VIDAS® D-Dimer New is an automated, quantitative test for use on the VIDAS analyzer for the immunoenzymatic determination of cross-linked fibrin degradation products (FbDP) containing the D-dimer domain in citrated human plasma using the Enzyme Linked Fluorescent Assay (ELFA) technique. VIDAS D-Dimer New is indicated for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude deep vein thrombosis (DVT) and pulmonary embolism (PE) in outpatients suspected of DVT or PE.

Device Description

The VIDAS® D-Dimer New (DD2) Assay is an automated quantitative test for use on the VIDAS instrument (K891385) for the immunoenzymatic determination of fibrin degradation products (FbDP) in human plasma using the enzyme-linked fluorescent immunoassay (ELFA) technique. The instrument controls all assay steps and assay temperatures. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR), serves as the solid phase as well as a pipettor for the assay. Reagents for the assay are ready-to-use and pre-dispensed in the sealed DD2 Reagent Strips.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the VIDAS D-Dimer New (DD2) Assay, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied by Predicate & Intended Use)	Reported Device Performance (DVT exclusion)
Sensitivity	High (critical for DVT/PE exclusion)	100% (95% CI, 93.6-100.0) for suspected DVT (All PTPs)
Negative Predictive Value	High (critical for DVT/PE exclusion)	100% (95% CI, 97.8-100.0) for suspected DVT (All PTPs)
Specificity	(No explicit threshold, but expected to be reasonable)	32.9% (95% CI, 28.8-37.2) for suspected DVT (All PTPs)

Note: The acceptance criteria are not explicitly stated as numerical thresholds in the provided text. However, for a diagnostic test intended to exclude DVT and PE, very high sensitivity and negative predictive value are paramount to ensure that patients with the condition are not missed. The study results demonstrate 100% sensitivity and 100% negative predictive value, which would be considered excellent performance for this intended use.

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

Test Set Sample Size:
- Pulmonary Embolism (PE) / Deep Venous Thrombosis (DVT) Study: 302 patients (initial study mentioned)
- Deep Vein Thrombosis (DVT) Exclusion Study: 555 patients (after one sample excluded due to volume limitations from an initial 556)
Data Provenance: Retrospective for the PE/DVT study (frozen samples) and prospective for the DVT exclusion study. The text does not specify the country of origin, but it mentions a "multi-center, prospective cohort study" and "three hospitals," suggesting multiple sites, likely within the same country where the submission was made (US, given the FDA filing).

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

The text does not provide information on the number or qualifications of experts used to establish the ground truth for the test set.

4. Adjudication Method for the Test Set

The text does not explicitly describe an adjudication method for establishing ground truth for the test set. The DVT exclusion study mentions "clinical outcome of the patients" and "serial compression ultrasound (CUS)" for patients with positive D-dimer/high PTP, implying a diagnostic workup to confirm or rule out DVT, but no specific adjudication panel or method (e.g., 2+1) is detailed.

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

A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The device is an automated quantitative assay for D-Dimer, not an AI-assisted imaging device or a system that requires human interpretation in the same way. Therefore, the concept of human readers improving with/without AI assistance does not apply here.

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

Yes, a standalone study was done. The VIDAS D-Dimer New assay is an "automated quantitative test" and "performed without knowledge of the PTP assessment results and the clinical outcome of the patients." This indicates that the device's performance was evaluated purely on its own diagnostic output (D-dimer levels) against the clinical ground truth. The "human-in-the-loop" aspect comes from the intended use, where the D-Dimer result is used in conjunction with a clinical PTP model for decision-making, but the assay itself is standalone.

7. The Type of Ground Truth Used

The ground truth for the test sets was based on clinical diagnosis/outcomes data.

For the PE/DVT study, "frequency of venous thromboembolic disease" was determined.
For the DVT exclusion study, patients "underwent no further diagnostic testing and were followed up for 3 months for development of DVT" if negative D-dimer and low/moderate PTP. Patients with positive D-dimer and/or high PTP "underwent serial compression ultrasound (CUS)." This implies that the presence or absence of DVT was confirmed or ruled out through standard clinical diagnostic methods and follow-up, which serves as the ground truth.

8. The Sample Size for the Training Set

The text does not specify a separate training set or its sample size. This is common for traditional laboratory assays where the "training" involves assay development and optimization, rather than a machine learning training phase on a distinct dataset. The performance data presented is likely from validation studies.

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

Since a distinct "training set" in the context of machine learning is not mentioned, the method for establishing its ground truth is not applicable/not provided in this document. The ground truth for the validation/performance studies was established via clinical diagnosis and follow-up, as described in point 7.

Summary

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K030328

510(k) Summary Section J.

