | Asymp | Total |
| Non-Infected | + | + | - | - | - | - | - | - | 0 | 1 | 1 |
| Non-Infected | + | + | - | - | - | Invalid | - | - | 1 | 0 | 1 |
| Non-Infected | - | + | - | - | - | + | + | - | 1 | 0 | 1 |
| Non-Infected | - | + | - | - | - | + | - | - | 1 | 0 | 1 |
| Non-Infected | - | - | + | + | + | - | - | - | 1 | 0 | 1 |
| Non-Infected | - | - | - | + | - | + | - | - | 0 | 1 | 1 |
| Non-Infected | - | - | - | - | - | - | + | + | 0 | 1 | 1 |
| Non-Infected | - | - | - | - | - | - | - | + | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | Failed | - | - | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | Failed | - | - | - | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | - | - | Failed | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | - | NA | - | 0 | 1 | 1 |
| Non-Infected | - | - | - | - | - | - | Invalid | - | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | NA | Invalid | - | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | - | Invalid | Invalid | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | Invalid | Invalid | Invalid | 1 | 0 | 1 |
| Non-Infected | - | - | - | - | - | - | Failed | - | 0 | 1 | 1 |
| Non-Infected | - | - | - | Invalid | - | - | - | - | 1 | 0 | 1 |
| Non-Infected | - | Invalid | - | - | - | Invalid | - | - | 1 | 0 | 1 |
| Total | 1416 | 2387 | 3803 |
ª Symp = symptomatic, Asymp = asymptomatic.
b Infected (Urine), Non-Infected (Swabs).
Note: In the scenario where one or more of the sample types are invalidinot available (NA), for female subjects, the remaining sample types with valid results from NAAT1 and NAAT2 must have concordant positive or concordant negative results to determine the PIS as Infected, respectively. For all other cases where one or more of the sample types are invalid/not available (NA), the PIS is indeterminate.
Note: Female subjects with designated infection status (Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table.
Note: cobas Invalid are the sum of instrument amplification errors and samples excluded due to protocol deviations
Note: cobas Failed are hardware, software or operator errors causing no result reported
Note: + denotes Positive, - denotes Negative, NA denotes Not Available.
Note: UR = urine, VS = vaginal swab, PC = PreservCyt®, ES = endocervical swab.
{34}------------------------------------------------
| NAAT1a | NAAT2a | NAAT3a | cobas®CT/NG | Symptom Statusb | |||
|---|---|---|---|---|---|---|---|
| PatientInfectedStatus | UR | UR | UR | UR | Symp | Asymp | Total |
| Infected | + | + | + | + | 81 | 5 | 86 |
| Infected | NA | + | + | + | 1 | 0 | 1 |
| Total Infected | 82 | 5 | 87 | ||||
| Non-Infected | - | - | - | - | 215 | 863 | 1078 |
| Non-Infected | + | - | - | - | 2 | 7 | 9 |
| Non-Infected | - | Invalid | - | - | 3 | 2 | 5 |
| Non-Infected | - | - | - | + | 2 | 2 | 4 |
| Non-Infected | Invalid | - | - | - | 0 | 3 | 3 |
| Non-Infected | - | - | Invalid | - | 0 | 3 | 3 |
| Non-Infected | - | + | - | + | 1 | 1 | 2 |
| Non-Infected | NA | - | - | - | 0 | 1 | 1 |
| Total Non-Infected | 223 | 882 | 1105* |
Table 17: NG positive/negative analysis for male Patient Infected Status
a Symp = symptomatic, Asymp = asymptomatic.
*One subject was missing symptom status and is not included in this table.
Note: If at least 2 out of the 3 test results, for male subjects, are concordant positive or negative then the PIS can be considered as infected or non-infected, respectively. If one test result is invalid/not available (NA) and the other two test results are discordant the PIS is indeterminate. If 2 or 3 test results are invalid/not available, then the PIS is indeterminate.
Note: Male subjects with designated patient infection status (Infected or Non-Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table.
Note: + denotes Positive, - denotes Negative, NA denotes Not Available.
Note: UR = urine.
Sensitivity, specificity, and predictive values of cobas® CT/NG for NG as defined by PIS are presented by gender, sample type, and symptom status in Table 18 (prospective fresh and archived specimens).
