CathWorks FFRangio™ is a software device for the clinical quantitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio™, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRangio™ analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio™ are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional evaluation.

Device Description

FFRancio uses standard angiographic images that are retrieved from the X-ray Imaging System (C-arm) in DICOM format. The user selects the images and, following the system prompts, marks key features on the images including the target lesion, ostium location, main vessel, target vessel, and its side branches. The system then matches the corresponding vessels among the projections and generates a 3D computer model of the vessels. The 3D model is used for blood flow analysis and determination of the FFRangio.

The modified FFRangio system, designated as model FAU4000, consists of the following components:

Touch screen control console located either as a fixed installation in the cath lab on . an extension arm mounted on the wall or from the ceiling, or on a desktop or mobile cart in the cath lab or control room
Processing Unit located in the cath lab machine room / control room ●
3D Mouse located at the patient bedside ●
Connection Box located in either the cath lab or control room ●

The system supports optional visual media output to the cath lab main displays, so the system GUI may be observed on both the system's Console display and on the cath lab's main display (boom monitor).

AI/ML Overview

The provided text describes a Special 510(k) submission for the FFRangio System, focusing on hardware and software changes to a previously cleared device. Therefore, the information regarding the acceptance criteria and the study proving the device meets these criteria primarily refers to the original FFRangio System (K182149), as the current submission (K192442) asserts that the changes do not affect the fundamental scientific technology or the indications for use.

Here's a breakdown of the requested information based on the provided text:

Acceptance Criteria and Device Performance

The core performance metrics presented are Sensitivity and Specificity, which were established during the pivotal clinical study of the predicate (original) FFRangio System.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria (from predicate study)	Reported Device Performance (from predicate study)
Sensitivity (Lower 95% CI)	93.5% (lower 95% CI, 87.8%)
Specificity (Lower 95% CI)	91.2% (lower 95% CI, 86.0%)

2. Sample Size and Data Provenance

The document does not explicitly state the sample size used for the test set of the original pivotal clinical study, nor does it specify the country of origin or whether the data was retrospective or prospective. It only mentions "the FFRangio pivotal clinical study."

For the current 510(k) submission (K192442), which pertains to modifications, the performance data cited is from the previous clearance. The specific tests conducted for this Special 510(k) (e.g., software validation, electrical safety, human factors) are not for clinical performance.

3. Number of Experts and Qualifications for Ground Truth Establishment

The document does not provide details on the number of experts or their specific qualifications (e.g., "radiologist with 10 years of experience") used to establish the ground truth for the pivotal clinical study. It refers to the FFRangio pivotal clinical study generally.

4. Adjudication Method for the Test Set

The document does not specify the adjudication method (e.g., 2+1, 3+1, none) used for the test set of the original pivotal clinical study.

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

The document does not indicate that a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done to show how much human readers improve with AI vs. without AI assistance. The described "FFRangio pivotal clinical study" provided standalone performance metrics (sensitivity and specificity).

6. Standalone (Algorithm Only) Performance

Yes, a standalone performance evaluation was implicitly done, as the sensitivity and specificity values are presented as performance characteristics of the FFRangio system itself, independent of human-in-the-loop performance improvement. These metrics ("Sensitivity* and specificity are the per vessel estimates as determined from the FFRangio pivotal clinical study") describe the algorithm's diagnostic accuracy.

7. Type of Ground Truth Used

The document does not explicitly state the type of ground truth used (e.g., expert consensus, pathology, outcomes data) for the FFRangio pivotal clinical study.

8. Sample Size for the Training Set

The document does not provide information about the sample size used for the training set.

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

The document does not provide information on how the ground truth for the training set was established.

Summary

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December 9, 2019

CathWorks Ltd % Sheila Hemeon-Heyer President Heyer Regulatory Solutions LLC 125 Cherry Lane Amherst, Massachusetts 01002

Re: K192442

Trade/Device Name: FFRangio System Regulation Number: 21 CFR 870.1415 Regulation Name: Coronary Vascular Physiologic Simulation Software Device Regulatory Class: Class II Product Code: QEK Dated: November 14, 2019 Received: November 18, 2019

Dear Sheila Hemeon-Heyer:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.

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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Stephen Browning Assistant Director Division of Cardiac Electrophysiology, Diagnostics and Monitoring Devices Office of Cardiovascular Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K192442

Device Name

FFRangio™ System

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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Special 510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted per the requirements of 21 CFR 807.92.

