The Navigator™ is indicated for the acquisition, processing, and display of hemodynamic parameters, in order to assist the clinician in achieving and maintaining a prescribed target hemodynamic stability.

Mean Systemic Filling Pressure (Pms) and Heart Efficiency (En) parameters are calculated by the Navigator from Cardiac Output (CO), Mean Arterial Pressure (MAP) and Right Atrial Pressure (RAP) data, obtained directly from patient monitoring equipment, and other data obtained by manual clinician entry. The Navigator system provides a visual indication of the patient's circulatory status in relation to predetermined goals.

Device Description

The Navigator is a physiologically integrated system designed to assist clinicians in the management of the systemic circulatory state in the critically ill patient.

AI/ML Overview

Here's an analysis of the provided text regarding the Navigator device's acceptance criteria and study, structured to include the requested information:

Acceptance Criteria and Device Performance Study for Navigator™

The Navigator™ device is a computer, diagnostic, pre-programmed, single-function system designed to assist clinicians in managing the systemic circulatory state in critically ill patients.

1. Table of Acceptance Criteria and Reported Device Performance

The primary efficacy endpoint for the Navigator™ device was its ability to demonstrate non-inferiority to conventional care with respect to maintaining hemodynamic stability.

Acceptance Criteria	Reported Device Performance
Efficacy: Non-inferiority to conventional care regarding the average distance (mean standardized) to the central point of the target cardiovascular zone.	The study "demonstrated non-inferiority to Navigator over conventional care." There was "no statistically significant difference between the two treatment arms with regards to the mean standardized distance to the central point of the cardiovascular zone."
Safety: Incidence of adverse events (AEs) and serious adverse events (SAEs) comparable to conventional care, and no AEs/SAEs considered device-related.	The incidence of AEs and SAEs was comparable across the two study arms ("no trends in the type, frequency or severity of adverse events per study arm"). "No adverse or serious adverse events [were] considered to be related to Navigator™." Minor device incidents occurred but were not associated with clinical consequences or patient safety impact.

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

Test Set Sample Size: 112 patients were initially enrolled (Intent-To-Treat population). 107 patients completed the study as planned. The Modified Intent-To-Treat (MITT) population, defined as patients connected to Navigator™ for three hours or more of data, comprised 105 patients (57 in the Navigator™ arm and 48 in the control arm).
Data Provenance: The study was a "multi-center, open, randomized, controlled human clinical trial." The document does not explicitly state the country of origin for the data, but the applicant (Applied Physiology Pty Ltd) is based in Sydney, NSW, Australia, suggesting the study likely took place in Australia, and possibly other international sites if it was a true "multi-center" global study. The study was prospective, as it involved enrolling patients and randomizing them to receive care guided by Navigator™ or conventional care.

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

The study was a comparative effectiveness trial aiming to show non-inferiority to conventional care, rather than validating the device's output against an independent "ground truth" established by experts. The "ground truth" for evaluating the device's effectiveness was based on the clinical outcome of maintaining patients within a target cardiovascular zone by clinicians using the device or conventional care.

Therefore, there were no specific experts explicitly mentioned as establishing a "ground truth" for the test set in the way one might with diagnostic accuracy studies. The "ground truth" was essentially the patient's physiological state and clinical course as monitored and managed by the attending clinicians in both the Navigator and control arms, with the primary endpoint being a physiological measure (distance to the central point of the target cardiovascular zone).

4. Adjudication Method for the Test Set

The study design describes a randomized controlled trial where patients were randomized to either receive care guided by Navigator™ or conventional care. The primary endpoint "the average distance (mean standardized) to the central point of the target cardiovascular zone" was a quantitative measure.

There is no specific adjudication method (e.g., 2+1, 3+1) described for establishing a "ground truth" of individual cases by expert review. Given the nature of the primary endpoint (a statistical comparison of a numerical physiological outcome), such an adjudication method would not be directly applicable. The data collection would have been direct physiological measurements from monitoring equipment.

