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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 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).

This document is a 510(k) summary for the HemosIL D-Dimer HS device, which is an in vitro diagnostic (IVD) test. This specific submission (K160885) is a "Special 510(k)" to update the Limit of Detection (LoD) claim for the device.

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

Key Takeaway: The "device" in this context is an in vitro diagnostic assay (HemosIL D-Dimer HS) used to quantitatively determine D-Dimer levels in human plasma. The primary focus of this specific 510(k) submission is to update a performance claim, specifically the Limit of Detection (LoD), rather than introducing a new product or a significant change in intended use.

Given this, the questions provided in the prompt, which are commonly associated with AI/ML-driven medical imaging devices, need to be reinterpreted or noted as "not applicable" for this type of IVD 510(k) submission.

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for this submission is the updated Limit of Detection (LoD). The device's performance is reported directly against this criterion.

1. Table of acceptance criteria and the reported device performance:

Note: The submission states that the only change is to the LoD claim based on additional testing. All other performance claims (linearity, cut-off, etc.) remain the same as the predicate device.

Study Details (Reinterpreted for IVD Context)

Many of the points in the prompt are more relevant to AI/ML image analysis rather than an IVD assay. Where applicable, the information is provided. Where not applicable, it is noted.

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

• Sample Size: The document states that the testing was "additional testing done to current CLSI EP17-A2 requirements" to establish the updated LoD. However, the specific number of samples (e.g., patient samples, spiked samples, replicates) used for this testing to calculate the LoD is not provided in this summary. CLSI EP17-A2 is a standard guideline for evaluation of detection capability for clinical laboratory measurement procedures. This guideline typically involves a statistically significant number of replicates (e.g., 20 or more) of blank/low-level samples across multiple runs.
• Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's an in vitro diagnostic, samples would typically be analyzed fresh or from appropriately stored biobanks.

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

• Not Applicable in this context. For an IVD assay like D-Dimer, the "ground truth" for the test set is established by the known concentrations of calibrators and controls, or by reference methods/materials of traceable value (e.g., a known concentration of D-Dimer in a sample matrix). It does not involve human expert interpretation in the same way an imaging study would.

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

• Not Applicable. This concept is for diagnostic interpretation, typically by human readers, not for quantitative analytical performance of an IVD assay.

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. This is an IVD assay, not an AI-assisted diagnostic imaging system. Its performance is measured analytically (e.g., precision, accuracy, LoD, linearity) against known values or reference methods, not against human reader performance.

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

• Yes, in the context of an IVD. The HemosIL D-Dimer HS device is an automated, standalone assay run on ACL TOP instruments. Its performance (e.g., LoD) is determined analytically by the instrument and reagents, independent of human interpretive input. Human operators load samples and reagents, and review results, but the analytical measurement itself is automated.

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

• For an analytical performance evaluation like Limit of Detection, the ground truth is established based on statistical analysis of replicate measurements of samples with very low (or zero) analyte concentration. This would involve:
  • Defined Calibrators: Solutions with known, precise concentrations of D-Dimer.
  • Controls: Materials with target D-Dimer concentrations used for quality control.
  • Reference Materials/Methods: Comparison to a highly accurate reference method or certified reference materials, if available, though for LoD, it's more about statistical confidence in detecting low levels.
  • Statistical Methods: LoD is determined using statistical approaches defined by guidelines like CLSI EP17-A2, which typically involves measuring blank samples and low-level samples and calculating the concentration at which detection is statistically reliable. This does not involve "expert consensus" in the clinical diagnostic sense.

8. The sample size for the training set:

• Not Applicable in the AI/ML sense. This is not an AI/ML algorithm that requires a "training set." The assay is a chemical and immunoturbidimetric reaction. The development of such an assay involves extensive R&D and optimization, but not typically a "training set" in the machine learning paradigm.

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

• Not Applicable. See point 8. The "ground truth" for developing the assay itself involves ensuring the reagents specifically bind to D-Dimer and that the turbidimetric measurement accurately correlates with its concentration. This is achieved through chemical and biological validation, not through annotated training data.

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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-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

This document, K151534, is a 510(k) premarket notification for the HemosIL D-Dimer HS device. The submission is a "Special 510(k)" to add information about the association of patient age with D-Dimer levels to the device's insert sheet. This means there are no changes to the device's performance, indications for use, or operating principles. Therefore, there is no new study conducted to demonstrate that the device meets new acceptance criteria. Instead, the focus is on the substantial equivalence to the predicate device (K070927) based on the absence of changes to performance claims.

Given that this is a Special 510(k) submission for minor labeling changes and explicitly states "No change to labeled performance claims", there isn't a new study presented in this document proving the device meets new acceptance criteria. The existing performance acceptance criteria and their proof are derived from the original clearance of the predicate device (K070927).

However, I can extract the reported performance of the device (which remains unchanged from the predicate) and details relevant to a typical device submission, even though a new study isn't detailed here for new acceptance criteria.

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a Special 510(k) for labeling changes, the acceptance criteria and reported performance are implicitly those established during the original clearance of the predicate device (K070927). The document explicitly states "No change to labeled performance claims."

