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The Diagnostic Hybrids, Inc. device, D3 FastPoint L-DFA Influenza A/Influenza B Virus Identification Kit is intended for the qualitative identification of influenza A virus and influenza B virus in nasal and nasopharyngeal swabs and aspirates/washes specimens from patients with signs and symptoms of respiratory infection by direct detection of immunofluorescence using monoclonal antibodies (MAbs).

It is recommended that specimens found to be negative for influenza A or influenza B virus after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude influenza A or influenza B virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Performance characteristics for influenza A virus detection and identification were established when influenza A (H3N2) and influenza A (H1N1) were the predominant influenza A strains circulating in the United States. Since influenza strains display antigenic drift and shift from year to year, performance characteristics may vary. If infection with a novel influenza A virus is suspected, based on clinical and epidemiological screening criteria communicated by public health authorities, collect specimens following appropriate infection control precautions and submit to state or local health departments, for testing. Viral culture should not be attempted in these cases unless a BSL 3+facility' is available to receive and culture specimens .

The D3 FastPoint L-DFA Influenza A/Influenza B Virus Identification Kit (D3 FastPoint A/B Kit) uses a blend (called a "L-DFA Reagent") of viral antigen-specific murine monoclonal antibodies that are directly labeled with either R-PE (influenza A virus) or fluorescein (influenza B virus) for the rapid identification of influenza A virus and influenza B virus in nasal and nasopharyngeal swabs and aspirates/washes specimens from patients with signs and symptoms of respiratory infection.

The cells to be tested are derived from respiratory specimens from patients with signs and symptoms of respiratory infection. The cells are permeabilized and stained concurrently in a liquid suspension format with the L-DFA reagent. After incubating at 35℃ to 37℃ for 5-minutes, the stained cell suspensions are rinsed with 1X PBS. The rinsed cells are pelleted by centrifugation and then re-suspended with the re-suspension buffer and loaded onto a specimen slide well. The cells are examined using a fluorescence microscope. Cells infected with influenza A virus will exhibit goldenyellow fluorescence due to the PE. Cells infected with influenza B virus will exhibit apple-green fluorescence due to the FITC. Non-infected cells will exhibit red fluorescence due to the Evans Blue counter-stain. Nuclei of intact cells will exhibit orange-red fluorescence due to the propidium iodide.

Here's a breakdown of the acceptance criteria and the study details for the D³ FastPoint L-DFA Influenza A/Influenza B Virus Identification Kit:

1. Table of Acceptance Criteria and Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" in a quantitative format for clinical performance beyond the presented sensitivity and specificity. However, based on the clinical trial results, these would be the implied performance metrics.

Analytical Performance (Reproducibility):

Analytical Performance (Limit of Detection - LoD):

Analytical Reactivity (Inclusivity):

The document states "MAbs are reactive with all listed strains" for both Influenza A and B. The acceptance criterion is implicitly 100% reactivity with the tested strains. The reported performance confirms this by showing detection of a specified number of fluorescent cells for all tested strains at 20x LoD.

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

• Clinical Test Set Sample Size:
  • Total Specimens Evaluated: 1519
  • Nasal/Nasopharyngeal Wash/Aspirate (Influenza A): 637 specimens
  • Nasal/Nasopharyngeal Wash/Aspirate (Influenza B): 628 specimens
  • Nasal/Nasopharyngeal Swab (Influenza A): 690 specimens
  • Nasal/Nasopharyngeal Swab (Influenza B): 711 specimens (Note: Summing these individual specimen counts for A and B across different sample types is not appropriate to get a single "total," as the same specimen might be tested for both A and B, and different subsets might be used for different sample types or sites.)
• Data Provenance: Prospective collection from symptomatic individuals suspected of respiratory infection in 4 geographically diverse U.S. clinical laboratories during the 2009 respiratory virus season (January 2009 - March 2009). The specimens were "excess, remnants" that would have otherwise been discarded, implying real-world clinical samples.

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

The document describes the ground truth as a "predetermined algorithm that used composite comparator methods" involving an FDA-cleared Direct Specimen Fluorescent Antibody (DSFA) test and viral culture confirmation. This method does not explicitly state the involvement of human experts establishing the ground truth beyond the likely requirement of trained laboratory personnel to perform and interpret the comparator tests. Therefore, details on the number and qualifications of experts for ground truth establishment are not provided in this document.

4. Adjudication Method for the Test Set:

The ground truth was established using a "composite comparator method":

• "True" positive: Any sample that tested positive by either the comparator DSFA test OR viral culture.
• "True" negative: Any sample that tested negative by BOTH the comparator DSFA test AND viral culture.
  This is a form of adjudication by algorithm/composite reference standard rather than human consensus.

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

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study of human readers with vs. without AI assistance was not done. The study compared the device (D3 FastPoint A/B Kit) directly against a composite reference standard, not against human readers. This device is a diagnostic kit, not an AI or imaging device that would typically involve human reader studies for interpretation.

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

Yes, the performance presented for the D3 FastPoint L-DFA Influenza A/Influenza B Virus Identification Kit is a standalone performance of the device (kit) itself, as read and interpreted by laboratory personnel according to its instructions. It is not an "algorithm" in the modern AI sense, but a lab kit where the reported accuracy reflects the kit's ability to correctly identify the viruses based on fluorescence.

