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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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The STA® - Liatest® D-Di kit is an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma (3.2% sodium citrate) for use on STA-R®, STA Compact® and STA Satellite® analyzers by professional laboratory personnel. The STA® - Liates® D-Di is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and deep venous thrombosis (DVT) in outpatients suspected of PE or DVT.

STA® - Liatest® D-Di kit contains: 6 x 5-ml vials of ready-for-use Tris buffer and 6 x 6-ml vials of a suspension of microlatex particles coated with two different mouse monoclonal anti-human D-dimer antibodies (8D2 and 2.1.16) stabilized with bovine albumin.

The test principle is based on the change in turbidity of a microparticle suspension that is measured by photometry. A suspension of latex microparticles, coated by covalent bonding with monoclonal antibodies specific for D-dimer is mixed with the test plasma for which the D-dimer level is to be assayed. An antigen-antibody reaction takes place, leading to an agglutination of the latex microparticles which causes an increase in turbidity of the reaction medium. This increase in turbidity is reflected by an increase in absorbance, the latter being measured photometrically. The increase in absorbance is a function of the D-dimer level present in the test sample.

This document describes the acceptance criteria and study proving the performance of the STA® - Liatest® D-Di kit, an immuno-turbidimetric assay for the quantitative determination of D-dimer.

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the STA® - Liatest® D-Di kit were based on achieving specific Negative Predictive Value (NPV) and Sensitivity targets for the exclusion of Pulmonary Embolism (PE) and Deep Venous Thrombosis (DVT) in outpatients with low to moderate pretest probability (PTP).

Note: The document explicitly states that the results "meet both confirmatory hypotheses relating to NPV and Sensitivity." While the predicate device's PE and DVT results are listed in the "Similarities Chart," the detailed performance data for the new device (STA® - Liatest® D-Di) in the clinical performance section is specifically for DVT exclusion. The indications for use state "to exclude pulmonary embolism (PE) and deep venous thrombosis (DVT)", but the detailed study results presented focus on DVT.

2. Sample Size and Data Provenance

• Test Set Sample Size: 980 samples of patients with a low or moderate PTP were included in the primary efficacy analyses. This consisted of 79 suspects of DVT and PE, and 901 suspects of DVT only. Of the 980 samples, 85 were DVT positive and 895 were DVT negative.
• Data Provenance: The data was collected from a prospective, multi-center clinical study conducted at 16 sites across the United States, Europe, and Canada. The patients were consecutive, ambulatory outpatients presenting at emergency units or outpatient clinics suspected of having venous thromboembolism (VTE).

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the "number of experts" or their "qualifications" in the context of establishing ground truth in the traditional sense of human readers adjudicating medical images. Instead, the ground truth was established through a clinical protocol:

• Patients with positive D-dimer results were considered for an imaging procedure (e.g., ultrasound, CT angiography).
• Patients with negative D-dimer results were assigned to a three-month follow-up to confirm the absence of DVT/PE.
• The "Reference" column in the results tables (Tables 1, 2) is a combination of "imaging or 3-month follow-up."

Therefore, the establishment of ground truth was based on clinical diagnostic pathways and follow-up, rather than expert interpretation of a specific dataset for the purpose of algorithm validation in the way one might see for an imaging AI. The "experts" in this context would be the clinicians and radiologists involved in the standard of care diagnostic work-up.

4. Adjudication Method for the Test Set

Not applicable in the typical sense of expert adjudication of AI outputs. The ground truth was established by standard clinical practice: a positive D-dimer result led to imaging, and a negative D-dimer result led to a 3-month clinical follow-up for confirmation.

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

No MRMC study was done, as this is an in-vitro diagnostic (D-dimer assay), not an imaging AI diagnostic device intended to assist human readers. The study evaluates the standalone performance of the assay in a clinical pathway.

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

Yes, this study represents a standalone (algorithm only) performance evaluation. The STA® - Liatest® D-Di kit itself is the "algorithm" or diagnostic tool, and its performance (sensitivity and NPV) is reported based on its direct results in conjunction with a clinical pretest probability assessment model. Its output (D-dimer level) is then used to guide clinical decisions (imaging vs. observation).

7. Type of Ground Truth Used

The ground truth was established by clinical outcomes data and definitive diagnostic imaging (e.g., ultrasound for DVT, CT angiography for PE) or clinical follow-up confirming the absence of the condition. Specifically, the "Reference" for the test set was determined by "imaging or 3-month follow-up."

8. Sample Size for the Training Set

The document does not specify a separate "training set" or its sample size. This is common for traditional in-vitro diagnostic assays, where product development and analytical validation are often not described in terms of "training sets" like machine learning models. The study described is primarily a clinical validation study demonstrating performance on a test set.

