(103 days)
The BD MAX™ CTGCTV2 assay, performed on the BD MAX™ System, incorporates automated DNA extraction and real-time polymerase chain reaction (PCR) for the direct, qualitative detection of DNA from:
- Chlamydia trachomatis (CT) ●
- Neisseria gonorrhoeae (GC) ●
- Trichomonas vaginalis (TV) ●
The assay may be used for detection of CT, GC and/or TV DNA in patient- or clinician-collected vaginal swab specimens (in a clinical setting), and male and female urine specimens. The assay may also be used for the detection of CT and GC DNA in endocervical swab and Liquid-Based Cytology (LBC) specimens in PreservCyt® Solution using an aliquot that is removed prior to processing for the ThinPrep™ Pap test.
The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial urogenital disease, gonococcal urogenital disease and/or trichomoniasis.
The BD MAX System and the BD MAX CTGCTV2 are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, and target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX System software automatically interprets test results. A test result may be called as POS, NEG, UNR, IND or INC for each of the assay's targets, based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX System level failure.
The provided information describes the BD MAX CTGCTV2 assay, a diagnostic device for detecting Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and Trichomonas vaginalis (TV).
Here's an analysis of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally established for diagnostic assays in terms of sensitivity (Positive Percent Agreement - PPA) and specificity (Negative Percent Agreement - NPA). The presented clinical performance results in Table 21 for CT and GC, and Table 22 for TV, serve as the reported device performance against these criteria.
| Specimen Type (Female) | Organism | Acceptance Criteria (Implicit from context, typical for diagnostic NAATs) | Reported Device Performance (PPA / Sensitivity) | Reported Device Performance (NPA / Specificity) |
|---|---|---|---|---|
| Vaginal (Clinician) | C. trachomatis | High sensitivity & specificity (typically >90% sensitivity, >98% specificity) | 98.4% (126/128) | 98.9% (2,348/2,374) |
| Vaginal (Clinician) | N. gonorrhoeae | High sensitivity & specificity | 97.7% (42/43) | 99.9% (2,457/2,460) |
| Vaginal (Clinician) | T. vaginalis | High sensitivity & specificity | 97.8% (182/186) | 99.6% (1,540/1,546) |
| Vaginal (Patient) | C. trachomatis | High sensitivity & specificity | 98.4% (126/128) | 98.7% (2,348/2,380) |
| Vaginal (Patient) | N. gonorrhoeae | High sensitivity & specificity | 100% (43/43) | 99.8% (2,459/2,463) |
| Vaginal (Patient) | T. vaginalis | High sensitivity & specificity | 97.9% (185/189) | 99.2% (1,540/1,553) |
| Endocervical | C. trachomatis | High sensitivity & specificity | 94.5% (121/128) | 99.2% (2,366/2,384) |
| Endocervical | N. gonorrhoeae | High sensitivity & specificity | 95.3% (41/43) | 100% (2,467/2,468) |
| LBC PreservCyt | C. trachomatis | High sensitivity & specificity | 92.7% (115/124) | 99.8% (2,340/2,345) |
| LBC PreservCyt | N. gonorrhoeae | High sensitivity & specificity | 92.9% (39/42) | 100% (2,427/2,428) |
| Urine (Female) | C. trachomatis | High sensitivity & specificity | 98.4% (121/123) | 99.3% (2,278/2,293) |
| Urine (Female) | N. gonorrhoeae | High sensitivity & specificity | 100% (39/39) | 100% (2,379/2,380) |
| Urine (Female) | T. vaginalis | High sensitivity & specificity | 100% (173/173) | 99.6% (1,467/1,473) |
| Urine (Male) | C. trachomatis | High sensitivity & specificity | 96.7% (148/153) | 99.4% (981/987) |
| Urine (Male) | N. gonorrhoeae | High sensitivity & specificity | 99.2% (122/123) | 99.9% (1,018/1,019) |
| Urine (Male) | T. vaginalis | High sensitivity & specificity | 97.9% (47/48) | 99.7% (1,090/1,093) |
2. Sample Size Used for the Test Set and Data Provenance
The clinical performance study included 2,547 female subjects and 1,159 male subjects from North America.
The study was prospective, as indicated by the enrollment of subjects and collection of specimens for the trial.
