Search Results

HemosIL CL HIT-IgG(PF4-H) is a qualitative, fully automated, chemiluminescent immunoassay (CIA) for the detection of IgG antibodies that react with Platelet Factor 4 (PF4) when complexed to heparin. The assay is for use in human 3.2% citrated plasma on the ACL TOP 970 CL in a laboratory setting.

The result provided by the assay should be interpreted as either positive or negative based on the assay cut-off (1.00 U/mL). The positive or negative result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings.

Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult population suspected of HIT. Not for use in isolation to exclude HIT.

For prescription use only.

HemosIL CL HIT-IgG(PF4-H) assay is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with PF4 complexed to polyvinyl sulfonate (PVS) which capture, if present, PF4/H antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind with the captured PF4/H IgG on the particles. After a second incubation, magnetic separation, and a wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL TOP 970 CL optical system. The RLUs are directly proportional to the PF4/H IgG concentration in the sample.

The HemosIL CL HIT-IgG(PF4-H) assay utilizes a 4 Parameter Logistic Curve fit (4PLC) data reduction method to generate a Master Curve. The Master Curve is predefined and lot dependent and it is stored in the instrument through the cartridge barcode. With the measurement of calibrators, the predefined Master Curve is transformed to a new, instrument specific 4PLC Working Curve. The concentration values of the calibrators are included in the reagent kit calibrator value sheet 2D barcode.

Here's a breakdown of the acceptance criteria and study information for the HemosIL CL HIT-IgG(PF4-H) device, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Precision Study: 5 plasma samples and 2 levels of controls. Tested over 20 days.
• Reproducibility Study: 6 plasma samples. Tested across 3 external sites, twice per day over 5 days with 3 replicates.
• Analytical Sensitivity (LoD): Not explicitly stated, but assessed using "three different lots" of reagent cartridges.
• Analytical Specificity: Not explicitly stated, but involved testing with various interfering substances and 24 citrated plasma samples from APS patients.
• Normal Reference Range Study: 132 Heparin-Exposed, Non-HIT Suspected Patients and 122 Healthy Donors.
• Cut-Off Validation Study (vs. SRA): 91 citrated plasma samples (45 SRA positive, 46 SRA negative).
• Method Comparison Study (vs. Predicate): 341 samples from HIT-suspected patients.

Data Provenance: The document does not explicitly state the country of origin for the patient data. It is implied to be retrospective as the samples were "from HIT-suspected patients" or "patients diagnosed with Antiphospholipid Syndrome (APS)", suggesting they were pre-collected. The reproducibility study explicitly states it was done at "3 external" sites.

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 used to establish the ground truth for the test set.

• For the Cut-Off Validation Study, Serotonin Release Assay (SRA) results were used as the reference standard, indicating a highly specialized laboratory assay.
• For the Method Comparison Study, the predicate device (HemosIL AcuStar HIT-IgG(PF4-H)) served as the reference standard.
• For the Normal Reference Range Study, patient classification as "Heparin Exposed, Non-HIT Suspected Patients" or "Healthy Donors" implies a clinical determination, but no expert involvement is specifically detailed.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the test set or for establishing ground truth. The SRA and predicate device results appear to be taken as the reference.

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 device is an in-vitro diagnostic (IVD) immunoassay, not an imaging or software device that would typically involve human readers. The study focuses on the analytical and clinical performance of the assay itself.

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

Yes, the studies described are standalone performance evaluations of the HemosIL CL HIT-IgG(PF4-H) assay. The device is a "fully automated, chemiluminescent immunoassay (CIA)" and the performance data reflects its direct measurement capabilities on an ACL TOP 970 CL instrument without explicit human-in-the-loop interpretation beyond standard laboratory procedures for running the assay and reporting results. The device provides a qualitative positive or negative result based on a cut-off.

7. The Type of Ground Truth Used

The types of ground truth used include:

• Serotonin Release Assay (SRA): For the cut-off validation study, which is considered a gold standard for HIT diagnosis.
• Predicate Device Results (HemosIL AcuStar HIT-IgG(PF4-H)): For the method comparison study, establishing equivalence to a previously cleared device.
• Clinical Diagnosis/Patient Classification: For the normal reference range study (e.g., "Heparin Exposed, Non-HIT Suspected Patients" and "Healthy Donors") and sample collection for methodology studies (e.g., "HIT-suspected patients", "patients diagnosed with Antiphospholipid Syndrome (APS)").

8. The Sample Size for the Training Set

The document does not explicitly describe a separate "training set" for the device. As an IVD immunoassay, the development process typically involves internal optimization and validation studies, but these are not usually structured as a distinct "training set" in the same way as machine learning algorithms. The mentioned studies are primarily for performance validation and substantial equivalence claims. A "Master Curve" is generated for the assay, which is "predefined and lot dependent" and stored in the instrument, indicating calibration and internal standardization but not a "training set" in the common sense for AI/ML.

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

Since an explicit "training set" in the context of AI/ML is not described, the method for establishing its ground truth is not applicable. The "Master Curve" concept implies calibration and validation using known standards and controls, which are part of the assay's design and manufacturing process.

Ask a specific question about this device

PF4 Enhanced assay is designed as a solid phase enzyme linked immunosorbent assay (ELISA). The product is intended to be used as an in vitro diagnostic kit by hematology, coagulation, or other pathology laboratories to assist in screening patient samples, 3.2% sodium citrate (plasma) or without anticoagulant (serum), for the presence of heparin associated commonly found in patients with heparin induced thrombocytopenia (HIT) or thrombosis.

PF4 Enhanced Assay is an Enzyme Linked Immunosorbent Assay (ELISA). The PF4 Enhanced ELISA is intended to detect antibodies in human serum or plasma that react with Platelet Factor 4 (PF4) when it is complexed to heparin or other polyanionic compounds. The PF4 Enhanced kit contains all of the reagents necessary to perform the assay.

Here's a breakdown of the acceptance criteria and supporting studies for the Immucor PF4 Enhanced assay, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

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

• Positive Serum Control Raw Material Change: 30 vials tested (total number of samples from 3 validation batches is not explicitly stated beyond this).
• Comparison of Serum and Plasma Sample Types: 174 paired (serum vs. plasma) fresh samples.
• Data Provenance for Serum/Plasma Comparison: Florida Hospital conducted the study. The data was retrospective as Genetic Testing Institute (the prior company) used the transcribed raw data for analysis. The country of origin is implicitly the U.S.
• Stopping Solution Lot-to-Lot Comparison: 3 lots of new Stopping Solution (ESS) and 3M NaOH (predicate). Number of actual test samples per lot not specified beyond implied sufficient testing to meet acceptance criteria.
• Stopping Solution Process Validation: 3 lots of new Stopping Solution (ESS) and 1 lot of 3M NaOH (predicate). Tested with a finished product QC panel of 21 positive and 24 negative samples (total 45 samples per lot/solution type).

