Annalise Enterprise CXR Triage Trauma

K222179 · Annalise-Ai Pty , Ltd. · QFM · Mar 28, 2023 · Radiology

Device Facts

• Record ID: K222179
• Device Name: Annalise Enterprise CXR Triage Trauma
• Applicant: Annalise-Ai Pty , Ltd.
• Product Code: QFM · Radiology
• Decision Date: Mar 28, 2023
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 892.2080
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device

Intended Use

Annalise Enterprise CXR Triage Trauma is a software workflow tool designed to aid the clinical assessment of adult chest X-ray cases with features suggestive of pleural effusion and pneumoperitoneum in the medical care environment. The device analyzes cases using an artificial intelligence algorithm to identify findings. It makes case-level output available to a PACS or RIS for worklist prioritization or triage. The device is intended to be used by trained clinicians who are qualified to interpret chest X-rays as part of their scope of practice. The device is not intended to direct attention to specific portions of an image or to anomalies other than pleural effusion and pneumoperitoneum. Its results are not intended to be used on a standalone basis for clinical decision making nor is it intended to rule out specific critical findings, or otherwise preclude clinical assessment of X-ray cases. Standalone performance evaluation of the device was performed on a dataset that included supine and erect positioning. Use of this device with prone positioning may result in differences in performance. Standalone performance evaluation of the device was performed on a dataset where most cases were of unilateral right sided and bilateral pneumoperitoneum. Use of this device for unilateral left sided pneumoperitoneum may result in differences in performance. Specificity may be reduced for pleural effusion in the presence of scarring and/or pleural thickening.

Device Story

Software workflow tool; integrates with PACS/RIS; processes adult chest X-ray (CXR) images. Uses convolutional neural network (deep learning) to identify pleural effusion and pneumoperitoneum. Operates in parallel to standard clinical workflow; provides case-level notifications to prioritize worklists. Does not downgrade existing study priority. Used by trained clinicians in medical care environments. Benefits include earlier review of studies with suggestive findings; improves triage efficiency. Performance may vary with prone positioning or unilateral left-sided pneumoperitoneum; specificity reduced by scarring/pleural thickening.

Clinical Evidence

Retrospective, standalone performance study on 1,269 adult CXR cases (582 positive, 687 negative) from four US hospital networks. Pleural effusion AUC: 0.980 (95% CI: 0.972-0.986); Pneumoperitoneum AUC: 0.969 (95% CI: 0.950-0.984). Triage turn-around time <30 seconds. Ground truth established by ABR-certified radiologists.

Technological Characteristics

Software-only device; convolutional neural network (deep learning) architecture. Inputs: DICOM-compliant CXR images. Outputs: Worklist notification via PACS/RIS. Operates on standard IT infrastructure. No hardware components.

Indications for Use

Indicated for adult patients undergoing chest X-ray imaging to aid clinical assessment by identifying features suggestive of pleural effusion and pneumoperitoneum. Intended for use by trained clinicians qualified to interpret chest X-rays. Not for standalone clinical decision-making, ruling out critical findings, or precluding clinical assessment.

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

• Annalise Enterprise CXR Triage Pneumothorax (K213941)
• HealthPPT (K211803)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and the word "ADMINISTRATION" in a smaller font size below that.

Annalise-AI Pty Ltd % Haylee Bosshard Regulatory Affairs Manager Level P, 24 Campbell St. Sydney, New South Wales 2000 AUSTRALIA

March 28, 2023

# Re: K222179

Trade/Device Name: Annalise Enterprise CXR Triage Trauma Regulation Number: 21 CFR 892.2080 Regulation Name: Radiological computer aided triage and notification software Regulatory Class: Class II Product Code: QFM, QAS Dated: February 24, 2023 Received: February 24, 2023

Dear Minta Chen:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

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

Sincerely.

Jessica Lamb

Jessica Lamb, Ph.D. Assistant Director Imaging Software Team DHT 8B: Division of Radiological Imaging Devices and Electronic Products OHT 8: 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) K222179

Device Name Annalise Enterprise CXR Triage Trauma

# Indications for Use (Describe)

Annalise Enterprise CXR Triage Trauma is a software workflow tool designed to aid the clinical assessment of adult chest X-ray cases with features suggestive of pleural effusion and pneumoperitoneum in the medical care environment.

The device analyzes cases using an artificial intelligence algorithm to identify findings. It makes case-level output available to a PACS or RIS for worklist prioritization or triage.

