Search Results

CRYOcheck Chromogenic Factor VIII is for clinical laboratory use in the quantitative determination of factor VIII activity in 3.2 % citrated human plasma. It is intended to be used in identifying factor VIII deficiency and as an aid in the management of hemophilia A in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor VIII is used for determination of FVIII activity and contains the following four components, packaged in glass vials and provided frozen to preserve the integrity of the components:

• Reagent 1: Bovine FX and a fibrin polymerization inhibitor, with activators and stabilizer.
• Reagent 2: Human FIIa, bovine FIXa, calcium chloride and phospholipids.
• Reagent 3: FXa substrate containing EDTA and a thrombin inhibitor.
• Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

In the first stage of the chromogenic assay, test plasma (containing an unknown amount of functional FVIII) is added to a reaction mixture comprised of calcium, phospholipids, human purified thrombin and FIXa, and bovine FX (Reagent 1 and Reagent 2). This mixture swiftly activates FVIII to FVIIIa, which works in concert with FIXa to activate FX. When the reaction is stopped, FXa production is assumed to be proportional to the amount of functional FVIII present in the sample. The second stage of the assay is to measure FXa through cleavage of a FXa-specific peptide nitroanilide substrate (FXa Substrate). P-nitroaniline is produced, giving a color that can be measured spectrophotometrically by absorbance at 405 nm.

Based on the provided FDA 510(k) Clearance Letter, the device in question is the CRYOcheck Chromogenic Factor VIII. This document details the clearance of a modified version of an existing device, emphasizing the differences from the previous version regarding interference claims and recovery of Factor VIII replacement therapies.

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

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" for each performance claim in a quantified manner (e.g., "Interference must be less than X%"). Instead, it reports the limits of non-interference found in their studies, implying these served as the de facto acceptance criteria. For the Factor VIII replacement therapy recovery, the acceptance criterion appears to be "accurate evaluation" across a range of concentrations, with specific over/under recovery noted.

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

• Interference Studies: Plasma samples were "spiked with possible interferents," and "10 replicates were tested alongside 10 replicates of the corresponding blank matrix control." The total number of individual patient samples from which this plasma was derived is not specified, nor is the country of origin. The study design implies a prospective spiking experiment in a laboratory setting.
• Recovery of Factor VIII Replacement Therapy: "Congenital FVIII deficient plasma was spiked with 14 FVIII replacement therapies at seven concentrations." The number of individual patient plasma units or lots of deficient plasma used is not specified. The study design implies a prospective spiking experiment in a laboratory setting.

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

N/A. This is an in vitro diagnostic device for quantitative determination of factor VIII activity, not an AI/imaging device requiring expert human readers for ground truth generation. The ground truth for these studies is established by the known concentrations of spiked interferents or FVIII replacement therapies, and the intrinsic properties of the FVIII deficient plasma.

4. Adjudication Method for the Test Set

N/A. As this is a quantitative in vitro diagnostic device, an adjudication method in the context of human expert review of imaging or clinical data is not applicable. The results are measured spectrophotometrically.

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

No, an MRMC study was not done. This type of study is relevant for AI imaging devices where human readers interpret medical images with and without AI assistance. This document describes an in vitro diagnostic device.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) was Done

Yes, this entire submission describes the standalone performance of the CRYOcheck Chromogenic Factor VIII assay. The device itself performs the quantitative determination of FVIII activity, entirely without a "human-in-the-loop" once the sample is loaded and the assay run according to protocol.

7. The Type of Ground Truth Used

• Interference Studies: The ground truth was the known concentration of the spiked interferent (e.g., Hemoglobin, Intralipid, Bilirubin, etc.) added to plasma samples, and the corresponding blank matrix control.
• Recovery of Factor VIII Replacement Therapy: The ground truth was the known concentration of the spiked FVIII replacement therapy added to congenital FVIII deficient plasma at various concentrations.

