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The Sysmex® Automated Blood Coagulation Analyzer CS-2500 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of:

• . Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
• . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• . Fibrinogen (Fbg) with Dade® Thrombin Reagent
• . Coagulation Factor V with Dade® Innovin®
• . Coagulation Factor VII with Dade® Innovin®
• . Coagulation Factor VIII with Dade® Actin® FSL
• . Coagulation Factor IX with Dade® Actin® FSL
• . Lupus Anticoagulant with LA1 Screening / LA2 Confirmation Reagent
• . Factor V Leiden with Factor V Leiden Assay
• . Protein C with Protein C Reagent
• . Antithrombin (AT) with INNOVANCE® Antithrombin
• Protein C with Berichrom® Protein C
• D-dimer with INNOVANCE® D-Dimer
  The performance of this device has not been established in neonate and pediatric patient populations.

Intended Use for Factor V Leiden Assay:
The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.

Intended Use for Coagulation Factor VIII Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for Coagulation Factor IX Deficient Plasma:
In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for LA1 Screening / LA2 Confirmation Reagents:
LA1 Screening Reagent / LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.

The Sysmex® CS-2500 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent / LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table. The instrument is capable of measuring in Normal mode and Micro-sample mode. Options and accessories include a waste tank and a 2D barcode reader.

The provided document describes the 510(k) premarket notification for the Sysmex® Automated Blood Coagulation Analyzer CS-2500. This is a medical device, and the "study that proves the device meets the acceptance criteria" refers to the performance data submitted to demonstrate substantial equivalence to a predicate device.

It's important to note that this document is for an In Vitro Diagnostic (IVD) device, not an AI/ML algorithm for image interpretation. Therefore, many of the typical acceptance criteria and study designs associated with AI/ML (like multi-reader multi-case studies, expert adjudication for ground truth of imaging, or effect size of AI assistance for human readers) do not directly apply in the same way. Instead, the study focuses on analytical performance characteristics compared to a predicate device.

Here's an interpretation based on the provided document:

Acceptance Criteria and Device Performance

The acceptance criteria for this type of IVD device are typically established based on:

1. Method Comparison: Showing agreement with a legally marketed predicate device. This is evaluated using statistical methods like Passing-Bablok regression and Bland-Altman plots. Acceptance criteria would involve a high correlation coefficient (r), and a slope close to 1 and intercept close to 0, indicating strong agreement.
2. Reproducibility (Precision): Demonstrating the consistency of results when the test is repeated under varying conditions (within-run, between-run, between-day, and total variability). Acceptance criteria are typically expressed as a maximum allowable coefficient of variation (%CV).
3. Detection Capability (Limit of Quantitation): Proving the lowest concentration of an analyte that can be reliably measured. Acceptance criteria are usually based on a predefined maximum total error.
4. Linearity & Measuring Range: Confirming that the device produces results proportional to the concentration of the analyte across its claimed analytical measuring range. Acceptance criteria mean the measured linear range must encompass the claimed clinically reportable range.
5. Reference Interval: Establishing the range of test results expected in a healthy population. Acceptance criteria would be the successful determination of these intervals or confirmation of existing ones.
6. Clinical Performance (e.g., Cut-off Study): For specific assays, validating clinical performance characteristics like diagnostic accuracy against a gold standard (e.g., genotype for Factor V Leiden). Acceptance criteria would typically involve achieving high positive and negative percentage agreement.

1. Table of Acceptance Criteria and the Reported Device Performance

The document does not explicitly list the "acceptance criteria" numerical targets. Instead, it states that "Results from each application met the predetermined acceptance criteria." and later, "All reagents met the predetermined acceptance criteria." This implies that Siemens had internal, pre-defined thresholds for these performance metrics, which were successfully met.

Based on the performance data presented, here is a summary table, inferring the intent behind the reported results as meeting acceptance:

2. Sample sizes used for the test set and the data provenance

• Method Comparison:
  • Sample Size (for each application): Varied by site and application, ranging from N=8 to N=173 for individual sites.
    • Factor V Leiden: Total N = 494 (Combined Sites)
    • Coagulation Factor VIII: Total N = 408 (Combined Sites)
    • Coagulation Factor IX: Total N = 459 (Combined Sites)
    • Lupus Anticoagulant (LA1, LA2, Ratio): Total N = 347-402 (Combined Sites)
  • Data Provenance: Conducted at four external sites; 3 in the United States and one in Germany. Samples were patient samples. Retrospective (implied by "patient samples collected," likely frozen/stored retrospectively as this is an analyzer validation, not a live clinical trial for patient outcomes).
• Reproducibility Studies:
  • Sample Size: Not explicitly stated as a number of distinct patient samples. The study design followed CLSI EP05-A2, which involves repetitive testing of control materials or pooled patient samples over multiple days/runs. "Twenty-day precision studies" were performed.
  • Data Provenance: One external site in Germany and two external sites in the United States.
• Detection Capability, Linearity & Measuring Range:
  • Sample Size: Not explicitly stated as a number of distinct patient samples. These studies typically use diluted samples or spiked samples to cover the analytical range.
  • Data Provenance: Not specified, but likely conducted at the same or similar labs as the other analytical performance studies.
• Reference Interval:
  • Sample Size: Between N=187 and N=193 samples per application.
  • Data Provenance: Three clinical study sites in the United States. Study population did not include neonate and pediatric patient populations.
• Factor V Leiden Cut-off Study:
  • Sample Size: N = 381 patients (combined from US and OUS sites), with N=127 patients from the US.
  • Data Provenance: Three different clinical sites (one site in the US and two sites in Germany). Samples were citrated plasma from patients submitted for thrombophilia screening, collected and then frozen.

