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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 ATV Assay with the modified TCR, referred to as ATV Assay (Version 2) in this submission is the subject of this premarket notification. The ATV Assay (Version 2) is similar to the ATV Assay originally cleared (ref: K102911), except for the formulation of the TCR. The TCR is a HEPES-buffered solution containing lithium salts and derivatized magnetic beads. A second target capture oligo was added to the TCR formulation in order to accommodate future specimen types.

The TCR modification did not result in the change of assay technology. The ATV Assay (Version 2) uses Target Capture (TC), Transcription Mediated Amplification (TMA), and Hybridization Protection Assay (HPA) technologies to qualitatively detect ribosomal RNA (rRNA) from Trichomonas vaginalis. The overall assay design as well as the assay procedural steps remain unchanged from that previously described in the original 510(k) for the ATV Assay (K102911).

The ATV Assay (Version 2) kit is comprised of 3 boxes:

1. Refrigerated Box Contains the Amplification Reagent, Enzyme Reagent, Probe Reagent and Target Capture Reagent-B
2. Room Temperature Box Contains Amplification Reconstitution Solution, Enzyme Reconstitution Solution, Probe Reconstitution Solution, Selection Reagent and Target Capture Reagent
3. Controls Box Contains the Negative and Positive Controls

The ATV Assay (Version 2) on PANTHER would utilize three specimen collection kits. These collection kits were cleared for use with the originally cleared ATV Assay and other commercialized APTIMA Assays.

1. APTIMA Unisex Swab Specimen Collection Kit for Endocervical and Male Urethral Swab Specimens
2. APTIMA Vaginal Swab Specimen Collection Kit
3. APTIMA Specimen Transfer Kit

Instrumentation
The ATV Assay (Version 2) was validated using the PANTHER System, which was previously cleared in May 2012 (Ref: K111409).

Acceptance Criteria and Device Performance Study for APTIMA® Trichomonas vaginalis Assay (PANTHER® System)

This section provides a summary of the acceptance criteria and the study conducted to demonstrate the APTIMA® Trichomonas vaginalis Assay on the PANTHER® System meets these criteria.

1. Table of Acceptance Criteria and Reported Device Performance

The primary acceptance criteria for this diagnostic device are its clinical sensitivity and specificity across different specimen types and symptom statuses.

Note: The document does not explicitly state numerical acceptance criteria in a structured table. However, the reported performance characteristics (Sensitivity, Specificity, PPV, NPV) with narrow 95% Confidence Intervals consistently demonstrate high agreement with the "patient infected status algorithm," indicating that the device performs as expected for a diagnostic test of this nature, meeting an implicit acceptance threshold for high diagnostic accuracy. The agreement studies with the predicate device further support this.

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

The clinical performance study used the following sample sizes for the test set:

• Vaginal Swabs: 667 (after exclusions for invalid results which were 11 out of 689 initial samples)
• Endocervical Swabs: 700 (after exclusions for invalid results which were 24 out of 737 initial samples)
• PreservCyt Solution liquid Pap specimens: 774 (after exclusions for invalid results which were 1 out of 791 initial samples)

Data Provenance: The study utilized retrospective, leftover specimens collected from consenting subjects during a previous, prospective, multicenter clinical study of the ATV Assay on the TIGRIS DTS System.

• Country of Origin: 9 US clinical sites (obstetrics and gynecology, family planning, and STD clinics).

For the agreement study with the TIGRIS DTS System for asymptomatic subjects:

• Vaginal Swabs: 227
• Endocervical Swabs: 227
• PreservCyt Solution liquid Pap specimens: 226
• Data Provenance: Prospectively collected specimens from asymptomatic subjects enrolled from 6 US clinical sites.

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

The document does not specify the number of experts or their specific qualifications (e.g., years of experience for radiologists) for establishing the ground truth for the clinical study.

4. Adjudication Method for the Test Set

The ground truth for the clinical performance study was established by a patient infected status algorithm based on the results from two reference tests performed on vaginal swab specimens:

1. Commercially available culture system
2. Wet mount microscopic examination

Adjudication Rule:

• Infected Patient Status: At least one of the reference test results was required to be positive.
• Non-infected Patient Status: Both reference tests were required to be negative.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This is a diagnostic assay (Nucleic Acid Amplification Test) and its performance is determined by its analytical and clinical characteristics against a defined ground truth, not by human reader interpretation. No human readers are involved in the direct interpretation of the assay results, which are automatically interpreted by the PANTHER System software.

6. Standalone Performance Study (Algorithm Only)

Yes, a standalone performance study (algorithm only, without human-in-the-loop performance) was done. The entire evaluation of the APTIMA® Trichomonas vaginalis Assay on the PANTHER® System, including its analytical and clinical performance, is based on the automated interpretation of the test results by the PANTHER System's software. The assay results (RLU values) are automatically interpreted as negative, positive, or invalid by the system.

7. Type of Ground Truth Used

The type of ground truth used for the clinical studies was an expert consensus-based algorithm derived from established diagnostic methods:

• Culture for Trichomonas vaginalis
• Wet mount microscopic examination

This algorithm defined the "patient infected status" against which the device's performance was measured.

8. Sample Size for the Training Set

The document does not explicitly state the sample size for a "training set" in the context of developing the algorithm itself. The information provided focuses on the validation data set used for clinical performance evaluation. Medical devices, especially diagnostic assays, often undergo development and internal validation on various sample sets, but these are typically not reported as explicitly as training sets in the context of machine learning model development. The focus here is on the analytical and clinical validation of the final assay.

