(276 days)
HemosIL D-Dimer is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on IL Coagulation Systems for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary cmbolism (PE).
The D-Dimer Latex Reagent is a suspension of polystyrenc latex particles of uniform size coated with a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of D-Dimer in the sample and is determined by measuring the decrease of the transmitted light at 405 nm caused by the aggregates (turbidimetric immunoassay).
Here's a breakdown of the acceptance criteria and study findings for the HemosIL D-Dimer, based on the provided text:
Acceptance Criteria and Device Performance
The acceptance criteria for the HemosIL D-Dimer device are demonstrated through its clinical performance metrics, specifically focusing on its ability to exclude venous thromboembolism (VTE) in outpatients suspected of Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE), when used in conjunction with a clinical pretest probability (PTP) assessment model. The key performance metrics are Sensitivity and Negative Predictive Value (NPV), as a high value in these indicates the device's effectiveness in ruling out the condition.
The reported device performance aims to demonstrate that the HemosIL D-Dimer test effectively rules out DVT and PE when the D-Dimer result is negative and the PTP is low/moderate.
Table of Acceptance Criteria (Implied by Intended Use) and Reported Device Performance:
| Performance Metric | Implied Acceptance Criteria (High for exclusion) | ACL TOP (Reported Performance - Low + Moderate PTP) | ACL ELITE (Reported Performance - Low + Moderate PTP) |
|---|---|---|---|
| DVT Sensitivity | High (e.g., >95%) | 100.0% (32/32) | 100.0% (32/32) |
| DVT Negative Predictive Value (NPV) | High (e.g., >95%) | 100.0% (92/92) | 100.0% (74/74) |
| PE Sensitivity | High (e.g., >95%) | 100.0% (43/43) | 97.6% (41/42) |
| PE Negative Predictive Value (NPV) | High (e.g., >95%) | 100.0% (79/79) | 99.1% (109/110) |
Note on Implied Acceptance Criteria: The document does not explicitly state numerical acceptance criteria in a dedicated section. However, for a device intended to exclude a condition, high sensitivity and a high negative predictive value are critical to minimize false negatives and ensure patient safety. The reported 100% sensitivity and NPV (or very close to it) for low and moderate PTP groups are indicative of meeting the implicit requirement for a safe exclusion test.
Study Details:
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Sample Size Used for the Test Set and Data Provenance:
- ACL TOP:
- DVT Suspected Patients: 302 samples
- PE Suspected Patients: 330 samples
- ACL ELITE:
- DVT Suspected Patients: 298 samples
- PE Suspected Patients: 331 samples
- Total Patients (ACL TOP & ELITE): 632 samples (ACL TOP) and 629 samples (ACL ELITE) according to the text, implying a total of approximately 1261 samples for the general study. The specific breakdown for DVT/PE cases are provided above.
- Data Provenance: The study was a "multi-center management study performed at four hospitals on patients admitted consecutively to the emergency unit." This indicates a prospective, real-world clinical study. The country of origin for the data is not explicitly stated, but the FDA submission and US regulatory context suggest a US-based or internationally recognized clinical trial standard.
- ACL TOP:
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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.
- It mentions that for patients with a positive D-Dimer test result or a high PTP score, they "underwent imaging techniques." For patients with negative D-Dimer and moderate PTP, "it was the physician's decision whether to follow-up after 3 months or to undergo imaging techniques." Finally, patients with a negative D-Dimer and low PTP "underwent no further diagnostic testing and were followed-up after 3 months for development of DVT or PE."
- This implies that the ground truth was established through a combination of:
- Diagnostic Imaging (e.g., ultrasound, CT angiography): For "positive" cases or those requiring further investigation.
- Clinical Follow-up (3 months): For "negative" cases, to confirm the absence of VTE.
- Physician's Decision/Clinical Judgment: For moderate PTP cases.
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Adjudication Method for the Test Set:
- The document does not explicitly detail an adjudication method in the typical sense of multiple readers reviewing results.
- However, the clinical pathway describes a form of outcome-based validation: "Patients with a negative D-Dimer test result and a low PTP score underwent no further diagnostic testing and were followed-up after 3 months for development of DVT or PE." This 3-month follow-up for outcomes serves as a de-facto adjudication for negative cases. Positive cases or those with high PTP were adjudicated by "imaging techniques."
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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, an MRMC comparative effectiveness study involving human readers and AI assistance was not done. This device is an in-vitro diagnostic (IVD) immunoassay, not an imaging-based AI diagnostic tool. The "AI" referred to in the question is not applicable to this type of device. The device itself performs the D-Dimer measurement.
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If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance data presented is for the HemosIL D-Dimer immunoassay in a standalone capacity (i.e., the algorithm/device only), to determine D-Dimer levels. The device itself is an automated laboratory test.
- However, its intended use is in conjunction with a clinical pretest probability (PTP) assessment model, which represents a human-in-the-loop component (the physician's clinical judgment to establish PTP). The reported sensitivity and NPV are for the D-Dimer test result within this clinical context (i.e., when combined with PTP).
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The Type of Ground Truth Used:
- As inferred from point 2, the ground truth was established through a combination of:
- Diagnostic imaging techniques (e.g., ultrasound, CT scans) to confirm or rule out DVT/PE in symptomatic patients or those with positive D-Dimer/high PTP.
- Patient outcomes data (3-month follow-up) to confirm the absence of DVT/PE in patients with negative D-Dimer and low/moderate PTP.
- As inferred from point 2, the ground truth was established through a combination of:
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The Sample Size for the Training Set:
- The document does not provide specific details on a dedicated "training set" for the HemosIL D-Dimer assay. This is typical for an immunoassay, where the assay's fundamental chemistry and measurement parameters (e.g., calibration, reagent concentrations, reaction times) are developed and optimized internally. The clinical study described is a validation study for the established assay, not a training phase for a machine learning model.
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How the Ground Truth for the Training Set Was Established:
- Given that this is an immunoassay and not an AI/machine learning device, there isn't a "ground truth for a training set" in the same sense. The "ground truth" for developing such an assay would relate to internal analytical validation, where known concentrations of D-Dimer are used to establish a standard curve, linearity, precision, etc. These methods are typically internal to the manufacturer's development process and not part of the clinical validation described here.
§ 864.7320 Fibrinogen/fibrin degradation products assay.
(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).