A.	Submitter: Heyer Regulatory Solutions LLCP.O. Box 2151Amherst, MA 01004-2151Contact: Sheila Hemeon-HeyerSheila@heyer-regulatory.com
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B. Manufacturer: CathWorks, Ltd. Contact: Miriam Ivenshitz 3 Rappaport St. Kfar Saba 4465141, ISRAEL Tel: +972 9 7467387 miriam@cath.works

C. Date Prepared: November 12, 2019

D. Device Name and Classification Information:

Trade Name:	FFRangioTM System
Common/Usual Name:	Digital FFR System
Classification Name:	Coronary Vascular Physiologic Simulation Software
Regulation:	21 CFR 870.1415
Product Code:	QEK
Review Panel:	Cardiovascular
Class:	II

E. Predicate Device(s): K182149 FFRangio™ System

F. Summary Device Description:

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The modified FFRangio system, designated as model FAU4000, consists of the following components:

Touch screen control console located either as a fixed installation in the cath lab on . an extension arm mounted on the wall or from the ceiling, or on a desktop or mobile cart in the cath lab or control room
Processing Unit located in the cath lab machine room / control room ●
3D Mouse located at the patient bedside ●
Connection Box located in either the cath lab or control room ●

Image /page/4/Picture/7 description: The image shows a medical imaging machine in a hospital room. The machine has a large, curved arm with a monitor attached to it. There is also a table in the center of the room, and another monitor is suspended above the table. The room is clean and well-lit, and the equipment appears to be modern and advanced.

G. Indications for Use Statement:

CathWorks FFRangio is a software device for the clinical quantitative and qualitative analysis of previously acquired angiography DICOM data for patients with coronary artery disease. It provides FFRangio, a mathematically derived quantity, computed from simulated blood flow information obtained from a 3D computer model, generated from coronary angiography images. FFRango analysis is intended to support the functional evaluation of coronary artery disease. The results of this analysis are provided as a supportive aid for qualified clinicians in the evaluation and assessment of coronary arteries physiology. The results of CathWorks FFRangio are intended to be used by qualified clinicians in conjunction with the patient's clinical history, symptoms, and other diagnostic tests, as well as the clinician's professional evaluation.

H. Comparison with Predicate Device

This is a Special 510(k) for hardware and software changes to the previously cleared FFRance ™ System. These changes do not alter the fundamental scientific technology of

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the device or the indications for use. There have been no changes to the underlying data processing algorithm. The changes are implemented primarily to improve the system ease of use.

The table below provides a technological comparison between the modified and previously cleared FFRangio Systems. Discussion of the differences is provided following the table.

	Predicate FFRangioTM(model FAU1000)	Modified FFRangio TM(model FAU4000)
Indications forUse	CathWorks FFRangio is a software device forthe clinical quantitative and qualitativeanalysis of previously acquired angiographyDICOM data for patients with coronary arterydisease. It provides FFRangio, amathematically derived quantity, computedfrom simulated blood flow informationobtained from a 3D computer model,generated from coronary angiographyimages. FFRangio analysis is intended tosupport the functional evaluation of coronaryartery disease. The results of this analysisare provided as a supportive aid for qualifiedclinicians in the evaluation and assessmentof coronary arteries physiology. The resultsof CathWorks FFRangio are intended to beused by qualified clinicians in conjunctionwith the patient's clinical history, symptoms,and other diagnostic tests, as well as theclinician's professional evaluation.	CathWorks FFRangio is a software device forthe clinical quantitative and qualitativeanalysis of previously acquired angiographyDICOM data for patients with coronary arterydisease. It provides FFRangio, amathematically derived quantity, computedfrom simulated blood flow informationobtained from a 3D computer model,generated from coronary angiographyimages. FFRangio analysis is intended tosupport the functional evaluation of coronaryartery disease. The results of this analysisare provided as a supportive aid for qualifiedclinicians in the evaluation and assessmentof coronary arteries physiology. The resultsof CathWorks FFRangio are intended to beused by qualified clinicians in conjunctionwith the patient's clinical history, symptoms,and other diagnostic tests, as well as theclinician's professional evaluation.
Systemoverview	Computer system with software thatconstructs and displays a 3D computermodel of the coronary arteries to simulateblood flow	Computer system with software thatconstructs and displays a 3D computermodel of the coronary arteries to simulateblood flow
Systemcomponentsand setup	LCD screen with keyboard and mouseHewlett-Packard HPz240 Tower WorkstationSystem on a moveable cart in the cath labConnections to enable display on the cathlab boom monitor	Touchscreen console with virtual keyboardand mouseHewlett-Packard Z2 Tower WorkstationWorkstation in the cath lab control room ormachine room and console in a fixed locationor on moveable cart in the cath lab or controlroomConnections to enable display on the cathlab boom monitorOptional 3D mouse mounted on the patientbedrail used to rotate and zoom the 3Dvessel image that appears on the Resultsscreen on the cath lab main display. Notused during FFRangio processing.Optional connection box, which can belocated in the control room or in the cath labfor optional additional display on an AUXmonitor in the control room by means of a
	Predicate FFRangioTM(model FAU1000)	Modified FFRangioTM(model FAU4000)
		communication between the 3D mouse andconsole if the console is located outside ofthe cath lab procedure room.
Image source	Standard DICOM angiographic imagestaken in Cath Lab	Standard DICOM angiographic images takenin Cath Lab
Softwarecontrolled	Yes	Yes
Real-timeresults	Yes	Yes
Sensitivity*	93.5% (lower 95% CI, 87.8%)	93.5% (lower 95% CI, 87.8%)
Specificity*	91.2% (lower 95% CI, 86.0%)	91.2% (lower 95% CI, 86.0%)