7. The Type of Ground Truth Used:

The ground truth used was a composite reference standard consisting of:

• An FDA-cleared Direct Specimen Fluorescent Antibody (DSFA) test.
• Viral culture confirmation for all negatives from the comparator DSFA test.

8. The Sample Size for the Training Set:

The document does not explicitly mention a separate "training set" for the D3 FastPoint L-DFA Influenza A/Influenza B Virus Identification Kit in the context of machine learning or algorithm development. This device is a traditional in-vitro diagnostic kit. Its development would involve analytical studies and optimization (e.g., antibody selection, reagent formulation) rather than a separate "training set" in the AI sense.

However, the "Analytical Reactivity (inclusivity)" study, which tested the reactivity against 13 influenza A strains and 7 influenza B strains, could be considered part of the analytical development and validation process to ensure the kit's broad detection capabilities for known strains.

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

As there is no explicitly defined "training set" in the AI sense for this traditional diagnostic kit, the concept of establishing ground truth for a training set is not applicable here. The analytical studies (like inclusivity) involved preparing known infected cell suspensions with specified viral strains, where the "ground truth" was inherent in the preparation of these controlled samples.

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The Diagnostic Hybrids. Inc. D Ultra DFA (direct fluorescent antibody) Respiratory Virus Screening & ID Kit is intended for the qualitative detection and identification of the Influenza A. Influenza B, Respiratory Syncytial Virus (RSV), Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 virus in respiratory specimens, by either direct detection or cell culture method, by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

• Performance characteristics for influenza A were established when influenza A/H3 and A/H1 were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.
• 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 BSL3+ facility is available to receive and culture specimens.

The Diagnostic Hybrids, Inc. D3 Ultra DFA RESPIRATORY VIRUS SCREENING & ID KIT uses viral antigen-specific murine monoclonal antibodies that are directly labeled with fluorescein for the rapid detection and identification of respiratory viruses. The kit includes a DFA Screening Reagent that contains a blend of murine monoclonal antibodies (MAbs) directed against seven respiratory viruses (Influenza A, Influenza B, Respiratory Syncytial Virus, Adenovirus, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3) plus seven separate DFA Reagents, each consisting of MAb blends directed against a single respiratory virus. The kit can be used for direct specimen or cell culture screening and final virus identification. The cells to be tested, either derived from a clinical specimen or cell culture, are fixed in acetone. The DFA Screening Reagent is added to the cells to determine the presence of viral antigens. After incubating at 35℃ to 37℃, the stained cells are rinsed with the diluted Wash Solution. A drop of the supplied Mounting Fluid is added and a coverslip is placed on the prepared cells. The cells are examined using a fluorescence microscope. Virus infected cells will be stained with viral specific apple-green fluorescence when stained with the DFA Screening Reagent while uninfected cells will contain no fluorescence but will be stained red by the Evan's Blue counter-stain. If the specimen contains fluorescent cells, the particular virus is identified using the separate DFA Reagents on new, separate cell preparations.

Here's an analysis of the provided text regarding the acceptance criteria and supporting study for the D3 Ultra DFA Respiratory Virus Screening & ID Kit:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implied by its comparison to a "Predicate" device (D3 Ultra DFA Respiratory Virus Screening & ID Kit, K061101) which is already legally marketed. The study focuses on demonstrating high agreement between the modified device ("Subject" test) and the predicate device. Specific numerical acceptance criteria are not explicitly stated in the provided text as pass/fail thresholds against a gold standard, but rather presented as high concordance rates.

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

• Study 1-DS (Direct Specimen Method - Fresh):
  • Sample Size: 326 evaluated specimens (329 collected, 3 had insufficient cells).
  • Data Provenance: Prospectively collected from February through May 2006, from a reference laboratory in the northeast United States.
• Study 2-DS (Direct Specimen Method - Frozen):
  • Sample Size: 192 specimens.
  • Data Provenance: Residual specimen material from December 2005 through February 2006, stored at -70°C, from a hospital laboratory in the northeast United States. Processed between Feb 13-17, 2006.
• Study 2-CC (Cell Culture Method - Frozen):
  • Sample Size: 192 specimens.
  • Data Provenance: Same as Study 2-DS.
• Study 3-DS (Direct Specimen Method - Frozen):
  • Sample Size: 282 evaluated specimens (298 collected, 16 inadequate).
  • Data Provenance: Residual specimen material from January through March 2006, stored at -70°C, from a hospital laboratory in the eastern US. Processed between May 30 - June 1, 2006, at DHI.
• Study 3-CC (Cell Culture Method - Frozen):
  • Sample Size: 298 specimens.
  • Data Provenance: Same as Study 3-DS.
• Study 3a-DS (Direct Specimen Method - Frozen, Non-prospective archival):
  • Sample Size: 26 evaluated specimens (30 collected, 4 had insufficient cells).
  • Data Provenance: Non-prospective archival specimens, previously determined to contain Parainfluenza (types 1, 2, or 3) from October 2005 through April 2006, stored at -70°C, from a hospital laboratory in Italy. Tested at an internal reference laboratory (DHI) between June 7-8, 2006.
• Study 3a-CC (Cell Culture Method - Frozen, Non-prospective archival):
  • Sample Size: 29 specimens (30 collected, 1 unsuitable).
  • Data Provenance: Same as Study 3a-DS.
• Study 3b-CC (Cell Culture Method - Frozen, Non-prospective archival clinical isolates):
  • Sample Size: 81 clinical isolates.
  • Data Provenance: Banked clinical isolates from a frozen archival repository known to contain respiratory viruses from the 2005/2006 respiratory season.

