(88 days)
The BD Probe Tec Chlamydia trachomatis (CT) Q* Amplified DNA Assay, when tested with either the BD Viper™ System in Extracted Mode or the BD Viper™ LT System, uses Strand Displacement Amplification technology for the direct, qualitative detection of Chlamydia trachomatis 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 or PreservCyt™ Solution using an aliquot that is removed prior to processing for either the BD SurePath or ThinPrep™ Pap test. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial urogenital disease.
The BD ProbeTec CTO Assay is based on the simultaneous amplification and detection of target DNA using amplification primers and a fluorescently-labeled detector probe The reagents for strand displacement amplification (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. In alignment with the FDA Guidance Document, "Assay Migration Studies for In Vitro Diagnostic Devices, Guidance for Industry and FDA Staff", April 25, 2013 the BD ProbeTec CTQ Assay is being migrated from the existing BD Viper System operating in extracted mode (Viper XTR) to the new BD Viper LT System. The BD Viper LT System is a table-top instrument that is designed to be fully contained on a standard laboratory bench-top. The system performs automated extraction of nucleic acids from multiple specimen types in addition to amplification and detection of target nucleic acid sequences when utilized with legally marketed in vitro diagnostic assays.
The BD ProbeTec™ Chlamydia trachomatis (CT) Q* Amplified DNA Assay on the BD Viper LT System underwent a study to demonstrate its performance and establish substantial equivalence to a predicate device.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds for Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA). However, the clinical performance study aimed to compare the performance of the BD ProbeTec CTQ Assay on the BD Viper LT System against the existing BD Viper System in extracted mode. The presented data represents the "reported device performance."
| Metric | Specimen Type (Gender) | Reported Performance (Total) | 95% Confidence Interval |
|---|---|---|---|
| Positive Percent Agreement (PPA) | Vaginal Swab (Female) | 100.0% (138/138) | Not provided (NA) |
| Negative Percent Agreement (NPA) | Vaginal Swab (Female) | 95.0% (171/180) | (90.6%, 98.3%) |
| PPA | Q*UPT (Female) | 97.2% (137/141) | (92.2%, 100.0%) |
| NPA | Q*UPT (Female) | 98.9% (175/177) | (96.6%, 100.0%) |
| PPA | BD SurePath (Female) | 100.0% (117/117) | Not provided (NA) |
| NPA | BD SurePath (Female) | 97.0% (195/201) | (93.0%, 100.0%) |
| PPA | PreservCyt (Female) | 95.8% (115/120) | (89.2%, 100.0%) |
| NPA | PreservCyt (Female) | 98.0% (194/198) | (96.0%, 99.5%) |
| PPA | Q*UPT (Male) | 96.5% (139/144) | (92.4%, 100.0%) |
| NPA | Q*UPT (Male) | 99.5% (194/195) | (98.5%, 100.0%) |
| PPA (Overall) | All Specimen Types (Total) | 97.9% (646/660) | (96.0%, 99.4%) |
| NPA (Overall) | All Specimen Types (Total) | 97.7% (929/951) | (96.3%, 98.8%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Performance (Test Set):
- 617 compliant female subjects
- 167 compliant male subjects
- Total number of individual specimens tested on the BD Viper LT System and compared against the reference method is not explicitly stated as a single number but can be derived from the "Total" rows in Table 3:
- Positive tests: 660 total (sum of individual specimen types)
- Negative tests: 951 total (sum of individual specimen types)
- This suggests a total of 1611 comparison panel tests.
- Data Provenance: The specimens were collected from clinical sites in North America. The study involved prospective collection of samples from symptomatic and asymptomatic individuals. All specimens were shipped to BD for screening, aliquoting, and comparison panel assembly.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not describe the use of human experts to establish ground truth for the test set. Instead, the "BD Viper System in extracted mode reference results" were used as the basis for classifying specimens as positive or negative to create the comparison panels (ground truth). The nature and qualifications of personnel performing the predicate device testing are not specified beyond being part of "one internal site."
4. Adjudication Method for the Test Set
The document describes how comparison panels were assembled: "Each comparison panel consisted of randomly chosen positive and negative specimens (based on BD Viper System in extracted mode reference results). The positive and negative specimens were randomized within the panel, and labeled such that the instrument user was blinded to the specimen results." This indicates that the reference results from the predicate BD Viper System served as the adjudicated ground truth, and there was no further human expert adjudication process described for the test set.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
This is not a multi-reader multi-case (MRMC) comparative effectiveness study involving human readers or AI assistance in interpretation. This study evaluates the performance of an in vitro diagnostic (IVD) device (the BD ProbeTec CTQ Assay on the BD Viper LT System) compared to a predicate device. The results are quantitative (Positive Percent Agreement, Negative Percent Agreement) based on instrument output, not human interpretation.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, a standalone performance study was done. The BD ProbeTec CTQ Assay on the BD Viper LT System is an automated, qualitative molecular diagnostic test. The clinical performance data presented (Table 3) represents the performance of the device itself (algorithm and system) in detecting Chlamydia trachomatis DNA, with no direct human interpretation component in the primary outcome. The "instrument user was blinded to the specimen results," implying a standalone evaluation of the device.
7. The Type of Ground Truth Used
The ground truth used for the clinical performance study (test set) was established by the results from the predicate device, the BD Viper System in extracted mode. "Each comparison panel consisted of randomly chosen positive and negative specimens (based on BD Viper System in extracted mode reference results)."
8. The Sample Size for the Training Set
The document implies that the BD ProbeTec CTQ Assay formulation for the BD Viper LT System has not changed from that used with the existing BD Viper System. Therefore, there isn't a "training set" in the context of an algorithm learning from data. The device itself (reagents, amplification, detection) is pre-established. The studies conducted are for "migrating" the assay to a new instrument platform (BD Viper LT). Thus, the concept of a training set for algorithm development is not directly applicable here.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, a training set for an algorithm is not described or applicable in this context. The "ground truth" for the original development and validation of the BD ProbeTec CTQ Assay on the predicate BD Viper System would have been established through a combination of well-characterized positive and negative clinical specimens, spiked samples, and potentially confirmatory testing methods, but details are not provided in this submission for the predicate device's original development.
§ 866.3120 Chlamydia serological reagents.
(a)
Identification. Chlamydia serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to chlamydia in serum. Additionally, some of these reagents consist of chlamydia antisera conjugated with a fluorescent dye used to identify chlamydia directly from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genusChlamydia and provides epidemiological information on these diseases. Chlamydia are the causative agents of psittacosis (a form of pneumonia), lymphogranuloma venereum (a venereal disease), and trachoma (a chronic disease of the eye and eyelid).(b)
Classification. Class I (general controls).