Brainomix 360 e-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

The software automatically registers images and uses an atlas to segment and analyze ASPECTS regions. Brainomix 360 e-ASPECTS extracts image data from individual voxels in the image to provide analysis and computer analytics and relates the analysis to the atlas defined ASPECTS regions. The imaging features are then synthesized by an artificial intelligence algorithm into a single ASPECTS (Alberta Stroke Program Early CT) score.

Brainomix 360 e-ASPECTS is indicated for evaluation of patients presenting for diagnostic imaging workup for evaluation of extent of disease. Extent of disease refers to the number of ASPECTS regions affected which is reflected in the total score. Brainomix 360 e-ASPECTS provides information that may be useful in the characterization of ischemic brain tissue injury during image interpretation (within 24 hours from time last known well).

Brainomix 360 e-ASPECTS provides a comparative analysis to the ASPECTS standard of care radiologist assessment by providing highlighted ASPECTS regions and an automated editable ASPECTS score for clinician review. Brainomix 360 e-ASPECTS additionally provides a visualization of the voxels contributing to and excluded from the automated ASPECTS score, and a calculation of the voxel volume contributing to ASPECTS score.

Limitations:

Brainomix 360 e-ASPECTS is not intended for primary interpretation of CT images. It is used to assist physician evaluation.
The Brainomix 360 e-ASPECTS score should be only used for ischemic stroke patients following the standard of care.
Brainomix 360 e-ASPECTS has only been validated and is intended to be used in patient populations aged over 21 years.
Brainomix 360 e-ASPECTS is not intended for mobile diagnostic use. Images viewed on a mobile platform are compressed preview images and not for diagnostic interpretation.
Brainomix 360 e-ASPECTS has been validated and is intended to be used on Siemens Somatom Definition scanners.

Contraindications/ Exclusions/Cautions:

· Patient motion: Excessive patient motion leading to artifacts that make the scan technically inadequate.
· Hemorrhagic Transformation, Hematoma.

Device Description

Brainomix 360 e-ASPECTS (also referred to as e-ASPECTS in this submission) is a medical image visualization and processing software package compliant with the DICOM standard and running on an off-the-shelf physical or virtual server.

Brainomix 360 e-ASPECTS allows for the visualization, analysis and post-processing of DICOM compliant Non-contrast CT (NCCT) images which, when interpreted by a trained physician or medical technician, may yield information useful in clinical decision making.

Brainomix 360 e-ASPECTS is a stand-alone software device which uses machine learning algorithms to automatically process NCCT brain image data to provide an output ASPECTS score based on the Alberta Stroke Program Early CT Score (ASPECTS) guidelines.

The post-processing image results and ASPECTS score are identified based on regional imaging features and overlayed onto brain scan images. e-ASPECTS provides an automatic ASPECTS score based on the input CT data for the physician. The score includes which ASPECTS regions are identified based on regional imaging features derived from NCCT brain image data. The results are generated based on the Alberta Stroke Program Early CT Score (ASPECTS) guidelines and provided to the clinician for review and verification. At the discretion of the clinician, the scores may be adjusted based on the clinician's judgment.

Brainomix 360 e-ASPECTS can connect with other DICOM-compliant devices, for example to transfer NCCT scans from a Picture Archiving and Communication System (PACS) to Brainomix 360 e-ASPECTS software for processing.

Results and images can be sent to a PACS via DICOM transfer and can be viewed on a PACS workstation or via a web user interface on any machine contained and accessed within a hospital network and firewall and with a connection to the Brainomix 360 e-ASPECTS software (e.g. a LAN connection).

Brainomix 360 e-ASPECTS notification capabilities enable clinicians to preview images through a mobile application or via e-mail.

Brainomix 360 e-ASPECTS email notification capabilities enable clinicians to preview images via e-mail notification with result image attachments. Images that are previewed via e-mail are compressed, are for informational purposes only, and not intended for diagnostic use beyond notification.

Brainomix 360 e-ASPECTS is not intended for mobile diagnostic use. Notified clinicians are responsible for viewing non-compressed images on a diagnostic viewer and engaging in appropriate patient evaluation and relevant discussion with a treating physician before making care-related decisions or requests.

Brainomix 360 e-ASPECTS provides an automated workflow which will automatically process image data received by the system in accordance with pre-configured user DICOM routing preferences.

Once received, image processing is automatically applied. Once any image processing has been completed, notifications are sent to pre-configured users to inform that the image processing results are ready. Users can then access and review the results and images via the web user interface case viewer or PACS viewer.

The core of e-ASPECTS algorithm (excluding image loading or result output format) can be summarised in the following 3 key steps of the processing pipeline:

Pre-processing: brain extraction from the three dimensional (3D) non-enhanced contrast CT head dataset and its reorientation/normalization by 3D spatial registration to a standard template space.
Delineation of the 20 (10 for each cerebral hemisphere) pre-defined ASPECTS regions of interest on the normalized 3D image.
Image feature extraction and heatmap generation which consists of the computation of numerical values characterizing brain tissue, apply a trained predictive model to those features and generate a 3D heatmap from the models output for highlighting regions contributing towards the ASPECTS score.

The Brainomix 360 e-ASPECTS module is made available to the user through the Brainomix 360 platform. The Brainomix 360 platform is a central control unit which coordinates the execution image processing modules which support various analysis methods used in clinical practice today:

Brainomix 360 e-ASPECTS (K221564) (predicate device)
Brainomix 360 e-CTA (K192692)
Brainomix 360 e-CTP (K223555)
Brainomix 360 e-MRI (K231656)
Brainomix 360 Triage ICH (K231195)
Brainomix 360 Triage LVO (K231837)
Brainomix 360 Triage Stroke (K232496)

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study proving the device's performance, based on the provided text:

Brainomix 360 e-ASPECTS Device Performance Study

The Brainomix 360 e-ASPECTS device underwent performance testing to demonstrate its accuracy and effectiveness. This included both standalone algorithm performance and a multi-reader multi-case (MRMC) study to assess the impact of AI assistance on human readers.