8. The Sample Size for the Training Set

N/A. This document describes an in vitro diagnostic assay based on chromogenic principles, not an AI/ML algorithm that requires a "training set" in the computational sense. The device's components (reagents, diluent buffer) and their interaction define the assay, which is then validated through performance studies.

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

N/A. See point 8. The "ground truth" for developing and optimizing such a chromogenic assay would stem from extensive biochemical research, characterization of reagents, and titrations against known standards, which is inherent in the development of any diagnostic assay, but not referred to as a "training set" or "ground truth establishment" in the AI/ML context.

Ask a specific question about this device

CRYOcheck Factor VIII Deficient Plasma with VWF is for clinical laboratory use as a deficient substrate in the quantitative determination of Factor VIII activity in 3.2% citrated human plasma based on the activated partial thromboplastin time (APTT) assay. It is intended to be used in identifying factor VIII deficiency and as an aid in the management of hemophilia A in individuals aged 2 years and older. For in vitro diagnostic use

CRYOcheck Factor VIII Deficient Plasma with VWF is normal human citrated plasma which has been immunodepleted of factor VIII and to which an exogenous source of human von Willebrand Factor (vWF) has been added and buffered with HEPES. Factor VIII has been assayed at less than 1% of normal activity levels and vWF antigen and activity are >50%. It will be provided to users frozen in small-volume aliquots (25 vials of 1.0 mL, and 25 vials of 1.5 mL). Vials will be packaged into boxes; these will be frozen during the manufacturing process and will be shipped and stored frozen until use to preserve the integrity of the components

The provided FDA 510(k) summary for the "CRYOcheck Factor VIII Deficient Plasma with VWF" describes various performance studies and their results. Based on the document, here's a structured breakdown of the acceptance criteria and the study details:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a table of pre-defined acceptance criteria for each performance characteristic in a pass/fail format. Instead, it presents the results of various studies and implies that these results met internal or regulatory expectations for substantial equivalence to the predicate device. However, we can infer performance targets based on the documented results and common regulatory expectations for in vitro diagnostic devices.

Here's a table summarizing the reported device performance, with inferred acceptance "criteria" based on the conclusions drawn in the report:

Ask a specific question about this device

CRYOcheck Chromogenic Factor IX is for clinical laboratory use in the quantitative determination of factor IX activity in 3.2% citrated human plasma. It is intended to be used in identifying factor IX deficiency and as an aid in the management of hemophilia B in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor IX is used for determination of FIX activity and contains the following four components, packaged in vials, and provided frozen to preserve the integrity of the components:
Reagent 1: Human FVIII, human FX, bovine FV and a fibrin polymerization inhibitor.
Reagent 2: Human FXIa, human FII, calcium chloride and phospholipids
Reagent 3: FXa Substrate containing EDTA and a thrombin inhibitor.
Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

The provided text describes the performance of the CRYOcheck Chromogenic Factor IX device. Here's a breakdown of the acceptance criteria and the study that proves the device meets these criteria, based on the information provided:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with pass/fail thresholds for each performance characteristic. Instead, it presents study results and concludes that the device performed effectively and demonstrates substantial equivalence. However, we can infer some criteria from the performance data presented.

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

• Multi-Reagent Lot Precision: 6 samples (1 normal reference control, 2 abnormal reference controls, 3 patient plasma samples).
• Multi-Reagent Lot Site to Site Reproducibility: 6 samples (1 normal reference control, 2 abnormal reference controls, 3 patient plasma samples).
• Linearity/Assay Reportable Range: 14 sample dilutions.
• Reference Interval: 128 normal, ostensibly healthy individuals.
• Shelf-Life Stability: Not specified, but likely involved multiple reference controls and patient plasma samples at each time point.
• In-Use Stability: Not specified, but involved multiple reference controls and patient plasma samples.
• Detection Limit (LoB): 4 blank plasma samples from individuals with severe congenital hemophilia B.
• Detection Limit (LoD): 4 plasma samples with low FIX activity from congenital hemophilia B donors.
• Detection Limit (LoQ): 4 plasma samples with low FIX activity from congenital hemophilia B donors.
• Interferences: Not specified, but likely involved spiked plasma samples.
• Recovery of FIX Replacements: Congenital FIX deficient plasma spiked with 7 FIX replacement therapies at 7 concentrations.
• Method Comparison Studies: 368 human plasma samples. These samples were from normal ostensibly healthy individuals, patients with von Willebrand disease, patients with congenital and acquired hemophilia A and B, and patients on recombinant factor IX treatments.
• Sample Integrity: 65 plasma samples.

