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The cobas liat CT/NG nucleic acid test is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes realtime polymerase chain reaction (PCR) for the direction of Chlamydia (CT) and Neisseria gonorthoeae (NG) nucleic acid in male urine and vaginal swabs, all in cobas PCR Media (Roche Molecular Systems, Inc.).

This test is intended as an aid in the diagnosis of urogenital infections in both symptomatic individuals.

The test is performed on the cobas® liat analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time PCR assays. The assay targets both the Cryptic plasmid and 23S rRNA of Chlamydia trachomatis and the pivNG and NGR9 of Neisseria gonorrhoeae. An Internal Control (IC) is also included. The IC is present to control for adequate processing of the target bacteria through steps of sample purification, nucleic acid amplification, and to monitor the presence of inhibitors in the PCR processes.

Here's a summary of the acceptance criteria and study details for the cobas® liat CT/NG nucleic acid test, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily provides performance metrics rather than explicitly stated acceptance criteria with numerical targets. However, based on the demonstrated performance and the context of a 510(k) submission, the implicit acceptance criteria would be high sensitivity and specificity, indicating reliable detection of CT and NG infections.

2. Sample Size and Data Provenance

• Clinical Study Test Set (Prospectively collected):
  • Total Evaluated Subjects: 4780 (2304 males, 2476 females)
  • Male Urine Specimens: 2302 (from 2302 male subjects)
  • Vaginal Swabs: 2476 (1240 clinician-collected, 1236 self-collected from 2476 female subjects)
  • Data Provenance: Multi-site, prospective study collected at 13 geographically diverse clinical sites across the US.
• Clinical Study Test Set (Archived Specimens - Supplementation):
  • Archived Male Urine Specimens: 163
  • Archived Vaginal Swabs: 90
  • Data Provenance: Prospectively collected samples from a prior clinical trial (K173887).
• Reproducibility Study Test Set: Total 1618 tests (811 vaginal, 807 urine) across 3 external sites. Each panel member tested in triplicate. Low positive (1-2x LoD), moderate positive (3-5x LoD), and negative panel members used.
• Supplemental Precision Study (for CT in urine): 810 evaluable tests on urine panel members (negative, 1x-2x LoD, 3x-5x LoD).

3. Number of Experts and Qualifications for Ground Truth

The ground truth for the clinical study was established using a Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA), which relied on a combination of three FDA-cleared NAATs (NAAT1, NAAT2, and NAAT3). The document does not specify the number of human experts used to establish the ground truth or their qualifications for the clinical study. The "ground truth" was algorithmically derived from the results of the comparator NAATs.

4. Adjudication Method for the Test Set

The adjudication method for the clinical study ground truth (PIS/CCA) followed a rule-based algorithm:

• If NAAT1 and NAAT2 were concordant, that result was the final PIS/CCA.
• If NAAT1 and NAAT2 were discordant, NAAT3 was performed as the tiebreaker.

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

• No, an MRMC comparative effectiveness study was not done. This study assesses the performance of a diagnostic test (the cobas® liat CT/NG nucleic acid test), which is an automated, qualitative in vitro nucleic acid diagnostic test. It replaced human assessment with an automated process, and the comparison was against a PIS/CCA derived from other reference NAATs, not human readers with and without AI assistance. Therefore, there is no effect size for human readers improving with AI.

6. Standalone (Algorithm Only) Performance

• Yes, a standalone (algorithm only) performance study was done. The entire clinical performance evaluation, reproducibility studies, and analytical studies assess the performance of the cobas® liat CT/NG nucleic acid test itself, which is an automated device performing real-time PCR. It is designed to operate without human intervention beyond sample loading and results interpretation from the automated output.

7. Type of Ground Truth Used

• Clinical Study: Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA) derived from the concordant results of FDA-cleared Nucleic Acid Amplification Tests (NAATs).
• Analytical Studies (LoD, Inclusivity, Specificity, Interference): Known concentrations of specific strains or culture subtypes of bacteria/viruses, spiked into negative clinical specimens.

8. Sample Size for the Training Set

The document does not explicitly describe a separate "training set" for an AI/ML model for the cobas® liat CT/NG nucleic acid test. As a nucleic acid diagnostic test (real-time PCR), it operates based on established biochemical principles and does not typically involve machine learning training in the same way an imaging AI algorithm would. All the data presented is for validation and performance evaluation.

9. How Ground Truth for the Training Set Was Established

Since there is no explicitly mentioned "training set" for an AI/ML model in this context, the method for establishing ground truth for such a set is not applicable or described. The clinical performance is evaluated against a PIS/CCA derived from other NAATs, and analytical performance is against known concentrations.

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The cobas® liat CT/NG/MG nucleic acid test is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR) for the direct detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) nucleic acid in male urine and vaginal swabs, all in cobas® PCR Media (Roche Molecular Systems, Inc.).

This test is intended as an aid in the diagnosis of urogenital infections in both symptomatic and asymptomatic individuals.

The test is performed on the cobas® liat analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time PCR assays. The assay targets both the Cryptic plasmid and 23S rRNA of Chlamydia trachomatis, the pivNG and NGR9 of Neisseria gonorrhoeae, and the 23S rRNA and mgpC of Mycoplasma genitalium. An Internal Control (IC) is also included. The IC is present to control for adequate processing of the target bacteria through steps of sample purification, nucleic acid amplification, and to monitor the presence of inhibitors in the PCR processes.

The provided document describes the cobas® liat CT/NG/MG nucleic acid test, an automated in vitro diagnostic test for the direct detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) nucleic acid.

Here's the breakdown of the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance:

The document doesn't explicitly state numerical "acceptance criteria" but rather presents the sensitivity/PPA and specificity/NPA as "performance results." Assuming the performance values achieved in the clinical study are the de facto acceptance criteria for market clearance, the table is compiled from the "Clinical Performance Evaluation" section (Tables 20, 21, and 22).

