The Triage® BNP Test is intended for use with the Triage® Meter for the rapid in vitro quantitative measurement of B-Type Natriuretic Peptide (BNP) in human whole blood or plasma specimens using EDTA as the anticoagulant. The test is used as an aid in the diagnosis and assessment of severity of congestive heart failure. The test also is used for the risk stratification of patients with acute coronary syndromes.

Device Description

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the Triage® B-Type Natriuretic Peptide (BNP) Test:

1. Table of Acceptance Criteria and Reported Device Performance

The provided 510(k) summary does not explicitly state specific quantitative acceptance criteria or thresholds for the device's performance in a table format. Instead, it focuses on the device's intended use, its substantial equivalence to a predicate device for the methodology, and its substantial equivalence to other predicate methods for the conceptual use of a biochemical marker for prognostic information.

However, the summary does describe the performance in the context of risk stratification for ACS patients:

Metric (Implied Acceptance Criteria)	Reported Device Performance (as demonstrated in the study)
Aid in risk stratification of patients with Acute Coronary Syndromes (ACS) by identifying patients at higher risk for adverse outcomes.	Patients whose BNP concentration was at least 80 pg/mL had higher rates of death, myocardial infarction, and Congestive Heart Failure (CHF) both at 30 days and at 10 months after presentation, compared to patients whose BNP concentration was below 80 pg/mL. This indicates the test provides "useful predictive information to aid in the risk stratification of patients with ACS."
Substantial equivalence to predicate methods for the physical test method (sandwich ELISA) and calibration.	"The device and test method described in the labeling are identical to the predicate device, the Triage® BNP Test. The antibodies used in the microplate assays and the Triage® BNP Test are identical, and both platforms utilize a sandwich ELISA assay. Furthermore, the same reagents used to calibrate the Triage® BNP Test also were used to calibrate the microplate assays." (Implies the new device performs equivalently to the existing Triage® BNP Test in terms of its underlying technology and calibration).
Substantial equivalence to predicate methods for the conceptual use of a biochemical marker to provide prognostic information to a physician.	"The Dade Stratus Cardiac Troponin-I and Dade Dimension RxL Cardiac Troponin-I are used as predicate methods for the conceptual description of how a biochemical marker can be used to provide prognostic information to a physician. Although these predicate methods describe a different analyte, the description of how the test results should be interpreted with respect to the prognosis of the patient are substantially equivalent." (Implies the utility of BNP as a prognostic marker is conceptually similar to established cardiac troponin markers, even though the specific analyte is different).

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

Sample Size for Test Set: 2525 high-risk ACS patients.
Data Provenance: The study was observational and retrospective. The patients were from a population that met standard diagnostic criteria for ACS. The country of origin is not explicitly stated in the provided text.

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

The document does not explicitly state the number of experts used to establish the ground truth for the test set.
It mentions "standard diagnostic criteria for ACS," implying that the initial diagnosis of ACS for the patient cohort was established through accepted medical protocols, likely involving physician diagnosis, clinical presentation, and other diagnostic tests.
The "ground truth" for the device's prognostic utility seems to have been based on subsequent clinical outcomes (death, myocardial infarction, CHF at 30 days and 10 months), rather than an expert consensus on individual BNP values.

4. Adjudication Method for the Test Set

The document does not specify an adjudication method for the test set in terms of expert review of cases. The study's nature was observational and retrospective, linking BNP levels to subsequent clinical outcomes.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No, an MRMC comparative effectiveness study was not done. This study assesses the prognostic utility of a quantitative biochemical marker (BNP), not the performance of human readers with or without AI assistance in interpreting images or clinical data. The device is an in vitro diagnostic test, not an AI imaging or diagnostic algorithm designed to assist human interpretations of complex cases.

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

Yes, a standalone study was done. The study's focus was on the quantitative measurement of BNP and its ability to predict future clinical events (death, MI, CHF) without direct human intervention in the interpretation of the BNP value for individual patient prognosis within the study design. The test itself, performed by the Triage® Meter, provides a quantitative result. The interpretation of that result for risk stratification is then done by a healthcare professional, but the study validates the standalone predictive power of the BNP value.

7. The Type of Ground Truth Used

The type of ground truth used to evaluate the device's prognostic utility was outcomes data. Specifically, the endpoints were:
- Death
- Myocardial Infarction
- Congestive Heart Failure
- These outcomes were observed at 30 days and 10 months after presentation.

8. The Sample Size for the Training Set

The document does not mention a separate "training set" in the context of an algorithm or machine learning. The clinical study described with 2525 patients appears to be the sole clinical study presented to support the prognostic claim. For a traditional medical device (like an IVD), "training set" is typically not applicable in the same way it is for AI/ML. The 2525 patient cohort was used to demonstrate the association between BNP levels and outcomes.

