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The Caltag Fetal Hemoglobin Test, containing either FITC, R-PE or TRI-COLOR® conjugated monoclonal antibodies to fetal hemoglobin (hemoglobin F), is intended for the identification followed by enumeration of fetal red blood cells. Fetal red cells are identified by the presence of fetal hemoglobin by a flow cytometric method. Fetal cells, when found in the maternal circulation, may be an indication of fetal or maternal complications. The hemorrhage of Rh+ fetal blood into Rh- maternal blood may result in the formation of sensitizing Rh antibodies in the mother. This Rh immunization may be prevented by the administration to the mother of Rh immune globulin (RhIg) soon after delivery. The Caltag Fetal Hemoglobin Test may be used as an aid in detecting incompatible fetal-maternal hemorrhage and determining the need for immunoprophylaxis with Rh immune globulin.

An anticoagulated peripheral blood sample is drawn from an appropriate donor. The erythrocyte count is determined and adjusted, followed by brief fixation of the cells in gluteraldehyde. Fixed and washed cells are permeabilized with a detergent in a manner that is frequently used to enable macromolecules such as monoclonal antibodies to penetrate cellular membranes. Caltag HbF FITC, HbF R-PE and HbF TRI-COLOR monoclonal antibodies bind to fetal hemoglobin in fetal red cells. To identify cells containing fetal hemoglobin, fixed and permeabilized cells are incubated with the monoclonal antibody, and washed to remove unbound antibody. Antibody stained cells are subsequently analyzed by flow cytometric methods. Positive and negative control samples must be used with sample analysis, to establish that all reagents are performing in a consistent manner and that the positive fluorescence attributed to antibody-stained fetal red cells is differentiated from unstained normal red blood cells, leukocytes and any cellular debris. If cord blood is not available for the performance of positive controls, the assay cannot be performed reliably. The recommended positive control samples consist of both 1% and 5% fetal erythrocyte-containing placental cord blood in normal adult blood. The recommended negative control sample consists of 1% anticoagulated sample from a normal male or non-pregnant adult female.

Here's a breakdown of the acceptance criteria and the study details for the Caltag Fetal Hemoglobin Test, based on the provided text:

Acceptance Criteria and Device Performance

The core of the acceptance criteria for this device revolves around demonstrating substantial equivalence to the predicate device (Sure-Tech Fetal Hemoglobin Test, K892241). This is primarily shown through correlation studies and assessments of expected values and reproducibility.

1. Table of Acceptance Criteria and Reported Device Performance

Given that this is a 510(k) summary for a diagnostic device, the acceptance criteria are not explicitly stated as pass/fail thresholds in the same way they might be for a therapeutic device. Instead, the performance is demonstrated by showing strong correlation with the predicate device and acceptable levels of specificity, reproducibility, and linearity.

2. Sample Size and Data Provenance

• Correlation Studies (Test Set):

  • Site 1: 50 prepared samples, 30 patient samples.
  • Site 2: 15 prepared samples, 38 patient samples.
  • Site 3: 15 prepared samples, 13 patient samples.
  • Total: 80 prepared samples, 81 patient samples (summing across sites, noting some overlap in prepared samples).
  • Provenance: "patient samples were obtained from women having clinical indications that were consistent with fetal-maternal hemorrhage and prepared samples consisted of mixtures of fetal cord blood in normal adult blood." The studies were conducted in three independent laboratories in geographically diverse areas within the United States. This implies retrospective for patient samples with specific clinical indications, and prospectively prepared for mixed samples.

• Expected Values Data:

  • Sample Size: 161 adult female normal donors.
  • Provenance: Collected from "adult female normal donors" across "three independent laboratories" in "geographically diverse areas within the United States, including the Northern, South-central and Western regions." Donors were of "differing ethnic origins, including adult Caucasians, Blacks, Orientals and Hispanics." This data is prospective.

• Specificity Data:

  • Sample Size: Not explicitly stated but "blood samples were obtained from healthy normal donors of Caucasian, Black, Hispanic and Oriental ethnic origins." (likely a subset of the 161 from expected values, or similar cohort).
  • Provenance: Healthy normal donors, likely prospective.