The device is intended to be used by trained clinicians who are qualified to interpret chest X-ravs as part of their scope of practice.

The device is not intended to direct attention to specific portions of an image or to anomalies other than pleural effusion and pneumoperitoneum.

Its results are not intended to be used on a standalone basis for clinical decision making nor is it intended to rule out specific critical findings, or otherwise preclude clinical assessment of X-ray cases.

Standalone performance evaluation of the device was performed on a dataset that included supine and erect positioning. Use of this device with prone positioning may result in differences in performance.

Standalone performance evaluation of the device was performed on a dataset where most cases were of unilateral right sided and bilateral pneumoperitoneum. Use of this device for unilateral left sided pneumoperitoneum may result in differences in performance.

Specificity may be reduced for pleural effusion in the presence of scarring and/or pleural thickening.

| Type of Use (Select one or both, as applicable) |
|--------------------------------------------------------------------------------------|
| <span> <span></span>Prescription Use (Part 21 CFR 801 Subpart D) </span> |
| <span> <span></span>Over-The-Counter Use (21 CFR 801 Subpart C) </span> |

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K222179

^annalise.ai

# 510(k) Summary

### SUBMITTER I.

| Company Name | Annalise-AI Pty Ltd |
|----------------|----------------------------------------------------------|
| Address | Level P, 24 Campbell St<br>Sydney, NSW 2000<br>Australia |
| Phone Number | [phone] |
| Contact Person | Haylee Bosshard |
| Date Prepared | July 22, 2022 |

## II. SUBJECT DEVICE

| Manufacturer Name | Annalise-AI Pty Ltd |
|---------------------|---------------------------------------------------------------------------------|
| Device Name | Annalise Enterprise CXR Triage Trauma |
| 510(k) reference | K222179 |
| Classification Name | Radiological computer aided triage and notification software<br>(21CFR892.2080) |
| Regulatory Class | II |
| Product Code | QFM+, QAS* |

+ Note that the product code QFM applies to pleural effusion.

* Note that the product code QAS applies to pneumoperitoneum.

## PREDICATE DEVICE III.

| Manufacturer Name | Annalise-AI Pty Ltd |
|---------------------|---------------------------------------------------------------------------------|
| Device Name | Annalise Enterprise CXR Triage Pneumothorax |
| 510(k) reference | K213941 |
| Classification Name | Radiological computer aided triage and notification software<br>(21CFR892.2080) |
| Regulatory Class | II |
| Product Code | QFM |

This predicate has not been subject to a design-related recall.

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# Aanr

| Manufacturer Name | Zebra Medical Vision Ltd. |
|---------------------|---------------------------------------------------------------------------------|
| Device Name | HealthPPT |
| 510(k) reference | K211803 |
| Classification Name | Radiological computer aided triage and notification software<br>(21CFR892.2080) |
| Regulatory Class | II |
| Product Code | QFM |

# IV. REFERENCE DEVICE

## V. DEVICE DESCRIPTION

Annalise Enterprise CXR Triage Trauma is a software workflow tool which uses an artificial intelligence (AI) algorithm to identify suspected findings on chest X-ray (CXR) studies in the medical care environment. The findings identified by the device include pleural effusion and pneumoperitoneum.

Radiological findings are identified by the device using an AI algorithm - a convolutional neural network trained using deep-learning techniques. Images used to train the algorithm were sourced from datasets across three continents, including a range of equipment manufacturers and models. The performance of the device's AI algorithm was validated in a standalone performance evaluation, in which the case-level output from the device was compared with a reference standard ('ground truth'). This was determined by two ground truthers, with a third truther used in the event of disagreement. All truthers were US board-certified radiologists.

The device interfaces with image and order management systems (such as PACS/RIS) to obtain CXR studies for processing by the AI algorithm. Following processing, if any of the clinical findings of interest are identified in a CXR study, the device provides a notification to the image and order management system for prioritization of that study in the worklist. This enables users to review the studies containing features suggestive of these clinical findings earlier than in the standard clinical workflow. It is important to note that the device will never decrease a study's existing priority in the worklist. This ensures that worklist items will never have their priorities downgraded based on AI results.

The device workflow is performed parallel to and in conjunction with the standard clinical workflow for interpretation of CXRs. The device is intended to aid in prioritization and triage of radiological medical images only.

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# VI. INDICATIONS FOR USE

The Indications for Use statement is as follows:

Annalise Enterprise CXR Triage Trauma is a software workflow tool designed to aid the clinical assessment of adult chest X-ray cases with features suggestive of pleural effusion and pneumoperitoneum in the medical care environment.