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

Not applicable in the context of this IVD device. Ground truth for clinical assays is typically established by:

• Comparison to a legally marketed predicate device: As seen in the method comparison.
• Defined analytical standards: For precision, linearity, and detection limits.
• Clinical gold standard: For the Factor V Leiden cut-off study, genetic testing (Factor V Leiden PCR method) served as the "reference," which is an objective laboratory test, not expert interpretation.

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

Not applicable for an IVD device analytical performance study. Adjudication is relevant for subjective assessments, particularly in imaging or clinical endpoints. This study measures quantitative values from blood samples.

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 device (blood coagulation analyzer), not an AI imaging algorithm. There are no "human readers" interpreting images assisted by AI in this context.

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

Yes, in a way. The device (Sysmex® CS-2500) functions as a standalone instrument to measure coagulation parameters. The performance studies (method comparison, reproducibility, detection capability, linearity, reference interval) evaluate the device's output without direct human "interpretation" of raw signals for diagnosis, but rather human use of the device and its generated numerical reports. The "algorithm" here refers to the instrument's internal measurement and calculation procedures rather than a predictive AI model.

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

The "ground truth" or reference for this device's performance evaluation was primarily:

• Predicate Device: For method comparison (Sysmex® CA-1500). The predicate itself is a legally marketed device with established performance.
• Analytical Standards/Reference Materials: For studies like reproducibility, detection capability, and linearity.
• External Laboratory Test (PCR): For the Factor V Leiden study, the "Reference (Factor V Leiden PCR method)" served as the objective ground truth for the genetic variant.

8. The sample size for the training set

Not applicable. This document is for the validation of an IVD medical device (a physical instrument and associated reagents), not a machine learning model that requires a "training set" in the conventional sense. The "training" of such a device refers to its design, calibration, and internal programming by the manufacturer, which is distinct from data-driven machine learning.

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

Not applicable, as there is no "training set" in the context of an AI/ML model. The "ground truth" (or design specifications and analytical performance ranges) for such a device is established through comprehensive engineering, chemical, and biological research and development, following recognized industry standards (e.g., CLSI guidelines).

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The Sysmex® Automated Blood Coagulation Analyzer CS-5100 is a fully automated blood coagulation analyzer intended for in vitro diagnostic use using plasma collected from venous blood samples in 3.2% sodium citrate tubes to analyze clotting, chromogenic and immunoassay methods in the clinical laboratory. For determination of:

• . Prothrombin Time (PT) seconds and PT INR with Dade® Innovin®
• . Activated Partial Thromboplastin Time (APTT) with Dade® Actin® FSL
• . Fibrinogen (Fbg) with Dade® Thrombin Reagent
• . Coagulation Factor V with Dade® Innovin®
• . Coagulation Factor VII with Dade® Innovin®
• . Coagulation Factor VIII with Dade® Actin® FSL
• . Coagulation Factor IX with Dade® Actin® FSL
• . Lupus Anticoagulant with LA1 Screening and LA2 Confirmation Reagent
• . Factor V Leiden with Factor V Leiden Assay
• . Protein C with Protein C Reagent
• . Antithrombin (AT) with INNOVANCE® Antithrombin
• Protein C with Berichrom® Protein C
• D-dimer with INNOVANCE® D-Dimer

The performance of this device has not been established in neonate and pediatric patient populations.

Intended Use for Factor V Leiden Assay:

The Siemens Healthcare Diagnostics Factor V Leiden Assay is a simple functional clotting test system intended for screening of resistance to Activated Protein C (APC) in plasma from individuals with Factor V (Leiden) defect. For in vitro diagnostic use.

Intended Use for Coagulation Factor VIII Deficient Plasma:

In vitro diagnostic reagents for the determination of the activity of coagulation factors VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for Coagulation Factor IX Deficient Plasma:

In vitro diagnostic reagents for the determination of the activity of coagulation factor VIII, IX, XI and XII in human plasma by coagulation methods.

Intended Use for LA1 Screening and LA2 Confirmation Reagents:

LA1 Screening Reagent and LA2 Confirmation Reagent are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests. LA1 Screening Reagent: Simplified DRVV reagent to the presence of Lupus Anticoagulants. LA2 Confirmation Reagent: Phospholipid-rich DRVV reagent for the specific correction of Lupus Anticoagulants.

The Sysmex® CS-5100 is an automated blood coagulation instrument which can analyze samples using clotting, chromogenic and immunoassay methods. Analysis results are displayed on the Information Processing Unit (IPU) screen. They can be printed on external printers or transmitted to a host computer. Sold separately from the instrument are the associated Reagents, Controls, Calibrators, and Consumable materials. The subject of this 510(k) notification are reagent applications which perform the coagulation tests Factor V Leiden with Factor V Leiden Assay, Coagulation Factor VIII with Dade® Actin FSL®, Coagulation Factor IX with Dade® Actin FSL®, Lupus Anticoagulant with LA 1 Screening Reagent and LA 2 Confirmation Reagent. The analysis principles used on the instrument are reflected by the reagent application testing provided in this 510(k) notification and is described in the below table.

