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Alinity m EBV is an in vitro polymerase chain reaction (PCR) assay for the quantitation of Epstein-Barr Virus (EBV) DNA in human EDTA plasma on the automated Alinity m System.

Alinity m EBV is intended for use as an aid in the management of EBV in transplant patients undergoing monitoring of EBV, serial DNA measurements can be used to indicate the need for potential treatment changes and to assess viral response to treatment.

The results from Alinity m EBV must be interpreted within the context of all relevant clinical and laboratory findings. Alinity m EBV is not cleared for use as a screening test for donors of blood products, or human cells, tissues, and cellular and tissue-based products (HCT/Ps) for EBV.

Alinity m EBV is an in vitro polymerase chain reaction (PCR) assay for the quantitation of EBV DNA in human plasma.

The steps of the Alinity m EBV assay consist of sample preparation, real-time PCR assembly, amplification/detection, result calculation, and reporting. All stages of the Alinity m EBV procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m EBV assay in parallel with other Alinity m assays on the same instrument.

Alinity m EBV requires three separate assay specific kits as follows:

• . Alinity m EBV AMP Kit (List No. 09N43-095) consisting of multi-well amplification trays (AMP Trays) containing lyophilized, unit-dose PCR amplification/detection reagents and multi-well activation trays (ACT Trays) containing liquid, unit-dose activation reagents (MgCl2, TMAC, KCl, and ProClin). The intended storage condition for the Alinity m EBV AMP Kit is 2°C to 8°C.
• Alinity m EBV CTRL Kit (List No. 09N43-085) consisting of a negative control, a low positive control, and a high positive control, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m EBV CTRL Kit is —15°C to —25°C.
• . Alinity m EBV CAL Kit (List No. 09N43-075) consisting of two levels of calibrators (CAL A and CAL B), each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m EBV CAL Kit is -15°C to -25°C.

EBV DNA from specimens is extracted automatically on-board in the Alinity m System using the Alinity m Sample Prep Kit 2, Alinity m Lysis Solution, and Alinity m Diluent Solution. The Alinity m System employs magnetic microparticle technology to facilitate nucleic acid capture, wash and elution. The resulting purified nucleic acids are then combined with the liquid unit-dose Alinity m EBV activation reagent and lyophilized unit-dose Alinity m EBV amplification/detection reagents and transferred into a reaction vessel. Alinity m Vapor Barrier Solution is then added to the reaction vessel which is then transferred to an amplification/detection unit for PCR amplification and real-time fluorescence detection of EBV targets.

An EBV calibration curve is required for the quantitation of EBV targets. Two levels of calibrators are processed through sample preparation and real-time PCR to generate the calibration curve. The concentration of EBV DNA in specimens and controls is then calculated from the stored calibration curve.

Assay controls are tested at or above an established minimum frequency to help ensure that instrument and reagent performance remain satisfactory. During each control event, a negative control, a low-positive control, and a high-positive control are processed through sample preparation and real-time PCR procedures that are identical to those used for specimens.

At the beginning of the Alinity m EBV sample preparation process, a lyophilized unit -dose of Internal Control on the AMP Tray is rehydrated by the Alinity m System and delivered into each sample preparation reaction. The Internal Control is then processed through the entire sample preparation and real-time PCR procedure along with the specimens, calibrators and controls to demonstrate proper sample processing and assay validity.

The Alinity m EBV amplification and detection reagents include primers and probes that amplify and detect dual targets in the EBV genome. Amplification and detection of the two EBV targets ensures sensitive detection of the viral genome even at low levels.

The Alinity m EBV assay also utilizes the following accessories:

• . Alinity m EBV Application Specification File, List No. 09N43-05A
• . Alinity m System and System Software, List No. 08N53-002
• . Alinity m Sample Prep Kit 2, List No. 09N12-001
• . Alinity m Specimen Dilution Kit I, List No. 09N50-001
• . Alinity m Tubes and Caps, List No. 09N49:
  • . Alinity m LRV Tube, List No. 09N49-001
  • Alinity m Transport Tubes Pierceable Capped, List No. 09N49-010 ●
  • Alinity m Transport Tube, List No. 09N49-011 .
  • . Alinity m Pierceable Cap, List No. 09N49-012
  • . Alinity m Aliquot Tube, List No. 09N49-013
• . Alinity m System Solutions, List No. 09N20:
  • . Alinity m Lysis Solution, List No. 09N20-001
  • Alinity m Diluent Solution, List No. 09N20-003 .
  • . Alinity m Vapor Barrier Solution, List No. 09N20-004

Here's a summary of the acceptance criteria and study details for the Alinity m EBV AMP Kit, extracted from the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document describes performance characteristics but doesn't explicitly state "acceptance criteria" for each in a table. Instead, it presents the validated performance values. I've constructed a table based on the key performance metrics and their demonstrated values.

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

• Limit of Detection (LoD) Study (Test Set):
  • Sample Size: 24 replicates per EBV DNA concentration level, tested with 4 lots of amplification reagents. This means 96 replicates for each concentration level shown in Tables 2-5 (24 * 4).
  • Data Provenance: Dilutions of the 1st World Health Organization (WHO) International Standard for Epstein-Barr virus (NIBSC code: 09/260) prepared in EBV negative human plasma. No country of origin is specified for the EBV negative human plasma, but the WHO standard is internationally recognized. This is retrospective/contrived data.
• Linearity Study (Test Set):
  • Sample Size: 16 panel levels (dilution series). Number of replicates per panel level not explicitly stated for individual tests but the figures show mean concentrations.
  • Data Provenance: Dilution series of EBV type 1 (prepared using clinical specimen for lower concentrations, synthetic DNA for higher) and EBV type 2 (prepared using cultured virus for lower concentrations, synthetic DNA for higher) in negative human plasma. Quantitation values traceable to WHO International Standard. This is retrospective/contrived data.
• Precision Study (Test Set):
  • Sample Size: 9-member plasma panel, each panel member tested in 4 replicates, twice each day for 12 days, on 3 systems by 3 operators using 3 AMP kit lots, totaling 288 replicates per panel member.
  • Data Provenance: Panel members prepared with positive clinical sample, cultured virus, or synthetic DNA spiked into EBV negative plasma. This is retrospective/contrived data.
• Analytical Specificity (Test Set):
  • Sample Size: Undisclosed number of individual microorganisms and drug compounds tested in EBV negative plasma and positive plasma (60 IU/mL and 10,000 IU/mL EBV DNA).
  • Data Provenance: Various microorganisms and drug compounds. This is retrospective/contrived data.
• Carryover Study (Test Set):
  • Sample Size: 648 valid replicates of EBV negative samples and 647 valid replicates of high concentrated EBV positive samples.
  • Data Provenance: Contrived EBV negative and high positive samples. This is retrospective/contrived data.
• Clinical Reproducibility Study (Test Set):
  • Sample Size: 9-member reproducibility panel (8 positive, 1 negative). 6 replicates of each panel member tested on each of 5 non-consecutive days for each of 2 reagent lot combinations per site, across 3 clinical sites. (6 * 5 * 2 * 3 = 180 replicates per panel member usually, but tables show 172-180 for positive, 180 for negative).
  • Data Provenance: Positive panel members prepared using EBV positive clinical specimen, cultured virus, or plasmid DNA diluted in human EDTA plasma. This is a mix of retrospective (clinical specimens) and contrived data.
• Clinical Performance Study (Test Set):
  • Sample Size: 558 EDTA plasma samples (542 clinical specimens, 16 contrived).
  • Data Provenance: Clinical specimens from hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) subjects. The 16 contrived samples were prepared by spiking inactivated EBV virus into individual clinical specimens. The text does not specify the country of origin for these clinical specimens, but it's implied they are from a clinical setting. This is a mix of retrospective clinical data and contrived data.

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

The provided text does not explicitly mention the use of human experts or their qualifications to establish ground truth for the test set.

For the analytical studies (LoD, linearity, precision, specificity, carryover), the ground truth was established by:

• Using internationally recognized standards (1st WHO International Standard for EBV).
• Precisely diluting known concentrations of virus or synthetic DNA.
• Using confirmed EBV negative plasma.