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

As no specific "training set" (in the context of machine learning) is discussed for this in-vitro diagnostic device, this point is not applicable. The development and analytical validation of such assays typically involve laboratory studies (e.g., linearity, precision, interference) and internal developmental studies that establish the assay's performance characteristics, rather than a "ground truth" derived from a clinical dataset used for training, as would be the case for an AI/ML 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).

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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For VIDAS H. pylori IgG:
VIDAS® H. pylori IgG (HPY) is an automated qualitative test for use on the instruments of the VIDAS family, for the detection of anti-Helicobacter pylori IgG antibodies in human serum or plasma (EDTA) using the ELFA technique (Enzyme Linked Fluorescent Assay). The VIDAS HPY assay is intended as an aid in diagnosis of H. pylori infection in an adult symptomatic population.
This device is an in vitro diagnostic medical device for professional use only.

For VIDAS 3:
The VIDAS 3 system is a complete standalone immunodiagnostic system intended for trained and qualified laboratory technicians (daily routine use) and laboratory administrators (application configuration). This device is an in vitro diagnostic medical device for professional use only.

For VIDAS Lyme IgG II:
The VIDAS Lyme IgG II (LYG) assay is an automated qualitative enzyme immunoassay intended for use on the instruments of the VIDAS family in the presumptive detection of human IgG antibodies to Borrelia burgdorferi in human serum (plain or separation gel) or plasma (sodium heparin). It should be used to test patients with a history and/or symptoms of infection with B. burgdorferi. All VIDAS Lyme IgG II positive specimens should be further tested with a Western Blot IgG assay to obtain supportive evidence of infection with B. burgdorfei. This device is an in vitro diagnostic medical device for professional use only.

For VIDAS RUB IgG:
The VIDAS® RUB IgG (RBG) assay uses Enzyme Linked Fluorescent Assay (ELFA) technology on the instruments of the VIDAS family for the in vitro quantitative measurement of IgG antibodies to rubella virus in human serum. The VIDAS RUB IgG (RBG) assay is intended as an aid in the determination of immune status to rubella. The performance of this device has not been established for screening of cord blood, or for neonatal samples. Likewise, performance characteristics of the assay have not been established for immunocompromised or immunosuppressed individuals.
This device is an in vitro diagnostic medical device for professional use only.

For VIDAS TOXO IgM:
The VIDAS® TOXO IgM (TXM) assay is intended for use on the instruments of the VIDAS family (VITEK ImmunoDiagnostic Assay System) as an automated enzyme-linked fluorescent immunoassay (ELF A) for the presumptive qualitative detection of anti-Toxoplasma gondii IgM antibodies in human serum, as an aid in the diagnosis of acute, recent, or reactivated Toxoplasma gondii infection. This assay must be performed in conjunction with an anti-Toxoplasma gondii lgG antibody assay. VIDAS TOXO IgM (TXM) assay performance has not been established for prenatal screening or newborn testing. This assay has not been cleared by the FDA for blood/plasma donor screening. This device is an in vitro diagnostic medical device for professional use only.

For VIDAS Human Chorionic Gonadotropin:
The VIDAS® HCG (HCG) assay is intended for use on the instruments of the VIDAS family as an automated quantitative enzyme linked fluorescent immunoassay (ELFA) for the determination of human Chorionic Gonadotropin (hCG) concentration in human serum or plasma. The VIDAS HCG (HCG) assay is intended to aid in the early detection of pregnancy.
This device is an in vitro diagnostic medical device for professional use only.

For VIDAS T4:
The VIDAS® T4 (T4) assay is intended for use on the instruments of the VIDAS family as an automated quantitative enzyme-linked fluorescent immunoassay for the determination of human thyroxine (T4) concentration in serum or plasma (heparin). It is intended for use as an aid in the diagnosis and treatment of thyroid disorders. This device is an in vitro diagnostic medical device for professional use only.

For VIDAS Testosterone:
The VIDAS Testosterone (TES) assay is an automated quantitative test for use on the instruments of the VIDAS family for the enzyme immunoassay measure of total testosterone in human serum or plasma (lithium heparin), using the ELFA technique (Enzyme Linked Fluorescent Assay). It is intended as an aid in the diagnosis and management of conditions involving excess or deficiency of this androgen.
This device is an in vitro diagnostic medical device for professional use only.

For VIDAS TSH:
The VIDAS® TSH (TSH) assay is intended for use on the instruments of the VIDAS family as an automated quantitative enzyne-linked fluorescent immunoassay (ELFA) for the determination of human thyroid stimulating hormone- (TSH) concentration in human serum or plasma (heparin). It is intended for use as an aid in the diagnosis of thyroid or pituitary disorders.
This device is an in vitro diagnostic medical device for professional use only.