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

As a training set is not explicitly mentioned in the context of an algorithm, this question is not directly applicable. If we consider the 2525 patient cohort as the dataset used to establish the evidence for the claim, the "ground truth" was established based on clinical outcomes (death, MI, CHF) observed for these patients over 30 days and 10 months, following their diagnosis of ACS based on "standard diagnostic criteria."

Summary

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510(k) Summary

Triage® B-Type Natriuretic Peptide (BNP) Test

This 510(k) summary is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

510(k) Number: K021317

Name and Address of Submitter

Company Name:	Biosite Diagnostics, Incorporated
Address:	11030 Roselle Street
	San Diego, CA 92121
Telephone:	(858) 455-4808
Fax:	(858) 535-8350
Contact Person:	Jeffrey R. Dahlen, Ph.D.
Date Summary Prepared:	6/28/02

Device Names

1. Trade Name
  Triage® B-Type Natriuretic Peptide (BNP) Test
1. Common / Usual Name

BNP Test

1. Classification Name
  B-Type Natriuretic Peptide Test System

Device Description and Intended Use

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Summary of Clinical Data

BNP concentrations measured in patients with acute coronary syndromes (ACS) or cardiovascular disease provide prognostic information about the patient's risk for death and the development of CHF. Statistically significant increases in death, future myocardial infarction, and CHF have been associated with higher BNP concentrations measured within the first 72 hours after the onset of ACS symptoms. In a recent clinical study, BNP concentrations were evaluated in an observational, retrospective manner in patients with ACS (consisting of unstable angina, myocardial infarction with ST-segment elevation, or myocardial infarction without ST-segment elevation). BNP measurements were performed on specimens obtained within 72 hours after the onset of ischemic discomfort from a population of 2525 high-risk ACS patients that met standard diagnostic criteria for ACS. Patients whose BNP concentration was at least 80 pg/mL had higher rates of death, myocardial infarction, and CHF both at 30 days and at 10 months after presentation than patients whose BNP concentration was below 80 pg/mL. In this population of patients with ACS. BNP measurements within the first 72 hours after the onset of symptoms provide useful predictive information to aid in the risk stratification of patients with ACS.

Comparison to Predicate Methods

The device and test method described in the labeling are identical to the predicate device, the Triage® BNP Test. The antibodies used in the microplate assays and the Triage® BNP Test are identical, and both platforms utilize a sandwich ELISA assay. Furthermore, the same reagents used to calibrate the Triage® BNP Test also were used to calibrate the microplate assays. In this regard, the two assay formats are substantially equivalent.

The Dade Stratus Cardiac Troponin-I and Dade Dimension RxL Cardiac Troponin-I are used as predicate methods for the conceptual description of how a biochemical marker can be used to provide prognostic information to a physician. Although these predicate methods describe a different analyte, the description of how the test results should be interpreted with respect to the prognosis of the patient are substantially equivalent.

Conclusion

The use of the Triage® BNP Test to aid in the risk stratification of patients with ACS is substantially equivalent to the predicate methods.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized symbol resembling a person with outstretched arms, composed of three curved lines. The symbol is encircled by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA". The text is arranged in a circular fashion around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

1 2002 ர்பட

Jeffery Dahlen, Ph.D. Principal Scientist Clinical Regulatory Affairs Biosite, Inc. 11030 Roselle Street San Diego, CA 92121

Re: K021317

Trade/Device Name: Triage® B-Type Natriuretic Peptide (BNP) Test Regulation Number: 21 CFR 862.1117 Regulation Name: B-type natriuretic peptide test system Regulatory Class: Class II Product Code: NBC Dated: April 24, 2002 Received: April 25, 2002

Dear Dr. Dahlen:

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, listing 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice reguirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and : additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/dsmaldsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number (if known): K021317

Device Name: Triage® B-Type Natriuretic Peptide (BNP) Test

Indications For Use:

yan
Cooper
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K021312

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)

Over-The Counter Use

(Optional Format 1-2-96)

Regulation Number and Section

§ 862.1117 B-type natriuretic peptide test system.

(a)
Identification. The B-type natriuretic peptide (BNP) test system is an in vitro diagnostic device intended to measure BNP in whole blood and plasma. Measurements of BNP are used as an aid in the diagnosis of patients with congestive heart failure.(b)
Classification. Class II (special controls). The special control is “Class II Special Control Guidance Document for B-Type Natriuretic Peptide Premarket Notifications; Final Guidance for Industry and FDA Reviewers.”