1. Acceptance Criteria and Reported Device Performance

Digital Phantom Validation (for "volume contributing to e-ASPECTS")

Metric Name	Acceptance Criteria	Reported Performance	Pass/Fail
Absolute Bias (upper 95% CI)	< 12 mL	7.61 mL	Pass
Standard Deviation (upper 95% CI)	< 19 mL	1.99 mL	Pass
Pearson's correlation - r (lower 95% CI)	> 0.86	0.993	Pass

Standalone Performance Testing (for ASPECTS score accuracy)

Metric Name	Acceptance Criteria (Implied by positive results)	Reported Performance (Model only)	Outcome
AUC	High diagnostic accuracy	83% (95% CI: 80-86%)	Good
Sensitivity	Good detection of affected regions	69% (56-75%)	Good
Specificity	Good identification of unaffected regions	97% (80-97%)	Good

Multi-Reader Multi-Case (MRMC) Study (Human + AI vs. Human only for ASPECTS score accuracy)

Metric Name	Acceptance Criteria (Implied by statistical significance)	Reported Performance (Human only)	Reported Performance (Human + AI assistance)	Effect Size (Improvement)	Statistical Significance
AUC	Improvement in AUC with AI assistance	78%	85%	6.4%	p=.03 (statistically significant)
Sensitivity	Improvement in Sensitivity with AI assistance	61%	72%	11%	Not explicitly stated as statistically significant, but driving AUC improvement
Specificity	Improvement in Specificity with AI assistance	96%	98%	2%	Not explicitly stated as statistically significant, but contributing to AUC improvement
Cohen's Kappa	Improvement with AI assistance	Not explicitly stated	Improved significantly	-	Significantly improved
Weighted Kappa	Improvement with AI assistance	Not explicitly stated	Improved significantly	-	Significantly improved

2. Sample Sizes and Data Provenance

Digital Phantom Validation Test Set: n=110 synthetic datasets
Standalone Performance Test Set: n=137 non-contrast CT scans
- Data Provenance: From 3 different USA institutions (Siemens, GE, Philips, and Toshiba scanners).
- Retrospective/Prospective: The data appears to be retrospective based on the description of patient admission dates (March 2012 and August 2023) and clinical context.
MRMC Study Test Set: n=140 NCCT scans
- Data Provenance: Cases collected from various clinical sites (specific countries not explicitly stated, but the mention of US neuroradiologists for ground truth suggests US data). Scanners included Siemens, GE, Philips, and Toshiba.
- Retrospective/Prospective: The study used "retrospective data" (explicitly stated on page 12).
Training Set Sample Size: The document does not specify the sample size for the training set. It mentions the algorithm is based on "machine learning" and a "trained predictive model" but provides no details on the training data.

3. Number of Experts and Qualifications for Ground Truth Establishment

Standalone Performance Test Set: Three board-certified US neuroradiologists. No information on years of experience is provided.
MRMC Study Test Set: Three board-certified US neuroradiologists for establishing the ground truth that human readers were compared against. No information on years of experience is provided.

4. Adjudication Method for the Test Set(s) Ground Truth

Standalone Performance Test Set: "Consensus of three board-certified US neuroradiologists." This implies that the ground truth was established by agreement among the three experts. The specific method (e.g., 2-out-of-3, or discussion to reach full consensus) is not detailed, but "consensus" suggests agreement.
MRMC Study Test Set: "Consensus of three board-certified US neuroradiologists." Similar to the standalone study, ground truth was established by consensus.

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

Was it done?: Yes, an MRMC study was conducted.
Effect Size: The study showed a 6.4% improvement in AUC for readers with e-ASPECTS support (85%) compared to without e-ASPECTS support (78%). This improvement was statistically significant (p=.03). There was also an improvement in sensitivity (from 61% to 72%) and a small improvement in specificity (from 96% to 98%). Cohen's Kappa and weighted Kappa also improved significantly.
Readers: 7 clinical readers (1 "expert" neuroradiologist and 6 "non-expert" radiologists or neurologists).

6. Standalone Performance (Algorithm Only)

Was it done?: Yes, a standalone performance testing was conducted.
Performance Metrics: The algorithm achieved an AUC of 83% (95% CI: 80-86%), with a sensitivity of 69% (56-75%) and a specificity of 97% (80-97%) on a case-level as compared to expert consensus. Area under the curve (AUC) specifically refers to overall region-level performance.

7. Type of Ground Truth Used

Digital Phantom Validation: Synthetic volumes/known phantom volumes.
Standalone Performance Testing: Expert consensus (of three board-certified US neuroradiologists).
MRMC Study: Expert consensus (of three board-certified US neuroradiologists).

8. Sample Size for the Training Set

The document does not provide a specific sample size for the training set. It only states that the device uses "machine learning algorithms" and a "trained predictive model."

9. How Ground Truth for Training Set Was Established

The document does not describe how the ground truth for the training set was established. It only refers to a "trained predictive model."

Summary

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February 14, 2025

Brainomix Limited Delanyo Mensah Regulatory Affairs Specialist First Floor, Seacourt Tower West Way Oxford. OX2 0JJ United Kingdom

Re: K243294

Trade/Device Name: Brainomix 360 e-ASPECTS Regulation Number: 21 CFR 892.2060 Regulation Name: Radiological computer-assisted diagnostic software for lesions suspicious of cancer Regulatory Class: Class II Product Code: POK Dated: October 18, 2024 Received: January 17, 2025

Dear Delanyo Mensah:

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 (the 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 available 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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510/k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change reguires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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.