For VIDAS D-Dimer Exclusion II:
VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay).
VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE. This device is an in vitro diagnostic medical device for professional use only.

The VIDAS® 3 instrument is an automated multiparametric immunoassay system, which uses ELFA (Enzyme Linked Fluorescent Assay) technology. The VIDAS 3 system offers primary tube sampling, automated sample dilution, reagent/sample detection and reagent traceability.
The technology used, which is adaptable to a wide range of assays, combines the EIA method with a final fluorescence reading: this technology is known as ELFA (Enzyme Linked Fluorescent Assay). The enzyme used in the VIDAS product range is alkaline phosphatase, which catalyzes the hydrolysis of the substrate 4-methyl umbelliferyl phosphate (4-MUP) into a fluorescent product 4-methyl umbelliferone (4-MU) the fluorescence of which is measured at 450nm. The immunological methods are either indirect ElA, immunocapture, sandwich or competition, all involving a conjugate using the alkaline phosphatase.

This document describes the performance data for several VIDAS assays when used on the VIDAS 3 instrument, comparing them to their performance on the predicate VIDAS instrument. The tests are primarily for establishing substantial equivalence for the new VIDAS 3 instrument and do not typically include detailed acceptance criteria for the assays themselves, which are already established for the predicate devices. The studies focus on method comparison, precision, linearity, and detection limits.

Here's a breakdown of the requested information based on the provided text, focusing on the VIDAS H. pylori IgG assay as a primary example, and generalizing for others where appropriate:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state acceptance criteria in a quantitative format for method comparison. Instead, it demonstrates "correlation" and "equivalency" between the new device (VIDAS 3) and the predicate device (VIDAS). For precision, specific CV% ranges are reported.

Here's an example for the VIDAS H. pylori IgG assay's method comparison:

Note: For quantitative assays like VIDAS RUB IgG, VIDAS HCG, VIDAS T4, VIDAS Testosterone, VIDAS TSH, and VIDAS D-Dimer Exclusion II, method comparison relies on slope, intercept, and correlation coefficient, implying acceptance criteria for these values (e.g., slope close to 1, intercept close to 0, high correlation coefficient). Precision for these assays also includes CV% for various components.

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

• VIDAS H. pylori IgG:

  • Test Set Size: 250 serum samples (positive, equivocal, and negative).
  • Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). The study compares performance between two instruments, implying samples are run on both.

• VIDAS Lyme IgG II:

  • Test Set Size: 220 serum samples (positive and negative).
  • Data Provenance: Not explicitly stated.

• VIDAS RUB IgG:

  • Test Set Size (Quantitative Method Comparison): 112 serum samples (ranging from 0 to 225 IU/mL).
  • Test Set Size (Qualitative Method Comparison): 220 serum samples (positive, equivocal, and negative).
  • Test Set Size (CDC Reference Panel): 100 specimens (50 pairs of sera).
  • Data Provenance: Not explicitly stated for general samples. The CDC panel implies a curated and standardized set.

• VIDAS TOXO IgM:

  • Test Set Size: 198 serum samples.
  • Data Provenance: Not explicitly stated.

• VIDAS Human Chorionic Gonadotropin (hCG):

  • Test Set Size: 113 serum samples.
  • Data Provenance: Not explicitly stated.

• VIDAS T4:

  • Test Set Size: 105 serum samples.
  • Data Provenance: Not explicitly stated.

• VIDAS Testosterone:

  • Test Set Size: 172 serum samples.
  • Data Provenance: Not explicitly stated.

• VIDAS TSH:

  • Test Set Size: 179 serum samples.
  • Data Provenance: Not explicitly stated.

• VIDAS D-Dimer Exclusion II:

  • Test Set Size: 219 plasma samples.
  • Data Provenance: Not explicitly stated.

Across all assays, the studies are described as "Method Comparison" and "Precision" studies, which are typically retrospective analyses of patient samples to compare device performance to an established method.

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

This information is not provided in the document. For in vitro diagnostic devices, ground truth is typically established by comparative methods (e.g., predicate device, reference methods, clinical diagnosis, or other laboratory gold standards) rather than expert consensus on individual cases. The document states that performance was evaluated against the predicate device (e.g., "VIDAS H. pylori IgG assay on the VIDAS 3 to the VIDAS H. pylori IgG assay on the VIDAS"). The "ground truth" for these studies is the result obtained from the predicate VIDAS instrument using its established methodology.

