Search Results

The Vysis CLL FISH Probe Kit is intended to detect deletion of the LS1 TP53, LSI ATM, and LSI D13S319 probe targets and gain of the D12Z3 sequence in peripheral blood specimens from untreated patients with B-cell chronic lymphocytic leukemia (CLL). The assay may be used to dichotomize CLL (the 13q-, +12, or normal genotype group versus the 11q- or 17p- group) and may be used as an aid in determining disease prognosis in combination with additional biomarkers, morphology, and other clinical information. The Vysis CLL FISH Probe Kit is not intended for use in selection of therapy or in monitoring of residual disease.

The Vysis CLL FISH Probe Kit uses fluorescence in situ hybridization (FISH) DNA probe technology to determine deletions of the locus-specific identifier (LSI) TP53, LSI ATM, and LSI D13S319 probe targets and gain of the D12Z3 sequence.

The Vysis CLL FISH Probe Kit (List No. 4N02-020) consists of two DNA FISH probe sets and three general purpose reagents sufficient to process 20 assays.

• . LSI TP53 SpectrumOrange/ATM SpectrumGreen Probe
• LSI D13S319 SpectrumOrange/13q34 SpectrumAqua/CEP 12 SpectrumGreen Probe .
• DAPI II Counterstain .
• NP-40 .
• 20X SSC Salt .

Here's a summary of the acceptance criteria and the study details for the Vysis CLL FISH Probe Kit, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

Note: The 510(k) summary for the Vysis CLL FISH Probe Kit primarily focuses on analytical performance (specificity, sensitivity, normal cut-off values, precision, reproducibility) and concordance with an existing clinical assay rather than traditional "acceptance criteria" related to a new AI/CADe device. The provided tables outline the device's technical performance.

Study Details

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

   • Analytical Specificity: 5 karyotypically normal male peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Analytical Sensitivity: 25 karyotypically normal patient peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Analytical Characterization of Normal Cut-off Values: 25 karyotypically normal patient peripheral blood cultures (retrospective, assumed domestic, not explicitly stated).
   • Precision:
     • Precision Study 1: 2 negative peripheral blood specimens (lacking abnormalities) and 8 additional specimens with at least one abnormality. Likely retrospective, but not explicitly stated.
     • Precision Study 2: 8 different patient specimens (blinded panel). Likely retrospective, but not explicitly stated.
   • Reproducibility: A blinded 20-member slide panel representing five Döhner classifications. Likely retrospective, but not explicitly stated.
   • Method Concordance: 64 specimens with pre-established Döhner classifications. Retrospective, as classifications were "based on previous results using the RFT." Provenance not explicitly stated.

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

   • Analytical Specificity: One technologist. Qualifications not specified beyond being a "technologist."
   • Analytical Sensitivity: Not explicitly stated, but each technologist evaluated 100 nuclei per specimen, implying multiple technologists were involved. Qualifications not specified.
   • Analytical Characterization of Normal Cut-off Values: Not explicitly stated, but implies multiple technologists based on the sensitivity study. Qualifications not specified.
   • Precision: Not specified, but involved counting signals, implying trained technologists.
   • Reproducibility: Not specified, but involved three different laboratories, implying multiple trained personnel.
   • Method Concordance: The "Reference FISH Test (RFT)" was used to establish initial Döhner classifications. The original Shanafelt study (referred to as the RFT) implies multiple pathologists/cytogeneticists. This study used "previous results" from the RFT as its ground truth.

3. Adjudication method for the test set:

   • No formal adjudication method (like 2+1 or 3+1) is explicitly described for establishing the ground truth or validating results in the analytical studies. Results were typically enumerated by technologists and aggregated.
   • For the Reproducibility study, "overall agreement" between three testing sites was assessed, but a specific adjudication process for discrepancies is not detailed beyond reporting disagreement counts.
   • For Method Concordance, the ground truth was the "Reference FISH Test (RFT) used in the Shanafelt study," which effectively served as the gold standard, and the AMT results were compared against it.

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 MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was reported. This device is a FISH probe kit, not an AI-powered diagnostic system. The studies focused on the analytical and clinical validity of the probe kit itself.

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

   • This is not an algorithm-only device. It is a laboratory assay (FISH probe kit) where human technologists perform the analysis by counting fluorescent signals under a microscope. The studies performed were of the laboratory kit's performance, not an automated algorithm.

6. The type of ground truth used:

   • Analytical Specificity, Sensitivity, Normal Cut-off, Precision: Based on visual identification and enumeration of FISH signals by trained technologists, comparing observed signal patterns to expected normal or abnormal patterns in karyotypically normal and patient samples. The "expected normal" pattern serves as a form of expert-derived ground truth.
   • Reproducibility: Comparison of results across multiple labs/readers for the same samples. The "agreement" between sites implies a consensus or majority rule for comparison, but the ultimate ground truth for a given sample's true Döhner classification is not explicitly detailed but likely derived from expert pathological/cytogenetic review.
   • Method Concordance: The ground truth was established by a "Reference FISH Test (RFT) used in the Shanafelt study," which is stated to have its clinical validity documented via peer-reviewed literature. This implies a ground truth based on established clinical and pathological diagnosis as determined by a validated method.

