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CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2)
The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
• · To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 3)
The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• · To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)
The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• · To provide epidemiological information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

Here's a breakdown of the acceptance criteria and study information for the CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are primarily related to analytical sensitivity (Limit of Detection - LOD) and inclusivity for various influenza A strains, and analytical specificity (cross-reactivity and exclusivity). The clinical performance evaluation also serves as a form of acceptance criteria for positive and negative agreement with previously characterized samples.

Study Details:

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

• LOD Equivalency & Confirmation:

  • Sample Size: Varies by virus strain and specific assay. For LOD equivalency, triplicate samples of serial dilutions were tested. For LOD confirmation, 20 individually extracted samples were tested for each target.
  • Data Provenance: Virus strains are identified by name and origin (e.g., A/Michigan/45/2015, A/Illinois/20/2018, A/Hong Kong/4801/2014, A/Abu Dhabi/240/2018, A/duck/Vietnam/NCVD-1544/2012, A/duck/Vietnam/NCVD-17A231/2016). Specific country of origin for all strains is not explicitly stated but implied from nomenclature.
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized virus stocks.

• Inclusivity:

  • Sample Size: 10 influenza A(H1N1)pdm09 viruses and 24 influenza A viruses of various types/subtypes. Each virus sample was tested in triplicate.
  • Data Provenance: Virus strains represented temporal, geographic, and genetic diversity (e.g., A/Florida/81/2018, A/Alaska/35/2018, A/Switzerland/8060/2017).
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized virus stocks.

• Analytical Specificity (Cross-Reactivity & Exclusivity):

  • Sample Size: Cross-reactivity: Various influenza viruses (e.g., A/Perth/16/2009, B/Maryland/15/2016) tested in triplicate. Exclusivity: 35 organisms (16 viruses, 18 bacteria, 1 yeast) tested.
  • Data Provenance: Organisms are identified by strain name.
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized stocks of various organisms.

• Clinical Performance Evaluation:

  • Sample Size:
    • Modified InfA Assay: 62 positive (35 A(H1N1)pdm09, 27 A(H3N2)) and 50 negative residual human respiratory clinical specimens.
    • Modified pdmInfA and pdmH1 Assays: 35 positive (for A(H1N1)pdm09) and 50 negative residual human respiratory clinical specimens.
  • Data Provenance: Residual human respiratory clinical specimens collected from patients during previous influenza seasons in the United States (2011-12 and 2013-14).
  • Retrospective/Prospective: Retrospective.

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

The document does not specify the number or qualifications of experts used to establish ground truth. For the analytical studies (LOD, inclusivity, specificity), the ground truth is based on the known identity and titer of the cultured virus or bacterial/yeast strains. For the clinical performance evaluation, the ground truth for "positive" or "negative" status was established by prior testing (comparator) with the FDA-cleared CDC Human Influenza Real-Time RT-PCR Diagnostic Panel (K190302), which implicitly would have been validated using established laboratory methods or expert consensus in its own clearance process.

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

No explicit adjudication method (like 2+1 or 3+1 consensus) is described. The analytical studies often cite "number of positive replicates out of three total replicates tested," implying a direct comparison to the expected outcome from the known sample. For clinical studies, the comparator is the already FDA-cleared predicate 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

This is not applicable. The device is an in vitro diagnostic real-time RT-PCR diagnostic panel, not an AI-assisted diagnostic tool that humans interpret. There are no "human readers" in the context of interpreting the device's output, nor is there a multi-reader multi-case study described.

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

Yes, the studies described are standalone because the device itself is a diagnostic assay (a collection of reagents and controls) that produces a result (detection/characterization of viral RNA) through a real-time RT-PCR instrument. While laboratory personnel operate the instrument and interpret the output, the core performance studies evaluate the assay's ability to detect the target without human intervention influencing the assay's chemical and enzymatic reactions. The term "algorithm" is not directly applicable in the same way as with AI software, but the assay's 'logic' for detection is intrinsic to its design.

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

• For Analytical Studies (LOD, Inclusivity, Specificity): The ground truth is based on known, characterized viral and microbial strains with established titers (e.g., TCID50/mL or EID50/mL) or concentrations (CFU/mL, ng/µL). This is a highly controlled laboratory ground truth.
• For Clinical Performance Evaluation: The ground truth was established by prior testing with the FDA-cleared CDC Human Influenza Real-Time RT-PCR Diagnostic Panel (K190302), acting as the comparator or reference method for the collected residual human respiratory clinical specimens.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI. This device is a RT-PCR based assay, and its development would typically involve empirical optimization and validation against a variety of known strains and clinical samples rather than a formal training set for an AI model.

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

As there is no explicit "training set" described for an AI model, this question is not directly applicable. For the development and optimization of the RT-PCR assays, ground truth for evaluating probe and primer design would have been established through a combination of sequencing data to identify conserved regions and target specificity, and testing against known, characterized viral isolates/strains to ensure desired reactivity.

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The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3), and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR ) assays on an in vitro diagnostic realtime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR ) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

Here's a breakdown of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document focuses on demonstrating substantial equivalence of the modified device (with new PCR instruments) to a predicate device. The key acceptance criteria are related to analytical sensitivity (Limit of Detection or LOD) and reproducibility, and clinical agreement.

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

• Analytical Sensitivity (LOD):

  • For each virus type and dilution: Triplicate samples were tested. The testing involved multiple influenza viruses (e.g., A/H3N2, A/H1N1pdm09, B/Victoria, B/Yamagata, A/H5N8) and two enzyme systems (SuperScript and qScript) across the original instrument and the two new instruments. It's difficult to give a single "sample size" number but it involved a substantial number of replicates across various conditions to establish LOD.
  • Data Provenance: The samples were "characterized influenza viruses of known egg infectious dose 50% titer," diluted in BPL-treated A549 cells in viral transport medium (VTM). This indicates laboratory-prepared, controlled samples.

• Analytical Precision (Reproducibility):

  • Sample Size: A blinded panel of 5 contrived samples (moderate positive A/H3N2, moderate positive B/Victoria, negative, low positive A/H3N2, low positive B/Victoria). Each sample was tested by two analysts at each of three sites, over five different days. This means for each contrived sample, there were $3 \text{ sites} \times 2 \text{ analysts} \times 5 \text{ days} = 30$ results. Across the 5 samples this totals $5 \text{ samples} \times 30 \text{ tests/sample} = 150$ tests for the QSDx and 150 for the QMDx.
  • Data Provenance: Contrived samples (BPL-treated A549 cells in VTM, spiked with BPL-treated influenza A(H3N2) or B/Victoria virus).