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

The document does not explicitly state the number of experts used or their specific qualifications (e.g., "radiologist with 10 years of experience"). However, the studies compare the "Subject" device's performance to a "Predicate" device. The results of the Predicate device were considered the reference for comparison, implying that the ground truth for the test set was established by the predicate device's results. It's likely that the predicate device's results themselves were established through expert interpretation of a DFA assay.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1). The performance is assessed by comparing the Subject device's results directly against the Predicate device's results. Any discrepancies were noted, for example: "With the exception of 4 specimens, the DS test results were concordant... the Predicate device identified 4 specimens as being negative while the Subject device identified one as Flu B and three as Para 3 infections. All but one of the Para 3 specimens were confirmed by culture." This suggests a follow-up investigation for discordant results, but not a formal adjudication panel.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, Effect Size of Human-AI Improvement

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This study is focused on the performance of the device itself (DFA kit), not on how human readers (e.g., clinicians interpreting the results) improve with or without AI assistance. The D3 Ultra DFA assay is a laboratory diagnostic test.

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

This refers to a traditional in vitro diagnostic device, not an AI-powered one. The performance reported is that of the assay itself, which is inherently "standalone" in its ability to detect viral antigens based on the immunofluorescence reaction. The "human-in-the-loop" aspect would be a trained technologist interpreting the fluorescent microscopy, which is part of the standard procedure for such assays. The study design implicitly describes the standalone performance of the assay kit as interpreted by laboratory personnel, not an AI algorithm.

7. Type of Ground Truth Used

The primary "ground truth" used for comparison in the performance studies was the results obtained from the legally marketed Predicate device (D3 Ultra DFA Respiratory Virus Screening & ID Kit, K061101). In cases of discrepancies or for certain non-prospective archival specimens, viral cell culture was used for confirmation (e.g., "All but one of the Para 3 specimens were confirmed by culture"). Cross-reactivity testing used known virus strains, bacterial cultures, and cell types.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/algorithm-driven device. This is a traditional IVD. The performance data presented are from various "test sets" as described above. The development of the monoclonal antibodies (MAbs) in the kit would have involved internal validation and optimization, but not in the sense of an algorithm training on a dataset.

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

Since there is no "training set" in the AI/algorithm sense, this question is not applicable. The device relies on specific fluoresceinated monoclonal antibodies. The ground truth for developing these antibodies would be established by isolating and characterizing known viral strains, then producing antibodies that specifically bind to antigens from those strains. The "cross-reactivity testing" (Table 15) provides insight into the specificity of these antibodies against a wide range of other organisms, which is crucial for the reliability of the "ground truth" the antibodies are built upon.

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The Diagnostic Hybrids, Inc. device, D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, is intended for the qualitative detection and identification of influenza A, while screening for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2 and 3 viral antigens, in nasal and nasopharyngeal swabs and aspirates or in cell culture. The assay detects viral antigens by immunofluorescence using monoclonal antibodies (MAbs), from patients with signs and symptoms of respiratory infection.

It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Performance characteristics for influenza A virus detection and identification were established when influenza A H3N2 and influenza A H1N1 were the predominant influenza A strains circulating in the United States. When other Influenza A viruses are emerging, performance characteristics may vary. 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 in these cases unless a BSL 3+ facility is available to receive and culture specimens.

The Diagnostic Hybrids, Inc. device, D Duet DFA Influenza A/Respiratory Virus Screening Kit, uses a blend of viral antigen-specific murine MAbs. MAbs for influenza A virus are directly labeled with R-phycoerythrin (R-PE) for the rapid detection and identification of influenza A virus. MAbs for influenza B virus, respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3 are directly labeled with fluorescein isothiocyanate (FITC), for rapid detection of these agents.

Kit components:

• D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent Rphycoerythrin-labeled murine MAbs directed against influenza A virus and a mixture of fluorescein-labeled murine MAbs directed against influenza B. respiratory syncytial virus, adenovirus, and parainfluenza virus types 1, 2, and 3. The buffered, stabilized, aqueous solution also contains Evans Blue as a counterstain and 0.1% sodium azide as preservative.
• Normal Mouse Gamma Globulin DFA Reagcnt a mixture of fluorescein labeled murine gamma globulin that has been shown to be non-reactive with any of the listed respiratory viruses. The buffered, stabilized, aqueous solution contains Evans Blue as a counter-stain and 0.1% sodium azide as preservative.
• Respiratory Virus Antigen Control Slides five individually packaged control slides containing wells with cell culture-derived positive and negative control cells. Each positive well is identified with the virus infected cells present, i.e., influenza A virus, influenza B virus, respiratory syncvtial virus, adenovirus, and parainfluenza virus types 1, 2 and 3. The negative well contains uninfected cultured cells. Each slide is intended to be stained only one time.
• Wash Solution Concentrate a 40X concentrate consisting of Tween 20 and 4% sodium azide (0.1% sodium azide after dilution in de-mineralized water) in a 40X phosphate buffered saline solution.
• Mounting Fluid an aqueous, buffered, stabilized solution of glycerol and . 0.1% sodium azide.

