BriefCase

K180647 · Aidoc Medical , Ltd. · QAS · Aug 1, 2018 · Radiology

Device Facts

• Record ID: K180647
• Device Name: BriefCase
• Applicant: Aidoc Medical , Ltd.
• Product Code: QAS · Radiology
• Decision Date: Aug 1, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 892.2080
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

BriefCase is a radiological computer aided triage and notification software indicated for use in the analysis of non-enhanced head CT images. The device is intended to assist hospital networks and trained radiologists in workflow triage by flagging and communication of suspected positive findings of pathologies in head CT images, namely Intracranial Hemorrhage (ICH). BriefCase uses an artificial intelligence algorithm to analyze images and highlight cases with detected ICH on a standalone desktop application in parallel to the ongoing standard of care image interpretation. The user is presented with notifications for cases with suspected ICH findings. Notifications include compressed preview images that are meant for informational purposes only and not intended for diagnostic use beyond notification. The device does not alter the original medical image and is not intended to be used as a diagnostic device. The results of BriefCase are intended to be used in conjunction with other patient information and based on professional judgment to assist with triage/prioritization of medical images. Notified clinicians are responsible for viewing full images per the standard of care.

Device Story

BriefCase is a radiological computer-aided triage and notification software; operates in parallel to standard-of-care (SOC) image interpretation. Inputs: non-enhanced head CT DICOM images. Processing: deep learning AI algorithm analyzes images for suspected Intracranial Hemorrhage (ICH); de-identifies and filters images before analysis. Outputs: pop-up notifications on radiologist's desktop application; includes patient name, accession number, and compressed preview image. Usage: installed on hospital server; integrates with PACS/workstations. Workflow: device flags suspected ICH cases; notifies radiologist; radiologist performs preemptive triage; radiologist must view full images in local PACS per SOC. Benefits: reduces time-to-exam-open by prioritizing suspected positive cases over standard FIFO queue; facilitates faster clinical intervention for time-sensitive pathologies.

Clinical Evidence

Retrospective, blinded, multicenter, multinational study (n=198 cases from 3 sites). Primary endpoint: sensitivity and specificity for ICH detection. Results: sensitivity 93.6% (95% CI: 86.6%-97.6%); specificity 92.3% (95% CI: 85.4%-96.6%). Secondary endpoint: clinical benefit (time-to-exam-open). Mean time-to-notification (4.5 min) vs. SOC time-to-exam-open (72.6 min); mean difference 68.1 min (p<0.0001).

Technological Characteristics

Software-based triage system; utilizes deep learning AI algorithm. Components: Aidoc Hospital Server (AHS), Aidoc Cloud Server (ACS), and Aidoc Worklist Application. Platform: Microsoft Windows Server 2012 64bit, PostgreSQL, DICOM module. Connectivity: networked; processes DICOM images. No hardware components; does not segment or mark original images.

Indications for Use

Indicated for use in hospital networks and by trained radiologists to assist in workflow triage by flagging and communicating suspected Intracranial Hemorrhage (ICH) in non-enhanced head CT images.

Regulatory Classification

Identification

Radiological computer aided triage and notification software is an image processing prescription device intended to aid in prioritization and triage of radiological medical images. The device notifies a designated list of clinicians of the availability of time sensitive radiological medical images for review based on computer aided image analysis of those images performed by the device. The device does not mark, highlight, or direct users' attention to a specific location in the original image. The device does not remove cases from a reading queue. The device operates in parallel with the standard of care, which remains the default option for all cases.

Special Controls

Radiological computer aided triage and notification software must comply with the following special controls: 1. Design verification and validation must include: i. A detailed description of the notification and triage algorithms and all underlying image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, how the algorithm affects or relates to clinical practice or patient care, and any algorithm limitations. ii. A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will provide effective triage (e.g., improved time to review of prioritized images for pre-specified clinicians). iii. Results from performance testing that demonstrate that the device will provide effective triage. The performance assessment must be based on an appropriate measure to estimate the clinical effectiveness. The test dataset must contain sufficient numbers of cases from important cohorts (e.g., subsets defined by clinically relevant confounders, effect modifiers, associated diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals for these individual subsets can be characterized with the device 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; description of verification and validation activities including system level test protocol, pass/fail criteria, and results). 2. Labeling must include the following: i. A detailed description of the patient population for which the device is indicated for use. ii. A detailed description of the intended user and user training that addresses appropriate use protocols for the device. iii. Discussion of warnings, precautions, and limitations must include situations in which the device may fail or may not operate at its expected performance level (e.g., poor image quality for certain subpopulations), as applicable. iv. A detailed description of compatible imaging hardware, imaging protocols, and requirements for input images. v. Device operating instructions. vi. A detailed summary of the performance testing, including: test methods, dataset characteristics, triage effectiveness (e.g., improved time to review of prioritized images for pre-specified clinicians), diagnostic accuracy of algorithms informing triage decision, and results with associated statistical uncertainty (e.g., confidence intervals), including a summary of subanalyses on case distributions stratified by relevant confounders, such as lesion and organ characteristics, disease stages, and imaging equipment.