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size for Clinical Study (Test Set):
  • Total Subjects: 4852 subjects (2512 females, 2340 males) were enrolled.
  • Evaluable Subjects: 4780 evaluable subjects (2304 males, 2476 females).
  • Specimens:
    • 2302 male urine specimens.
    • 1240 clinician-collected vaginal swabs (females).
    • 1236 self-collected vaginal swabs (females).
  • Archived Specimens: Supplementation included archived specimens from a prior clinical trial (K173887) due to low NG prevalence in prospectively collected male urine and vaginal swabs. The exact breakdown of archived vs. prospective in the final evaluable numbers is not explicitly separated for all analytes, but separate tables are provided for "Archived Male Urine" and "Archived Vaginal Swabs" for NG (which states 163 archived male urine and 90 archived vaginal swabs were used for NG).
• Data Provenance:
  • Country of Origin: United States (13 geographically diverse intended use clinical sites across the US).
  • Study Design: Multi-site, prospective study, with supplementation from prospectively collected archived specimens for certain analytes.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The ground truth was established using a Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA) derived from a combination of three FDA-cleared NAATs (NAAT1, NAAT2, and NAAT3).

• Number of Experts: Not applicable, as the ground truth was established by algorithmic comparison of results from FDA-cleared NAATs, not by human expert opinion or adjudication.
• Qualifications of Experts: Not applicable.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The adjudication method used was a "2+1" algorithm based on FDA-cleared NAATs:

• If NAAT1 and NAAT2 were concordant, that result was taken as the PIS/CCA.
• If NAAT1 and NAAT2 were discordant, NAAT3 was performed as a tiebreaker.

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

• MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done.
• Effect Size of Human Readers with/without AI: Not applicable, as this is an automated diagnostic test that detects nucleic acids, not an AI-assisted interpretation device for human readers.

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

• Standalone Performance: Yes, the clinical performance evaluation (Section 6) assesses the standalone performance of the cobas® liat CT/NG/MG nucleic acid test. The device is described as an "automated, qualitative in vitro nucleic acid diagnostic test," indicating it operates without human "interpretation" of the final result. The study compared the device's output directly against the PIS/CCA ground truth.

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

The ground truth used was a Patient Infected Status (PIS) or Composite Comparator Algorithm (CCA) result. This PIS/CCA was derived from the results of three FDA-cleared Nucleic Acid Amplification Tests (NAATs). This is a form of reference standard derived from multiple laboratory tests.

8. The sample size for the training set

The document does not provide details about a "training set" for the algorithm. This is typical for PCR-based diagnostic devices, which rely on established molecular biology principles and analytical validation rather than machine learning on large training datasets for their core functionality. The performance data presented are for clinical validation against a reference standard.

9. How the ground truth for the training set was established

Not applicable, as no explicit training set for an algorithm is described. The device's underlying technology (real-time PCR) is not typically "trained" in the machine learning sense. Analytical studies (Limit of Detection, Inclusivity, Specificity, Interference) form the basis of validating the reagent and assay design.

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The Aptima Neisseria gonorrhoeae (GC) Assav is an in vitro qualitative nucleic acid amplification (NAAT) the detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonocccal urogenital disease using the Panther System. The assay may be used to test male urine specimens from symptomatic and asymptomatic individuals.

The Aptima GC assay is a target amplification nucleic acid probe test for in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC). The Aptima Neisseria gonorrhoeae Assay combines the technologies of target capture, transcription-mediated amplification (TMA), and hybridization protection assay (HPA). Specimens are collected and transferred into their respective specimen transport tubes. The transport solution in these tubes releases the rRNA target and protects it from degradation during storage. When the Aptima Neisseria gonorrhoeae Assay is performed in the laboratory, the target rRNA molecule is isolated from the specimens by use of a capture oligomer via target capture that utilizes magnetic microparticles. The capture oligomer contains a sequence complementary to a specific region of the target molecule as well as a string of deoxyadenosine residues. During the hybridization step, the sequence specific region of the capture oligomer binds to a specific region of the target molecule. The capture oligomer:target complex is then captured out of solution by decreasing the temperature of the reaction to room temperature. This temperature reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the poly-deoxythymidine molecules that are covalently attached to the magnetic particles. The micro particles, including the captured target molecule bound to them, are pulled to the side of the reaction vessel using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification reaction inhibitors. After the target capture steps are completed, the specimens are ready for amplification. Target amplification assays are based on the ability of complementary oligonucleotide primers to specifically anneal and allow enzymatic amplification of the target nucleic acid strands. The Hologic TMA reaction replicates a specific region of the 16S rRNA from GC via DNA intermediates. A unique set of primers is used for the target molecule. Detection of the rRNA amplification product sequences (amplicon) is achieved using nucleic acid hybridization. A single-stranded chemiluminescent DNA probe, which is complementary to a region of the target amplicon, is labeled with an acridinium ester molecule. The labeled DNA probe combines with amplicon to form stable RNA:DNA hybrids. The Selection Reagent differentiates hybridized from unhybridized probe, eliminating the generation of signal from unhybridized probe. During the detection step, light emitted from the labeled RNA:DNA hybrids is measured as photon signals in a luminometer, and are reported as Relative Light Units (RLU). The device reagents are identical to the Aptima Neisseria gonorrhoeae Assay reagents for use on the Tigris DTS system but are intended for use on the Panther system with different specimen type indications. The Panther and Tigris DTS systems use the same principles of operation.

Here's a breakdown of the acceptance criteria and study details for the Aptima Neisseria gonorrhoeae Assay, based on the provided FDA 510(k) summary:

This device is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of Neisseria gonorrhoeae (GC) rRNA to aid in the diagnosis of gonococcal urogenital disease in male urine specimens using the Panther System. It does not appear to involve AI assistance or human reader studies.

1. Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria for clinical performance (sensitivity and specificity) as a set of numerical thresholds. Instead, it states that the study data demonstrate that performance of the Aptima Neisseria gonorrhoeae Assay on the Panther system is substantially equivalent to that of currently FDA-cleared assays for male urine specimens.