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

As noted above, an explicit "training set" for the algorithm's development is not detailed. The ground truth for validating the assay's performance (the clinical test set) was established using a patient infected status algorithm based on a combination of culture and wet mount microscopic examination results. This is a common practice for validating new diagnostic tests against existing gold standards or established diagnostic pathways.

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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, and patient-collected vaginal swab specimens.

The APTIMA Combo 2 Assay combines the technologies of target capture, TMA, and 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.

This FDA 510(k) summary describes the APTIMA Combo 2® Assay on the PANTHER System, a device for in vitro qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (GC). The submission is for clearing the assay for use on the PANTHER System, as it was previously cleared on the TIGRIS System.

Here's an analysis of the provided information:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly tied to the performance characteristics, specifically sensitivity and specificity, as demonstrated in the clinical study. While explicit "acceptance criteria" values for sensitivity and specificity are not directly stated in the summary, the reported performance characteristics are presented with 95% confidence intervals, suggesting that the observed values met predefined thresholds for regulatory approval. The fact that the device received 510(k) clearance further indicates that its performance was deemed acceptable by the FDA.

Table of Performance for APTIMA Combo 2® Assay on the PANTHER System (Clinical Study Results)

Analytical Sensitivity (Limits of Detection):

• CT: Claimed 1 IFU/assay (7.25 IFU/swab, 9.75 IFU/mL, PreservCyt Solution liquid Pap). 100% positivity was observed in samples containing CT concentrations of 0.03 IFU/mL.
• GC: Claimed 50 cells/assay (362 cells/swab, 488 cells/mL PreservCyt Solution liquid Pap). 100% positivity was observed in samples containing GC concentrations of 0.04 CFU/mL.

Within Laboratory Precision (STM matrix, selected rows as an example):

Carryover Study: Overall carryover rate was 0% with a 95% confidence interval of 0-0.1%. This meets an implicit acceptance criterion of negligible or acceptable carryover.

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

The clinical study was a prospective, multicenter clinical study conducted across 7 geographically and ethnically diverse US clinical sites.

Test Set Sample Sizes:

• Male subjects: 580 enrolled, 567 evaluable male urethral swab samples.
  • 18 male urethral swab specimens had final invalid results and were excluded.
• Female subjects: 1332 enrolled.
  • 1319 evaluable vaginal swab samples (clinician-collected/patient-collected combined).
  • 1330 evaluable PreservCyt Solution liquid Pap samples.
  • 1310 evaluable endocervical swab samples.
  • 1 vaginal swab and 1 endocervical swab had final CT equivocal results and were excluded.
  • 1 PreservCyt and 1 endocervical swab had final GC equivocal results and were excluded.
  • Female urine specimens were collected but used as part of the "infected status algorithm" (ground truth definition) rather than directly tested as a primary specimen type for performance against the APTIMA Combo 2 Assay on PANTHER for this 510(k).

Data Provenance: United States (7 US clinical sites). The study was prospective.

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

The ground truth was established using an "infected status algorithm" based on results from two specimen types and two reference NAATs (Nucleic Acid Amplification Tests). The specific number and qualifications of experts directly involved in adjudicating the "infected status" or interpreting the reference NAATs are not explicitly stated in the provided text.

However, for a device like this, standard practice for establishing ground truth for NAATs in clinical trials typically involves:

• Use of one or more FDA-cleared and/or highly sensitive and specific reference NAATs.
• Concordance of positive results across multiple tests/specimens to define an "infected status."
• Discrepancies often resolved by a third, highly sensitive method or expert clinical review, though this detail is not provided.

The text states: "Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs." This implies a rule-based algorithm for ground truth rather than individual expert adjudication for each case.

4. Adjudication Method for the Test Set

The adjudication method for determining the "infected status" (ground truth) was an algorithm-based approach:

• For male subjects and female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected.
• "Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs."

This indicates a 2-out-of-2 (or 2+0) concordance rule for positivity to establish infection status. The text doesn't mention a tie-breaking or expert review process if results were discordant between the two reference NAATs, but specimens with "invalid, equivocal, or error results" were retested, and those with final invalid/equivocal results were excluded from analysis.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done.

This device is an in vitro diagnostic test, specifically a nucleic acid amplification test (NAAT). These types of tests are designed to provide a qualitative result (positive/negative) based on an analytical assay run on an automated system, not to be interpreted by human readers in the same way an imaging device or pathology slide might be. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply to this type of device. The "AI" (algorithm) here is the test.

6. Standalone (Algorithm Only) Performance

Yes, standalone performance was done.

The entire clinical study described, including the sensitivity and specificity values provided in Tables 6, 7, 8, 9, 10, and 11, represents the standalone performance of the APTIMA Combo 2 Assay on the PANTHER System. The results are compared against an "infected status algorithm" which serves as the ground truth, not against human interpretation of raw assay data. The device's output is the final diagnostic result.

7. Type of Ground Truth Used

The ground truth used was an algorithm-based "infected status" derived from the results of two reference nucleic acid amplification tests (NAATs) on two different specimen types (e.g., male urethral swab and male urine for males, and PreservCyt and urine for females).

