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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 Chlamydia trachomatis (CT) assay is an in vitro qualitative nucleic acid amplification test (NAAT) for the detection of ribosomal RNA (rRNA) from Chlamydia trachomatis to aid in the diagnosis of chlamydia urogenital disease using the Panther System.

The assay may be used to test the following specimens from symptomatic individuals: patient-collected vaginal swab specimens1 (in a clinical setting); 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 Aptima Multitest Swab Specimen Collection Kit has not been evaluated for home use.

The Aptima Chlamydia trachomatis assay (Aptima CT assay) is a target amplification nucleic acid probe test for in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT). The Aptima CT 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 CT 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 reduction allows hybridization to occur between the deoxyadenosine region on the capture oligomer and the polydeoxythymidine 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 CT 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 CT 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.

The provided document is a 510(k) summary for the Aptima Chlamydia trachomatis Assay, which focuses on demonstrating substantial equivalence to a predicate device. It details various analytical and clinical studies conducted to support the performance of the assay on the Panther system.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

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

The document does not present a single, comprehensive table outlining pre-defined acceptance criteria for each study and then directly reporting the device's performance against those criteria in a tabular format. Instead, acceptance criteria are generally described within the text of each study and the conclusion states whether those criteria were met.

However, based on the descriptions, we can infer some acceptance criteria and the reported performance.

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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 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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The cobas® CT/NG on the cobas® 6800/8800 system 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), clinician-collected vaginal swab specimens, and endocervical 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.

cobas® CT/NG is a new qualitative test performed on the cobas® 6800 System and cobas® 8800 System. cobas® CT/NG enables the detection of CT/NG DNA in endocervical, vaginal, urine and cervical specimens of infected female patients and urine specimens in infected male patients. Target-specific primers and two probes are used to detect but not discriminate between the CT cryptic plasmid and the ompA gene. Additionally, target-specific primers and two probes are used to detect but not discriminate between two conserved sequences in the NG DR-9 region. The DNA Internal Control, used to monitor the entire sample preparation and PCR amplification process, is introduced into each specimen during sample processing. In addition, the test utilizes a low titer positive and a negative control. cobas® CT/NG is based on fully automated sample preparation (nucleic acid extraction and purification) followed by PCR amplification and detection. The cobas® 6800/8800 Systems consist of the sample supply module, the transfer module, the processing module, and the analytic module. Automated data management is performed by the cobas® 6800/8800 software which assigns test results for all tests as positive, negative or invalid. Results can be reviewed directly on the system screen, exported, or printed as a report.

Here's a breakdown of the acceptance criteria and study information for the cobas® CT/NG for use on the cobas® 6800/8800 Systems device, extracted from the provided text:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the clinical performance and reproducibility study results. The device aims for high sensitivity, specificity, and reproducibility.

Table of Acceptance Criteria and Reported Device Performance

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

Clinical Performance Study:

• Total Subjects Enrolled: 5,197
• Eligible Subjects: 5,105
• Evaluable Subjects (Prospective): 5,053 (3,860 females, 1,193 males)
• Archived Specimens (Female): 371 urogenital samples from 295 female subjects (used for NG detection). These originated from a previous clinical study for cobas® CT/NG v2 test on the cobas® 4800 System.
• Total Samples Tested (across both CT & NG analyses, including prospective and archived): 17,169

Data Provenance:

• Geographic Origin: 9 geographically diverse sites in the US.
• Retrospective/Prospective: Primarily prospective data collection. Some female NG archived specimens were used, which were "archived prospectively collected" from a previous study.

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

The ground truth was established using a Patient Infected Status (PIS) algorithm, which relied on the results of multiple FDA-cleared NAATs (Nucleic Acid Amplification Tests) rather than human expert interpretation of images or clinical findings directly.

• Number of "Experts" (for constructing ground truth):
  • For females: A combination of results from 2 commercially available FDA-cleared NAATs.
  • For males: A combination of results from 3 commercially available FDA-cleared NAATs.
• Qualifications of "Experts": The "experts" in this context are the FDA-cleared NAATs themselves, which are established diagnostic tests for CT/NG. The text does not mention human experts delineating ground truth for individual cases.

4. Adjudication Method for the Test Set

The adjudication method was a Patient Infected Status (PIS) algorithm based on the concordance of results from multiple FDA-cleared NAATs.

• For females:
  • Infected: One or more positive results in each of the two NAATs. A scenario where one NAAT is positive/negative and the other is positive/positive also leads to "Infected".
  • Not Infected: Varied combinations of negative results or discordant results between the two NAATs, where the majority are negative.
  • Indeterminate: If one or more sample types are invalid for the NAATs, or if there are discordant results with invalid/missing data, the PIS is indeterminate.
• For males:
  • Infected/Not Infected: At least 2 out of the 3 test results must be concordant positive or negative, respectively.
  • Indeterminate: If one test result is invalid/missing and the other two are discordant, or if 2 or 3 test results are invalid/missing, the PIS is indeterminate.

This method essentially acts as a "majority vote" or expert consensus (of diagnostic tests) ground truth.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly performed or described in the provided text. This study focuses on the diagnostic accuracy of the device compared to a composite reference standard (PIS), not on how human readers' performance might improve with the AI (an in vitro diagnostic device) as an aid.

Effect Size: N/A (since an MRMC study was not described)

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

Yes, the study describes the standalone performance of the cobas® CT/NG system. The device is referred to as an "automated, qualitative in vitro nucleic acid diagnostic test" that uses real-time PCR. It directly detects CT/NG DNA, and the system software "assigns test results for all tests as positive, negative or invalid." This clearly indicates an algorithm-only standalone performance evaluation.

7. The Type of Ground Truth Used

The type of ground truth used was a composite reference standard known as Patient Infected Status (PIS).

• This PIS was determined by a combination of results from multiple FDA-cleared NAATs.
• Therefore, the ground truth is based on a consensus of highly accurate molecular diagnostic tests, which is a form of expert consensus (where the "experts" are established diagnostic technologies). It is not based on pathology reports, simple expert visual review, or patient outcomes data directly.

8. The Sample Size for the Training Set

The document does not provide information regarding a specific "training set" sample size. This is typical for a diagnostic device undergoing FDA clearance, where the focus is on validation against an independent test set rather than reporting on the development (training) phase of an AI or algorithm. The device is a PCR-based test, which generally involves laboratory optimization and locked-down algorithms rather than iterative machine learning training sets in the same way an image-based AI would.

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

As no specific training set and its associated ground truth establishment were described in this document, this information is not available / not applicable based on the provided text.

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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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