However, analytical studies do present performance metrics that implicitly act as acceptance criteria, for example, for Limit of Detection (LoD), precision, and specificity (no interference).

Here's a summary of reported device performance based on the provided text:

Table of Reported Device Performance

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

• Clinical Test Set:
  • Total Enrolled Subjects: 2085 male subjects.
  • Evaluable Subjects: 1959 male subjects (126 subjects not evaluable).
  • Specimens Included in Performance Analysis: 1958 male urine specimens (one specimen with final GC equivocal result was excluded).
  • Data Provenance: Prospective, multi-center clinical study conducted at 11 geographically and ethnically diverse US clinical sites.
    • Sites included obstetrics and gynecology, family planning, and STI clinics.
    • Specimens were collected from symptomatic and asymptomatic men.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

• The document does not explicitly state the number of experts used to establish ground truth for the clinical test set.
• The ground truth (Patient Infected Status - PIS) was established using up to 3 FDA-cleared NAATs (Nucleic Acid Amplification Tests). This implies that a consensus or reference standard approach using multiple existing, cleared diagnostic methods was used, rather than individual expert review or pathological examination for individual cases.

4. Adjudication Method for the Test Set

• The document states that the Patient Infected Status (PIS) was established using "up to 3 FDA-cleared NAATs". This indicates a composite reference standard approach.
• The specific adjudication rule (e.g., 2/3 positive, 3/3 positive) is not detailed, but the use of multiple FDA-cleared methods implies a robust, multi-test consensus for the ground truth.

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

• No, an MRMC comparative effectiveness study was not done.
• This device is an in vitro diagnostic (IVD) assay (a qualitative nucleic acid amplification test), not an imaging AI device that assists human readers. Therefore, there is no "human-in-the-loop" component or an effect size for human readers improving with AI assistance.

6. Standalone Performance

• Yes, standalone performance was done.
• The described clinical study evaluates the performance of the "Aptima Neisseria gonorrhoeae Assay on the Panther System" directly against a composite reference standard (PIS derived from FDA-cleared NAATs). This is a standalone performance assessment of the algorithm/device itself, without human intervention in the result interpretation.

7. Type of Ground Truth Used

• The ground truth used for the clinical test set was a composite reference standard, referred to as "Patient Infected Status (PIS)".
• PIS was established by testing male urine specimens with "up to 3 FDA-cleared NAATs". This is a highly robust method, relying on multiple well-validated diagnostic tests to determine the true infection status.

8. Sample Size for the Training Set

• The document does not specify the sample size for the training set.
• This document is a 510(k) summary for premarket notification, focusing on the validation of the device for its intended use. Information regarding the development and training of the assay (e.g., specific molecular sequences, probe design) is generally proprietary and not included in this type of submission. The focus is on the performance of the final, locked version of the device.

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

• The document does not specify how the ground truth for any potential training set was established, nor explicitly mention a distinct training set.
• For an IVD such as this, the "training" (or development and optimization) typically involves extensive analytical studies (e.g., primer design, probe specificity, optimization of reaction conditions, LoD determination, cross-reactivity testing) rather than machine learning-style "training data" with a "ground truth" in the same sense as an AI imaging algorithm. The core of the assay relies on well-established molecular biology principles and target identification.

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The NeuMoDx CT/NG Assay 2.0, as implemented on the NeuMoDx 96 Molecular System and NeuMoDx 288 Molecular System, is an automated, qualitative test for the direct detection of Chlamydia trachomatis (CT) and or Neisseria gonorrhoeae (NG) DNA as an aid in the diagnosis of chlamydial and gonococcal urogenital disease in symptomatic and asymptomatic individuals. The Assay utilizes real-time Polymerase Chain Reaction (PCR) and may be used to test male and female urine, and self-collected vaginal swab specimens (collected in a clinical setting).

The NeuMoDx CT/NG Assay 2.0 is an automated in vitro diagnostic test for the direct detection of Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) DNA from asymptomatic and symptomatic patient specimens. The assay utilizes real-time polymerase chain reaction (PCR) for the amplification of CT and/or NG DNA and fluorogenic targetspecific TaqMan probes for the detection of the amplified DNA. At the end of the test, a determination of the presence/absence of CT and/or NG DNA in the specimen is automatically made based on the amplification status of the CT and/or NG DNA and/or Sample Process Control sequences using pre-established decision criteria. The NeuMoDx CT/NG Assay 2.0 is intended as an aid to diagnose CT and NG infections in symptomatic or asymptomatic individuals, but not to guide or monitor treatment for CT and NG infections. Concomitant cultures may be necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The NeuMoDx CT/NG Assay 2.0 is an automated, qualitative test for the direct detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) DNA, designed to aid in the diagnosis of chlamydial and gonococcal urogenital disease in symptomatic and asymptomatic individuals.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for sensitivity and specificity are not explicitly stated as distinct acceptance criteria in the provided text. However, the FDA review process implies that the observed performance must be deemed acceptable. We will present the observed clinical performance as the reported device performance.

Chlamydia trachomatis (CT) Performance

Neisseria gonorrhoeae (NG) Performance

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

• Test Set Sample Size:
  • Male Urine (CT): 1691
  • Male Urine (NG): 1698
  • Female Urine (CT): 2007
  • Female Urine (NG): 2006
  • Self-Collected Vaginal Swabs (SCVS) (CT): 2016
  • Self-Collected Vaginal Swabs (SCVS) (NG): 2016
• Data Provenance: The study was a "multicenter, pivotal, prospective urogenital specimen collection study" conducted at "14 geographically and demographically diverse U.S. sites."

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The ground truth was established by a "patient infected status (PIS) algorithm" based on results from two FDA-cleared, legally marketed Nucleic Acid Amplification Tests (NAATs). The text does not mention the involvement of human experts (e.g., radiologists, clinicians) for establishing the ground truth directly. It relies on the performance of existing, cleared diagnostic devices.