• Carryover and Cross-contamination:

  • Sample Size: An alternating pattern of high positive (HP) and negative (N) contrived samples. There were 5 high positive samples and 5 negative samples tested across 5 runs. The tables show 5 sets of HP samples and 5 sets of N samples for each assay (InfA, H5a, H5b, RP). For each assay, this means $5 \text{ HP samples} \times 5 \text{ runs} = 25$ tests and $5 \text{ N samples} \times 5 \text{ runs} = 25$ tests.
  • Data Provenance: Contrived samples (BPL-inactivated influenza A/gyrfalcon/41088-6/2014 (H5N8) in A549 cells).

• Clinical Performance Evaluation:

  • Sample Size: A total of 50 clinical specimens and 10 contrived samples with influenza A(H5) were used as positive samples (totaling 60 positive samples if the contrived A(H5) are counted separate from the 50 general clinical positives). And 50 negative specimens. So, a total of 100 retrospective samples (50 positive, 50 negative) were evaluated against the QSDx and QMDx independently.
  • Data Provenance:
    • Retrospective clinical specimens: Collected during the 2013-2014 influenza seasons. (Country of origin not specified, but given the CDC involvement, likely U.S.)
    • Contrived samples: The 10 A(H5) samples were "prepared with BPL-inactivated influenza A(H5) virus in a suspension of human A549 cells and virus transport medium."

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 mention the number of experts or their specific qualifications for establishing ground truth for the test set (clinical performance evaluation).

• For the analytical studies (LOD, reproducibility, carryover), the ground truth was established by the known characteristics of the prepared viral stocks and dilutions.
• For the clinical performance, the ground truth was established by the "previously determined" results using the FDA-cleared Applied Biosystems™ 7500 Fast Dx. This implies that the predicate device serves as the ground truth. It does not state that independent experts re-adjudicated these samples, but rather that the previously established results from a gold-standard method were used.

4. Adjudication Method for the Test Set:

No explicit adjudication method (e.g., 2+1, 3+1) is described for the clinical test set. The clinical samples were "previously determined to be positive using the Applied Biosystems™ 7500 Fast Dx." This implies the predicate device's results were considered the reference standard for comparison.

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:

This device is an in-vitro diagnostic (IVD) RT-PCR kit, not an AI-assisted diagnostic imaging device that involves human "readers" or AI assistance to humans. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The entire study focuses on the standalone performance of the device (RT-PCR kit with its associated instruments). The device is an automated molecular diagnostic assay, not an AI algorithm. Its performance is evaluated objectively based on its ability to detect and characterize viral RNA. While human analysts perform the procedure and interpret the output, the core 'performance' refers to the analytical and clinical accuracy of the molecular reactions and instrument readings.

7. The Type of Ground Truth Used:

• Analytical Studies (LOD, Reproducibility, Carryover): The ground truth was based on known concentrations of characterized viral stocks (EID50/mL titer) and the specific composition of contrived samples (known to be positive or negative for certain influenza strains). This is a form of laboratory-established ground truth.
• Clinical Performance Evaluation: The ground truth for the clinical specimens was derived from results previously obtained using the FDA-cleared Applied Biosystems™ 7500 Fast Dx. This acts as a reference standard from a legally marketed and established device. For the A(H5) samples, it was based on the known composition of the contrived samples.

8. The Sample Size for the Training Set:

The document describes an evaluation study for substantial equivalence of a molecular diagnostic kit with new instrument platforms. It does not mention a "training set" in the context of machine learning. The "training" for such a molecular kit would involve the extensive R&D and optimization of the primer/probe sets and PCR conditions during the device's development, not a data-based training set for an AI algorithm.

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

As mentioned above, there is no explicit "training set" in the machine learning sense described in this document. The ground truth for the development and optimization of such a diagnostic panel typically involves:

• Known viral isolates/strains: Using cultured viruses with confirmed identity and titer.
• Sequencing data: To design highly specific and sensitive primers/probes targeting conserved regions of the viral genome.
• Clinical validation: Testing against a large panel of clinical samples, where the true infection status (ground truth) is established through gold-standard methods (e.g., viral culture, sequencing, or other highly sensitive and specific molecular tests) performed by expert laboratories.

The document briefly states: "Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes." This suggests an established ground truth based on genomic sequencing and bioinformatic analysis to design the assay.

Ask a specific question about this device

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

• For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

• For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3), and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/ Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/ throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (tRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

• For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• To provide epidemiologic information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the Applied Biosystems® (ABI) 7500 Fast Dx Real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization of influenza A(H3) and A(H1)pdm09 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

This document describes the performance evaluation of a modified CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, specifically focusing on the addition of new nucleic acid isolation options. The study aims to demonstrate that the modified device is substantially equivalent to its predicate.

Here's an analysis based on your request:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the demonstration of equivalence to a cleared predicate device. This equivalence is shown through specific performance metrics: Limit of Detection (LOD) and Analytical Precision (Reproducibility), and Clinical Performance.

Table of Acceptance Criteria and Reported Device Performance:

Additional Information:

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

   • LOD Equivalency: For each investigational instrument/kit combination, a single characterized influenza A(H3N2) virus (A/Hong Kong/4801/2014) was serially diluted. Triplicate samples of each dilution were tested for both the cleared and investigational methods. The exact number of dilutions is not explicitly stated as a fixed sample size, but the tables show 5 dilution points for each test. This is an analytical study, not directly using human patient samples.
   • Reproducibility: A blinded panel (contrived samples) containing a moderate positive, a low positive (near LOD), and a negative sample was used. For each of the three instrument/method combinations, the sample panel was tested 5 times by two different analysts at three separate sites over 5 different days. This means 5 samples (3 test specimens, plus internal controls likely) x 5 days x 2 analysts x 3 sites = 150 test events for each instrument/method. The specific agreement percentages shown in the tables are for 30 samples (presumably 10 runs per site over 5 days by 2 analysts, combined for totals of 30 for each category, e.g., A(H3) Moderate). Data provenance is not explicitly stated as country of origin, but it is an internal study of the CDC's diagnostic panel. The samples for reproducibility were contrived.
   • Clinical Performance: A total of 60 retrospective clinical specimens were used for each investigational instrument/kit combination: 30 positive for influenza A(H3) and 30 negative. The specimens were collected during the 2011-2012 and 2013-2014 influenza seasons. Data provenance is internal ("study was performed internally") using retrospective specimens, likely from the U.S. (given CDC's location).

