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The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Influenza A & B Detection Kit is intended for use on the JBAIDS instruments, for the in vitro qualitative detection of influenza A and influenza B viral nucleic acids isolated and purified nasopharygeal swab (NPS) and nasopharygeal wash (NPW) specimens from human patients with signs and symptoms of respiratory infection.

The JBAIDS Influenza A & B Detection Kit contains reverse transcriptase real-time polymerase chain reaction (rRT-PCR) assays that target the Matrix protein gene of influenza A viruses, and the Non-structural protein gene of influenza B viruses. This kit is not intended to detect influenza C viruses.

Test results are to be used in conjunction with other clinical and epidemiological information. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.

Performance characteristics for detection of influenza A were established when 2009 H1N1 Influenza, Influenza A H1N1, and Influenza A H3N2 were the predominant influenza A viruses in circulation. Due to low seasonal prevalence, performance characteristics for detection of seasonal Influenza A/H1 were established primarily with retrospective and surrogate clinical specimens. When other influenza A viruses are present, performance characteristics may vary.

All users, analysts, and any person reporting diagnostic results from use of this device should be trained to perform and interpret the results from this procedure by JBAIDS instructors or designees prior to use. Use of this device is limited to designated Department of Defense (DoD) laboratories equipped with the JBAIDS instruments.

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 departments for testing. Viral culture should not be attempted in these cases unless a biosafety (BSL) 3+ facility is available to receive and culture specimens.

The JBAIDS Influenza A & B Detection Kit is a rRT-PCR test kit, which, when used with the JBAIDS instrument and software, allows the qualitative in vitro detection of influenza A and B viral RNA. These two assays have been optimized as freeze-dried assays with primer and fluorescent-probe sets for the detection of influenza A and B viral RNA. In particular, the influenza A assay targets a region of the matrix gene specific to the influenza A virus genera, and the influenza B assay targets a region of the nonstructural gene specific to the influenza B virus genera. The tests are performed using the previously FDA-cleared JBAIDS instrument and software. A human gene target assay (RNAse P target) will be used as an inhibition and extraction control.

The provided text describes the JBAIDS Influenza A & B Detection Kit, a real-time PCR assay for the qualitative in vitro detection of influenza A and B viral nucleic acids. The information primarily focuses on the technical aspects of the device and its substantial equivalence to a previously cleared predicate device, especially regarding the detection of specific influenza strains.

However, the document does not contain the kind of information typically found in a study proving a new device meets acceptance criteria, specifically not for an AI/ML-based diagnostic or imaging device. The document is a 510(k) summary for a premarket notification, which focuses on demonstrating substantial equivalence to a legally marketed predicate device rather than presenting a performance study against acceptance criteria in the way one would for a novel device, especially one involving AI.

Therefore, many of the requested items (e.g., sample size for training set, number of experts for ground truth, MRMC study, effect size of AI assistance) are not applicable or cannot be extracted from this document, as it describes a PCR-based diagnostic kit, not an AI/ML device.

Given the constraints of the provided document, I will extract the available relevant information and note where information is not present or non-applicable given the nature of the device described.

Acceptance Criteria and Device Performance (Limited to Analytical Sensitivity/LoD)

The document describes selected analytical studies to determine the Limit of Detection (LoD) for certain influenza A strains, specifically H3N2 and H7N9, which were additions to the device's labeling. This can be interpreted as demonstrating the device's performance against an implicit analytical sensitivity acceptance criterion.

Table 1: Acceptance Criteria (Implied Analytical Sensitivity) and Reported Device Performance

• Estimated LoD: 4 x 10^4^ EID50/mL (confirmed)
• 3/3 replicates positive at 4 x 10^4^ EID50/mL
• 2/3 replicates positive at 8.0 x 10^3^ EID50/mL
  Influenza A H3N2 (seasonal):
• A/Victoria/361/2011: LoD = 63.0 TCID50/mL
• A/Perth/16/2009: LoD = 6.3 TCID50/mL
  Influenza A swine variant H3N2v:
• A/West/Virginia/06/2011: LoD = 31.6 TCID50/mL
• A/Minnesota/11/2010: LoD = 2.0 TCID50/mL |

Note: The document explicitly states: "Serial dilutions were run in triplicate, with all three replicates required to read positive in order for that dilution to be called positive." This stringent requirement for calling a dilution positive influences the reported LoD values.