For the VIDAS RUB IgG, a "CDC reference panel" and "CDC low-titer rubella antibody standard" are mentioned, where the reference panel sera were "titered by Hemagglutination Inhibition." This implies that the ground truth for this specific part of the study was established by a recognized reference method (Hemagglutination Inhibition) and certified reference materials from the CDC.

4. Adjudication Method for the Test Set

This information is not explicitly provided. For method comparison studies, typically, discordant results between the new device and the predicate device (or reference method) are investigated. However, the exact adjudication process (e.g., by a third, more definitive test, or expert review of patient clinical history) is not detailed. The phrase "results were evaluated according to CLSI EP12-A2" or CLSI EP9 suggests standard statistical methods for agreement or correlation, which do not necessarily involve expert adjudication of individual discrepancies beyond reporting them.

For quantitative assays where method comparison statistics (slope, intercept, correlation coefficient) are used, "outliers" were removed in some cases (e.g., VIDAS RUB IgG quantitative comparison), implying some form of review or statistical exclusion, but not necessarily expert "adjudication" in the sense of clinical decision-making.

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

No. This document describes performance studies for in vitro diagnostic instruments and assays, not imaging or similar devices that would typically involve human readers interpreting results. Therefore, an MRMC comparative effectiveness study, which assesses improvements in human interpretation with AI assistance, is not applicable and was not performed.

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

The studies described are for the standalone in vitro diagnostic instruments and their associated assays. These are standalone tests, meaning the algorithm (or assay chemistry in this case) processes the sample and provides a result without direct human interpretation of raw data for diagnosis. The "human-in-the-loop" here refers to trained laboratory technicians operating the instrument and interpreting the final quantitative or qualitative results according to established cut-offs/guidelines, rather than interpreting complex images or signals. The purpose of these studies is to confirm that the new instrument (VIDAS 3) produces equivalent results to the predicate instrument (VIDAS) for these assays.

7. The Type of Ground Truth Used

The primary type of "ground truth" used in these studies is the results obtained from the predicate device (VIDAS instrument) for the same assays. The goal is to demonstrate "substantial equivalence" of the new instrument (VIDAS 3) to the predicate.

For the VIDAS RUB IgG assay, a CDC reference panel where samples were "titered by Hemagglutination Inhibition" served as an additional, external reference for ground truth in a specific subset of testing. This is a form of reference method/standardized panel data.

8. The Sample Size for the Training Set

This information is not explicitly provided in the document. For in vitro diagnostic assays, "training sets" are usually involved in the initial development and optimization of the assay itself (e.g., establishing reagents, parameters, cut-offs). The studies described in this document are focused on the validation and verification of the new instrument's performance with existing, already developed assays, often referred to as "test sets" or "evaluation sets." The assays themselves were presumably developed and "trained" using various sample sets prior to these studies.

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

Since information on a distinct "training set" for the new instrument's validation isn't provided (as the assays were pre-existing), details on its ground truth establishment are also not available in this document. For the development of the original assays, ground truth would have been established through a combination of clinical diagnoses, established reference methods, and correlation with disease status.

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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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The STA® - Liatest® D-Di kit is an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma (in 3.2% sodium citrate) for use on STA-R®, STA Compact® and STA Satellite® analyzers by professional laboratory personnel. The STA® - Liates® D-Di is intended for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) and as an aid in the diagnosis of deep venous thrombosis (DVT) in outpatients suspected of PE or DVT.

STA® - Liatest® D-Di kit contains: 6 x 5-ml vials of ready-for-use Tris buffer and 6 x 6-ml vials of a suspension of microlatex particles coated with two different mouse monoclonal anti-human D-dimer antibodies (8D2 and 2.1.16) stabilized with bovine albumin.

The test principle is based on the change in turbidity of a microparticle suspension that is measured by photometry. A suspension of latex microparticles, coated by covalent bonding with monoclonal antibodies specific for D-dimer is mixed with the test plasma for which the D-dimer level is to be assayed. An antigen-antibody reaction takes place, leading to an agglutination of the latex microparticles which causes an increase in turbidity of the reaction medium. This increase in turbidity is reflected by an increase in absorbance, the latter being measured photometrically. The increase in absorbance is a function of the D-dimer level present in the test sample.

Here's a breakdown of the acceptance criteria and the study details for the STA® - Liatest® D-Di device, based on the provided document:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the STA® - Liatest® D-Di device are implicitly tied to its ability to
safely rule out Pulmonary Embolism (PE) in patients with low or moderate pretest probability (PTP).
The key performance metric for exclusion of PE is the Negative Predictive Value (NPV).