For the clinical performance study, the ground truth appears to be established by comparison to an "FDA-cleared EBV nucleic acid test" (the predicate device). The results of the comparator assay served as the reference for agreement analysis.

4. Adjudication Method for the Test Set

No adjudication method (e.g., 2+1, 3+1) is mentioned or implied for any of the studies described. The "ground truth" for the clinical performance study was primarily the results of the FDA-cleared comparator device.

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

No MRMC comparative effectiveness study was done. The device is an in vitro diagnostic (IVD) assay quantifying viral nucleic acid directly, not an imaging device requiring human interpretation, so the concept of human readers improving with AI assistance is not applicable here. The clinical performance section compares the device's quantitative results to those of a predicate IVD device.

6. Standalone Performance Done

Yes, the studies evaluate the standalone performance of the Alinity m EBV assay. The precision, analytical specificity, limit of detection, and linearity are all measures of the algorithm and system's performance without human intervention in the result generation or interpretation beyond operating the instrument and following its procedures. The "Clinical Performance" section compares the standalone device results to a predicate device.

7. Type of Ground Truth Used

• Analytical Studies (LoD, Linearity, Precision, LLoQ, Carryover): Ground truth was established by known, precisely prepared concentrations of EBV (WHO International Standard, cultured virus, synthetic DNA) in EBV negative plasma.
• Analytical Specificity (Cross-Reactants/Interfering Substances): Ground truth was based on the presence of specific microorganisms or substances at known concentrations, with the expectation of no interference.
• Clinical Reproducibility: Similar to precision, ground truth was based on known concentrations of EBV positive clinical specimens, cultured virus, or plasmid DNA in human plasma.
• Clinical Performance: Ground truth was primarily defined by the results of an FDA-cleared predicate EBV nucleic acid test. For a subset, "confirmed EBV DNA negative clinical specimens" were used.

8. Sample Size for the Training Set

The document does not provide information on the training set for the device. As an IVD assay, the development process differs from AI/ML-based algorithms that typically involve explicit training data sets for model development. The assays are developed based on established molecular biology principles (PCR) and optimized through internal R&D, rather than machine learning on a distinct "training set" of patient data.

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

Since no explicit "training set" is mentioned in the context of an AI/ML algorithm, this question is not directly applicable to the information provided for this IVD device. The development and optimization of such assays typically involve laboratory experiments using characterized viral strains, reference materials, and defined concentrations, which would implicitly form the basis for establishing assay parameters and performance.

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The Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay for use with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of disease(s) caused by infection from these organisms. The assay may be used to test the following specimens from symptomatic and asymptomatic individuals for the following analytes:

CT: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, male urine, oropharyngeal swabs, and rectal swabs

NG: vaginal swabs (clinician-collected and self-collected in a clinical setting). endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, male urine, oropharyngeal swabs, and rectal swabs

TV: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, gynecological specimens in ThinPrep PreservCyt Solution, female urine, and male urine

MG: vaginal swabs (clinician-collected and self-collected in a clinical setting), endocervical swabs, and male urine

A vaginal swab (self-collected or clinician-collected) is the preferred specimen type for MG testing in females due to higher clinical sensitivity compared to endocervical swabs. If endocervical swab specimens test negative, testing with a vaginal swab may be indicated if M. genitalium infection is suspected.

The Alinity m STI Assay is a real time polymerase chain reaction (PCR) assay for the amplification and detection of Chlamydia trachomatis (CT) ribosomal RNA sequences, Neisseria gonorrhea (NG) genomic DNA sequences, Trichomonas vaginalis (TV) ribosomal RNA sequences, Mycoplasma genitalium (MG) ribosomal RNA sequences, and human genomic DNA sequences. The assay can be used with endocervical swab specimens, vaginal swab specimens, male and female urine specimens, gynecological specimens in ThinPrep® PreservCyt® Solution, oropharyngeal swab specimens, and rectal swab specimens. Endocervical swab, vaginal swab, oropharyngeal swab, rectal swab and urine specimens are collected with the Alinity m multi-Collect Specimen Collection Kit. PreservCyt Solution specimens are transferred to an Alinity m Transport Tube for processing on the Alinity m System.

The steps of the Alinity m STI Assay consist of sample preparation, RT-PCR assembly, amplification/detection, and result calculation and reporting. All stages of the Alinity m STI Assay procedure are executed automatically by the Alinity m System. No intermediate processing or transfer steps are performed by the user. The Alinity m System is designed to be a random-access analyzer that can perform the Alinity m STI Assay in parallel with other Alinity m assays on the same instrument.

The Alinity m STI Assay requires two separate assay specific kits as follows:

• . Alinity m STI AMP Kit, List No. 09N17-095 consisting of multi-well amplification plates containing lyophilized, unit-dose PCR amplification/detection reagents and multi-well activator plates containing liquid, unit-dose activation reagents (MgCl2, TMAC, and KCl). The intended storage condition for the Alinity m STI AMP Kit is 2℃ to 8℃.
• . Alinity m STI CTRL Kit, List No. 09N17-085 consisting of negative controls and positive controls, each supplied as liquid in single-use tubes. The intended storage condition for the Alinity m STI Control Kit is -15°C to -25°C.

Nucleic acids from specimens are extracted automatically on-board the Alinity m System using the Alinity m Sample Prep Kit 1, Alinity m Lysis Solution, Alinity m Ethanol Solution, and Alinity m Diluent Solution. The Alinity m System employs magnetic microparticle technology to facilitate nucleic acid capture, wash and elution. The resulting purified nucleic acids are then combined with the liquid unit-dose activator reagent, lyophilized unit-dose Alinity m STI amplification reagents, and Alinity m Vapor Barrier Solution, and transferred by the instrument to an amplification/detection module for reverse transcription, PCR amplification, and real-time fluorescence detection.

Assay controls are tested at or above an established minimum frequency of every 24 hours to help ensure that instrument and reagent performance remain satisfactory. During each control event, a negative control and a positive control are processed through sample preparation and RT-PCR procedures that are identical to those used for specimens. Assay controls are used to demonstrate proper sample processing and assay validity. The controls do not indicate if bacterial cells have been adequately lysed.

The Alinity m STI amplification reagents include primers and a probe that amplify and detect the single copy human gene, ß-globin. Amplification and detection of the ß-globin gene demonstrates proper sample processing and adequate sample input. In addition, an exogenous internal control (containing an armored RNA sequence) is included in the lyophilized Alinity m STI amplification reagents to assess amplification efficiency and to confirm that no PCR inhibitors are present in the sample. The cellular control and internal control are both used to demonstrate assay validity.

The Alinity m STI Assay also utilizes the following accessories:

• . Alinity m STI Assay Application Specification File, List No. 09N17-03A
• . Alinity m System and System Software, List No. 08N53-002
• Alinity m Sample Prep Kit 1, List No. 09N18-001 .
• Alinity m multi-Collect Specimen Collection Kit, List No. 09N19-010 .
• . Alinity m Tubes and Caps, List No. 09N49:
  • Alinity m Transport Tubes Pierceable Capped, List No. 09N49-010 .
  • . Alinity m Transport Tube, List No. 09N49-011
  • Alinity m Pierceable Cap, List No. 09N49-012 .
• Alinity m System Solutions, List No. 09N20: .
  • Alinity m Lysis Solution, List No. 09N20-001 .
  • Alinity m Ethanol Solution, List No. 09N20-002 .
  • Alinity m Diluent Solution, List No. 09N20-003
  • Alinity m Vapor Barrier Solution, List No. 09N20-004 •

The Abbott Alinity m STI Assay is an in vitro polymerase chain reaction (PCR) assay used with the automated Alinity m System for the direct, qualitative detection and differentiation of ribosomal RNA from Chlamydia trachomatis (CT), DNA from Neisseria gonorrhoeae (NG), ribosomal RNA from Trichomonas vaginalis (TV), and ribosomal RNA from Mycoplasma genitalium (MG), to aid in the diagnosis of sexually transmitted infections.