Here's a breakdown of the acceptance criteria and study information for the Sysmex® Automated Blood Coagulation Analyzer CS-5100, based on the provided text:

Important Note: The provided document is a 510(k) summary for a medical device. This type of submission focuses on demonstrating substantial equivalence to a legally marketed predicate device, rather than proving absolute safety and effectiveness from scratch. Therefore, the "acceptance criteria" discussed are primarily related to showing that the new device performs comparably to the predicate for specific applications, and "ground truth" is often established by comparing to the predicate device's results.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria values in the format of a table as it pertains to specific numerical thresholds for accuracy, sensitivity, or specificity. Instead, the acceptance criteria for most studies (Method Comparison, Reproducibility, Detection Capability, Linearity) are generally described as "met the predetermined acceptance criteria." However, for the Factor V Leiden Cut-off Study, specific performance metrics (Sensitivity and Specificity) are provided and imply acceptance criteria. For the Method Comparison, the implicit acceptance criterion is that the results demonstrate equivalence to the predicate device, as confirmed by Passing-Bablok regression and Bland-Altman plots.

Here's an attempt to extract and summarize:

2. Sample Size and Data Provenance for Test Set

• Method Comparison:
  • Sample Sizes:
    • Factor V Leiden: N = 495 (combined from 4 sites)
    • Coagulation Factor VIII: N = 432 (combined from 4 sites)
    • Coagulation Factor IX: N = 475 (combined from 4 sites)
    • LA 1 Screening Reagent: N = 369 (combined from 3 sites, 1 site had N=4)
    • LA 2 Confirmation Reagent: N = 353 (combined from 3 sites, 1 site had N=17)
    • LA Ratio: N = 306 (combined from 3 sites, 1 site had N=4)
  • Data Provenance: 4 external sites, 3 in the United States and 1 in Germany. Retrospective or prospective is not explicitly stated for individual samples, but the comparison uses "patient samples" and "were measured on both the predicate device... as well as the new device."
• Reproducibility Studies:
  • Sample Sizes: Not explicitly stated as number of patient samples, but testing used 2 runs per day, 2 replicates per run, over 20 days. These studies typically use control materials at various levels rather than a large set of unique patient samples for performance assessment.
  • Data Provenance: 1 external site in Germany, 2 external sites in the United States.
• Detection Capability Studies:
  • Sample Sizes: Not specified beyond stating "calibrated assays."
  • Data Provenance: Not specified beyond referring to the method.
• Linearity & Measuring Range:
  • Sample Sizes: Not specified beyond stating "calibrated assays."
  • Data Provenance: Not specified beyond referring to the method.
• Reference Interval Studies:
  • Sample Sizes:
    • Factor V Leiden: N = 193
    • Coagulation Factor VIII: N = 190
    • Coagulation Factor IX: N = 188
    • LA 1 Screening Reagent (fresh): N = 185
    • LA 1 Screening Reagent (frozen): N = 191
    • LA 2 Confirmation Reagent (fresh): N = 185
    • LA 2 Confirmation Reagent (frozen): N = 191
    • LA1/LA2 Ratio (fresh): N = 184
    • LA1/LA2 Ratio (frozen): N = 191
  • Data Provenance: 3 clinical study sites in the United States.
• Factor V Leiden Cut-off Study:
  • Sample Size: N = 381 (of which N = 127 from the US)
  • Data Provenance: Citrated plasma samples from patients submitted for thrombophilia screening were collected by three different clinical sites (one site in the US and two sites in Germany). The samples were frozen.

3. Number of Experts and Qualifications for Ground Truth

The document does not mention the use of "experts" in the traditional sense of clinicians or radiologists establishing ground truth. For coagulation analyzers, the "ground truth" is typically established by comparing the new device's measurements to a reference method or a predicate device's measurements that are already accepted as accurate and reliable.

• In the Method Comparison study, the predicate device (Sysmex® CA-1500) serves as the reference for comparison, meaning its results are the "ground truth" against which the new device's results are measured for equivalence.
• In the Factor V Leiden Cut-off Study, the "ground truth" for confirming the presence of the Factor V Leiden variant was established by the Factor V Leiden genotype (PCR method). The number of experts involved in performing or interpreting these PCR tests is not specified, but they would typically be laboratory professionals trained in molecular diagnostics.

4. Adjudication Method for the Test Set

No explicit adjudication method (like "2+1" or "3+1") is described, as the studies are primarily quantitative comparisons against established methods or predicate device results, rather than subjective interpretations requiring adjudication by multiple readers.

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

No MRMC study was done. This type of study (comparing human reader performance with and without AI assistance) is typically relevant for interpretative diagnostic devices, such as imaging systems, where human experts make diagnoses. The Sysmex® CS-5100 is an automated blood coagulation analyzer that provides quantitative measurements, not interpretations, so an MRMC study is not applicable here.

6. Standalone Performance Study (Algorithm Only)

Yes, standalone performance studies were done. All the studies described (Method Comparison, Reproducibility, Detection Capability, Linearity, Reference Interval, Factor V Leiden Cut-off Study) assess the performance of the Sysmex® CS-5100 device itself, functioning independently, without human-in-the-loop interpretation or intervention in the measurement process. The device outputs quantitative results, and these studies evaluate the accuracy, precision, and clinical relevance of those outputs.

7. Type of Ground Truth Used

• Method Comparison: Comparison against the results obtained from the predicate device (Sysmex® CA-1500), which is itself a legally marketed device with established performance.
• Factor V Leiden Cut-off Study: Factor V Leiden genotype (PCR method). This is a definitive molecular pathology test.
• Detection Capability, Linearity, Reference Interval studies: These generally establish the device's inherent analytical characteristics against internal standards or established statistical methodologies (CLSI guidelines), rather than using an external "ground truth" from experts or a pathology panel in the same way an interpretative diagnostic device might.

8. Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of machine learning. The Sysmex® CS-5100 is a an automated laboratory instrument for performing coagulation tests, not a software algorithm that undergoes a training phase with a distinct dataset. The performance data presented are for validation/testing of the device's operational capabilities across predefined assays using various samples.