Study Details:

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

   • Test set sample size: Not specified as a distinct "test set" in the context of clinical validation data for a new device. The data presented is for analytical sensitivity (LoD) testing.
     • For LoD, serial dilutions of viral strains were tested. The number of replicates per dilution is specified: "Serial dilutions were run in triplicate." It is implied that multiple concentrations were tested for each strain.
   • Data provenance: Not explicitly stated for all strains, but the H3N2v and H7N9 strains suggest a focus on variant strains that would have emerged more recently (e.g., A/Anhui/1/2013 for H7N9). The samples were "simulated nasopharyngeal swab samples" meaning they were laboratory-prepared samples rather than clinical patient specimens. The study is described as "Selected Analytical Studies", indicating a laboratory-based evaluation of the assay itself. This falls under retrospective data generated in a controlled lab setting, not real-world clinical samples. No country of origin for test data is specified beyond the DoD context.

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

   • Not applicable. For an analytical sensitivity study of a PCR-based diagnostic kit, the "ground truth" is typically defined by the known concentration of the purified viral standard used to prepare the simulated samples. This does not involve human expert interpretation of results, as the device provides a qualitative "positive, negative, or uncertain" result based on fluorescence thresholds.

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

   • Not applicable. As the "ground truth" is based on known viral concentrations in simulated samples and the device provides an automated qualitative result, there is no human adjudication process involved in interpreting the device's output or establishing the true state of the samples. The requirement for positivity was "all three replicates required to read positive".

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

   • Not applicable. This device is a molecular diagnostic (PCR-based) kit, not an AI-assisted imaging device or a diagnostic requiring human reader interpretation in the context of an MRMC study design. It delivers an objective "positive/negative" result based on molecular detection.

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

   • Yes, this is a standalone device. The JBAIDS kit itself, when used with the JBAIDS instrument and software, performs the detection and provides a result (positive, negative, or uncertain) without requiring human diagnostic interpretation of complex outputs like images. The document states: "JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, or uncertain."

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

   • For the analytical studies described, the ground truth was based on known concentrations of purified viral strains (e.g., EID50/mL or TCID50/mL) in simulated samples. This is a highly controlled laboratory ground truth, not clinical ground truth from patients (like pathology or outcomes data).

7. The sample size for the training set:

   • Not applicable/Not specified. This document describes a traditional real-time PCR diagnostic kit, not an AI/ML device that requires a training set in the machine learning sense. The "training" of such a device involves optimizing primer/probe sets and reaction conditions during its development, not training on a large dataset like an AI model.

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

   • Not applicable. (See point 7). The "ground truth" during the development of such a PCR kit would involve characterizing the specificity and sensitivity of the molecular components against known viral targets and non-targets, rather than establishing ground truth for a training set in an AI/ML context.

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The Joint Biological Agent Identification and Diagnostic System (JBAIDS) Influenza A Subtyping Kit is intended for the in vitro qualitative detection and differentiation of seasonal Influenza A/H1, seasonal Influenza A/H3, and 2009 H1N1Influenza viral nucleic acids isolated and purified from nasopharyngeal swab (NPS) and nasopharyngeal wash (NPW) specimens from human patients with signs and symptoms of respiratory infection, in conjunction with clinical and epidemiological risk factors. The JBAIDS Influenza A Subtyping Kit contains reverse transcriptase real-time polymerase chain reaction (rRT-PCR) assays for use on the JBAIDS instruments. The Flu A H1. Flu A H3. and Flu A H1 2009 assays of the JBAIDS Influenza A Subtyping Kit target a region of the hemagglutinin (HA) gene of the respective Influenza A virus. The Flu A Sw assay of the JBAIDS Influenza A Subtyping Kit targets a region of the nucleocapsid protein (NP) gene of the 2009 H1N1 Influenza virus, as well as some other Influenza A viruses of swine lineage. This kit is not intended to detect Influenza B or Influenza C viruses.