Specifically:

• "Male urethral swab, male and female urine, and PreservCyt samples were tested with cleared nucleic acid amplification tests (NAATs) to establish the infected status."
• "The infected status algorithm used results from two specimen types and two reference NAATs. Subjects were categorized as infected if a positive result occurred in each of the 2 reference NAATs."
• "For female subjects, if the positive NAAT results occurred only in the urine specimens and not in the PreservCyt specimens, the subject was categorized as infected; however, for the evaluation of the non-urine specimen types, the specimens were considered non-infected."

8. Sample Size for the Training Set

The provided text does not specify a sample size for a training set. This document is a 510(k) summary for a diagnostic test, not a submission for a de novo machine learning algorithm that typically requires a distinct training and test set with explicit disclosure of training data. The "device" in this context is the analytical assay and automated system. While the assay itself (APTIMA Combo 2) was developed and validated, the data tables presented relate to the performance evaluation (test set) for the new platform (PANTHER System).

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

As no explicit training set is detailed for the purpose of a machine learning algorithm in this 510(k) summary, the process for establishing ground truth for a training set is not applicable here. The provided data focuses on the validation of the device on a new platform (PANTHER System) for regulatory clearance, where the clinical study (test set) is the primary evidence for performance.

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The GEN-PROBE APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease using the TIGRIS® DTS® Automated Analyzer or semiautomated 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 swab specimens; patient-collected 'vaginal swab specimens; and female and male urine. The assay is also intended for use with the testing of gynecological specimens, from both symptomatic and asymptomatic patients collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System.

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE®APTIMA® Assay for Neisseria gonorrhoeae with the testing of gynecological specimens collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System, for use on the TIGRIS® DTS® System. The ancillary kit for this application is commercially available as the GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Transfer Kit may only be used in conjunction with the APTIMA Assays.

This document describes the GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae on the TIGRIS DTS System. The goal of the submission appears to be to expand the clinical performance claims of the existing assay to include gynecological specimens collected in PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System, for use on the TIGRIS DTS System.

Here's the breakdown of the acceptance criteria and study information:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria provided in the document are primarily related to agreement studies and analytical performance targets rather than explicit numerical thresholds for clinical sensitivity/specificity against a gold standard for the new use case (PreservCyt specimens on the TIGRIS DTS System). The clinical studies focus on demonstrating equivalence between the TIGRIS DTS System and previously validated DTS Systems.

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

• Analytical Sensitivity (LOD): N=60 for post-processed PreservCyt liquid Pap specimen. The data provenance is from laboratory spiking experiments.
• Analytical Specificity: 24 culture isolates. The data provenance is from laboratory testing of known organisms.
• Specimen-Caused Inhibition: N=240 negative clinical post-processed PreservCyt liquid Pap specimens. Data provenance is from clinical specimens presumably collected in the US (not explicitly stated for this part, but the clinical study below is multi-center in the US).
• Interference by Whole Blood: Not specified as a precise "test set" size, but involved three negative PreservCyt liquid Pap specimen pools, tested in the absence and presence of N. gonorrhoeae and varying blood concentrations. Data provenance is from laboratory spiking experiments.
• Clinical Specimen Study: N=51 PreservCyt specimens (34 symptomatic, 17 asymptomatic female subjects).
  • Data Provenance: Prospective, multi-center clinical study. Patients were enrolled from family planning, OB/GYN, public health, and STD clinics. While not explicitly stated, multi-center studies for FDA submissions are typically conducted in the USA.
• Clinical Panel Study: 132 replicates (30 aliquots for each of 4 positive panel members, and 12 aliquots for the negative panel member). These were created from pooled residual negative PreservCyt specimens from female subjects.

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

There is no mention of "experts" in the context of establishing ground truth for the test sets in this submission.

• Clinical Specimen Study: The "ground truth" or reference method for comparison was the AGC Assay performed on the previously validated DTS Systems, following an initial screening with FDA-cleared APTIMA COMBO 2 (AC2) Assay. The AC2 Assay results determined whether specimens were selected for the clinical specimen or panel study. This is a comparison between two automated systems rather than expert interpretation of a gold standard.
• Clinical Panel Study: The "ground truth" for the panel members was their known N. gonorrhoeae ribosomal RNA (rRNA) concentration (spiked or not spiked).
• Analytical Studies: Ground truth was based on known concentrations of spiked organisms or rRNA, or confirmed negative samples.

4. Adjudication Method for the Test Set

Not applicable in the typical sense of expert adjudication of imaging or clinical findings.

• For the Clinical Specimen Study, the comparison was made between the results of the AGC Assay on the DTS Systems (predicate) and the TIGRIS DTS System (new system). No explicit adjudication process between discordant results from these two systems is described; rather, the agreement between them was calculated.
• For the Analytical Studies and Clinical Panel Study, the "ground truth" was established by experimental design (e.g., spiking known quantities of analyte, using confirmed negative samples), not through adjudication of expert opinions.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done, If So, What was the Effect Size of How Much Human Readers Improve with AI vs without AI Assistance

This submission is for an in vitro diagnostic (IVD) assay, specifically a nucleic acid amplification test (NAAT) for Neisseria gonorrhoeae. It is a standalone diagnostic device with no "human reader" component in the interpretation of results in the way an imaging AI device would have. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this device.

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

Yes, the studies presented are essentially standalone performance evaluations of the GEN-PROBE APTIMA Assay on the TIGRIS DTS System. The assay generates a qualitative (positive/negative) result without human interpretation of raw data beyond confirming valid assay run parameters. The purpose of this submission was to demonstrate equivalence of this assay on a new automated platform (TIGRIS DTS) for a new specimen type (PreservCyt).