9. How Ground Truth for the Training Set Was Established

Since a "training set" in the machine learning sense is not applicable or explicitly mentioned for this device, a method for establishing its ground truth is also not provided. The development and calibration of such instruments typically involve rigorous analytical methods and the use of certified reference materials and control samples, rather than a "ground truth" established from a large dataset for algorithm training.

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Frozen Format LA Screen (FFLAS) and Frozen Format LA Confirm (FFLAC) are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests.

Frozen Format LA Confirm is a phospholipid-rich DRVVT reagent for the specific correction of Lupus Anticoagulants.

This product is for in-vitro diagnostic use only.

Frozen Format LA Confirm is a phospholipid-rich DRVVT reagent for the specific correction of Lupus Anticoagulants.

The provided text is a 510(k) premarket notification summary for a medical device called "Frozen Format LA Confirm." It's a regulatory document from the FDA, not a study report detailing acceptance criteria and performance data. Therefore, the requested information about acceptance criteria, study design, sample sizes, expert involvement, and ground truth cannot be extracted from this document.

This document primarily indicates that the FDA has reviewed the device and determined it to be substantially equivalent to a legally marketed predicate device for its stated indications for use, thereby allowing DSRV, Inc. to market it. It discusses regulatory compliance and general controls, but not the specific technical performance data or study details required to fill out the requested table and answer the questions.

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Frozen Format LA Screen (FFLAS) and Frozen Format LA Confirm (FFLAC) are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests.

Frozen Format LA Screen is a simplified DRVVT reagent to screen for the presence of Lupus Anticoagulants.

This product is for in-vitro diagnostic use only.

Frozen Format LA Screen (FFLAS) and Frozen Format LA Confirm (FFLAC) are simplified DRVVT reagents for detection of Lupus Anticoagulants (LA) in one-stage clotting tests.

I apologize, but the provided text from the FDA 510(k) clearance letter for the "Frozen Format LA Screen" device does not contain the detailed information necessary to answer your request.

Specifically, the document focuses on the regulatory clearance process and substantial equivalence determination, and it does not include any study data, acceptance criteria, or performance metrics for the device.

Therefore, I cannot provide:

1. A table of acceptance criteria and reported device performance.
2. Sample sizes used for test sets or data provenance.
3. Number or qualifications of experts used for ground truth.
4. Adjudication method for the test set.
5. Information about MRMC comparative effectiveness studies or effect sizes.
6. Information about standalone algorithm performance.
7. The type of ground truth used.
8. The sample size for the training set.
9. How the ground truth for the training set was established.

The 510(k) clearance process generally focuses on demonstrating substantial equivalence to a predicate device, which often relies on comparison of device characteristics and intended use, rather than a full clinical study with detailed performance metrics and ground truth establishment as you've described for AI/CADe devices. This document is a clearance letter, not a full study report or technical specification.

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The HemosIL dRVVT Screen and HemosIL dRVVT Confirm assays are qualitative in-vitro diagnostic products to aid in the detection of lupus anticoagulants in human citrated plasma by the diluted Russell's Viper Venom method, on the ACL TOP® Family. The HemosIL dRVVT Screen and HemosIL dRVVT Confirm assays are intended to evaluate patients who have unexplained prolonged APTT test results The HemosIL dRVVT Screen and HemosIL dRVVT Confirm assays should be used in parallel as an integrated test for Lupus Anticoagulant detection.

DRVVT Screen and dRVVT Confirm are improved dRVVT reagents, intended to simplify and standardize the detection of Lupus Anticoagulant (LA) disorder in clinical chemistry evaluations. DRVVT Screen is poor in phospholipid, making it sensitive to LA. The additional amount of phospholipid in dRVVT Confirm neutralizes LA to give shorter clotting times. Russell's viper venom, in the presence of calcium, directly activates factor X (in a test sample). DRVVT Screen and dRVVT Confirm are therefore unaffected by contact factor abnormalities, factor VII, VIII and IX deficiencies, or inhibitors. As a result, dRVVT Screen and dRVVT Confirm are more specific tests for the evaluation of LA than APTT.

Acceptance Criteria and Device Performance Study for HemosIL® dRVVT Screen and Confirm Assays

1. Table of Acceptance Criteria and Reported Device Performance

The device (HemosIL® dRVVT Screen and HemosIL® dRVVT Confirm assays) is a qualitative in-vitro diagnostic product. Instead of traditional sensitivity/specificity acceptance criteria for quantitative devices, the performance is demonstrated through comparison with a predicate device and via inter-laboratory validation studies using established cut-offs.