4. Adjudication Method for the Test Set

The adjudication method was a pre-specified patient infected status (PIS) algorithm rather than human expert adjudication:

• Female PIS: Established from the results of female urine (FU) and clinician-collected vaginal swab (CCVS) specimens tested by two FDA-cleared NAAT comparator assays. Females were classified as infected if at least one positive result was obtained by each assay. Any other combination was considered non-infected.
• Male PIS: Established using urine results from two FDA-cleared comparator NAATs. If the male urine results were conflicting (one positive, one negative), a third FDA-cleared NAAT method was performed as a tie-breaker to adjudicate male infection status.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

No MRMC comparative effectiveness study was done. The study evaluated the standalone performance of the NeuMoDx CT/NG Assay 2.0 against a PIS algorithm and did not involve human readers interpreting results with or without AI assistance.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone performance study was done. The clinical performance characteristics (sensitivity and specificity) were established by comparing the results of the NeuMoDx CT/NG Assay 2.0 (an automated molecular test, essentially an algorithm-only device in its interpretation of PCR data) directly to the patient infected status algorithm. No human interpretation of the device's output and subsequent diagnosis was explicitly included in the reported performance metrics.

7. The Type of Ground Truth Used

The type of ground truth used was an expert consensus (of NAATs) / composite reference standard, referred to as a "patient infected status (PIS) algorithm," which was derived from the results of multiple (two, sometimes three) FDA-cleared, legally marketed Nucleic Acid Amplification Tests (NAATs).

8. The Sample Size for the Training Set

The document does not explicitly state a training set sample size. This device is a diagnostic assay (molecular test), not typically an AI/machine learning algorithm that undergoes a distinct training phase in the same way an image recognition AI would. The "training" or development of the assay (e.g., primer design, cutoff optimization) would have utilized various analytical studies, but a 'training set' in the context of machine learning is not reported here.

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

As noted above, a distinct "training set" with ground truth established for it in the context of machine learning is not described. The assay's analytical performance (e.g., Limit of Detection, linearity, exclusivity) was characterized using contrived samples (spiked with known concentrations of CT/NG) and known negative samples. For example, the LoD was determined by testing separate dilutions of CT elementary bodies and NG cells in negative matrices, confirming 95% positivity. Inclusivity and cross-reactivity studies used known strains and organisms.

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The BD CTGCTV2 assay 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 ThinPrep 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 CTGCTV2 assay is available for use on the BD MAX System or the BD COR System.

As with the existing BD CTGCTV2 for BD MAX System, K182692, the BD COR PX/MX (BD COR) high throughput system conducts sample extraction steps to isolate and concentrate DNA which is then amplified to detect specific sequences for diagnostic purposes.

The BD COR System is designed to allow the user to place clinical specimens directly into designated transport racks to be loaded into the System. Once the specimens are loaded, the System will perform the necessary pre-analytical steps such as vortexing, aliquoting into a molecular tube with the correct diluent, sorting/grouping of the secondary samples for testing by assay, pre-warming and cooling of the sample (where required), and transport of the sample into a molecular analyzer, where extraction, amplification and detection will take place.

Additionally, the steps of ordering tests on the instrument for specific samples will be managed directly by the user interaction with the Laboratory Information System (LIS), which communicates with the instrument.

Once the clinical specimens are received in the laboratory and loaded into the transport racks, the user will not be required to directly handle the specimen again prior to result reporting and removal from the system.

Here's a breakdown of the acceptance criteria and study details for the BD CTGCTV2 assay, based on the provided document:

Acceptance Criteria and Device Performance

The core of this submission focuses on demonstrating the substantial equivalence of the BD CTGCTV2 assay when run on the BD COR System to its previously cleared performance on the BD MAX System. Therefore, the acceptance criteria are implicitly tied to demonstrating comparable analytical and clinical performance between the two platforms.

Key Performance Metrics (Implicit Acceptance Criteria) and Reported Device Performance:

Study Information: BD CTGCTV2 Assay on BD COR System

This submission pertains to the BD CTGCTV2 assay being used on the BD COR System. The key study is a clinical agreement study and analytical performance studies designed to demonstrate that the performance of the assay on the BD COR System is equivalent to its already cleared performance on the BD MAX System (K182692).

1. A table of acceptance criteria and the reported device performance:
* See table above.

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
* Analytical Performance (Precision & Reproducibility Test Set):
* Precision (within-laboratory): 72 replicates for each target (CT, GC, TV) at each of 4 concentration levels (MP, LP, HN, TN) for PreservCyt samples and 4 concentration levels for Urine samples. Total N is not explicitly stated as a single number but is derived. For example, for CT in PreservCyt, it's 72 * 4 = 288 data points.
* Reproducibility (multi-site): For each target and concentration level, 36 replicates per site across 3 sites (36 * 3 = 108 total replicates per target/level).
* Analytical Sensitivity Confirmation: 4 panel members (A, B, C, D) created with 1.5x LoD and 3x LoD for various target organisms and strains in pooled female urine, pooled vaginal swab, and pooled PreservCyt LBC matrix. The study compared performance between BD COR and BD MAX. The exact number of replicates for each panel member for this confirmation study is not explicitly stated as a total N, but implied to be sufficient for statistical comparison (mean Ct.Scores and 95% CIs are reported).
* Cross-Contamination: 540 positive samples and 540 negative samples for a total of 1080 samples.
* Clinical Agreement Study (Test Set):
* Sample Size: 433 independent panel members.
* Provenance: "Remnant urine specimens from the previous clinical trial for BD CTGCTV2 on BD MAX as well as urine specimens obtained from both internal and external collections were used for the comparison study." This suggests a retrospective collection of remnant urine specimens combined with potentially prospective collections from internal and external sources to create the clinical panels. The country of origin is not explicitly stated, but given the FDA submission, it can be inferred to be primarily US-based or at least compliant with US regulations.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
* For the Precision, Reproducibility, Analytical Sensitivity, and Cross-Contamination studies: The ground truth was established by the known concentrations or presence/absence of organisms in contrived samples or spiked matrices. These are analytical studies, not clinical studies requiring expert interpretation.
* For the Clinical Agreement Study: The BD MAX System results served as the reference/ground truth. The positive or negative status of a panel member was defined by "≥2 out of 3 evaluable results obtained on the BD MAX." This is a comparator method, not direct expert consensus on patient samples. Therefore, no human experts were used to establish the ground truth for the clinical agreement study beyond the definition of the BD MAX as the reference standard.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
* For the Clinical Agreement Study: The "ground truth" (reference comparator result from BD MAX) was established by "≥2 out of 3 evaluable results obtained on the BD MAX". This functions as a form of "consensus" or adjudication among multiple runs (3 aliquots) on the reference system.
* For the analytical studies (precision, reproducibility), ground truth was based on known concentrations, so no adjudication by a panel of experts was necessary.