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The D-Dimer Assay is for the quantitative determination of fibrin degradation products (D-Dimer) in human plasma. Measurement of D-Dimer is used as an aid in detecting the presence of intravascular coagulation and fibrinolysis. For in vitro diagnostic use only.

The Diazyme D-Dimer Calibrator Set is intended for use of the calibration of the Diazyme D-Dimer Assay only. For in vitro diagnostic use only.

The Diazyme D-Dimer Control Set is intended for use as quantitative quality controls for the Diazyme D-Dimer Assay only. For in vitro diagnostic use only.

Diazyme's D-Dimer Assay is based on a latex enhanced immunoturbidimetric assay. D-Dimer proteins in the sample bind to the specific anti-D-Dimer antibody, which is coated on latex particles, and causes agglutination. The degree of the turbidity caused by agglutination can be measured optically and is proportional to the amount of D-Dimer in the sample. The instrument calculates the D-Dimer concentration of a patient specimen by interpolation of the obtained signal of a 6-point calibration curve.

Here's a breakdown of the acceptance criteria and study information for the Diazyme D-Dimer Assay Kit, Diazyme D-Dimer Assay Calibrator Set, and Diazyme D-Dimer Assay Control Set, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

• Plasma Samples Within Run: 1.4% - 5.0%
• Plasma Samples Total: 2.7% - 6.2%
• Control Samples Within Run: 1.4% - 2.9%
• Control Samples Total: 2.8% - 4.4%
  External Study:
• Total CV%: 3.5% - 11.5% |
  | Correlation Coefficient (Method Comparison) | 0.775 (Predicate: vs. Asserachrom D-Dimer K862156) | 0.939 (vs. Roche Tina-Quant D-Dimer K062203) |
  | Slope (Method Comparison) | 1.03 (Predicate: vs. Asserachrom D-Dimer K862156) | 0.979 (vs. Roche Tina-Quant D-Dimer K062203) |
  | Intercept (Method Comparison) | -0.11 (Predicate: vs. Asserachrom D-Dimer K862156) | -0.106 (vs. Roche Tina-Quant D-Dimer K062203) |
  | Bias around medical decision point | Not explicitly stated for predicate in summary, but typical for method comparison studies. | -0.12 µg/mL FEU |
  | Limit of Blank (LOB) | Not explicitly stated for predicate. | 0.06 µg/mL FEU |
  | Limit of Detection (LOD) | Not explicitly stated for predicate. | 0.09 µg/mL FEU |
  | Limit of Quantitation (LOQ) | Not explicitly stated for predicate. | 0.15 µg/mL FEU (target CV

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VIDAS® D-Dimer Exclusion II™ is an automated quantitative test for use on the instruments of the VIDAS family for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma (sodium citrate, CTAD) using the ELFA technique (Enzyme Linked Fluorescent Assay). VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

The VIDAS® D-Dimer Exclusion II assay is an automated quantitative test for use on the instruments of the VIDAS family for the determination of fibrin degradation products (FbDP) in human plasma (sodium citrate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. VIDAS D-Dimer Exclusion II is indicated for use in conjunction with a clinical pretest probability assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) disease in outpatients suspected of DVT or PE.

The assay principle combines a two-step enzyme immunoassay sandwich method with a final fluorescent detection (ELFA). The Solid Phase Receptacle (SPR), a pipette tip-like device, serves as the solid phase as well as the pipetting device for the assay. The assay reagents are ready-to-use and pre-dispensed in the sealed reagent strips (STRs). The individual kit components are described in detail on the following pages.

All of the assay steps are performed automatically by the instrument. The reaction medium is cycled in and out of the SPR several times.

First, the sample is taken by the SPR, diluted and then cycled in and out of the SPR several times. The antigen binds to the anti-FbDP immunodobulins coated on the SPR. Unbound components are eliminated during a washing step. In the second step, the conjugate that contains an alkaline phosphatase labeled anti-FbDP monoclonal antibody is cvcled in and out of the SPR to form a sandwich. Unbound components are eliminated during the washing steps.

A detection step is then performed. The substrate (4-Methyl-umbellifery) phosphate) is cycled in and out of the SPR. The conjugate enzyme catalyzes the hydrolysis of this substrate into a fluorescent product (4-Methyl-umbelliferone), the fluorescence of which is measured at 450 nm. The intensity of fluorescence is proportional to the concentration of antigen present in the sample. At the end of the assay, results are automatically calculated by the instrument in relation to the calibration curve stored in memory. The results are then printed.

Acceptance Criteria and Study for VIDAS® D-Dimer Exclusion II Assay

This analysis focuses on the information provided in the 510(k) Summary for the VIDAS® D-Dimer Exclusion II Assay (K112818).