*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 notification and triage algorithms and all underlying image analysis algorithms including, but not limited to, a detailed description of the algorithm inputs and outputs, each major component or block, how the algorithm affects or relates to clinical practice or patient care, and any algorithm limitations. (ii) A detailed description of pre-specified performance testing protocols and dataset(s) used to assess whether the device will provide effective triage ( *e.g.,* improved time to review of prioritized images for pre-specified clinicians).(iii) Results from performance testing that demonstrate that the device will provide effective triage. The performance assessment must be based on an appropriate measure to estimate the clinical effectiveness. The test dataset must contain sufficient numbers of cases from important cohorts ( *e.g.,* subsets defined by clinically relevant confounders, effect modifiers, associated diseases, and subsets defined by image acquisition characteristics) such that the performance estimates and confidence intervals for these individual subsets can be characterized with the device for the intended use population and imaging equipment.(iv) Stand-alone 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; description of verification and validation activities including system level test protocol, pass/fail criteria, and results).(2) Labeling must include the following: (i) A detailed description of the patient population for which the device is indicated for use; (ii) A detailed description of the intended user and user training that addresses appropriate use protocols for the device; (iii) Discussion of warnings, precautions, and limitations must include situations in which the device may fail or may not operate at its expected performance level ( *e.g.,* poor image quality for certain subpopulations), as applicable;(iv) A detailed description of compatible imaging hardware, imaging protocols, and requirements for input images; (v) Device operating instructions; and (vi) A detailed summary of the performance testing, including: test methods, dataset characteristics, triage effectiveness ( *e.g.,* improved time to review of prioritized images for pre-specified clinicians), diagnostic accuracy of algorithms informing triage decision, and results with associated statistical uncertainty (*e.g.,* confidence intervals), including a summary of subanalyses on case distributions stratified by relevant confounders, such as lesion and organ characteristics, disease stages, and imaging equipment.

Predicate Devices

• Viz.AI's ContaCT (DEN170073)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the U.S. Food & Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. Food & Drug Administration" in blue text. The word "Administration" is on the second line.

August 1st, 2018

Aidoc Medical, Ltd. % John J. Smith, M.D., J.D. Regulatory Counsel/Partner Hogan Lovells US LLP 555 Thirteenth Street, NW WASHINGTON DC 20004

Re: K180647

Trade/Device Name: BriefCase Regulation Number: 21 CFR 892.2080 Regulation Name: Radiological computer aided triage and notification software Regulatory Class: II Product Code: QAS Dated: July 5, 2018 Received: July 5, 2018

Dear Dr. Smith:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. 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 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

{1}------------------------------------------------

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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Jeff Rodgers

Digitally signed by Jeffrey J.
Ballyns -S
DN: c=US, o=U.S. Government,
ou=HHS, ou=FDA, ou=People,
0.9.2342.19200300.100.1.1=200
9569725, cn=Jeffrey J. Ballyns -S
Date: 2018.08.01 09:12:29
04'00'

for Robert Ochs, Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use

510(k) Number (if known) K180647

Device Name

#### BriefCase

Indications for Use (Describe)

BriefCase is a radiological computer aided triage and notification software indicated for use in the analysis of non-enhanced head CT images. The device is intended to assist hospital networks and trained radiologists in workflow triage by flagging and communication of suspected positive findings of pathologies in head CT images, namely Intracranial Hemorrhage (ICH) .

BriefCase uses an artificial intelligence algorithm to analyze images and highlight cases with detected ICH on a standalone desktop application in parallel to the ongoing standard of care image interpretation. The user is presented with notifications for cases with suspected ICH findinas. Notifications include compressed preview images that are meant for informational purposes only and not intended for diagnostic use beyond notification. The device does not alter the original medical image and is not intended to be used as a diagnostic device.