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:
* No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic (IVD) assay that detects nucleic acids. It's an automated molecular system, not an AI-assisted diagnostic tool that human readers would interpret. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
* Yes, this is a standalone performance study in the context of an IVD assay. The BD CTGCTV2 assay on the BD COR System is an automated system for qualitative detection of DNA. The studies described (analytical and clinical agreement) evaluate the performance of this automated system directly, without human interpretation of its diagnostic output. The output itself (positive/negative) is the final result.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
* Analytical Studies (Precision, Reproducibility, Cross-Contamination, Analytical Sensitivity): The ground truth was based on known concentrations of purified organisms or specific strains spiked into negative matrices. This is an analytical ground truth.
* Clinical Agreement Study: The ground truth was the result from the legally marketed predicate device, the BD MAX System, determined by a "consensus" of ≥2 out of 3 evaluable results from the BD MAX. This is a (predicate) comparator ground truth.

8. The sample size for the training set:
* The document describes studies for validation and equivalency demonstration of the BD CTGCTV2 assay on the BD COR System compared to the BD MAX System. It does not mention "training sets" in the context of machine learning or AI models.
* For IVD assays, "training" typically refers to the initial development and optimization of the assay performed by the manufacturer. The data used for this developmental phase is not typically detailed in 510(k) summaries, which focus on formal validation studies.
* The assay itself incorporates "automated DNA extraction and real-time PCR," which are well-established molecular biology techniques, not typically "trained" in the AI sense.

9. How the ground truth for the training set was established:
* As noted above, the document does not describe a "training set" in the context of an AI/machine learning model. Therefore, this question is not applicable. The development of the PCR assay and its parameters would have involved extensive laboratory work by the manufacturer, but the "ground truth" for those developmental phases would be based on well-characterized materials and samples, similar to the analytical studies described for validation.

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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 cobas® CT/NG for use on the cobas® 6800/8800 Systems is an automated, qualitative in vitro nucleic acid diagnostic test, that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA in male and female urine, clinician-instructed self-collected vaginal swab specimens (collected in a clinical setting), and clinician-collected vaginal swab specimens, endocervical swab specimens, oropharyngeal (throat) swab specimens and anorectal swab specimens all collected in cobas® PCR Media (Roche Molecular Systems, Inc.), and cervical specimens collected in PreservCyt® Solution. This test is intended as an aid in the diagnosis of chlamydial and gonococcal disease in both symptomatic and asymptomatic individuals.

The cobas® CT/NG for use on the cobas® 6800/8800 systems is an automated, qualitative in vitro nucleic acid diagnostic test that utilizes real-time polymerase chain reaction (PCR), for the direct detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG) DNA. The current submission is a device modification for the claim extension to include oropharyngeal (throat) and anorectal swab specimens to cleared clinical specimen types. The assay’s principle relies on polymerase chain reaction (PCR) for amplification and a paired reporter and quencher fluorescence-labeled probes (TaqMan Technology) using fluorescence resonance energy transfer (FRET) for detection. Results are analyzed based on PCR cycle threshold analysis.

Here's a summary of the acceptance criteria and study details for the cobas CT/NG device, extracted from the provided FDA 510(k) clearance letter:

1. Table of Acceptance Criteria (Implicit) and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a separate table, but the clinical performance results serve as the evidence to meet the implied criteria for sensitivity and specificity in the new specimen types.

Note: The confidence intervals (CIs) are provided as ranges for the reported performance.

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

• Sample Size for Test Set:
  • Subjects Enrolled: 2,390 (2,439 subjects were consented, but 49 excluded).
  • Anorectal Specimens Tested: 2,365
  • Oropharyngeal Specimens Tested: 2,382
  • Total Samples: 4,747 (2,365 anorectal + 2,382 oropharyngeal)
• Data Provenance: Multi-site, prospective collection study from 8 geographically diverse clinic sites (STD, HIV, Family Planning, and STD Research). The country of origin is not explicitly stated but is implied to be the US given the FDA clearance.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications

The ground truth was established by a composite reference method using three commercially available CT/NG NAATs. There's no mention of human experts defining the ground truth for individual cases.

4. Adjudication Method for the Test Set

The adjudication method used for establishing the "Infection Status (IS)" (ground truth) was a 2-out-of-3 concordance rule involving three comparator NAAT assays:

• A positive IS was derived when at least 2 of the 3 comparator reference assays were positive.
• If one of the comparator assays was Uninterpretable/Invalid/Failed, the two remaining assays had to be concordant to define the IS as Positive (+) or Negative (-).
• Any other combination of Uninterpretable/Invalid/Failed and valid results were excluded from the analyses.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not conducted. This study focused on the standalone performance of the cobas CT/NG system against a composite reference standard, not on comparing human reader performance with and without AI assistance.

6. If a Standalone Study Was Done

Yes, a standalone study was done. The clinical performance evaluation directly tested the cobas CT/NG system against the established Infection Status (ground truth) for each specimen type. The results are presented as the device's sensitivity and specificity.

7. The Type of Ground Truth Used

The ground truth used was an expert consensus of commercially available NAATs, forming a "Infection Status (IS)" algorithm. It is a composite reference standard.