• ACL TOP & ACL TOP 500 CTS: PPA 100.0% (35/35), NPA 100.0% (80/80), Overall 100% (115/115) (CI 95% provided)
  3 US Field Sites (100+ samples each):
• Site 1: PPA 92.7% (38/41), NPA 98.9% (91/92), Overall 97% (129/133)
• Site 2: PPA 90.2% (46/51), NPA 98.9% (91/92), Overall 95.8% (137/143)
• Site 3: PPA 98.1% (52/53), NPA 100.0% (80/80), Overall 99.2% (132/133) (CI 95% provided for all sites) |
  | Matrix Comparison (Citrate Type) | Normalized Ratio should not be significantly affected by 3.8% versus 3.2% sodium citrate sample tubes, demonstrating high PPA and NPA. | ACL TOP: PPA 100% (19/19), NPA 92% (24/26) (CI 95% provided). Results showed the dRVVT NR is not affected by citrate tube type. |
  | Matrix Comparison (Fresh vs. Frozen) | Normalized Ratio should not be significantly affected by fresh versus frozen and once-thawed samples, demonstrating high PPA and NPA. | ACL TOP: PPA 100% (28/28), NPA 100% (26/26) (CI 95% provided). The method comparison demonstrated the dRVVT NR is not affected by fresh or frozen use. |
  | Specificity to LA | The assay should detect LA specifically and not be significantly affected by other conditions like oral anticoagulants, LMWH, UFH, DIC, or Factor Deficiency. | Known LA Positive: 100% (35/35)
  Oral Anticoagulants: 40% (2/5)
  LMWH: 0% (0/5)
  UFH: 20% (1/5)
  DIC: 0% (0/5)
  Factor Deficiency: 0% (0/6) (Performance on both ACL TOP and ACL TOP 500CTS were similar). |
  | Reference Range | A normal range study should be performed with a sufficient number of normal healthy individuals to establish reference intervals for the Normalized Ratio (NR). | A normal range study (n=120) established reference intervals for dRVVT Screen/Confirm Normalized Ratio:
  ACL TOP: Lower Limit 0.92 (0.91-0.93), Upper Limit 1.11 (1.10-1.15)
  ACL TOP 500 CTS: Lower Limit 0.91 (0.89-0.92), Upper Limit 1.13 (1.11-1.16) |

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

• Precision/Reproducibility Study Test Set:
  • Sample Size: N=80 per instrument per lot (Total: 3 lots x 2 instruments x 80 = 480 individual measurements for each control level). Specifically, 20 days, 2 runs/day, 2 replicates/run for each sample level (Negative, Weakly Positive, Positive controls).
  • Data Provenance: Not explicitly stated, but implied to be in-house laboratory testing as part of the manufacturer's analytical performance assessment.
• Interference Studies Test Set:
  • Sample Size: Not explicitly stated, but different concentrations of interferent were spiked into pooled normal plasma, weak LA positive plasma, and high LA positive plasma. The number of samples for each interferent type is not given.
  • Data Provenance: Not explicitly stated, but implied to be in-house laboratory testing.
• Assay Cut-off Determination Test Set:
  • Sample Size: 40 normal healthy individual samples.
  • Data Provenance: Not explicitly stated, but likely from a healthy donor pool.
• "Clinical Sample" Testing (LA Positive, Oral Anticoagulants, etc.) Test Set:
  • Sample Size: Known LA Positive (35 samples), Oral Anticoagulants (5 samples), LMWH (5 samples), UFH (5 samples), DIC (5 samples), Factor Deficiency (6 samples).
  • Data Provenance: Not explicitly stated, but these are patient samples with specific conditions.
• Comparison Studies (Primary In-house) Test Set:
  • Sample Size: 115 samples (80 Normal / 35 known LA Positive).
  • Data Provenance: Not explicitly stated, but implied to be in-house, possibly from a reference laboratory.
• Comparison Studies (US Field Sites) Test Set:
  • Sample Size: Site 1: 133 samples (41 LA positive + 92 normal); Site 2: 143 samples (51 LA positive + 92 normal); Site 3: 133 samples (53 LA positive + 80 normal). Over 100 samples per site.
  • Data Provenance: US field sites (presumably clinical laboratories in the US).
• Matrix Comparison (Citrate Type) Test Set:
  • Sample Size: Plasma from 26 donors. Artificial LA-Positive samples were prepared by spiking this pool.
  • Data Provenance: Not explicitly stated, but implied healthy donors.
• Matrix Comparison (Fresh vs. Frozen) Test Set:
  • Sample Size: Blood samples from 26 normal healthy donors. LA-Positive samples were prepared by spiking this pool.
  • Data Provenance: Not explicitly stated, but implied healthy donors.
• Expected Values/Reference Range Study Test Set:
  • Sample Size: 120 normal healthy individuals.
  • Data Provenance: Not explicitly stated, but implied healthy donors.

3. 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 of experts or their qualifications used to establish the ground truth for the test sets.

• For the "Known LA Positive" samples and samples from patients with specific conditions (Oral Anticoagulants, LMWH, UFH, DIC, Factor Deficiency), the ground truth is implied to be based on established clinical diagnosis and/or previous laboratory results for those conditions. The method of determining if a sample was "Known LA Positive" (e.g., diagnosis by a hematologist, positive by multiple other LA tests) is not detailed.
• For the "Normal" samples, ground truth is based on samples from supposedly healthy individuals.

4. Adjudication Method for the Test Set

No explicit adjudication method is described for conflicting results in the test set.

• For the comparison studies, the device's results (dRVVVT NR) were compared against the predicate device's results (LAC NR) which served as the reference/ground truth for in-house validation.
• For the field site validations, "LAC Screen/Confirm" is listed as the reference, suggesting comparison against the predicate device or a combination of standard diagnostic practices at those sites.

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

No, an MRMC comparative effectiveness study was not done. This device is a diagnostic reagent for automated analyzers, not an imaging device requiring human reader interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable. The study focuses on comparing the new reagent's performance against a predicate device and assessing analytical validity.

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

Yes, the studies presented are essentially "standalone" performance studies for the reagent and instrument combination. The device (reagent) and the automated analyzer (ACL TOP Family) generate the results without human interpretive input for the final Normalized Ratio. Human involvement is in sample collection, running the assay on the instrument, and interpreting the final numerical ratio against the established cut-off, but the diagnostic determination of the ratio itself is automated.

