(155 days)
The BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, when tested with the BD Viper™ System in Extracted Mode, uses Strand Displacement Amplification technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in clinician-collected female endocervical and male urethral swab specimens, patient collected vaginal swab specimens (in a clinical setting), and male and female urine specimens (both UPT and Neat). The assay is also intended for use with gynecological specimens collected in BD SurePath™ Preservative Fluid using an aliquot that is removed prior to processing for the BD SurePath™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of gonococcal urogenital disease.
The BD ProbeTec GC Q* Amplified DNA Assay is based on the simultaneous amplification and detection of target DNA using amplification primers and a fluorescently-labeled detector probe. The reagents for SDA are dried in two separate disposable microwells: the Priming Microwell contains the amplification primers, fluorescently-labeled detector probe, nucleotides and other reagents necessary for amplification, while the Amplification Microwell contains the two enzymes (a DNA polymerase and a restriction endonuclease) that are required for SDA. The BD Viper 10 System pipettes a portion of the purified DNA solution from each Extraction Tube into a Priming Microwell to rehydrate the contents. After a brief incubation, the reaction mixture is transferred to a corresponding, pre-warmed Amplification Microwell which is sealed to prevent contamination and then incubated in one of the two thermally-controlled fluorescent readers. The presence or absence of N. gonorrhoeae DNA is determined by calculating the peak fluorescence (Maximum Relative Fluorescent Units (MaxRFU)) over the course of the amplification process and by comparing this measurement to a predetermined threshold value.
In addition to the fluorescent probe used to detect amplified N. gonorrhoeae target DNA, a second labeled oligonucleotide is incorporated in each reaction. The Extraction Control (EC) oligonucleotide is labeled with a different dye than that used for detection of the N. gonorrhoeae -specific target and is used to confirm the validity of the extraction process. The EC is dried in the Extraction Tubes and is rehydrated upon addition of the specimen and extraction reagents. At the end of the extraction process, the EC fluorescence is monitored by the BD Viper System and an automated algorithm is applied to both the EC and N. gonorrhoede -specific signals to report results as positive, negative, or EC failure.
Here's an analysis of the BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay based on the provided document, focusing on acceptance criteria and supporting study details:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined "acceptance criteria" in a numerical format that the device must meet. Instead, it presents the results of its clinical performance study and concludes that these results "support the determination of substantial equivalence." Therefore, the reported performance itself, particularly sensitivity and specificity, serves as the de-facto measure of whether the device is considered acceptable for its intended use.
| Metric | Acceptance Criteria (Implicit) | Reported Device Performance (BD SurePath Specimens) |
|---|---|---|
| Sensitivity | Sufficiently high to detect N. gonorrhoeae in positive cases (exact threshold not stated, but 90%+ would be typical for diagnostics) | Total: 100.0% (51/51) |
| Symptomatic: 100.0% (19/19) | ||
| Asymptomatic: 100.0% (32/32) | ||
| Specificity | Sufficiently high to correctly identify negative cases (exact threshold not stated, but 95%+ would be typical for diagnostics) | Total: 99.9% (1662/1664) |
| Symptomatic: 100.0% (539/539) | ||
| Asymptomatic: 99.8% (1123/1125) | ||
| Limit of Detection (LOD) | Max. 100 GC cells per mL (based on predicate/similar devices) | ≤ 100 GC cells per mL (with > 95% proportion positive at 50 cells/mL) |
| Interference | No significant interference from common substances | No interference observed from various substances (Blood, Seminal Fluid, Mucus, OTC vaginal products, etc.) |
| Reproducibility | Consistent results across runs, sites, and systems | High percentage of correct results (100%) and low %CV for MaxRFU values for positive and negative controls. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Performance):
- Female Subjects: 1728 compliant female subjects enrolled, 1715 included in final data analysis.
- Specimens:
- 3 randomized endocervical swab specimens per subject (for reference methods).
- 1 BD SurePath specimen per subject (for the device under evaluation).
- Data Provenance:
- Country of Origin: North America (specifically, "eleven geographically diverse clinical sites in North America").
- Retrospective or Prospective: The study describes specimen collection from "subjects attending family planning, OB/GYN, and sexually transmitted disease clinics," implying a prospective collection for the purpose of this study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not mention the use of "experts" to establish ground truth in the traditional sense of a human review panel. Instead, the ground truth was established using a Patient Infected Status (PIS) algorithm rather than expert consensus on individual cases.
4. Adjudication Method for the Test Set
The adjudication method for establishing the Patient Infected Status (PIS) was algorithmic, not human adjudication:
- Method: A PIS algorithm based on the results of three reference endocervical swab methods:
- BD ProbeTec ET CT/GC/AC assay
- BD ProbeTec GC Q* assay (the predicate device)
- Another commercially available NAAT (Nucleic Acid Amplification Test)
- Criteria:
- PIS-positive: At least two positive reference results were required.
- PIS-negative: At least two negative reference results were required.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an in vitro diagnostic (IVD) assay that directly detects DNA using a machine (BD Viper System), not an image-based AI system that assists human interpretation.
6. Standalone Performance
Yes, the study primarily evaluates the standalone performance of the BD ProbeTec GC Q* Amplified DNA Assay integrated with the BD Viper System. The clinical performance table (Table 4) presents the sensitivity and specificity of the device against the "Patient Infected Status" (ground truth). This is the algorithm's performance without a human in the loop interpreting the results, as the output is a "positive, negative, or EC failure."
7. Type of Ground Truth Used
The ground truth used was a Patient Infected Status (PIS) algorithm derived from the results of multiple established reference Nucleic Acid Amplification Tests (NAATs) on endocervical swab specimens. While not direct pathology (like tissue biopsy), it represents a "composite reference standard" or "latent class analysis" approach, which is common and often considered highly accurate for infectious disease diagnostics when a single gold standard is imperfect or invasive.
8. Sample Size for the Training Set
The document does not explicitly state the sample size for a "training set." This is typical for in vitro diagnostic assays like this one. Unlike machine learning algorithms that require distinct training and test sets, the development of IVD assays often involves an iterative process of reagent optimization and analytical validation (LOD, interference, etc.) using spiked samples and smaller initial specimen panels, followed by a larger, independent clinical validation set (which is what is described here). The "training" in this context refers to the development and optimization of the assay itself and its algorithm, which is not typically quantified by a specific "training set" sample size in the same way an AI model would be.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" with a formally established ground truth, as understood in machine learning, is not described for this IVD assay. The development and optimization of the assay's internal algorithms (e.g., for calculating MaxRFU and applying the automated algorithm for positive/negative/EC failure) would have been based on analytical studies and perhaps smaller, internal clinical sample sets where results were correlated with known positive and negative samples, often confirmed by reference methods or culture. The document focuses on the validation of the final assay on a robust clinical test set.
§ 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).