(25 days)
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.
| Acceptance Criteria Category | Specific Criteria/Metric | Target Performance (Implied from Study Design) | Reported Device Performance (Summary) |
|---|---|---|---|
| Analytical Sensitivity (LOD Equivalency) | 100% positivity (3/3 replicates) at either the same endpoint LOD concentration or within a 5-fold dilution of the predicate device for benchmark strains. | Demonstrated. | Met for all tested benchmark and current strains across both enzyme systems (Invitrogen Superscript and Quanta qScript). |
| Analytical Sensitivity (LOD Confirmation) | ≥95% of 20 individually extracted replicates testing positive at the confirmed LOD. | Demonstrated. | Met for all modified InfA, pdmInfA, and pdmH1 assays with various influenza strains and both enzyme systems. |
| Analytical Sensitivity (Inclusivity) | All tested influenza A strains (10 for pdmInfA/pdmH1, 24 for InfA) at low titer (near LOD) should result in 3/3 positive replicates. | 100% positive agreement for all inclusivity strains. | Achieved 3/3 positive replicates for all 10 pdmInfA/pdmH1 inclusivity strains and all 24 InfA inclusivity strains. |
| Analytical Specificity (Cross-Reactivity) | No cross-reactivity with non-targeted influenza viruses at high titers, with the exception of specific known cross-reactivity where noted. | Limited to no cross-reactivity. | Modified InfA assay showed expected positive results for B/Victoria and B/Yamagata lineages. Modified pdmInfA assay showed cross-reactivity with one non-targeted influenza virus at very high titer (specifying A/Iowa/1/2006, A/Texas/14/2008, A/Ohio/09/2015 [A(H1N1)v], A/Minnesota/19/2011, A/Ohio/35/2017 [A(H1N2)v], A/Ohio/13/2017 [A(H3N2)v], A/gyrfalcon/Washington/41088-6/2014 [A(H5N8)]). |
| Analytical Specificity (Exclusivity) | No cross-reactivity with 35 common non-influenza respiratory pathogens (bacteria, yeast, other viruses) at high titers. | No amplification for non-influenza pathogens. | No cross-reactivity observed with any of the 35 tested non-influenza respiratory pathogens. |
| Clinical Performance (Positive Agreement) | High positive agreement with the predicate device on residual clinical specimens. | 100% agreement expected. | Modified InfA Assay: 100% positive agreement across all specimen types and both enzyme systems (e.g., NPS, NS: 51/51). Modified pdmInfA and pdmH1 Assays: 100% positive agreement across all specimen types and both enzyme systems (e.g., NPS, NS: 28/28). |
| Clinical Performance (Negative Agreement) | High negative agreement with the predicate device on residual clinical specimens. | 100% agreement expected. | Modified InfA Assay: 100% negative agreement (54/54 NPS) for both enzyme systems. Modified pdmInfA and pdmH1 Assays: 100% negative agreement (54/54 NPS) for both enzyme systems. |
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.
- Sample Size:
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.
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.