The acceptance criteria and the study results are detailed below:

1. Table of Acceptance Criteria and Reported Device Performance

The device performance is reported as Sensitivity (Positive Percent Agreement or PPA) and Specificity (Negative Percent Agreement or NPA). The document does not explicitly state pre-defined acceptance criteria (e.g., a specific threshold like "Sensitivity must be >= X%"). However, the reported performance values are the outcome of the clinical trials conducted to demonstrate the device's effectiveness.

Urogenital Specimens

Extragenital Specimens

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

• Urogenital Specimens: A total of 7,099 male and female subjects were enrolled for the urogenital clinical study. Specimens were collected across 33 geographically diverse sites in the United States, including STI clinics, primary care offices, and gynecology practices. This was a prospective study. Data provenance is United States, from prospective collection.
  • Number of results used in analysis for each analyte:
    • CT: 12,903
    • NG: 15,655
    • TV: 18,843
    • MG: 12,829
• Extragenital Specimens: A total of 2,373 male and female subjects were enrolled. Specimens were previously collected and archived. Data provenance is United States, from archived specimens (retrospective).
  • Number of results used in analysis for each analyte:
    • CT (oropharyngeal): 2,316
    • CT (rectal): 2,053
    • NG (oropharyngeal): 2,312
    • NG (rectal): 2,049

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

The document does not explicitly state the "number of experts" or their "qualifications" involved in establishing the ground truth. Instead, the ground truth was established using comparator assays, which are commercially available nucleic acid amplification tests (NAATs) and, in some cases, culture. The results from these comparator assays were combined to derive a Patient Infected Status (PIS) or Composite Comparator (CC).

4. Adjudication Method for the Test Set

• Urogenital Specimens (PIS):
  • CT or NG (Female): A minimum of 2 positive results (at least 1 from each comparator NAAT) for infection, or at least 1 comparator NAAT reported negative results for all sample types for not infected.
  • TV or MG (Female): First 2 swab comparator NAAT results both positive, or 2 of 3 swab comparator NAAT results positive (if 3rd NAAT was a tie-breaker) for infection. First 2 swab comparator NAAT results both negative, or 2 of 3 swab comparator NAAT results negative (if 3rd NAAT was a tie-breaker) for not infected.
  • CT, NG, TV, or MG (Male): A minimum of two comparator positive results for infection. If the comparator TV culture assay result was positive, the subject was categorized as infected for TV regardless of NAAT results. Two or more comparator NAAT results negative for not infected (for CT, NG, MG). For TV, negative culture AND one or more negative comparator NAATs for not infected.
• Extragenital Specimens (CC): A specimen was categorized as infected (for CT or NG) if a minimum of 2 comparator positive results were reported. It was categorized as not infected if a minimum of 2 comparator negative results was reported.

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

No, an MRMC comparative effectiveness study was not done. The study compares the Alinity m STI Assay's performance against a composite ground truth derived from multiple established comparator assays, not directly evaluating human reader performance with and without AI assistance.

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

Yes, this was a standalone performance study. The Alinity m STI Assay is an automated PCR assay, and its results are directly compared to the established ground truth without involving human interpretation or modifications of its output in the primary performance analysis.

7. The Type of Ground Truth Used

The ground truth used was a Composite Comparator / Patient Infected Status (PIS/CC), derived from the combined results of multiple commercially available and clinically cleared comparator nucleic acid amplification tests (NAATs) and, for male TV, culture results.

8. The Sample Size for the Training Set

The document does not explicitly provide the sample size for the training set for the Alinity m STI Assay. The provided performance data (Sensitivity and Specificity tables) are from the validation (test) sets.

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

Since the document does not provide information about a separate training set, it is assumed that the analytical studies and the design of the assay would have utilized reference materials and potentially early clinical samples for optimization and establishment of analytical performance characteristics (like LoD, inclusivity, cross-reactivity). However, specific details on how ground truth was established for a training set are not available in this document. The clinical studies described are for validation/testing, with ground truth established by comparator assays as detailed in point 4.

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The Abbott RealTime CT/NG assay is an in vitro polymerase chain reaction (PCR) assay for the direct, qualitative detection of the plasmid DNA of Chlamydia trachomatis and the genomic DNA of Neisseria gonorthoeae. The assay may be used to test the following specimens from symptomatic individuals: female endocervical swab, clinician-collected vaginal swab, and patient-collected vaginal swab specimens; 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 vaginal swab and patient-collected vaginal swab specimens; female and male urine specimens.

The Abbott multi-Collect Specimen Collection Kit is intended for the collection and transportation of male and female swab and urine specimens for the detection of Chlamydia trachomatis and Neisseria gonorrheae per instructions provided. Refer to the specimen collection procedure in the package insert for specimen collection instructions for specific sample types.

Self-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Abbott multi-Collect Specimen Collection Kit is not intended for home use.

The Abbott multi-Collect Specimen Collection Kit can be used to collect either a swab or a urine specimen. Each Abbott multi -Collect Specimen Collection Kit contains:

• . One capped Transport Tube containing 1.2 mL Specimen Transport Buffer
• . One Individually Packaged Sterile Specimen Collection Swab
• . One disposable transfer pipette.

The Specimen Transport Buffer is used to stabilize DNA until sample preparation. The individually packaged sterile Specimen Collection Swab is used for swab sample collection and placed directly into the Transport Tube. The transfer pipette is used to add approximately 3 mL of urine to the Transport Tube. The Abbott multi -Collect Specimen Collection Kit is for single use only.

The Abbott multi-Collect Specimen Collection Kit Swab is approximately 14 cm in length with a polyester fiber tip. The swab shaft has a polystyrene solid core that is orange in color. The swab has a molded score completely around the shaft, between 7.86 cm and 7.89 cm from the swab tip, to provide a clean break-point. The polyesterfiber swab tip is approximately 1.3 cm in length and less than 3.28 mm in diameter.

This document describes the regulatory submission for a modification to the Abbott multi-Collect Specimen Collection Kit, specifically a change in the swab fiber component. The submission focuses on demonstrating that the new swab is substantially equivalent to the previously cleared swab and does not impact the performance of the Abbott RealTime CT/NG assay.

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly state "acceptance criteria" in a numerical, threshold-based format. Instead, the studies demonstrate performance relative to the existing device and expected assay performance (e.g., detection rates approaching 100% for low positive samples). The goal of these studies is to confirm that the new swab material does not negatively impact the assay's performance.

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

• Biocompatibility: The specific sample sizes for cytotoxicity, irritation, and sensitization tests are not provided in the summary.
• 90-Day Specimen Stability: Not explicitly stated, but involved testing "simulated high and low positive swab specimens."
• Sample Freeze-Thaw Stability: 90 CT analyte samples and 90 NG analyte samples (total 180 samples) were tested.
• LOD Confirmation: 234 samples were tested for both CT and NG.
• Reproducibility: 189 replicates were tested for each panel member. There were 4 panel members (3 concentrations + 1 negative) for each analyte (CT and NG). This suggests a total of 189 replicates/panel member * 4 panel members * 2 analytes = 1512 individual tests for quantification, or more accurately, 189 replicates per panel member across the different conditions. Seven replicates of each panel member were tested in each run, with nine runs performed across three m2000 instrument systems.
• Accelerated Stressed Swab Stability: Not explicitly stated, but involved "testing simulated low positive swab specimens containing a target concentration of 320 copies of CT and 320 copies of NG in each 400 uL sample preparation input volume."
• Provenance: All data appears to be retrospective experimental data generated in a laboratory setting using simulated specimens rather than prospective clinical samples. The country of origin of the data is not explicitly stated but is implicitly associated with Abbott Molecular Inc. in the USA.

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

No human experts were used to establish the "ground truth" in these studies. The studies are analytical performance studies, not clinical studies involving patient diagnoses. The "ground truth" (e.g., presence and concentration of CT/NG DNA) was established by spiking known concentrations of target analytes into simulated specimens in a laboratory setting.