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Table 18: NG clinical performance compared with Patient Infected Status by gender, sample type, and symptom status (prospective and archived prospectively collected specimens)
| SampleTypea | SymptomStatusb | Total(n) | SENS | 95% ScoreCI | SPEC | 95%Score CI | PREV(%) | PPV(%) | NPV(%) |
|---|---|---|---|---|---|---|---|---|---|
| Female | |||||||||
| UR(prospective) | Symp | 1441 | 92.3%(24/26) | (75.9%,97.9%) | 99.8%(1412/1415) | (99.4%,99.9%) | 1.8 | 88.9 | 99.9 |
| Asymp | 2418 | 87.1%(27/31) | (71.1%,94.9%) | 100.0%(2387/2387) | (99.8%,100.0%) | 1.3 | 100.0 | 99.8 | |
| Overall | 3859 | 89.5%(51/57) c | (78.9%,95.1%) | 99.9%(3799/3802) | (99.8%,100.0%) | 1.5 | 94.4 | 99.8 | |
| UR(archived) | Symp | 94 | 100.0%(35/35) | (90.1%,100.0%) | 100.0%(59/59) | (93.9%,100.0%) | 37.2 | 100.0 | 100.0 |
| Asymp | 101 | 97.6%(41/42) | (87.7%,99.6%) | 100.0%(59/59) | (93.9%,100.0%) | 41.6 | 100.0 | 98.3 | |
| Overall | 195 | 98.7%(76/77) | (93.0%,99.8%) | 100.0%(118/118) | (96.8%,100.0%) | 39.5 | 100.0 | 99.2 | |
| UR(prospectiveand archived) | Symp | 1535 | 96.7%(59/61) | (88.8%,99.1%) | 99.8%(1471/1474) | (99.4%,99.9%) | 4.0 | 95.2 | 99.9 |
| Asymp | 2519 | 93.2%(68/73) | (84.9%,97.0%) | 100.0%(2446/2446) | (99.8%,100.0%) | 2.9 | 100.0 | 99.8 | |
| Overall | 4054 | 94.8%(127/134) | (89.6%,97.4%) | 99.9%(3917/3920) | (99.8%,100.0%) | 3.3 | 97.7 | 99.8 | |
| VS-C | Symp | 711 | 100.0%(11/11) | (74.1%,100.0%) | 99.7%(698/700) | (99.0%,99.9%) | 1.5 | 84.6 | 100.0 |
| Asymp | 1225 | 100.0%(17/17) | (81.6%,100.0%) | 99.8%(1205/1208) | (99.3%,99.9%) | 1.4 | 85.0 | 100.0 | |
| Overall | 1936 | 100.0%(28/28) | (87.9%,100.0%) | 99.7%(1903/1908) | (99.4%,99.9%) | 1.4 | 84.8 | 100.0 | |
| VS-S | Symp | 720 | 100.0%(14/14) | (78.5%,100.0%) | 99.7%(704/706) | (99.0%,99.9%) | 1.9 | 87.5 | 100.0 |
| Asymp | 1187 | 100.0%(14/14) | (78.5%,100.0%) | 99.7%(1169/1173) | (99.1%,99.9%) | 1.2 | 77.8 | 100.0 | |
| Overall | 1907 | 100.0%(28/28) | (87.9%,100.0%) | 99.7%(1873/1879) | (99.3%,99.9%) | 1.5 | 82.4 | 100.0 | |
| PC(prospective) | Symp | 1438 | 100.0%(25/25) | (86.7%,100.0%) | 99.9%(1412/1413) | (99.6%,100.0%) | 1.7 | 96.2 | 100.0 |
| Asymp | 2413 | 93.5%(29/31) | (79.3%,98.2%) | 100.0%(2381/2382) | (99.8%,100.0%) | 1.3 | 96.7 | 99.9 | |
| Overall | 3851 | 96.4%(54/56) | (87.9%,99.0%) | 99.9%(3793/3795) | (99.8%,100.0%) | 1.5 | 96.4 | 99.9 | |
| SampleTypea | SymptomStatusb | Total(n) | SENS | 95% ScoreCI | SPEC | 95%Score Cl | PREV(%) | PPV(%) | NPV(%) |
| PC(archived) | Symp | 48 | 95.7%(22/23) | (79.0%,99.2%) | 100.0%(25/25) | (86.7%,100.0%) | 47.9 | 100.0 | 96.2 |
| Asymp | 23 | 100.0%(10/10) | (72.2%,100.0%) | 100.0%(13/13) | (77.2%,100.0%) | 43.5 | 100.0 | 100.0 | |
| Overall | 71 | 97.0%(32/33) | (84.7%,99.5%) | 100.0%(38/38) | (90.8%,100.0%) | 46.5 | 100.0 | 97.4 | |
| РС(prospective | Symp | 1486 | 97.9%(47/48) | (89.1%,99.6%) | 99.9%(1437/1438) | (99.6%,100.0%) | 3.2 | 97.9 | 99.9 |
| and archived) | Asymp | 2436 | 95.1%(39/41) | (83.9%,98.7%) | 100.0%(2394/2395) | (99.8%,100.0%) | 1.7 | 97.5 | 99.9 |
| Overall | 3922 | 96.6%(86/89) | (90.6%,98.8%) | 99.9%(3831/3833) | (99.8%,100.0%) | 2.3 | 97.7 | 99.9 | |
| ES(prospective) | Symp | 1433 | 100.0%(24/24) | (86.2%,100.0%) | 99.9%(1408/1409) | (99.6%,100.0%) | 1.7 | 96.0 | 100.0 |
| Asymp | 2410 | 90.3%(28/31) | (75.1%,96.7%) | 100.0%(2378/2379) | (99.8%,100.0%) | 1.3 | 96.6 | 99.9 | |
| Overall | 3843 | 94.5%(52/55) | (85.1%,98.1%) | 99.9%(3786/3788) | (99.8%,100.0%) | 1.4 | 96.3 | 99.9 | |
| ES(archived) | Symp | 51 | 100.0%(21/21) | (84.5%,100.0%) | 100.0%(30/30) | (88.6%,100.0%) | 41.2 | 100.0 | 100.0 |
| Asymp | 54 | 100.0%(24/24) | (86.2%,100.0%) | 100.0%(30/30) | (88.6%,100.0%) | 44.4 | 100.0 | 100.0 | |
| Overall | 105 | 100.0%(45/45) | (92.1%,100.0%) | 100.0%(60/60) | (94.0%,100.0%) | 42.9 | 100.0 | 100.0 | |
| ES(prospective | Symp | 1484 | 100.0%(45/45) | (92.1%,100.0%) | 99.9%(1438/1439) | (99.6%,100.0%) | 3.0 | 97.8 | 100.0 |
| and archived) | Asymp | 2464 | 94.5%(52/55) | (85.1%,98.1%) | 100.0%(2408/2409) | (99.8%,100.0%) | 2.2 | 98.1 | 99.9 |
| Overall | 3948 | 97.0%(97/100) | (91.5%,99.0%) | 99.9%(3846/3848) | (99.8%,100.0%) | 2.5 | 98.0 | 99.9 | |
| UR | Symp | 305 | 100.0%(82/82) | (95.5%,100.0%) | 98.7%(220/223) | (96.1%,99.5%) | 26.9 | 96.5 | 100.0 |
