(167 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 (SDA) technology for the direct, qualitative detection of Neisseria gonorrhoeae DNA in cliniciancollected female endocervical and male urethral swabs, patient-collected vaginal swab specimens (in a clinical setting), and female and male urine specimens. The assay is indicated for use with asymptomatic and symptomatic female individuals and symptomatic male individuals to aid in the diagnosis of gonococcal urogenital disease.
The BD ProbeTec GC O' 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™ 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 thermallycontrolled 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 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. gonorrhoeae-specific signals to report results as positive, negative, or EC failure.
The document describes the BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay, a diagnostic device for detecting Neisseria gonorrhoeae.
Here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds that the device must meet. Instead, it presents the assay's performance characteristics (Sensitivity, Specificity, PPV, NPV) against a "Patient Infected Status (PIS) algorithm" as a measure of its effectiveness.
However, based on the submission being for a 510(k) and the conclusion stating "The analytical and clinical study results... support the determination of substantial equivalence in accordance with the intended use," it can be inferred that the reported performance metrics were considered acceptable for deeming the device substantially equivalent to predicate devices.
Here's a summary of the clinical performance:
| Metric | Overall Reported Performance (Across all specimen types, symptomatic statuses) |
|---|---|
| Sensitivity | 99.3% (95% CI: 98.2% - 99.8%) |
| Specificity | 99.4% (95% CI: 99.2% - 99.6%) |
| PPV | 95.5% |
| NPV | 99.9% |
Analytical Acceptance Criteria and Reported Performance:
| Criterion | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Limit of Detection (Analytical Sensitivity) | To detect N. gonorrhoeae at low concentrations. | Urine: ≤ 50 cells per mL (for neat and UPT treated urine) |
| Swabs: ≤ 100 GC cells per mL (for expressed vaginal and endocervical swab specimens) | ||
| Detected 17 GC strains with ≥ 95% proportion positive at 50 cells per mL in Q* Swab Diluent. | ||
| Analytical Specificity | To avoid cross-reactivity with common microorganisms. | Tested against 141 organisms. Two N. cinerea and two N. lactamica strains showed cross-reactivity. All other tested organisms did not cross-react. |
| Interfering Substances | Performance should not be significantly impacted by common substances. | No Interference Observed: Blood, seminal fluid, mucus, various vaginal products/contraceptives, hemorrhoidal cream, prescription vaginal treatments, antibiotics, analgesics, deodorant sprays/powders, hormones, leukocytes, albumin, glucose, acidic/alkaline urine, bilirubin, organisms associated with UTIs. |
| May cause EC failures: Blood (>60%) in Swab specimens. | ||
| Reproducibility | Consistent results across different sites and runs. | Assessed by proportion positive/negative and coefficient of variation (SD, %CV) (details in Table 4 and 5). Demonstrated high reproducibility for both positive and negative samples, and even for samples below LOD. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Performance:
- Female Subjects: 994
- Male Subjects: 472
- Total BD ProbeTec GC Q Assay results used for sensitivity/specificity calculations:* 5387
- Data Provenance:
- Country of Origin: North America (seven geographically diverse clinical sites).
- Retrospective or Prospective: Prospective. Specimens were "collected from 1059 female subjects and 479 male subjects attending OB/GYN, sexually transmitted disease (STD) and family planning clinics."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth was not established by medical experts' consensus or interpretation. Instead, it was established by a Patient Infected Status (PIS) algorithm relying on the results of two other commercially available Nucleic Acid Amplification Tests (NAATs). Therefore, the concept of "number of experts" and "qualifications of those experts" does not directly apply in this context for the clinical performance ground truth.
4. Adjudication Method for the Test Set
The adjudication method for determining the "Patient Infected Status (PIS)" was an algorithm based on the results of the two reference NAATs:
- For females: Subjects were considered infected with GC if two of the four endocervical swab and urine specimens (from a total of two endocervical swabs and two urine specimens) tested positive in both the BD ProbeTec ET GC/AC assay AND the other commercially available NAAT (i.e., one specimen testing positive in each NAAT).
- For males: Subjects were considered infected with GC if two of the three or four urethral swab and urine specimens tested positive in both the BD ProbeTec ET GC/AC assay AND the other commercially available NAAT (i.e., one specimen testing positive in each NAAT).
- Non-infected: Subjects were considered non-infected if less than two reference NAAT results were positive.
This is a form of composite reference standard or adjudication by algorithm based on multiple reference tests.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not performed. The study evaluates the performance of the device (assay) in standalone mode against a composite reference standard, not its impact on human reader performance or diagnostic accuracy with AI assistance. This device is a diagnostic assay, not an AI-assisted interpretation tool for human readers.
6. Standalone Performance
Yes, a standalone (algorithm only without human-in-the-loop performance) study was performed. The entire clinical performance evaluation described in the document, comparing the BD ProbeTec GC Q* Assay results to the PIS algorithm, is a standalone performance study of the diagnostic assay. This assay is designed to provide a qualitative (positive/negative) result without human interpretation of raw data for diagnosis.
7. Type of Ground Truth Used
The ground truth used for clinical performance was a composite reference standard or Patient Infected Status (PIS) algorithm. This algorithm was established using the results from two other commercially available Nucleic Acid Amplification Tests (NAATs): the BD ProbeTec ET GC/AC assay and another unnamed commercially available NAAT. It is not pathology, expert consensus, or outcomes data in the traditional sense, but rather a best available evidence standard from established molecular diagnostics.
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" or "validation set" in the context of machine learning. The clinical performance study described used a total of 994 female subjects and 472 male subjects as the test set to evaluate the device. For analytical performance (LOD, specificity), various spiked samples and clinical isolates were used. For the clinical study, it appears the entire subject cohort served as the evaluation set against the composite reference standard.
9. How the Ground Truth for the Training Set Was Established
Since a distinct "training set" for an AI or machine learning model is not explicitly mentioned, the question of how its ground truth was established is not directly applicable. If one considers the overall development of the assay, the analytical studies (LOD, specificity) would have informed the assay's design and cutoff values, where the ground truth was known by design (e.g., specific concentrations of N. gonorrhoeae for LOD, known organisms for specificity). The clinical ground truth relied on the PIS algorithm as detailed in point 4 and 7.
§ 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).