A negative result for all assays in the JBAIDS Influenza A Subtyping Kit is a presumptive negative result for Influenza A. These results should be confirmed using the JBAIDS Influenza A & B Detection Kit.

Test results are to be used in conjunction with other clinical and epidemiological information. Negative results do not preclude influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions.

Due to low seasonal prevalence, performance characteristics for detection of seasonal Influenza A/H1 were established primarily with retrospective and contrived clinical specimens.

All users, analysts, and any person reporting diagnostic results from use of this device should be trained to perform and interpret the results from this procedure by JBAIDS instructors or designees prior to use. Use of this device is limited to designated Department of Defense (DoD) laboratories equipped with the JBAIDS instruments.

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 departments for testing. Viral culture should not be attempted in these cases unless a biosafety laboratory (BSL) 3+ facility is available to receive and culture specimens.

The JBAIDS Influenza A Subtyping Kit is a real time RT-PCR test kit, which, when used with the JBAIDS instrument and software, allows the qualitative in vitro detection and identification of influenza A subtypes H1, H3, and H1 2009 (swine lineage) viral RNA. The assays have been optimized as freeze-dried assays with primer and fluorescent-probe sets for the detection of influenza A/H1, A/H3, and A/2009 H1 viral RNA. In particular, the Flu A H1, Flu A H3, and Flu A H1 2009 assays target distinct regions of the hemagglutinin gene specific to those subtypes, and the Flu A Sw assay targets a region of the nucleocapsid protein gene as a secondary target for the influenza A/2009 H1(swine lineage) virus. The tests are performed using the JBAIDS instrument and software.

Here's an analysis of the acceptance criteria and study details for the JBAIDS Influenza A Subtyping Kit based on the provided text:

Preamble Regarding Acceptance Criteria:
The document provided, a 510(k) Summary, details performance data but does not explicitly state pre-defined "acceptance criteria" in the format of pass/fail thresholds for the clinical study. Instead, it presents the achieved performance metrics (PPA and NPA with 95% Confidence Intervals) from the clinical and analytical studies, implicitly demonstrating that these achieved results were deemed sufficient for substantial equivalence. For the purpose of this response, I will present the reported performance as the "acceptance criteria met," recognizing that the specific numerical targets for acceptance are not explicitly listed in this summary.

1. Table of Acceptance Criteria and Reported Device Performance

As described above, explicit acceptance criteria (i.e., specific numerical targets prior to testing) were not provided in the 510(k) summary. However, the reported performance from the clinical studies served as the basis for the device's clearance. The table below summarizes the reported clinical performance.

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

• Clinical Performance (Prospective Study):

  • Sample Size: 795 valid specimens (312 NPS, 483 NPW) were analyzed. 6% (44/795) required retesting due to invalid/inconclusive/unsubtypeable initial results.
  • Data Provenance: Prospective, collected from 5 geographically separated military clinical sites in the U.S. during the 2010-2011 influenza season (December 2010 to April 2011).

• Testing of Preselected Archived Samples (for Seasonal Influenza A/H1):

  • Sample Size: 51 NPS specimens (30 known positive seasonal Influenza A/H1, 21 influenza-negative).
  • Data Provenance: Retrospective, pre-selected archived clinical NPS specimens obtained and confirmed at two different clinical study sites in the U.S.

• Testing of Surrogate Clinical Specimens (for Seasonal Influenza A/H1):

  • Sample Size: 136 individual influenza-negative clinical specimens (68 NPS, 68 NPW) were spiked with known concentrations of seasonal Influenza A/H1 virus. Valid results obtained for 128 (62 NPW, 66 NPS).
  • Data Provenance: Contrived clinical samples generated from residual influenza-negative NPS and NPW samples. Sent to two different clinical trial sites in the U.S.

