(68 days)
The BD ProbeTec™ Chlamydia trachomatis (CT) 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 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 PreservCyt® Solution using an aliquot that is removed prior to processing for additional gynecological testing. The assay is indicated for use with asymptomatic and symptomatic individuals to aid in the diagnosis of chlamydial 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 CT Q* Amplified DNA Assay is based on the simultaneous amplification and detection of target DNA using amplification primers and a fluorescently-labeled detector probe (8, 9). 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 thermally-controlled fluorescent readers. The presence or absence of C. trachomatis 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 C. trachomatis 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 C. trachomatisspecific 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 C. trachomatis-specific signals to report results as positive, negative, or EC failure.
Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate, pre-defined set of thresholds. Instead, it presents clinical performance characteristics (sensitivity and specificity) that are implicitly the targets for the device to be considered effective. The reported device performance is then compared against these implied expectations.
| Metric | Acceptance Criteria (Implied) | Reported Device Performance (BD ProbeTec CT Q* Assay) |
|---|---|---|
| Sensitivity | High sensitivity for C. trachomatis detection | Symptomatic: 96.7% (95% C.I. 88.7% - 99.6%) |
| Asymptomatic: 91.9% (95% C.I. 83.2% - 97.0%) | ||
| Total: 94.1% (95% C.I. 88.7% - 97.4%) | ||
| Specificity | High specificity for C. trachomatis detection | Symptomatic: 99.8% (95% C.I. 99.2% - 100.0%) |
| Asymptomatic: 99.8% (95% C.I. 99.4% - 100.0%) | ||
| Total: 99.8% (95% C.I. 99.5% - 100.0%) | ||
| LOD (Analytical Sensitivity) | ≤ 30 CT EB per mL in PreservCyt specimens (or ≤ 1 IFU per mL) | ≤ 30 CT EB per mL in PreservCyt specimens (corresponds to ≤ 1 IFU per mL) |
| Detection of Serovars | > 95% proportion positive at 15 EB per mL | Detected 16 CT serovars with > 95% proportion positive at 15 EB per mL |
| Interfering Substances | No interference from common vaginal products, blood, etc. | No interference from most listed substances; Glacial Acetic Acid + Blood (≤5%/1% V/V) may cause EC failures or false negatives. |
Study Details
1. Sample sized used for the test set and the data provenance:
- Sample Size: 2071 female subjects were evaluated in the clinical study.
- Data Provenance: The data was collected from prospective clinical sites in North America. Specifically, specimens were collected from female subjects attending family planning, OB/GYN, and sexually transmitted disease clinics at eleven geographically diverse clinical sites in North America.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing the ground truth. It refers to a "patient infected status (PIS) algorithm" which relied on results from three reference methods.
3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- The adjudication method was based on a "patient infected status (PIS) algorithm".
- 2+1: At least two positive reference results were required to establish a subject as PIS-positive.
- 2+1: At least two negative reference results were required to establish a subject as PIS-negative.
- This implies a 2-out-of-3 consensus approach using results from the three reference endocervical swabs (BD ProbeTec ET CT/GC/AC assay, BD ProbeTec CT Q* assay, and another commercially available NAAT).
4. 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:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This study evaluates the performance of an in vitro diagnostic (IVD) device (DNA assay) and not an AI-assisted diagnostic system where human readers would be involved in interpreting AI output.
5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this was a standalone study in the context of an IVD device. The BD ProbeTec CT Q* Amplified DNA Assay, when used with the BD Viper System, automatically processes and reports results (positive, negative, or EC failure) based on fluorescence measurements and an automated algorithm. There is no human interpretation step being evaluated as part of results generation within the device's operational workflow.
6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth was established by expert consensus based on multiple reference methods. Specifically, it was determined by a Patient Infected Status (PIS) algorithm which required at least two concordant results (positive or negative) from three different commercially available NAATs on endocervical swab specimens.
7. The sample size for the training set:
- The document does not specify a training set size. This is typical for a traditional IVD assay development, where "training" in the machine learning sense isn't applicable. The assay's parameters would have been optimized during earlier development (e.g., analytical performance characteristics like LOD, specificity for serovars, interfering substances), but a distinct "training set" as understood in AI/ML is not part of this documentation.
8. How the ground truth for the training set was established:
- As no "training set" in the AI/ML sense is explicitly mentioned, the method for establishing ground truth for such a set is not applicable/not provided. The analytical performance characteristics were established using controlled laboratory experiments (e.g., seeding known concentrations of C. trachomatis serovars).
§ 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).