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 was not a Multi-Reader Multi-Case (MRMC) comparative effectiveness study in the typical sense of evaluating human reader performance on diagnostic images. Instead, it was a randomized controlled clinical trial comparing the impact of a computer-assisted decision support system (Navigator™) versus conventional care on patient management and physiological outcomes.

Therefore, the concept of "human readers improve with AI vs without AI assistance" as a direct effect size (e.g., AUC improvement) is not applicable to this study design. The study demonstrated that care guided by Navigator™ was non-inferior to conventional care in achieving and maintaining hemodynamic stability. The benefit is implied as enabling clinicians to achieve comparable outcomes with the aid of the system.

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

No, a standalone (algorithm-only) performance study was not described or performed. The Navigator™ is explicitly described as a system "designed to assist clinicians" and its indications for use state it is "to assist the clinician." The clinical trial evaluated the device with a human-in-the-loop (i.e., care guided by Navigator™). The device calculates parameters and provides visual indications, which clinicians then use for management.

7. The Type of Ground Truth Used

The "ground truth" used for efficacy was the patient's physiological state and clinical course, specifically measured by the "average distance (mean standardized) to the central point of the target cardiovascular zone." This is an outcomes data / physiological measurement type of ground truth, rather than expert consensus on a diagnostic finding or pathology.

For safety, the "ground truth" was established through the monitoring and reporting of adverse events by study personnel and clinicians, with subsequent assessment of relatedness to the device or study procedures.

8. The Sample Size for the Training Set

The document does not provide information on a training set sample size. This device is a pre-programmed diagnostic computer mentioned as having "Software Verification and Validation testing" rather than a machine learning/AI model that typically requires a distinct "training set." While it's a "single-function pre-programmed diagnostic computer," the "computer-assisted decision support" implies pre-defined physiological models and algorithms, not necessarily a data-driven machine learning model requiring a large training dataset as understood in modern AI.

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

Since no training set and associated machine learning algorithm development are described, there is no information provided on how ground truth for a training set was established. The device relies on "physiologically integrated systems" and algorithms that calculate parameters from direct patient monitoring data and clinician input, based on established physiological principles.

Summary

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510(k) Number:

Date: ________________________________________________________________________________________________________________________________________________________________________

Page 1 of 4

510(k) Summary

Introduction

MAY 1 2 2010

This summary is intended to comply with requirements of the SMDA and 21CFR 807.92. FDA may make this summary available to the public within 30 days following a finding of substantial equivalence.

510(k) Applicant

Applied Physiology Pty Ltd 119 Willoughby Rd., Crows Nest 2065 Sydney, NSW, Australia Tel: +61 (2) 9956 3838 / Fax: +61 (2) 9439 2157

510(k) Correspondent

Robert N. Clark, President and Senior Consultant Medical Device Regulatory Advisors, Inc. 13605 West 7th Ave., Golden, CO 80401 USA Tel: 303-463-0900 / Fax: 303-558-3833

Date Prepared

April 30, 2010

Trade Name of Device

Navigator™M

Common Name of Device

Computer, diagnostic, pre-programmed, single-function

Classification Name

Single function pre-programmed diagnostic computer

510(k) Classification

· Class II 21 CFR 870.1435

Predicate Devices

The Navigator is substantially equivalent to the following predicate device(s):

K072735 Pulsion PiCCO2 .
K023960 LiDCOplus Hemodynamic Monitor .

Device Description

The Navigator is a physiologically integrated system designed to assist clinicians in the management of the systemic circulatory state in the critically ill patient.

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Indications for Use:

Mean Systemic Filling Pressure (Pms) and Heart Efficiency (En) parameters are calculated by the Navigator from Cardiac Output (CO), Mean Arterial Pressure (MAP) and Right Atrial Pressure (RAP) da'n, obtained directly from patient monitoring equipment, and other data obtained by manual clinician entry. The Navigator system provides a visual indication of the patient's circulatory status in relation to predetermined goals.