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

   • Analytical studies (LOD and Reproducibility): Ground truth was established by precise laboratory preparation of known viral concentrations and by a reference method (the cleared predicate method and the CDC's established influenza real-time RT-PCR diagnostic panel). Human experts were involved in performing the tests and interpreting results (e.g., "All users, analysts, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use"). However, the ground truth itself is based on the inherent properties of the prepared samples and the established performance of the predicate device, not on expert consensus of clinical cases.
   • Clinical Performance: The ground truth for the retrospective clinical specimens was their prior determination as positive or negative for influenza A(H3) virus. The document does not specify how this prior determination was made (e.g., by culture, another PCR, or an expert committee). It implies that the "comparator" (Roche MagNA Pure Compact instrument using the RNA Isolation Kit) served as the reference standard for this equivalency study.

3. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
   Not applicable (N/A). This study evaluates a laboratory diagnostic test (RT-PCR) with objective results (positive/negative based on PCR signal) and quantitative metrics (Ct values, EID50/mL). It does not involve human interpretation of images or clinical assessments requiring adjudication.

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:
   N/A. This is a study of an in vitro diagnostic (IVD) device (RT-PCR), not an AI-based imaging or interpretation tool. It does not involve human readers interpreting cases or AI assistance.

5. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
   This is an IVD device. Its performance is inherent in the device itself (reagents, instrumentation, assay design). The tests performed (LOD, reproducibility, clinical equivalency) are standalone evaluations of the analytical and clinical performance of the new nucleic acid extraction methods in conjunction with the existing PCR panel. While human analysts operate the device, the "performance" refers to the device's output, not human interpretation.

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

   • Analytical Studies (LOD & Reproducibility): "Spiked" or "contrived" samples with known concentrations of influenza virus.
   • Clinical Performance: Previously determined positivity/negativity of retrospective clinical specimens, with the results from the predicate device serving as the comparator/reference.

7. The sample size for the training set:
   N/A. This is a 510(k) submission for a device modification, focusing on testing the performance of added components (nucleic acid extraction systems) within an already established diagnostic panel. There is no mention of a "training set" in the context of machine learning or algorithm development. The "training" described in the document refers to human analysts being trained to use the device.

8. How the ground truth for the training set was established:
   N/A, as there is no machine learning training set in this context.

Ask a specific question about this device

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyneed swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a seasonal influenza viruses A(HIN1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N) Jodm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted unless a BSL 3E facility is available to receive and culture specimens.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel Influenza A Subtyping Kit is a realtime RT-PCR (rRT-PCR) assay that utilizes the Applied Biosystems® (ABI) 7500 Fast Dx Real-time PCR system. The Influenza A Subtyping Kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). The oligonucleotide primers and probes for detection of influenza A and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), and the nucleoprotein (NP), respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses were selected from highly conserved regions of their HA genes. The Influenza A Subtyping kit also contains primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens.

This document describes the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A Subtyping Kit (VER 2), which is intended for the qualitative detection and characterization of influenza virus RNA. The document outlines changes from a predicate device (K140851) including modifications to the pdmH1 assay and the removal of the H1 assay.

Here's an analysis of the acceptance criteria and supporting studies as presented in the document:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on demonstrating the analytical and clinical performance of the modified pdmH1 assay and the H3 assay. While explicit acceptance criteria (e.g., "PPA must be >X%") are not formalized in a table of the document, the studies demonstrate a high level of performance. Based on the results, implicit acceptance criteria would involve:

• Analytical Sensitivity (LOD): Consistent detection at low viral concentrations for A(H1)pdm09 and A(H3) assays using both enzyme kits.
• Inclusivity: Successful detection of diverse A(H1)pdm09 strains.
• Clinical Performance (Positive Agreement): High percentage of agreement with previously positive clinical samples for A(H1)pdm09 and A(H3).
• Clinical Performance (Negative Agreement): High percentage of agreement with previously negative clinical samples for influenza A for both pdm and H3 assays.

• BW: 1/1 (100.0% PPA, 95% CI: 20.7-100.0)
• NPS, NS: 34/35 (97.1% PPA, 95% CI: 85.5-99.5)
• NW: 4/4 (100.0% PPA, 95% CI: 51.0-100.0)
• TS: 2/2 (100.0% PPA, 95% CI: 34.2-100.0)
  Quanta qScript™:
• BW: 1/1 (100.0% PPA, 95% CI: 20.7-100.0)
• NPS, NS: 33/33 (100.0% PPA, 95% CI: 89.6-100.0)
• NW: 4/4 (100.0% PPA, 95% CI: 51.0-100.0)
• TS: 2/2 (100.0% PPA, 95% CI: 34.2-100.0) |
  | Clinical Performance - A(H3) Positive Agreement | High positive agreement with previously positive clinical samples (e.g., >95% PPA with tight CI). | Invitrogen SuperScript™:
• NA: 1/1 (100.0% PPA, 95% CI: 20.7-100.0)
• NPS, NS: 30/30 (100.0% PPA, 95% CI: 88.7-100.0)
• NW: 1/1 (100.0% PPA, 95% CI: 20.7-100.0)
  Quanta qScript™:
• NA: 1/1 (100.0% PPA, 95% CI: 20.7-100.0)
• NPS, NS: 30/30 (100.0% PPA, 95% CI: 88.7-100.0)
• NW: 1/1 (100.0% PPA, 95% CI: 20.7-100.0) |
  | Clinical Performance - A(H1)pdm09 Negative Agreement | High negative agreement with previously negative clinical samples (e.g., >95% NPA with tight CI). | Invitrogen SuperScript™:
• NPS: 53/53 (100.00% NPA, 95% CI: 93.2-100.0)
  Quanta qScript™:
• NPS: 52/52 (100.00% NPA, 95% CI: 93.1-100.0) |
  | Clinical Performance - A(H3) Negative Agreement | High negative agreement with previously negative clinical samples (e.g., >95% NPA with tight CI). | Invitrogen SuperScript™:
• NPS: 29/29 (100.00% NPA, 95% CI: 88.3-100.0)
  Quanta qScript™:
• NPS: 28/28 (100.00% NPA, 95% CI: 87.9-100.0) |

