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The Visby Medical Sexual Health Click Test is a single-use (disposable), fully-integrated, automated Polymerase Chain Reaction (PCR) in vitro diagnostic test intended for use in point of-care or clinical laboratory settings for the rapid detection and differentiation of DNA from Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in seff-collected female vaginal swab specimens using the Visby Medical Sexual Health Vaginal Specimen Collection Kit in a health care setting. The test results are to aid in the diagnosis of symptomatic infections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis.

The test system includes the Visby Medical Sexual Health Click device, the Visby Medical power supply, the Visby Medical Vaginal Collection kit, and fixed-volume transfer pipettes. The device processes a vaginal swab sample by automatically performing all steps required to complete lysis, polymerase chain reaction, and amplicon detection.

The patient uses the Visby Medical Vaginal Collection Kit to self-collect a vaginal specimen with the provided flocked swab, and then the patient elutes the specimen into the Visby Medical Collection Media. The test operator transfers the collection media containing the patient specimen into the sample port of the device using the provided fixed-volume pipette where it rehydrates a lyophilized internal process control. The sample enters a lysis module, where the DNA of the sample and the internal process control are extracted using a combination of chemical lysis and high temperature. The extracted DNA enters a mixing chamber where it rehydrated lyophilized PCR reagents, followed by thermocycling to amplify target DNA. If present, the amplified pathogen target (CT, NG, and/or TV) and internal process control hybridize to specific probes located on a flow channel. Detection of the target-specific PCR product is accomplished via an enzyme-linked colorimetric assay using streptavidin bound horseradish peroxidase (HRP) and a colorimetric substrate that forms a purple precipitate. Test results can be expected in approximately 30 minutes: a green check mark will appear, and a purple color will appear in the "Control" spot, indicating a valid test. A purple spot adjacent to "Chlamydia," "Gonorrhoeae," and/or "Trichomonas" signifies the presence of amplified CT, NG, and/or TV DNA in the sample. Tests with invalid results due to an error (indicated by a red X status light) or failure to develop a purple spot in the "Control" spot, are retested with a new Visby device.

The Visby Medical Sexual Health Click Test is an automated Polymerase Chain Reaction (PCR) in vitro diagnostic test for the rapid detection and differentiation of DNA from Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) in self-collected female vaginal swab specimens.

Here's an analysis of its acceptance criteria and the study that proves its performance:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the clinical performance observed in the study, aiming for high sensitivity and specificity. The reported device performance is based on the achieved Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) or Sensitivity and Specificity against a Composite Comparator Result (CCR) or Patient Infected Status (PIS).

2. Sample Size Used for the Test Set and Data Provenance

• Test Set Sample Size:
  • CT: 1774 subjects
  • NG: 1786 subjects
  • TV: 1765 subjects
  • Initially, 1899 subjects were enrolled, 1881 were eligible, and 1789 were included in the data analysis.
• Data Provenance: The study was conducted at 14 clinical sites geographically distributed across the United States. The study subjects were prospectively enrolled females.

3. Number of Experts Used to Establish Ground Truth and Their Qualifications

• The document does not specify the number of experts explicitly used to establish the ground truth.
• The ground truth was established by a Composite Comparator Result (CCR) for CT and NG, and a Patient Infected Status (PIS) algorithm for TV, which were comprised of three FDA-cleared NAAT assays.
• The qualifications of the individuals interpreting the results of these FDA-cleared NAAT assays are not explicitly stated, but it can be inferred that they would be trained laboratory personnel given the nature of NAAT testing.

4. Adjudication Method for the Test Set

• Adjudication Method: For all three organisms (CT, NG, TV), the ground truth (CCR/PIS) was determined as follows:
  • A study participant was considered infected if a positive result was reported from two of the three FDA-cleared NAAT tests.
  • If the test results of the first two NAATs were discordant (one positive, one negative), the CCR/PIS was determined by the third NAAT. This is often referred to as a "2 out of 3" or "tie-breaker" adjudication method.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC comparative effectiveness study was done in the context of human readers improving with or without AI assistance. This device is a fully-automated in vitro diagnostic test, and the clinical study evaluated the device's performance directly against a laboratory-based ground truth, not human reader performance.
• However, a reproducibility study was conducted with "untrained users" (non-laboratorians) in CLIA waived settings, to assess the device's performance when used by typical healthcare professionals in such environments. This indirectly assesses the device's usability and reliability in a real-world setting where "human readers" (the operators) process samples and interpret simple visual results (green check mark for valid, purple spots for positive). The study demonstrated robust reproducibility and that untrained users could perform and interpret results accurately, but it wasn't a comparative effectiveness study of human reader improvement.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)