1. Table of Acceptance Criteria and Reported Device Performance

The provided document primarily focuses on demonstrating substantial equivalence to a predicate device rather than explicitly stating acceptance criteria for new device performance. However, by comparing the VIDAS® D-Dimer Exclusion II (DEX2) with its predicate (VIDAS® D-Dimer Exclusion), we can infer the performance metrics that were deemed acceptable for the new device. The "reported device performance" are the values presented for the VIDAS® D-Dimer Exclusion II Assay.

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

The document states "A summary of the non-clinical results is presented in the table below," referring to the detailed comparison table. This table includes analytical performance data.

• Sample Size for Test Set: The specific sample sizes for each analytical performance test (e.g., linearity, precision, interference, specificity) are not provided in this summary. The table indicates values for these tests (e.g., CV at specific ng/mL levels), implying that tests were conducted, but the number of samples or replicates used for each test is not detailed.
• Data Provenance: Not explicitly stated. Given that bioMérieux, Inc. is the submitter (located in Hazelwood, MO, USA), the studies were likely conducted in the USA or through their global facilities. The summary does not specify whether the data is retrospective or prospective.

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

This is a an in vitro diagnostic device measuring D-Dimer levels. For such devices, "ground truth" for analytical performance studies is typically established by:

• Reference Methods: Comparing the new assay's results against established reference methods or highly accurate laboratory techniques.
• Reference Materials: Using certified reference materials or plasma samples with known D-Dimer concentrations.
• Clinical Diagnosis: For clinical performance, the ground truth for DVT/PE would be established by definitive diagnostic imaging (e.g., ultrasonography, CTPA) and/or medical record review, not by "experts" in the sense of adjudicating images.

The summary does not mention any "experts" being used to establish ground truth for the analytical test set in the way one would for diagnostic imaging. Instead, the performance is compared to the predicate device and established analytical methodologies.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1, 3+1) are primarily used in studies involving subjective interpretation, often in imaging or clinical assessments where multiple readers provide opinions, and inconsistencies need resolution.

Since the VIDAS® D-Dimer Exclusion II Assay is an automated quantitative immunoassay, the results are numerical and objective. Therefore, an adjudication method in the sense of resolving conflicting interpretations is not applicable to the analytical performance tests described in this summary. The "results are automatically calculated by the instrument," which minimizes the need for human adjudication of raw data.

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

No. An MRMC comparative effectiveness study is not mentioned. Such studies are typically conducted for diagnostic imaging devices where human readers interpret medical images, and the AI's impact on their performance is assessed. The VIDAS® D-Dimer Exclusion II Assay is an in vitro diagnostic device, and its performance is assessed analytically and clinically, not through human-in-the-loop image interpretation.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, in essence. The VIDAS® D-Dimer Exclusion II is an automated assay. Its "performance" as described (assay range, linearity, precision, specificity, etc.) is the standalone performance of the instrument and reagents. The results are automatically calculated by the instrument.

However, it's crucial to note that the device's intended use is "in conjunction with a clinical pretest probability assessment model." This means that while the assay itself is standalone, its clinical utility for DVT/PE exclusion requires human interpretation of the assay result combined with a clinical pretest probability assessment. The output of the device (D-Dimer concentration) is an algorithmic result, but its application in patient management involves a human clinician.

7. The Type of Ground Truth Used

For the analytical performance characteristics summarized, the ground truth would be established by:

• Reference Standards/Materials: For linearity, detection limit, hook effect, and precision, samples with known, precisely measured concentrations of D-Dimer or related substances are used.
• Interference Substances: Known concentrations of interfering substances (e.g., hemoglobin, bilirubin, rheumatoid factor, drugs) are added to samples to determine their impact.
• Reference Assays: For method comparison (implicitly to the predicate, and typically to other established D-Dimer assays), results are compared against those from a recognized reference method.

For the stated Intended Use (exclusion of DVT/PE in outpatients), the ultimate ground truth in clinical studies (which are not detailed in this analytical performance summary but are foundational for such devices) would be definitive clinical diagnosis of DVT or PE, typically established by objective imaging studies (e.g., compression ultrasonography for DVT, CT Pulmonary Angiography for PE) and clinical follow-up. This summary focuses on the analytical performance, not the full clinical validation study details.

8. The Sample Size for the Training Set

This document is a 510(k) summary for an immunoassay, not a machine learning or AI-based device that would typically have a separate "training set" for an algorithm. The "training set" concept is not applicable here in the conventional AI/ML sense.