7. The sample size for the training set:

   • This device is a diagnostic kit, not an AI/machine learning algorithm, so there is no "training set" in the conventional sense of AI development. The studies described are for analytical validation and clinical concordance.

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

   • Since there's no AI "training set," this question is not applicable. The device's performance characteristics (specificity, sensitivity, cut-offs) are established through testing on defined sets of samples (e.g., karyotypically normal individuals, patients with confirmed CLL aberrations) where the expected outcome is known or determined by expert review using established cytogenetic methods.

Ask a specific question about this device

The CEP 12 SpectrumOrange Direct Labeled Chromosome Enumeration DNA Probe Kit is designed to be an adjunct to standard cytogenetic analysis for in vitro diagnostic use in identifying and enumerating chromosome 12 via fluorescence in situ hybridization (FISH) in interphase nuclei of cells obtained from peripheral blood lymphocytes in patients with chronic lymphocytic leukemia (CLL). Results from the CEP 12 SpectrumOrange Direct Labeled Chromosome Enumeration DNA Probe Kit are intended for use in conjunction with standard cytogenetics and for further assessing the trisomy 12 status in normal and abnormal tissue specimens characterized by standard cytogenetics, in patients with and/or without clinical symptoms of CLL. It is not intended to be a stand alone assay for test reporting.

The CEP 12 SpectumOrange DNA Probe is a SpectumOrange fluorescent labeled DNA probe specific for the centromeric region of chronosome 12. This assey is designed IDN provide a rapid and reliable method for the desertion and quantification of chromosome 12 In interphase nuclei by fluorescence in situ hybridization (FISH).

Here's a breakdown of the acceptance criteria and study information for the CEP 12 SpectrumOrange DNA Probe Kit, based on the provided text:

Acceptance Criteria and Reported Device Performance

Study Details

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

• Pivotal Study (Hybridization Efficiency): 402 peripheral blood specimens.
• Analytical Specificity: 56 metaphase spreads.
• Reproducibility Study:
  • 0% specimen: 22 replicates
  • 5% specimen: 23 replicates
  • 10% specimen: 23 replicates
  • 13% specimen: 24 replicates
  • Provenance: Hematologically derived human cells (mixtures with known percentages of trisomy 12).
• Clinical Specimens (Methods Comparison):
  • Total 402 peripheral blood specimens from patients with B-cell chronic lymphocytic leukemia (B-CLL).
  • Provenance: Multi-center study; specimens from three sites (Site 1: 97 specimens, Site 2: 205 specimens, Site 3: 100 specimens). One site (from the United Kingdom) provided 157 specimens.
  • Retrospective/Prospective: Not explicitly stated, but the collection of "peripheral blood specimens... from a total of 402 patients" suggests they were likely retrospective, selected for the study.

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

• Analytical Specificity: Examination "sequentially by G-banding" followed by FISH. This implies cytogeneticists, but the number and specific qualifications are not detailed.
• Reproducibility Study: "Known percentages of trisomy 12" in the cell mixtures suggests a predefined truth, likely established by advanced cytogenetic techniques, but no "experts" are explicitly described for this part of ground truth establishment.
• Clinical Specimens (Methods Comparison): Standard cytogenetic analysis was used as the comparator (ground truth). Each site followed "its own in-house protocol for standard cytogenetic analysis." This implies trained cytogeneticists performed the standard cytogenetic analysis and interpretation due to the nature of G-banding and karyotyping. The number of experts per site is not specified, nor are their detailed qualifications (e.g., years of experience).

4. Adjudication Method for the Test Set:
The document does not explicitly describe a formal adjudication method (e.g., 2+1, 3+1) for the interpretation of either the FISH results or the standard cytogenetic results. For clinical specimens, it notes that "inter-site and observer-to-observer variations were observed" in the reproducibility study, suggesting independent assessments without a specific adjudication process mentioned for discrepancies in the broader clinical study.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study, in the sense of evaluating how much human readers improve with AI vs. without AI assistance, was not performed. This study compares a device (FISH probe) to a standard clinical method (cytogenetics), which are both human-interpreted methods, not an AI system.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
Yes, the analytical sensitivity, specificity, and reproducibility studies for the CEP 12 SpectrumOrange DNA Probe Kit essentially represent standalone performance where the probe kit itself is being evaluated. The reading of the FISH signals is a human-in-the-loop step, but the performance metrics (hybridization efficiency, LOD, cross-hybridization) are inherent to the probe and its interaction with the biological sample.

7. Type of Ground Truth Used:

• Analytical Specificity: G-banding (a traditional cytogenetic technique for chromosome identification).
• Reproducibility: "Known percentages of trisomy 12" in cell mixtures, implying a highly characterized true state.
• Clinical Specimens (Methods Comparison): Standard cytogenetic analysis (G-banded karyotyping).

8. Sample Size for the Training Set:
The document does not mention a training set or machine learning/AI algorithms that would require one. This submission is for a DNA probe kit, not an AI-powered diagnostic device.

9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no training set mentioned.

Ask a specific question about this device