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

The document does not explicitly state the number of experts or their qualifications for establishing ground truth. For the Comparison of Serum and Plasma Sample Types, it mentions "Florida Hospital conducted a study" and "Genetic Testing Institute used the transcribed raw data to perform the analysis." This suggests clinical outcomes or internal lab testing might have served as ground truth, rather than expert consensus on individual cases. For other studies, "established acceptance criteria" and "expected qualitative result" imply pre-defined truths based on known characteristics of control materials or validated samples.

4. Adjudication Method for the Test Set

The document does not mention an explicit adjudication method (e.g., 2+1, 3+1). For the Comparison of Serum and Plasma Sample Types, it notes an "investigation of the ninth discrepant sample," where "additional testing for the plasma and serum sample both matched that of the fresh plasma sample," suggesting a form of re-evaluation or retesting for discrepant results.

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

No, an MRMC comparative effectiveness study was not done. The device is an in vitro diagnostic (ELISA) kit.

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

Yes, the studies presented are all standalone performance evaluations of the assay components and the assay as a whole, without human-in-the-loop performance being a specific metric. The device itself is an assay kit.

7. The Type of Ground Truth Used

• Positive Serum Control Raw Material Change: Ground truth was based on pre-defined expected optical density (OD) values and variation limits for the control material.
• Comparison of Serum and Plasma Sample Types: Ground truth for sample positivity/negativity would have been established by the clinical laboratory (Florida Hospital) using the predicate device or a clinical diagnosis, which the new method was compared against. It's implied this was based on the "qualitative results obtained."
• Stopping Solution Lot-to-Lot Comparison: Ground truth was based on the performance of the predicate Stopping Solution (3M NaOH) and established qualitative results for known samples.
• Stopping Solution Process Validation: Ground truth was based on the expected positive/negative qualitative results of a "finished product QC panel" and the performance of the predicate 3M NaOH Stopping Solution.

8. The Sample Size for the Training Set

The document does not specify a training set for algorithm development, as the device is an ELISA kit and not an AI/ML algorithm that typically requires a separate training set. The studies described are validation and performance testing of the kit's components and overall function.

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

Not applicable, as there is no mention of an algorithm training set.

Ask a specific question about this device

PF4 IgG assay is a qualitative screening assay for the detection of heparin associated IgG antibodies in human serum or plasma. The presence of heparin-associated antibodies are commonly found in patients with Heparin Induced Thrombocytopenia (HIT).

PF4 IgG assay is an enzyme linked immunosorbent assay (ELISA). The PF4 IgG ELISA is intended to detect IgG antibodies in human serum or plasma that react with Platelet Factor 4 (PF4) when it is complexed to heparin or other polyanionic compounds. The PF4 IgG kit contains all of the reagents necessary to perform the assay.

The Immucor GTI Diagnostics, Inc. PF4 IgG assay is a qualitative screening assay for the detection of heparin-associated IgG antibodies in human serum or plasma, commonly found in patients with Heparin Induced Thrombocytopenia (HIT). The device is a Class II medical device, product code LCO.

This 510(k) submission is for modifications to a previously cleared device (K071781) and includes: a change in the Positive Serum Control raw material, the addition of plasma as a sample type, and a change in the Stopping Solution.

1. Table of acceptance criteria and reported device performance:

2. Sample size used for the test set and the data provenance:

• Positive Serum Control Raw Material Change (Precision Study):
  • No specific "test set" sample size for patient samples is provided. The study focused on the performance of the new positive serum control material within the assay.
  • The study used a single lot of the PF4 IgG kit and three validation lots of the Positive Serum Control.
  • Data provenance is internal, generated as part of process validation.
• Addition of Plasma as a Sample Type:
  • Test set size: 174 frozen serum and plasma samples.
  • Data provenance: Samples obtained from Florida Hospital for an internal study. Retrospective, as samples were frozen.
  • Sub-study for ACD/Sodium Citrate vs. Serum: Blood collected from 24 individuals. Origin not specified beyond "internal study." Retrospective.
• Stopping Solution Change:
  • Test set size: No patient samples explicitly mentioned in the summary for the Stopping Solution evaluation itself. The testing involved comparing the performance of the new Stopping Solution with the predicate using various assay components and a QC panel.
  • QC Panel: 21 positive samples and 24 negative samples.
  • Data provenance: Internal, generated as part of lot-to-lot comparison and process validation.

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

The document does not provide information on the number or qualifications of experts used to establish ground truth for the test sets. For the plasma sample type study, it states 174 frozen serum and plasma samples were used, and for the ACD/Sodium Citrate comparison, blood was collected from 24 individuals "known to be PF4: heparin antibody negative." How this "known" status was established (e.g., by experts, by a predicate device, by clinical diagnosis) is not detailed. The ground truth for the QC panel used in the stopping solution study is based on "expected qualitative result," implying pre-characterized samples, not expert consensus at the time of the study.

4. Adjudication method for the test set:

The document does not describe any adjudication method for establishing ground truth for the test sets. The studies appear to rely on the inherent reactivity of the samples (e.g., "known to be PF4: heparin antibody negative," "high level reacting anti:PF4 heparin antibody sample," "expected qualitative result" for QC panels).

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:

This device is an in vitro diagnostic (IVD) assay, specifically an ELISA. It is not an AI-assisted diagnostic tool that involves human readers interpreting images or data. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The device is an IVD assay, not an algorithm. Its performance is evaluated biochemically based on optical density measurements, which are then interpreted qualitatively (positive/negative) according to the assay's cut-offs. The studies described are standalone performance evaluations of the modified assay components and sample compatibility.

7. The type of ground truth used:

• For the plasma sample type comparison, the ground truth appears to be based on the qualitative results obtained from the serum sample, as the goal was to demonstrate equivalence between serum and plasma samples. For the sub-study on ACD/Sodium Citrate, it refers to individuals "known to be PF4: heparin antibody negative" and "high level reacting anti:PF4 heparin antibody sample," indicating pre-characterized samples.
• For the stopping solution change, the ground truth for the QC panel was based on "expected qualitative result," implying pre-defined and characterized positive and negative samples.
• The primary ground truth for the assay itself (predicate and candidate) would typically be established against either clinical diagnosis of HIT (outcome data) or a well-established reference method, but this is not explicitly detailed for these specific modification studies. The studies focus on demonstrating that the modifications do not adversely affect the device's performance compared to its previous state.