Data Provenance: The document does not explicitly state the country of origin for the patient or donor samples. The studies involve both internal and external sites for reproducibility and method comparison. The mention of "congenital hemophilia B donors" and "patients with von Willebrand disease, and congenital and acquired hemophilia A and B" suggests the use of patient samples, implying a clinical or diagnostic context. The studies are retrospective in nature as they involve testing existing plasma samples.

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

For the studies described, the "ground truth" for Factor IX activity is established by:

• Reference controls: These are quality control materials with known or assigned values for FIX activity.
• Patient plasma samples: Their FIX activity is determined either by the device itself (for precision and reproducibility) or by a "comparator method" or "validated laboratory developed chromogenic factor IX assay" (for method comparison and LoQ studies).
• Spiked samples: For linearity, interference, and recovery studies, known amounts of FIX or interfering substances are added to samples to create a controlled "ground truth."
• Congenital FIX deficient plasma: For LoB, LoD, and recovery studies, plasma from individuals with a known severe deficiency serves as a baseline.

The document does not mention specific "experts" in the context of radiologists or similar roles establishing ground truth through consensus. Instead, the ground truth is based on:

• Established assay methods: The comparator method and the validated laboratory developed chromogenic factor IX assay are implicitly considered accurate for determining FIX activity. The qualifications of the personnel running these assays are not individually listed but are assumed to be trained laboratory professionals.
• Reference materials: Reference controls have assigned values.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (like 2+1 or 3+1) is typically relevant for studies where human expert interpretation is compared, e.g., in medical image analysis. In this context of an in vitro diagnostic device for quantitative determination in plasma, such an adjudication method is not described or applicable. The "ground truth" is based on the results of the reference methods, reference materials, and defined sample preparations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and 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 type of study is not relevant for an in vitro diagnostic device like the CRYOcheck Chromogenic Factor IX, which directly measures a biomarker rather than assisting human readers in interpreting complex data like medical images. The device itself is the "reader" providing a quantitative result.

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

Yes, the studies presented are all standalone (algorithm only) performance assessments for the CRYOcheck Chromogenic Factor IX device. The device itself performs the quantitative determination of factor IX activity. The results are generated by the instrument (IL ACL TOP Series or TOP 50 Series Instruments) based on the reagents and the plasma sample, without human interpretative input in the output. Human operators are involved in running the tests, but not in interpreting the quantitative output in a way that typical human-in-the-loop AI studies would assess.

7. The Type of Ground Truth Used

The ground truth used in these studies includes:

• Assigned values of reference controls: For precision and reproducibility.
• Results from a "comparator device" or "validated laboratory developed chromogenic factor IX assay": For method comparison and limit of quantitation. These are considered gold standards for FIX activity measurement.
• Known concentrations in spiked samples: For linearity, interference, and recovery studies.
• Known characteristics of congenital FIX deficient plasma: For detection limits and recovery studies.
• Plasma samples from "normal, ostensibly healthy individuals": For establishing reference intervals.

This primarily falls under the category of established assay methods and reference materials.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. The CRYOcheck Chromogenic Factor IX is an in vitro diagnostic assay, not an AI/ML algorithm that requires training data. Its performance is based on chemical and enzymatic reactions, and its parameters are established through conventional analytical validation studies like those described.