The data provenance is North America, specifically from "Twelve geographically diverse clinical sites."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the "number of experts" used to establish ground truth or their individual qualifications (e.g., radiologist with 10 years of experience). Instead, the ground truth was established using an algorithmic approach with multiple FDA-cleared NAATs (Nucleic Acid Amplification Tests). This is a common and accepted method for determining the true infection status in diagnostic studies for infectious diseases, rather than relying on individual expert interpretation.
4. Adjudication Method for the Test Set
The adjudication method for establishing the Patient Infected Status (PIS) was as follows:
- Female PIS for C. trachomatis and N. gonorrhoeae: Established by testing urine and cervical specimens with two different FDA cleared NAATs. Females were designated as infected if at least two different reference NAATs were positive for urine and cervical specimens. For swab specimens, if only urine was positive with two comparator NAATs (and swabs were negative with both), they were considered non-infected.
- Male PIS for C. trachomatis and N. gonorrhoeae: Established by testing urine specimens using up to three different FDA cleared NAATs. Males were designated as infected if 2 out of 3 reference NAAT results were positive. They were categorized as non-infected if 2 out of 3 reference NAAT results were negative.
- Female PIS for T. vaginalis: Established by testing vaginal specimens with two different FDA cleared molecular tests, across three different instrument platforms. Females were designated as infected if 2 out of 3 reference test results were positive. They were categorized as non-infected if 2 out of 3 reference test results were negative.
- Male PIS for T. vaginalis: Established by testing urine specimens using up to three different FDA cleared NAATs. Males were designated as infected if 2 out of 3 reference test results were positive. They were categorized as non-infected if 2 out of 3 reference test results were negative.
- Female Urine CCA for C. trachomatis, N. gonorrhoeae, and T. vaginalis: Urine samples were used from up to three reference NAATs. Designated as positive if 2 out of 3 reference NAAT results were positive, and negative if 2 out of 3 reference NAAT results were negative.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study was done. This type of study is more common for image-based diagnostic aids where human interpretation is a primary component, and the AI assists human readers. For an automated molecular diagnostic assay like the BD MAX CTGCTV2, the device's performance is standalone.
6. Standalone (Algorithm Only) Performance
Yes, the study primarily presents standalone performance of the BD MAX CTGCTV2 assay. The assay is an "automated DNA extraction and real-time polymerase chain reaction (PCR)" system, and its interpretation is done "automatically" by the BD MAX System software. The clinical performance tables (Table 21, 22, 23) reflect the algorithm-only performance against the established PIS.
7. Type of Ground Truth Used
The ground truth used was expert consensus derived through an algorithm based on multiple FDA-cleared Nucleic Acid Amplification Tests (NAATs). This is a common and robust method for establishing ground truth in molecular diagnostics, as these reference NAATs are highly sensitive and specific.
8. Sample Size for the Training Set
The document does not explicitly mention a separate "training set" sample size for the development of the BD MAX CTGCTV2 assay. This is typical for a 510(k) submission for an in vitro diagnostic (IVD) device, where the focus is on the validation of the finalized product's performance rather than the detailed development (training) process. The analytical studies (LoD, inclusivity, specificity) demonstrate the characteristics of the assay, which would have been refined during development.
9. How the Ground Truth for the Training Set Was Established
As no specific training set and its ground truth establishment are detailed, this information is not available in the provided text. The analytical studies like Limits of Detection (LoD), inclusivity, and analytical specificity use well-characterized microbial suspensions and established methods for their testing. These analytical studies are part of the broader validation, implying that the assay's design was based on such principles during its development.
§ 866.3860
Trichomonas vaginalis nucleic acid assay.(a)
Identification. ATrichomonas vaginalis nucleic acid assay is a device that consists of primers, probes, enzymes, and controls for the amplification and detection of trichomonas nucleic acids in endocervical swabs, vaginal swabs, and female urine specimens, from women symptomatic for vaginitis, cervicitis, or urethritis and/or to aid in the diagnosis of trichomoniasis in asymptomatic women. The detection of trichomonas nucleic acids, in conjunction with other laboratory tests, aids in the clinical laboratory diagnosis of trichomoniasis caused byTrichomonas vaginalis .(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Nucleic Acid Amplification Assays for the Detection ofTrichomonas vaginalis; Guideline for Industry and Food and Drug Administration Staff.” See § 866.1(e) for information on obtaining this document.