8. The Sample Size for the Training Set

The document does not provide information on the sample size used for the training set. The 510(k) pertains to a "device change" (claim extension) for an already cleared device (K173887). The training would have occurred during the development of the original cleared device. This submission focuses on the validation for new specimen types.

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

The document does not provide information on how the ground truth for the training set was established. Similar to the training set size, this information would likely be part of the original K173887 submission for the device development. This current submission focuses on evaluating the device's performance for expanded claims.

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The Aptima Combo 2® Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal disease using the Panther® System as specified. On the Panther System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal, throat, rectal, and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt® Solution, patient-collected vaginal swab specimens,1 and female and male urine specimens.

The Aptima Combo 2® Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the Tigris® DTS® Automated Analyzer or semi-automated instrumentation as specified. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens; patient-collected vaginal swab specimens1; and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients, collected in the PreservCyt® Solution.

The Aptima Trichomonas vaginalis Assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Panther System. The assay may be used to test the following specimens from symptomatic or asymptomatic women: clinician-collected endocervical swabs. clinician-collected vaginal swabs, and specimens collected in PreservCyt Solution.

The Aptima Trichomonas vaginalis Assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Trichomonas vaginalis to aid in the diagnosis of trichomoniasis using the Tigris® DTS® System. The assay may be used to test the following specimens from symptomatic or asymptomatic women: clinician-collected endocervical swabs, clinician-collected vaginal swabs, female urine specimens, and specimens collected in PreservCyt Solution.

The clearance of this Special 510(k) application will allow the use of a Ready-Made Reagent format for the Aptima Combo 2 assay (AC2) and the Aptima Trichomonas Vaginalis assay (ATV) on the Tigris and Panther systems. The use of Ready-Made Reagent assays does not change the principles of procedure, intended use, or primary technological characteristics.

Currently, each of the AC2 and ATV Amplification, Enzyme, and Probe reagents are provided in two parts: a lyophilized reagent (cake form) and a reconstitution solution (liquid form). Per the instructions provided in the respective assay's package inserts, the customers are instructed to prepare the reagents by reconstituting each reagent by combining the bottles of lyophilized reagent with the reconstitution solution and mixing reagents manually prior to placing on the Panther or Tigris system. Hologic developed "Ready Made Reagents" (RMRs), which are liquid format or pre-reconstituted Amplification, Enzyme, and Probe reagents available for customers to procure in the 250-Test Kit size available for use on both the Tigris and Panther systems.

Changes to the user interface are minimal as the RMRs are identical to the lyophilized reagents once they have been reconstituted at the laboratory. In order to prepare the current format reagents (lyophilized format), the laboratory personnel pairs each reconstitution solution (Amplification, Enzyme, and Probe) with its respective lyophilized reagent. Using the RMR format, the customer eliminates the reconstitution step and is only required to bring the three reagents to room temperature following the same process currently done for the previously reconstituted reagents. All subsequent steps by the operator are unchanged. All assay principles and processing steps on the Panther or Tigris systems remain unchanged. There are no changes to the instrument hardware or software based on this change.

The provided text describes a 510(k) summary for new "Ready-Made Reagents" (RMRs) for the Aptima Combo 2 Assay and Aptima Trichomonas Vaginalis Assay, designed to simplify reagent preparation for laboratory personnel. The submission aims to demonstrate substantial equivalence to previously cleared predicate devices.

Here's an analysis of the acceptance criteria and study proving the device meets them, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a numerical table format with pre-defined thresholds. However, the implicit acceptance criteria for demonstrating substantial equivalence are based on comparability to the predicate devices, particularly in the analytical performance studies (Limit of Detection and Intended Use) and clinical performance studies. The goal is to show that the RMR format performs equivalently to the existing lyophilized format.

Implicit Acceptance Criteria (based on study design and conclusions):

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

• Intended Use Study:
  • The document mentions "negative and positive panels" and "CT positive, GC positive, and CT/GC dual positive panels" but does not specify the exact number of samples/panels used for each test.
  • Data provenance is implicitly laboratory-generated (panels with known analytes), not clinical patient samples for this specific study section.
• Limit of Detection Study:
  • The document mentions using "stocks of CT and GC organisms in negative clinical liquid pap specimens" and "stocks of TV organisms in negative clinical liquid pap specimens".
  • Does not specify a sample size (number of specimens/replicates) explicitly for the LoD determination.
  • Data provenance appears to be laboratory-prepared samples using clinical specimen matrices.
• Clinical Performance Study:
  • Sample Size: Three hundred (300) remnant clinical swab specimens.
  • Data Provenance: Retrospective, clinical samples ("remnant clinical swab specimens"). The country of origin is not specified but implicitly within the US as this is an FDA submission.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

• Not applicable in the traditional sense of image-based AI studies using human expert consensus.
• For these in vitro diagnostic (IVD) assays, the "ground truth" for the analytical and clinical studies is established through:
  • Known concentrations in prepared panels (Intended Use, LoD).
  • Reference assay results (the "current AC2 assay" or "current ATV assay" is used as the baseline/reference result in the clinical comparability study). This assumes the predicate device's performance is the established truth for comparison.

4. Adjudication Method for the Test Set

• Not applicable in the context of human expert adjudication for a test set.
• The "adjudication" is essentially the comparison of the RMR assay results against the predicate assay results or against known panel concentrations. Discrepancies would be investigated, but there's no mention of a multi-reader/adjudicator process.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

• No, an MRMC comparative effectiveness study was not done. This type of study is more common for imaging AI devices where human readers interpret images with and without AI assistance.
• This submission is for an in vitro diagnostic (IVD) assay where the device output is typically a qualitative (positive/negative) or quantitative result, not an interpretation by a human reader that is then augmented by AI. The comparison is directly between the new reagent format and the existing reagent format.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

• Yes, in spirit, the studies are analogous to standalone performance. The performance evaluation of the RMR assays (the "device") is measured directly against established analytical and clinical benchmarks (predicate assay performance, known concentrations). There isn't a human-in-the-loop component for the performance evaluation of the assay itself, beyond the manual steps involved in sample preparation or loading described in the "Differences" section. The assay's output (presence/absence of target RNA) is the direct result.