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

As there is no "training set" in the AI/ML sense for this device, this question is not applicable. The device's operational parameters and performance are intrinsically defined by its design, chemical components, and the analytical validation tests presented.

Ask a specific question about this device

HemosIL ReadiPlasTin is an in vitro diagnostic thromboplastin reagent, based on recombinant human tissue factor, for the quantitative determination, in human citrated plasma, of Prothrombin Time (PT) and Fibrinogen, on the ACL TOP Family and ACL TOP Family 50 Series of analyzers. The product is intended to be used for the extrinsic coagulation pathway and the monitoring of Oral Vitamin K Antagonist Therapy.

The thromboplastin reagent included in the ReadiPlasTin kit, after mixing with the ReadiPlasTin Diluent, is a liposomal preparation that contains recombinant human tissue factor (RTF), re-lipidated in a synthetic phospholipid blend. In the PT test, the addition of the tissue thromboplastin (ReadiPlasTin reagent) to the patient plasma in the presence of calcium ions initiates the activation of the extrinsic pathway. This results ultimately in the conversion of fibrin, with formation of a solid gel. The fibrinogen is quantitated (PT-based method) by relating the absorbance or light-scatter during clotting to a calibrator.

The provided text is a 510(k) Summary for a medical device called "HemosIL ReadiPlasTin." This document doesn't describe an AI/ML-based device, but rather an in vitro diagnostic (IVD) reagent used for Prothrombin Time (PT) and Fibrinogen determination. Therefore, many of the requested categories related to AI/ML device testing (e.g., number of experts for ground truth, adjudication method, MRMC study, training set information) are not applicable to this type of submission.

However, I can extract the relevant information regarding acceptance criteria and performance studies for this IVD device.

Here's a breakdown of the requested information, adapted for an IVD reagent:

Device: HemosIL ReadiPlasTin (In vitro diagnostic thromboplastin reagent)
Purpose: Quantitative determination of Prothrombin Time (PT) and Fibrinogen in human citrated plasma.
Reason for Submission (K213426): Reformulation of the existing HemosIL ReadiPlasTin by adding EDTA as a stabilizer and removing unnecessary fillers.

1. Table of Acceptance Criteria and Reported Device Performance

For this IVD, "acceptance criteria" are typically defined by the method validation standards (e.g., CLSI guidelines) and the equivalence to the predicate device. The performance data presented are the results of meeting these criteria.

• PT: UFH (1.0 IU/mL), LMWH (1.4 IU/mL), Hemoglobin (500 mg/dL), Triglycerides (1000 mg/dL), Bilirubin (Conjugated & Unconjugated) (50 mg/dL), Daptomycin (100 µg/mL)
• Fibrinogen: UFH (1.5 IU/mL), LMWH (1.7 IU/mL), Hemoglobin (500 mg/dL), Triglycerides (600 mg/dL), Bilirubin (Conjugated & Unconjugated) (50 mg/dL), Daptomycin (200 µg/mL) | New claims for daptomycin and conjugated bilirubin interference were added. The study used 2 clinical sample levels for both PT and Fibrinogen. |
  | Method Comparison | Strong correlation and agreement between the subject device and the predicate device (HemosIL RecombiPlasTin 2G). Slope should be near 1, intercept near 0, and correlation coefficient (r) close to 1. | ACL TOP Family:
• PT (INR): Slope 1.031 (95% CI 1.009, 1.053), Intercept -0.043 (-0.068, -0.018), r 0.997
• Fibrinogen (mg/dL): Slope 0.975 (95% CI 0.963, 0.986), Intercept 7.171 (3.842, 10.50), r 0.995
  ACL TOP Family 50 Series:
• PT (INR): Slope 1.021 (95% CI 0.999, 1.043), Intercept -0.034 (-0.060, -0.009), r 0.996
• Fibrinogen (mg/dL): Slope 1.015 (95% CI 1.003, 1.027), Intercept -0.811 (-4.148, 2.527), r 0.994 | All method comparison results demonstrated excellent correlation and agreement, supporting substantial equivalence. |
  | Open Vial Stability | Maintain performance for 10 days at 2-8°C in closed original vial after preparation. | "The results support the following labeled open vial stability claim: Once prepared for use, 10 days at 2-8℃ in closed original vial" | Tested across 3 lots per CLSI EP25-A. |
  | On-board Instrument Stability | Maintain performance for 10 days at 15°C on the ACL TOP Family and ACL TOP Family 50 Series after preparation. | "The results support the following labeled on-board instrument stability claim: Once prepared for use, 10 days at 15°C on the ACL TOP Family and ACL TOP Family 50 Series" | Tested across 3 lots per CLSI EP25-A. |
  | Real-time Shelf-life Stability | Device maintains stated performance throughout its claimed shelf-life. | "The study will continue to a point past final claim." (Ongoing assessment to support shelf-life). | Tested across 3 lots per CLSI EP25-A. |