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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.

Jessica Lamb

Jessica Lamb, Ph.D. Assistant Director Imaging Software Team DHT8B: Division of Radiological Imaging Devices and Electronic Products OHT8: Office of Radiological Health 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) K243294

Device Name Brainomix 360 e-ASPECTS

Indications for Use (Describe)

Brainomix 360 e-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

The software automatically registers images and uses an atlas to segment and analyze ASPECTS regions. Brainomix 360 e-ASPECTS extracts image data from individual voxels in the image to provide analysis and relates the analysis to the atlas defined ASPECTS regions. The imaging features are then synthesized by an artificial intelligence algorithm into a single ASPECTS (Alberta Stroke Program Early CT) score.

Brainomix 360 e-ASPECTS is indicated for evaluation of patients presenting for diagnostic imaging workup for evaluation of extent of disease. Extent of disease refers to the number of ASPECTS regions affected in the total score. Brainomix 360 e-ASPECTS provides information that may be useful in the characterization of ischemic brain tissue injury during image interpretation (within 24 hours from time last known well).

Limitations:

Brainomix 360 e-ASPECTS is not intended for primary interpretation of CT images. It is used to assist physician evaluation.
The Brainomix 360 e-ASPECTS score should be only used for ischemic stroke patients following the standard of care.
Brainomix 360 e-ASPECTS has only been validated and is intended to be used in patient populations aged over 21 years.
Brainomix 360 e-ASPECTS is not intended for mobile diagnostic use. Images viewed on a mobile platform are compressed preview images and not for diagnostic interpretation.
Brainomix 360 e-ASPECTS has been validated and is intended to be used on Siemens Somatom Definition scanners.

Contraindications/ Exclusions/Cautions:

· Patient motion: Excessive patient motion leading to artifacts that make the scan technically inadequate.

· Hemorrhagic Transformation, Hematoma.

Type of Use (Select one or both, as applicable)

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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Image /page/5/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon is a gradient of light blue to white, and the letters "AI" in the word "BRAINOMIX" are also in the same light blue gradient, while the rest of the letters are in dark gray.

K243294

510(K) Summary Brainomix Limited – Brainomix 360 e-ASPECTS

Date Prepared:	13Feb2025
Applicant's Name:	Brainomix Limited
Applicant's Address:	First Floor, Seacourt Tower, West WayOxford, OX2 0JJUnited Kingdom
Official Contact:	Delanyo Mensah+44 (0) 7375 967 695regulatory@brainomix.com
Device Proprietary Name:	Brainomix 360 e-ASPECTS
Regulation Name:	Radiological computer-assisted diagnostic software for lesionssuspicious of cancer
Regulatory Class:	Class II
Product Code:	POK
Regulation Number:	21 C.F.R. §892.2060

1. Predicate Device

Brainomix 360 e-ASPECTS is Substantially Equivalent to the following Legally Marketed device:

Trade Name: Brainomix 360 e-ASPECTS Manufacturer: Brainomix Limited Regulation Number: 21 C.F.R. §892.2060 Regulatory Class: Class II Regulation Name: Radiological computer-assisted diagnostic software for lesions suspicious of cancer Product Code: POK Submission Number: K221564

2. Reference Device

Trade Name: Rapid ASPECTS (v3) Manufacturer: iSchemaView, Inc. Regulation Number: 21 C.F.R. §892.2060 Regulatory Class: Class II Regulation Name: Radiological computer-assisted diagnostic software for lesions suspicious of cancer Product Code: POK Submission Number: K232156

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Image /page/6/Picture/0 description: The image shows the logo for BRAINOMIX. To the left of the company name is a teal-colored graphic that resembles a brain. The company name is in all caps and the "A" in BRAINOMIX is also teal.

3. Device Description

Brainomix 360 e-ASPECTS notification capabilities enable clinicians to preview images through a mobile application or via e-mail.

Brainomix 360 e-ASPECTS provides an automated workflow which will automatically process image data received by the system in accordance with pre-configured user DICOM routing preferences.

Once received, image processing is automatically applied. Once any image processing has been completed, notifications are sent to pre-configured users to inform that the image processing

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Image /page/7/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The "A" in "BRAINOMIX" is a slightly different color than the rest of the letters. The brain icon is a gradient of blue and green.

results are ready. Users can then access and review the results and images via the web user interface case viewer or PACS viewer.

The core of e-ASPECTS algorithm (excluding image loading or result output format) can be summarised in the following 3 key steps of the processing pipeline:

Pre-processing: brain extraction from the three dimensional (3D) non-enhanced contrast CT 1. head dataset and its reorientation/normalization by 3D spatial registration to a standard template space.
1. Delineation of the 20 (10 for each cerebral hemisphere) pre-defined ASPECTS regions of interest on the normalized 3D image.
1. Image feature extraction and heatmap generation which consists of the computation of numerical values characterizing brain tissue, apply a trained predictive model to those features and generate a 3D heatmap from the models output for highlighting regions contributing towards the ASPECTS score.

Brainomix 360 e-ASPECTS (K221564) (predicate device)
Brainomix 360 e-CTA (K192692)
Brainomix 360 e-CTP (K223555)
Brainomix 360 e-MRI (K231656)
Brainomix 360 Triage ICH (K231195)
Brainomix 360 Triage LVO (K231837)
Brainomix 360 Triage Stroke (K232496)

4. Clinical Characteristics

The primary users of the Brainomix 360 platform are medical imaging professionals. The outputs generated by Brainomix 360 e-ASPECTS may be used by clinicians to inform onward treatment decisions as part of a wider set of other imaging to identify signs of ischemic damage on a per-voxel basis and relate these to ASPECTS regions to determine a per-ASPECTS region result and an overall ASPECTS score. Clinicians can edit the automated ASPECTS score based on their interpretation of both the unprocessed NCCT scan and the e-ASPECTS processing results. The following figure provides a general layout of the ASPECTS display image as provided from Brainomix 360 e-ASPECTS.