7. The Type of Ground Truth Used

• Analytical Truth: Known concentrations of target organisms in prepared panels (for Intended Use and Limit of Detection studies).
• Comparative Truth: The previously cleared predicate devices (Aptima Combo 2 Assay and Aptima Trichomonas Vaginalis Assay using the lyophilized reagent format) served as the "reference result" or "baseline" for comparison in both analytical and clinical studies. This is a common approach in 510(k) submissions for modifications to existing devices.

8. The Sample Size for the Training Set

• Not applicable. This submission is for a modification to an existing IVD assay (a change in reagent format), not for a machine learning or AI algorithm that requires a "training set." The assays are nucleic acid amplification tests (NAATs) based on established biochemical principles, not on learned patterns from a dataset.

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

• Not applicable as there is no training set for this type of device.

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The binx health io CT/NG Assay, when tested using the binx health io Instrument, is a fully automated, rapid, qualitative test intended for use in point-of-care or clinical laboratory settings for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae DNA in female vaginal swab specimens collected either by a clinician or self-collected by a patient in a clinical setting, to aid in the diagnosis of symptomatic or asymptomatic infection in female patients with Chlamydia trachomatis and/or Neisseria gonorrhoeae.

The binx health io CT/NG Assay System (the "binx io System", "binx io CT/NG Assay" or the "System") is a rapid qualitative in vitro diagnostic system consisting of the following:

1. The binx io Instrument for running the Cartridge (the "Instrument")
2. The binx io CT/NG Cartridge (the "CT/NG Cartridge", "Cartridge" or "Cartridges"), which contains all the necessary reagents to perform the binx io CT/NG Assay (the "Assay") on the binx io Instrument
3. A single-use, fixed-volume transfer pipet (packaged with the Cartridge) for transferring the sample to the Cartridge
4. A female Vaginal Swab Specimen Collection Kit consisting of a swab and a sample Collection tube containing preservation medium (the "Vaginal Swab Specimen Collection Kit")

The binx io CT/NG Cartridge is a single-use assay-specific cartridge for use on a single patient. All reagents are contained in the Cartridge as a combination of liquid reagents in blister packs and dried reagents. The Instrument is a small, bench top, fully integrated Instrument that uses air pressure to open and close valves on the CT/NG Cartridge which, in turn, controls the movement of solutions within the Cartridge; the Instrument takes full control of the Cartridges once they are inserted. The operation of the Instrument requires a minimal number of steps that a user follows via a graphical user interface (GUI) screen to load the Cartridge onto the Instrument. Once the Cartridge is loaded, no further interaction by the user is required as no sample preparation is needed. Turnaround time from adding a raw patient sample to a result on the Instrument takes about 30 minutes.

The Vaginal Swab Collection Kit consists of a sterile flocked swab and a tube of preservative medium. The Cartridge has a visual sample loading indicator window which turns from light to dark to confirm to the user that a sample has been added to the Cartridge.

The Cartridge has three fully automated assay steps, (i) sample preparation to isolate and purify target DNA, (ii) ultra-rapid polymerase chain reaction (PCR), which amplifies specific regions of DNA from the target organisms, and (iii) a proprietary electrochemical detection to identify the presence of amplified DNA.

When the specimen is added to the Cartridge, it is automatically mixed with a lysis solution to disrupt the cells present and release DNA which also rehydrates the Internal Process Control (IPC) sample. DNA extraction takes place and the eluted DNA is transferred to a homogenization chamber.

Ultra-rapid PCR is carried out using sequence-specific primers for CT, NG (two separate genomic targets) and the IPC.

Amplified target DNA is detected by hybridization to electrochemically labeled probes and cleavage of the label using a double-strand specific exonuclease. The free label diffuses to the electrode surface and generates an electrical current measured at a distinct voltage in nano Amps (nA) for each electrochemical label used.

The presence of a measurable peak to a fixed cut-off parameter for each target returns a qualitative result with no requirement for interpretation or calculations.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as numerical targets before the results are presented. However, the study aims to demonstrate substantial equivalence to predicate devices and acceptable clinical performance. We can infer the performance targets from the reported results and the fact that the device received clearance. The performance is reported as sensitivity, specificity, and predictive values against a Composite Infected Status (CIS).

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The Aptima Combo 2® Assay is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection and differentiation of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC) to aid in the diagnosis of chlamydial and/or gonococcal urogenital disease using the Panther® System as specified.

On the Panther System, the assay may be used to test the following specimens from symptomatic and asymptomatic individuals: clinician-collected endocervical, vaginal and male urethral swab specimens, clinician-collected gynecological specimens collected in the PreservCyt® Solution, patient-collected vaginal swab specimens, 1 and female and male urine specimens.

1 Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal and multitest swab specimen collection kits are not for home use.

Clearance of this pre-market application will add female urine as an acceptable specimen type using the Aptima Combo 2 assay on the Panther system.

The Aptima Combo 2 Assay combines the technologies of target capture, Transcription-Mediated Amplification (TMA), and Dual Kinetic Assay (DKA). Specimens are collected and transferred into their respective specimen transport tubes. The transport solutions in these tubes release the rRNA targets and protect them from degradation during storage. When the Aptima Combo 2 Assay is performed in the laboratory, the target rRNA molecules are isolated from specimens by use of capture oligomers via target capture that utilizes magnetic microparticles. The capture oligomers contain sequences complementary to specific regions of the target molecules as well as a string of deoxyadenosine residues. A separate capture oligomer is used for each target. During the hybridization step, the sequence specific regions of the capture oligomers bind to specific regions of the target molecules. The capture oligomer:target complex is then captured out of solution by decreasing the temperature of the reaction to room temperature. This temperature reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the poly-deoxythymidine molecules that are covalently attached to the magnetic particles. The microparticles, including the captured target molecules bound to them, are pulled to the side of the reaction vessel using magnets and the supernatant is aspirated. The particles are washed to remove residual specimen matrix that may contain amplification reaction inhibitors. After the target capture steps are completed, the specimens are ready for amplification.