8. The sample size for the training set:

The document does not describe a training set as this is not an algorithm requiring machine learning. The studies are performance and validation studies for changes to an IVD assay.

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

Not applicable, as there is no training set for this type of device.

Ask a specific question about this device

HemosIL AcuStar HIT-IgG(PF4-H) is a qualitative, fully automated, chemiluminescent immunoassay (CIA) for the detection of IgG antibodies that react with Platelet Factor 4 (PF4) when complexed to heparin. The assay is for use in human 3.2% or 3.8% citrated plasma and serum on the ACL AcuStar instrument in a laboratory setting.

The result provided by the assay should be interpreted as either positive or negative based on the assay cut-off (1.00 U/ mL). The positive or negative result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings.

Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult population suspected of HIT. Not for use in isolation to exclude HIT.

HemosIL AcuStar HIT Controls are for the quality control of the HemosIL AcuStar HIT-IgG(PF4-H) assay as performed on the ACL AcuStar.

For prescription use.

The HemosIL AcuStar HIT-IgG(PF4-H) assay is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with PF4 complexed to polyvinyl sulfonate (PVS) which capture, if present, the PF4/Heparin antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgG antibody is added and may bind with the captured PF4/Heparin IgG on the particles. After a second incubation, magnetic separation, and a wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL AcuStar optical system. The RLUs are directly proportional to the PF4/Heparin IgG concentration in the sample.

The HemosIL AcuStar HIT-IgG(PF4-H) kit consists of:
R HIT-IgG(PF4-H) Cartridge for 25 determinations: Cartridge containing 1 vial of magnetic particle suspension coated with PF4/PVS complex, 1 vial of assay buffer, 1 vial of tracer consisting of an mAb anti-human IgG antibody labeled with isoluminol, and 1 vial of sample diluent used for the regular predilution of the sample. The reagents are in a phosphate or Tris buffer containing bovine serum albumin, bovine fetal serum, PF4/PVS complex, mouse monoclonal IgG, stabilizers, and preservative.

C1 HIT-IgG(PF4-H) Calibrator 1: Barcoded tube of a solution with humanized mAb anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers and preservative.

C2 HIT-IgG(PF4-H) Calibrator 2: Barcoded tube of a solution with humanized mAb anti-PF4-Heparin in Tris buffer containing bovine serum albumin, stabilizers, and preservative.

The calibrators are lot specific and they cannot be used with other lots of reagents.

Controls:
The Low and High HIT Controls are prepared by means of a dedicated process and contain different concentrations of humanized monoclonal anti-PF4-Heparin.

Low HIT Control: Control intended for the assessment of precision and accuracy of the HemosIL AcuStar HIT-IgG(PF4-H) assay below the cut-off.

High HIT Control: Control intended for the assessment of precision and accuracy of the HemosIL AcuStar HIT-IgG(PF4-H) assay above the cut-off.

Use of both controls is recommended for a complete quality control program.

Here's a breakdown of the acceptance criteria and the study details for the HemosIL AcuStar HIT-IgG(PF4-H) device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for all performance metrics in a pass/fail format. However, by comparing the device to the predicate and the SRA, and given the FDA clearance, a reasonable inference of acceptable performance can be made from the reported results. The critical performance metrics are related to agreement with the predicate device and a reference method (SRA).

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

• Multicenter Method Comparison (vs. Predicate and SRA):
  • Sample Size:
    • N=802 for comparison to predicate (Zymutest HIA IgG).
    • N=790 for comparison to Serotonin Release Assay (SRA). (12 samples removed due to invalid/indeterminate SRA results).
  • Data Provenance: Samples were obtained from patients exposed to heparin and showing HIT-related symptoms. The study was conducted at three (3) external clinical sites (hospitals). This indicates a prospective clinical study environment across multiple locations, likely within the country where the study was performed (not explicitly stated, but typically FDA submissions refer to studies conducted in, or acceptable to, the US or EU). The status is prospective in the sense that these were newly tested samples within the framework of this study, even if collected from ongoing patient care.
• Precision and Reproducibility Studies: Sample pools and native patient samples were used. Actual number of unique patient samples used for these studies is not explicitly stated, but the studies involve repeated testing of these samples.
• Cut-off Determination: 87 citrated plasma samples from hospitalized patients exposed to heparin and with clinical signs consistent with HIT.
• Reference Intervals:
  • Heparin Exposed, Non-HIT Suspected: 91 citrated plasma samples.
  • Healthy Donors: 154 citrated plasma samples.

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

• For Cut-off Determination: The Serotonin Release Assay (SRA) served as the reference method (ground truth). It is implied that the SRA results themselves were established by experts in the hospitals where the samples were tested. No specific number or qualifications of experts are given in this document.
• For Multicenter Method Comparison: The SRA was again used as the primary reference method ("gold standard"). The results of the SRA are taken as the ground truth. There is no mention of an expert panel specifically adjudicating the SRA results or the clinical diagnoses used in the study.

4. Adjudication Method for the Test Set

• No explicit adjudication method (e.g., 2+1) is described for the test set of the primary clinical study.
• The comparison relies directly on the results of the Serotonin Release Assay (SRA) as the reference standard, and the predicate device.
• The "cut-off determination" section mentions that the 87 samples were tested by the hospital with SRA, and these results (45 SRA positive, 42 SRA negative) were used to perform ROC analysis to establish the device's cut-off. This suggests the SRA results are considered the definitive truth.

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

• No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) immunoassay, not an imaging or interpretive device that typically involves human readers in the output interpretation directly. The output is a numerical value (U/mL) and a categorical interpretation (Positive/Negative) which is then used by clinicians. There is no "human-in-the-loop" component in the sense of interpreting the AI's output in comparison to interpreting raw data.

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

• Yes, the provided performance data represents the standalone performance of the HemosIL AcuStar HIT-IgG(PF4-H) assay. This is an automated immunoassay where the instrument and reagents perform the analytical steps and output the result (U/mL) and interpretation (Positive/Negative). There is no "human-in-the-loop" interaction with the algorithm's immediate output that would alter its performance metrics as presented here.

7. The Type of Ground Truth Used

• Serotonin Release Assay (SRA) results were used as the primary reference method or "gold standard" for establishing clinical performance (e.g., PPV, NPV, and cut-off determination).
• The predicate device (Zymutest HIA IgG) was also used as a comparator for demonstrating substantial equivalence.