The results of BriefCase are intended to be used in conjunction with other patient information and based on professional judgment to assist with triace/prioritization of medical images. Notified clinicians are responsible for viewing full images per the standard of care.

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

[X] Prescription Use (Part 21 CFR 801 Subpart D)

| Prescription Use (Part 21 CFR 801 Subpart D)

# CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

# *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services

Food and Drug Administration

Office of Chief Information Officer

Paperwork Reduction Act (PRA) Staff

#### PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

# 510(k) Summary

## Aidoc Medical, Ltd.'s BriefCase (K180647)

#### Submitter:

| Aidoc Medical, Ltd.<br>Yigal Alon 92<br>Tel-Aviv, Israel | |
|----------------------------------------------------------|--------------------------------------------------------------|
| Phone: | [phone] |
| Contact Person: | N. Epstein, Ph.D. |
| Date Prepared: | July 31, 2018 |
| Name of Device: | BriefCase |
| Classification Name: | Radiological computer aided triage and notification software |
| Regulatory Class: | Class II |
| Product Code: | QAS (21 C.F.R. 892.2080) |
| Predicate Device: | Viz.Al's ContaCT (DEN170073) |

### Device Description

BriefCase is a radiological computer-assisted triage and notification software device. The software system is based on an algorithm programmed component and is comprised of a standard off-the-shelf operating system, the Microsoft Windows server 2012 64bit, and additional applications, which include PostgreSQL. DICOM module and the BriefCase Image Processing Application. The device consists of the following three modules: (1) Aidoc Hospital Server (AHS); (2) Aidoc Cloud Server (ACS); and (3) Aidoc Worklist Application that is installed on the radiologist' desktop and provides the user interface in which notifications from the BriefCase software are received.

DICOM images are received, saved and filtered and de-identified before processing. Series are processed chronologically by running an algorithm on each series to detect suspected findings and then notifications on flagged series are sent to the Worklist desktop application, thereby prompting preemptive triage and prioritization.

The Worklist Application displays the pop-up notifications of new studies with suspected findings when they come in. Notifications are in the form of a small pop-up containing patient name and accession number. A list of all incoming cases with suspected findings is also displayed. In addition, a compressed, small black and white image that is marked "not for diagnostic use" is displayed as a preview function. This compressed preview is meant for informational purposes only, does not contain any marking of the findings, and is not intended for primary diagnosis bevond notification. Presenting the radiologist with notification facilitates earlier triage by allowing one to assess the available images in the PACS. Thus, the suspect case receives attention earlier than would have been the case in the standard of care practice alone.

{4}------------------------------------------------

#### Intended Use / Indications for Use

BriefCase is a radiological computer aided triage and notification software indicated for use in the analysis of non-enhanced head CT images.

The device is intended to assist hospital networks and trained radiologists in workflow triage by flagging and communication of suspected positive findings of pathologies in head CT images, namely Intracranial Hemorrhage (ICH).

BriefCase uses an artificial intelligence algorithm to analyze images and highlight cases with detected ICH on a standalone desktop application in parallel to the ongoing standard of care image interpretation. The user is presented with notifications for cases with suspected ICH findings. Notifications include compressed preview images that are meant for informational purposes only and not intended for diagnostic use beyond notification. The device does not alter the original medical image and is not intended to be used as a diagnostic device.

The results of BriefCase are intended to be used in conjunction with other patient information and based on professional judgment, to assist with triage/prioritization of medical images. Notified clinicians are responsible for viewing full images per the standard of care.

### Comparison of Technological Characteristics

The subject and predicate devices are radiological computer-assisted triage and notification software programs. Both devices are artificial intelligence algorithms incorporated software packages for use with CT scanners, PACS, and workstations. Both devices process images intended to aid in prioritization and triage of radiological medical images. The predicate device processes brain CT angiogram images and is indicated for the detection of large vessel occlusion, while the subject device processes head CT images and is indicated for Intracranial Hemorrhage. While the subject device's indications for use differ slightly from the predicate device, both devices are intended to provide notifications and preview head images of potential findings to radiologists and other clinicians for the purpose of treatment planning and follow up.

Both software devices notify a designated list of clinicians (the predicate device - a neurovascular specialist, the subject device - a radiologist) of the availability of time sensitive radiological medical images for review based on computer aided image analysis performed by the device's Al algorithm. The subject device sends notifications and compressed previews to the workstations' desktop of the radiologist. Those notifications work in the standard of care. Thev prompt the radiologist to start preemptive triage of a flagged case, upon which he may decide after observing the preview on his desktop, to turn to the local PACS to perform the evaluation. If a notification is rejected, the case still remains in the queue to be handled per the standard of care.