7. The Type of Ground Truth Used

• Analytical Sensitivity: Known spiked concentrations of N. gonorrhoeae rRNA.
• Analytical Specificity: Known culture isolates.
• Specimen-Caused Inhibition and Interference: Known negative samples and known spiked concentrations (for inhibition/recovery).
• Clinical Specimen Study: The results of the AGC Assay on the predicate DTS Systems, following initial screening with the FDA-cleared APTIMA COMBO 2 (AC2) Assay. This acts as a reference method for the comparison between the old and new platforms.
• Clinical Panel Study: Known spiked concentrations of N. gonorrhoeae ribosomal RNA (rRNA) into confirmed negative PreservCyt specimens.

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of device development or algorithm training. This is a molecular diagnostic assay, not a machine learning or AI algorithm in the conventional sense that would require a dedicated training set. The assay's parameters (e.g., cut-offs) would have been established during its initial development and validation, which is not detailed in this specific 510(k) summary, as this submission is an extension of claims for an already cleared assay.

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

As no specific "training set" for an AI/ML algorithm is mentioned or applicable here, this question is not relevant to the provided documentation. The assay relies on target amplification and detection of rRNA, with predetermined analytical characteristics, rather than learning from a training dataset.

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The GEN-PROBE APTIMA® Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) to aid in the diagnosis of chlamydial urogenital disease using the TIGRIS® DTS® Automated Analyzer or semiautomated 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 specimens, 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 and processed with the Cytyc ThinPrep® 2000 System.

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE®APTIMA® Assay for Chlamydia trachomatis with the testing of gynecological specimens collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System, for use on the TIGRIS® DTS® System. The ancillary kit for this application is commercially available as the GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for ruse regarding decontamination and specimen processing procedures. The APTIMA Transfer Kit may only be used in conjunction with the APTIMA Assays.

Acceptance Criteria and Device Performance for APTIMA® Assay for Chlamydia trachomatis

The APTIMA® Assay for Chlamydia trachomatis (CT) on the TIGRIS® DTS® System extends the clinical performance claims for testing gynecological specimens collected in PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System. The study aimed to demonstrate equivalent performance between the previously validated DTS Systems and the TIGRIS DTS System.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Analytical Sensitivity: 60 replicates of C. trachomatis rRNA spiked into post-processed PreservCyt liquid Pap specimen pool.
• Analytical Specificity: 24 culture isolates tested.
• Specimen-Caused Inhibition: 239 negative clinical post-processed PreservCyt liquid Pap specimens.
• Interference by Whole Blood: Clinical post-processed PreservCyt liquid Pap specimen pools, tested with 0% and 10% whole blood, both unspiked and spiked with CT rRNA.
• Clinical Specimen Study: 116 PreservCyt specimens from female subjects (81 symptomatic, 35 asymptomatic).
• Clinical Panel Study: 5 panel members, including a negative control and 4 positive concentrations of CT rRNA, prepared by spiking. Total of 132 replicates (12 for negative, 30 for each positive concentration).

Data Provenance: The report indicates a "prospective, multi-center clinical study" was conducted for the clinical performance data. Patient enrollment occurred at "family planning, OB/GYN, public health, and STD clinics." This suggests the clinical data is prospective and collected from various clinical sites. The country of origin is not explicitly stated but implied to be the USA given the FDA 510(k) submission.

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the "number of experts" or their specific "qualifications" used to establish ground truth in the traditional sense of expert review for image interpretation or diagnosis.

• For the Clinical Specimen Study, specimens were first screened using "FDA-cleared applications of the APTIMA COMBO 2 (AC2) Assay." The results from this FDA-cleared assay served as the reference standard (ground truth proxy) for comparing the DTS Systems and TIGRIS System results.
• For the Clinical Panel Study, negative PreservCyt specimens were pooled and confirmed negative by testing with the ACT Assay on the DTS Systems. Then, CT ribosomal RNA (rRNA) was spiked at known concentrations to create panel members. The "expected CT results" based on the known spiked concentrations served as the ground truth.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method like 2+1 or 3+1. For the clinical specimen study, the "ground truth" was established by prior testing with an "FDA-cleared" assay (APTIMA COMBO 2 Assay), implying it was considered a reliable reference. Discrepancies, if any, between the test systems (TIGRIS vs. DTS) were analyzed for percent agreement, rather than adjudicated by independent readers. "Specimens with final invalid or equivocal screening results were not selected for testing," suggesting a pre-screening step to ensure data quality.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was performed as this is an in vitro diagnostic (IVD) assay detection system, not an imaging device requiring human reader interpretation. The study compares the performance of two automated systems (TIGRIS DTS System vs. DTS Systems) for detecting Chlamydia trachomatis. There is no human-in-the-loop component for which an improvement effect size with AI assistance would be relevant.

6. Standalone Performance Study

Yes, a standalone performance study was done for the algorithm (the APTIMA Assay on the TIGRIS DTS System). The entire document describes the analytical and clinical performance of the device on its own, comparing it against a reference standard or a previously cleared device. The "overall % agreement" in the clinical studies directly reflects the standalone performance of the TIGRIS DTS System relative to the DTS system and the expected results.