8. The Sample Size for the Training Set

• The document does not explicitly mention a "training set" in the context of machine learning or AI algorithm development. This device is an IVD immunoassay, and its development follows more traditional analytical validation processes rather than AI model training.
• However, the "Cut-Off Determination" study, which involved 87 samples with known SRA results, effectively served a similar purpose to a training/validation set in establishing an optimal operating point (the 1.00 U/mL cut-off) for the device. These patients had been exposed to heparin and displayed clinical signs consistent with HIT.
• The "Reference Interval" studies (healthy donors and heparin-exposed non-HIT suspected patients) also contribute to understanding the assay's behavior in different populations, which could be seen as part of foundational data.

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

• As noted above, for the "Cut-Off Determination" study (serving a similar role to a training set), the ground truth for the 87 samples was established by Serotonin Release Assay (SRA) results performed by the hospital. The results were categorized as SRA positive (45 samples) and SRA negative (42 samples). These SRA classifications then allowed for Receiver Operating Characteristics (ROC) analysis to determine the optimal assay cut-off.

Ask a specific question about this device

HemosIL HIT-Ab(PF4-H) is a qualitative, fully automated, latex enhanced immunoassay for the detection of anti-platelet factor 4/heparin (PF4/H) antibodies. The assay is for use in human 3.2% or 3.8% citrated plasma on the ACL TOP® Family of instruments in a laboratory setting.

The result provided by the assay should be interpreted as either positive based on the assay cut-off (1.0 U/ mL). The positive or negative result aids in determining the risk for heparin induced thrombocytopenia (HIT) when used in conjunction with other laboratory and clinical findings.

Anti-PF4/Heparin antibodies are commonly found in patients with HIT. For use in adult population suspected of HIT. Not for use in isolation to exclude HIT.

HemosIL HIT-Ab(PF4-H) Controls are for the Quality Control of the HemosIL HIT-Ab(PF4-H) assay as performed on the ACL TOP® Family of instruments.

For prescription use.

The HemosIL HIT-Ab(PF4-H) kit is a latex particle enhanced immuno-turbidimetric assay to detect total Anti-PF4/Heparin (PF4/H) antibodies found in HIT patients. A monoclonal antibody that mimics human HIT antibodies is coated onto latex particles.
In the presence of PF4 from human platelets complexed to polyvinyl sulfonate (PVS), and the patient sample, a competitive agglutination reaction occurs.
The degree of agglutination is inversely proportional to the concentration of antibodies in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates.
The HemosIL HIT- Ab(PF4-H) kit consists of:
Latex Reagent: Suspension of polystyrene latex particles coated with purified mouse monoclonal anti-PF4-Heparin in Tris buffer, containing bovine serum albumin, stabilizers and preservative.
Stabilizer: PBS buffer containing bovine serum albumin, stabilizers and preservative.
Complex: Solution of PF4-PVS complex (PF4 from human platelets complexed to PVS), in PBS buffer containing bovine serum albumin, stabilizers and preservative. Contains 0.02% Bronidox™ as a preservative.
Calibrator: Lyophilized solution of a monoclonal anti- PF4-Heparin antibody in Tris buffer containing bovine serum albumin, stabilizers and preservative.

The Low and High HIT-Ab(PF4-H) Controls are prepared by means of a dedicated process and contain different concentrations of humanized monoclonal anti-PF4-Heparin-human IgG.
Low HIT-Ab(PF4-H) Control: Control intended for the assessment of precision and accuracy of the assay at PF4/H antibody levels at or below the cut-off.
High HIT-Ab(PF4-H) Control: Control intended for the assessment of precision and accuracy of the assay at abnormal PF4/H antibody levels.
Use of both controls is recommended for a complete quality control program.

Here's a breakdown of the acceptance criteria and the studies performed for the HemosIL HIT-Ab(PF4-H) device, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a singular section with numerical targets for clinical performance. Instead, it presents various performance metrics derived from different studies. The conclusion states that the device is "substantially equivalent" to the predicate and "safe and effective."

Given this, I will infer "acceptance criteria" from the comparative studies presented and consider the reported performance to be the "device performance."

2. Sample Sizes Used for Test Sets and Data Provenance

• Multi-Reagent Lot Precision:

  • Sample Size: 2 controls (low and high) and 5 patient plasma pools. Each tested in duplicate, twice a day for 20 days (80 replicates per level per lot). Total of 7 levels * 80 replicates = 560 data points per reagent lot. With 3 reagent lots, this is 1680 data points for the precision study itself.
  • Data Provenance: Not explicitly stated for patient pools, but controls are internal. Patient plasma samples 1-5's origin is not specified but are described as "prepared at different levels to span the assay range", implying they are manufactured or manipulated samples.
  • Nature: Prospective (testing conducted for the study).

• Multi-Reagent Lot Site-to-Site Reproducibility:

  • Sample Size: 2 controls (low and high), 3 patient pools, and 1 manufactured material (Plasma Sample 4). Each tested in triplicate, twice a day for 5 days (30 replicates per level). Total of 6 levels * 30 replicates = 180 data points per site per reagent lot. With 3 sites and 3 reagent lots, this is 180 * 3 * 3 = 1620 data points.
  • Data Provenance: Not explicitly stated for patient pools or manufactured material, but they are "patient pools (2 positive)" and "a manufactured material containing a citrated plasma sample spiked with monoclonal anti-PF4-Heparin antibody."
  • Nature: Prospective (testing conducted for the study).

• Multi-Control Lot Precision:

  • Sample Size: 2 control levels (low and high) from 3 different control lots. Each tested in duplicate, twice a day for 20 days (80 replicates per level per lot). Total of 6 levels * 80 replicates = 480 data points.
  • Data Provenance: Controls are manufactured by Instrumentation Laboratory (IL).
  • Nature: Prospective (testing conducted for the study).

• Multi-Control Lot Reproducibility:

  • Sample Size: 2 control levels (low and high). Each tested in triplicate, twice a day for 5 days (30 replicates per level). Total of 2 levels * 30 replicates = 60 data points per site. With 3 sites, 180 data points.
  • Data Provenance: Controls are manufactured by Instrumentation Laboratory (IL).
  • Nature: Prospective (testing conducted for the study).

• Multi-Calibrator Lot Precision:

  • Sample Size: 3 different calibrator lots. Each tested in duplicate, twice a day for 20 days (80 replicates per lot). Total of 3 lots * 80 replicates = 240 data points.
  • Data Provenance: Calibrators are kit components from the manufacturer.
  • Nature: Prospective (testing conducted for the study).

