(167 days)
HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP 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 embolism (PE).
For in vitro diagnostic use.
The D-Dimer HS Latex Reagent is a suspension of polystyrene latex particles of uniform size coated with the F(ab)2 fragment of a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. The use of the F(ab)2 fragment allows a more specific D-Dimer detection avoiding the interference of some endogenous factors like the Rheumatoid Factor. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer HS 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 caused by the aggregates (turbidimetric immunoassay).
The HemosIL D-Dimer HS device is designed to quantitatively determine D-Dimer in human citrated plasma using an automated latex-enhanced immunoassay on the ACL TOP system. It is intended 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 embolism (PE).
Here's an analysis of its acceptance criteria and the study proving its performance:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria for the HemosIL D-Dimer HS device are implicitly demonstrated through its performance in a clinical management study, aiming to show high sensitivity and Negative Predictive Value (NPV) for VTE exclusion. While explicit "acceptance criteria" in terms of target percentages are not stated as such in the provided summary, the reported performance demonstrates its suitability for the stated intended use. A reasonable interpretation of "acceptance criteria" for a diagnostic device intended for exclusion would be very high sensitivity and NPV.
| Performance Metric | Target (Implicit Acceptance Criteria for exclusion) | Reported Device Performance (95% CI) - All Samples (DVT) | Reported Device Performance (95% CI) - All Samples (PE) |
|---|---|---|---|
| Sensitivity | Very High (e.g., >95%, ideally 100%) | 100.0% (94.2%-100.0%) | 100.0% (93.8%-100.0%) |
| Specificity | (Not primary for exclusion, but clinically relevant) | 38.4% (32.2%-44.8%) | 35.6% (30.2%-41.3%) |
| Negative Predictive Value (NPV) | Very High (e.g., >95%, ideally 100%) | 100.0% (96.2%-100.0%) | 100.0% (96.6%-100.0%) |
| Positive Predictive Value (PPV) | (Clinically relevant) | 29.1% (23.1%-35.7%) | 22.9% (17.9%-28.6%) |
| Prevalence | (Contextual) | 20.2% (15.8%-25.1%) | 16.1% (12.4%-20.3%) |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- DVT Study: 307 patients
- PE Study: 361 patients
- Total Patients: 668 patients
- Data Provenance:
- Country of Origin: Not explicitly stated, but the study was described as a "multi-center management study was performed at four hospitals," suggesting a clinical setting likely within the country of the applicant (USA, based on address) or a close region.
- Retrospective or Prospective: The study was prospective. Patients were "admitted consecutively to the emergency unit with suspected DVT or PE" and underwent a PTP assessment followed by D-Dimer testing and subsequent diagnostic or follow-up procedures based on the results. The 3-month follow-up for negative D-Dimer patients confirms a prospective design.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The ground truth was established through a clinical management study involving diagnostic testing and 3-month follow-up, rather than expert review of images or specific clinical data points in isolation.
- Number of Experts: Not applicable in the context of establishing a ground truth for a diagnostic test like DVT/PE in this manner. The "experts" were the treating physicians who made decisions based on PTP and D-Dimer results, and the diagnostic imaging specialists who confirmed or ruled out DVT/PE.
- Qualifications of Experts: Not explicitly stated for specific individuals involved in ground truth determination. However, the study involved "patients admitted consecutively to the emergency unit" and "physician's decision" for follow-up, implying that the diagnostic and follow-up procedures were managed by qualified medical professionals (e.g., emergency physicians, radiologists, vascular specialists).
4. Adjudication Method for the Test Set
The adjudication method was based on a clinical management algorithm:
- Negative D-Dimer + Low PTP: No further diagnostic testing, followed up after 3 months for development of DVT or PE.
- Negative D-Dimer + Moderate PTP: Physician's decision for 3-month follow-up or imaging techniques.
- Positive D-Dimer or High PTP: Underwent imaging techniques (e.g., ultrasound/venography for DVT, CTPA/V/Q scan for PE).
- 3-Month Follow-up: "As of the 3 month followup, none of the patients that were negative through D-Dimer testing had developed DVT or PE," which serves as a crucial part of the ground truth confirmation for the exclusion criteria.
This is a treatment-based or outcome-based adjudication that integrates diagnostic test results with clinical assessment and subsequent diagnostic pathways/follow-up.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, an MRMC comparative effectiveness study was not done. This is a diagnostic immunoassay, not an imaging device that typically requires human reader interpretation. The device's output is a quantitative D-Dimer value. The study evaluated the device's effectiveness within a clinical management pathway, not how human readers improve with or without AI assistance.
6. Standalone (Algorithm Only) Performance
- Yes, standalone performance was done. The reported sensitivity, specificity, and NPV values reflect the performance of the HemosIL D-Dimer HS assay at its clinical cut-off (230 ng/mL) within the context of a PTP model. The device itself generates the D-Dimer value, and the study assesses how that value performs in conjunction with PTP to exclude VTE. It's the performance of the assay in combination with PTP that is being evaluated in a standalone manner from further human interpretation of the D-Dimer value itself.
7. Type of Ground Truth Used
- The ground truth was a combination of definitive diagnostic imaging (e.g., ultrasound, CTPA) and 3-month clinical outcome data.
- Patients with positive D-Dimer or high PTP were sent for imaging, which is considered a definitive diagnostic method.
- Patients with negative D-Dimer and low/moderate PTP were followed up for 3 months to confirm the absence of VTE. If VTE didn't develop, that confirmed the initial exclusion. This integrates clinical outcomes into the ground truth.
8. Sample Size for the Training Set
- Not explicitly stated in the provided text. The summary focuses on the clinical validation study to support the intended use expansion. For immunoassay devices, "training sets" are typically used during assay development and optimization (e.g., establishing calibrator curves, cut-offs, interference profiles), which occurred before this 510(k) submission. The provided performance data (Sensitivity, Specificity, NPV) is from the test set (668 patients).
9. How the Ground Truth for the Training Set Was Established
- Not explicitly stated. As noted above, the concept of a "training set" and "ground truth establishment" for it is less applicable in the same way as for AI/ML algorithms in imaging. For a diagnostic immunoassay, the "ground truth" for developing the assay and establishing initial cut-offs (like the 230 ng/mL) would typically involve:
- Known positive and negative samples: Panels of samples from individuals definitively diagnosed with and without DVT/PE (e.g., confirmed by imaging or long-term follow-up).
- Correlation with predicate devices or established methods: Comparing results from the developing assay with well-established D-Dimer assays or gold-standard diagnostic procedures.
- Repeatability and reproducibility studies: Using control materials to ensure consistent performance.
The 230 ng/mL clinical cut-off is mentioned as "previously established," indicating it was determined prior to this specific multi-center management study. The details of how this initial cut-off was established and what data was used are not provided in this 510(k) summary.
§ 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).