| Asymp | 887 | 100.0%(5/5) | (56.6%,100.0%) | 99.7%(879/882) | (99.0%,99.9%) | 0.6 | 62.5 | 100.0 | |
| Overall | 1192* | 100.0%(87/87) | (95.8%,100.0%) | 99.5%(1099/1105) | (98.8%,99.8%) | 7.3 | 93.5 | 100.0 |
{36}------------------------------------------------
{37}------------------------------------------------
| SampleTypea | SymptomStatusb | Total(n) | SENS | 95% ScoreCI | SPEC | 95%Score CI | PREV(%) | PPV(%) | NPV(%) |
|---|---|---|---|---|---|---|---|---|---|
| ----------------- | -------------------- | -------------- | ------ | ----------------- | ------ | ----------------- | ------------- | ------------ | ------------ |
a UR = urine, VS-C = clinician-collected vaginal swab, VS-S = self-collected vaginal swab, PC = PreservCyt®, ES = endocervical swab.
b Symp = symptomatic. Asymp = asymptomatic.
^ Five NG PIS infected females had a NG negative urine specimen with NAAT1 and NAAT2 while they had a NG positive vaginal swab with NAAT1 and NAAT2
- One subject was missing symptom status and is not included in this table.
Note: In the scenario where one or more of the sample types are invalid/not available, for female subjects, the remaining sample types with valid results from NAAT2 must have concordant positive or concordant negative results to determine the PIS as Infected, respectively. For all other cases where one or more of the sample types are invalid/ not available, the PIS is indeterminate.
Note: If at least 2 out of the 3 test results, for male subjects, are concordant positive or negative then the PIS can be considered as Infected or Non-Infected, respectively. If one test result is invalidinot available and the other two test results are discordant then the PIS is indeterminate. If 2 or 3 test results are invalid/not available, then the PIS is indeterminate.
Note: Subjects with designated patient infection status (Infected) and final valid cobas® CT/NG test results are considered evaluable and included in this summary table. An evaluable subject may not have all available sample types or valid test results.
Note: Archived prospectively collected specimens were from COB-CTNG-282 study and included female PIS positive subjects that have available sample with adequate volume for testing.
Note: Cl = confidence interval, PREV = prevalence, SENS = sensitivity, SPEC = specificity, PPV = positive predictive value, NPV = negative predictive value.
5.2. Clinical Reproducibility
Study Design 5.2.1.
A Reproducibility Study was performed across different sites, lots, operators/batches days, for cobas® CT/NG using three panels prepared from swabs and urine in cobas® PCR Media and cervical specimens in PreservCyt® Solution. PCR testing was performed at two external sites and one site that was in-house at Roche Molecular Systems. One panel consisted of the three sample matrices, with six concentrations per matrix, and three replicates per concentration for a total of 54 samples in one panel. A batch was comprised of one 54-sample panel and two controls (one positive control and one negative control). Two operators at each site tested one batch each per day. Two valid batches had to be completed within a 24-hour period. Each site received two of three reagent lots and performed 6 days of testing per reagent lot for a total of 12 days of testing.
{38}------------------------------------------------
5.2.2. Results
The Reproducibility Study was executed with a total of 3.888 tests performed on the 6 panel groups, consisting of 1.296 tests for each panel type (urine, swab, and PreservCyt®), with only two failed tests each from PreservCyt®. No false positive results for either CT or NG were observed in the three panel types for negative panel members; thus the negative percent agreement was 100% for each analyte. Results for the positive panel members were highly reproducible across different lots, sites/instruments, days and operators/batches.
5.2.2.1. Negative panel results
For each sample type, all of the 216 valid tests from the negative panel members resulted in "Negative Results". Hence, for both CT and NG, the percent of correct results (analytical specificity) was estimated as 100% with a corresponding 95% exact confidence interval of 98.3%, 100% for cobas® PCR Media/urine, for cobas® PCR Media/swab and for PreservCyt®/cervical sample types.
Chlamydia trachomatis results 5.2.2.2.