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Image /page/8/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon is split into two halves, with the left half being a solid teal color and the right half being an outline of the same color. The "AI" in "BRAINOMIX" is also teal, while the rest of the letters are a dark gray color.

Head office First Floor, Seacourt Tower, West Way Oxford OX2 0JJ, United Kingdom

Image /page/8/Picture/2 description: The image shows a brain scan with an ASPECTS score of 7. The scan on the left is labeled as 'Unannotated scan' and shows a standard view of the brain. The scan on the right, labeled 'Results', has areas highlighted in red and yellow, indicating regions of interest or concern. The heatmap indicates that 27 ml is contributing to the e-ASPECTS score on the right side.

5. Intended Use / Indications for Use

Brainomix 360 e-ASPECTS is a computer-aided diagnosis (CADx) software device used to assist the clinician in the assessment and characterization of brain tissue abnormalities using CT image data.

Limitations:

1. Brainomix 360 e-ASPECTS is not intended for primary interpretation of CT images. It is used to assist physician evaluation.
1. The Brainomix 360 e-ASPECTS score should be only used for ischemic stroke patients following the standard of care.

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Image /page/9/Picture/0 description: The image shows the logo for Brainomix. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon is a gradient of light blue to white, and the letters "AI" in the word "BRAINOMIX" are also in the same light blue color, while the rest of the letters are in a dark gray color.

1. Brainomix 360 e-ASPECTS has only been validated and is intended to be used in patient populations aged over 21 years.
1. Brainomix 360 e-ASPECTS is not intended for mobile diagnostic use. Images viewed on a mobile platform are compressed preview images and not for diagnostic interpretation.
ഗ് Brainomix 360 e-ASPECTS has been validated and is intended to be used on Siemens Somatom Definition scanners.

Contraindications/ Exclusions/Cautions:

. Patient motion: Excessive patient motion leading to artifacts that make the scan technically inadequate.
Hemorrhagic Transformation, Hematoma.

6. Technological Characteristics

Brainomix 360 e-ASPECTS principal workflow for NCCT includes the following key steps:

NCCT image loading.
. Automated image analysis and processing to identify and visualize the voxels which have been included in the ASPECTS score and the voxels which have been excluded from the ASPECTS score (also referred to as a 'heatmap').
. Automated image analysis and processing to register the subject image to an atlas to segment and highlight ASPECTS regions and to display whether or not each region is qualified as contributing to the ASPECTS score.
. Notifications and alerts sent to users.
. Generation of a summary results report.
Presentation of results for review and analysis by users.

Once the user has been notified of availability of the ASPECTS results, including the ASPECTS score, indication of affected side, affected ASPECTS regions and voxel-wise analysis (shown as a heatmap of voxels 'contributing to e-ASPECTS score' and a heatmap of voxels 'excluded from e-ASPECTS score') can be exported as a report and/or sent to the PACS.

7. Performance Data

Summary of Digital Phantom Validation Activities 7.1

Digital phantom evaluation was performed to validate the "volume contributing to e-ASPECTS" output as calculated by Brainomix 360 e-ASPECTS where performance criteria were derived from the literature (Cereda, et al., 2016). For the comparison of the volumes computed by the sum of the voxels contributing to the e-ASPECTS score against the synthetic volumes (n=110, synth datasets) of the digital phantom values, 3 metrics were derived and assessed against a performance requirement value previously derived from the literature. Those metrics with their associated threshold were 1) absolute bias of the difference between volumes computed and ground truth (< 12 mL); 2) the standard

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Image /page/10/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in capital letters. The brain icon is a gradient of blue and green, while the letters "AI" in the word "BRAINOMIX" are also in the same gradient of blue and green.

deviation (SD) of the difference between volumes computed and the ground truth (< 19 mL); and 3) Pearson's correlation between volume contributing to e-ASPECTS and known phantom volumes (> 0.86). The testing demonstrated that all 3 performance criteria were met and evidenced a good agreement between the synthetic digital phantom volumetric values (mL) and the calculated volumetric values (mL) by Brainomix 360 e-ASPECTS. This is summarized in Table 1 below.

Metric Name	Value	Criteria	Pass/Fail
Absolute Bias (upper95% CI)	7.61	<12	Pass
Standard deviation(upper 95% CI)	1.99	<19	Pass
Pearson'scorrelation - r(lower 95% CI)	0.993	>0.86	Pass

Table 1 Summary of the results for performance evaluation with the 3 metrics (name, value, criteria)

Summary of Standalone Performance Testing 7.2

Standalone performance testing was conducted to comply with special controls for this device type. Standalone performance testing demonstrated that the proposed device provides accurate representation of key processing parameters under a range of clinically relevant parameters and perturbations associated with the intended use of the software. The stand-alone performance testing demonstrates the generalized performance for a range of typical patient demographics which is the same as for the predicate device. The standalone performance dataset was additionally enriched to include a greater number of cases within late time-window sub-groups and cases with and without large vessel occlusions. Ground truth was determined by the consensus of three board-certified US neuroradiologists.