The cells to be tested, derived from a clinical specimen or cell culture, are placed onto a glass slide and allowed to air dry. The cells are fixed in acetone. The D3 Duet DFA Influenza A/Respiratory Virus Screening Reagent is added to the cells which are then incubated for 15 to 30 minutes at 35° to 37°C in a humidified chamber or humidified incubator. The stained cells are then washed with the diluted wash solution, a drop of the supplied Mounting Fluid is added and a coverslip is placed on the prepared cells. The cells are examined using a fluorescence microscope. The influenza A virus infected cells will fluoresce golden-yellow, while cells infected with any of the other six viruses will fluoresce apple-green. Uninfected cells will contain no fluorescence but will be stained rcd by the Evans Blue counter-stain. If only golden-yellow fluorescent cells are present the specimen can be reported as positive for influenza A antigen. If only apple-green fluorescent cells are present, the particular virus may be identified using the individual reagents from the DS Ultra™ DFA Respiratory Virus Screening & ID Kit (D3 Ultra) on new, separate cell preparations. If both golden-yellow and apple-green are present, the additional virus may be identified using the individual reagents from the D3 Ultra on new, separate cell preparations.

Here's a breakdown of the acceptance criteria and the study details for the D3 Duet DFA Influenza A/Respiratory Virus Screening Kit, based on the provided text:

Acceptance Criteria and Device Performance

The acceptance criteria for the D3 Duet DFA Influenza A/Respiratory Virus Screening Kit are established by demonstrating substantial equivalence to a legally marketed predicate device, the D3 Ultra DFA Respiratory Virus Screening & ID Kit (K061101). The performance is measured primarily through Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to the predicate device.

Table 1: Acceptance Criteria and Reported Device Performance (Clinical Study - Direct Specimens)

Table 2: Acceptance Criteria and Reported Device Performance (Clinical Study - Cultured Specimens)

Study Details

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

• Direct Fresh Clinical Specimens:
  • Sample Size: 1184 specimens (from an initial 1203, with 19 excluded).
  • Data Provenance: Prospective study conducted at three unnamed clinical sites. The country of origin is implicitly the United States as it is reviewed by the FDA.
• Cultured Clinical Specimens:
  • Sample Size: 298 frozen specimens.
  • Data Provenance: Conducted at a fourth unnamed clinical site (Study Site 4) using frozen specimens that were processed for cell culture. The specimens were "derived from nasopharyngeal specimens." The country of origin is implicitly the United States.

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

The ground truth for the clinical studies (both direct and cultured specimens) was established by comparison to a "cleared DSFA device" (D3 Ultra DFA Respiratory Virus Screening & ID Kit). While clinical experts read the comparator and subject device results, the document does not specify the number of experts used for establishing the ground truth or their qualifications beyond implying standard laboratory personnel performing the D3 Ultra assay. The D3 Ultra itself would have been interpreted by trained laboratory professionals.

4. Adjudication Method for the Test Set

The document describes comparing the D3 Duet results to the "D3 Ultra Final Identification." This implies that the D3 Ultra's result was considered the reference standard or adjudicated ground truth for the clinical studies. There is no mention of a separate adjudication panel or consensus process for discrepancies between the D3 Duet and D3 Ultra results; the D3 Ultra's result is taken as the benchmark.

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

No MRMC comparative effectiveness study was done to assess the effect size of human readers improving with AI vs. without AI assistance. The study compares the performance of the new device (D3 Duet) to a predicate device (D3 Ultra) in a standalone manner, with both being manual assays performed by laboratory personnel.

6. Standalone (Algorithm Only) Performance

Yes, the studies evaluate the D3 Duet as a standalone diagnostic device. It is a manual immunofluorescence assay performed by laboratory technicians, not an AI algorithm. Its performance is measured directly against the predicate device.

7. Type of Ground Truth Used

• For Clinical Studies (Direct and Cultured Specimens): The ground truth was the "D3 Ultra Final Identification" results. The D3 Ultra is also an immunofluorescence assay.
• For Analytical Studies (Sensitivity, Specificity, Reactivity): The ground truth was established by prepared viral stocks with known concentrations (TCID50) and identification of specific virus strains.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning or AI. This device is a manual laboratory test using monoclonal antibodies, not an AI system. The analytical and precision/reproducibility studies can be considered as validation work that informs the device's design and reliability before full clinical evaluation.

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

As this is not an AI/ML device, there isn't a "training set" in that sense. The development of the D3 Duet's monoclonal antibodies and reagents would have involved extensive laboratory testing and characterization against known viral isolates and cultures to establish their specificity and reactivity, analogous to establishing ground truth for individual components during development. These methods are detailed in the analytical specificity and reactivity sections, where viral strains and dilutions are tested.

