(733 days)
The AMPLICOR® CT/NG Test for Neisseria gonorrhoeae is a qualitative in vitro test for the detection of Neisseria gonorrhoeae in clinical specimens. The test utilizes polymerase chain reaction (PCR) for the multiplex nucleic acid amplification of Neisseria gonorrhoeae and Chlamydia trachomatis DNA in endocervical and male urethral swab specimens and in male and female urine specimens from symptomatic and asymptomatic patients, and target-specific probe hybridization capture for the detection of the amplified Neisseria gonorrhoeae DNA.
The AMPLICOR CT/NG Test for Neisseria gonorrhoeae is a multiplex in vitro diagnostic test that enables the simultaneous amplification of Neisseria gonorrhoeae, Chlamydia trachomatis and an Internal Control sequence in a sample. The Test is designed for use with the Perkin Elmer 2400 or the Perkin Elmer 9600 thermal cycler for nucleic acid amplification of target DNA by polymerase chain reaction, and colorimetric detection using a conventional microwell plate washer and reader. The AMPLICOR CT/NG Test also incorporates an Internal Control for the identification of specimens that contain inhibitory substances to the PCR amplification reaction.
Here's an analysis of the acceptance criteria and study detailed in the provided K974503 submission for the Roche AMPLICOR® CT/NG Test for Neisseria gonorrhoeae:
Acceptance Criteria and Device Performance for Roche AMPLICOR® CT/NG Test for Neisseria gonorrhoeae
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state quantitative acceptance criteria in a table format. However, based on the clinical performance data presented, the implicit acceptance criteria would relate to demonstrating substantial equivalence to culture methods, with acceptable sensitivity and specificity values across different specimen types and patient populations.
The reported device performance metrics are as follows:
| Metric | Category / Specimen Type | Symptom Status | Reported Device Performance |
|---|---|---|---|
| Sensitivity | Female CTM | Asymptomatic | 98.0% (95% CI: 89.3-99.9) |
| Female CTM | Symptomatic | 94.5% (95% CI: 86.6-98.5) (with IC) / 91.9% (95% CI: 85.7-98.1) (without IC) | |
| Male CTM (Total) | (Combined) | 98.6% (95% CI: 96.6-99.5) | |
| Male Urine | Asymptomatic | 72.7% (95% CI: 39.0-94.0) | |
| Male Urine | Symptomatic | 95.1% (95% CI: 92.7-97.4) (with IC) / 89.2% (95% CI: 85.8-92.5) (without IC) | |
| Specificity | Female CTM | Asymptomatic | 98.9% (95% CI: 98.2-99.5) |
| Female CTM | Symptomatic | 98.5% (95% CI: 97.7-99.2) | |
| Male CTM (Total) | (Combined) | 95.8% (95% CI: 94.4-97.1) (Note: Site #6 had lower specificity at 89.5% for frozen specimens) | |
| Male Urine | Asymptomatic | 99.4% (95% CI: 98.5-99.8) | |
| Male Urine | Symptomatic | 97.1% (95% CI: 96.0-98.2) |
Analytical Performance (Limit of Detection):
- Sensitivity (LoD): 5 CFU/test for each of 15 isolates tested. The device gave positive results for all strains at 20, 10, and 5 CFU/test. At 1 CFU/test, at least one replicate was positive for all 15 strains, and at 2 CFU/test, all three replicates were positive for 14 of 15 strains.
2. Sample Size Used for the Test Set and Data Provenance:
- Test Set Sample Size: A total of 5374 specimens were collected and tested in the clinical study. After excluding 33 repeatedly inhibitory specimens, 5341 specimens were used in the primary analyses (when the Internal Control result was used).
- Data Provenance: The clinical study was conducted at six geographically diverse sites. The document does not specify the country of origin, but given the submission to the US FDA, it is highly likely the data includes, or is primarily from, studies conducted in the United States. The study appears to be prospective, as it describes the evaluation of the test comparing its results to culture, implying these were collected and processed specifically for this evaluation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- The ground truth was established by Neisseria gonorrhoeae culture results. The document does not specify the number of individuals or "experts" involved in performing and interpreting these culture results, nor their specific qualifications (e.g., medical technologists, microbiologists). However, culture with confirmation by biochemical and immunologic assays is referred to as "the international gold standard methods," implying established and accepted laboratory practices were followed.
4. Adjudication Method for the Test Set:
- For specimens with discrepant results between the AMPLICOR CT/NG Test and the Neisseria gonorrhoeae culture, an alternate primer (16S rRNA) PCR test was used.
- Crucially, the alternate primer PCR test results were not used to calculate the clinical performance characteristics (sensitivity, specificity) of the AMPLICOR test. They were reported "for information purposes only," primarily to investigate apparent false positives and potential true positives missed by culture. This suggests a form of modified discrepant analysis, where the third method (16S rRNA PCR) helped to understand discrepancies but did not directly alter the primary performance calculations derived solely from comparison to culture.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not conducted as part of this submission. This is a diagnostic test where the output is directly reported by the instrument based on molecular detection, not interpreted by a human reader in the traditional MRMC sense. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.
6. Standalone Performance:
- Yes, a standalone performance study was done. The entire clinical performance section describes the algorithm-only performance (AMPLICOR CT/NG Test) against the culture-based ground truth. There is no human-in-the-loop component for interpretation or decision-making inherent in the device described.
7. Type of Ground Truth Used:
- The primary ground truth used was Neisseria gonorrhoeae culture results. This is considered the "international gold standard methods for detection" at the time of the submission.
- For discrepant analysis, an alternate primer (16S rRNA) PCR test was used, but its results did not directly modify the primary calculation of sensitivity and specificity based on culture.
8. Sample Size for the Training Set:
- The document does not explicitly state a separate training set sample size. This is common for older diagnostic assay submissions, where a "discovery" or "development" phase dataset might have been used but is not formally disclosed as a "training set" in the same way machine learning models typically define it. The non-clinical performance (analytical sensitivity, specificity, precision) demonstrates rigorous characterization of the assay's fundamental properties.
9. How the Ground Truth for the Training Set Was Established:
- As a dedicated "training set" is not explicitly mentioned, the establishment of ground truth specifically for it cannot be detailed. However, for the analytical studies (non-clinical performance), ground truth was established by:
- Known concentrations of Neisseria gonorrhoeae CFU/test for analytical sensitivity and precision studies.
- Known organisms (bacteria, fungi, protozoa, viruses) at specified genomic DNA concentrations for analytical specificity studies. These would have been characterized externally (e.g., from American Type Culture Collection) to confirm their identity.
§ 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).