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*Sensitivity and specificity are the per vessel estimates as determined from the FFRango pivotal clinical study. The changes described in this Special 510(k) do not affect the system sensitivity or specificity,

Discussion of Differences

The modified FFRango System has the same intended use/indications for use, uses the same imaging source for system input (standard core lab angiograms), and same data processing algorithms to determine the FFRance. The system components and system operation are essentially the same as the originally cleared system.

The key differences between the original and modified FFRangio™ Systems are:

Both the processing unit and console components of the original system were . resident on a mobile cart in the cath lab. The modified system offers an approach that allows for different physical configurations, i.e., there can be a physical separation between the system components when the processing unit is located in the cath lab control room and the console is installed in the cath lab or the system units can be located together in the control room.
The original system used an LCD screen with separate keyboard and mouse while . the modified console is a touch screen with mouse.
The modified system offers an optional 3D mouse mounted on the patient bed rail ● that allows the physician to rotate and zoom to view the 3D coronary vessel image that appears on the Results screen after FFRancio processing. The 3D mouse communicates with the system console via wireless Bluetooth.
An optional connection box is available for the modified system that enables . display on an AUX monitor in the control room by means of a DVI Video cable or for Bluetooth communication between the 3D mouse and console if the console is located outside of the cath lab procedure room.

In addition, minor changes have been made to the workflow software and user interface to reduce idle time and improve the user experience. None of these changes affect the

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indications for use, fundamental scientific technology, or raise new questions of safety or effectiveness of the CathWorks FFRangio.

l. Performance Data to Support Substantial Equivalence

The hardware and software modifications to the FFRanco System were implemented under the CathWorks design controls that are compliant with 21 CFR 820.30. A risk analysis was conducted in accordance with ISO 14971:2007 Medical devices - Application of risk management to medical devices to assess the risks and risk mitigations for the device hardware and software modifications. Based on this risk assessment, the following verification tests were identified and conducted. All tests met the pre-defined acceptance criteria and were passed.

Software Validation: Software documentation consistent with FDA's guidance "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices," May 11, 2005, for moderate level of concern software including a comprehensive risk analysis of the changes, software verification and validation, off-the-shelf software integrity, and cybersecurity considerations. The software in the FFRancis complies with ISO 62304:2015 Medical device software - Software life cycle processes.

Electrical Safety Testing: The FFRangio computer system components were evaluated and found to be in compliance with the applicable requirements of IEC 60601-1:2005 (30 Edition) +C1:2006 +C2:2007 +A1:2012, "Medical electrical equipment - Part 1: General requirements for basic safety and essential performance." All emissions and immunity tests were passed.

Electromagnetic Compatibility Testing: The FFRangio computer system components were tested and found to be in compliance with the applicable requirements of IEC 60601-1-2:2014 (4th edition), "Medical electrical equipment - Part 1-2: General requirements for basic safety and essential performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests."

FCC Compliance Testing: The 3D Mouse and receiver were tested and found to be in compliance with FCC Part 15, Subpart C, Sections 15.203, 15.205, 15.207, 15.209, and 15.249 for RF wireless communications systems operating in frequency range 2404-2477 Mhz. Measurements were in compliance with ANSI C63.4-2003 American National Standards of Measurement of Radio-Noise emissions from Low-Voltage Electrical and Electronic Equipment in the range of 9 KHz to 40 GHz.

Hardware Verification Testing: The FFRango computer system components and system connections underwent type testing per an internal CathWorks protocol. All hardware requirements of the system were evaluated/tested and found to meet the pre-defined acceptance criteria.

