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This assay is designed to provide a method for the detection and quantification of chromosome 8 in both interphase nuclei and metaphase spreads by fluorescence in situ hybridization (FISH).

The CEP 8 SpectrumOrange DNA Probe is a SpectrumOrange fluorescent labeled DNA probe specific for the centromeric region of chromosome 8.

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance for CEP 8 SpectrumOrange DNA Probe Kit

1. Table of Acceptance Criteria and Reported Device Performance

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

• Analytical Sensitivity & Specificity:
  • Hybridization Efficiency: Pilot study had 35 bone marrow (BM) specimens. Pivotal study had 60 BM specimens.
  • Analytical Specificity: 62 metaphase spreads.
  • Data Provenance: Not explicitly stated (e.g., country of origin), assumed to be within the US given FDA submission. It's retrospective for analytical specificity (archived metaphase spreads).
• Reproducibility:
  • Pilot Study: One normal bone marrow specimen. N=24 observations/measurements.
  • Pivotal Study: One low-level (approximately 7%) trisomy 8 bone marrow specimen. N=24 observations/measurements.
  • Data Provenance: Not explicitly stated, likely multi-site within the US. Retrospective (single specimens used for repeated testing).
• Clinical Performance (Methods Comparison):
  • Test Set Size: 368 archived bone marrow specimens.
  • Data Provenance: Multi-center study involving four laboratories providing specimens (Site 1: 101, Site 2: 57, Site 3: 130, Site 4: 80, with Site 4 specimens analyzed at Site 3). The source of the specimens is described by the diseases: Acute myeloid leukemia (AML), Myeloproliferative disorder (MPD), Myelodysplastic syndrome (MDS), Chronic myelogenous leukemia (CML), Hematological disorder, not otherwise specified (HIDNOS). The data is retrospective as it used "archived bone marrow specimens." The country of origin is not specified but the study was submitted to the FDA.

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

• The ground truth for the clinical studies (Methods Comparison) was established by "standard cytogenetic analysis" performed by the participating laboratories.
• The text does not specify the number of individual experts per lab or their specific qualifications (e.g., "radiologist with 10 years of experience"). However, "standard cytogenetic analysis" implies trained and qualified cytogeneticists or laboratory personnel are performing the traditional karyotyping and interpretation.

4. Adjudication Method for the Test Set

• The text does not explicitly describe an adjudication method for the ground truth (standard cytogenetics) in the methods comparison study. It implies that the "standard cytogenetic analysis" results from each participating laboratory were accepted as the ground truth.
• For the device's own FISH analysis, inter-observer and inter-site variability were assessed in the reproducibility studies, suggesting that multiple observers/sites independently evaluated the samples, but it doesn't detail a formal adjudication process for discordant results.

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

• No, a MRMC comparative effectiveness study was not explicitly conducted to assess human readers' improvement with AI vs. without AI assistance.
• This device is a DNA probe kit for Fluorescence In Situ Hybridization (FISH), which is a laboratory assay where trained personnel visually count signals or use automated enumeration systems. It is not an "AI" device as described in modern AI/ML contexts that would assist radiologists or other human readers. The study compares the performance of the FISH assay (both interphase and metaphase interpretation) against the standard cytogenetic analysis.
• The reproducibility studies assessed inter-observer variability for the FISH assay itself, reflecting the inherent subjectivity of visual enumeration, but not the impact of an AI assistance tool on human performance.

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

• Yes, standalone performance was assessed. The CEP 8 SpectrumOrange DNA Probe Kit is the "algorithm" in this context (or more accurately, the assay and its interpretation guidelines).
• The entire clinical methods comparison study (comparing FISH interphase and metaphase analysis to standard cytogenetics) represents the standalone performance of the assay and its associated interpretation criteria (e.g., 2.2% cutoff for interphase, >=2 tri-signaled metaphases for metaphase). The sensitivity, specificity, and correlation coefficients reported are for the device's performance when applied according to its instructions.

7. Type of Ground Truth Used

• For the clinical methods comparison study, the ground truth was expert consensus / established diagnostic method: Standard Cytogenetic Analysis. This method is referred to as "the standard of care."

8. Sample Size for the Training Set

• The text does not explicitly describe a separate training set in the way modern machine learning models would have one.
• The "pilot study" and "pivotal study" results for hybridization efficiency and reproducibility involve smaller numbers of specimens (35 BM, 60 BM, single normal and single trisomy 8 specimens) that could be considered part of the development and refinement of the assay and its interpretation rules, but not a formal "training set" for an algorithm. The 2.2% cutoff for interphase analysis appears to have been 'validated by the same pivotal clinical study,' suggesting it was developed and then verified within the context of the overall validation.

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

• Since there's no explicitly defined "training set" for an algorithm in the modern sense, the concept of establishing ground truth for it doesn't directly apply here.
• However, the underlying biological understanding and the methodology of interpreting FISH signals (e.g., what constitutes a "tri-signaled nuclei") would be based on established cytogenetic principles and likely refined through internal studies during the probe's development, informed by standard cytogenetic analysis, which is the gold standard for chromosomal abnormalities. The cutoff values (like 2.2%) were likely empirically determined and then validated against the clinical performance.

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