• Yes, the clinical performance described in section H is a standalone performance study (device only without human-in-the-loop performance influencing the result generation). The device processes a vaginal swab sample fully-integrated and automatically, performing lysis, PCR, and amplicon detection, and then provides a visual result (a green check mark for valid and purple spots for positive). The study evaluated how this automated device's results compared to the established ground truth.
• While human operators handled the samples and initiated the test, the test interpretation is designed to be straightforward and automatic (visual detection of colored spots), making the clinical performance metrics largely reflective of the algorithm's standalone capability to detect the presence of pathogens. The reproducibility study explicitly confirmed that "untrained users can perform the test and interpret the results accurately."

7. Type of Ground Truth Used

• The ground truth used was a Composite Comparator Result (CCR) for CT and NG, and a Patient Infected Status (PIS) algorithm for TV.
• This ground truth was derived from the results of three FDA-cleared NAAT (Nucleic Acid Amplification Test) assays. This is a common and robust method for establishing ground truth in molecular diagnostics, as NAATs are highly sensitive and specific.

8. Sample Size for the Training Set

• The document focuses on the validation of the device through non-clinical and clinical studies. It does not specify the sample size for a training set.
• As an in vitro diagnostic (IVD) device, its development likely involves extensive internal optimization and testing (which could be considered analogous to "training" in the context of AI/ML, though this device is PCR-based with colorimetric detection, not explicitly a machine learning algorithm) using characterized samples and analytical performance studies (Limit of Detection, Inclusivity, Cross-Reactivity, etc.). These analytical studies serve as a rigorous "training" and development phase, but specific "training set sizes" as might be reported for a machine learning model are not applicable or provided here.

9. How the Ground Truth for the Training Set Was Established

• Since a specific "training set" with established ground truth as in AI/ML model development is not explicitly mentioned or applicable to this type of PCR-based diagnostic, this question cannot be directly answered from the provided text.
• However, the analytical studies (LoD, Inclusivity, Cross-Reactivity, Competitive Interference, Interfering Substances, Reproducibility) described in section G involve using well-characterized organisms (known strains/serovars with specified concentrations) spiked into negative clinical vaginal sample matrix. The "ground truth" for these analytical samples is the known presence/absence and concentration of the spiked organisms. This rigorous analytical characterization serves to ensure the robust performance of the assay.

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The Xpert CT/NG Assay, performed on the GeneXpert Instrument Systems, is a qualitative in vitro real-time PCR test for the automated detection and differentiation of genomic DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) to aid in the diagnosis of chlamydial and gonorrheal urogenital disease. The assay may be used to test the following specimens from asymptomatic individuals: female and male urine, endocervical swab, and patient-collected vaginal swab (collected in a clinical setting).

Ancillary Collection Kits:

Xpert Vaginal/Endocervical Specimen Collection Kit

The Cepheid Xpert Vaginal/Endocervical Specimen Collection Kit is designed to collect, preserve, and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in endocervical swab specimens (collected by a clinician) and patient-collected vaginal swab specimens (collected in a clinical setting) from symptomatic and asymptomatic women prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

Xpert Urine Specimen Collection Kit

The Cepheid Xpert Urine Specimen Collection Kit is designed to preserve and transport Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis DNA in first-catch female and male urine specimens from symptomatic and asymptomatic individuals prior to analysis with the Xpert CT/NG Assay and the Xpert TV Assay.

The Xpert CT/NG Assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of DNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG). The assay is performed on the Cepheid GeneXpert Instrument Systems. The Xpert CT/NG Assay on the GeneXpert Instrument System automates and integrates sample purification, nucleic acid amplification and detection of the target sequences in simple or complex samples using real-time PCR. The system consists of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The system requires the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, crosscontamination between samples is minimized.

The Xpert CT/NG Assay includes reagents for the detection and differentiation of CT and NG. A Sample Processing Control (SPC), a Sample Adequacy Control (SAC), and a Probe Check Control (PCC) are also included. The SPC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the PCR reaction. The SAC reagents detect the presence of a single copy human gene and monitor whether the specimen contains human cells. The PCC verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The GeneXpert Instrument Systems, comprised of the GeneXpert Dx Systems, the GeneXpert Infinity-48 System and the GeneXpert Infinity-80 System, have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real-time PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and detection.

The ancillary specimen collection kits for use with the Xpert CT/NG Assay are the Cepheid® Xpert® Vaginal/Endocervical Specimen Collection kit and the Cepheid® Xpert® Urine Specimen Collection kit.