For each positive panel member, precision was evaluated using a random effects model by sample type with terms for lot, site, day, operator/batch within site, lot and day, and within-batch components on the corresponding analyte cycle threshold (Ct) values of cobas® CT/NG. Table 19 presents the total SD, and total percent CV (%) from these analyses for each panel type, respectively. The range of the total coefficient of variation, among positive panel members, was from 0.9% to 3.2%. The maximum total coefficient of variation was observed in the lowest concentration of positive panel members (0.3x LoD CT, 0.3x LoD NG) and most of that variability (98.6% for urine, 100% for swab and 81.7% for cervical) was explained by random error (within-batch).
{39}------------------------------------------------
Table 19: CT: overall mean, attributable percentage of total variance, total precision standard deviation, and CV(%) of cobas® CT/NG cycle threshold (Ct) values by CT positive panel member for each media type
| Panel Member | Mean CT value | Percentage of Total Variance (CV[%]) | Total Precision | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Media Type | Concentration | N a | Mean Estimate b | Site | Lot | Day | Operator /Batch | Within-Batch | SD c | CV(%) d |
| PCR Media/Urine | 0.3xLOD CT, 0.3xLOD NG | 154 | 39.2 | 1.4% (0.4) | 0.0% (0.0) | 0.0% (0.0) | 0.0% (0.0) | 98.6% (3.0) | 1.20 | 3.1 |
| 1xLOD CT, Negative NG | 216 | 36.8 | 0.0% (0.0) | 0.0% (0.0) | 0.0% (0.0) | 0.0% (0.0) | 100.0% (1.5) | 0.54 | 1.5 | |
| 3xLOD CT, 1xLOD NG | 216 | 35.4 | 2.4% (0.1) | 0.0% (0.0) | 21.1% (0.4) | 0.0% (0.0) | 76.5% (0.8) | 0.33 | 0.9 | |
| 1xLOD CT, 3xLOD NG | 216 | 36.9 | 0.0% (0.0) | 0.0% (0.0) | 10.3% (0.5) | 4.4% (0.3) | 85.3% (1.5) | 0.59 | 1.6 | |
| PCR Media/Swab | 0.3xLOD CT, 0.3xLOD NG | 128 | 39.5 | 0.0% (0.0) | 0.0% (0.0) | 0.0% (0.0) | 0.0% (0.0) | 100.0% (3.2) | 1.26 | 3.2 |
| 1xLOD CT, Negative NG | 216 | 37.2 | 0.0% (0.0) | 1.6% (0.2) | 6.6% (0.5) | 0.0% (0.0) | 91.8% (1.7) | 0.66 | 1.8 | |
| 3xLOD CT, 1xLOD NG | 216 | 35.5 | 4.7% (0.2) | 0.0% (0.0) | 9.0% (0.3) | 4.8% (0.2) | 81.6% (0.9) | 0.37 | 1.0 | |
| 1xLOD CT, 3xLOD NG | 216 | 37.2 | 0.0% (0.0) | 0.0% (0.0) | 3.6% (0.4) | 0.0% (0.0) | 96.4% (2.3) | 0.87 | 2.3 | |
| PreservCyt/Cervical | 0.3xLOD CT, 0.3xLOD NG | 92 | 39.9 | 0.0% (0.0) | 0.0% (0.0) | 18.3% (1.4) | 0.0% (0.0) | 81.7% (2.9) | 1.29 | 3.2 |
| 1xLOD CT, Negative NG | 216 | 37.0 | 12.0% (0.6) | 1.9% (0.2) | 0.0% (0.0) | 0.0% (0.0) | 86.2% (1.5) | 0.60 | 1.6 | |
| 3xLOD CT, 1xLOD NG | 216 | 35.6 | 0.6% (0.1) | 3.7% (0.2) | 0.0% (0.0) | 6.3% (0.3) | 89.3% (0.9) | 0.36 | 1.0 | |
| 1xLOD CT, 3xLOD NG | 214 | 36.8 | 13.1% (0.6) | 3.7% (0.3) | 5.3% (0.4) | 2.3% (0.3) | 75.6% (1.5) | 0.63 | 1.7 |
Note: The table only includes results with detectable analyte. SD = standard deviation. CV(%) = percent coefficient of variation.
ª Number of valid tests with detectable analyte.
b Calculated using SAS MIXED procedure.
َ Calculated using the total variability from the SAS MIXED procedure.
d CV(%) = (SD/Mean) * 100.
LOD= Limit of Detection; CT= Chlamydia trachomatis ; NG = Neisseria gonorrhoeae.