• Reproducibility Data (Intra-lab & Inter-lab):

  • Sample Size: 6 replicated determinations for each antibody at high, medium, and low levels, performed across three independent laboratories. The samples were "varying mixtures of placental cord blood in normal adult blood." For inter-lab, "unstained and unfixed samples containing mixtures of cord blood in normal adult blood representing the appropriate ranges were prepared by one of the participating laboratories for staining and analysis by each of the participating laboratories." This involved prepared samples, likely prospective.

• Linearity of Measurement:

  • Sample Size: 10 samples (mixtures of cord blood cells in normal adult blood).
  • Provenance: Prepared samples, prospective.

• Detection of 100% Cord Blood:

  • Sample Size: 5 different cord blood samples.
  • Provenance: Cord blood samples, likely prospective.

3. Number of Experts Used to Establish Ground Truth and Qualifications

• The document does not explicitly mention "experts" being used to establish ground truth for this device in the sense of trained clinicians making diagnoses that the device is then compared against.
• Instead, the Kleihauer-Betke (KB) test is used as the comparative "ground truth" to which the Caltag device is correlated. The KB test is an established, widely used microscopic staining method for detecting fetal hemoglobin. The interpretation of KB tests typically involves trained laboratory technicians or pathologists.
• The document states that the correlation study was conducted in 3 independent laboratories, implying that personnel trained in both flow cytometry and the KB method were involved in generating the data. No specific qualifications (e.g., "Radiologist with 10 years of experience") are provided for these individuals, as the device measures a quantitative biological marker rather than interpreting images.

4. Adjudication Method for the Test Set

• No explicit adjudication method (e.g., 2+1, 3+1) is mentioned.
• The "ground truth" for the correlation studies was the result from the Kleihauer-Betke (KB) test. This is a laboratory test with an established protocol, and the agreement is between the Caltag device's quantitative output and the KB test's quantitative output, rather than human expert interpretations requiring adjudication.

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

• No MRMC comparative effectiveness study was done.
• This device is a diagnostic assay that directly quantifies fetal hemoglobin. It is not an AI-assisted interpretation tool for human readers, so comparing human readers with and without AI assistance is not applicable to this type of device.

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

• Yes, the performance presented for the Caltag Fetal Hemoglobin Test is its standalone performance. The flow cytometric analysis is an automated process after sample preparation and staining with the monoclonal antibodies. The reported percentages of positive cells (e.g., mean % positive, r² values) represent the device's output. While human technicians perform the sample preparation and operate the flow cytometer, the measurement itself is performed by the instrument and its associated software, making it a standalone quantitative measurement.

7. Type of Ground Truth Used

• The primary ground truth used for comparison and validation is the Kleihauer-Betke (KB) microscopic staining method. This is a laboratory-based, established diagnostic test for quantifying fetal red blood cells.
• For the 100% cord blood samples, the "ground truth" is the known composition of the sample (i.e., that it should be 100% fetal cells), effectively using known sample composition.
• For expected values and specificity, healthy normal donors were the "ground truth" for what constitutes a normal, non-pregnant sample result.

8. Sample Size for the Training Set

• The document describes studies for validation and substantial equivalence, not a machine learning "training set" in the modern sense. Therefore, there isn't a "training set" sample size like one would find for an AI/ML algorithm.
• The "expected value" data (161 donors) and "specificity" data implicitly contribute to defining the normal operating parameters and behavior of the test, which could be considered analogous to internal validation or establishing reference ranges.

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

• As mentioned, there isn't a "training set" in the AI/ML context.
• For the data that helps define the device's characteristics (e.g., expected values, specificity), the ground truth was established by:
  • Using healthy normal donors to determine normal ranges and confirm specificity (i.e., no fetal cells expected, or very low baseline).
  • Using known prepared samples (mixtures of cord blood and adult blood) to assess linearity and reproducibility. These samples have a known, pre-determined percentage of fetal cells.

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