Target amplification assays are based on the ability of complementary oligonucleotide primers to specifically anneal and allow enzymatic amplification of the target nucleic acid strands. The Aptima Combo 2 Assay replicates a specific region of the 23S rRNA from CT and a specific region of the 16S rRNA from GC via DNA intermediates. A unique set of primers is used for each target molecule. Detection of the rRNA amplification product sequences (amplicon) is achieved using nucleic acid hybridization. Single-stranded chemiluminescent DNA probes, which are complementary to a region of each target amplicon, are labeled with different acridinium ester molecules. The labeled DNA probes combine with amplicon to form stable RNA:DNA hybrids. The Selection Reagent differentiates hybridized from unhybridized probe, eliminating the generation of signal from unhybridized probe. During the detection step, light emitted from the labeled RNA:DNA hybrids is measured as photon signals in a luminometer, and are reported as Relative Light Units (RLU). In DKA, differences in the kinetic profiles of the CT and GC labeled probes allow for the differentiation of signal; kinetic profiles are derived from measurements of photon output during the detection read time. The chemiluminescent detection for CT signal has very rapid kinetics and has the "flasher" kinetic type. The chemiluminescent detection reaction for GC signal is relatively slower and has the "glower" kinetic type. Assay results are determined by a cut-off based on the total RLU and the kinetic curve type.

The Aptima Combo 2 assay has been designed for and validated on the Panther system. The Panther system is an integrated hardware and software system that together with the Aptima Combo 2 assay fully automates all the steps necessary to perform the assay from sample preparation through amplification of nucleic acid, detection, data reduction and amplicon inactivation.

Here's an analysis of the provided text regarding the Aptima Combo 2 Assay (Panther System), focusing on acceptance criteria and the supporting study:

The provided document describes a 510(k) premarket notification for the Aptima Combo 2 Assay (Panther System) to add female urine as an acceptable specimen type. The study aimed to demonstrate substantial equivalence to the predicate device, which already included other specimen types.

1. Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a table format with numerical targets. Instead, it presents the Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) of the device compared to a Composite Comparator Algorithm (CCA) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) in female urine samples. For regulatory clearance, these performance metrics are implicitly the acceptance criteria; the observed performance must be deemed sufficient for the intended use and comparable to similar marketed devices.

Based on the performance tables provided, here's a summary of the reported device performance, which likely served as the basis for acceptance:

Reported Performance of Aptima Combo 2 Assay (Panther System) for Female Urine

Note: The confidence intervals provide the range within which the true PPA/NPA is likely to fall. For asymptomatic GC, the PPA has a wider confidence interval due to a smaller number of positive cases.

2. Sample Size and Data Provenance

• Sample Size for Test Set:
  • Total subjects initially enrolled: 2640
  • Subjects with valid Aptima Combo 2 Assay results on Panther System: 2581
  • Evaluable subjects for performance (conclusive CCA status): 2580
  • Final Sample Size for CT performance: 2572 (1379 symptomatic, 1193 asymptomatic) after accounting for equivocal results and non-evaluable subjects.
  • Final Sample Size for GC performance: 2579 (1383 symptomatic, 1196 asymptomatic) after accounting for equivocal results and non-evaluable subjects.
• Data Provenance: Retrospective study.
  • Specimens originated from women enrolled in a previously completed prospective study.
  • The study participants (women) were enrolled from 17 geographically and ethnically diverse US clinical sites, including family planning, academic centers, and public health clinics.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number of experts used to establish the ground truth or their qualifications. The ground truth (Composite Comparator Algorithm, CCA) was established using multiple FDA-cleared NAATs, not directly by human experts adjudicating individual cases based on clinical information or pathology.

4. Adjudication Method for the Test Set

The adjudication method used to establish the Composite Comparator Algorithm (CCA) for the ground truth was:

• 2 out of 3 rule: When 2 out of 3 FDA-cleared CT/GC NAATs were positive, the CCA was considered positive. When 2 out of 3 NAATs were negative, the CCA was considered negative.
• Tie-breaker: If the results from the initial two comparator NAATs did not determine the CCA, a third FDA-cleared CT/GC NAAT was performed using remnant urine samples to determine the CCA.

This is a form of consensus-based ground truth, but using other diagnostic tests rather than direct clinical expert consensus.

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

No MRMC comparative effectiveness study was done. This study evaluated the standalone performance of a diagnostic assay (Aptima Combo 2 Assay) against a reference standard (CCA), not the effect of AI assistance on human readers.

6. Standalone Performance

Yes, a standalone performance study was done. The entire clinical study described evaluates the performance of the Aptima Combo 2 assay on the Panther System (the algorithm/device itself) directly against the Composite Comparator Algorithm (CCA) without human interpretation as part of the primary outcome measure. The PPA and NPA values reported are the standalone performance metrics.

7. Type of Ground Truth Used

The ground truth used was a Composite Comparator Algorithm (CCA), which was derived from the results of multiple (up to 3) FDA-cleared nucleic acid amplification tests (NAATs). While this is a common method for establishing a "gold standard" in diagnostic test evaluations, it is not direct pathology, clinical outcomes data, or expert consensus in the traditional sense of clinicians reviewing patient records or images. It establishes the "truth" based on a highly sensitive and specific panel of existing diagnostic tools.

8. Sample Size for the Training Set

The document does not provide information on the sample size for a training set. This is a diagnostic assay (a lab test), not an AI/machine learning model in the typical sense that would require a separate, explicit "training set" for model parameters. The "development" or "training" of such an assay involves reagent formulation, assay protocol optimization, and establishing cut-offs, typically done using characterized samples, but not usually reported with a distinct "training set" size in the same manner as an AI algorithm. The study described is a clinical validation or "test set" evaluation.

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

As mentioned above, there is no explicit "training set" described in the context of this 510(k) submission. The performance study evaluated the device against a CCA, as detailed in point 4 and 7.

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