For an immunoassay, the "training" equivalent would be the extensive R&D and validation work done to optimize reagent concentrations, incubation times, antibody selection, and assay parameters. This process would involve many experiments with various sample types and concentrations, but it's not described as a discrete "training set" like in AI.

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

As noted above, the concept of a "training set" in the AI/ML context with an established ground truth is not applicable to this immunoassay. The development and optimization of the assay would rely on:

• Biochemical Principles: Understanding antigen-antibody reactions, enzyme kinetics, and fluorescent detection.
• Calibrators and Controls: Precisely manufactured substances with known concentrations, used to establish the calibration curve and monitor assay performance.
• Validation Studies: Iterative experiments using a wide range of patient samples (with D-dimer levels determined by reference methods or clinical diagnosis) to optimize and verify performance characteristics like sensitivity, specificity, and linearity.

These activities during the assay development process serve a similar function to a training set in that they guide the refinement of the assay, but the specifics are not detailed in this regulatory summary.

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The Stratus® CS Acute Care™ D-dimer assay (DDMR) is an in vitro diagnostic test for the quantitative measurement of cross-linked fibrin degradation products (D-dimer) in human citrated or heparinized plasma on the Stratus® CS analyzer. The Stratus® CS Acute Care™ DDMR assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude pulmonary embolism (PE) disease and as an aid in the diagnosis of venous thromboembolism (VTE) [deep vein thrombosis (DVT) or pulmonary embolism (PE)]. This assay is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

The Stratus® CS Acute Care™ D-Dimer method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. In this procedure, dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the DDMR TestPak. This antibody recognizes a distinct antigenic site on the D-dimer molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme-labeled monoclonal antibody directed against a second distinct antigenic site on the D-dimer molecule is pipetted onto the reaction zone of the paper. During this second incubation period, enzyme-labeled antibody reacts with the bound D-dimer, forming an antibodyantigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS STAT Fluorometric Analyzer (Stratus® CS analyzer) by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of D-dimer in the sample. The reaction rate can then be measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

Acceptance Criteria and Device Performance for Stratus® CS Acute Care™ D-Dimer Assay

This document summarizes the acceptance criteria and performance of the Stratus® CS Acute Care™ D-Dimer assay as described in the provided 510(k) summary (K110303).

1. Table of Acceptance Criteria and Reported Device Performance

The study evaluated the performance of the Stratus® CS Acute Care™ D-Dimer assay against a clinical cutoff of 450 ng/mL [µg/L] (FEU) for the exclusion of Pulmonary Embolism (PE).

Acceptance Criteria (Implied by Predicate Device Equivalence and Clinical Relevance for PE Exclusion):
While explicit numerical acceptance criteria for sensitivity, specificity, and NPV are not directly stated as pass/fail thresholds, the study aims to demonstrate substantial equivalence to the Innovance D-Dimer assay and clinical utility for PE exclusion, implying that the performance metrics should be comparable to or ideally exceed those required for safe and effective PE exclusion. For D-dimer assays used to exclude PE, high sensitivity and negative predictive value (NPV) are critical. The reported values are generally considered acceptable for this application.

Reported Device Performance:

Citrated Plasma: In all patients

Citrated Plasma: In Patients with low and moderate pre-test probability

Heparinized Plasma: In all patients

Heparinized Plasma: In Patients with low and moderate pre-test probability

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

• Citrated Plasma: 730 consecutive patients initially, 655 patients remaining after exclusions for final analysis.
• Heparinized Plasma: 468 consecutive patients initially, 427 patients remaining after exclusions for final analysis.
• Data Provenance: The study was a multi-center study. The document does not specify the countries of origin but states it's a "multi-center study." The data is prospective, collected from consecutive patients presenting to the emergency department with suspected PE.

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

The document does not explicitly state the number of experts used to establish the ground truth or their qualifications in detail. However, the ground truth for PE diagnosis appears to be established through a combination of imaging methods (e.g., spiral CT and/or VQ scan) for patients with positive D-dimer and/or high PTP, and a three-month follow-up for patients with negative D-dimer/low/moderate PTP or negative imaging results. This implies that the diagnosis of PE was made by medical professionals (e.g., radiologists, clinicians) utilizing established diagnostic protocols but does not specify individual expert roles for establishing a "ground truth" for the test set.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for establishing the ground truth diagnoses. The diagnostic process involved imaging (spiral CT, VQ scan) and clinical follow-up for three months. It is implied that standard clinical practices and interpretations were followed for these diagnostic procedures, rather than a specific consensus or adjudication process among multiple independent experts to establish the ground truth for each case.

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

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not performed. This study focuses on the performance of the device (assay) itself in a standalone manner, rather than as an aid to human interpretation.

