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HemosIL D-Dimer HS 500 is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP® Family and ACL TOP Family 50 Series 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 embolism (PE). For in vitro diagnostic use.

The D-Dimer HS 500 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 HemosIL D-Dimer HS 500 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 transmitted light caused by the aggregates (turbidimetric immunoassay).

The provided document is a 510(k) summary for the HemosIL D-Dimer HS 500 device. This particular submission (K172903) is a Special 510(k), meaning it's for modifications to an already cleared device (predicate K090264) and not for a de novo clearance. Special 510(k)s typically do not require new clinical studies to demonstrate device performance against acceptance criteria, as the performance claims are carried over from the predicate device.

The main purpose of K172903 is to add general information from peer-reviewed published literature to the Summary and Principle section of the HemosIL D-Dimer HS 500 insert sheet regarding the association of patient age with D-Dimer levels and to clarify that the device's performance has not been validated for age-adjusted cut-off values.

Therefore, many of the requested items regarding a new clinical study and ground truth establishment would not be applicable to this specific submission. However, I can extract the acceptance criteria and performance claims that apply to the predicate device and are carried over to this modified device.

Here's the breakdown based on the provided text:

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

Since this is a Special 510(k) for an insert sheet modification and not a new device, the acceptance criteria and reported performance are implicitly the same as the predicate (K090264). The document explicitly states "No change to labeled performance claims, including no change to the assay cut-off."

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This information is not provided in this Special 510(k) summary (K172903) because no new clinical test set was used or presented for this particular submission. The performance claims are based on the predicate device (K090264). To obtain this information, one would need to refer to the 510(k) summary for K090264.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in this Special 510(k) summary (K172903) as no new clinical test set (requiring expert ground truth) was used for this submission. This type of detail would be found in the original 510(k) for the predicate device (K090264) which established the clinical performance.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not provided in this Special 510(k) summary (K172903) as no new clinical test set requiring adjudication was used for this submission. This type of detail would be found in the original 510(k) for the predicate device (K090264).

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 for D-Dimer measurement, not an imaging device typically analyzed by human readers in the context of MRMC studies or AI assistance in reading. Therefore, an MRMC comparative effectiveness study, as described, is not applicable.

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

The HemosIL D-Dimer HS 500 is an automated immunoassay for quantitative determination. Its performance is inherently "standalone" in the sense that it provides a quantitative result based on the immunoassay reaction, without direct human cognitive input in interpreting the raw signal for the D-Dimer concentration. The result is then used in conjunction with a clinical pretest probability (PTP) assessment model by a clinician. The validation of its quantitative accuracy would have been performed during the original clearance (K090264).

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

For an in vitro diagnostic device like a D-Dimer assay, the ground truth for performance measures like linearity, detection limit, and cut-off would typically be established by:

• Reference methods/calibrators: For analytical performance (linearity, detection limit), certified reference materials or highly accurate reference methods would be used.
• Clinical outcomes/diagnosis: For the diagnostic performance (sensitivity, specificity, NPV for VTE exclusion), the ground truth for DVT/PE would be established through definitive diagnostic imaging (e.g., ultrasound, CTPA, ventilation-perfusion scan) or other established clinical diagnostic criteria for the patient cohort recruited for the original predicate study (K090264).

This specific Special 510(k) (K172903) does not provide these details as it relies on the predicate (K090264).

8. The sample size for the training set

This information is not provided in this Special 510(k) summary (K172903). For an immunoassay, the concept of a "training set" in the context of machine learning (as often implied by this question) is not directly applicable. However, method development and optimization would involve numerous samples, with calibration curves and reagents being "trained" or optimized during the development phase of the original predicate device (K090264), but described in terms of analytical validation rather than a machine learning 'training set'.

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

As above, while not a "training set" in the common AI sense, the ground truth for optimizing assay parameters and establishing analytical performance (for the original predicate K090264) would have been established using reference standards or established, validated methods. Clinical training data, if any, for setting the original cut-off would have involved patients with confirmed (or ruled out) DVT/PE, as validated by definitive diagnostic tests. This information is not within this K172903 document.