Intendod Use

The Navivator TM is valuable in any environment where resuscitation, stabilization and optimize . . . I hemodynamic and oxygen metabolism is required. It provides clinicians with monitori… and support information that assists with management of the circulatory state of ' critically in patients. The device provides clinicians with a graphical display of monitoring and support in inning as a visual aid in determining a patient's circulatory state. Navigator ™ is used in cc rjunction with standard monitoring in the following environments including:

Intensive care .
OR/cu: · thesia .
High .. vendency and step-down units .
rey departments Emer .
. Coro .
Achie care. �

This inc : es a broad range of patients (between the ages of 15-90 and weights of 40-150 with unstable circulations presenting to the intensive care unit (ICU) or critical care kilogram» units and ose undergoing or suffering from:

Pre vost open heart surgery. .
. Pre : iost major surgery.
. Secte . stients.
Drug rdose .
Septi · . rock
. Renn lure
Maje. . . 1718.
Muje. unnu.
Hyp. ni_shock
� Car. ic shock

is applicable to critically ill patients requiring circulatory support in whom MAP, The dev RAP ar. O are being monitored regularly.

Risk । nagement

has been designed to either completely eliminate or mitigate known health hazards This de ith the use of the device. Health hazard risk reduction has been accomplished by associ:: rigoroı. > >ication of a risk management program according to standard ISO 14971:2007.

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Non-{ ical Testing

Non-cl al testing was performed in order to validate the design against the company's esign requirements, and to assure conformance with the following voluntary specific standar،

IEC 60(0) .- 1: Medical Electrical Equipment -- Part 1: General Requirements for Safety (1988), .mendment 1 (1991) & Amendment 2 (1995). includir

BS EN 01-1-2:2002, incorporating amendment A1:2006. This standard is identical with EMC s ard IEC 60601-1-2:2001, incorporating amendment 1:2004: Medical electrical - Part 1-2: General requirements for safety - Collateral Standard: Electromagnetic equipm· Compa .ity - Requirements and Tests (Edition 2:2001 with Amendment 1:2004).

Rigorors ofiware verification and validation testing was successfully performed by an indeper ' t software testing service. Testing included verification and validation to approved iystem Requirements, Operational Requirements, and Data Processing Requirements. Naviga

iation of Electrical Safety testing, EMC testing, and Software Verification and The co Valida provide a high level of confidence that both the Navigator hardware and software are ale and effective as the predicate devices. at least

Clinica Testing

Applier viology Pty Ltd conducted multi-center, open, randomized, controlled human clinica' Is in order to collect safety and efficacy data supporting substantial equivalence.

Meth c ogy:

Follow Ingerv, cligible patients were to be randomized on admission to ICU to receive care guideu. invigator™ or conventional care while CO was being monitored. All patients were to be coni I to the Navigator™. The screen of the patients in the control group was to have the graphic ction blank, the right hand side was to display actual values of MAP. CO and Right Atrial I ur. (RAP) as slaved from the bedside monitor, along with the patient's screening and randon ion number and initials. The arm of the study to which the patient was randomized (contro vigator™), was also to be shown.

Numl. َ subjects (planned and analyzed):

Suffici mients were to be consented to allow 100 patients to complete the study (50 in each :n). A total of 112 patients were enrolled into the study and formed the intent to treat treatme O. these, 107 patients completed the study as planned. A total of 105 patients formed popula יוו the mo i intent to treat (MITT) population (57 patients in the Navigator™ arm and 48 patient he control arm) these being the patients connected to Navigator™ with three hours or more o !.

c :ults:

Effic :.

The pr chopoint was the average distance (mean standardized) to the central point of the targeı ı >> >scular zone over the period the patient was connected to the Navigator™.

instrated non-inferiority to Navigator over conventional care. There was no The st: statist i significant difference between the two treatment arms with regards to the mean standa • · I distance to the central point of the cardiovascular zone.