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

• Precision:

  • Sample Size: 80 measurements per instrument per lot (n=80/instrument/lot) for PT (controls + 6 native patient samples) and Fibrinogen (controls + 6 fibrinogen sample pools at 3 levels). Tested across 3 lots and representative members of both ACL TOP Family and ACL TOP Family 50 Series.
  • Data Provenance: Not explicitly stated, but "native (unadulterated) patient samples" and "fibrinogen sample pools" suggest human biological samples. Typically, these studies are conducted in a controlled laboratory setting (Likely within the manufacturer's R&D facilities or a contract research organization). The document is submitted to the US FDA, implying relevance to the US market. The retrospective/prospective nature is generally prospective for these types of validation studies.

• Interference:

  • Sample Size: Two clinical sample levels each for PT (normal pooled plasma and a high INR clinical sample) and Fibrinogen (normal pooled plasma and a low fibrinogen sample). Specific "n" per concentration/sample type is not given, but refers to CLSI EP07, 3rd Ed and CLSI EP37, 1st Ed which define the study design.
  • Data Provenance: Not explicitly stated, but "clinical sample levels" implies human biological samples.

• Method Comparison:

  • Sample Size:
    • PT (INR): 160 samples (normal and abnormal) for both ACL TOP Family and ACL TOP Family 50 Series.
    • Fibrinogen (mg/dL): 135 samples for ACL TOP Family, 134 samples for ACL TOP Family 50 Series.
  • Data Provenance: Not explicitly stated, but "normal and abnormal samples" implies human biological samples. The study was "in-house."

• Open Vial and On-board Instrument Stability:

  • Sample Size: For PT, controls and four native (unadulterated) patient samples were tested in eight replicates at each time interval. For Fibrinogen, controls and six fibrinogen sample pools at three levels were tested in eight replicates at each time interval.
  • Data Provenance: Not explicitly stated, but "native (unadulterated) patient samples" and "fibrinogen sample pools" imply human biological samples.

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

This is not applicable for this type of IVD device. The ground truth for chemical assays like PT and Fibrinogen is established through precise measurement methods and reference materials, not through expert consensus of visual or diagnostic interpretations. The "truth" is the quantitative value derived from the reference method or calibrator.

4. Adjudication Method for the Test Set

Not applicable, as this is an IVD reagent and not an AI/ML-based diagnostic system requiring human interpretation or adjudication.

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

Not applicable, as this is an IVD reagent and not an AI/ML-based diagnostic system involving human interpretation.

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

Not applicable, as this is an IVD reagent. Its performance is inherent to the chemical reaction and the analytical instrument it is used with.

7. The Type of Ground Truth Used

The "ground truth" for this IVD is established by:

• Reference Methods/Materials: For PT and Fibrinogen, this would rely on internationally recognized standards and calibrators, and the values obtained from a validated reference method (or the predicate device in method comparison studies).
• Known Concentrations: For linearity and interference studies, samples are often spiked with known concentrations of analytes or interfering substances.
• Validated Predicate Device: In the method comparison study, the predicate device (HemosIL RecombiPlasTin 2G) serves as the comparator for verifying the new formulation's performance.