The predicate device also sends notifications and compressed previews, but to the mobile phone of a neuro-specialist independent of the standard of care, thus both devices work in parallel to the standard of care. Both compressed previews are for informational purposes only and not for diagnostic use, and in both cases, the notified clinicians are responsible for using the local imaging system for viewing the original images and engage the referring clinician for diagnosis and treatment decision.

The predicate and subject devices process CT images using similar techniques and a similar artificial intelligence algorithm. Specifically, the subject and predicate software utilize a deep learning algorithm trained on medical images. The deep-learning process allows for high accuracy in the detection of initial suspect locations. As a system, the BriefCase raises the same types of safety and effectiveness questions as the predicate; namely, accurate detection of

{5}------------------------------------------------

findings within the reviewed and processed study on which a physician can base a clinically useful triage/prioritization assessment considering all available clinical information.

lt is important to note that, like the predicate, the device does not remove cases from a reading queue. Again, both devices operate in parallel with the standard of care, which remains the default option for all cases.

| | Aidoc Briefcase Software | Viz.AI ContaCT Software<br>(DEN170073) |
|--------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use /<br>Indications for<br>Use | BriefCase is a radiological<br>computer aided triage and<br>notification software indicated for<br>use in the analysis of non-<br>enhanced head CT images.<br><br>The device is intended to<br>assist hospital networks and<br>trained radiologists in workflow<br>triage by flagging and<br>communication of suspected<br>positive findings of pathologies in<br>head CT images, namely<br>Intracranial Hemorrhage (ICH).<br><br>BriefCase uses an artificial<br>intelligence algorithm to analyze<br>images and highlight cases with<br>detected ICH on a standalone<br>desktop application in parallel to<br>the ongoing standard of care<br>image interpretation. The user is<br>presented with notifications for<br>cases with suspected ICH<br>findings. Notifications<br>include compressed preview<br>images that are<br>meant for informational purposes<br>only and not intended for<br>diagnostic use<br>beyond notification. The device<br>does not alter the original medical<br>image and is not intended to be<br>used as a diagnostic device.<br><br>The results of BriefCase are<br>intended to be used in<br>conjunction with other<br>patient information and based on<br>professional judgment, to assist<br>with triage/prioritization of medical<br>images. Notified clinicians are<br>responsible for viewing<br>full images per the standard of<br>care. | ContaCT is a notification-only,<br>parallel workflow tool for use by<br>hospital networks and<br>trained clinicians to identify and<br>communicate images of specific<br>patients to a specialist, independent<br>of standard of care workflow.<br><br>ContaCT uses an artificial<br>intelligence algorithm to analyze<br>images for findings<br>suggestive of a pre-specified clinical<br>condition and to notify an<br>appropriate medical specialist of<br>these findings in parallel to standard<br>of care image interpretation.<br>Identification of suspected findings<br>is not for diagnostic use beyond<br>notification.<br><br>Specifically, the device analyzes CT<br>angiogram images of the brain<br>acquired in the acute setting, and<br>sends notifications to a<br>neurovascular specialist that a<br>suspected large vessel occlusion<br>has been identified and<br>recommends review of those<br>images. Images can be previewed<br>through a mobile application.<br>Images that are previewed through<br>the mobile application are<br>compressed and are for<br>informational purposes only and not<br>intended for diagnostic use beyond<br>notification.<br><br>Notified clinicians are responsible<br>for viewing non-compressed images<br>on a diagnostic viewer and<br>engaging in appropriate patient<br>evaluation and relevant discussion<br>with a treating physician before<br>making care-related decisions or<br>requests. ContaCT is limited to<br>analysis of imaging data and should |
| | | |
| User population | Radiologist | not be used in-lieu of full patient evaluation or relied upon to make or confirm diagnosis.<br>Clinician (e.g. neurovascular specialist) |
| Anatomical<br>region of interest | Head | Head |
| Data acquisition<br>protocol | Non contrast CT scan of the head or neck | CT angiogram images of the brain |
| View DICOM<br>data | DICOM Information about the patient, study and current image | DICOM Information about the patient, study and current image |
| Segmentation of<br>region of interest | No; device does not mark, highlight, or direct users' attention to a specific location in the original image | No; device does not mark, highlight, or direct users' attention to a specific location in the original image |
| Algorithm | Artificial intelligence algorithm with database of images | Artificial intelligence algorithm with database of images |
| Notification/Prioritization | Yes | Yes |
| Preview images | Presentation of a preview of the study for initial assessment not meant for diagnostic purposes<br>The device operates in parallel with the standard of care, which remains the default option for all cases | Presentation of notification and preview of the study for initial assessment not meant for diagnostic purposes<br>The device operates in parallel with the standard of care, which remains the default option for all cases |
| Alteration of<br>original image | No | No |
| Removal of<br>cases from<br>worklist queue | No | No |