Applicant Name and Address
Applicant:	bioMerieux, Inc.
Address:	595 Anglum RoadHazelwood, MO 63042
Contact Person:	Sandra Perreand
Phone Number:	(314) 731-8594
Fax Number:	(314) 731-8689
Date of Preparation:	August 25, 2003
Device Name
Trade Name:	VIDAS D-Dimer New (DD2) Assay
Common Name:	Enzyme-linked Fluorescent Immunoassay (ELFA) for the quantitativedetection of fibrin degradation products (FbDP)
Classification Name:	Fibrinogen and Fibrin Split Products, Antigen, Antiserum, Control
Predicate Device
Trade Name:	VIDAS D-Dimer (DD) New Assay, K020810

Device Description

Intended Use

The VIDAS® D-Dimer New is an automated quantitative test for use on the VIDAS analyzer for the immunoenzymatic determination of fibrin degradation products (FbDP) in citrated human plasma using the ELFA techniques (Enzyme Linked Fluorescent Assay). The VIDAS" D-Dimer New assay is indicated for use in conjunction with a clinical Pre-test Probability Assessment (PTP) model in excluding deep venous thrombosis (DVT) and Pulmonary Embolism (PE).

Technological Characteristic Summary

Summary of Similarities and Differences to Predicate Device

Major Similarities Include:

1. The VIDAS D-Dimer assays are identical except for the proposed modification in the Indications for Use.

Major Differences Include:

1. The major difference between the two VIDAS assays is that we are expanding the indications for use for the assay.

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Performance Data

Data was taken from a study carried out on 302 patients admitted consecutively to the emergency unit with suspected pulmonary embolism or deep venous thrombosis (frequency of venous thromboembolic disease: 23.7%).

For a cutoff at 500ng/ml, the results of the VIDAS D-Dimer New assay were as follows:

Sensitivity:	100% (95% CI, 95.0-100)
Specificity:	33% (95% CI, 27.0-39.1)
Neg. Predictive Value:	100% (95% CI, 95.3-100)

Frozen samples collected from patients enrolled in a multi-center, prospective cohort study were used to validate the diagnostic utility of VIDAS D-Dimer New to exclude a diagnosis of deep vein thrombosis (DVT). Consecutive eligible outpatients (n = 556) with a first suspected DVT episode were evaluated at three hospitals during the course of the study. Using the previously validated, standardized clinical Wells model to estimate the probability of DVT, patients were classified as having a high, moderate, or low pretest probability (PTP) of DVT.

The VIDAS D-Dimer New assay was performed without knowledge of the PTP assessment results and the clinical outcome of the patients from which the samples were derived. A clinical cut off value of 500 ng FEU/ml was used. A D-dimer result of >>= 500 ng FEU/ml was considered positive and a result of < 500 ng FEU/ml was considered negative.

This study was designed as a management clinical trial and patients were grouped according to PTP. Those patients having a negative D-dimer test result and a low or moderate PTP of DVT underwent no further diagnostic testing and were followed up for 3 months for development of DVT. Patients with a positive D-dimer test result and/or high PTP underwent serial compression ultrasound (CUS).

The overall prevalence of DVT in the total population studied was 10.1% (56/556). One sample from the original study was not tested due to volume limitations. The sensitivity, specificity and negative predictive value of the VIDAS D-Dimer New assay using a clinical cut off of 500 ng FEU/ml is summarized below with the corresponding 95% confidence intervals (CI).

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All Patients

Patients	N	% ClinicalSensitivity(95% CI)	% ClinicalSpecificity(95% CI)	% NegativePredictiveValue (95% CI)
Suspected DVTAll PTP's	555	100.0(56/56)(93.6-100.0)	32.9(164/499)(28.8 - 37.2)	100.0(164/164)(97.8 - 100.0)

Patients with low PTP

Patients	N	% ClinicalSensitivity(95% CI)	% ClinicalSpecificity(95% CI)	% NegativePredictiveValue (95% CI)
Suspected DVTwithLow PTP	295	100.0(18/18)(81.5-100.0)	39.7(110/277)(33.9-45.7)	100.0(110/110)(96.7 - 100.0)

Patients with moderate PTP

Patients	N	% Clinical Sensitivity (95% CI)	% Clinical Specificity (95% CI)	% Negative Predictive Value (95% CI)
Suspected DVT with Moderate PTP	189	100.0(17/17)(80.5 - 100.0)	26.7(46/172)(20.3 - 34.0)	100.0(46/46)(92.3 - 100.0)

Patients with high PTP

Patients	N	% ClinicalSensitivity(95% CI)	% ClinicalSpecificity(95% CI)	% NegativePredictiveValue (95% CI)
Suspected DVTwithHigh PTP	71	100.0(21/21)(83.9–100.0)	16.0(8/50)(7.2–29.1)	100.0(8/8)(63.1–100.0)

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Image /page/3/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized image of an eagle with three lines representing its wings. The eagle is positioned in the center of a circular border, with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" encircling it.

SEP - 2 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Sandra Perreand Director, Regulatory Affairs BioMérieux, Inc. 595 Anglum Road Hazelwood, Missouri 63042

Re: K030328

Trade/Device Name: VIDAS® D-Dimer New Assay Regulation Number: 21 CFR § 864.7320 Regulation Name: Fivrinogen and Fibrin Split Products, Antigen, Antiserum, Control Regulatory Class: II Product Code: DAP Dated: July 21, 2003 Received: July 21, 2003

Dear Ms. Perreand:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 -

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known):

VIDAS D-Dimer New (DD2) Assay Device Name:

Indications for Use:

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Regulation Number and Section

§ 864.7320 Fibrinogen/fibrin degradation products assay.

(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).