8. The Sample Size for the Training Set

Not applicable. This is an IVD reagent, not an AI/ML model that requires a "training set." The development of the reagent involves chemical formulation and optimization, not data-driven machine learning.

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

Not applicable, as there is no "training set" for an IVD reagent.

Ask a specific question about this device

CRYOcheck Chromogenic Factor VIII is for clinical laboratory use in the quantitative determination of factor VIII activity in 3.2% citrated human plasma. It is intended to be used in identifying factor VIII deficiency and as an aid in the management of hemophilia A in individuals aged 2 years and older. For in vitro diagnostic use.

CRYOcheck Chromogenic Factor VIII is used for determination of FVIII activity and contains the following four components, packaged in glass vials and provided frozen to preserve the integrity of the components:
Reagent 1: Bovine FX and a fibrin polymerization inhibitor, with activators and stabilizers.
Reagent 2: Human FIIa, human FIXa, calcium chloride and phospholipids.
Reagent 3: FXa substrate containing EDTA and a thrombin inhibitor.
Diluent Buffer: Tris buffer solution containing 1% BSA and a heparin antagonist.

The CRYOcheck Chromogenic Factor VIII device is intended for the quantitative determination of Factor VIII (FVIII) activity in human plasma to identify FVIII deficiency and aid in Hemophilia A management.

Here's an analysis based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the successful outcomes of various studies, aligning with CLSI guidelines and demonstrating performance comparable to the predicate device. Specific numerical acceptance criteria were not explicitly stated as pass/fail thresholds in the document, but the reported performance values are presented as the fulfillment of these criteria.

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

• Precision Study: One normal and two abnormal reference controls, and five patient plasma samples (representing very low, mid, normal, and high FVIII activity). Each sample was measured in duplicate, twice a day for 20 days (total 80 replicates per sample per lot) with 3 lots of the device. Data provenance is internal (as it's an internal study).
• Reproducibility Study: One normal and two abnormal reference controls, and three patient plasma samples (representing very low, normal, and high FVIII activity). Each sample was measured in triplicate, twice a day for 5 days at each of 3 sites with 3 lots of the device. Data provenance includes one internal and two external sites, but specific countries are not mentioned beyond "Canada" for the submitter. This appears to be prospective data collection for the study.
• Linearity/Assay Reportable Range Study: Fifteen sample dilutions created by combining high FVIII plasma (260%) with congenital FVIII deficient plasma (0%). Each level was tested in quadruplicate. Data provenance is internal (as it implies an internal study).
• Reference Interval Study: One hundred and twenty ostensibly healthy individuals $\geq$ 18 years. Data provenance is not specified beyond "citrated plasma samples collected from". This appears to be prospective data collection.
• Shelf-Life Stability Study: Six plasma samples representing low to normal FVIII activity levels. Three lots of the device were tested at various time points up to 37 months (13 months completed). Data provenance is internal.
• In-Use Stability Study: Six plasma samples representing low to normal FVIII activity levels. Three lots of the device were tested at various time points. Data provenance is internal.
• Detection Limit (LoB/LoD/LoQ) Studies:
  • LoB: Four blank plasma samples from individuals with severe congenital hemophilia A.
  • LoD: Four plasma samples with low FVIII activity from congenital hemophilia A donors.
  • LoQ: Aliquots of four plasma samples with low FVIII activity from congenital hemophilia A donors.
    All samples for LoB/LoD were measured in triplicate over five days using three lots of the device. For LoQ, samples were tested in triplicate on five different days at an external laboratory. Data provenance for LoB/LoD/LoQ samples is from individuals with hemophilia A.
• Interference Studies: Plasma samples spiked with possible interferents. Ten replicates of each spiked sample and 10 replicates of corresponding blank matrix control were tested. Data provenance is internal.
• Method Comparison Studies: Three hundred and eighteen human plasma samples from normal individuals, patients with congenital or acquired hemophilia A, and various types of von Willebrand disease. Samples were distributed across three sites. Data provenance spans "normal ostensibly healthy individuals and from patients". This appears to be prospective data collection.
• Sample Integrity Study: Forty-six plasma samples. Data provenance is not further specified. This appears to be prospective data collection at two external sites.