4. Adjudication Method for the Test Set

Not applicable. As described above, the ground truth was established by precise laboratory spiking of analytes, not by expert consensus or clinical adjudication.

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

No. This is not an MRMC study. The device is a specimen collection kit the performance of which is measured using an in vitro assay (Abbott RealTime CT/NG assay). There are no human readers or interpretation involved in the performance evaluation of the collection device itself. The studies focus on the analytical performance of the kit to collect and preserve DNA for subsequent automated testing.

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

Yes, this is an algorithm-only (assay-only) performance evaluation. The "device" being evaluated is the Abbott multi-Collect Specimen Collection Kit, specifically its swab component. Its performance is assessed by how effectively it allows the Abbott RealTime CT/NG assay (an automated PCR assay) to detect targets. Therefore, the performance demonstrated is that of the collection kit in conjunction with the fully automated assay, without any human interpretation steps directly related to the collection kit's function.

7. The Type of Ground Truth Used

The ground truth used was based on known concentrations of spiked target analytes (DNA for Chlamydia trachomatis and Neisseria gonorrhoeae) in simulated laboratory specimens. This is a form of analytical truth or definitive measurement through controlled experimental design.

8. The Sample Size for the Training Set

These studies are analytical validation studies for a medical device modification (swab component), not a machine learning or AI model development. Therefore, there is no concept of a "training set" in the context of these studies. The experiments described are test/validation studies for the physical collection device.

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

Not applicable, as there was no training set for an AI model.

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The Vysis D7S486/CEP 7 FISH Probe Kit is a device intended for specimen characterization, and detects the LSI D7S486 probe target on chromosome 7q31 and the CEP 7 probe target on chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens from patients with acute myeloid leukemia or myelodysplastic syndrome. The assay results are intended to be interpreted by a qualified pathologist or cytogeneticist. This device is not intended for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening. The use of this device for diagnosis, prognosis, monitoring or risk assessment has not been established.

The Vysis D7S486/CEP 7 FISH Probe Kit is for specimen characterization and detects the LSI D7S486 (7q31) probe target on chromosome 7q31 and CEP 7 probe target chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens.

DNA Probe Description

Vysis LSI D7S486 SpectrumOrange/ CEP 7 SpectrumGreen Probes:

The SpectrumOrange labeled LSI D7S486 probe is approximately 308 kb in length (chr7:115983468-115675366; February 2009 Assembly UCSC Human Genome Browser).

The SpectrumGreen labeled CEP 7 probe targets the D7Z1 alpha satellite sequence at the centromere of chromosome 7.

The Vysis D7S486/CEP 7 FISH Probe Kit (List No. 04N78-020) consists of a mixture of two DNA FISH probes and four general reagents sufficient to process 20 assays.

• . Vysis LSI D7S486 SpectrumOrange/ CEP 7 SpectrumGreen Probes
• . Vysis LSI/WCP Hybridization Buffer
• . DAPI II Counterstain
• NP-40 .
• . 20X SSC

The Vysis D7S486/CEP 7 FISH Probe Kit is designed for specimen characterization, specifically detecting the LSI D7S486 probe target on chromosome 7q31 and the CEP 7 probe target on chromosome 7p11.1-q11.1 in bone marrow and peripheral blood specimens from patients with acute myeloid leukemia or myelodysplastic syndrome.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Analytical Specificity: 4 male and 1 female karyotypically normal specimen slides.
• Analytical Sensitivity and Verification of Upper Reference Limit: 25 bone marrow and 25 peripheral blood specimens. These were from either karyotypically normal individuals or patients lacking monosomy 7 and loss of 7q. The provenance is not explicitly stated (e.g., country of origin, retrospective/prospective).
• Reproducibility (Site-to-Site & Lot-to-Lot): The panel members for the reproducibility studies were prepared by mixing positive cells with normal cells. The exact number of individual patient samples from which these positive and normal cells originated is not specified. The study used 2 high-positive, 2 low-positive, and 2 negative panel members for each specimen type (bone marrow and peripheral blood). The data provenance is not specified as retrospective or prospective, nor is the country of origin explicitly mentioned.

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

• Analytical Specificity: 1 technologist for evaluating metaphase chromosomes.
• Analytical Sensitivity and Verification of Upper Reference Limit: 2 technologists for evaluating interphase nuclei.
• Reproducibility: The ground truth for the reproducibility studies (negative, low positive, high positive categories) was established by mixing positive cells with normal cells to achieve desired levels of positivity, implying a predefined "known status" based on these mixtures. The expertise used to determine the initial "positive cells" or "normal cells" is not detailed.

The qualifications of these technologists/experts are not explicitly stated (e.g., years of experience, specific certifications like "radiologist with 10 years of experience").

4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set

For Analytical Sensitivity and Verification of Upper Reference Limit, the document states that each technologist evaluated 100 nuclei per specimen, implying independent scoring. There is no mention of an adjudication method (like 2+1 or 3+1) if scores differed between the two technologists, nor is an adjudication method specified for other tests.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done, 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 a FISH probe kit, not an AI-assisted diagnostic tool. Therefore, there is no discussion of human reader improvement with or without AI assistance.

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

This is a laboratory diagnostic kit (FISH probe) that requires human interpretation (a qualified pathologist or cytogeneticist). Therefore, a standalone algorithm-only performance assessment is not applicable and was not performed. The performance studies evaluate the kit's analytical characteristics.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

• Analytical Specificity: Karyotypically normal specimens were used, with the "correct locus" pre-defined based on known chromosomal locations.
• Analytical Sensitivity and Verification of Upper Reference Limit: Karyotypically normal individuals or patients lacking the specific abnormalities (monosomy 7 and loss of 7q) were used. The expected typical signal pattern (2R2G) served as the ground truth for normalcy. The "atypical" patterns (1R1G, 1R2G) were defined based on the biological expectation of monosomy 7 or 7q deletion.
• Reproducibility: The ground truth for the panel members was established by preparing mixtures of positive and normal cells to achieve predefined "negative," "low positive," and "high positive" statuses. The origin of the "positive cells" would implicitly be from samples with confirmed deletion 7q or monosomy 7, likely established through standard cytogenetic or FISH methods.

8. The Sample Size for the Training Set

This document describes a diagnostic kit and its analytical validation. It does not refer to a machine learning or AI algorithm development pipeline, so there is no specific mention of a "training set" in the context of algorithm development. The studies performed are for analytical validation.

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

As there is no mention of a "training set" for an algorithm, this question is not applicable. The kit is based on established FISH technology, and its performance is validated through analytical studies.

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The Vysis EGR1 FISH Probe Kit - SC detects the LSI EGR1 probe target on chromosome 5q in bone marrow specimens. The Vysis EGR1 FISH Probe Kit -SC assay results characterize bone marrow specimens from patients with acute myeloid leukemia or myelodysplastic syndrome. The assay results are intended to be interpreted by a qualified pathologist or cytogeneticist. This device is not intended for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening. The use of this product for diagnosis, monitoring or risk assessment has not been established.

The Vysis EGR1 FISH Probe Kit - Specimen Characterization uses fluorescence in situ hybridization (FISH) DNA probe technology to detect probe target LSI EGR1 (containing early growth response 1 gene; location chromosome 5g31). The LSI D5S23, D5S721 probe (location chromosome 5p15.2) serves as a control.

The Vysis EGR1 FISH Probe Kit – SC (List No. 04N37-001) consists of the following components which are sufficient to process 20 assays:

1. Vysis LSI EGR1 SpectrumOrange/D5S23, D5S721 Spectrum Green Probes
2. Vysis LSI/WCP Hybridization Buffer
3. DAPI II Counterstain
4. NP-40
5. 20X SSC Salt

Items 2 through 5 above are general purposes reagents.

DNA Probes: Vysis LSI EGR1 SpectrumOrange/ D5S23, D5S721 SpectrumGreen.

a. The SpectrumOrange-labeled LSI EGR1 probe, approximately 209 kb in length (chr5:137654208-137862738; February 2009 Assembly; UCSC Human Genome Browser) is located at 5g31 and contains the complete EGR1 gene.
b. The SpectrumGreen-labeled LSI D5S23, D5S721 probe, approximately 561 kb in length (chr5:9397109-9958407; February 2009 Assembly; UCSC Human Genome Browser) is located at 5p15.2.