2. Sample size used for the test set and the data provenance
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
4. Adjudication method for the test set
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
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
8. The sample size for the training set
9. How the ground truth for the training set was established

The provided document (K151534) is a Special 510(k) submission that does not include a new study to establish performance for the device. It states, "No change to labeled performance claims, including no change to the assay cut-off." This submission is solely to add general information to the device's insert sheet regarding the association of patient age with D-Dimer levels, citing "peer-reviewed published literature."

Therefore, the information requested in points 2-9 about test sets, experts, adjudication, MRMC studies, standalone performance, ground truth, and training sets is not available in this document. Such details would have been part of the original 510(k) submission (K070927) for the predicate device, which established its performance characteristics. This current submission does not involve new clinical or performance studies for the device itself.

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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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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.

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.

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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 as an aid in the diagnosis of venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism (PE)]. For in vitro diagnostic use.

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 as an aid in the diagnosis of venous thromboembolism (VTE) [deep venous thrombosis (DVT) and pulmonary embolism (PE)]. 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 Latcx 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).

Here's an analysis of the acceptance criteria and study detailed in the provided K050544 submission for the HemosIL D-Dimer HS device:

1. Table of Acceptance Criteria and Reported Device Performance

The submission does not explicitly state pre-defined acceptance criteria for the "Management Study" in terms of specific sensitivity, specificity, and NPV values. Rather, it presents the results of the study. However, the intent is clearly to demonstrate the device's utility in a clinical context, and thus, the reported performance itself serves as the de facto "met" criteria for this submission. For precision and method comparison, the results are presented, implying they met internal or regulatory expectations for substantial equivalence.

2. Sample Size and Data Provenance for the Test Set

• Precision Test Set: Not explicitly stated as a separate "test set" in the context of the management study. For precision, three levels of control plasma were used over multiple runs.
• Method Comparison Test Set:
  • Sample Size: n=229
  • Data Provenance: Not explicitly stated, but given it's a 510(k) submission from a US-based company, it's highly probable the samples were from the US. The samples were "citrated plasma samples ranging in D-Dimer concentration from 87 to 20869 ng/mL." Retrospective or prospective is not explicitly stated, but the nature of comparing archived samples suggests it could be retrospective.
• Management Study Test Set:
  • Sample Size: 300 frozen samples.
  • Data Provenance: The samples were from "patients admitted consecutively to an emergency unit with suspected PE or DVT." The country of origin is not specified, but the submission is for the US market. The samples were "frozen," suggesting a retrospective study design where samples were collected and then later analyzed.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

• Precision and Method Comparison: No external experts were used to establish ground truth for these studies, as they are analytical performance evaluations against instrument controls or a predicate device.
• Management Study: The ground truth for VTE positive and negative status was established by "standard objective tests." The specific number or qualifications of experts (e.g., radiologists interpreting imaging, clinicians making a final diagnosis based on multiple tests) used to interpret these objective tests are not specified in the document.

4. Adjudication Method (Test Set)

• Precision and Method Comparison: Not applicable, as these are analytical performance studies.
• Management Study: An adjudication method for determining the "standard objective tests" outcome (VTE positive/negative) is not described in the document. It simply states "standard objective tests" were used.

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

• No, a multi-reader multi-case (MRMC) comparative effectiveness study of human readers with vs. without AI assistance was not done. This device is an automated in vitro diagnostic immunoassay, not an imaging analysis or decision support AI tool designed to assist human readers directly.

6. Standalone (Algorithm Only) Performance Study

• Yes, the "Management Study" represents a standalone performance evaluation. The HemosIL D-Dimer HS is an automated immunoassay device. The reported sensitivity, specificity, and NPV were generated by the algorithm (the automated immunoassay system) interpreting the D-Dimer levels in the plasma samples, independent of human interpretation of the assay results, other than reading the final numerical output. The performance metrics reflect the device's ability to classify patients based on a single D-Dimer concentration cut-off.

7. Type of Ground Truth Used (Test Set)

• Precision and Method Comparison: Not applicable in the same way as a diagnostic study. Ground truth for precision is based on statistical measures of repeatability using known controls. Ground truth for method comparison is the measurement obtained from the predicate device.
• Management Study: The ground truth for VTE (DVT/PE) diagnosis was established using "standard objective tests." These typically include imaging modalities like ultrasound (for DVT) and CT pulmonary angiography (CTPA) or ventilation/perfusion (V/Q) scans (for PE), potentially combined with clinical assessment. This is a form of clinical outcome/reference standard ground truth.

8. Sample Size for the Training Set

• The document does not provide information about a separate "training set" for the HemosIL D-Dimer HS device. Automated immunoassays like this are typically developed and validated using a structured process that involves reagent optimization, calibration, and then performance verification studies as described. They are not "trained" in the machine learning sense with large datasets to learn features. The "training" in this context refers to the initial development and optimization of the assay's chemical and optical properties, and calibration procedures.

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

• As no "training set" in the machine learning sense is described, this question is not applicable. The "ground truth" for developing such an assay would be precisely measured D-Dimer concentrations in various samples to ensure the assay accurately quantifies the analyte.

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