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

• Analytical Sensitivity (LOD):
  • pdmH1 assay: For each of the two A(H1)pdm09 strains tested, 20 replicates of the highest virus dilution were used to confirm LOD.
  • H3 assay: A range finding study used 3 replicates per dilution for the LOD equivalency, but the confirmatory LOD for H3 is not explicitly stated in the same manner as pdmH1. However, the study concludes equivalency based on consistent positive results for 3/3 replicates across a range of dilutions.
• Inclusivity Testing: Ten (10) A(H1)pdm09 strains were tested, with each strain tested in triplicate.
• Cross-Reactivity Testing: Five (5) influenza A(H1) virus strains were tested, each in triplicate.
• Clinical Performance Evaluation:
  • Positive A(H1)pdm09: A total of 42 retrospective clinical samples previously determined positive for A(H1)pdm09 were evaluated. The breakdown by specimen type for reported results is 1 BW, 35 NPS/NS, 4 NW, and 2 TS for Invitrogen; and 1 BW, 33 NPS/NS, 4 NW, and 2 TS for Quanta.
  • Positive A(H3): A total of 32 retrospective clinical samples previously determined positive for A(H3) were evaluated. The breakdown by specimen type is 1 NA, 30 NPS/NS, and 1 NW for both enzyme systems.
  • Negative for Influenza A (pdm assays): A total of 53 retrospective clinical samples (NPS) previously determined negative for influenza A were tested for pdm assays.
  • Negative for Influenza A (H3 assay): A total of 30 retrospective clinical samples (NPS) previously determined negative for influenza A were tested for H3 assay.
• Data Provenance: Retrospective clinical samples collected during the 2011-2012, 2013-2014, and 2015-2016 influenza seasons. The country of origin is not explicitly stated but implied to be the US given the CDC context.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the clinical test set. The ground truth for clinical samples was based on prior determination using the "CDC Human Influenza rRT-PCR Diagnostic Panel" and, for the 2015-2016 samples, confirmation by genetic sequence analysis. This implies the use of laboratory professionals and possibly virologists or epidemiologists, but specific details on their expertise are not provided.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for the test set results. For the analytical studies, replicates are used, and the standard reporting of "X/X (+)" indicates all replicates were positive. For clinical samples, results were compared against prior determinations and genetic sequencing, suggesting these served as the reference standards rather than a separate adjudication process.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not performed. This device is a diagnostic assay (RT-PCR kit), not an imaging or interpretation device that would typically involve multiple human readers. The study focuses on the analytical and clinical performance of the assay itself.

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

Yes, the studies conducted are standalone performance evaluations of the diagnostic assay. The device is a "Real-Time RT-PCR Diagnostic Panel," meaning the "algorithm" is the biochemical and molecular process of the assay itself, followed by data interpretation based on established thresholds (e.g., Ct values). The results presented are the output of this assay system.

7. The Type of Ground Truth Used

• Analytical Studies (LOD, Inclusivity, Cross-Reactivity): Ground truth was established using characterized viruses of known titers (ID50/mL or EID50/mL).
• Clinical Performance Studies:
  • For positive samples: Ground truth was based on previous positive determination with the "CDC Human Influenza rRT-PCR Diagnostic Panel" and, for some 2015-2016 samples, confirmed by genetic sequence analysis.
  • For negative samples: Ground truth was based on previous negative determination for influenza A with the "CDC Human Influenza rRT-PCR Diagnostic Panel."

8. The Sample Size for the Training Set

The document does not explicitly describe a "training set" in the context of machine learning, as this is a molecular diagnostic assay. The development of the oligonucleotide primers and probes would involve extensive bioinformatics and laboratory work, but these are not referred to as a "training set" in the presented material. The "characterization" of the device involves testing its performance with known inputs rather than training an algorithm.

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

As no explicit "training set" for a machine learning algorithm is described, this question is not directly applicable. The "ground truth" for the development of the assay components (primers and probes) would have been established through molecular biology techniques, genomic sequencing, and epidemiological data on circulating influenza strains to identify conserved regions and ensure specificity. The document mentions that the primers and probes were "selected from highly conserved regions" of the viral genes, implying this foundational work.

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The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR instrument in conjunction with clinical and epidemiological information:

• For the presumptive identification of virus in patients who may be infected with influenza A subtype A/HS (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a seasonal influenza viruses A/H1 and A/ H3 were the predominant influenza A viruses in circulation and during a season when the A/H1pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the most current U.S. Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A/ H5 specimens. The definitive identification of influenza A/H5 (Asian lineage) either directly from patient or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent influenza viruses and sent to a state or local health department for testing. Viral culture should not be attempted unless a BSL 3+ facility is available to receive and culture specimens.

All users, and any person reporting results from use of this device should be trained to perform and interpret the results from this procedure by a competent instructor prior to use. CDC Influenza Division will limit the distribution of this device to only those users who have successfully completed a training course provided by CDC instructors or designees.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel Influenza A/H5 Subtyping Kit is a real-time RT-PCR) assay that utilizes the Applied Biosystems® (ABI) 7500 Fast Dx Realtime PCR system. The Influenza A/H5 Subtyping Kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). The oligonucleotide primers and probes for detection of influenza A viruses (InfA) were selected from highly conserved regions of the matrix (M) protein. Oligonucleotide primers and probes for characterization of avian influenza A/H5 (Asian lineage) viruses (H5a and H5b) were selected from highly conserved regions of their HA genes. The Influenza A/H5 Subtyping kit also contains primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens.

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

Device Name: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Kit (VER 3)
K Number: K153148

1. Table of Acceptance Criteria and Reported Device Performance

The document describes the analytical and clinical performance studies, but directly stated "acceptance criteria" for each metric are not explicitly listed in a formatted table with pass/fail thresholds. Instead, the results are presented as the device's performance, implying these values met internal criteria for submission and approval. Inferring from the nature of diagnostic device validation, these would typically be high percentages for sensitivity and specificity.