Here's a summary of the acceptance criteria and the studies performed for the Vysis EGR1 FISH Probe Kit - SC, based on the provided text:

Acceptance Criteria and Device Performance for Vysis EGR1 FISH Probe Kit - SC

1. Table of Acceptance Criteria and Reported Device Performance:

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

• Precision/Reproducibility (Intra-Day, Inter-Day, Inter-Site, Lot-to-Lot):
  • Test Set Sample Size: 6 bone marrow specimens (2 high positive, 2 low positive, 2 negative).
  • Nuclei evaluated: 200 nuclei per panel member (100 by each of 2 technologists) for a total of 1200 nuclei per study type (e.g., Intra-day, Inter-day, etc.).
  • Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be prospective analytical testing conducted by the manufacturer.
• Analytical Sensitivity:
  • Test Set Sample Size: 25 bone marrow specimens (karyotypically normal or 5p15 and 5q31 deletion-free).
  • Nuclei evaluated: 200 nuclei per specimen (100 by each of 2 technologists) for a total of 5000 scoreable nuclei.
  • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
• Analytical Specificity:
  • Test Set Sample Size: Metaphase chromosomes prepared from peripheral blood cultures of five karyotypically normal males (pooled).
  • Nuclei evaluated: 100 consecutive metaphase nuclei by one technologist, for a total of 200 target loci (100 for each probe).
  • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
• Reference Range Validation:
  • Test Set Sample Size: 25 bone marrow specimens (karyotypically normal or 5p15.2 and 5q31 deletion-free).
  • Nuclei evaluated: 200 nuclei per specimen (100 by each of 2 technologists).
  • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
• Clinical Supportive Data (Clinical Validity):
  • Test Set Sample Size:
    • Data Source 1 (Sun et al.): 320 bone marrow specimens
    • Data Source 2 (Galvan et al.): 28 bone marrow specimens
    • Data Source 3 (Vance et al.): 181 bone marrow specimens
  • Data Provenance: Retrospective, derived from peer-reviewed published literature (implicitly based on patient data from the respective study locations, not specified).

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

• Analytical Performance Studies (Precision, Sensitivity, Specificity, Reference Range):
  • "Two technologists" or "one technologist" were involved in evaluating nuclei. Their specific qualifications (e.g., "cytogeneticist with X years of experience") are not explicitly stated, beyond being referred to as "technologists."
  • The overall interpretation is intended for a "qualified pathologist or cytogeneticist."
• Clinical Supportive Data:
  • Ground truth for the clinical studies would have been established by the methods described in those published papers, likely involving consensus diagnostics by pathologists and/or cytogeneticists based on conventional cytogenetics and clinical information. The number and qualifications of these experts are not detailed in this summary document.

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

• For the analytical performance studies where two technologists evaluated slides (e.g., Precision, Analytical Sensitivity, Reference Range Validation), the text states "each technologist evaluated 100 nuclei per panel member" or "100 nuclei per specimen." It does not explicitly describe an adjudication method (e.g., 2+1, 3+1) if their readings disagreed. It simply reports aggregated results.

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, an MRMC comparative effectiveness study was not done.
• This device is described as an assay (FISH probe kit) intended to be interpreted by a qualified pathologist or cytogeneticist, not an automated system or AI-assisted diagnostic tool. The text explicitly states: "These devices do not include automated systems that directly report results without review and interpretation by a qualified pathologist or cytogeneticist." Therefore, the concept of human readers improving with AI assistance is not applicable to this submission.

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

• No, a standalone (algorithm only) performance study was not done.
• As noted above, this is a FISH probe kit, which is a laboratory assay requiring manual interpretation by human experts. It is not an algorithm that performs standalone analysis.

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

• Analytical Performance Studies:
  • Expected signal pattern: This serves as the ground truth for parameters like precision and sensitivity. It's based on the known genetic characteristics of the specimens (e.g., high positive, low positive, negative, normal karyotype).
  • Known chromosomal location: For analytical specificity, the ground truth is the established chromosomal location of the gene targets.
• Clinical Supportive Data:
  • The ground truth for the clinical studies (validation of clinical utility) was likely established through a combination of pathology reports, conventional cytogenetics, and clinical diagnoses of AML or MDS as carried out in the respective peer-reviewed studies. The "percentage of cells with 1R2G signal pattern" would have been correlated with these clinical states.

8. The sample size for the training set:

• Not applicable. The Vysis EGR1 FISH Probe Kit is a diagnostic assay (chemical reagents and probes), not a machine learning algorithm. Therefore, there is no "training set" in the context of AI/ML. All samples discussed are for analytical or clinical validation/support.

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 Vysis EGR1 FISH Probe Kit is intended to detect deletion of the LSI EGR1 probe target on chromosome 5q in bone marrow specimens and to be used, in addition to cytogenetics, other biomarkers, morphology and other clinical information, at the time of acute myeloid leukemia (AML) diagnosis as an aid in determining prognosis. Deletion of chromosome 5q has been associated with an unfavorable prognosis in AML patients.

The Vysis EGR1 FISH Probe Kit uses fluorescence in situ hybridization (FISH) DNA probe technology to determine deletion status of the LSI EGR1 (containing early growth response 1 gene; location chromosome 5q31) probe target in AML specimens. The Vysis EGR1 FISH Probe Kit also contains the LSI D5S23, D5S721 probe (location chromosome 5p15.2) and serves as a control. The kit consists of one vial containing two DNA FISH probes and four general purpose reagents sufficient to process 20 specimens.

Here's a summary of the acceptance criteria and the study details for the Vysis EGR1 FISH Probe Kit, based on the provided text:

Vysis EGR1 FISH Probe Kit: Acceptance Criteria and Study Details

1. Table of Acceptance Criteria and Reported Device Performance

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

• Analytical Specificity: Metaphase chromosomes from 5 karyotypically normal males.
• Analytical Sensitivity: Interphase nuclei from 25 bone marrow specimens (karyotypically normal or 5p15 and 5q31 deletion-free).
• Verification of Normal Cut-off: Interphase nuclei from 25 bone marrow specimens (karyotypically normal or 5p15.2 and 5q31 deletion-free).
• Reproducibility (Site-to-Site): 2 high-positive, 2 low-positive, and 2 normal specimens (bone marrow cells mixed to create positive controls).
• Reproducibility (Lot-to-Lot): Same 2 high-positive, 2 low-positive, and 2 normal specimens.
• Clinical Utility (Agreement with Karyotype): 181 bone marrow specimens from an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900) for AML diagnosis. This appears to be retrospective data from a specific clinical trial. The country of origin is implied to be the US given the ECOG trial.

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

• Analytical Specificity: "one technologist" evaluated 100 metaphase nuclei per sample. No specific qualifications are provided for this technologist beyond being a "technologist."
• Analytical Sensitivity: "two technologists" evaluated 100 nuclei per specimen. No specific qualifications provided.
• Verification of Normal Cut-off: "two technologists" evaluated 100 nuclei per specimen. No specific qualifications provided.
• Clinical Utility (Agreement with Karyotype): The ground truth for this section is based on "karyotype" results. While the text refers to a publication by Vance et al. from an ECOG clinical trial, it does not explicitly state the number or qualifications of the experts establishing the karyotype ground truth for this specific study. However, karyotyping is a specialized cytogenetic analysis performed by trained professionals (cytogeneticists/pathologists).

4. Adjudication Method for the Test Set

• Analytical Specificity, Sensitivity, Normal Cut-off: The text mentions evaluation by one or two technologists. For cases where two technologists evaluated, it doesn't explicitly state an adjudication method if discrepancies occurred. It simply states "Each technologist evaluated..." or "evaluated by two technologists." This suggests independent evaluation, but no formal adjudication process is described for reconciling differences.
• Reproducibility: A mean and standard deviation were calculated across replicates and sites/lots, indicating a statistical comparison of results, not a consensus-based adjudication of individual cases.
• Clinical Utility (Agreement with Karyotype): The comparison is against established karyotype results, which are considered the ground truth. There's no further adjudication stated for these 181 specimens beyond that initial karyotype.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done comparing human readers with AI assistance vs. without AI assistance. This device is a FISH probe kit, not an AI-assisted diagnostic tool.