6. If a Standalone Study Was Done

Yes, a standalone study of the algorithm's performance (the D-dimer assay) was done. The reported sensitivity, specificity, and negative predictive value are directly from the assay's performance against the established clinical ground truth for PE. There is no human-in-the-loop component for these reported performance metrics.

7. The Type of Ground Truth Used

The ground truth used was a combination of:

• Imaging Data: Spiral CT and/or VQ scans were used for patients with positive D-dimer results and/or high pre-test probability (PTP).
• Outcomes Data (Clinical Follow-up): Patients with negative D-dimer results and low or moderate PTP (or negative imaging results) were followed for three months to evaluate potential development of PE. This follow-up serves as an outcome-based ground truth to confirm the absence of PE.

8. The Sample Size for the Training Set

The document does not specify a separate training set. This 510(k) submission describes a clinical validation study, implying that the D-dimer assay and its cutoff of 450 ng/mL [µg/L] (FEU) were already established, likely based on previous research or predicate device characteristics. The study described here acts as a test set for validating the performance of the assay rather than for training a new algorithm.

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

As no explicit training set is described, the method for establishing ground truth for a training set is not applicable to the information provided. The study focuses on evaluating the assay's performance on a validation dataset.

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For the quantitative determination of cross-linked fibrin degradation products (D-dimers) in human plasma on Siemens Healthcare Diagnostics and Sysmex® Coagulation Systems. The INNOVANCE® D-Dimer assay is intended for use in conjunction with a non-high clinical pretest probability (PTP) assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE).

Polystyrene particles covalently coated with a monoclonal antibody (8D3) are aggregated when mixed with samples containing D-dimer. The D-dimer crosslinkage region has a stereosymmetrical structure, i.e. the epitope for the monoclonal antibody occurs twice. Consequently, one antibody suffices in order to trigger an aggregation reaction, which is then detected turbidimetrically via the increase in turbidity.

Here's a breakdown of the acceptance criteria and study information for the INNOVANCE® D-Dimer assay:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly stated as distinct numerical targets in the provided text. However, the study aims to demonstrate that the device performs with sufficient sensitivity and Negative Predictive Value (NPV) to reliably exclude DVT, especially in patients with an unlikely pre-test probability. Based on the presented data, the implied acceptance criteria would be a sensitivity and NPV close to or at 100% for the intended use.

Study Proving Device Meets Acceptance Criteria:

The study referenced is a multi-center clinical evaluation evaluating the INNOVANCE® D-Dimer assay on the BCS® / BCS® XP System to exclude DVT.

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

• Sample Size for Test Set:
  • Total Patients: 455 consecutive patients initially enrolled.
  • Patients for Final Analysis: 426 patients (29 were excluded)
  • Patients with unlikely pre-test probability: 267 patients.
• Data Provenance: The study was a "multi-center study," suggesting data was collected from multiple clinical sites. The text doesn't explicitly state the country of origin, but the manufacturer is German, and the contact information is for the US. It is a prospective study as it involved "consecutive patients presenting to the emergency department" and follow-up for three months.

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

The text does not specify the number of experts used or their qualifications to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The text does not explicitly state an adjudication method for the test set. The diagnostic certainty (ground truth) appears to have been established through a combination of imaging methods (compression ultrasound and/or venography) for positive D-dimer results, and a three-month follow-up for negative D-dimer and negative imaging results. This implicitly suggests that the attending clinicians/radiologists' assessments, informed by these methods, served as the ground truth.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This study focuses on the standalone performance of the D-dimer assay.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, a standalone performance study was done. The results presented (Sensitivity, Specificity, NPV) are for the INNOVANCE® D-Dimer assay performed at a specific cutoff, independent of human interpretation of the D-dimer value itself, other than applying the PTP model. The assay's performance is then compared to the established ground truth of DVT.

7. The Type of Ground Truth Used

The ground truth used was a combination of:

• Imaging methods: Compression ultrasound and/or venography for patients with positive D-dimer results.
• Outcomes data: Three-month follow-up for patients with negative D-dimer results and those with negative imaging results, to evaluate for the potential development of DVT.

8. The Sample Size for the Training Set

The document does not specify a separate training set or its sample size. The study described appears to be a validation study of the device against clinical outcomes, rather than a development and training study for an algorithm. D-dimer assays traditionally involve established biochemical principles and cutoffs, rather than machine learning algorithms that require explicit training sets.

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

Since no explicit training set or machine learning algorithm development is described, the method for establishing ground truth for a training set is not applicable in this context. The 0.50 mg/L (FEU) cutoff is a pre-established clinical cutoff for D-dimer assays.

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