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

{6}------------------------------------------------

# Performance Data

Aidoc conducted a retrospective, blinded, multicenter, multinational study with the BriefCase software with the primary endpoint to evaluate the software's performance in identifying noncontrast CT head images containing intracranial hemorrhage (ICH) findings in 198 cases from 3 clinical sites (2 US and 1 OUS). There were approximately an equal number of positive and negative cases (images with ICH versus without ICH) included in the analysis.

Sensitivity and specificity exceeded the 80% performance qoal. Specifically, sensitivity was observed to be 93.6% (95% Cl: 86.6%-97.6%) and specificity was observed to be 92.3% (95% Cl: 85.4%-96.6%).

In addition, a secondary endpoint measure was Briefcase's potential clinical benefit of worklist prioritization for true positive ICH cases. For that purpose, in two medical centers, one in Israel and one in the US, Aidoc compared the key standard-of-care metric of time-to-exam-open to the software's time-to-notification metric.

The BriefCase time-to-notification includes the time to get the DICOM exam, de-identify it, upload it to the cloud, analyze and send a notification back to the worklist application. The standard of care time-to-open-exam consisted of the time from the initial scan of the patient to when the radiologist first opened the exam for review.

{7}------------------------------------------------

BriefCase time-to-notification has been documented for all 198 cases. Fifty-nine (59) cases have been identified as true positive (i.e., identified as positive by both the BriefCase and the ground truth) and the time-to-exam-open has been also collected for these cases.

As shown in the table below, analysis demonstrated that standard of care time-to-exam-open (72.6 minutes: 95% Cl 45.0-100.2) is significantly longer than the parallel time-to-notification of the BriefCase software (4.5 minutes: 95% Cl 4.1-4.8). The mean difference of 68.1 minutes (95% Cl 40.5-95.7) for these two metrics is statistically significant and assuming the radiologist receives a notification on a true positive ICH case and acts on it immediately, it can on average save 68.1 (95% Cl 40.5-95.7) minutes compared to the time-to-exam-open in a FIFO reading queue. The value of 68.1 is based on the study of 59 cases, taken from 2 medical centers (1 US, 1 OUS), and may vary in practice.

| Parameter | Mean estimate | Lower<br>Confidence<br>Limit | Upper<br>Confidence<br>Limit | Median | P-value |
|----------------------------------------------|---------------|------------------------------|------------------------------|--------|---------|
| Time-to-open-exam in<br>the standard of care | 72.58 | 45.02 | 100.14 | 41.00 | |
| Time-to-notification of<br>BriefCase | 4.46 | 4.10 | 4.83 | 3.95 | |
| Difference | 68.11 | 40.50 | 95.72 | 37.42 | <0.0001 |

In summary, performance validation data, combined with real-world evidence, establish the achievement of effective triage by the BriefCase image analysis algorithm as well as effective notification functionality of the BriefCase application, as compared to the standard of care for improved time-to-exam-open of a notified case.

# Conclusions

The subject BriefCase and the ContaCT predicate devices are both intended to aid in prioritization and triage of radiological head medical images for the indications of Intracranial Hemorrhage and large vessel occlusion, respectively. The labeling of both devices clearly states that the devices are not for diagnostic use. Both devices are software packages with similar technological characteristics and principles of operation, incorporating deep learning Al algorithms that process images, and software to send notifications and compressed preview images to pre-designated clinicians that are instructed to further evaluate the original images in the local PACS and engage the referring clinician for diagnosis.

Both devices operate in parallel to the standard of care workflow in the sense that they do not change the original image, do not provide any marking on the output preview, and do not remove images from the standard of care FIFO queue, thus not disturbing standard interpretation of the images by trained clinicians. The minor differences between the subject device and the predicate raise no new issues of safety or effectiveness. In addition, performance testing demonstrates that the BriefCase performs as intended.

The BriefCase device is thus substantially equivalent to the ContaCT predicate.