The provided text describes a 510(k) premarket notification for the Xpert CT/NG Assay, a qualitative in vitro real-time PCR test for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). This submission is primarily to support the removal of a limitation statement regarding the device's performance in pregnant women, building upon a previously cleared predicate device (K121710).

It's important to note that this document does not describe an AI/ML-based device. It is a molecular diagnostic test. Therefore, many of the requested criteria related to AI/ML device validation (e.g., number of experts for ground truth, MRMC study, training set details) are not applicable to this type of medical device submission.

However, I can extract the relevant information regarding performance criteria and the study conducted to support the change in the intended use.

Here's the breakdown based on the provided document:

Acceptance Criteria and Reported Device Performance

The "acceptance criteria" for this type of submission are typically demonstrating substantial equivalence to a predicate device and showing that the device performs as intended for its specified use. In this specific case, the main goal was to re-evaluate the device's performance in pregnant women to remove a previous limitation.

Since this is a diagnostic test and not an AI/ML device, the performance is typically measured by sensitivity and specificity against a confirmed ground truth, or by demonstrating equivalent performance to a legally marketed predicate device. The document refers back to the original 510(k) (K121710) for most of the detailed analytical and clinical performance characteristics, as the core technology of the device itself has not changed.

Table of Acceptance Criteria and Reported Device Performance (as inferred from the context of a 510(k) for a diagnostic test, particularly the focus within this document):

Note: For a molecular diagnostic test like this, the "acceptance criteria" are usually based on assay validation metrics (e.g., LOD, inclusivity, exclusivity, clinical agreement with a reference method) that would have been established in the predicate device's clearance. This submission focuses on a specific clinical population.

Study Details:

1. Sample sizes used for the test set and the data provenance:

   • Test Set Sample Size: The document states "Reanalysis of the clinical data from 510(k) #K121710 was performed for the specimens collected from women who were pregnant at the time of collection." The exact number of pregnant women's specimens re-analyzed is not provided in this document but would be found in the K121710 submission details.
   • Data Provenance: The data comes from the original clinical study conducted for the predicate device (K121710). The document does not specify the country of origin, nor whether the original study was retrospective or prospective, but clinical studies for FDA clearance are typically prospective.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • Not Applicable in the traditional sense for a PCR test. Ground truth for diagnostic tests like this is typically established by:
     • Reference standard methods: Usually a combination of culture, a highly sensitive and specific laboratory-developed test (LDT), or another gold standard for detecting the bacterial DNA/organism.
     • Discrepancy resolution algorithms: In many PCR studies, samples that show discordant results between the investigational device and a comparator method are further tested by a third, highly reliable method (e.g., an in-house PCR with different targets, sequencing).
   • The document does not specify the ground truth method or expert involvement in establishing it, as it refers back to the K121710 submission.

3. Adjudication method for the test set:

   • Not Applicable in the traditional sense of human reader adjudication. For molecular diagnostic tests, ground truth is established by laboratory methods, not by human interpretation of images. Discrepancy resolution for discordant results between methods is a common practice, but it's not "adjudication" by experts in the context of image interpretation. The document doesn't detail this process for the K121710 data reanalysis.

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:

   • Not Applicable. This is a molecular diagnostic test (PCR), not an AI-assisted imaging device. Human readers are not involved in interpreting results in the way they would be with an AI device for radiology, for example.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

   • Partially Applicable / This is a Standalone Device. The Xpert CT/NG Assay is a fully automated, standalone in vitro diagnostic device. It performs sample purification, nucleic acid amplification, and detection without human intervention in the assay process itself. The "performance" is the direct output of the instrument.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • Likely a composite reference standard or culture/validated PCR. For sexually transmitted infections (STIs) detected via nucleic acid amplification tests (NAATs), the ground truth is typically established by using a combination of other highly sensitive and specific laboratory methods (e.g., another validated NAAT, potentially culture for NG, or a rigorous discrepancy resolution algorithm). The document refers to the original K121710 for details.

7. The sample size for the training set:

   • Not Applicable / No separate "training set" for an AI/ML model. For a molecular diagnostic test, there isn't a "training set" in the sense of an AI model. The assay's performance characteristics (e.g., primer design, probe specificity, assay conditions) are optimized during development and then validated using analytical and clinical studies. The data from K121710 was likely used as a "test set" for performance evaluation, not for training a model.

8. How the ground truth for the training set was established:

   • Not Applicable. (As there is no "training set" for an AI/ML model here). The ground truth for the clinical validation would have been established using the accepted reference methods for CT/NG detection, as described in point 6.

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