The standalone performance testing dataset comprised 137 non-contrast CT scans from patients scanned for suspected acute ischemic stroke, from 3 different USA institutions. The data was distributed from Siemens (75), GE (32), Philips (16) and Toshiba (14). Patients were admitted between March 2012 and August 2023. The median age was 70 years, and 51% were female. The distribution by race/ethnicity was that 35.5%(50) of patients were white, 10.2% (14) were Black/African America, 5.8% (8) were Hispanic or Latino, 1 (0.7%) was Asian, 1 (0.7%) was American Indian/ Native American, 2.2% (3) were Other and 43.8% (60) were unknown. Median NIHSS was 18 with an interquartile range of 11 to 22. 91 patients (66%) presented within 6 hours of time last seen well, 21 (15%) presented between 6 and 16 hours, 13 (9.5%) presented between over 16 hours and 12 (9%) were unknown onset time. 80 patients (58%) had an acute ICA or MCA large vessel occlusion ('with LVO') and 57 (42%) did not ('without LVO').

Region-level sensitivity, specificity, and AUC were calculated. Overall performance in 137 showed an area under the curve (AUC) of 83% (95% Cl: 80-86%), with a sensitivity of 69% (56-75%) and a specificity of 97% (80-97%). Case-level agreement, positive percentage agreement, and negative percentage agreement were analyzed for the overall cohort and for individual ASPECT regions and compared to pairwise agreement between the three truthers. The detailed results are reported in the labeling.

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Image /page/11/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon is a gradient of blue and green, while the "AI" in "BRAINOMIX" is also a similar gradient of blue and green, while the rest of the word is dark gray.

The standalone performance testing demonstrated that the e-ASPECTS performance generalized to a range of clinically-relevant subgroups (including stratification by time-window, LVO status, age, gender and clinical site). Consistent performance was also observed between the grouped cortical ASPECTS regions compared to grouped basal ganglia ASPECTS regions. Detailed performance testing results including these subgroups as well as performance for each ASPECTS region are reported in the labeling.

7.3 Summary of Reader Performance Testing

A multiple reader multiple case (MRMC) study was conducted to assess the impact of support from Brainomix 360 e-ASPECTS on reader performance. The reader study evaluated the performance of 7 clinical readers (1 'expert' neuroradiologist, and 6 'non-expert' radiologists or neurologists) when scoring the ASPECTS for 140 clinically-representative NCCT scans with and without the support of Brainomix 360 e-ASPECTS. Ground truth was determined by the consensus of three board-certified US neuroradiologists.

The reader study dataset comprised 140 NCCT scans from patients scanned in the clinical context of suspected acute stroke. Of these, 66 patients (47%) had confirmed LVO in the ICA or MCA M1; 56 (40%) had suspected stroke without LVC; and 18 (13%) were confounder or stroke mimic cases, with an alternative diagnosis to acute stroke and additional radiological findings. The median age was 68 years and 47% were female. Median NHSS was 18 (interquartile range: 10-22). 78 patients (56%) were scanned within 6 hours of time since symptom onset (or last known well); 22 patients (16%) were between 6-16 hours; 12 patients (9%) were over 16 hours; and 28 patients (20%) had unknown time of onset. The data was distributed from Siemens (79), GE (36), Philips (19) and Toshiba (6).

Comparison of the area under the curve (AUC) for readers with and without e-ASPECTS support showed a statistically significant improvement of 6.4%, from 78% without e-ASPECTS to 85% with e-ASPECTS (p=.03), which was the primary outcome measure of the study. This was driven by an improvement in sensitivity (from 61% to 72%), and a small improvement in specificity (from 96% to 98%). Cohen's Kappa and weighted Kappa also improved significantly with versus without e-ASPECTS.

Subgroup analyses showed that the improvements were driven by change in performance by nonexpert readers (radiologists and neurologists); the improvement was smaller but consistent positive in the expert reader (neuroradiologist). Stratification of cases was conducted and demonstrated an improvement in reader performance when aided by the device, though the performance improvement was not statistically significant, consistently across clinically-relevant subgroups, including by time since onset, LVO status, age, gender, and clinical site.

Out of 126 reads (18 confounder cases times seven readers), 18 reads (14.3%) changed when e-ASPECTS was used. 12 cases were not scored 10 with e-ASPECTS support compared to 10 without e-ASPECTS support. However, the misinterpretations by readers without e-ASPECTS support were of higher magnitude (ASPECTS scores of 4,5, or 6), compared to with e-ASPECTS (8 or 9), therefore no clinically significant impact was observed. Hence, the reads changed with versus without e-ASPECTS, as readers tended to be more accurate when e-ASPECTS support was available.

As the study used retrospective data, there were no specific safety endpoints in the reader study.

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Image /page/12/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in bold, sans-serif font. The brain icon is split into two halves, with the left half being a solid teal color and the right half being white. The letters "AI" in "BRAINOMIX" are also teal, while the rest of the letters are dark gray.

This study demonstrates substantial equivalence of the Brainomix 360 e-ASPECTS software for improving reader performance, compared to the predicate device. The results showed statistically significant improvement in the agreement between the readers and a reference standard when using the Brainomix 360 e-ASPECTS software compared to routine clinical practice.

8. Prescriptive Statement

Caution: Federal law restricts this device to sale by or on the order of a physician.

9. Safety and Effectiveness

Brainomix 360 e-ASPECTS has been designed, verified and validated in compliance with 21 CFR, Part 820.30 requirements. The device has been designed to meet the requirements associated with ISO 14971:2019 (risk management).

Cybersecurity 10.

Brainomix 360 e-ASPECTS has been designed to follow the FDA Cybersecurity Guidance and IEC 81001-5-1.

Substantial Equivalence 11.

The subject device, Brainomix 360 e-ASPECTS, provides new claims based on the comprehensive software verification and validation activities performed. The substantial equivalence comparison table (below) summarizes and compares the characteristics of the proposed and the predicate device, along with the reference device.