7. Type of Ground Truth Used

• Analytical Studies (Sensitivity, Specificity, Inhibition, Interference): Ground truth was established by known concentrations of C. trachomatis rRNA or culture isolates, or by the absence of target/interfering substance in controlled laboratory settings.
• Clinical Specimen Study: Ground truth was established by results from a previously FDA-cleared assay (APTIMA COMBO 2 Assay), acting as the reference standard.
• Clinical Panel Study: Ground truth was established by known spiked concentrations of CT ribosomal RNA (rRNA) into confirmed negative PreservCyt specimens.

8. Sample Size for the Training Set

The document describes an analytical validation and clinical performance study for a diagnostic assay, not a machine learning or AI algorithm in the context of a "training set." Therefore, a "training set" as understood in AI/ML development is not applicable here. The assays are based on target amplification nucleic acid probe technology.

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

As explained in point 8, there is no explicit "training set" as this is not an AI/ML device that requires machine learning for its core function. The assay's parameters and cut-offs would have been established during earlier development and validation phases (not detailed in this 510(k) summary), likely using characterized positive and negative samples, similar to the "panel" approach seen in the clinical panel study.

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The APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease. 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: cliniciancollected endocervical and vaginal swab specimens; and patient-collected vaginal swab specimens 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 and processed with the Cytyc ThinPrep 2000 System.

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the commercially available GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae.

The provided document describes the GEN-PROBE APTIMA Assay for Neisseria gonorrhoeae, specifically its expanded indication for use with ThinPrep Specimens. The acceptance criteria and the study proving the device meets these criteria are detailed below.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for sensitivity and specificity are not explicitly stated as numerical targets in the document. However, the study results are presented as the "Summary of Clinical Performance Data" and indicate the device's performance attributes. The general expectation for such a diagnostic assay is high sensitivity and specificity. The reported performance is based on the clinical study.

2. Sample Sizes and Data Provenance

• Test Set Sample Size: 1,646 symptomatic and asymptomatic female subjects were evaluated in the clinical study. (Page 8)
• Data Provenance: The data was collected from a prospective multi-center clinical study (Page 8). The study subjects were enrolled from sites with GC prevalence ranging from 0.0% to 5.0% (Page 8). While the exact country of origin is not explicitly stated, the context of an FDA submission (K062440) for a device from "San Diego, California" implies the study was likely conducted in the United States.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of experts to establish ground truth for the clinical study.

4. Adjudication Method for the Test Set

The adjudication method used to establish the "patient infected status" (ground truth) for the clinical study was based on a reference standard involving two other tests:

• The APTIMA Combo 2 Assay (for Chlamydia trachomatis and Neisseria gonorrhoeae).
• The APTIMA GC Assay (performed on endocervical swab specimens). (Page 8)

The criteria were:

• Infected Patient Status: Both reference NAATs (APTIMA Combo 2 Assay and APTIMA GC Assay on endocervical swab) were required to be positive.
• Non-Infected Patient Status: At least one reference NAAT was required to be negative.
• Inconclusive: If an equivocal result was obtained from any one of the reference NAATs, the patient infected status was categorized as inconclusive, and these specimens were not included in sensitivity and specificity calculations. (Page 8)

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

No MRMC comparative effectiveness study was mentioned. The study focuses on the performance of the device itself against a defined ground truth, not on human readers with or without AI assistance.

6. Standalone Performance

Yes, a standalone (algorithm only) performance study was performed. The clinical study directly evaluated the performance of the APTIMA GC Assay in PreservCyt liquid Pap specimens against a defined patient infected status (ground truth) derived from other laboratory tests, without human-in-the-loop performance described. (Page 8)

7. Type of Ground Truth Used

The ground truth used was based on a composite reference standard derived from the results of two other Nucleic Acid Amplification Tests (NAATs) – the APTIMA Combo 2 Assay and the APTIMA GC Assay – performed on endocervical swab specimens. Specifically, two positive reference NAATs defined an infected patient, and at least one negative defined a non-infected patient. (Page 8)

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its sample size for model development. Diagnostic assays like this typically undergo extensive analytical validation to determine performance characteristics (e.g., limit of detection, specificity) and then clinical validation using a distinct clinical sample set. The analytical studies describe testing with various organisms and dilutions, which might be considered part of the development and refinement process, but not a formally delineated "training set" in the context of machine learning.

9. How Ground Truth for the Training Set Was Established

Since a distinct "training set" is not described, the method for establishing its ground truth is not provided. For the analytical studies (e.g., Limit of Detection, Analytical Specificity), organism concentrations were precisely controlled by direct comparison/dilution of clinical isolates or by spiking known concentrations of organisms/cells into samples. (Page 3-4)

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The APTIMA Assay for Chlamydia trachomatis is a target amplification nucleix acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens1, and female and male urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease using the TIGRIS DTS Automated Analyzer or semi-automated instrumentation as specified.

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

Not Found

The provided text is a 510(k) premarket notification letter from the FDA to Gen-Probe Incorporated regarding their TIGRIS® DTS® Automated Analyzer APTIMA® Assay for Chlamydia trachomatis. While it outlines the device's indications for use and classification, it does not contain the detailed acceptance criteria or the study data that proves the device meets those criteria.

Therefore, I cannot fulfill most of your request directly from this document. The information typically found in a 510(k) summary (which is a separate document often submitted alongside the initial notification) would contain such details.