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The Diagnostic Hybrids, Inc. D3 Ultra DFA (direct fluorescent antibody) RESPIRATORY VIRUS SCREENING & ID KIT is intended for the qualitative detection and identification of the Influenza A, Influenza B, Respiratory Syncytial Virus (RSV), Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 virus in respiratory specimens, by either direct detection or cell culture method, by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

The Diagnostic Hybrids, Inc. D3 Ultra DFA RESPIRATORY VIRUS SCREENING & ID KIT includes a DFA Screening Reagent that contains a blend of murine monoclonal antibodies (MAbs) directed against seven respiratory viruses (Influenza A. Influenza B. Respiratory Syncytial Virus, Adenovirus, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3) plus seven separate DFA Reagents, each consisting of MAb blends directed against a single respiratory virus. The kit can be used for direct specimen or cell culture screening and final virus identification.

Here's a breakdown of the acceptance criteria and study information for the Diagnostic Hybrids, Inc. D3 Ultra DFA Respiratory Virus Screening & ID Kit, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance (Comparison of Subject Device vs. Predicate Device)

The study's acceptance criteria are implicitly defined by the demonstration of substantial equivalence to the predicate device. The performance is reported in terms of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with 95% Confidence Intervals (CI).

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

• Comparison Studies (Primary Clinical Evaluation):
  • Total specimens: 849 original specimens.
  • Direct Specimen (DS) Testing:
    • Fresh prospectively collected: 326 specimens.
    • Frozen prospectively collected: 474 specimens.
  • Cell Culture (CC) Method Testing: 520 specimens (subset of the 849). Of these, 490 were frozen prospectively collected.
  • Archived Parainfluenza Specimens (Study 3a-DS/CC):
    • DS: 26 specimens
    • CC: 29 specimens
  • Archived Clinical Isolates (Study 3b-CC): 81 clinical isolates.
• Data Provenance:
  • Main study (849 specimens): All but 30 were prospectively collected during the 2005-2006 season. These 30 were archived as Parainfluenza-positive.
  • Archived Parainfluenza Specimens (Study 3a): Frozen original specimens previously determined to contain Parainfluenza (types 1, 2, or 3) during the 2006 "respiratory season," obtained from an additional laboratory.
  • Archived Clinical Isolates (Study 3b): Banked clinical isolates known to contain respiratory viruses from the 2005/2006 respiratory season.
  • Country of Origin: Not explicitly stated, but the submission is to the US FDA by "Diagnostic Hybrids, Inc. Athens, OHIO 45701", implying US-based studies.

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

• The document implies that the "Predicate device" results acted as the reference or ground truth for the comparison studies. Therefore, the "experts" are the lab personnel who interpreted the predicate device results.
• The number and specific qualifications of these experts are not explicitly stated in the provided text. The evaluation was conducted at three laboratory sites.

3. Adjudication method for the test set:

• The document does not describe a specific adjudication method (e.g., 2+1, 3+1). It states that the "Subject" results were compared to "Predicate Results." This implies the predicate results were taken as the standard. In the case of Study 3a (Archived Parainfluenza), it mentions that "Original results reported by the laboratory were unknown to the study investigator," suggesting an independent comparison to pre-existing results rather than a real-time adjudication process.

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

• No, this section is not applicable. The device is an in vitro diagnostic (IVD) test kit for direct detection or cell culture by immunofluorescence using monoclonal antibodies. It is not an AI-assisted diagnostic tool for human readers. Therefore, an MRMC study comparing human readers with and without AI assistance was not performed.

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

• Yes, in a sense. The described performance is the "Subject device" (the test kit itself) compared against a "Predicate device" (another test kit). This represents the performance of the assay/reagent system in a laboratory setting, which is analogous to a "standalone" performance for such an IVD device, as it doesn't involve an AI algorithm or human interpretation outside of standard microscopy and reading of fluorescent signals.

6. The type of ground truth used:

• The primary ground truth used for the comparison studies was the results obtained from a legally marketed predicate device (Diagnostic Hybrids, Inc. DFA Respiratory Virus Screening & ID Kit, K022713).
• For the "Archived Parainfluenza Specimens" (Study 3a) and "Archived Clinical Isolates" (Study 3b), the ground truth was also based on previously determined results (implicitly from a predicate or similar method) for known positive specimens/isolates.

7. The sample size for the training set:

• For the comparative effectiveness studies (clinical evaluations), there is no explicit mention of a separate "training set" for the device itself in the context of an algorithm or machine learning. The studies described are validation studies comparing the performance of the new device to a predicate. The device is a reagent-based test kit, not an algorithm that requires a training set in the typical AI sense.
• However, during the development of the monoclonal antibodies (MAbs) and the kit, internal analytical studies would have been performed. The closest equivalent to "training" for such a device would be the extensive analytical testing described, such as detection limits and analytical specificity testing across various viral strains, host cell types, and bacterial cultures.

