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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. 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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