However, based on the information provided in this letter, I can extract the following:

• Device Name: TIGRIS® DTS® Automated Analyzer APTIMA® Assay for Chlamydia trachomatis
• Indications for Use: The APTIMA Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens¹, and female and male urine specimens. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease using the TIGRIS DTS Automated Analyzer or semi-automated instrumentation as specified.
  • ¹Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

To answer the rest of your questions, I would need access to the full 510(k) submission, specifically the sections detailing the performance data and clinical studies.

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The APTIMA® Assay for Neisseria gonorrhoeae is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of 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 patient-collected female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: clinician-collected endocervical and vaginal swab specimens; and patient-collected vaginal swab specimens¹ and female and male urine specimens. ¹Patient-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The vaginal swab specimen collection kit is not for home use.

Not Found

This document is a 510(k) clearance letter for the TIGRIS® DTS® GEN-PROBE® APTIMA Assay® for Neisseria gonorrhoeae. It confirms that the device is substantially equivalent to a legally marketed predicate device. However, this letter does not contain the detailed study results, acceptance criteria, or performance data that would typically be found in the actual 510(k) submission or a clinical study report.

Therefore, I cannot fulfill most of your request directly from this document. The information provided is primarily an FDA clearance letter and an "Indications for Use Statement."

Here's what I can extract and what is explicitly missing from the provided text:

Information Extracted from the Document:

• Device Name: TIGRIS® DTS® GEN-PROBE® APTIMA Assay® for Neisseria gonorrhoeae
• Intended Use: In vitro qualitative detection of ribosomal RNA (rRNA) from Neisseria gonorrhoeae (GC) to aid in the diagnosis of gonococcal urogenital disease, using specified specimens from symptomatic and asymptomatic individuals.
• Sample Types: Clinician-collected endocervical, vaginal, and male urethral swab specimens; patient-collected female and male urine specimens; patient-collected vaginal swab specimens.

Missing Information (Not provided in the document):

1. A table of acceptance criteria and the reported device performance: This document does not include a table of acceptance criteria or performance metrics (e.g., sensitivity, specificity, PPV, NPV). These would be in the original 510(k) submission.
2. Sample sizes used for the test set and the data provenance: No information on sample sizes or data provenance (country, retrospective/prospective) is present.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not mentioned. For an in vitro diagnostic (IVD) like this, the "ground truth" is typically established by well-characterized reference tests (e.g., culture, another FDA-approved NAAT), not by human experts adjudicating images.
4. Adjudication method for the test set: Not applicable in the traditional sense for an IVD diagnostic assay primarily detecting genetic material. The ground truth is usually determined by reference methods.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size: Not applicable. This is an IVD assay, not an imaging device requiring human reader interpretation or assistance.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The device itself is a standalone assay. Its performance is measured directly against a reference standard.
7. The type of ground truth used: While not explicitly stated, for Neisseria gonorrhoeae detection, the ground truth for such an assay is typically established through culture or a comparator FDA-approved nucleic acid amplification test (NAAT). The document refers to "in vitro qualitative detection of ribosomal RNA," strongly suggesting laboratory-based reference methods.
8. The sample size for the training set: The concept of a "training set" as understood in machine learning (which this question implies) is generally not applicable to a traditional IVD chemical/molecular assay like this one. These assays are developed and validated using a series of laboratory experiments and clinical studies, but not typically "trained" in the AI sense.
9. How the ground truth for the training set was established: See point 8.

In summary, this document is an FDA clearance letter and does not contain the detailed technical and clinical study information required to answer most of your questions. That data would be found in the actual 510(k) submission that was reviewed by the FDA, but is not included in this publicly available letter.

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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 and/or Neisseria gonorrhoeae in clinician-collected endocervical, vaginal and male urethral swab specimens, patientcollected vaginal swab specimens', female and male urine specimens and gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease using the TIGRIS DTS Automated Analyzer or semi-automated instrumentation as specified.

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 and/or Neisseria gonorrhoeae.

This document is an FDA 510(k) clearance letter for an in vitro diagnostic device, not an AI/ML medical device. Therefore, the requested information about acceptance criteria, study design, and performance metrics (especially those related to AI/ML such as multi-reader multi-case studies, human reader improvement with AI, or standalone algorithm performance) is not applicable or cannot be extracted from this document.

The document discusses the substantial equivalence of the TIGRIS® DTS® GEN-PROBE® APTIMA COMOBO 2® Assay to a legally marketed predicate device for the qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis and/or Neisseria gonorrhoeae.

Here's the information that can be extracted, noting the limitations related to your AI/ML specific questions:

1. Table of Acceptance Criteria and Reported Device Performance:

This document does not provide a table of quantitative acceptance criteria (e.g., sensitivity, specificity thresholds) or specific performance metrics (e.g., reported sensitivity, specificity values) from a clinical study. It is a clearance letter acknowledging substantial equivalence to a predicate device, not a detailed performance report. Such data would typically be found in the 510(k) submission itself, not the clearance letter.

2. Sample size used for the test set and the data provenance:

• Test set sample size: Not specified in this document.
• Data provenance: Not specified. Clinical studies supporting clearance typically involve multiple sites, which could be domestic or international, and data could be retrospective or prospective. This information is usually detailed in the submission, not the clearance letter.

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

This is irrelevant for an in vitro diagnostic assay like the APTIMA COMBO 2 Assay. The "ground truth" for such assays is typically established by reference laboratory methods (e.g., culture, NAATs) or clinical diagnosis, not by human expert interpretation of images or other data. Therefore, there's no concept of "experts establishing ground truth" in the way described for AI/ML imaging devices.