The proposed device (Brainomix 360 e-ASPECTS), predicate (Brainomix 360 e-ASPECTS, K221564) and reference device (Rapid ASPECTS (v3), K232156) are software packages that assist the user (neuroradiologist/ clinician) in the assessment and characterization of brain tissue abnormalities using non-contrast CT brain image data. The proposed device includes similar NCCT processing features and technological characteristics as compared to the predicate device, which provides viewing, quantification, analysis and reporting capabilities based on acquired DICOM compliant medical image data. The proposed and predicate device segment and analyze ASPECTS regions to aid in evaluation of adult patients presenting for diagnostic imaging workup, for evaluation of extent of disease. Therefore, the proposed device has substantially similar intended use and indications for use compared to the predicate device.

Where the proposed device differs from the predicate device are:

. Voxel volume contributing to ASPECTS score: the proposed device displays a calculation of the volume of the voxels contributing to ASPECTS score which was not present in the predicate. The heatmap does not have an impact on clinical decisions beyond aiding the understanding of the automated ASPECTS score and as such, no risks associated with the use of the voxel volume feature have been identified. Validation of the heatmaps and resulting volumes of the

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Image /page/13/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon and the "A" in "BRAINOMIX" are colored in a gradient of teal, while the rest of the letters are dark gray.

voxels identified as contributing towards the ASPECTS score has been extensively validated through digital phantom testing, which corroborates that the proposed device is safe and effective and does not raise different questions of safety and effectiveness.

. Removal of gating conditions: the proposed device removes a gating condition by which the user must confirm that the patient is confirmed with having an MCA or ICA occlusion. The performance of ASPECTS scoring was validated by comparing radiological ground truth in patients with suspected stroke and demonstrated that the proposed device improves the performance of representative users when evaluating ASPECTS in patients with suspected stroke. The dataset included cases with and without large vessel occlusion (LVO), and a subset of cases with alternative final diagnoses that are commonly encountered confounders in the population of suspected stroke patients. Therefore, the removal of the gating condition in proposed device does not raise new questions of safety or effectiveness compared to the predicate device.
. Extension of use to 24 hours: the proposed device extends the timeframe of the device's usefulness to 24 hours since the patient is last known to be well. This change does not introduce any new or unanswered questions of safety and effectiveness of the device as validated through clinical study. The study included data from a broad range of times after last known well, including patients with a time since onset unknown up to 24 hours.

Substantial Equivalence Comparison 12.