• Unadulterated Patient Plasma Precision:

  • Sample Size: 2 patient plasma samples. Each tested in duplicate, twice a day for 10 days (40 replicates per sample). Total of 2 samples * 40 replicates = 80 data points.
  • Data Provenance: Collected at a hospital in the United States.
  • Nature: Retrospective (though tested prospectively for precision study, samples were previously collected).

• Instrument Model Equivalency:

  • Sample Size: 51 citrated plasma samples.
  • Data Provenance: Individual clinical patients suspected of HIT.
  • Nature: Retrospective (samples previously collected, tested on multiple instruments).

• Linearity and Test Ranges:

  • Sample Size: Not explicitly stated as a number of patient samples, but 10 concentrations across 0.6-5.7 U/mL and a third extremely high positive sample for 2.1-16.0 U/mL. Two positive patient samples were used to prepare serial dilutions.
  • Data Provenance: Patient samples spiked into donor plasma from a blood bank.
  • Nature: Prospective (dilution series prepared and tested).

• Heparin Sensitivity:

  • Sample Size: 126 citrated plasma samples.
  • Data Provenance: Non-HIT suspected, heparin treated patients (UFH or LMWH).
  • Nature: Retrospective (samples previously collected).

• Antiphospholipid Syndrome (APS):

  • Sample Size: 40 citrated plasma samples.
  • Data Provenance: Patients diagnosed with Antiphospholipid Syndrome (APS).
  • Nature: Retrospective (samples previously collected).

• Reference Interval – Healthy Donors:

  • Sample Size: 131 citrated plasma samples.
  • Data Provenance: Apparently healthy individuals.
  • Nature: Retrospective (samples previously collected).

• Reference Interval – Heparin Exposed, HIT Suspected Patients (HIT Negative):

  • Sample Size: 122 citrated plasma samples.
  • Data Provenance: HIT-suspected, but negative by a commercially available ELISA.
  • Nature: Retrospective (samples previously collected).

• Cut-Off Determination:

  • Sample Size: 63 citrated plasma samples (31 SRA positive, 32 SRA negative).
  • Data Provenance: Hospitalized patients exposed to heparin with clinical signs of HIT.
  • Nature: Retrospective (samples previously collected and tested by SRA).

• Method Comparison (Internal):

  • Sample Size: 118 frozen citrated patient plasma samples.
  • Data Provenance: Patients referred for HIT testing from a hospital in the US and a hospital in France.
  • Nature: Retrospective (samples previously collected, tested against predicate).

• Multicenter Method Comparison (against predicate and SRA):

  • Sample Size: 632 patient samples initially (N=537 for SRA comparison after removing invalid/indeterminate SRA results).
  • Data Provenance: From patients exposed to heparin who showed HIT related symptoms, collected at three (3) hospitals.
  • Nature: Multicenter, Retrospective (samples previously collected, tested against predicate and SRA).

• HemosIL HIT-Ab(PF4-H) Assay vs. 2013 American Society of Hematology (ASH) Guidelines:

  • Sample Size: 537 patient samples (subset of the multicenter study).
  • Data Provenance: From patients exposed to heparin who showed HIT related symptoms, collected at three (3) hospitals.
  • Nature: Retrospective (analysis of previously collected data against clinical guidelines).

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

• For studies comparing to a predicate device (Asserachrom HPIA Test Kit), the predicate itself served as the comparator, and its established performance and cut-offs formed the "ground truth" for comparison. The predicate device's ground truth would have been established during its own clearance.
• For studies comparing to the Serotonin Release Assay (SRA), the SRA results were considered the "reference device" and "ground truth." The SRA is a functional assay for HIT antibodies and is often considered the gold standard, although the document doesn't specify how the SRA results themselves were "ground-truthed" (e.g., if multiple SRA runs were done, or expert interpretation). No specific number of experts or their qualifications for interpreting SRA results is mentioned.
• For the Cut-Off Determination study, SRA results (31 SRA positive and 32 SRA negative) from hospitalized patients were used as the ground truth. Again, no specific information on experts for SRA.
• For the ASH Guidelines comparison, the 2013 ASH diagnostic algorithm, which incorporates clinical probability (4T score), ELISA results, and SRA results, served as the "ground truth" or reference framework. This is a clinical guideline, not directly "expert-established ground truth" for individual cases in this context, but rather an established diagnostic framework.
• For other analytical studies (precision, reproducibility, linearity, etc.), the ground truth is based on the inherent properties of the samples and controls used, not dependent on expert interpretation.

4. Adjudication Method for the Test Set

• The document does not specify an adjudication method for establishing ground truth for the clinical samples. For studies comparing to the SRA or the predicate, it appears the results of these reference methods were taken directly without a separate adjudication process by additional experts.
• For the ASH guideline comparison, the algorithm itself incorporates different types of evidence.

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 comparative effectiveness study was not done.
• This device, HemosIL HIT-Ab(PF4-H), is an in-vitro diagnostic (IVD) immunoassay, which performs automated detection of antibodies. It is not an AI-assisted diagnostic imaging or interpretation device that would involve human "readers" or benefit from "AI assistance" in the way described for an MRMC study. Its output is a quantitative (U/mL) and qualitative (positive/negative) result based on an assay cut-off.

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

• Yes, the primary performance studies are standalone algorithm-only performance. The HemosIL HIT-Ab(PF4-H) assay is a "fully automated, latex enhanced immunoassay" performed on the ACL TOP Family of instruments. The results generated by the instrument are quantitative (U/mL) and then interpreted as positive or negative based on a fixed cut-off (1.0 U/mL). All the precision, reproducibility, linearity, and method comparison studies described are evaluating the performance of this automated assay directly, without human interpretation of raw data beyond the standard laboratory operation of running the assay and reporting the final result.

7. The Type of Ground Truth Used

• Predicate Device Performance: The primary ground truth for demonstrating substantial equivalence was the performance of the Asserachrom HPIA Test Kit, a legally marketed predicate ELISA device.
• Serotonin Release Assay (SRA): For clinical validity, the SRA, a functional assay for HIT antibodies, was used as a reference device and
  considered the functional ground truth.
• Clinical Guidelines: The 2013 American Society of Hematology (ASH) guidelines (incorporating 4T score, ELISA, and SRA) were used as a comprehensive clinical framework for comparison.
• Internal Controls and Materials: For analytical performance studies (precision, linearity), the ground truth was established by the known concentrations/compositions of manufacturer-prepared controls, calibrators, and spiked plasma pools.