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Transportation Testing: The FFRancio computer system components and accessories are shipped in a padded, wooden box. Environmental conditioning was conducted in accordance with ASTM D4332-14 "Standard Practice for Conditioning Containers, Packages, or Package Components." Transportation testing was conducted in accordance with ASTM D4169-16, "Standard Practice for Performance Testing of Shipping Containers and Systems." All tests were passed.

Human Factors Testing: Usability testing of the modified FFRancio system and its operator manual was conducted in accordance with ANSI/AAMI/IEC 62366-1:2015, "Application of usability engineering to medical devices" and the FDA guidance document "Applying Human Factors and Usability Engineering to Medical Devices," February 3, 2016. Fifteen participants performed all of the tasks necessary to process an FFRango using the modified workflow and user manual while the test moderator observed each user performance throughout the individual steps. This was followed by a knowledge-based assessment of the labeling, warnings and precautions and analysis process. All critical tasks identified for the use of the FFRangio system were completed in the usability testing without any use errors. The conclusion of the testing was that the FFRancis system can be used safely and effectively by the intended user population. No residual use-related risks were identified.

No clinical testing was necessary to support the device modifications described in this Special 510(k).

Special Controls (abbreviated fromregulation)	How Fulfilled
1) Adequate software verification andvalidation based on comprehensivehazard analysis, with identification ofappropriate mitigations, must beperformed.	The changes to the FFRangio system software weredeveloped, implemented and tested in accordancewith ISO 62304:2006 Medical device software --Software life cycle processes and includedcomprehensive hazard analysis, identification ofappropriate risk mitigations, and software testingappropriate to verify the changes in the workflowsoftware. There were no changes to the FFRangiosoftware algorithms. Documentation as requiredby FDA's "Guidance for the Content of PremarketSubmissions for Software Contained in MedicalDevices" for moderate level of concern softwarewas provided.
2. Adequate non-clinical performancetesting must be provided to demonstrate thevalidity of computational modeling methodsfor flow measurement.	Not applicable. There have been no changes tothe computational modeling methods for flowmeasurement.
3. Clinical data supporting the proposedintended use must be provided.	Not applicable. None of the changes documented inthis Special 510(k) required clinical testing.
Special Controls (abbreviated fromregulation)	How Fulfilled
(4) Adequate validation must be performedand controls implemented to characterizeand ensure consistency (repeatability andreproducibility) of measurement output.	Not applicable. None of the changes documented inthis Special 510(k) could affect the repeatability andreproducibility of the measurement output.
(5) Human factors evaluation and validationmust be provided to demonstrate adequateperformance of the user interface to allow forusers to accurately measure intendedparameters, particularly where parametersettings that have impact on measurementsrequire significant user intervention.	A human factors study was conducted in accordancewith FDA's Guidance Applying Human Factors andUsability Engineering to Medical Devices, 2016. Allcritical tasks identified for the use of the FFRangiosystem were completed in the usability testing withoutany use errors. The conclusion of the testing was thatthe FFRangio system can be used safely and effectivelyby the intended user population. No residual use-related risks were identified.
(6) Device labeling must be provided thatadequately describes the following:(i) The device's intended use,(ii) Appropriate warnings(iii) Key assumptions(iv) The measurement performance of thedevice for all presented parameters(v) A detailed description of the clinicalstudy subjects and results(vi) A detailed description of the analysisprocedure using the device and anydata features that could affect accuracyof results.	The device instructions for use include all of theelements required by this special control, including:Intended use statement, the devicemechanism of action and intended patientpopulation Appropriate warnings and precautions for safeuse of the device, including factors that couldadversely affect the device output and cautionsto use the device output in context with otherclinical factors for patient care Limitations describing patient populationsand lesion types for which the safety andeffectiveness of FFRangio has not beenevaluated Instructions for use providing guidelines for thecompatible image acquisition systems and therequired criteria for the images to process theFFRangio. Detailed steps for the system operation andanalysis procedures A detailed summary of the FAST-FFR clinicalstudy protocol

J. Compliance with Special Controls for 21 CFR 870.1415

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K. Conclusion

The information and testing presented in this 510(k) demonstrate that the modified CathWorks FFRangio is substantially equivalent to the original CathWorks FFRangio cleared under K182149.

Regulation Number and Section

§ 870.1415 Coronary vascular physiologic simulation software device.