Characteristics/Parameter	Proposed DeviceBrainomix 360 e-ASPECTS(K243294)	Predicate DeviceBrainomix 360 e-ASPECTS(K221564)	Reference DeviceRapid ASPECTS (v3)(K232156)
510(k) Number	K243294	K221564	K232156
Product Code	POK	POK	POK
Regulation Number	21 CFR §892.2060	21 CFR §892.2060	21 CFR §892.2060
IntendedUse/Indications forUse	Brainomix 360 e-ASPECTS is acomputer-aided diagnosis(CADx) software device usedto assist the clinician in theassessment andcharacterization of braintissue abnormalities using CTimage data.	Brainomix 360 e-ASPECTS is acomputer-aided diagnosis(CADx) software device usedto assist the clinician in theassessment andcharacterization of braintissue abnormalities using CTimage data.	Rapid ASPECTS is a computer-aided diagnosis (CADx)software device used to assistthe clinician in the assessmentand characterization of braintissue abnormalities using CTimage data.
	The software automaticallyregisters images and uses anatlas to segment and analyzeASPECTS regions. Brainomix360 e-ASPECTS extracts imagedata from individual voxels inthe image to provide analysisand computer analytics andrelates the analysis to theatlas defined ASPECTS regions.	The software automaticallyregisters images and uses anAtlas to segment and analyzeASPECTS regions. Brainomix360 e-ASPECTS extracts imagedata from individual voxels inthe image to provide analysisand computer analytics andrelates the analysis to theatlas defined ASPECTS regions.	The Software automaticallyregisters images and segmentsand analyzes ASPECTS Regionsof Interest (ROIs). RapidASPECTS extracts image datafor the ROI(s) to provideanalysis and computeranalytics based onmorphological characteristics.The imaging features are thensynthesized by an artificial
Characteristics/Parameter	Proposed DeviceBrainomix 360 e-ASPECTS(K243294)	Predicate DeviceBrainomix 360 e-ASPECTS(K221564)	Reference DeviceRapid ASPECTS (v3)(K232156)
	The imaging features are thensynthesized by an artificialintelligence algorithm into asingle ASPECTS (Alberta StrokeProgram Early CT) score.	The imaging features are thensynthesized by an artificialintelligence algorithm into asingle ASPECTS (Alberta StrokeProgram Early CT) Score.	intelligence algorithm into asingle ASPECT (Alberta StrokeProgram Early CT) Score.
	Brainomix 360 e-ASPECTS isindicated for evaluation ofpatients presenting fordiagnostic imaging workup forevaluation of extent ofdisease. Extent of diseaserefers to the number ofASPECTS regions affectedwhich is reflected in the totalscore. Brainomix 360 e-ASPECTS provides informationthat may be useful in thecharacterization of ischemicbrain tissue injury duringimage interpretation (within24 hours from time last knownwell).	Brainomix 360 e-ASPECTS isindicated for evaluation ofpatients presenting fordiagnostic imaging workupwith known MCA or ICAocclusion, for evaluation ofextent of disease. Extent ofdisease refers to the numberof ASPECTS regions affectedwhich is reflected in the totalscore. Brainomix 360 e-ASPECTS provides informationthat may be useful in thecharacterization of ischemicbrain tissue injury duringimage interpretation (within 6hours from time last knownwell).	Rapid ASPECTS is indicated forevaluation of adult patientspresenting for diagnosticimaging workup, forevaluation of extent ofdisease. Extent of diseaserefers to the number ofASPECTS regions affectedwhich is reflected in the totalscore. This device providesinformation that may beuseful in the characterizationof early ischemic brain tissueinjury for ischemic strokepatient (typically, < 24 hourssince last known well) duringimage interpretation followingthe standard of care. RapidASPECTS provides acomparative analysis to theASPECTS standard of careradiologist assessment using
	Brainomix 360 e-ASPECTSprovides a comparativeanalysis to the ASPECTSstandard of care radiologistassessment by providinghighlighted ASPECTS regionsand an automated editableASPECTS score for clinicianreview. Brainomix 360 e-ASPECTS additionally providesa visualization of the voxelscontributing to and excludedfrom the automated ASPECTSscore and a calculation of thevoxel volume contributing toASPECTS score.	Brainomix 360 e-ASPECTSprovides a comparativeanalysis to the ASPECTSstandard of care radiologistassessment by providinghighlighted ASPECTS regionsand an automated editableASPECTS score for clinicianreview. Brainomix 360 e-ASPECTS additionally providesa visualization of the voxelscontributing to the automatedASPECTS score and the voxelsexcluded from the automatedASPECTS score.	the ASPECTS atlas definitionsand atlas display includinghighlighted ROIs andnumerical scoring. RapidASPECTS presents the originaland annotated images forconcurrent reads.
	Limitations:	Limitations:	Limitations:
	1. Brainomix 360 e-ASPECTS isnot intended for primaryinterpretation of CT images. Itis used to assist physicianevaluation.	1. Brainomix 360 e-ASPECTS isnot intended for primaryinterpretation of CT images. Itis used to assist physicianevaluation.	1. The ASPECTS score shouldbe only used for ischemicstroke patients following thestandard of care.
	2. The ASPECTS score shouldbe only used for ischemicstroke patients following thestandard of care.	2. Brainomix 360 e-ASPECTShas been validated in patientswith known MCA or ICAocclusion prior to ASPECTSscoring.	2. Rapid ASPECTS is an adjuncttool and is not intended toreplace a clinicians review ofthe original imaging or theirclinical judgement.
	3. Brainomix 360 e-ASPECTShas only been validated and is		3. Physicians should not usethe CAD generated output asthe primary interpretationwithout their concurrence.
			Contraindications/Exclusions/Cautions:
Characteristics/Parameter	Proposed DeviceBrainomix 360 e-ASPECTS(K243294)	Predicate DeviceBrainomix 360 e-ASPECTS(K221564)	Reference DeviceRapid ASPECTS (v3)(K232156)
	intended to be used in patientpopulations aged over 21years.4. Brainomix 360 e-ASPECTS isnot intended for mobilediagnostic use. Images viewedon a mobile platform arecompressed preview imagesand not for diagnosticinterpretation.	3. Brainomix 360 e-ASPECTS isnot suitable for use on brainscans displaying neurologicalpathologies other than acutestroke, such as tumors orabscesses, hemorrhagictransformation andhematoma.4. Use of Brainomix 360 е-ASPECTS Module in clinical	• Patient Motion: excessivemotion leading to artifactsthat make the scantechnically inadequate.• HemorrhagicTransformation,Hematoma• Very thin or no Ventricles
	5. Brainomix 360 e-ASPECTShas been validated and isintended to be used onSiemens Somatom Definitionscanners.	settings other than brainischemia within 6 hours fromtime last known well, causedby known ICA or MCAocclusions has not beentested.
	Contraindications/Exclusions/Cautions:	5. Brainomix 360 e-ASPECTShas been validated and isintended to be used onSiemens Somatom Definition
	• Patient motion: Excessivepatient motion leading toartifacts that make the scantechnically inadequate	scanners.6. Brainomix 360 e-ASPECTS
	• HemorrhagicTransformation, Hematoma	has only been validated and isintended to be used in patientpopulations aged over 21years.
		7. Brainomix 360 e-ASPECTS isnot intended for mobilediagnostic use. Images viewedon a mobile platform arecompressed preview imagesand not for diagnosticinterpretation.
		Contraindications/Exclusions/Cautions:
		• Patient motion: Excessivepatient motion leading toartifacts that make the scantechnically inadequate
		• HemorrhagicTransformation, Hematoma
Environment of use	Clinical/Hospital environment	Clinical/Hospital environment	Clinical/Hospital environment
Energy used and/ordelivered	None - software onlyapplication. The softwareapplication does not deliver ordepend on energy delivered to	None - software onlyapplication. The softwareapplication does not deliver ordepend on energy delivered to	None - software onlyapplication. The softwareapplication does not deliver ordepend on energy delivered to
Characteristics/Parameter	Proposed DeviceBrainomix 360 e-ASPECTS(K243294)	Predicate DeviceBrainomix 360 e-ASPECTS(K221564)	Reference DeviceRapid ASPECTS (v3)(K232156)
Primary Users	Neuroradiologist/Clinician	Neuroradiologist/Clinician	Neuroradiologist/Clinician
Clinical Application/Anatomical region	Stroke/Head	Stroke/Head	Stroke/Head
Standard of Care	ASPECTS Scoring	ASPECTS Scoring	ASPECTS Scoring
Design: Modalitiesfor image processingand visualization	CT	CT	CT
TechnicalImplementation	ML/AI/Random Forest	ML/AI/Random Forest	ML/AI/Random Forest
Image Overlay	ASPECTS regions, highlightedby algorithms. Voxel-wiseanalysis visualized as a heatmap.	ASPECTS regions, highlightedby algorithms. Voxel-wiseanalysis visualized as a heatmap.	ASPECTS Atlas ROIs,highlighted by algorithms
Gating Conditions	None	Users must confirm ICA orMCA occlusion prior toaccessing Brainomix 360 e-ASPECTS results.	None
Design: PACSfunctionality	View process and analyzemedical images. Performsstandard PACS functions withrespect to querying andlisting.	View process and analyzemedical images. Performsstandard PACS functions withrespect to querying andlisting.	View process and analyzemedical images. Performsstandard PACS functions withrespect to querying andlisting.
Design: DICOMcompliance	Yes	Yes	Yes
Design: ComputerPlatform	Standard off-the-shelf serveror virtual server	Standard off-the-shelf serveror virtual server	Standard off-the-shelf serveror virtual server
Design: Dataacquisition	Acquires medical image datafrom DICOM compliantimaging devices andmodalities	Acquires medical image datafrom DICOM compliantimaging devices andmodalities	Acquires medical image datafrom DICOM compliantimaging devices andmodalities
Alters Standard ofCare Workflow	In parallel to	In parallel to	In parallel to
Materials	N/A – Software only device	N/A – Software only device	N/A – Software only device
Biocompatibility	N/A – Software only device	N/A – Software only device	N/A – Software only device
Sterility	N/A – Software only device	N/A – Software only device	N/A – Software only device
Electrical Safety	N/A – Software only device	N/A – Software only device	N/A – Software only device
Mechanical Safety	N/A – Software only device	N/A – Software only device	N/A – Software only device
Chemical Safety	N/A – Software only device	N/A – Software only device	N/A – Software only device
Thermal Safety	N/A – Software only device	N/A – Software only device	N/A – Software only device
Radiation Safety	N/A – Software only device	N/A – Software only device	N/A – Software only device