8. The Sample Size for the Training Set

• The document does not explicitly delineate separate "training" and "test" sets in the context of machine learning or AI development, as this is an IVD immunoassay.
• Instead, development and optimization of the assay (analogous to training in ML) would involve internal R&D studies. The summary primarily focuses on the validation studies (analogous to testing).
• The "Cut-Off Determination" study describes using 63 samples (31 SRA positive, 32 SRA negative) and performing ROC analysis to determine the clinical cut-off of 1.0 U/mL. While this is not a "training set" in the AI sense, these samples were used to establish a critical parameter for the device's interpretation.

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

• As noted above, there isn't a "training set" in the AI sense.
• For the "Cut-Off Determination" study, which used samples to establish the 1.0 U/mL cut-off:
  • Ground Truth was established using Serotonin Release Assay (SRA) results. These SRA results classified the 63 samples as positive or negative for HIT antibodies.
  • These samples were from "hospitalized patients who had been exposed to heparin, and who displayed clinical signs consistent with Heparin Induced Thrombocytopenia (HIT)," and were "tested by the hospital with the Serotonin Release Assay (SRA)." This implies the SRA results were clinical results from a standard reference method.

Ask a specific question about this device

PF4 IgG™ is a qualitative solid phase enzyme linked immunosorbent assay (ELISA) designed to detect antibodies reactive with Platelet Factor 4 (PF4) when it is complexed to polyanionic compounds such as polyvinyl sulfonate (PVS). These antibodies are found in some patients undergoing heparin therapy.

PF4 IgG™ is designed as a solid phase enzyme-linked immunosorbent assay (ELISA). This product is intended to be used as an in vitro diagnostic kit by hematology, coagulation, or other pathology laboratories to assist in screening patient samples for the presence of heparin-associated antibodies commonly found in patients with heparin-induced thrombocytopenia or thrombosis.

PF4 IgG™ is a qualitative screening assay for the detection of heparin associated IgG antibodies in human serum. The presence of heparin associated antibodies are commonly found in patients with Heparin Induced Thrombocytopenia (HIT).

The PF4 IgGTM assay is an Enzyme Linked Immunosorbent Assay (ELISA). The PF4 IgG™ ELISA is intended to detect IgG antibodies in human serum that react with Platelet Factor 4 (PF4) when it is complexed to heparin or other polyanionic compounds. The PF4 IgG™ kit contains all of the reagents necessary to perform the assay.

In the PF4 IgG™ assay, a complex of PF4/PVS, which has been immobilized in the microwells serve as a target for the binding of antibodies associated with Type II HIT.

In the PF4 IgG™ assay, patient serum is first diluted (1:4), with the specimen diluent provided in the kit. The diluted sample is then added to microwells to which Platet Factor 4 (PF4) complexed to polyvinyl sulfonate (PVS) has been immobilized. The sample is then incubated for 30 minutes at 37°C. If an antibody which recognizes a site on PF4/PVS complex is present in the patient sample, binding will occur. Following this incubation, a wash step then removes any unbound antibodies. A goat anti-human IgG - alkaline phosphatase conjugate is then added to the wells. The conjugate is incubated for 30 minutes at 37°C. Following this incubation, a wash step then removes any unbound conjugate. The alkaline phosphate substrate, p-nitrophenyl phosphate (pNPP) is then added to the microwells. After a 30 minute incubation at room temperature (22 -- 25°C), the reaction is stopped by addition of the stopping solution (3 M sodium hydroxide). The optical density of the color that develops is measured in a spectrophotometer at 405 or 410 nm using a reference wavelength of 490 nm.

1. Table of Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state pre-defined acceptance criteria values for sensitivity, specificity, and agreement. Instead, it presents the results of the comparison studies and concludes that the device "performs comparable to the predicate device." The conclusion for assay imprecision and reportable results states that the assay "showed acceptable assay imprecision" and "100% agreement."

2. Sample size used for the test set and the data provenance

• Test Set Sample Size: 229 serum samples.
• Data Provenance: The samples were obtained from the BloodCenter of Wisconsin (BCW) and were from patients receiving heparin treatment. The data is retrospective as the samples had been previously tested by BCW for PF4/heparin antibodies using the SRA. The country of origin is the USA.

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

The document does not specify the number of experts or their qualifications for establishing the ground truth using the Serotonin Release Assay (SRA). It refers to the SRA as an "in house assay" at BCW.

4. Adjudication method for the test set

The document does not describe an adjudication method for conflicting results. The SRA results from BCW were used as the primary comparator (gold standard). For the PF4 IgG™ and PF4 ENHANCED® assays, samples were tested in duplicate, and the mean of the O.D. values was obtained. Results were considered positive if the mean O.D. value was ≥0.400.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study describes an in vitro diagnostic (IVD) ELISA test, not an AI-assisted diagnostic tool that would involve human readers for interpretation of results.

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

This study describes a standalone assay's performance, which is an analogous concept to an algorithm-only performance for an IVD test. The PF4 IgG™ assay itself is the "algorithm only" in this context, providing a quantitative optical density value that is then interpreted as positive or negative based on a cutoff. No human-in-the-loop performance data is provided beyond implicitly trained lab technicians performing the assay.

7. The type of ground truth used

The primary ground truth for the comparison of methods study was the Serotonin Release Assay (SRA). The document states that the SRA is "considered to be the gold standard for testing for antibodies that can cause HIT."

8. The sample size for the training set

The document does not explicitly describe a "training set" in the context of machine learning or algorithm development. However, for determining the normal range and assay cutoff, 120 serum samples from normal healthy individuals were used. This set of samples was used to statistically establish the assay's cutoff, which plays a role similar to calibrating or "training" a threshold.

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

For the "training set" (120 normal healthy individuals used for normal range and cutoff determination):

• The ground truth was established by defining these individuals as "normal healthy" and their serum samples were tested with the PF4 IgG™ and PF4 ENHANCED® assays.
• The normal range was determined non-parametrically using these samples, and the cutoff for the assays (≥0.400) was set based on the upper end of these calculated normal ranges.
• Calculations for the normal range were performed by GTI's Manager of Clinical and Scientific Affairs (Melissa Pressman, Ph.D.), using the Med Calc software program. This implies statistical analysis of the optical density values from these known normal samples.

Ask a specific question about this device

ZYMUTEST HIA IgG and IgGAM kits are designed as a solid phase enzyme- linked immunosorbent assay (ELISA). These products are intended to be used as an in vitro diagnostics kit by Hematology, coagulation or other pathology laboratories to assist in screening patients samples for the presence of heparin- associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis (HIT).