6. Standalone (Algorithm Only) Performance

This device is a physical FISH probe kit designed for laboratory use with microscopic interpretation by trained personnel. It does not involve a standalone algorithm or AI for interpretation. Performance metrics like analytical specificity, sensitivity, and reproducibility are for the kit's ability to produce expected signal patterns when interpreted by human technologists.

7. Type of Ground Truth Used

• Analytical Specificity: Metaphase chromosomes from karyotypically normal individuals, with "correct locus" hybridization serving as the ground truth.
• Analytical Sensitivity: Expected normal signal pattern (2R2G) in interphase nuclei from karyotypically normal or deletion-free bone marrow specimens.
• Verification of Normal Cut-off: Normal bone marrow specimens that were karyotypically normal or 5p15.2 and 5q31 deletion-free.
• Reproducibility: Known status of specimens (high-positive, low-positive, normal) created by mixing positive and normal bone marrow cells.
• Clinical Utility (Agreement with Karyotype): Cytogenetic results (karyotype) from clinical AML diagnosis ("-5/del5q" vs. normal karyotype).

8. Sample Size for the Training Set

The document does not explicitly describe a separate "training set" in the context of machine learning or algorithm development, as this device is a probe kit. The studies described are for analytical validation and clinical correlation.

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

Not applicable, as there's no mention of a traditional "training set" for an algorithm in this submission. The validation studies rely on established biological principles and comparisons to conventional cytogenetic methods.

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The Vysis CLL FISH Probe Kit is intended to detect deletion of the LS1 TP53, LSI ATM, and LSI D13S319 probe targets and gain of the D12Z3 sequence in peripheral blood specimens from untreated patients with B-cell chronic lymphocytic leukemia (CLL). The assay may be used to dichotomize CLL (the 13q-, +12, or normal genotype group versus the 11q- or 17p- group) and may be used as an aid in determining disease prognosis in combination with additional biomarkers, morphology, and other clinical information. The Vysis CLL FISH Probe Kit is not intended for use in selection of therapy or in monitoring of residual disease.

The Vysis CLL FISH Probe Kit uses fluorescence in situ hybridization (FISH) DNA probe technology to determine deletions of the locus-specific identifier (LSI) TP53, LSI ATM, and LSI D13S319 probe targets and gain of the D12Z3 sequence.

The Vysis CLL FISH Probe Kit (List No. 4N02-020) consists of two DNA FISH probe sets and three general purpose reagents sufficient to process 20 assays.

• . LSI TP53 SpectrumOrange/ATM SpectrumGreen Probe
• LSI D13S319 SpectrumOrange/13q34 SpectrumAqua/CEP 12 SpectrumGreen Probe .
• DAPI II Counterstain .
• NP-40 .
• 20X SSC Salt .

Here's a summary of the acceptance criteria and the study details for the Vysis CLL FISH Probe Kit, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

Note: The 510(k) summary for the Vysis CLL FISH Probe Kit primarily focuses on analytical performance (specificity, sensitivity, normal cut-off values, precision, reproducibility) and concordance with an existing clinical assay rather than traditional "acceptance criteria" related to a new AI/CADe device. The provided tables outline the device's technical performance.

Study Details

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

   • Analytical Specificity: 5 karyotypically normal male peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Analytical Sensitivity: 25 karyotypically normal patient peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Analytical Characterization of Normal Cut-off Values: 25 karyotypically normal patient peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Precision:
     • Precision Study 1: 2 negative peripheral blood specimens (lacking abnormalities) and 8 additional specimens with at least one abnormality. Likely retrospective, but not explicitly stated.
     • Precision Study 2: 8 different patient specimens (blinded panel). Likely retrospective, but not explicitly stated.
   • Reproducibility: A blinded 20-member slide panel representing five Döhner classifications. Likely retrospective, but not explicitly stated.
   • Method Concordance: 64 specimens with pre-established Döhner classifications. Retrospective, as classifications were "based on previous results using the RFT." Provenance not explicitly stated.

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

   • Analytical Specificity: One technologist. Qualifications not specified beyond being a "technologist."
   • Analytical Sensitivity: Not explicitly stated, but each technologist evaluated 100 nuclei per specimen, implying multiple technologists were involved. Qualifications not specified.
   • Analytical Characterization of Normal Cut-off Values: Not explicitly stated, but implies multiple technologists based on the sensitivity study. Qualifications not specified.
   • Precision: Not specified, but involved counting signals, implying trained technologists.
   • Reproducibility: Not specified, but involved three different laboratories, implying multiple trained personnel.
   • Method Concordance: The "Reference FISH Test (RFT)" was used to establish initial Döhner classifications. The original Shanafelt study (referred to as the RFT) implies multiple pathologists/cytogeneticists. This study used "previous results" from the RFT as its ground truth.

3. Adjudication method for the test set:

   • No formal adjudication method (like 2+1 or 3+1) is explicitly described for establishing the ground truth or validating results in the analytical studies. Results were typically enumerated by technologists and aggregated.
   • For the Reproducibility study, "overall agreement" between three testing sites was assessed, but a specific adjudication process for discrepancies is not detailed beyond reporting disagreement counts.
   • For Method Concordance, the ground truth was the "Reference FISH Test (RFT) used in the Shanafelt study," which effectively served as the gold standard, and the AMT results were compared against it.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

   • No MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was reported. This device is a FISH probe kit, not an AI-powered diagnostic system. The studies focused on the analytical and clinical validity of the probe kit itself.

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

   • This is not an algorithm-only device. It is a laboratory assay (FISH probe kit) where human technologists perform the analysis by counting fluorescent signals under a microscope. The studies performed were of the laboratory kit's performance, not an automated algorithm.

6. The type of ground truth used:

   • Analytical Specificity, Sensitivity, Normal Cut-off, Precision: Based on visual identification and enumeration of FISH signals by trained technologists, comparing observed signal patterns to expected normal or abnormal patterns in karyotypically normal and patient samples. The "expected normal" pattern serves as a form of expert-derived ground truth.
   • Reproducibility: Comparison of results across multiple labs/readers for the same samples. The "agreement" between sites implies a consensus or majority rule for comparison, but the ultimate ground truth for a given sample's true Döhner classification is not explicitly detailed but likely derived from expert pathological/cytogenetic review.
   • Method Concordance: The ground truth was established by a "Reference FISH Test (RFT) used in the Shanafelt study," which is stated to have its clinical validity documented via peer-reviewed literature. This implies a ground truth based on established clinical and pathological diagnosis as determined by a validated method.

7. The sample size for the training set:

   • This device is a diagnostic kit, not an AI/machine learning algorithm, so there is no "training set" in the conventional sense of AI development. The studies described are for analytical validation and clinical concordance.

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

   • Since there's no AI "training set," this question is not applicable. The device's performance characteristics (specificity, sensitivity, cut-offs) are established through testing on defined sets of samples (e.g., karyotypically normal individuals, patients with confirmed CLL aberrations) where the expected outcome is known or determined by expert review using established cytogenetic methods.

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The Abbott RealTime CT/NG (List No. 8L07-91) assay is an in vitro polymerase chain reaction (PCR) assay for the direct, qualitative detection of the plasmid DNA of Chlamydia trachomatis and the genomic DNA of Neisseria gonorrhoeae. The assay may be used to test the following specimens from symptomatic individuals: female endocervical swab, clinician-collected vaginal swab, and patient-collected vaginal swab specimens; 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 vaginal swab and patient-collected vaginal swab specimens; female and male urine specimens.

