(134 days)
The APTIMA Combo 2 Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal ribonucleic acid (rRNA) from Chlamydia trachomatis and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal, and male urethral swab specimens, patient-collected vaginal swab specimens* and male and female urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease.
*Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.
The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The APTIMA Vaginal Swab Specimen Collection Kit is not for home use.
Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Combo 2 Assay to include clinician-collected and patient-collected vaginal swabs (in a medical setting) as acceptable testing specimens. The ancillary kit formulated for this specific application is the GEN-PROBE APTIMA Vaginal Swab Specimen Collection Kit. The components of the APTIMA Vaginal Swab Specimen Collection Kit include: (1) a sterile swab for the collection of vaginal specimens and (2) a transport tube containing transport media with a penetrable cap.
The APTIMA Vaginal Swab Specimen Collection Kit is for use with the APTIMA Assays for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. The APTIMA Vaginal Swab Specimen Collection Kit is intended to be used for clinician and patient collection of vaginal swab specimens according to the instructions provided. The APTIMA Vaginal Swab Specimen Collection Kit not for home use.
The APTIMA Combo 2 Assay incorporates the technologies of target capture, in vitro nucleic acid amplification, and hybridization of target amplicons with acridinium ester-labeled DNA probes to specifically detect and differentiate both C. trachomatis and N. gonorrhoeae nucleic acids in clinical specimens. GEN-PROBE's proprietary technologies are combined in this product to allow qualitative detection of C. trachomatis rRNA and N. gonorrhoeae rRNA.
Here's a breakdown of the acceptance criteria and study details for the GEN-PROBE® APTIMA® Combo 2 Assay, based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied through the sensitivity and specificity values reported, which are compared against a "patient infected status algorithm" as the ground truth. While explicit numerical acceptance thresholds are not stated in the provided text (common in older 510(k) summaries which often relied on substantial equivalence to predicate devices), the study aims to demonstrate high performance.
Chlamydia trachomatis (CT)
| Metric | Acceptance Criteria (Implied by High Performance) | Reported Performance (All Vaginal Swab Specimens) | Reported Performance (Patient-Collected Vaginal Swab) | Reported Performance (Clinician-Collected Vaginal Swab) |
|---|---|---|---|---|
| Sensitivity | High | 96.6% (95% CI: 92.8 - 98.8%) | 96.6% (95% CI: 92.8 - 98.8%) | 96.7% (95% CI: 92.9 - 98.8%) |
| Specificity | High | 97.8% (95% CI: 96.8 - 98.5%) | 97.8% (95% CI: 96.8 - 98.5%) | 97.1% (95% CI: 96.0 - 97.9%) |
Neisseria gonorrhoeae (NG)
| Metric | Acceptance Criteria (Implied by High Performance) | Reported Performance (All Vaginal Swab Specimens) | Reported Performance (Patient-Collected Vaginal Swab) | Reported Performance (Clinician-Collected Vaginal Swab) |
|---|---|---|---|---|
| Sensitivity | High | 98.7% (95% CI: 93.0 - 100%) | 98.7% (95% CI: 93.0 - 100%) | 96.2% (95% CI: 89.2 - 99.2%) |
| Specificity | High | 99.6% (95% CI: 99.0 - 99.8%) | 99.6% (95% CI: 99.0 - 99.8%) | 99.4% (95% CI: 98.8 - 99.7%) |
2. Sample Size Used for the Test Set and Data Provenance
The study was a multi-center clinical study involving 1,464 symptomatic and asymptomatic female subjects.
- Sample Size:
- For CT analysis: 2,868 vaginal swab test results.
- For NG analysis: 2,867 vaginal swab test results.
- These numbers represent the combined results from patient-collected and clinician-collected vaginal swabs.
- Data Provenance: The data was collected from subjects attending STD, OB/GYN, teen, and family planning clinics. The text does not explicitly state the country of origin, but given it's a US FDA submission, it's highly likely to be a prospective multi-center clinical study conducted in the United States.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth was established using an algorithm, not directly by human experts interpreting images or test results. Therefore, the concept of "number of experts" and "qualifications of those experts" as typically applied to expert review in imaging studies, does not directly apply here. The accuracy of the reference standard relies on the performance of the commercially available NAATs used.
4. Adjudication Method for the Test Set
The adjudication method for establishing the patient infected status was algorithmic (rule-based):
- Subjects were considered infected with C. trachomatis or N. gonorrhoeae if two of the four reference NAAT results were positive (one specimen testing positive in each NAAT: APTIMA Combo 2 Assay and another commercially available NAAT, using endocervical swab and urine specimens).
- Subjects were considered non-infected if less than two reference NAAT results were positive.
This method uses concordant results from multiple tests/specimens to define the "true" infection status.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. This study is for an in vitro diagnostic (IVD) assay detecting biomarkers, not an AI-assisted diagnostic imaging device that involves human reader interpretation. Therefore, the concept of human readers improving with AI vs. without AI assistance does not apply.
6. Standalone Performance Study
Yes, a standalone performance study was done for the algorithm (the APTIMA Combo 2 Assay). The entire clinical study described evaluates the performance of the device on its own, comparing its results from vaginal swab specimens to the defined patient infected status algorithm. The reported sensitivity and specificity values are for the device operating as a standalone diagnostic tool for vaginal swab specimens.
7. Type of Ground Truth Used
The ground truth used was an algorithmic consensus based on multiple reference nucleic acid amplification tests (NAATs). Specifically:
- Endocervical swab and urine specimen results from the commercially-available APTIMA Combo 2 Assay and another commercially-available NAAT were used.
- Infection status was determined by requiring a positive result from both reference NAATs.
- Culture was not used as a reference test for this specific study, as the APTIMA Combo 2 Assay had previously been evaluated against culture for other specimen types (as per K003395).
8. Sample Size for the Training Set
The document does not provide information regarding a distinct "training set" sample size. For an IVD assay like this, development typically involves analytical validation (sensitivity, specificity, interference etc.) and then clinical validation with a distinct set of clinical samples. The analytical studies (like analytical sensitivity, specificity, recovery, interference) might be considered analogous to early-stage development/testing, but a formal "training set" in the machine learning sense is not explicitly mentioned or typically applicable for this type of assay in this context. The clinical study described served as the primary performance evaluation.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a separate "training set" with established ground truth in the machine learning context is not detailed. The primary clinical study used the algorithmic consensus described in point 4 as its ground truth for evaluating the device's performance.
§ 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).