The ZYMUTEST HIA is solid phase enzyme linked immunosorbent assay (ELISA) designed to detect antibodies. These antibodies are found in some patients undergoing heparin therapy.

The provided 510(k) summary describes the ZYMUTEST HIA IgG and ZYMUTEST HIA IgGAM devices, which are ELISA kits designed to detect heparin-associated antibodies related to Heparin Induced Thrombocytopenia (HIT). The submission establishes substantial equivalence to existing predicate devices (ASSERACHROM ®HPIA Test Kit and PF4 ENHANCED Solid Phase ELISA).

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly based on establishing substantial equivalence with the predicate devices. The primary performance metrics reported are agreement, co-positivity, and co-negativity with the predicate devices, along with intra- and inter-assay reproducibility. Specific numerical acceptance criteria are not explicitly stated as target percentages for agreement, co-positivity, or co-negativity, but the general conclusion implies that the observed values meet the FDA's criteria for substantial equivalence.

2. Sample Size for the Test Set and Data Provenance

• Zymutest IgGAM vs. Asserachrom (internal study): 44 plasma samples. Provenance not specified, but stated as an "internal study," suggesting it was conducted by Hyphen BioMed. Retrospective or prospective nature is not specified.
• Zymutest IgGAM vs. Asserachrom (clinical studies): 243 plasma samples. Provenance from "Combined Site 1 & 2." Specific country of origin or whether retrospective/prospective is not specified.
• Zymutest IgGAM vs. GTI PF4 Enhanced (clinical studies): 345 plasma samples. Provenance from "Combined Sites 1,2,3." Specific country of origin or whether retrospective/prospective is not specified.
• Zymutest IgG vs. Serotonin Release Assay (SRA) (clinical studies): 174 samples. Provenance not specified. This appears to be a reference method rather than a predicate.
• Zymutest IgG vs. Asserachrom (clinical studies): 243 samples. Provenance from "Combined Sites 1 & 2." Specific country of origin or whether retrospective/prospective is not specified.

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

The ground truth for the comparison studies was established by the predicate devices (ASSERACHROM ®HPIA and PF4 ENHANCED) and the Serotonin Release Assay (SRA). There is no mention of human experts being used to establish ground truth for the test set; instead, the results of existing, legally marketed diagnostic tests are used as the reference.

4. Adjudication Method for the Test Set

Not applicable. The comparisons are directly against the results of the predicate devices or the SRA, not against expert consensus.

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

No. This is an in vitro diagnostic device, and the evaluation focuses on its performance compared to other diagnostic assays, not on human reader performance with or without AI assistance.

6. Standalone Performance Study

Yes, the studies presented are standalone performance studies of the ZYMUTEST HIA IgG and IgGAM devices, comparing their results directly with established predicate devices and a reference method (SRA). The performance metrics (agreement, co-positivity, co-negativity, reproducibility) characterize the algorithm's (device's) performance.

7. Type of Ground Truth Used

The ground truth used for the comparison studies was the results obtained from legally marketed predicate in vitro diagnostic devices (ASSERACHROM ®HPIA and PF4 ENHANCED) and a reference assay (Serotonin Release Assay - SRA). This falls under the category of using established, validated diagnostic tests as the reference standard.

8. Sample Size for the Training Set

The document does not provide information about a "training set" in the context of machine learning or AI. This device is an ELISA kit, not an AI-powered diagnostic system. The validation studies instead compare the device's performance against existing methods.

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

Not applicable, as there is no mention of a training set for machine learning or AI in this 510(k) submission.

Ask a specific question about this device

GTI PF4 ENHANCED® is designed as a solid phase enzyme-linked immunosorbent assay (ELISA). The product is intended to be used as an in vitro diagnostics kit by hematology, (ELIG/Y). The produce is the pathology laboratories to assist in screening patient samples for the presence of heparin-associated antibodies commonly found in patients with heparin induced thrombocytopenia or thrombosis.

PF4 ENHANCED® Solid Phase ELISA microwells provide immobilized PF4:PVS complexes as a target for the detection of antibodies associated with Type II HIT which are found in some patients undergoing heparin therapy. The presence of these antibodies has been shown to be associated with heparin induced thrombocytopenia Type II (Type II HIT).

Patient serum is added to microwells coated with platelet factor 4 (PF4) complexed to polyvinyl sulfonate (PVS). If an antibody recognizing a site on PF4:PVS is present, binding will occur. Unbound antibodies are then washed away. An alkaline phosphatase labeled anti-human globulin reagent (Anti-IgG/A/M) is added to the wells and incubated. The unbound Anti-IgG/A/M is washed away and the substrate PNPP (p-nitrophenyl phosphate) is added. After a 30-minute incubation period, the reaction is stopped by addition of a sodium hydroxide solution. The optical density of the color that develops is measured in a spectrophotometer.

The document describes a 510(k) premarket notification for a device called "PF4 ENHANCED® Solid Phase ELISA" and its substantial equivalence to a predicate device, the "GTI-PF4 ELISA". The focus of the provided text is on demonstrating that the new device performs as well as the predicate device, especially considering changes to certain materials.

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

1. Table of Acceptance Criteria and the Reported Device Performance

The document does not explicitly state numerical "acceptance criteria" in a typical table format with specific thresholds (e.g., sensitivity > 90%). Instead, the acceptance criteria are implicitly defined by the goal of demonstrating substantial equivalence to the predicate device, the GTI-PF4 ELISA. The performance data was used to show that the PF4 ENHANCED® device performs "as well as" the predicate.

The reported device performance is a qualitative statement of equivalence rather than specific quantitative metrics against pre-defined thresholds.

2. Sample size used for the test set and the data provenance

The document explicitly states that the studies used "known patient samples." However, it does not provide the specific sample size for the test set or the data provenance (e.g., country of origin, retrospective or prospective nature of the samples). The summary refers to "Section 8: Performance Data Section" for details, which is not included in the provided text.

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

The document does not provide information on the number of experts used or their qualifications to establish ground truth for the test set. Given that it's an ELISA for detecting antibodies, the "ground truth" would likely be derived from a combination of clinical diagnosis of Type II HIT and potentially other laboratory tests, rather than expert interpretation of an image or signal that requires adjudication. The document states "known patient samples," implying the status of these samples (e.g., positive or negative for the target antibodies/HIT) was already established.