(a)
Identification. A coronary vascular physiologic simulation software device is a prescription device that provides simulated functional assessment of blood flow in the coronary vascular system using data extracted from medical device imaging to solve algorithms and yield simulated metrics of physiologic information (e.g., blood flow, coronary flow reserve, fractional flow reserve, myocardial perfusion). A coronary vascular physiologic simulation software device is intended to generate results for use and review by a qualified clinician.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Adequate software verification and validation based on comprehensive hazard analysis, with identification of appropriate mitigations, must be performed, including:
(i) Full characterization of the technical parameters of the software, including:
(A) Any proprietary algorithm(s) used to model the vascular anatomy; and
(B) Adequate description of the expected impact of all applicable image acquisition hardware features and characteristics on performance and any associated minimum specifications;
(ii) Adequate consideration of privacy and security issues in the system design; and
(iii) Adequate mitigation of the impact of failure of any subsystem components (
e.g., signal detection and analysis, data storage, system communications and cybersecurity) with respect to incorrect patient reports and operator failures.(2) Adequate non-clinical performance testing must be provided to demonstrate the validity of computational modeling methods for flow measurement; and
(3) Clinical data supporting the proposed intended use must be provided, including the following:
(i) Output measure(s) must be compared to a clinically acceptable method and must adequately represent the simulated measure(s) the device provides in an accurate and reproducible manner;
(ii) Clinical utility of the device measurement accuracy must be demonstrated by comparison to that of other available diagnostic tests (
e.g., from literature analysis);(iii) Statistical performance of the device within clinical risk strata (
e.g., age, relevant comorbidities, disease stability) must be reported;(iv) The dataset must be adequately representative of the intended use population for the device (
e.g., patients, range of vessel sizes, imaging device models). Any selection criteria or limitations of the samples must be fully described and justified;(v) Statistical methods must consider the predefined endpoints:
(A) Estimates of probabilities of incorrect results must be provided for each endpoint,
(B) Where multiple samples from the same patient are used, statistical analysis must not assume statistical independence without adequate justification, and
(C) The report must provide appropriate confidence intervals for each performance metric;
(vi) Sensitivity and specificity must be characterized across the range of available measurements;
(vii) Agreement of the simulated measure(s) with clinically acceptable measure(s) must be assessed across the full range of measurements;
(viii) Comparison of the measurement performance must be provided across the range of intended image acquisition hardware; and
(ix) If the device uses a cutoff threshold or operates across a spectrum of disease, it must be established prior to validation, and it must be justified as to how it was determined and clinically validated;
(4) Adequate validation must be performed and controls implemented to characterize and ensure consistency (
i.e., repeatability and reproducibility) of measurement outputs:(i) Acceptable incoming image quality control measures and the resulting image rejection rate for the clinical data must be specified, and
(ii) Data must be provided within the clinical validation study or using equivalent datasets demonstrating the consistency (
i.e., repeatability and reproducibility) of the output that is representative of the range of data quality likely to be encountered in the intended use population and relevant use conditions in the intended use environment;(A) Testing must be performed using multiple operators meeting planned qualification criteria and using the procedure that will be implemented in the production use of the device, and
(B) The factors (
e.g., medical imaging dataset, operator) must be identified regarding which were held constant and which were varied during the evaluation, and a description must be provided for the computations and statistical analyses used to evaluate the data;(5) Human factors evaluation and validation must be provided to demonstrate adequate performance of the user interface to allow for users to accurately measure intended parameters, particularly where parameter settings that have impact on measurements require significant user intervention; and
(6) Device labeling must be provided that adequately describes the following:
(i) The device's intended use, including the type of imaging data used, what the device measures and outputs to the user, whether the measure is qualitative or quantitative, the clinical indications for which it is to be used, and the specific population for which the device use is intended;
(ii) Appropriate warnings specifying the intended patient population, identifying anatomy and image acquisition factors that may impact measurement results, and providing cautionary guidance for interpretation of the provided measurements;
(iii) Key assumptions made in the calculation and determination of simulated measurements;
(iv) The measurement performance of the device for all presented parameters, with appropriate confidence intervals, and the supporting evidence for this performance. Per-vessel clinical performance, including where applicable localized performance according to vessel and segment, must be included as well as a characterization of the measurement error across the expected range of measurement for key parameters based on the clinical data;
(v) A detailed description of the patients studied in the clinical validation (
e.g., age, gender, race or ethnicity, clinical stability, current treatment regimen) as well as procedural details of the clinical study (e.g., scanner representation, calcium scores, use of beta-blockers or nitrates); and(vi) Where significant human interface is necessary for accurate analysis, adequately detailed description of the analysis procedure using the device and any data features that could affect accuracy of results.