{40}------------------------------------------------
Table 20 through Table 22 present the percent agreement of CT test results for panel members by lot, site, and day for each media type, respectively.
| CT Percent Agreementa | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||||
| Negative CT, NegativeNG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 0.3x LoD CT, 0.3x LoDNG | 1.20 | 3.1 | 1 | 76.4 | 55/72 | 1 | 68.1 | 49/72 | 1 | 80.6 | 29/36 |
| 2 | 70.8 | 51/72 | 2 | 73.6 | 53/72 | 2 | 77.8 | 28/36 | |||
| 3 | 66.7 | 48/72 | 3 | 72.2 | 52/72 | 3 | 66.7 | 24/36 | |||
| 4 | 77.8 | 28/36 | |||||||||
| 5 | 69.4 | 25/36 | |||||||||
| 6 | 55.6 | 20/36 | |||||||||
| 1x LoD CT, Negative NG | 0.54 | 1.5 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| Negative CT, 1x LoD NG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||||
| 3x LoD CT, 1x LoD NG | 0.33 | 0.9 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 1x LoD CT, 3x LoD NG | 0.59 | 1.6 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 |
Table 20: CT: Percent agreement by panel member for lot, site and day - cobas® PCR Media/urine
{41}------------------------------------------------
ª For CT Negative samples, Percent Agreement = (number of CT negative results/total valid results) x 100. For CT Positive samples, Percent Agreement = (number of CT positive results/total valid results) x 100. b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection.
CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
Table 21: CT: Percent agreement by panel member for lot, site and day - cobas® PCR Media/swab
| CT Percent Agreementa | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||||
| Negative CT, NegativeNG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 0.3x LoD CT, 0.3x LoDNG | 1.26 | 3.2 | 1 | 61.1 | 44/72 | 1 | 56.9 | 41/72 | 1 | 50.0 | 18/36 |
| 2 | 59.7 | 43/72 | 2 | 61.1 | 44/72 | 2 | 63.9 | 23/36 | |||
| 3 | 56.9 | 41/72 | 3 | 59.7 | 43/72 | 3 | 55.6 | 20/36 | |||
| 4 | 61.1 | 22/36 | |||||||||
| 5 | 66.7 | 24/36 | |||||||||
| 6 | 58.3 | 21/36 |
{42}------------------------------------------------
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1x LoD CT, Negative NG | 0.66 | 1.8 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| Negative CT, 1x LoD NG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 3x LoD CT, 1x LoD NG | 0.37 | 1.0 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 1x LoD CT, 3x LoD NG | 0.87 | 2.3 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 |
ª For CT Negative samples, Percent Agreement = (number of CT negative results/total valid results) x 100.
For CT Positive samples, Percent Agreement = (number of CT positive results/total valid results) x 100.
b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection.
CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
Table 22: CT: Percent agreement by panel member for lot, site and day -PreservCyt®/cervical
| CT Percent Agreementa | |
|---|---|
| -- | ----------------------- |
{43}------------------------------------------------
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Negative CT, Negative NG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 0.3x LoD CT, 0.3x LoDNG | 1.29 | 3.2 | 1 | 38.9 | 28/72 | 1 | 34.7 | 25/72 | 1 | 40.0 | 14/35 |
| 2 | 47.9 | 34/71 | 2 | 48.6 | 35/72 | 2 | 52.8 | 19/36 | |||
| 3 | 41.7 | 30/72 | 3 | 45.1 | 32/71 | 3 | 38.9 | 14/36 | |||
| 4 | 47.2 | 17/36 | |||||||||
| 5 | 41.7 | 15/36 | |||||||||
| 6 | 36.1 | 13/36 | |||||||||
| 1x LoD CT, Negative NG | 0.60 | 1.6 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| Negative CT, 1x LoD NG | n/a | n/a | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 3x LoD CT, 1x LoD NG | 0.36 | 1.0 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 | |||||||||
| 1x LoD CT, 3x LoD NG | 0.63 | 1.7 | 1 | 98.6 | 71/72 | 1 | 98.6 | 71/72 | 1 | 97.2 | 35/36 |
| 2 | 100.0 | 71/71 | 2 | 100.0 | 71/71 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 |
{44}------------------------------------------------
| CT Percent Agreementa | |||||||
|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||
| 4 | 100.0 | 35/35 | |||||
| 5 | 100.0 | 36/36 | |||||
| 6 | 100.0 | 36/36 |
a For CT Negative samples, Percent Agreement = (number of CT negative results/total valid results) x 100. For CT Positive samples, Percent Agreement = (number of CT positive results/total valid results) x 100. b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection. CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
Neisseria gonorrhoeae results 5.2.2.3.
Analysis of variance components of the Ct values from valid NG test results were performed on positive panel members. Table 23 presents the total CV (%) from these analyses. The range of the total coefficient of variation, among positive panel members, was from 1.0% to 3.1%. The maximum total coefficient of variation was observed in the lowest concentration of positive panel members (0.3x LoD CT, 0.3x LoD NG) and most of that variability (98.7% for urine, 98.1% for swab and 85.3% for cervical) was explained by random error (within-batch).