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HemosIL D-Dimer HS 500 Controls are assayed, human-sourced controls intended for the quality control of the HemosIL D-Dimer HS 500 assay as performed on the ACL TOP Family System, in a clinical laboratory setting. The controls are intended for in vitro diagnostic use.

Level 1 D-D HS 500 Control is intended for the assessment of the assay around the clinical cutoff for VTE (500 ng/mL FEU).

Level 2 D-D HS 500 Control is intended for the assessment of precision and accuracy of the assay at abnormal D-Dimer levels (above the cut-off).

Not Found

I am sorry, but based on the provided text, there is no information about acceptance criteria or a study proving the device meets acceptance criteria. The document is a 510(k) clearance letter for the HemosIL D-Dimer HS 500 Controls, outlining its intended use and regulatory information. It does not contain details about specific performance studies, sample sizes, ground truth establishment, or expert reviews.

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HemosIL D-Dimer HS 500 is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP® Family 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 embolism (PE).

HemosIL D-Dimer HS 500 Controls are intended for the quality control of the D-Dimer HS 500 assay performed on the ACL TOP® Family Systems.

For in vitro diagnostic use.

HemosIL D-Dimer HS 500: The D-Dimer HS 500 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'), 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 HemosIL D-Dimer HS 500 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 transmitted light caused by the aggregates (turbidimetric immunoassay).

HemosIL D-Dimer HS 500 Controls: The Low and High D-Dimer HS 500 Controls are prepared by means of a dedicated process and contain different concentrations of partially purified D-Dimer obtained by digestion of Factor XIIIa cross-linked human fibrin with human plasmin.

Here's an analysis of the provided text, outlining the acceptance criteria and the study data that supports the device's performance, as requested:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the HemosIL D-Dimer HS 500 assay are primarily focused on its sensitivity and negative predictive value (NPV) for excluding 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 reported performance from the outcome study and multi-center management study directly addresses these criteria.

Study Proving Device Meets Acceptance Criteria:

The device's ability to meet the acceptance criteria is demonstrated through two primary clinical studies and supporting analytical studies:

• "Outcome Study" (Section 2, paragraph 3)
• "Multi-center Management Study" (Section 3, paragraph 1)
• "Precision" study (Section 2, paragraph 1)
• "Method Comparison" study (Section 2, paragraph 2)

These studies collectively show that the HemosIL D-Dimer HS 500, with a clinical cut-off of 500 ng/mL, consistently achieved 100% sensitivity and 100% negative predictive value for both DVT and PE in the studied outpatient populations when used in conjunction with a PTP assessment. This indicates that no VTE events were missed by the test, effectively "excluding" the condition when the D-Dimer result was negative. The precision and method comparison studies demonstrate the analytical reliability and equivalence to existing commercial methods.

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

Due to the nature of this in-vitro diagnostic device (IVD), there isn't a traditional "test set" in the sense of a medical imaging AI algorithm. Instead, there are clinical samples used in performance evaluations.

• Outcome Study (Clinical Performance):

  • Sample Size: 295 frozen samples.
  • Data Provenance: Patients admitted consecutively to an emergency unit with suspected PE or DVT. The country of origin is not explicitly stated but implies a clinical setting. The samples are retrospective as they were "frozen samples" from past admissions.

• Multi-center Management Study (Clinical Performance):

  • Sample Size: 747 samples (401 suspected DVT, 346 suspected PE).
  • Data Provenance: Patients admitted consecutively to the emergency unit with suspected DVT or PE at four hospitals. The country of origin is not explicitly stated. This appears to be a prospective study because it describes patient management pathways and follow-up, indicating data collected as patients were presented.

• Precision and Method Comparison Studies: These appear to be in-house laboratory studies using controls, plasma pools, and patient samples (n=100 for method comparison). Further specifics on provenance are not detailed.