7. The Type of Ground Truth Used

The ground truth used depends on the specific study:

• Comparison Studies: The predicate device (HemosIL LAC Screen & LAC Confirm) served as the reference/ground truth.
• Specificity Studies (LA Positive, Oral Anticoagulants, etc.): Ground truth was based on the "known" status of the plasma samples (e.g., "Known LA Positive," "Oral Anticoagulants"). How these "known" statuses were originally established (e.g., clinical diagnosis, other laboratory methods) is not detailed.
• Assay Cut-off and Reference Range Studies: Ground truth was based on plasma samples from "normal healthy individuals."

8. The Sample Size for the Training Set

The concept of a "training set" in the context of an AI/machine learning algorithm does not directly apply here, as this is a chemical reagent-based diagnostic assay. Therefore, there is no explicit training set in the AI sense.

However, if "training set" is interpreted as data used to establish device parameters or optimize its performance before formal validation, the following might be considered:

• The development process of the improved dRVVT reagents (HemosIL dRVVT Screen and dRVVT Confirm) would have involved extensive R&D and internal testing to optimize their composition and function. This internal optimization data is not detailed in the 510(k) summary.
• The "Assay cut-off" was determined using 40 normal healthy individual samples, which could be seen as an "internal" reference set for parameter setting.
• The normal range study used 120 normal healthy individuals to establish reference intervals.

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

As noted in point 8, a formal "training set" as understood in AI/ML is not applicable. For the data used to establish parameters like the assay cut-off or reference ranges, the ground truth was established by using plasma samples from normal healthy individuals, indicating they were free from the condition the test aims to detect (lupus anticoagulants). The method for confirming their "normal healthy" status (e.g., physical examination, medical history review, other lab tests) is not specified.

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LupoTek Detectin VL and Correctin VL test kits are qualitative tests intended to aid in the detection of lupus anticoagulants (LA) in citrated human plasma by the dilute Russell's viper venom method in professional clinical laboratories.

PlasmaCon LA is intended for use as an LA positive, abnormal quality control plasma to monitor the performance of diagnostic assays, performed in professional clinical laboratories, for the presence of lupus anticoagulants in citrated plasma.

LupoTek Detectin VL and LupoTek Correctin VL use Vipera lebetina venom rather than Vipera russelli (Russell's Viper) venom in the dRVVT assay for lupus anticoagulant. Vipera lebetina venom, like Russell's viper venom, will directly activate Factor X without requiring Factor VII. The activated Factor X in conjunction with Factors V, II, calcium ions and phospholipid will generate thrombin which converts fibrinogen to fibrin, producing a clot in the test system. LupoTek Detectin VL, the low phospholipid reagent, is designed as the screening reagent to detect a prolongation of the clotting time. LupoTek Correctin VL is the high phospholipid reagent that neutralizes the LA and corrects the clotting time to normal, confirming the presence of a Lupus Anticoagulant.

PlasmaCon LA is a lyophilized Lupus Anticoagulant (LA) positive plasma suitable for use as a quality control plasma for in vitro diagnostic assays in the clinical coagulation laboratory sensitive for the presence of LA

The provided text describes the LupoTek Detectin VL, LupoTek Correctin VL, and PlasmaCon LA devices, which are related to the detection of lupus anticoagulants (LA).

Here's an analysis of the acceptance criteria and the study as described in the text:

1. Table of Acceptance Criteria and Reported Device Performance

The text does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for positive or negative agreement percentages. Instead, it presents the results of a comparative study to demonstrate substantial equivalence to predicate devices. The implicit acceptance criterion is likely to be a high level of agreement with the predicate devices.

For PlasmaCon LA, the text states it is for use as an LA positive, abnormal quality control plasma to monitor diagnostic assays. Its performance is compared to a predicate device (American Diagnostica LAtrol Abnormal Control) based on similarities in intended use, constituent material, measurement principle, format, and analyte. Specific performance metrics like agreement percentages are not provided for PlasmaCon LA itself, as its role is a control.

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

• Sample Size for LupoTek Detectin VL / Correctin VL: 155 patient samples.
• Data Provenance: The text states "three sites" were used for analysis, indicating a multi-center study. The country of origin is not specified, nor is whether the data was retrospective or prospective.

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

The text does not provide information on the number of experts used or their qualifications to establish ground truth. It implies that the predicate device's results (Stago DRVV Screen / Confirm kits) served as the reference standard for comparison.

4. Adjudication Method for the Test Set

The text does not specify any adjudication method. It describes a comparison between the investigational device and predicate devices.

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

• No MRMC study was done. The described study compares the device's performance to a predicate device, not the improvement of human readers with or without AI assistance. The devices in question are diagnostic reagents, not AI-based image analysis tools or decision support systems.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, a standalone study was done. The described study evaluates the performance of the LupoTek Detectin VL / Correctin VL kits themselves in detecting lupus anticoagulants in patient samples by comparing their results directly to those of the predicate devices. There is no mention of human-in-the-loop performance in this context.

7. Type of Ground Truth Used

The ground truth was established by the results obtained from the predicate devices (Stago DRVV Screen / Confirm kits). This is a form of comparative effectiveness or reference standard based on an already marketed and accepted diagnostic method.

8. Sample Size for the Training Set

The text does not mention a training set in the context of device development or performance evaluation. This type of diagnostic reagent typically undergoes initial development and validation, but the reported study is a performance comparison for regulatory submission, not machine learning model training.

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

As no training set is mentioned for the reported study, this information is not applicable/provided.

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The STA®-Staclot® dRVV Screen and STA®-Staclot® dRVV Confirm kits are intended for the detection of lupus anticoagulants (LA) in plasma by the dilute Russell's viper venom method (1) performed with analyzers of the STA® line suitable to these reagents.

