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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."

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.

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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.

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).

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