Based on the provided data, here's a table summarizing the observed performance:

• Invitrogen SuperScript™: 10^3.8 EID50/mL
• Quanta qScript™: 10^2.4 EID50/mL
• A/duck/Vietnam/NCVD-1544/2012 (A/H5N1):
  • Invitrogen SuperScript™: 10^3.1 EID50/mL
  • Quanta qScript™: 10^3.1 EID50/mL
• A/gyrfalcon/Washington/41088-6/2014 (A/H5N8):
  • Invitrogen SuperScript™: 10^3.35 EID50/mL
  • Quanta qScript™: 10^3.35 EID50/mL
    Reported as the lowest concentration where InfA and both H5a/H5b showed uniform detection. |
    | Analytical Inclusivity | Detection of all listed A/H5 (Asian lineage) isolates representative of different geographic locations and phylogenetic clades, at or near the established LOD. | - Reactive with all 15 tested H5 (Asian lineage) isolates (all 3/3 positive for InfA, H5a, and H5b) with both enzyme systems.
• Predicted to be reactive with A/Bangladesh/3222/2011 (in silico analysis). |
  | Analytical Specificity (Cross-Reactivity) | No detection of common human influenza A (non-H5), human influenza B, swine influenza, avian influenza (non-H5), canine influenza, or equine influenza viruses when tested at high titers. | - InfA assay detected all tested human influenza A and various animal influenza A strains (as expected for an InfA primer/probe set).
• H5a and H5b assays showed no cross-reactivity with human influenza A (non-H5), human influenza B, most animal influenza A (non-H5), and specifically did not detect A/duck/Singapore-Q/F119-3/1997 (H5N3) when tested with Invitrogen SuperScript™. (Note: The H5a/H5b assays did detect A/duck/Singapore-Q/F119-3/1997 H5N3, which is an H5 subtype, albeit not specified as Asian lineage. This is an expected positive result for H5 detection.) |
  | Analytical Specificity (Exclusivity) | No detection (no false positives) of common non-influenza human respiratory viruses, respiratory bacteria, and commensal organisms of the human respiratory tract when tested at high concentrations. | - No detection (all negative) for all 18 bacteria, 1 yeast, and 16 non-influenza human respiratory viruses tested with Invitrogen SuperScript™ for InfA, H5a, and H5b assays. |
  | Clinical Performance (Positive Agreement) | High Positive Agreement (e.g., >90% with a reasonable lower bound for 95% CI). | - Quanta qScript™: 100% (95% CI: 92.9 – 100.00) (50/50)
• Invitrogen SuperScript™: 88.0% (95% CI: 76.2 - 94.4) (44/50) |
  | Clinical Performance (Negative Agreement) | High Negative Agreement (e.g., >90% with a reasonable lower bound for 95% CI). | - Quanta qScript™: 100% (95% CI: 94.4 – 100.00) (65/65)
• Invitrogen SuperScript™: 100% (95% CI: 94.4 - 100.00) (65/65) |

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

• Analytical Sensitivity (LOD):

  • Test Set Sample Size: 20 replicates for each enzyme kit (Invitrogen SuperScript™ and Quanta qScript™) for the highest virus dilution for each of the three A/H5 strains to confirm LOD. Initial testing used 3 replicates.
  • Data Provenance: Laboratory-generated (characterized viruses).

• Analytical Inclusivity:

  • Test Set Sample Size: 3 replicates per virus isolate for 15 A/H5 (Asian lineage) viruses for both enzyme systems. One virus was tested in silico. Total real wet-lab tests: 15 viruses * 3 replicates * 3 assays (InfA, H5a, H5b) * 2 enzyme systems = 270 individual reactions.
  • Data Provenance: Laboratory-generated (characterized viruses representing different geographic locations and phylogenetic clades).

• Analytical Specificity (Cross-Reactivity):

  • Test Set Sample Size: 3 replicates per virus for 14 human and animal influenza A and influenza B viruses tested. Total: 14 viruses * 3 replicates * 3 assays (InfA, H5a, H5b) = 126 individual reactions.
  • Data Provenance: Laboratory-generated (characterized viruses).

• Analytical Specificity (Exclusivity):

  • Test Set Sample Size: A single test for each of 35 non-influenza organisms (16 viruses, 18 bacteria, 1 yeast). Total: 35 organisms * 3 assays (InfA, H5a, H5b) = 105 individual reactions.
  • Data Provenance: Laboratory-generated (propagated, titered, and characterized organisms).

• Clinical Performance Evaluation:

  • Test Set Sample Size:
    • Positive Contrived Samples: 50 samples.
    • Negative Specimens: 65 specimens.
  • Data Provenance:
    • Positive Contrived Samples: Laboratory-generated (grown virus added to A549 cell suspension).
    • Negative Specimens: Obtained from a clinical study conducted during the 2011-2012 influenza season. This suggests the negative specimens were retrospective clinical samples (human respiratory specimens), originating likely from the US where CDC studies are typically conducted.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth for the test set.

• For analytical studies (LOD, Inclusivity, Specificity), the ground truth is established by the known characteristics of the laboratory-controlled and characterized viral and bacterial stocks. This does not typically involve human expert consensus in the same way clinical diagnostics do.
• For the clinical performance evaluation:
  • The "positive contrived samples" have their ground truth by definition (known virus added).
  • The "negative specimens" were previously tested as negative for influenza A by the CDC Human Influenza rRT-PCR Diagnostic Panel. The ground truth for these would have been established by the predicate device's results, which were likely interpreted by trained laboratory personnel, rather than experts in a concensus panel for the purpose of this study.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set.

• For analytical studies, the results are typically quantitative (e.g., Cq values) or qualitative (positive/negative call) based on predetermined assay thresholds. There's no indication of a need for expert adjudication of these raw results.
• For clinical performance, the comparison is made against the known status of contrived samples or the prior result from a predicate device. An adjudication process (like 2+1, 3+1, etc.) is typically used when the ground truth itself is uncertain or to resolve discrepancies between readers/tests, which is not stated as part of this study design.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.

• MRMC studies are typically used to compare the performance of human readers (e.g., radiologists, pathologists) with and without AI assistance or against another diagnostic method, often looking at reader agreement and diagnostic accuracy.
• This submission describes a RT-PCR diagnostic panel, which is an in vitro diagnostic (IVD) device. The performance is determined by the assay's ability to detect viral RNA, not by human reader interpretation of complex images or clinical data in the same way an MRMC study would apply. Therefore, the concept of "how much human readers improve with AI vs without AI assistance" is not applicable here.

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

Yes, the studies described are essentially standalone performance evaluations of the device (assay) itself.

• The analytical studies (LOD, Inclusivity, Specificity, Exclusivity) inherently assess the algorithm/reagent's ability to detect targets or avoid off-target detection.
• The 'clinical performance evaluation' also tests the device's ability to correctly identify positive and negative contrived/clinical samples.
• While a human laboratory technologist performs the PCR steps and interprets the output (e.g., reads Cq values and applies the interpretation algorithm to call positive/negative), the study evaluates the device's performance characteristics given those outputs, not the technologist's diagnostic ability with or without the device. The data presented is the direct output of the device's reaction, not a human interpretation layer being separately assessed for its impact.