A table comparing the key features of the subject and predicate devices is provided below.

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Image /page/14/Picture/0 description: The image shows the logo for Brainomix. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The "AI" in "BRAINOMIX" is colored in a gradient from blue to green, matching the color of the brain icon.

Head office

First Floor, Seacourt Tower, West Way Oxford OX2 0JJ, United Kingdom

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Image /page/15/Picture/0 description: The image shows the logo for Brainomix. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain icon is two semi-circles, one filled with a gradient of blue and green. The "AI" in "BRAINOMIX" is also colored with the same gradient.

Head office First Floor, Seacourt Tower, West Way Oxford OX2 0JJ, United Kingdom

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Image /page/16/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain icon on the left, followed by the word "BRAINOMIX" in a sans-serif font. The "A" in "BRAINOMIX" is colored in a gradient from teal to blue, while the rest of the letters are dark gray.

Head office First Floor, Seacourt Tower, West Way Oxford OX2 0JJ, United Kingdom

13. Conclusion

The proposed device has the same intended use as the predicate and the reference device. The proposed and predicate/reference devices utilize similar NCCT image processing and technological

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Image /page/17/Picture/0 description: The image shows the logo for BRAINOMIX. The logo consists of a stylized brain image on the left, followed by the word "BRAINOMIX" in a sans-serif font. The brain image is teal, and the letters "AI" in the word "BRAINOMIX" are also teal, while the rest of the letters are gray.

features. The extensions in the indications for use and differences in technological characteristics for the proposed device do not raise different questions of safety or effectiveness.

We conclude that the proposed device does not raise different questions with regards to safety and efficacy and demonstrates substantial equivalence to the predicate, Brainomix 360 e-ASPECTS (K221564) and reference, Rapid ASPECTS (v3) (K232156).

Regulation Number and Section

§ 892.2060 Radiological computer-assisted diagnostic software for lesions suspicious of cancer.

(a)
Identification. A radiological computer-assisted diagnostic software for lesions suspicious of cancer is an image processing prescription device intended to aid in the characterization of lesions as suspicious for cancer identified on acquired medical images such as magnetic resonance, mammography, radiography, or computed tomography. The device characterizes lesions based on features or information extracted from the images and provides information about the lesion(s) to the user. Diagnostic and patient management decisions are made by the clinical user.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) A detailed description of the image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, and algorithm limitations.
(ii) A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will improve reader performance as intended.
(iii) Results from performance testing protocols that demonstrate that the device improves reader performance in the intended use population when used in accordance with the instructions for use. The performance assessment must be based on appropriate diagnostic accuracy measures (
e.g., receiver operator characteristic plot, sensitivity, specificity, predictive value, and diagnostic likelihood ratio). The test dataset must contain sufficient numbers of cases from important cohorts (e.g., subsets defined by clinically relevant confounders, effect modifiers, concomitant diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals of the device for these individual subsets can be characterized for the intended use population and imaging equipment.(iv) Standalone performance testing protocols and results of the device.
(v) Appropriate software documentation (
e.g., device hazard analysis; software requirements specification document; software design specification document; traceability analysis; and description of verification and validation activities including system level test protocol, pass/fail criteria, results, and cybersecurity).(2) Labeling must include:
(i) A detailed description of the patient population for which the device is indicated for use.
(ii) A detailed description of the intended reading protocol.
(iii) A detailed description of the intended user and recommended user training.
(iv) A detailed description of the device inputs and outputs.
(v) A detailed description of compatible imaging hardware and imaging protocols.
(vi) Warnings, precautions, and limitations, including situations in which the device may fail or may not operate at its expected performance level (
e.g., poor image quality or for certain subpopulations), as applicable.(vii) Detailed instructions for use.
(viii) A detailed summary of the performance testing, including: Test methods, dataset characteristics, results, and a summary of sub-analyses on case distributions stratified by relevant confounders (
e.g., lesion and organ characteristics, disease stages, and imaging equipment).