4. Adjudication method for the test set:

Not applicable for an in vitro diagnostic assay. Adjudication methods (like 2+1 or 3+1) are used to resolve disagreements among human readers, typically in image interpretation, which is not the function of this device.

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:

Not applicable. This is an in vitro diagnostic test for direct pathogen detection, not an AI-assisted diagnostic imaging or decision support system. Therefore, MRMC studies and the concept of human readers improving with AI assistance are irrelevant to this device.

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

The device itself is a standalone assay. It performs the detection of rRNA from Chlamydia trachomatis and/or Neisseria gonorrhoeae without human interpretation influencing the result of the assay itself. However, this is not an "algorithm only" in the sense of an AI model; it's a biochemical assay for pathogen identification. The results are typically interpreted by laboratory personnel. Performance studies for such devices evaluate the accuracy of the device's output against a reference standard.

7. The type of ground truth used:

While not explicitly stated in this clearance letter, for in vitro diagnostic assays detecting pathogens, the ground truth is typically established by:

• Culture: For bacterial infections like N. gonorrhoeae.
• Other highly sensitive and specific Nucleic Acid Amplification Tests (NAATs): Often used as a gold standard or "truth" for comparison, especially for C. trachomatis where culture is difficult.
• Clinical diagnosis: Supported by other laboratory findings and patient symptoms.

8. The sample size for the training set:

Not applicable. This document refers to a molecular diagnostic assay, not an AI/ML model that requires a training set. The development of such assays involves analytical studies (assay optimization, limit of detection, cross-reactivity) and clinical studies (evaluating performance on patient samples), but there's no "training set" in the context of machine learning.

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

Not applicable, as there is no "training set" in the AI/ML sense for this device. Ground truth in the context of assay development is established through rigorous analytical and clinical validation against established reference methods.

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The APTIMA Assay for Chlamydia trachomatis is a target amplification nucleic acid probe test that utilizes target capture for the in vitro qualitative detection of ribosomal RNA (rRNA) from Chlamydia trachomatis (CT) in clinician-collected endocervical, vaginal and male urethral swab specimens, patient-collected vaginal swab specimens, and female and male urine specimens. The assay is also intended for use with the testing of gynecological specimens collected in the PreservCyt® Solution and processed with the Cytyc ThinPrep® 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of chlamydial urogenital disease.

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Assay for Chlamydia trachomatis to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the commercially available GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae.

The GEN-PROBE® APTIMA® Assay for Chlamydia trachomatis, specifically for its expanded indication with ThinPrep Specimens, underwent a clinical study to evaluate its performance.

1. Table of Acceptance Criteria and Reported Device Performance:

The document describes the performance in terms of sensitivity and specificity. While explicit acceptance criteria are not called out as "acceptance criteria," the clinical study results are presented, suggesting that these performance metrics were deemed acceptable for the device's expanded use.

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

• Sample Size: 1,647 female subjects were evaluated in the clinical study.
  • 1,288 asymptomatic subjects
  • 359 symptomatic subjects
• Data Provenance: The study was a prospective multi-center clinical study. The data was collected from OB/GYN, family planning, public health, women’s, and STD clinics. The country of origin is not explicitly stated, but the submission to the FDA and use of brand names like Cytyc ThinPrep 2000 System suggest a US-centric study or at least a study adhering to US regulatory standards.

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

• The document does not mention the use of experts to establish the ground truth in the traditional sense of human readers adjudicating images or cases.
• Instead, the ground truth (patient infected status) was established using a patient infected status algorithm. This algorithm relied on the results of two reference Nucleic Acid Amplification Tests (NAATs) on endocervical swab specimens.

4. Adjudication Method for the Test Set:

• Adjudication Method: The patient infected status was determined by an algorithm that used two reference NAATs (APTIMA Combo 2 Assay and APTIMA CT Assay) on endocervical swab specimens.
  • An infected patient status required both reference NAATs to be positive.
  • A non-infected patient status required at least one reference NAAT to be negative.
  • This can be considered a form of "2-out-of-2" positive for infection, and "1-out-of-2" negative for non-infection, rather than human adjudication.

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

• No MRMC comparative effectiveness study was done. This study focuses on the standalone performance of the APTIMA Assay for Chlamydia trachomatis when using PreservCyt liquid Pap specimens, not a comparison involving human readers with and without AI assistance.

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

• Yes, a standalone performance evaluation was done. The clinical study directly assessed the performance of the APTIMA CT Assay on PreservCyt liquid Pap specimens against the defined patient infected status algorithm. This represents the algorithm's performance without direct human interpretation of the assay results, other than performing the lab test.

7. The Type of Ground Truth Used:

• Algorithm Consensus (from reference NAATs): The ground truth for the clinical study was established by a patient infected status algorithm based on the results of two highly sensitive and specific reference Nucleic Acid Amplification Tests (NAATs) – the APTIMA Combo 2 Assay and the APTIMA CT Assay – performed on endocervical swab specimens. This is a common and robust method for establishing ground truth for infectious disease diagnostics.

8. The Sample Size for the Training Set:

• The document does not explicitly state the sample size for a training set. Diagnostic assays like the APTIMA Assay are developed through extensive research and analytical validation (limit of detection, analytical specificity, interference, recovery studies) before large-scale clinical validation. The details provided primarily cover the validation study for the expanded indication. It is typical for the assay to have been developed and optimized using various samples, but a specific "training set" in the machine learning sense is not described.