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

• As mentioned above, the concept of a "training set" in the context of an algorithm is not directly applicable here.
• For the analytical studies (detection limit, analytical specificity), the "ground truth" was established by:
  • Known viral stocks: Inoculating cell culture plates with specific viruses at known concentrations (e.g., "50 viral particles," "1 viral particle per every 2 wells," "250 virus/mL").
  • Known microorganisms and cell types: Testing against "64 virus strains (cultured and processed for staining)," "18 host culture cell types," and "18 bacterial cultures," where their identity was pre-established.

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The Diagnostic Hybrids, Inc. DFA (Direct Fluorescent Antibody) Respiratory Virus Screening & ID Kit is intended for the qualitative detection and identification of the common respiratory viruses, Influenza A, Influenza B, Respiratory Syncytial Virus (RSV), Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 directly in prepared patient specimens and in cell cultures following viral amplification. Specimens found to be negative after examination of the direct specimen result must be confirmed by cell culture.

The subject device consists of a series of reagents that are used to screen for and identify 7 common respiratory viruses using murine monoclonal antibodies directly labeled with fluorescein (Direct Fluorescence Assay or DFA) and which are specific for antigenic determinants found on each virus. The subject device provides the following materials: Respiratory Virus DFA Screening Reagent, Seven Individual DFA Solutions, Antigen Control Slides, Normal Mouse Gamma Globulin DFA Reagent, Wash Solution Concentrate, and Mounting Fluid. The device is used for direct testing of patient specimens (aspirates, washes or swabs from the nasopharyngeal area) and cell culture testing of specimens.

This document describes the Diagnostic Hybrids, Inc. DFA (Direct Fluorescent Antibody) Respiratory Virus Screening & ID Kit, which is intended for the qualitative detection and identification of 7 common respiratory viruses. The study aims to demonstrate substantial equivalence to a predicate device, the Bartels Viral Respiratory Screening and Identification Kit and the Diagnostic Hybrids, Inc. IFA Respiratory Viruses Screening and Identification Kit (manufactured by Trinity Biotech, Plc). The primary difference between the new device and the predicate is the use of Direct Fluorescent Antibody (DFA) methodology versus Indirect Fluorescent Antibody (IFA).

Here's an analysis of the provided information concerning acceptance criteria and supporting studies:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly state numerical acceptance criteria for sensitivity, specificity, or agreement rates. Instead, the general acceptance criterion appears to be "substantially equivalent" to the predicate device.

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

The exact sample size for the clinical test set is not explicitly stated in numerical terms. The document mentions "clinical specimens" and "specimen data generated by each Study Site."

• Sample Size: Not explicitly quantified. The phrase "clinical specimens" in two study sites suggests a collection of patient samples.
• Data Provenance: Retrospective (clinical specimens were tested), source is two unnamed "study sites" (Appendices 1 and 2, which are not provided in the input). No country of origin is specified, but given the context of FDA submission, it's likely to be the USA.

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

The document does not specify the number of experts or their qualifications for establishing the ground truth of the test set. The ground truth appears to be established by the results of the predicate device.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method. The comparison is made directly between the results of the subject assay and the predicate assay on the same specimens.

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

No, an MRMC comparative effectiveness study involving human readers is not mentioned. The study focuses purely on comparing the performance of the new DFA device against the predicate IFA device. The advantage of DFA is stated as "less than half the time and with fewer reagents and steps," which is an operational efficiency claim rather than improved human effectiveness with AI assistance.

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

Yes, this appears to be a standalone performance study. The device is a diagnostic kit (reagents and procedures) that is compared to another diagnostic kit. The "performance" being evaluated is the accuracy of the DFA test results compared to the IFA test results, not an AI algorithm.

7. The Type of Ground Truth Used

The ground truth for the clinical studies was established using the predicate device's results. The study directly compared the subject assay's results to those of the predicate assay. For the cross-reactivity studies, the ground truth was based on known properties of 92 potentially cross-reacting organisms obtained from the American Type Culture Collection, where the absence of cross-reactivity was expected.

8. The Sample Size for the Training Set

There is no mention of a "training set" in the context of this device. This is a diagnostic kit (reagents and procedures), not an AI algorithm that requires a training set. The "studies" described are validation studies.

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

As there is no training set for this type of device, this question is not applicable.

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The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is intended for the detection and identification of influenza A and influenza B in respiratory specimens such as throat, nasal and nasopharyngeal swabs, nasopharyngeal aspirates, broncho-alveolar lavages from patients with febrile respiratory illness and following amplification of virus in cell culture. Specimens found to be negative on direct specimen examination must be confirmed with culture. For in vitro diagnostic use.

Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay utilizes a single reagent for the simultaneous detection and identification of influenza A and influenza B. The primary component, specific for influenza A, will bind to influenza A nucleoprotein in influenza A-infected cells. The secondary component, specific for influenza B, will bind to influenza B nucleoprotein in influenza B-infected cells. Unbound reagent is removed by rinsing with phosphate-buffered saline (PBS). The complexes are visualized with a fluorescence microscope. The influenza A antigenantibody complex will exhibit an apple-green fluorescence and the influenza B antigenantibody complex will be yellow-gold. Uninfected cells stain a dull red due to the presence of Evans blue in the reagent. antibodies ensures increased specificity of the reagent and reduces the risk of non-specific background or interference.