7. The Type of Ground Truth Used

• Analytical Studies (LOD, Inclusivity, Cross-Reactivity, Exclusivity):
  • Known Characteristics of Propagated and Characterized Viruses/Organisms: For these studies, the ground truth is established by the known identity, titer, and genetic makeup of the laboratory-prepared viral and bacterial stocks. For example, an A/H5N1 virus is known to be A/H5N1 because it was characterized as such.
• Clinical Performance Evaluation:
  • Contrived Samples: The ground truth for positive samples was established by the known addition of virus to a cell suspension.
  • Negative Specimens: The ground truth for negative specimens was established by their prior categorization as "negative for influenza A" using the CDC Human Influenza rRT-PCR Diagnostic Panel (likely the predicate device or a similar established method) in a previous clinical study. This is a form of comparator method ground truth.

8. The Sample Size for the Training Set

The document does not explicitly mention a training set or its sample size.

• For IVD assays like RT-PCR, the development process (which would involve "training" or optimization) typically focuses on primer/probe design, reaction conditions, and calibration using initial lab-generated samples. The 'training' in this context is implicit in the assay development and refinement, rather than a distinct, formal training set for a machine learning algorithm.
• The studies described are for validation (testing), not for development or training.

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

As no explicit training set is mentioned (see point 8), the document does not describe how ground truth for a training set was established.

• If an implicit 'training' phase (assay development) occurred, the ground truth would have been established through well-characterized laboratory reference materials and known viral isolates, similar to the ground truth for the analytical validation studies.

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The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real Time PCR Instrument in conjunction with clinical and epidemiological information:

· For the presumptive identification of virus in patients who may be infected with influenza A subtype A/H5(Asian Lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A/H5 Subtyping Kit contains components of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel that is used in real-time RT-PCR (rRT-PCR) assays on the ABI 7500 Fast Dx Real-Time PCR Instrument. The Influenza A/H5 Subtyping Kit consists of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

The Influenza A/H5 Subtyping Kit is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reverse-transcribe specific regions of RNA into cDNA copies. The cDNA then serves as a template for a polymerase chain reaction that utilizes a thermocyclic heating and cooling of the reaction to logarithmically amplify a specific region of DNA. The probe anneals to a specific internal target sequence located between the target loci of the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of Tag polymerase degrades any probe molecules hybridized to amplified target sequence, causing the reporter dye to separate from the quencher dye, and generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle. Amplification of targets is reflected by logarithmic increase in fluorescence over time in comparison to the background signal.

This document is a 510(k) premarket notification from the FDA, asserting substantial equivalence for the "CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, Influenza A/H5 Subtyping Kit." The document does not contain acceptance criteria or a study proving device performance against such criteria. Instead, it compares the proposed device to a predicate device (K132508) and concludes that the changes are primarily for labeling and do not alter the device's design, technological attributes, or intended use.

Therefore, I cannot provide the requested information from this document. The document explicitly states:

• "The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel subject to this special 510(k) are for labeling purposes only and will not alter the technological attributes of the device." (Page 6)
• "The changes proposed to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel do not alter the device's design or technological attributes. In addition, the indications for use and intended use of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel will remain the same." (Page 9)

This type of 510(k) submission (a Special 510(k)) is used for modifications to a manufacturer's own legally marketed device where the modification does not affect the device's fundamental scientific technology or its intended use. As such, it relies on the previous clearance of the predicate device (K132508) for performance data rather than presenting new performance studies against acceptance criteria.

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The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in realtime RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

• . For qualitative detection of influenza virus type A or B from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]), and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture:
• For determination of the subtype of seasonal human influenza A viruses as seasonal A/H1, . A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS. TS. NA. NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or ● B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW, and NPS/TS) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• . For the presumptive identification of virus in patients who may be infected with influenza A subtype A/H5 (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• To provide epidemiological information for surveillance of circulating influenza viruses. .

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR assays (rRT-PCR) on the ABI 7500 Fast Dx Real-Time PCR Instrument. The device consists of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is based on technology which is used in many molecular diagnostic assays. rRT-PCR assays are one-tube assays that first reverse-transcribe specific regions of RNA into cDNA copies. The cDNA then serves as a template for a polymerase chain reaction that utilizes thermocyclic heating and cooling of the reaction to logarithmically amplify a specific region of DNA. The probe anneals to a specific internal target sequence located between the target loci of the forward and reverse primers. During the extension phase of the 5' exonuclease activity of Tag polymerase degrades any probe molecules hybridized to amplified target sequence, causing the reporter dye to separate from the quencher dye, and generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes, increasing the fluorescence intensity. Fluorescence intensity is monitored at each PCR cycle. The amplification of each target is reflected by a logarithmic increase in fluorescence in comparison to the background signal.

Acceptance Criteria and Device Performance Study for K132508

This submission, K132508, describes modifications to the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel to add the capability to differentiate the two major lineages of influenza B viruses (B/Victoria or B/Yamagata). The predicate device is K130551.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are primarily demonstrated through analytical performance studies (Limit of Detection, Inclusivity, and Exclusivity) and clinical performance studies (Prospective and Retrospective). The specific quantitative acceptance criteria for percent agreement in clinical studies are implicitly represented by the reported 95% Confidence Intervals.

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The Prodesse® ProFAST + Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This Assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This Assay is not intended to detect Influenza B or Influenza C Viruses.

A negative ProFAST+ Assay result is a presumptive negative result for Influenza A. These results should be confirmed by an FDA cleared nucleic acid-based test (NAT) detecting Influenza A.

Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.

If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities. specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

The Prodesse® ProFAST + Assay is a multiplex Real Time RT-PCR in vitro diagnostic test for the qualitative detection and discrimination of seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza viral nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens from human patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. This Assay targets conserved regions of the Hemagglutinin (HA) gene for seasonal Influenza A/H1, seasonal Influenza A/H3 and 2009 H1N1 Influenza Virus, respectively. This Assay is not intended to detect Influenza B or Influenza C Viruses.

The ProFAST+ Assay enables detection and discrimination of Influenza A Virus subtypes: seasonal A/H1, seasonal A/H3, and 2009 H1N1 and internal control nucleic acid. Nasopharyngeal swab specimens are collected from patients with signs and symptoms of a respiratory infection using a polyester, rayon or nylon tipped swab and placed into viral transport medium.

A Universal Internal Control (UIC) is added to each sample prior to nucleic acid isolation to monitor for inhibitors present in the specimens. The isolation and purification of the nucleic acids is performed using either a MagNA Pure LC Instrument (Roche) and the MagNA Pure Total Nucleic Acid Isolation Kit (Roche) or a NucliSENS® easyMAG™ System (bioMérieux) and the Automated Magnetic Extraction Reagents (bioMérieux).