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

• As a specific "training set" and its ground truth establishment are not detailed in the provided document, this information cannot be extracted. The document focuses on the validation of an existing assay for an expanded specimen type. The ground truth for the extensive analytical studies would likely have been established using well-characterized culture isolates and spiked samples with known concentrations of C. trachomatis as described in the Limit of Detection, Analytical Specificity, and Recovery sections (e.g., using IFU/assay as a measure for CT organisms).

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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) in clinician-collected endocervical, vaginal, and male urethral swab specimens, patientcollected vaginal swab specimens*, and female and male urine specimens. The assay is also intended for use with testing of gynecological specimens collected in the PreservCyt Solution and processed with the Cytyc ThinPrep 2000 System. The assay may be used to test specimens from symptomatic and asymptomatic individuals to aid in the diagnosis of gonococcal and/or chlamydial urogenital disease.

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

The GEN-PROBE® APTIMA® Specimen Transfer Kit is only for use with GEN-PROBE APTIMA assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae. The GEN-PROBE APTIMA Specimen Transfer Kit allows for APTIMA Assay testing of gynecological specimens collected and processed by the Cytyc ThinPrep 2000 Processor according to the instructions provided.

Clearance of this premarket notification extends the clinical performance claims of the commercially available GEN-PROBE APTIMA Combo 2 Assay to include PreservCyt liquid Pap specimens (collected and processed by the Cytyc ThinPrep 2000 Processor) as acceptable testing specimens. The ancillary kit formulated for this specific application is the GEN-PROBE APTIMA Specimen Transfer Kit. The components of the APTIMA Specimen Transfer Kit include: (1) a transport tube containing transport media with a penetrable cap and (2) specific instructions for use regarding decontamination and specimen processing procedures. The APTIMA Specimen Transfer Kit may only be used in conjunction with GEN-PROBE APTIMA Assays for the detection of Chlamydia trachomatis and/or Neisseria gonorrhoeae..

The GEN-PROBE® APTIMA COMBO2® Assay performance has been evaluated through a multi-center clinical study.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample size used for the test set and the data provenance:

• Test Set Sample Size: 1,647 female subjects (1,288 asymptomatic, 359 symptomatic).
• Data Provenance: Prospective multi-center clinical study conducted in the United States (as implied by the FDA submission and the company's US address). The study involved subjects attending OB/GYN, family planning, public health, women's, and STD clinics.

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

• The document does not explicitly state the number or qualifications of experts used to establish the ground truth. Instead, the ground truth was established by a patient infected status algorithm based on the results of two commercially-available reference NAATs performed on endocervical swab specimens. This implies that the ground truth was determined by laboratory testing protocols rather than direct expert consensus on each individual case.

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

• Adjudication Method: "None" in the sense of expert human adjudication. The ground truth for the "patient infected status" was based on concordant positive results from two reference NAATs (APTIMA Combo 2 Assay and APTIMA CT Assay for C. trachomatis; APTIMA Combo 2 Assay and APTIMA GC Assay for N. gonorrhoeae). If the two reference NAATs disagreed or were negative, the patient was designated as non-infected. This is a form of algorithmic adjudication rather than human expert adjudication.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was NOT done. This study evaluates a laboratory diagnostic assay (APTIMA Combo 2 Assay) and does not involve human readers interpreting images or data to be assisted by AI. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

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

• Yes, this was effectively a standalone performance study for the device. The APTIMA Combo 2 Assay, as a nucleic acid amplification test, functions as an algorithm-only device (an in vitro diagnostic test kit that produces a qualitative result based on amplification and detection of rRNA). Its performance was evaluated against a defined ground truth without direct human interpretation in a diagnostic loop that would affect its result. The assay generates a direct qualitative result (positive/negative) which is then used by clinicians for diagnosis.

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

• Algorithm-based Patient Infected Status (Reference NAATs):
  • For C. trachomatis: A patient was considered infected if both the APTIMA Combo 2 Assay and the APTIMA CT Assay (both performed on endocervical swabs) returned positive results.
  • For N. gonorrhoeae: A patient was considered infected if both the APTIMA Combo 2 Assay and the APTIMA GC Assay (both performed on endocervical swabs) returned positive results.
  • A non-infected patient was established if the results from the two reference NAATs disagreed or were negative. This is effectively a composite reference standard based on other validated diagnostic tests.

8. The sample size for the training set:

• The document does not explicitly describe a separate training set for the APTIMA Combo 2 Assay in the context of this submission. The product being submitted for clearance is an existing assay (APTIMA Combo 2 Assay (K003395)) and the clearance sought is an extension of its clinical performance claims to include PreservCyt liquid Pap specimens.
• The non-clinical (analytical) studies (Limit of Detection, Specificity, Interference, Recovery, Stability, Precision) likely involved internal development and optimization, which could be considered an implicit "training" or development phase. However, a distinct "training set" in the machine learning sense is not mentioned. The clinical study described is solely for validation/testing of the assay's performance with the new specimen type.

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

• As a distinct training set is not explicitly mentioned for this 510(k) submission, the method for establishing its ground truth is also not detailed. The ground truth for the non-clinical (analytical) studies typically involved controlled laboratory experiments using known concentrations of organisms and interference substances, with results verified by standard laboratory methods.

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