The in vitro diagnostic device presented in this 510K submission, STA® -Staclote dRVV Screen and STA® -Staclot® dRVV Confirm, is substantially equivalent to the IL Test LAC Screen and Confirm manufactured by Instrumentation Laboratories.

Here's a breakdown of the acceptance criteria and study details based on the provided 510(k) summary:

1. Acceptance Criteria and Reported Device Performance

The submission implicitly uses "percent agreement" with a predicate device as its primary acceptance criterion for demonstrating substantial equivalence.

2. Sample Size and Data Provenance

• Sample Size for Test Set: 90 plasma samples.
• Data Provenance: The plasmas were obtained from "patients with various clinical pathologies." The country of origin is not explicitly stated. The study appears to be retrospective, as samples from existing patients were collected and tested.

3. Number of Experts and Qualifications for Ground Truth

This information is not provided in the summary. The study relies on agreement with a predicate device rather than an independently established expert ground truth for each sample being tested.

4. Adjudication Method

This information is not applicable/provided. The study focuses on agreement with a predicate device, not on adjudicating discrepancies between multiple readers or diagnostic methods for ground truth establishment.

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

An MRMC comparative effectiveness study was not performed. This study is an in vitro diagnostic device (reagent kit) and does not involve human readers interpreting results in the same way, for example, a medical imaging AI would. The comparison is between the new device's results and those of a predicate device.

6. Standalone Performance Study

A standalone performance study was implicitly done in the sense that the device was used independently to generate results. However, its effectiveness was measured by agreement with a predicate device, which inherently involves a comparison. If "standalone" refers to performance against an absolute gold standard established independently (e.g., pathology), that was not the primary focus or method of proving substantial equivalence in this submission. The "92% agreement" figure is the standalone device's performance relative to the predicate.

7. Type of Ground Truth Used

The ground truth for the study was established through the results obtained from a predicate device (IL Test LAC Screen and Confirm). The "ground truth" here is essentially the performance of the legally marketed predicate device.

8. Sample Size for Training Set

The sample size for a "training set" is not applicable/provided. This device is a reagent kit, not a machine learning algorithm that requires a distinct training phase on a dataset. The 90 plasma samples constitute the test set used for the substantial equivalence study.

9. How Ground Truth for Training Set Was Established

This information is not applicable as there is no training set mentioned in the context of a machine learning model.

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The ACTICLOT® dPT™ is intended for the qualitative determination of lupus anticoagulants (LA) in human plasma. This test is for in vitro diagnostic use.

ACTICLOT® dPT" is a test kit. It has three reagents that are used selectively for a screening protocol and a confirmatory protocol. LA Buffer" is used with dPT Activator" for the screening protocol. LA Phospholipids" is used with dPT Activator" for the confirmatory protocol. ACTICLOT® dPT" is a professional use qualitative test.

The provided document describes the ACTICLOT® dPT™ reagent kit, an in vitro diagnostic test for the qualitative determination of Lupus Anticoagulants (LA) in human plasma. The submission is a 510(k) summary, which aims to demonstrate substantial equivalence to a legally marketed predicate device (DVVtest® and DVVconfirm®). The study presented focuses on justifying this substantial equivalence rather than establishing novel acceptance criteria against a clinical gold standard.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria (Implied) and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" in a quantitative sense as might be seen for a new device with clinical claims. Instead, it demonstrates "substantial equivalence" to a predicate device in terms of performance characteristics. The implied acceptance criterion for each category is "equivalent" to the predicate device.

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

• Precision Studies:

  • Sample Size: The precision studies used control samples (LAtrol® Abnormal Control and LAtrol® Normal Control). The exact number of individual measurements or replicates for each control on each instrument is not explicitly stated, but it mentions "multiple tests performed over several days."
  • Data Provenance: The studies were performed by American Diagnostica Inc. and "one field trial laboratory." This indicates a mix of in-house and external testing. The country of origin for the field lab is not specified. The studies appear to be prospective, specifically designed to gather precision data for the submission.

• Method Comparison (Accuracy) Studies:

  • Sample Size:
    • Study 1: 54 patient samples.
    • Study 2: 93 patient samples.
  • Data Provenance:
    • Study 1: American Diagnostica, Inc. in Stamford, CT (USA).
    • Study 2: Centre hospitalier universitaire de Sherbrooke, Fleurimont (Québec), Canada.
    • The document describes testing "patient samples," which suggests these were clinical samples. It does not explicitly state if they were retrospective or prospectively collected for the study, but the context of "method comparison studies" implies they were collected and then tested with both devices.

• Sensitivity Studies:

  • Sample Size: 23 prescreened LA positive samples.
  • Data Provenance: Haemotology Department at University College London, UK. These were "prescreened LA positive samples," indicating they were likely retrospective samples with established LA status used for evaluating sensitivity.

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

• Precision Studies: Ground truth was based on the assigned values of the control materials. No human experts were involved in establishing "ground truth" for the controls beyond the manufacturer's quality control processes.
• Method Comparison (Accuracy) Studies: The "ground truth" for these studies was the result obtained from the predicate device (DVVtest® and DVVconfirm®). No independent experts were used to establish a separate ground truth for LA status. The comparison was device-to-device.
• Sensitivity Studies: The samples were described as "prescreened LA positive samples." This implies that the LA positive status of these 23 samples was established prior to the study by standard clinical methods, potentially involving expert interpretation of multiple tests. However, the exact number of experts or their qualifications for this prescreening are not specified in the document.