The purified nucleic acids are added to ProFAST+ Supermix along with enzymes included in the ProFAST+ Assay Kit. The ProFAST+ Supermix contains oligonucleotide primers and targetspecific oligonucleotide probes. The primers are complementary to highly conserved regions of the Hemagglutinin (HA) gene for seasonal influenza A/H1, seasonal influenza A/H3 and 2009 H1N1 Influenza Virus. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end.

Reverse transcription of the RNA in the sample into complementary DNA (cDNA) and subsequent amplification of DNA is performed in a Cepheid SmartCycler® II instrument. In this process, the probe anneals specifically to the template followed by primer extension and amplification. The ProFAST+ Assay is based on Tagman chemistry, which utilizes the 5' - 3' exonuclease activity of the Taq polymerase to cleave the probe thus separating the reporter dye from the quencher. This generates an increase in fluorescent signal upon excitation from a light source. With each cycle, additional reporter dye molecules are cleaved from their respective probes, further increasing fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification products present at that time. Fluorescent intensity is monitored during each PCR cycle by the SmartCycler II instrument.

The provided text describes a special 510(k) submission for the Prodesse® ProFAST®+ Assay, primarily focusing on modifications to the internal control and positive control, and an additional reactivity claim for H3N2v. The submission argues for substantial equivalence to a predicate device (K101855, ProFAST 101+ Assay).

Crucially, the document does not present acceptance criteria or detailed results from a study that "proves the device meets the acceptance criteria" in the format of a typical clinical validation study. Instead, it focuses on demonstrating that modifications did not negatively impact performance compared to the previously cleared predicate device.

Here's an attempt to extract the requested information, noting where details are missing based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state quantitative acceptance criteria (e.g., minimum sensitivity, specificity, or agreement percentages) for a clinical performance study of the modified device. Instead, it refers to the previous performance claims of the ProFAST+ Assay (the predicate device for the modifications) and states that the modified assay "continues to meet the performance claims."

The closest to "reported device performance" are the results of the verification/validation studies for the modifications:

Note: The document explicitly states that "the performance characteristics of this device with clinical specimens that are positive for H3N2v influenza virus have not been established." This means for H3N2v, only analytical reactivity was shown, not clinical performance.

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

• Sample Size for Test Set: The document mentions a "retrospective clinical comparison study" for the UIC modification but does not provide the sample size used in this study.
• Data Provenance: The document states "clinical comparison study," implying human patient samples were used. The term "retrospective" indicates that these samples were collected in the past. The country of origin is not specified but is implicitly the US given the FDA submission.

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

Not provided. The nature of the ground truth (e.g., a reference method like viral culture or another FDA-cleared NAT) is not detailed, nor is the number or qualifications of experts, if any, involved in establishing it. It's likely the "ground truth" for the clinical comparison study would have been established by the reference method against which the predicate device's original performance claims were made.

4. Adjudication Method for the Test Set

Not provided. Given that this appears to be a comparison study against a historical reference or predicate, an adjudication method might not have been
explicitly described in this type of submission.

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 device is an in vitro diagnostic (IVD) RT-PCR assay for detecting viral nucleic acids, not an AI-assisted diagnostic tool that would be used by "human readers" in the sense of image interpretation. Therefore, an MRMC study with human readers and AI assistance is not relevant to this device. The "reader" here is the instrument interpreting PCR amplification curves.

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

Yes, the device is inherently a standalone algorithm/assay without human-in-the-loop performance influencing its primary result. It provides a qualitative (positive/negative) detection and discrimination of influenza A subtypes. The "retrospective clinical comparison study" would represent the standalone performance of the modified assay.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

Not explicitly stated in the provided text. For RT-PCR assays, the ground truth for clinical studies is typically established by:

• A "gold standard" laboratory method (e.g., viral culture if available and sensitive enough, or a highly sensitive and specific FDA-cleared reference molecular test).
• A composite reference method combining multiple tests or clinical findings.

Given it's a "clinical comparison study," it implies comparison to established clinical diagnoses or reference lab results, but the specifics are absent.

8. The Sample Size for the Training Set

Not applicable/Not provided. This is an RT-PCR assay, not a machine learning or AI algorithm that requires a "training set" in the conventional sense. The "training" for such a device involves assay optimization and analytical validation using characterized samples (e.g., contrived samples with known viral concentrations, characterized clinical samples) to establish parameters like limit of detection, linearity, and specificity. The document refers to "Analytical Sensitivity, IC Interference, Extractor Equivalency, and Sample Stability studies," which utilize such characterized samples, but a specific "training set sample size" as per AI/ML terminology is not relevant here.

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

Not applicable/Not provided in the AI/ML context. For analytical studies, the "ground truth" (e.g., viral presence and concentration) is established by using characterized stocks, reference materials, or quantified clinical samples whose status is independently verified (e.g., by culture, sequencing, or quantitative PCR methods).

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The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

• For qualitative detection of influenza virus type A or B from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]), and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• For determination of the subtype of seasonal human influenza A viruses as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• For the presumptive identification of virus in patients who may be infected with influenza A subtype A/H5 (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• To provide epidemiological information for surveillance of circulating influenza viruses.

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR assays (rRT-PCR) on the ABI 7500 Fast Dx Real-Time PCR Instrument. The device consists of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

Here's a breakdown of the acceptance criteria and study information for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The 510(k) is for a modification to an existing device (K111507) to add a new enzyme kit (Quanta qScript™). Therefore, the acceptance criteria are implicitly demonstrating substantial equivalence to the predicate device (the panel using Invitrogen SuperScript™). The performance is shown as agreement with the predicate.

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

• Prospective Clinical Study:

  • Initial Sample Size: 1,002 respiratory specimens.
  • Analyzed Sample Size: 931 specimens (after exclusions for inconclusive results, technician/instrument error, or unspecified specimen type).
  • Data Provenance: Prospective, 2011-2012 influenza season. The country of origin is not explicitly stated but is implied to be the United States (references to U.S. DHHS, World Health Organization and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories in the United States).

• Retrospective Clinical Study (A/H1 supplement):

  • Sample Size: 30 positive specimens for seasonal influenza A/H1N1.
  • Data Provenance: Retrospective, from a previous clinical study conducted during the 2006-2007 influenza season. Implicitly United States.