{45}------------------------------------------------
Table 23: NG: overall mean, attributable percentage of total variance, total precision standard deviation, and CV(%) of cobas® CTNG cycle threshold (Ct) values by NG positive panel member for each media type
| Panel Member | Mean CT value | Percentage of Total Variance (CV[%]) | Total Precision | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Media Type | Concentration | N a | Mean Estimate b | Site | Lot | Day | Operator/Batch | Within-Batch | SD c | CV(%) d |
| PCR Media/Urine | 0.3xLOD CT, 0.3xLOD NG | 159 | 39.3 | 0.7%(0.3) | 0.0%(0.0) | 0.6%(0.2) | 0.0%(0.0) | 98.7%(3.0) | 1.20 | 3.0 |
| Negative CT, 1xLOD NG | 216 | 36.7 | 0.0%(0.0) | 0.5%(0.1) | 6.9%(0.5) | 0.0%(0.0) | 92.6%(1.7) | 0.63 | 1.7 | |
| 3xLOD CT, 1xLOD NG | 216 | 36.6 | 0.0%(0.0) | 2.5%(0.3) | 8.3%(0.5) | 0.0%(0.0) | 89.2%(1.6) | 0.61 | 1.7 | |
| 1xLOD CT, 3xLOD NG | 216 | 35.1 | 0.0%(0.0) | 0.0%(0.0) | 14.0%(0.4) | 0.0%(0.0) | 86.0%(1.0) | 0.37 | 1.0 | |
| PCR Media/Swab | 0.3xLOD CT, 0.3xLOD NG | 113 | 39.8 | 0.0%(0.0) | 0.0%(0.0) | 1.9%(0.4) | 0.0%(0.0) | 98.1%(3.1) | 1.25 | 3.1 |
| Negative CT, 1xLOD NG | 212 | 38.2 | 0.0%(0.0) | 0.1%(0.1) | 1.8%(0.4) | 6.5%(0.7) | 91.6%(2.6) | 1.04 | 2.7 | |
| 3xLOD CT, 1xLOD NG | 216 | 36.9 | 0.0%(0.0) | 0.0%(0.0) | 6.3%(0.6) | 0.0%(0.0) | 93.7%(2.1) | 0.82 | 2.2 | |
| 1xLOD CT, 3xLOD NG | 216 | 35.7 | 0.0%(0.0) | 3.8%(0.3) | 14.4%(0.5) | 0.0%(0.0) | 81.8%(1.3) | 0.50 | 1.4 | |
| PreservCyt/Cervical | 0.3xLOD CT, 0.3xLOD NG | 112 | 39.5 | 0.0%(0.0) | 0.0%(0.0) | 0.0%(0.0) | 14.7%(1.0) | 85.3%(2.4) | 1.04 | 2.6 |
| Negative CT, 1xLOD NG | 216 | 35.7 | 7.2%(0.4) | 4.9%(0.3) | 0.0%(0.0) | 0.0%(0.0) | 87.9%(1.3) | 0.49 | 1.4 | |
| 3xLOD CT, 1xLOD NG | 216 | 36.3 | 0.0%(0.0) | 0.0%(0.0) | 0.0%(0.0) | 9.6%(0.5) | 90.4%(1.6) | 0.61 | 1.7 | |
| 1xLOD CT, 3xLOD NG | 215 | 34.6 | 2.3%(0.2) | 0.0%(0.0) | 5.8%(0.2) | 12.0%(0.3) | 79.8%(0.9) | 0.34 | 1.0 | |
| Note: The table only includes results with detectable analyte. SD = standard deviation. CV(%) = percent coefficient of variation. |
a Number of valid tests with detectable analyte.
b Calculated using SAS MIXED procedure.
· Calculated using the total variability from the SAS MIXED procedure.
d CV(%) = (SD/Mean) * 100.
LOD= Limit of Detection; CT = Chlamydia trachomatis ; NG = Neisseria gonorrhoeae.
Table 24 through Table 26 present the percent agreement of NG test results for panel members
by lot, site, and day for each media type, respectively.
{46}------------------------------------------------
| NG Percent Agreementa | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||||
| Negative CT, Negative NG | n/a | n/a | 1 | 100.0 | 72/72 | 100.0 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 100.0 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 100.0 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||
| 5 | 100.0 | 36/36 | |||||||
| 6 | 100.0 | 36/36 | |||||||
| 0.3x LoD CT, 0.3x LoDNG | 1.20 | 3.0 | 1 | 79.2 | 57/72 | 70.8 | 1 | 77.8 | 28/36 |
| 2 | 73.6 | 53/72 | 76.4 | 2 | 75.0 | 27/36 | |||
| 3 | 68.1 | 49/72 | 73.6 | 3 | 72.2 | 26/36 | |||
| 4 | 80.6 | 29/36 | |||||||
| 5 | 61.1 | 22/36 | |||||||
| 6 | 75.0 | 27/36 | |||||||
| 1x LoD CT, Negative NG | n/a | n/a | 1 | 100.0 | 72/72 | 100.0 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 100.0 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 100.0 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||
| 5 | 100.0 | 36/36 | |||||||
| 6 | 100.0 | 36/36 | |||||||
| Negative CT, 1x LoD NG | 0.63 | 1.7 | 1 | 100.0 | 72/72 | 100.0 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 100.0 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 100.0 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||
| 5 | 100.0 | 36/36 | |||||||
| 6 | 100.0 | 36/36 | |||||||
| 3x LoD CT, 1x LoD NG | 0.61 | 1.7 | 1 | 100.0 | 72/72 | 100.0 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 100.0 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 100.0 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||
| 5 | 100.0 | 36/36 | |||||||
| 6 | 100.0 | 36/36 |
Table 24: NG: Percent agreement by panel member for lot, site and day - cobas® PCR Media/urine
{47}------------------------------------------------
| PanelMember | CtSD | CtCV% | NG Percent AgreementaLot | Siteb | Day | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1x LoD CT, 3x LoD NG | 0.37 | 1.0 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 |
| 2 | 100.0 | 72/72 | 2 | 100.0 | 72/72 | 2 | 100.0 | 36/36 | |||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | |||
| 4 | 100.0 | 36/36 | |||||||||
| 5 | 100.0 | 36/36 | |||||||||
| 6 | 100.0 | 36/36 |
ª For NG Negative samples, Percent Agreement = (number of NG negative results/total valid results) x 100.