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

The document does not explicitly state the number or qualifications of individual experts who established the ground truth. However, the ground truth for the clinical and archived samples was established using a reference method:

• "The reference method was the CDC rRT-PCT Flu Panel influenza A and influenza B assays, followed by subtype-specific PCR and bi-directional sequencing of amplicons."
• "the presence of Influenza A/H1 viral RNA was confirmed using 'validation' PCR assays. The validation PCR assays were identical to the comparator assays that were used for the prospective clinical evaluation study."

This implies that the "experts" were the personnel performing and interpreting the CDC assays and sequencing results, which would typically be highly trained laboratory professionals and molecular biologists proficient in these techniques, likely adhering to CDC protocols. No specific number of such experts is given.

4. Adjudication Method for the Test Set

The document states: "JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, or uncertain. A failure of the Positive or Negative Control will result in the entire run being called invalid. Retesting is required to resolve uncertain or invalid results."

For the clinical study, 6% of specimens (44/795) required retesting. Specifically, "Invalid" (32/44), "Inconclusive" (1/44), and "Unsubtypeable" (1/44). "Forty (40) out of 44 samples resolved upon a 1st retest and the remaining 4 samples required a re-extraction and retest and resolved." This indicates a retesting and re-extraction protocol for initial indeterminate or invalid results rather than a multi-expert adjudication panel for interpretive discrepancies. The ground truth itself (CDC rRT-PCR + sequencing) would have its own internal validation/adjudication processes, but this is not detailed for external review.

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

No multi-reader, multi-case (MRMC) comparative effectiveness study comparing human readers with and without AI assistance was performed. This device is a diagnostic kit (real-time RT-PCR assay) that provides automated qualitative results, not an imaging AI diagnostic aid for human interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not directly apply to this type of device.

6. Standalone Performance Study (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the studies described (clinical performance, archived samples, surrogate samples) represent standalone performance of the algorithm/device. The "JBAIDS Software analyzes the fluorescence amplification curves and reports results as positive, negative, or uncertain." While human operators perform the physical tests, the interpretation of the raw PCR data into a final qualitative result (positive/negative/uncertain) is automated by the device's software (algorithm). The clinical performance data presented (PPA and NPA) are a direct measure of this standalone performance against a defined ground truth.

7. Type of Ground Truth Used

The ground truth used was:

• Expert Consensus/Reference Method: For prospective clinical specimens and archived samples, the reference method was the CDC rRT-PCR Flu Panel influenza A and influenza B assays, followed by subtype-specific PCR and bi-directional sequencing of amplicons. This is a highly robust and accepted laboratory method for viral identification and subtyping.
• Known Spiked Concentration: For surrogate clinical specimens, the ground truth for positive samples was established by spiking influenza-negative clinical samples with known concentrations of seasonal Influenza A/H1 virus. Un-spiked negative samples also served as ground truth negatives.

8. Sample Size for the Training Set

The document does not provide details on a specific "training set" sample size or data for the development of the device's algorithm, as would typically be described for machine learning or AI models. This device is a PCR-based assay, where the "algorithm" is primarily the pre-defined thresholds and analysis logic within the JBAIDS software to interpret PCR amplification curves. Performance characteristics are primarily established through analytical validation (LoD, inclusivity, exclusivity) and clinical validation with independent test sets, rather than an explicit training-validation split in the context of an adaptive or learning algorithm. The design of the primers and probes, and the associated software interpretation, would have been iteratively developed and optimized, but a formal "training set" as understood in AI/ML is not mentioned.

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

As noted above, a formal "training set" for an AI/ML algorithm is not described for this diagnostic kit. The underlying principles of the PCR assay (primer/probe design, reaction conditions) are established through extensive analytical studies to ensure specificity and sensitivity. The "ground truth" for developing the analytical performance characteristics (like LoD, exclusivity, inclusivity) would involve testing well-characterized viral strains and non-target organisms with known concentrations, typically obtained from reference collections. This process establishes the analytical sensitivity and specificity that the device is designed to achieve when interpreting a sample.

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