4. Adjudication Method for the Test Set

• Precision, Accuracy, and Sensitivity Studies: The document does not describe any adjudication method (like 2+1 or 3+1 consensus) for the test results. The results appear to be direct outputs from the instruments. For the "prescreened LA positive samples" in the sensitivity study, the original method of establishing their "positive" status (which might have involved an adjudication process) is not detailed.

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

• No MRMC comparative effectiveness study was done. This device is an in vitro diagnostic reagent kit that provides a quantitative measurement (clotting time) which is then interpreted qualitatively as LA positive or negative. It does not involve human readers interpreting images or complex data that would typically be associated with an MRMC study.

6. Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance)

• Yes, the studies presented are all standalone. ACTICLOT® dPT™ is a reagent kit that provides a result (clotting time) on an automated coagulation analyzer. The "performance" described refers to the output of the instrument using the reagent. The test itself is described as a "professional use qualitative test," meaning a healthcare professional interprets the result. However, the studies evaluate the reagent's performance directly on the samples, without considering the variability introduced by different human interpretations of the final qualitative call, beyond what is inherent in reporting positive/negative for LA.

7. Type of Ground Truth Used

• Precision Studies: Manufacturer-assigned values for control materials.
• Method Comparison (Accuracy) Studies: The results obtained from the predicate device (DVVtest® and DVVconfirm®).
• Sensitivity Studies: "Prescreened LA positive samples," implying existing clinical diagnosis of LA based on other methods (which could involve expert consensus, pathology, or outcomes data, but this is not detailed). The document also mentions that no single LA test identifies all LA positive samples and recommends using a combination of two or more tests. This implies that the "true" LA positivity for the 23 samples was established by a combination of tests, rather than a single definitive ground truth.

8. Sample Size for the Training Set

• This submission is for a medical device (reagent kit). There is no "training set" in the context of machine learning. The device is not an AI/ML algorithm that learns from data.

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

• This question is not applicable as there is no "training set" for this type of device.

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IL Test™ LAC Screen and IL Test™ LAC Confirm are in vitro diagnostic products for the detection of lupus anticoagulants (a type of phospholipid interfering antibody) in human citrated plasma on IL Coagulation Systems. These tests are indicated for use with patients who have prolonged APTT test of undetermined origin.

This 510(k) is intended to extend the use of these reagents onto another member in the IL family of coagulation analyzers, the ACL Futura (K951891).

IL Test™ LAC Screen and IL Test™ LAC Confirm are in vitro diagnostic products for the detection of lupus anticoagulants (a type of phospholipid interfering antibody) in human citrated plasma on IL Coagulation Systems. This 510(k) is intended to extend the use of these reagents onto another member in the IL family of coagulation analyzers, the ACL Futura (K951891).

Here's a breakdown of the acceptance criteria and study information for the IL Test™ LAC Screen and IL Test™ LAC Confirm (Extension onto the ACL Futura), based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria. Instead, it demonstrates performance by comparing the device on the ACL Futura with its performance on an existing ACL 300 reference instrument and assessing precision. The reported performance suggests that the device operates comparably to the predicate device and within acceptable precision limits for diagnostic assays.

• CV of 6.32% (at mean ratio of 2.03)
• CV of 2.36% (at mean normalized ratio of 1.51) |

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

• Sample Size: n = 53 for the correlation study. "3 levels of plasma" were used for the precision study, but the exact number of runs or individual samples within each run is not specified beyond "multiple runs."
• Data Provenance: Not explicitly stated (e.g., country of origin). The study appears to be retrospective, using plasma samples, but this is not definitively stated. There's no mention of a prospective study design.

3. Number of Experts Used to Establish Ground Truth and Qualifications

• The document describes performance studies for an in-vitro diagnostic product, not an imaging or interpretive device that would typically rely on expert human assessment for ground truth. Therefore, no experts were used to establish ground truth in the traditional sense for this type of device. The "ground truth" for this assay lies in the chemical and biological reactivity of the reagents and the accuracy of the instrument's measurement capabilities.

4. Adjudication Method for the Test Set

• None specified. As this is a performance study for an in-vitro diagnostic assay rather than an interpretive clinical assessment, an adjudication method for a test set is not applicable. The measurements are objective numerical results from the instrument.

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

• No. This is an in-vitro diagnostic product validation, not a study involving human readers interpreting results. Therefore, an MRMC study was not performed, and there's no data on the effect size of human readers improving with AI assistance.

6. Standalone (Algorithm Only) Performance Study

• Yes, implicitly. The entire study describes the performance of the device (IL Test™ LAC Screen and IL Test™ LAC Confirm on the ACL Futura analyzer) as a standalone system. The measurements of correlation and precision are direct evaluations of the algorithm/instrument system without human intervention in the measurement process itself.

7. Type of Ground Truth Used

• Reference Instrument Comparison and Known Samples:
  • For the correlation study, the "ground truth" was established by comparing results from the new device/instrument combination (ACL Futura) to a predicate/reference instrument (ACL 300) which is presumably already validated and considered accurate.
  • For the precision study, "3 levels of plasma" were used. These would likely be characterized plasma samples with known or expected ranges of the analyte to assess the reproducibility of the measurements.

8. Sample Size for the Training Set

• Not applicable / Not specified. This document describes the validation of an existing diagnostic reagent on a new instrument platform, not the development or training of a new algorithm (like an AI model). Therefore, there is no "training set" in the context of machine learning. The reagents and assay methodology would have been developed and validated previously.

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

• Not applicable. As there is no training set for an AI/machine learning algorithm, this question is not relevant to the provided document. The development of the reagents and assay would have involved standard chemical and biological validation methods, which are not detailed here.

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