(60 days)
The BD ProbeTect™ 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 and male individuals to aid in the diagnosis of gonococcal urogenital disease.
The BD Viper System, when used with the BD ProbeTec amplified nucleic assay(s), is intended for the in vitro detection of targeted organisms from specimens as identified in the assay-specific reagent package insert(s).
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 "M 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. gonorrhoeae -specific signals to report results as positive, negative, or EC failure.
Here's an analysis of the acceptance criteria and study detailed in the provided text for the BD ProbeTec™ Neisseria gonorrhoeae (GC) Q* Amplified DNA Assay:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the clinical performance results, where high sensitivity and specificity are demonstrated across various specimen types and patient asymptomatic/symptomatic statuses. While explicit numerical acceptance criteria (e.g., "sensitivity must be >95%") are not explicitly stated as 'acceptance criteria' in the document, we can infer the achieved performance as the criteria met for substantial equivalence.
| Specimen Type & Symptomatic Status | Acceptance Criteria (Implied by Achieved Performance) | Reported Device Performance (Sensitivity) | Reported Device Performance (Specificity) |
|---|---|---|---|
| Female Endocervical Swab (FS) | High Sensitivity & Specificity | A: 96.3% (26/27) | |
| S: 100.0% (38/38) | |||
| Total: 98.5% (64/65) | A: 99.5% (421/423) | ||
| S: 99.8% (503/504) | |||
| Total: 99.7% (924/927) | |||
| Female Vaginal Swab (FV) | High Sensitivity & Specificity | A: 100.0% (27/27) | |
| S: 100.0% (38/38) | |||
| Total: 100.0% (65/65) | A: 98.6% (416/422) | ||
| S: 99.6% (504/506) | |||
| Total: 99.1% (920/928) | |||
| Female Neat Urine (FNU) | High Sensitivity & Specificity | A: 96.3% (26/27) | |
| S: 97.4% (37/38) | |||
| Total: 96.9% (63/65) | A: 99.3% (420/423) | ||
| S: 99.6% (503/505) | |||
| Total: 99.5% (923/928) | |||
| Female Urine in Q UPT (FUPT)* | High Sensitivity & Specificity | A: 100.0% (27/27) | |
| S: 97.4% (37/38) | |||
| Total: 98.5% (64/65) | A: 99.5% (421/423) | ||
| S: 99.8% (504/505) | |||
| Total: 99.7% (925/928) | |||
| Male Urethral Swab (MS) | High Sensitivity & Specificity | A: 100.0% (12/12) | |
| S: 100.0% (100/100) | |||
| Total: 100.0% (112/112) | A: 99.2% (492/496) | ||
| S: 98.7% (155/157) | |||
| Total: 99.1% (647/653) | |||
| Male Neat Urine (MNU1) | High Sensitivity & Specificity | A: 100.0% (12/12) | |
| S: 100.0% (100/100) | |||
| Total: 100.0% (112/112) | A: 99.2% (501/505) | ||
| S: 98.1% (154/157) | |||
| Total: 98.9% (655/662) | |||
| Male Urine in Q UPT (MUPT1)* | High Sensitivity & Specificity | A: 100.0% (12/12) | |
| S: 100.0% (100/100) | |||
| Total: 100.0% (112/112) | A: 99.2% (501/505) | ||
| S: 98.7% (155/157) | |||
| Total: 99.1% (656/662) | |||
| Overall (Total) | High Sensitivity & Specificity | 99.3% (592/596) | 99.3% (5650/5688) |
A = Asymptomatic, S = Symptomatic
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Test Set:
- Female subjects: 994 (eligible)
- Male subjects: 774 (eligible)
- Total BD ProbeTec GC Q* assay results used for performance calculations: 6284
- Data Provenance:
- Country of Origin: North America (seven geographically diverse clinical sites).
- Retrospective or Prospective: Prospective. The study involved collecting various specimens (endocervical swabs, male urethral swabs, vaginal swabs, and urine) from symptomatic and asymptomatic subjects.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Explicit details on the number of experts or their qualifications (e.g., radiologist with 10 years of experience) for establishing ground truth are not provided. The ground truth was established using an algorithm based on results from two commercially available Nucleic Acid Amplification Tests (NAATs) (the BD ProbeTec ET GC/AC assay and another commercially available NAAT). This method relies on the established performance of these reference NAATs rather than individual expert review of each case.
4. Adjudication Method for the Test Set
The adjudication method used to establish the "patient infected status" (PIS) for the ground truth was a 2-out-of-N rule (where N refers to the number of reference tests performed).
- For Female subjects (endocervical swab and urine specimens): Subjects were considered infected if "two of the four endocervical swab and urine specimens (or two of the three or four urethral swab and urine specimens) tested positive in the BD ProbeTec ET GC/AC assay and the other reference NAAT (one specimen testing positive in each NAAT)."
- For Male subjects (urethral swab and urine specimens): Similar algorithm applied.
- Non-infected: Subjects were considered non-infected if "less than two reference NAAT results were positive."
This implies specimens were tested by at least two reference NAATs (BD ProbeTec ET GC/AC and another commercial NAAT).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study evaluates the performance of an assay (device) directly against a ground truth, not the comparative improvement of human readers with or without AI assistance. The device is for direct detection of N. gonorrhoeae DNA, not for aiding human interpretation of images or other data.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone study was performed. The BD ProbeTec GC Q* Amplified DNA Assay is a fully automated system that detects N. gonorrhoeae DNA and reports results as positive, negative, or EC failure. The performance data presented (sensitivity and specificity) is based on the algorithm's direct output compared to the established patient infected status, without human intervention in result interpretation. The "BD Viper™ System and an automated algorithm is applied to both the EC and N. gonorrhoeae -specific signals to report results."
7. Type of Ground Truth Used
The ground truth used was a composite reference standard or patient infected status (PIS) algorithm, derived from the results of two different commercially available Nucleic Acid Amplification Tests (NAATs): the BD ProbeTec ET GC/AC assay and another commercially available NAAT. It is based on the concordance of these reference molecular tests, rather than pathology (histology), expert consensus of clinical symptoms, or long-term outcomes data.
8. Sample Size for the Training Set
The document does not explicitly state a separate training set size. The clinical performance characteristics are reported from a single clinical study dataset. In diagnostic assay development, initial algorithm development and optimization might occur using internal datasets, but this document describes the validation study for regulatory submission. It's common in IVD submissions for the entire clinical study population to be used for performance evaluation against the ground truth without a separate "training set" as understood in machine learning (where the algorithm learns from the data). If an algorithm's parameters were tuned on this specific dataset, it would be a form of internal validation rather than a truly independent test set. However, the text focuses on the device's performance measurement, implying that the algorithm's parameters were fixed by the time this validation study was conducted.
9. How the Ground Truth for the Training Set Was Established
As noted above, a separate "training set" is not explicitly mentioned. For the test set, the ground truth was established by a patient infected status (PIS) algorithm based on the concordance of two distinct commercially available NAATs (BD ProbeTec ET GC/AC assay and another commercially available NAAT) on various patient specimens.
§ 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).