4. Adjudication method for the test set

The document does not specify an adjudication method. This type of assay (ELISA) typically produces quantitative results (Optical Density) that are then interpreted against cut-offs to yield a qualitative (Positive/Negative) result. Adjudication by multiple readers is less common for such objective assays unless there are borderline results or discrepancies in initial interpretations, which isn't mentioned here.

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, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic (IVD) ELISA kit, which is a laboratory assay. It does not involve human readers interpreting images or data directly to make a diagnosis in a way that would be "assisted by AI." Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable to this device.

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

The device itself is a "standalone" assay in the sense that it produces an objective result (Optical Density) which leads to a qualitative determination (Positive/Negative). It is an "algorithm only" in the context of the assay's biochemical steps and optical density measurement leading to a result. However, this is not an "AI algorithm" in the common sense of the term. The performance data described are for the assay itself.

7. The type of ground truth used

The ground truth for the "known patient samples" would be based on clinical diagnosis of Type II HIT and potentially confirmatory laboratory tests, which establish whether the patient samples are truly positive or negative for the antibodies associated with Type II HIT. The document refers to "known patient samples," implying this established truth. It's not pathology (as in tissue biopsy) or purely outcomes data from a large cohort, but rather a pre-established clinical and laboratory status.

8. The sample size for the training set

The document does not mention a training set in the context of machine learning or AI. This is an ELISA kit validation, not an AI model development. The "known patient samples" mentioned would be considered the test set for validating the new device against the predicate.

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

As there is no mention of a training set in the context of AI, there's no information on how its ground truth was established. The "known patient samples" for the performance studies would have their ground truth established as described in point 7.

Ask a specific question about this device

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay is an in vitro diagnostic device designed for the detection of antibodies to Platelet Factor 4 complexed to polyanionic compounds such as polystyrene. These antibodies are found in some patients undergoing heparin therapy.

The HEALTHTEST® Heparin/Platelet Factor 4 Antibody Assay is a qualitative in vitro diagnostic device designed for the detection of antibodies to the Platelet Factor 4 complexed to polyanionic compounds such as polystyrene. These antibodies are found in some patients undergoing heparin therapy.

The risk of heparin induced thrombocytopenia (HIT) is greatly increased in patients with recent exposure to heparin. The presence of heparin/PF-4 antibody is associated with patients arisk. for HIT, and is rapidly becoming a standard of care in hematology and cardinlogy. The need for a rapid test to detect these antibodies from serum or plasma in less than 5 minutes is highly desired. This rapid manual assay should be easily performed when STAT results are required,

The HealthTEST® Heparin/Platelet Factor 4 Antibody Assay consists of two components: a Mini-reactor device containing a membrane filtration system and a results window, and a dispenser containing reaction reagents.

The Mini-reactor contains a reaction well that allows the sample to react with the reagents. The sample is added to the reaction well followed by the reagents contained in the reagent dispenser. The reagents contain microparticles coated with purified PF-4 protein as well as additional enhancing agents designed to promote rapid agglutination of the particles in the presence of specific antibodies in the test sample.

Once the reagents have reacted with the sample in the reaction well, the reaction mixture automatically collects over the membrane filtration system. This system acts to filter agglutinated particles, while allowing non-agglutinated particles to pass through. Thus, an agglutinated, reactive sample will be trapped within the membrane. Since the dyed particles are trapped by this filter, no particles and hence no color, are able to migrate past the positive/negative line on the results window. Conversely, a nonagglutinated, non-reactive sample will pass through the membrane filter and into the wicking layers, and no color will migrate past the positive/negative line.

Here's a breakdown of the acceptance criteria and study information for the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay:

1. Table of Acceptance Criteria and Reported Device Performance

Note: The acceptance criteria are "implied" because they are not explicitly stated as numerical targets. Instead, the submission demonstrates "substantial equivalence" to the predicate device by showing comparable or superior performance, particularly in specificity. The lower sensitivity in both plasma and serum for the HealthTEST® device compared to the predicate's serum sensitivity is noted but not deemed to raise new issues of safety and effectiveness.

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

• Study #1 (Plasma):
  • Total Samples: 175
  • Data Provenance: Fresh samples originating from "field sources." No specific country of origin is mentioned. The study is retrospective in that samples were collected and then tested, but the "fresh samples" suggest they were not archival.
• Study #2 (Serum):
  • Total Samples: 179
  • Data Provenance: Fresh samples originating from "field sources." No specific country of origin is mentioned. The study is retrospective in that samples were collected and then tested, but the "fresh samples" suggest they were not archival.

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

The ground truth was established by comparing the HealthTEST® device's results to a "commercially available, standard laboratory method" which is identified as the GTI PF4 Elisa Assay (K983379). It is implicit that the results from this predicate ELISA assay were considered the reference standard or "ground truth" for the comparison studies. No individual experts were used for adjudication of the test results themselves; the ELISA outcome was the benchmark.

4. Adjudication Method for the Test Set

No explicit human adjudication method (e.g., 2+1, 3+1) was used for the test set. The HealthTEST® device's results were directly compared against the results of a single reference method, the GTI PF4 Elisa Assay.

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

No MRMC comparative effectiveness study was described. This device is an in vitro diagnostic assay, where the output is directly generated by the device based on a chemical reaction, rather than being interpreted by human readers.

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

Yes, the described studies are standalone performance evaluations. The specificity and sensitivity percentages are for the device (HealthTEST® Heparin/Platelet Factor 4 Antibody Assay) itself, without human interpretation of the results beyond reading the positive/negative line on the device.

7. Type of Ground Truth Used

The ground truth used was based on the results from a predicate laboratory assay (GTI PF4 Elisa Assay). This is a form of comparative gold standard where a well-established and legally marketed diagnostic device's results are used as the benchmark.

8. Sample Size for the Training Set

The document does not provide information on a specific "training set" for the HealthTEST® Heparin/Platelet Factor 4 Antibody Assay. Diagnostic assays like this often undergo an extensive development and optimization phase, but the presented data focuses on performance verification (test set) against a predicate, rather than a separate training and validation split as might be seen with AI/machine learning models.

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

As no explicit training set is mentioned for the HealthTEST® device itself (it's a chemical assay rather than a predictive algorithm in the modern AI sense), the concept of "ground truth for the training set" as it applies to AI models is not directly applicable here. The development of such assays typically involves iterative formulation and testing, where the "ground truth" in development would stem from clinical diagnosis or an accepted reference method, guiding the optimization of the assay's reagents and detection mechanism.

Ask a specific question about this device

Ask a specific question about this device