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

The concept of "experts" establishing ground truth in this context is different from image-based AI where radiologists annotate images. Here, the ground truth for VTE (DVT and PE) status was established through "standard objective tests" and clinical follow-up, not by a panel of human reviewers interpreting the D-Dimer test itself.

• Outcome Study: VTE positive cases (75 samples) were confirmed by "standard objective tests." VTE negative cases (220 samples) were also confirmed. The specific tests (e.g., ultrasound, CT angiography) are not detailed, nor are the number or qualifications of the clinicians/technicians who performed or interpreted these objective tests.

• Multi-center Management Study: VTE status for DVT and PE was confirmed through a combination of imaging techniques (for positive D-Dimer or high PTP patients) and importantly, 3-month clinical follow-up for patients with negative D-Dimer and low/moderate PTP. Again, the number and specific qualifications of the clinicians involved in these diagnostic methods or follow-ups are not specified.

4. Adjudication Method for the Test Set

Not applicable in the conventional sense of human reviewers adjudicating results. The "adjudication" of definitive VTE status relied on a combination of objective diagnostic tests and clinical follow-up, which are the accepted standards for determining the presence or absence of DVT/PE. The clinical pretest probability (PTP) assessment using the Wells model served as an initial clinical judgment tool, guiding further diagnostic pathways, but the ultimate ground truth was based on objective methods and patient outcomes.

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 as described for AI assistance. This device is an in-vitro diagnostic (IVD) assay, a lab test intended to provide quantitative results directly, not to assist human readers in interpreting complex images or data in the same way an AI algorithm might augment a radiologist. The study evaluates the assay's performance in a clinical pathway, not the improvement of human readers with AI assistance.

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

Yes, the performance data presented is for the standalone performance of the HemosIL D-Dimer HS 500 assay, specifically the quantitative determination of D-Dimer. The "human-in-the-loop" aspect here refers to the physician integrating the D-Dimer result with the clinical pretest probability (PTP) assessment model. The device itself (the assay) provides a direct quantitative reading (e.g., 500 ng/mL) without human interpretation to arrive at that numerical value. The clinical utility is then determined by how this standalone result integrates into a diagnostic algorithm. The sensitivity and NPV reported are based on the assay's output.

7. The Type of Ground Truth Used

The ground truth used for the clinical studies (Outcome Study and Multi-center Management Study) was primarily:

• Objective Diagnostic Tests: For confirmed VTE cases (DVT and PE), standard objective tests (e.g., imaging techniques like ultrasound for DVT, CT angiography for PE) were used. These are considered highly definitive.
• Outcomes Data (Clinical Follow-up): Crucially, for patients with negative D-Dimer and low/moderate PTP, the absence of VTE was confirmed by 3-month clinical follow-up where the development of DVT or PE was monitored. This represents outcomes data as ground truth, which is a very strong form of evidence for exclusion criteria.

8. The Sample Size for the Training Set

The provided summary does not explicitly mention a "training set" in the context of machine learning. This is an in-vitro diagnostic device, which is typically developed through analytical validation (reagent formulation, calibration, interference studies) and clinical validation.

• The "Method Comparison" study (n=100) could be considered part of the validation data used to refine or confirm equivalence, but it's not a training set for an algorithm in the AI sense.
• The "Precision" study uses controls and a plasma pool, which are analytical samples for assessing assay performance, not a training set.

If earlier development involved optimizing the assay's parameters (e.g., antibody concentration, reaction conditions), that would have used various experimental samples, but a defined "training set" like in AI is not applicable here.

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

As there isn't a "training set" in the AI sense for this IVD, this question is not directly applicable. For analytical development and validation, the "ground truth" would be established through:

• Defined D-Dimer concentrations: For calibrators and controls used in precision studies.
• Comparison to established reference methods: For method comparison, the predicate device (VIDAS D-Dimer Exclusion Assay) served as the reference for comparison. The ground truth for the samples tested would be their D-Dimer concentration as determined by the predicate device.

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