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

For this in vitro diagnostic device, "ground truth" is typically established by reference methods or accepted clinical classifications rather than expert consensus on individual images or cases.

• For studies like Precision, Reproducibility, Linearity, Stability, and Detection Limits, the "ground truth" for the FVIII activity levels in controls and calibrators would be established by the manufacturer's internal characterization methods, traceable to international standards if applicable (though not explicitly stated as such for FVIII activity). The expertise would lie in clinical chemistry, hematology, and laboratory medicine for the development and validation of these reference materials and methods. No specific number or qualification of experts is mentioned for these.
• For the Reference Interval Study, the ground truth is derived from the statistical distribution of FVIII activity in a population of ostensibly healthy individuals. This doesn't involve individual expert ground-truthing but rather statistical analysis.
• For the Method Comparison Study, the ground truth for FVIII activity was established by a comparator device, Coatest SP FVIII (K042576), used at a central reference laboratory. The "experts" in this context are the trained laboratory personnel performing the reference method.
• For sample selection in studies involving "congenital hemophilia A donors" or "patients with congenital or acquired hemophilia A and various types of von Willebrand disease," the diagnosis (which forms part of the "ground truth" for classifying these samples) would have been made by medical professionals (e.g., hematologists) based on standard clinical and laboratory diagnostic criteria. No specific number or qualifications are given.

4. Adjudication Method for the Test Set

Adjudication methods like "2+1" or "3+1" are typically used for subjective diagnostic tasks, often involving image interpretation or clinical reviews. Since the CRYOcheck Chromogenic Factor VIII is a quantitative assay for FVIII activity, the "adjudication method" is the quantitative measurement itself, often with replicates and statistical analysis, as detailed in the study designs (e.g., "in duplicate," "in triplicate"). No expert adjudication in the traditional sense is described or expected for this type of device.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are primarily for evaluating the impact of a new diagnostic tool on the diagnostic performance of human readers, typically with subjective assessments. This device is a quantitative in vitro diagnostic, not a tool for human reading in the conventional sense.

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

Yes, the device operates as a standalone algorithm (assay) measuring FVIII activity. The performance studies described (Precision, Reproducibility, Linearity, Reference Interval, Stability, Detection Limits, Interferences, Method Comparison, Sample Integrity) all represent the performance of the device itself, without human-in-the-loop diagnostic interpretation as part of its core function, other than trained laboratory personnel operating the instrument and interpreting numerical output.

7. The Type of Ground Truth Used

The ground truth used for these studies varies by the specific test:

• Reference materials and controls: For precision, linearity, and detection limit studies, the ground truth for FVIII activity levels is based on established values of these materials, likely traceable to international standards or well-characterized internal standards.
• Healthy population data: For the reference interval, the ground truth for "normal" FVIII activity is derived from a statistically representative healthy population.
• Comparator device: For the method comparison study, the ground truth was established by the predicate device, Coatest SP FVIII (K042576).
• Clinical diagnosis: For studies involving patient samples (e.g., hemophilia A, von Willebrand disease), the ground truth for their disease status would be based on clinical diagnosis by medical professionals.

8. The Sample Size for the Training Set

The document describes performance studies (validation tests) for the device. It does not provide information on a "training set" in the context of machine learning. This is because the device is a chemical assay, not an AI/ML-based diagnostic system that would require a training set to develop its model.

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

As no training set is mentioned or applicable for this type of chemical assay device, this question is not relevant based on the provided information.

Ask a specific question about this device