Safet . : :ts:
on'ts cnrolled in the study were included in the safety evaluation. Adverse events All 11. e. Irom the time that the patient was connected to Navigator™ until the follow up were c

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visit. follow	us adverse events were collected from the time the patient was randomized until the visit.
Four hNavigstudy.	ed and thirteen (413) adverse events involving 99 patients (52 (88.1%) patients in the Navigator™ arm and 47 (88.7%) patients on the conventional care arm) were reported during the study.
The mohaemoby patihave a	equently reported adverse events were anaemia, hyperglycaemia, decreased in, hypotension and abnormal blood glucose. None of the adverse events experienced on the Navigator™ arm or the conventional care arm of the study were considered to ionship to the device.
One paconsidevents	was withdrawn from the study due to an adverse event (cardiac tamponade one serious but not related to the device). Two patients died during the study due to idered to be not related to the device.
Ten (1comp'correctcategor	vi re incidents occurred during the study, but none were associated with any clinical ns. All occurrences were recognizable by the operator or physician, and necessary were made in the production device. These incidents fell into the following
•Focc	urrences of Navigator screen buttons or settings that did not function as intended. These were recognizable by the operator.
•Foudat	urrences of data communication problems with peripheral equipment or failure to display peripheral equipment.
•Onesta	urrence where a Swan-Ganz catheter appeared to be incorrectly positioned on x-ray and confident of MAP, CO and CI readings.
•Onewa	errence where a discrepancy was reported with MAP display when an aortic balloon pump te.
Thirtyon the cconsid	) serious adverse events involving 24 patients (12 on the Navigator™ arm and 12 ional care arm) were reported during the study. No serious adverse events were e device related.
Reviewfrequer	rse events per treatment group, suggested no trends in the presentation (type, severity) of adverse events per study arm.
Conc
The s'tstatiststand:	instrated non-inferiority to Navigator over conventional care. There was no aificant difference between the two treatments arms with regards to the mean stance to the central point of the cardiovascular zone.
The inarms, wevents	of adverse events and serious adverse events was comparable across the two study ends in the type, frequency or severity of event. No adverse or serious adverse asidered to be related to Navigator™.
Deviccomp	ts which occurred during the study were not associated with any clinical and did not impact on patient safety.
Data	at the use of Navigator™ is safe when compared to conventional ICU care.
Subs	Equivalence
Applierinstruc	logy Pty Ltd believes that the Navigator is safe and effective when used as nowledgeable and trained personnel. Navigator performs at least as safely and

effec! onventional care using predicate devices, and is therefore substantially equivalent to the n rketed predicate device(s).

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Image /page/4/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle with three stripes forming its wing and body. The eagle is oriented diagonally, facing upwards and to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Room -WO66-G609 Silver Spring, MD 20993-0002

MAY 12 2010

Applied Physiology Pty., Ltd. c/o-Mr .- Robert-N .- Clark ---President and Senior Consultant Medical Device Regulatory Advisors, Inc. 4251 Kipling Street, Suite 565 Wheat Ridge, CO 80033-2899

Re: K092219

Device Name: Navigator™ Clinical Guidance System Regulation Number: 21 CFR 870.1435 Regulation Name: Single function pre-programmed diagnostic computer Regulatory Class: Class II (Two) Product Code: DXG Dated: April 30, 2010 Received: May 7, 2010

Dear Mr. Clark

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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.

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Page 2 - Mr. Robert N. Clark

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please go to http://www.fda.gov/AboutFDA/CentersOffices/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

am D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

K092219 - - -510(k) Number (if known): __

Device Name: Navigator™

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

Over-The-Counter Use (21 CFR 801 Subpart C)

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)

Division di Cardiovascular Devices 510(k) Number 120922

Regulation Number and Section

§ 870.1435 Single-function, preprogrammed diagnostic computer.

(a)
Identification. A single-function, preprogrammed diagnostic computer is a hard-wired computer that calculates a specific physiological or blood-flow parameter based on information obtained from one or more electrodes, transducers, or measuring devices.(b)
Classification. Class II (performance standards).