Abbott RealTime CT/NG consists of two reagent kits:

• · Abbott RealTime CT/NG Amplification Reagent Kit (List No. 8L07-91)
• · Abbott RealTime CT/NG Control Kit (List No. 8L07-80)
  The Abbott RealTime CT/NG assay uses PCR technology with homogenous real-time fluorescence detection on the m2000 System. The Abbott m2000 System consists of the Abbott m2000sp and Abbott m2000rt instruments. The Abbott m2000 System integrates sample preparation with nucleic acid amplification and detection to generate assay results. The Abbott m2000sp is used for processing samples and the Abbott m2000rt is used for amplification and detection.

Abbott RealTime CT/NG Assay: Acceptance Criteria and Supporting Study

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Abbott RealTime CT/NG assay are implied by the reported clinical sensitivity and specificity for various specimen types and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection. While explicit numerical acceptance criteria are not stated in the provided text, the reported performance values demonstrate the device's efficacy.

Table 1: Clinical Performance of Abbott RealTime CT/NG Assay

2. Sample Size and Data Provenance (Clinical Study)

• Sample Size for Test Set: A total of 3,832 male and female subjects were enrolled in the multi-center clinical study. For the analysis of the Abbott RealTime CT/NG assay, 6,555 CT results and 6,569 NG results were used.
• Data Provenance: The study was conducted in the United States across 16 geographically diverse sites, including physician private practices, public and private STD clinics, and a hospital emergency room. The study design implies a prospective collection of specimens from enrolled subjects, although it's not explicitly stated as retrospective or prospective in every detail of the summary. The phrase "Specimens were collected from subjects at...sites" supports a prospective approach for the clinical data.

3. Number of Experts and Qualifications (Ground Truth)

The document does not explicitly state the "number of experts" or their specific "qualifications" used to establish the ground truth in the clinical study. Instead, the ground truth was established by comparing the Abbott RealTime CT/NG assay to reference assays.

4. Adjudication Method (Test Set)

The adjudication method for determining the "patient infected status" (ground truth) was based on a combination of reference assay results:

• For CT or NG (Female Subjects): A female was categorized as infected if a minimum of two positive results were reported (at least one from each reference NAAT). A specific condition was also applied for CT: if reference urine specimens were positive and all three reference swab specimens were negative, the subject was considered infected for urine but not swab specimens.
• For CT or NG (Male Subjects): A male was categorized as infected if a minimum of two positive results were reported.
• For NG (All Subjects): If the reference NG culture assay result was positive, the subject was categorized as infected regardless of NAAT results.
• Non-Infected Status: For females, non-infected status was assigned if at least one reference NAAT reported negative results for all sample types AND the NG culture was negative. For males, at least two negative results from reference NAATs AND a negative NG culture result were required for non-infected status.
• Subjects with missing and/or indeterminate results from reference assays were excluded from the analysis (4 subjects for CT and 7 subjects for NG).

This multi-assay, rule-based approach serves as the adjudication method for establishing the ground truth.

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

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was mentioned in the provided document. The study is focused on the standalone performance of the Abbott RealTime CT/NG assay against established reference methods, not on comparing human reader performance with and without AI assistance.

6. Standalone Performance (Algorithm Only)

Yes, a standalone performance study was done. The entire clinical study described, measuring the sensitivity and specificity of the Abbott RealTime CT/NG assay against reference methods, represents the standalone performance of the algorithm. The results are summarized in Table 1 above, as well as Tables 3.10-3.13 in the original document.

7. Type of Ground Truth Used

The ground truth used for the clinical study was established by expert consensus using a combination of reference assays:

• Two commercially available Nucleic Acid Amplification Tests (NAATs) for CT and NG.
• Culture for NG.

This is a composite reference standard or adjudicated clinical truth based on multiple established diagnostic methods.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" or "training data" in the context of the Abbott RealTime CT/NG assay development or validation. This is expected given that the device is an in-vitro diagnostic (IVD) PCR assay, which typically relies on analytical validation and clinical performance studies described here, rather than machine learning models that require distinct training and test sets. The presented clinical study serves as the primary validation of the device's performance.

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

As noted above, the document does not refer to a distinct "training set." The Limit of Detection (LOD) and analytical sensitivity studies (Sections 3.14.1), which involve testing known concentrations of CT and NG target DNA and isolates, can be considered part of the analytical validation that informs the assay's performance characteristics. For these analytical studies:

• Known concentrations of CT and NG target DNA were used.
• Dilutions of various CT serovars and NG isolates were tested.

This is a form of defined analytical ground truth based on controlled laboratory preparations of the target organisms. For the clinical performance, the ground truth was established by the composite reference standard from the clinical study as detailed in point 7.

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The Abbott m2000 system is intended for in vitro diagnostic use in performing FDA cleared and approved nucleic acid testing in clinical laboratories. It comprises the Abbott m2000sp and the Abbott m2000rt instruments. The Abbott m2000sp is an automated system for performing sample preparation for nucleic acid testing. The Abbott m2000rt is an automated system for performing fluorescence-based PCR to provide quantitative and qualitative detection of nucleic acid sequences.

The Abbott m2000 System is an instrument platform that automates steps to perform nucleic acid amplification assays from sample processing through amplification, detection, and data reduction. The Abbott m2000 System comprises the m2000sp and m2000rt instruments, which are operated with separate System Control Center (SCC) workstations. Each instrument contains an independent software application; one for the m2000sp and a second for the m2000rt. The m2000sp instrument is a floor standing, automated sample preparation system. The three main components of the m2000sp are the: Instrument, Cabinet, System Control Center (SCC). The m2000rt instrument is a real-time PCR thermal cycler/reader instrument system. The two main components of the m2000rt are the: Instrument, System Control Center (SCC). The Abbott m2000 System software processes sample preparation and amplification/detection protocols based on pre-determined, assay-specific parameters that are contained in individual assay application specification files that are installed on the SCC. The Abbott m2000sp reads and processes bar coded primary sample tubes and processes up to 96 specimens, controls, and calibrators in batch mode. The m2000 System is capable of processing samples from various matrices, depending on the specific assay application, including plasma, serum, endocervical swabs, urethral swabs, vaginal swabs, and urine. At the completion of the automated sample preparation protocol, the operator seals and manually transfers the PCR plate to the Abbott m2000rt for nucleic acid detection. Bar code and m2000sp data is transferred to the m2000rt electronically.

The Abbott m2000 System is an automated instrument platform intended for in vitro diagnostic use in performing FDA-cleared and approved nucleic acid testing in clinical laboratories. This includes the Abbott m2000sp (automated sample preparation) and m2000rt (automated fluorescence-based PCR for quantitative and qualitative detection of nucleic acid sequences). The system was evaluated in conjunction with the Abbott RealTime CT/NG assay.

Here's an analysis of the acceptance criteria and the study that proves the device meets them:

1. Table of Acceptance Criteria and Reported Device Performance

While explicit "acceptance criteria" are not presented as a direct table in the provided document, the study aims to demonstrate substantial equivalence to predicate devices and establish performance characteristics. The key performance metrics reported are sensitivity and specificity for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG).

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

• Test Set (Clinical Study):
  • 3,832 male and female, asymptomatic and symptomatic subjects.
  • 3,832 subjects provided urine, endocervical swabs, self-collected vaginal swabs, and clinician-collected vaginal swabs (females) or urine and urethral swabs (males).
  • A total of 6,555 CT results and 6,569 NG results were used in the analysis after excluding subjects for whom patient infected status could not be determined (4 for CT, 7 for NG).
• Data Provenance: Prospective, multi-center clinical study conducted in the United States. Specimens were collected from 16 geographically diverse sites, including physician private practices, public and private STD clinics, and a hospital emergency room.

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 who established the ground truth in the traditional sense (e.g., radiologists interpreting images). Instead, the ground truth was established through a reference standard composed of multiple commercially available nucleic acid amplification tests (NAATs) and culture for NG.