The "Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay" is intended for the detection and identification of influenza A and influenza B in respiratory specimens.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity and specificity thresholds. However, the conclusion states that the device was shown to be "substantially equivalent" to predicate devices, implying that its performance characteristics were deemed acceptable compared to established methods.

Here's a table summarizing the reported device performance in the clinical evaluation against the cultural gold standard for direct patient specimens:

The document also provides performance relative to predicate devices for culture confirmation, which consistently show 97.8% to 100% sensitivity and 100% specificity for both Influenza A and B, suggesting the device performs very well in this context.

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

• Sample Size for Test Set:
  • Site 1: 147 specimens
  • Site 2: 252 specimens
• Data Provenance: The data is from "clinical evaluation" using "patient specimens." The specific country of origin is not explicitly stated, but given the submission is to the FDA, it is highly likely to be the USA. The study design appears to be prospective or a cross-sectional study collecting current patient specimens for evaluation, as it compares the new device's results to a "culture confirmation" method for those specimens.

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

The document does not specify the number or qualifications of experts involved in establishing the ground truth. It refers to "culture confirmation" as the gold standard. For laboratory culture, the interpretation would typically be done by trained laboratory personnel (e.g., medical technologists, microbiologists), but their specific qualifications or number are not detailed.

4. Adjudication Method for the Test Set

The document does not mention an adjudication method for the test set. Given that "culture confirmation" is used as the ground truth, it implies that the culture results themselves were considered definitive without needing further independent adjudication of the initial test results.

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. This study focuses on the standalone performance of the immunofluorescence assay against a gold standard (culture) and in comparison to predicate devices, not on human reader performance with or without AI assistance.

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

Yes, a standalone performance evaluation was done. The Light Diagnostics SimulFluor™ Flu A/Flu B Immunofluorescence Assay is a laboratory test, and its "performance characteristics" (sensitivity, specificity) were assessed directly. The "visualization with a fluorescence microscope" is a human-in-the-loop step, but the performance metrics are of the device (the reagent's ability to correctly stain infected cells) against the gold standard, implying a standalone evaluation of the diagnostic method itself, interpreted by a human.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical evaluation was culture confirmation. This means that after initial testing, specimens were cultured to grow and identify the influenza virus, providing a definitive diagnosis against which the immunofluorescence assay's results were compared.

8. The Sample Size for the Training Set

The document does not specify a training set for the device. Immunofluorescence assays typically rely on the specificity of monoclonal antibodies rather than machine learning algorithms that require separate training and test sets. The "non-clinical evaluation" involving testing against various microorganisms and cell lines can be considered an initial validation or characterization, but not a "training set" in the machine learning sense.

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

Since there is no explicit training set in the context of the device's development as described, the method for establishing its ground truth is not applicable. The "non-clinical evaluation" involved challenging the conjugated monoclonal antibodies with known viruses and bacteria, where the "ground truth" was the identity of the specific microorganism.

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The IMAGEN™ Respiratory Screen is a qualitative indirect immunofluorescence screening test for the presumptive detection of respiratory viruses; Respiratory Syncytial Virus (RSV). Influenza A and B. Parainfluenza types 1. 2 and 3 and Adenovirus in respiratory specimens (nasopharyngeal aspirates) and in cell cultures.

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Here's an analysis of the provided text regarding the IMAGEN™ Respiratory Screen, structured according to your requested information:

IMAGEN™ Respiratory Screen Acceptance Criteria and Study Details

The provided documents (K973954) consist of a summary of safety and effectiveness, the FDA's clearance letter, and the Indications for Use statement for the IMAGEN™ Respiratory Screen. It is a supplement to K962037.

1. A table of acceptance criteria and the reported device performance

The provided text does not explicitly state numerical acceptance criteria in a table format, nor does it provide detailed performance metrics (like sensitivity, specificity, accuracy) for the IMAGEN™ Respiratory Screen. Instead, it states that "Performance characteristics for the additional intended uses have been established by external clinical evaluation against the Bartels Viral Respiratory Screening and Identification Kit and standard viral isolation reference methods."

To fill this table accurately, we would need to refer to "Exhibit E," which is mentioned as containing the detailed performance data. Without "Exhibit E," specific numerical acceptance criteria and reported device performance cannot be provided.

Hypothetical Table (Illustrative, as actual data is missing from the provided text):

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

• Sample Size for Test Set: Not explicitly stated in the provided documents. The text mentions "clinical evaluation," but the number of specimens tested is not given.
• Data Provenance: The study was an "external clinical evaluation." The specific country of origin for the data is not mentioned. Given the regulatory contact is from the UK, it's possible some or all of the clinical evaluation was conducted there or in other European countries, but this is not confirmed. It is a retrospective evaluation, as the data was collected to establish performance characteristics.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• The ground truth for the test set was established using "standard viral isolation reference methods" and the "Bartels Viral Respiratory Screening and Identification Kit." These methods are considered the gold standard for viral detection.
• The text does not specify the number of individual experts or their qualifications involved in interpreting these reference methods for establishing ground truth. The implication is that the reference methods themselves (e.g., viral culture followed by identification) are the "experts" in this context.