• Retrospective Clinical Study (A/H5 simulated samples):

  • Sample Size: 36 samples (12 high concentration, 12 moderate concentration, 12 low concentration).
  • Data Provenance: Simulated samples prepared from a characterized and titered stock of influenza A/H5N1 virus and human A549 cells (Lednicky et al. method). This is an in vitro study, not from human patients directly.

• Retrospective Clinical Study (Negative specimens):

  • Sample Size: 50 negative specimens.
  • Data Provenance: Retrospective, from a previous clinical study conducted during the 2006-2007 influenza season. Implicitly United States.

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

The ground truth in this submission is established by the results of the predicate device (CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel using Invitrogen SuperScript™). The submission focuses on equivalency. There is no mention of external subject matter experts being used to establish a separate ground truth for the test set independent of the predicate device's results. The predicate device itself acts as the "gold standard" or "ground truth" for comparison.

4. Adjudication Method for the Test Set

Not applicable in the typical sense for this submission. The ground truth for the comparison is the result obtained by the predicate device. The study design is a comparison of the modified device's performance against the established performance of the predicate device. Discrepancies between the investigational device and the predicate device's results would be analyzed, but there's no mention of a separate expert adjudication panel for individual cases.

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) molecular assay (RT-PCR) and involves laboratory testing, not human reader interpretation of images or other data where AI assistance would be relevant. The "readers" are the laboratory instruments and trained technicians interpreting quantitative PCR curves, not human experts making diagnostic decisions from primary clinical data with or without AI aid.

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

The device is a diagnostic panel that requires human operation (sample preparation, instrument loading, interpretation of results, although interpretation of the raw PCR data is instrument-assisted). There is no "algorithm only" performance reported in the context of being a standalone diagnostic decision-making system. Its performance is always within a human-operated laboratory workflow. The analytical and clinical studies evaluate the performance of the assay itself when run by trained personnel.

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

For the clinical performance evaluation:

• The primary ground truth for comparison is the results obtained using the predicate device (CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel with Invitrogen SuperScript™). This effectively means the ground truth is established by a previously validated RT-PCR assay.
• The initial patient status (influenza-like illness symptoms, viral culture results) provides context, but the direct comparison is test-to-test.

For the analytical sensitivity and inclusivity studies:

• Characterized influenza virus strains (EID50/mL or TCID30/mL values) were used as the ground truth for establishing the Limit of Detection (LOD) and for inclusivity testing.

8. The Sample Size for the Training Set

This submission does not discuss a "training set" in the context of machine learning or AI models. The device is a RT-PCR diagnostic panel. There's no training phase described for an algorithm. The "training" of the assay itself would refer to the historical development and validation of the primers and probes, which isn't detailed here but precedes this 510(k) modification.

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

Not applicable as there is no "training set" for an algorithm. The development of the RT-PCR panel involves establishing the specificity and sensitivity of the primers and probes against known viral sequences and cultured viruses, which constitute the scientific basis for the assay. This information is assumed to be established for the predicate device.

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The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is intended for use in real-time RT-PCR (rRT-PCR) assays on an Applied Biosystems (ABI) 7500 Fast Dx Real-Time PCR Instrument in conjunction with clinical and epidemiological information:

• For qualitative detection of influenza virus type A or B from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS], and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• For determination of the subtype of seasonal human influenza A virus as seasonal A/H1, A/H3, and/or A/H1pdm09 from viral RNA in upper respiratory tract clinical specimens (including NPS, NS, TS, NA, NW and NPS/TS) and lower respiratory tract specimens (including BAL, BW, TA, sputum and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• For the presumptive identification of virus in patients who may be infected with influenza A subtype A/H5 (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• To provide epidemiologic information for surveillance of circulating influenza viruses.

The CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on the ABI 7500 Fast Dx Real-Time PCR Instrument. The panel consists of oligonucleotide primers and dual-labeled hydrolysis (TaqMan®) probes to be used in rRT-PCR for the in vitro qualitative detection and characterization of human influenza viruses from viral RNA in respiratory specimens from patients presenting with influenza-like illness (ILI).

Here's a breakdown of the acceptance criteria and study information for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, based on the provided text:

Acceptance Criteria and Device Performance

Study Information:

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

• Sample Size for Clinical Specimen Testing: 165 human respiratory specimens.
• Data Provenance: Retrospective. The specimens were "transferred from U.S. public health laboratories to the CDC for confirmatory testing." This indicates they were previously collected and tested. The country of origin is the U.S.

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

• The document does not specify the number or qualifications of experts used to establish the ground truth for the test set. It mentions that specimens were "transferred from U.S. public health laboratories to the CDC for confirmatory testing" and that "Results were confirmed through genetic sequence analysis." It also states "Performance characteristics for influenza were established during a season when seasonal influenza viruses A/H1 and A/H3 were the predominant influenza A viruses in circulation and during a season when the A/H1pdm09 influenza virus was the predominant influenza A virus in circulation." This implies the original diagnoses were clinical, but the ground truth for this specific study was molecular.

4. Adjudication method for the test set:

• The document implies that genetic sequence analysis served as the definitive "comparator" or gold standard. There is no mention of a traditional expert adjudication method (like 2+1 or 3+1 consensus) for establishing the ground truth of the clinical samples. The device's results were compared directly to the genetic sequencing (molecular) findings.

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. This is a diagnostic panel for molecular detection, not an AI-based imaging or interpretive device that would typically involve human "readers" or a MRMC study. The study focuses on the device's ability to detect specific viral markers.

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

• Yes, implicitly. The "Performance Summary" describes the analytical sensitivity (LOD, inclusivity) and clinical performance (positive percent agreement) of the "CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel" itself. It is evaluating the direct output of the RT-PCR assay against a ground truth, which constitutes a standalone performance evaluation of the diagnostic panel. The "human-in-the-loop" aspect comes in interpreting the results from InfA, pdmInfA, and H3 markers, but the performance metrics are for the assay's ability to produce those results.

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

• Molecular (Genetic Sequence Analysis). For the clinical specimen testing, the "comparator" used to establish the ground truth was "genetic sequence analysis." For analytical sensitivity and inclusivity, it was based on known concentrations of spiked viral isolates.

8. The sample size for the training set:

• Not specified. The document does not describe a training set for the device's development or a separate validation study using a distinct training set. The performance data presented are for validation/testing of the device itself.

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

• N/A (Not Applicable). As no training set is described, there's no information on how its ground truth would have been established. The device is a molecular diagnostic panel based on RT-PCR technology, not a machine learning algorithm that requires a labeled training set in the typical sense. Its development relies on designing primers and probes specific to target genetic sequences.

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