• For CT or NG infection in females: A minimum of two positive results (at least one from each reference NAAT).
• For CT in females (urine/swab discrepancy): Positive urine and negative endocervical swab from both reference assays resulted in categorization as infected for urine but not for swab specimens.
• For CT or NG infection in males: A minimum of two positive results were reported.
• For NG infection (regardless of NAAT) if NG culture positive: If the reference NG culture assay result was positive, the subject was categorized as infected regardless of NAAT results.
• For non-infection in females: At least one of the reference NAATs reported negative results for all sample types AND if the NG culture assay result was negative.
• For non-infection in males: A total of at least two negative results reported by the reference NAATs AND if the NG culture assay result was negative.

Therefore, the "ground truth" was established by a consensus of FDA-cleared diagnostic assays rather than individual expert interpretation.

4. Adjudication Method for the Test Set

The adjudication method for determining "patient infected status" (ground truth) was a composite reference standard based on the results of two commercially available NAATs and culture for NG. It essentially used a "2 out of 2" or "2 out of 3" (for NG cases with culture) positive rule for infection, and a "negative across multiple tests" rule for non-infection. In cases of internal discrepancy, specific rules were applied (e.g., for female CT urine vs. swab).

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, an MRMC comparative effectiveness study involving human readers and AI assistance was not mentioned. This device is an automated in vitro diagnostic system, not an AI-powered diagnostic imaging or interpretation tool designed to assist human readers. Its performance is evaluated as a standalone diagnostic.

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

Yes, the clinical study primarily evaluated the standalone performance of the Abbott RealTime CT/NG assay on the Abbott m2000 System. The reported sensitivity and specificity values are for the assay and system independent of human interpretation beyond typical lab procedures and result reporting.

7. The Type of Ground Truth Used

The ground truth used was a composite reference standard based on the results of:

• Two commercially available nucleic acid amplification tests (NAATs) for CT and NG.
• Culture for NG.

This is a frequently used method for establishing ground truth for infectious disease diagnostics when a single "gold standard" may not always be definitive. It combines multiple reliable diagnostic methods to increase confidence in the true infection status.

8. The Sample Size for the Training Set

The document does not explicitly specify a "training set" size for the Abbott RealTime CT/NG assay and m2000 system. For in vitro diagnostic devices like this, the development process (which would involve data akin to training) is typically extensive and proprietary, focusing on analytical performance and robustness. The clinical study described would be analogous to an independent validation or test set.

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

Since a dedicated "training set" with ground truth establishment in the AI/machine learning sense is not detailed, this question applies less directly. However, the development of the assay would inherently involve:

• Analytical studies: Determining Limit of Detection (LOD), analytical sensitivity (serovars, isolates), cross-reactivity, and interference using well-characterized samples (e.g., quantified pure cultures, spiked samples). The ground truth for these analytical studies is based on known concentrations of targets and the presence/absence of interfering substances or cross-reactants. These studies are detailed in Section 9.0 "Summary of Non-Clinical Testing."

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The Abbott RealTime CT/NG assay is an in vitro polymerase chain reaction (PCR) assay for the direct, qualitative detection of the plasmid DNA of Chlamydia trachomatis and the genomic DNA of Neisseria gonorrhoeae. The assay may be used to test the following specimens from symptomatic individuals: clinician-collected vaginal swab and male urethral swab specimens; patient-collected vaginal swab specimens; and female and male urine specimens. The assay may be used to test the following specimens from asymptomatic individuals: male and female urine.

The Abbott multi-Collect Specimen Collection Kit is intended for the collection and transportation of malc and female swab and urine specimens for the detection of Chlamydia trachomatis and Neisseria gonorrheae per instructions provided.

Self-collected vaginal swab specimens are an option for screening women when a pelvic exam is not otherwise indicated. The Abbott multi-Collect Specimen Collection Kit is not intended for home use.

Abbott RealTime CT/NG consists of two reagent kits:

• . Abbott RealTime CT/NG Amplification Reagent Kit (List No. 8L07-90)
• Abbott RealTime CT/NG Control Kit (List No. 8L07-80) .

The Abbott RealTime CT/NG assay uses PCR technology with homogenous real-time fluorescence detection on the m2000 System. The Abbott m2000 System consists of the Abbott m2000sp and Abbott m2000rt instruments. The Abbott m2000 System integrates sample preparation with nucleic acid amplification and detection to generate assay rcsults. The Abbott m2000sp is used for processing samples and the Abbott m2000rt is used for amplification and detection.

The Abbott multi-Collect Specimen Collection Kit can be used to collect either a swab or a urine specimen. Each Abbott multi -Collect Specimen Collection Kit (List No. 9K12) contains:

• One Transport Tube containing 1.2 mL Specimen Transport Buffer .
• . One Individually Packaged Sterile Specimen Collection Swab (Part No. CD650)
• . One disposable transfer pipette.

The Specimen Transport Buffer consists of guanidine thiocyanate, a chaotropic salt, in Tris buffer and is used to stabilize DNA until sample preparation. The individually packaged sterile Specimen Collection Swab is used for swab sample collection and placed directly into the Transport Tube. The transfer pipette is used to add approximately 3 mL of urine to the Transport Tube. The Abbott multi -Collect Specimen Collection Kit is for single use only.

Here's an analysis of the acceptance criteria and supporting studies for the Abbott RealTime CT/NG assay and Abbott multi-Collect Specimen Collection Kit, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implied by the reported clinical performance. The goal is to achieve high sensitivity and specificity compared to reference methods. The specific acceptance thresholds are not explicitly stated as numerical targets for sensitivity and specificity in the provided text, but the reported performance values are presented as demonstrating effective detection.

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

• Sample Size for Test Set: A total of 3,832 male and female subjects were enrolled in the multi-center clinical study.
• Data Provenance: The data was collected prospectively from subjects at 16 geographically diverse sites in the United States. The sites included physician private practices, public and private STD clinics, and a hospital emergency room.

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

The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that the ground truth was "determined based on the combined results from the reference assays." While these reference assays are commercially available NAATs and culture, the interpretation or consensus process by human experts is not described.

4. Adjudication Method (for the test set)

The adjudication method used to establish the "patient infected status" (ground truth) was a consensus-based approach using multiple reference assays:

• For females: A subject was categorized as infected for CT or NG if a minimum of two positive results (at least one from each reference NAAT) were reported.
• For males: A subject was categorized as infected for CT or NG if a minimum of two positive results were reported.
• For NG specifically (both sexes): If the reference NG culture assay result was positive, the subject was categorized as infected regardless of NAAT results.
• Not infected status:
  • Female: At least one of the reference NAATs reported negative results for all sample types.
  • Male: A total of at least two negative results were reported by the reference NAATs.
• Subjects with missing and/or indeterminate results from reference assays were excluded (33 for CT, 35 for NG).

This represents a form of consensus ground truth, leaning towards a "2 out of X positive" rule for infection status, with culture having overriding power for NG.

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 device is an in vitro diagnostic (IVD) assay designed for direct, qualitative detection using PCR technology, not an AI-assisted diagnostic tool that would involve human readers interpreting AI output. Therefore, there is no discussion of human reader improvement with or without AI assistance.

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

Yes, the clinical performance data presented (sensitivity and specificity tables) represents the standalone performance of the Abbott RealTime CT/NG assay (algorithm/device only). The assay itself performs the detection and reporting of qualitative results without a human interpretation loop of the assay's direct output.

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

The ground truth used was expert consensus based on multiple reference assays, specifically a combination of:

• Two commercially available nucleic acid amplification tests (NAATs) for CT and NG.
• Culture for NG.

8. The Sample Size for the Training Set

The document does not explicitly state a "training set" size for the clinical studies. For IVD assays like this, the development process typically involves internal analytical verification and validation, possibly using characterized samples or spiked samples, but these are generally not referred to as a "training set" in the same way as machine learning models. The reported clinical study of 3,832 subjects serves as the test set for performance evaluation.

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

Since a "training set" in the machine learning sense is not explicitly described or used for this IVD assay according to the provided text, the method for establishing its ground truth for training is not applicable. The device's "training," if interpreted as its development and optimization, would have involved extensive analytical studies (e.g., analytical sensitivity, specificity, interference) using well-characterized samples, which are distinct from the clinical performance evaluation.

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