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

• The provided text does not describe any specific adjudication method among human readers for the test set. Since the evaluation was against "standard viral isolation reference methods" and a predicate device (Bartels Kit), the ground truth was inherently established by these objective methods rather than through expert consensus requiring adjudication.

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

• No, an MRMC study was not done. This device is an in vitro diagnostic (IVD) immunofluorescence screening test, not an AI-powered diagnostic tool. The performance description focuses on the agreement of the device's output with reference methods, not on human-reader performance with or without AI assistance.
• Therefore, an effect size for human readers with/without AI assistance is not applicable and not reported.

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

• Yes, a standalone performance evaluation was done. The IMAGEN™ Respiratory Screen itself is an "algorithm only" in the sense that it produces a result (presumptive detection of respiratory viruses) based on the immunofluorescence reaction. The "clinical evaluation against the Bartels Viral Respiratory Screening and Identification Kit and standard viral isolation reference methods" directly assesses the standalone performance of the IMAGEN™ system. The text indicates it's for use in laboratories where "qualified technicians are familiar with routine indirect immunofluorescence testing," suggesting that while human technicians perform the test, the performance being evaluated is that of the assay itself compared to the gold standard.

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

• The ground truth used was "standard viral isolation reference methods" (e.g., cell culture with subsequent viral identification) and comparison against a legally marketed predicate device, the "Bartels Viral Respiratory Screening and Identification Kit." Viral isolation is considered a gold standard for detecting viable viruses. These are objective laboratory methods, not subjective expert consensus or pathology.

8. The sample size for the training set

• The provided documents do not mention a "training set" or its sample size. This is consistent with the nature of an immunofluorescence assay development, which typically undergoes analytical validation and then clinical validation against known specimens rather than learning from a "training set" like an AI model would.

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

• As there is no mention of a "training set" in the context of an immunofluorescence assay, this question is not applicable. The development process for such a device would involve extensive internal validation using characterized specimens, but it's not typically referred to as a "training set" with ground truth established in the same way as machine learning models.

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The IMAGENTM Respiratory Screen is a qualitative indirect immunofluorescence test for the detection of Respiratory Syncytial Virus, Influenza A virus, Parainfluenza virus type 3 and Adenovirus directly in respiratory specimens and Respiratory Syncytial Virus, Influenza A and B virus. Parainfluenza virus types 1, 2 and 3 and Adenovirus in cell culture monolayers.

The test consists of the following reagents: a Screening reagent, a Negative control reagent, a Fluorescein Isothiocyanate (FITC) Conjugate reagent, Mounting fluid, and Positive and Negative Control slides. It is a two-step direct immunofluorescence staining method.

This document describes the IMAGENTM Respiratory Screen, a qualitative indirect immunofluorescence test for detecting various respiratory viruses. The information provided focuses on its performance characteristics and safety.

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific performance metrics (e.g., sensitivity, specificity thresholds). Instead, it describes performance characteristics established through external clinical evaluations against a predicate device (Bartels Viral Respiratory Screening and Identification Kit) and standard viral isolation reference methods.

The reported device performance is presented as a summary of claims that have been established (or are ongoing).

Missing critical information includes:

• Specific sensitivity and specificity values (or other relevant metrics) that were considered acceptable.
• The statistical methods used to determine if the performance met any implicit criteria.

Study Information

The document provides limited details on the specific studies conducted:

• Sample size used for the test set and the data provenance: The document does not specify the sample size used for the external clinical evaluation (test set). It also does not mention the country of origin of the data or whether the studies were retrospective or prospective. It only states "external clinical evaluation."
• Number of experts used to establish the ground truth for the test set and the qualifications of those experts: This information is not provided.
• Adjudication method for the test set: The document does not describe any adjudication method.
• If a multi-reader multi-case (MRMC) comparative effectiveness study was done: An MRMC study is not mentioned. The evaluation was against a predicate device and standard viral isolation reference methods, not described as a comparative effectiveness study with human readers.
• If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: The IMAGENTM Respiratory Screen is a diagnostic kit (reagents) used by qualified technicians. Its performance is inherently linked to human interpretation, so a purely standalone (algorithm-only) performance is not applicable in the traditional sense for this type of test. Its "standalone" performance would be the performance of the assay itself when processed and interpreted by a technician, which is what the clinical evaluation would assess.
• The type of ground truth used: The ground truth for the test set was established using "the Bartels Viral Respiratory Screening and Identification Kit and standard viral isolation reference methods." This implies that viral isolation (a microbiological gold standard) was the primary ground truth, with the Bartels kit potentially used as a comparator or secondary reference.
• The sample size for the training set: This information is not provided. As an immunofluorescence assay kit, it doesn't typically have a "training set" in the machine learning sense. The "training" of the product would involve its development, antibody selection, and optimization, not a data-driven training set like an AI algorithm.
• How the ground truth for the training set was established: Not applicable in the context of an immunofluorescence test kit, as there's no "training set" in the AI sense. The development of the kit would rely on known positive and negative viral samples for reagent specificity and sensitivity optimization.

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