For NG Positive samples, Percent Agreement = (number of NG positive results/total valid results) x 100. b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection.
CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
| Table 25: NG: Percent agreement by panel member for lot, site and day - cobas® PCR |
|---|
| Media/swab |
| NG Percent Agreementa | |||||
|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day |
| Negative CT, NegativeNG | n/a | n/a | 1 100.0 72/72 | 1 100.0 72/72 | 1 100.0 36/36 |
| 2 100.0 72/72 | 2 100.0 72/72 | 2 100.0 36/36 | |||
| 3 100.0 72/72 | 3 100.0 72/72 | 3 100.0 36/36 | |||
| 4 100.0 36/36 | |||||
| 5 100.0 36/36 | |||||
| 6 100.0 36/36 | |||||
| 0.3x LoD CT, 0.3x LoDNG | 1.25 | 3.1 | 1 50.0 36/72 | 1 50.0 36/72 | 1 52.8 19/36 |
| 2 51.4 37/72 | 2 52.8 38/72 | 2 55.6 20/36 | |||
| 3 55.6 40/72 | 3 54.2 39/72 | 3 44.4 16/36 | |||
| 4 55.6 20/36 | |||||
| 5 52.8 19/36 | |||||
| 6 52.8 19/36 |
{48}------------------------------------------------
| NG Percent Agreementa | |||||||
|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | ||
| 1x LoD CT, Negative NG | n/a | n/a | 1 | 100.0 72/72 | 1 | 100.0 72/72 | 100.0 36/36 |
| 2 | 100.0 72/72 | 2 | 100.0 72/72 | 100.0 36/36 | |||
| 3 | 100.0 72/72 | 3 | 100.0 72/72 | 100.0 36/36 | |||
| 100.0 36/36 | |||||||
| 100.0 36/36 | |||||||
| 100.0 36/36 | |||||||
| Negative CT, 1x LoD NG | 1.04 | 2.7 | 1 | 100.0 72/72 | 1 | 97.2 70/72 | 100.0 36/36 |
| 2 | 100.0 72/72 | 2 | 100.0 72/72 | 100.0 36/36 | |||
| 3 | 94.4 68/72 | 3 | 97.2 70/72 | 97.2 35/36 | |||
| 100.0 36/36 | |||||||
| 97.2 35/36 | |||||||
| 94.4 34/36 | |||||||
| 3x LoD CT, 1x LoD NG | 0.82 | 2.2 | 1 | 100.0 72/72 | 1 | 100.0 72/72 | 100.0 36/36 |
| 2 | 100.0 72/72 | 2 | 100.0 72/72 | 100.0 36/36 | |||
| 3 | 100.0 72/72 | 3 | 100.0 72/72 | 100.0 36/36 | |||
| 100.0 36/36 | |||||||
| 100.0 36/36 | |||||||
| 100.0 36/36 | |||||||
| 1x LoD CT, 3x LoD NG | 0.50 | 1.4 | 1 | 100.0 72/72 | 1 | 100.0 72/72 | 100.0 36/36 |
| 2 | 100.0 72/72 | 2 | 100.0 72/72 | 100.0 36/36 | |||
| 3 | 100.0 72/72 | 3 | 100.0 72/72 | 100.0 36/36 | |||
| 100.0 36/36 | |||||||
| 100.0 36/36 | |||||||
| 100.0 36/36 |
ª For NG Negative samples, Percent Agreement = (number of NG negative results/total valid results) x 100.
For NG Positive samples, Percent Agreement = (number of NG positive results/total valid results) x 100. b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection.
CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
{49}------------------------------------------------
| PanelMember | CtSD | CtCV% | NG Percent Agreementa | ||
|---|---|---|---|---|---|
| Lot | Siteb | Day | |||
| Negative CT, Negative NG | n/a | n/a | 1 100.0 72/72 | 1 100.0 72/72 | 1 100.0 36/36 |
| 2 100.0 72/72 | 2 100.0 72/72 | 2 100.0 36/36 | |||
| 3 100.0 72/72 | 3 100.0 72/72 | 3 100.0 36/36 | |||
| 4 100.0 36/36 | |||||
| 5 100.0 36/36 | |||||
| 6 100.0 36/36 | |||||
| 0.3x LoD CT, 0.3x LoD NG | 1.04 | 2.6 | 1 63.9 46/72 | 1 59.7 43/72 | 1 54.3 19/35 |
| 2 47.9 34/71 | 2 52.8 38/72 | 2 55.6 20/36 | |||
| 3 44.4 32/72 | 3 43.7 31/71 | 3 47.2 17/36 | |||
| 4 55.6 20/36 | |||||
| 5 52.8 19/36 | |||||
| 6 47.2 17/36 | |||||
| 1x LoD CT, Negative NG | n/a | n/a | 1 100.0 72/72 | 1 100.0 72/72 | 1 100.0 36/36 |
| 2 100.0 72/72 | 2 100.0 72/72 | 2 100.0 36/36 | |||
| 3 100.0 72/72 | 3 100.0 72/72 | 3 100.0 36/36 | |||
| 4 100.0 36/36 | |||||
| 5 100.0 36/36 | |||||
| 6 100.0 36/36 | |||||
| Negative CT, 1x LoD NG | 0.49 | 1.4 | 1 100.0 72/72 | 1 100.0 72/72 | 1 100.0 36/36 |
| 2 100.0 72/72 | 2 100.0 72/72 | 2 100.0 36/36 | |||
| 3 100.0 72/72 | 3 100.0 72/72 | 3 100.0 36/36 | |||
| 4 100.0 36/36 | |||||
| 5 100.0 36/36 | |||||
| 6 100.0 36/36 | |||||
| 3x LoD CT, 1x LoD NG | 0.61 | 1.7 | 1 100.0 72/72 | 1 100.0 72/72 | 1 100.0 36/36 |
| 2 100.0 72/72 | 2 100.0 72/72 | 2 100.0 36/36 | |||
| 3 100.0 72/72 | 3 100.0 72/72 | 3 100.0 36/36 | |||
| 4 100.0 36/36 | |||||
| 5 100.0 36/36 | |||||
| 6 100.0 36/36 |
Table 26: NG: Percent agreement by panel member for lot, site and day -PreservCyt®/cervical
{50}------------------------------------------------
| NG Percent Agreementa | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PanelMember | CtSD | CtCV% | Lot | Siteb | Day | |||||||
| 1x LoD CT, 3x LoD NG | 0.34 | 1.0 | 1 | 100.0 | 72/72 | 1 | 100.0 | 72/72 | 1 | 100.0 | 36/36 | |
| 2 | 100.0 | 71/71 | 2 | 100.0 | 71/71 | 2 | 100.0 | 36/36 | ||||
| 3 | 100.0 | 72/72 | 3 | 100.0 | 72/72 | 3 | 100.0 | 36/36 | ||||
| 4 | 100.0 | 35/35 | ||||||||||
| 5 | 100.0 | 36/36 | ||||||||||
| 6 | 100.0 | 36/36 |
ª For NG Negative samples, Percent Agreement = (number of NG negative results/total valid results) x 100. For NG Positive samples, Percent Agreement = (number of NG positive results/total valid results) x 100.
b Site 1, Site 2, and Site 3, respectively.
Ct=Cycle threshold; SD=Standard Deviation; CV=Coefficient of Variation; LoD= Limit of Detection. CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae; n/a= not applicable.
Percentage agreement results 5.2.2.4.
Table 27 shows the percent agreement for each target (CT, NG) with the associated
95% Exact CI.
{51}------------------------------------------------
| CT | NG | ||||
|---|---|---|---|---|---|
| Media Type | PanelMember | PercentAgreement | PercentAgreement95% Exact Cl | PercentAgreement | PercentAgreement95% Exact Cl |
| PCRMedia/Urine | 1.0x LoD CT,Negative NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) |
| Negative CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| 3.0x LoD CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| 1.0x LoD CT,3.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| PCRMedia/Swab | 1.0x LoD CT,Negative NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) |
| Negative CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 98.1 (212/216) | (95.3, 99.5) | |
| 3.0x LoD CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| 1.0x LoD CT,3.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| PreservCyt®/Cervical | 1.0x LoD CT,Negative NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) |
| Negative CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| 3.0x LoD CT,1.0x LoD NG | 100.0 (216/216) | (98.3, 100.0) | 100.0 (216/216) | (98.3, 100.0) | |
| 1.0x LoD CT,3.0x LoD NG | 99.5 (214/215) | (97.4, 100.0) | 100.0 (215/215) | (98.3, 100.0) |
Table 27: Percent agreement for panel members with concentration at or near the LoD (1x LoD) or 3x LoD
Notes: LoD= Limit of Detection; CT= Chlamydia trachomatis; NG = Neisseria gonorrhoeae. For panel members with concentrations at or near the limit of detection (e.g., 1x LoD) of the test, the lower limit of the 2-sided 95% exact Cl of the percentage of correct test results should be equal to or greater than 91%. For panel members with concentrations 3-times above the limit of detection (e.g., 3x LoD) of the test, the lower limit of the 2-sided 95% exact Cl of the percentage of correct test results should be equal to or greater than 98%.
For panel members with concentrations at or near the limit of detection (e.g., 1x LoD) of the test, the lower limit of the 2-sided 95% exact CI of the percentage of correct test results was at least 97.4% for CT and 95.3% for NG.
{52}------------------------------------------------
For panel members with concentrations 3-times above the limit of detection (e.g., 3x LoD) of the test, the lower limit of the 2-sided 95% exact CI of the percentage of correct test results was 98.3% for both CT and NG.
CONCLUSIONS 6.
A comparison of the intended use, technological characteristics, and the results of non-clinical analytical and clinical performance studies demonstrate that cobas® CT/NG for use on the cobas® 6800/8800 systems is substantially equivalent to the predicate device.
§ 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).