The device analyzes cases using an artificial intelligence algorithm to identify findings. It makes case-level output available to a PACS or RIS for worklist prioritization or triage.

The device is intended to be used by trained clinicians who are qualified to interpret chest X-rays as part of their scope of practice.

The device is not intended to direct attention to specific portions of an image or to anomalies other than pleural effusion and pneumoperitoneum.

Its results are not intended to be used on a standalone basis for clinical decision making nor is it intended to rule out specific critical findings, or otherwise preclude clinical assessment of X-ray cases.

Standalone performance evaluation of the device was performed on a dataset that included supine and erect positioning. Use of this device with prone positioning may result in differences in performance.

Standalone performance evaluation of the device was performed on a dataset where most cases were of unilateral right sided and bilateral pneumoperitoneum. Use of this device for unilateral left sided pneumoperitoneum may result in differences in performance.

Specificity may be reduced for pleural effusion in the presence of scarring and/or pleural thickening.

The Indications for Use statement of the subject device differs to the predicate device only in the clinical conditions of interest, however a standalone performance evaluation was conducted and demonstrated that the device is safe and effective for its intended use. Both the subject and predicate devices are intended for use to assist with worklist triage by providing notifications of suspected findings and their associated priority.

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# Aannalisc

# VII. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The subject device was evaluated and compared to the predicate device with respect to the following characteristics:

- 1. Indications for Use
- Target population 2.
- 3. Anatomical site and modality
- 4. Intended user and clinical use environment
- 5. Technical method for notification and prioritization
- 6. Device input and radiological image protocol
- 7. Device output and means of notification to user
- 8. System components
- 9. Location where results are received
- 10. Prioritization relationship to standard of care workflow
- 11. Ability to support effective triage
- 12. Set of findings

The difference between the two devices is a configuration that limits the output to the set of findings that the subject device is intended to identify. To address this difference, standalone performance data was supplied to support the conclusion that the subject device does not raise different questions of safety and effectiveness and that the subject device is as safe and effective as the predicate device.

# VIII. PERFORMANCE DATA

The following performance data have been provided to support evaluation of substantial equivalence.

### A. Software Verification and Validation Testing

Software verification and validation testing was conducted, and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices", May 11, 2005.

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# ^annalise.ai

### B. Performance Testing

Performance of the subject device was assessed in two performance studies to satisfy requirements set forth in the special controls per 21CFR892.2080. These included standalone performance and triage effectiveness evaluations.

Standalone performance was assessed via a retrospective, anonymized study of adult patient, DICOM-compliant CXR cases. The test dataset used during the standalone performance evaluation was newly acquired and independent from the training dataset used in model development. The standalone performance study was conducted on two independent cohorts which equated to a total dataset of 1269 CXR cases (positive n=582 and negative n=687), collected consecutively from four US hospital network sites. The study included performance testing data obtained via an initial study protocol and additional performance testing data obtained via a study protocol addendum. Each of the two cohorts included representation across subgroups for patient demographics (gender, age, ethnicity, race), technical parameters (imaging equipment make, model), imaging parameters (positioning, projections), co-existing findings or abnormalities, finding characteristics (size and laterality) and common mimics. To determine the ground truth, each deidentified CXR case was annotated in a blinded fashion by ABR-certified and protocoltrained radiologists (ground truthers), with consensus determined by two ground truthers and a third ground truther in the event of disagreement for the primary finding. The key results of the study are summarized in the tables below.

| Finding | Product Code | AUC (95% CI) |
|------------------|--------------|---------------------|
| Pleural effusion | QFM | 0.980 (0.972-0.986) |
| Pneumoperitoneum | QAS | 0.969 (0.950-0.984) |

| Finding | Operating point | Sensitivity (95% CI) | Specificity (95% CI) |
|------------------|-----------------|----------------------|----------------------|
| Pleural effusion | 0.2302 | 96.0 (94.2,97.7) | 88.3 (85.3,91.1) |
| | 0.2990 | 93.8 (91.5,95.8) | 91.7 (89.3,94.1) |
| | 0.4355 | 86.3 (83.0,89.4) | 95.6 (93.7,97.2) |
| Pneumoperitoneum | 0.0322 | 90.1 (84.2,95.0) | 87.4 (82.4,92.3) |
| | 0.0484 | 86.1 (79.2,92.1) | 89.6 (85.2,94.0) |
| | 0.2266 | 82.2 (75.2,89.1) | 96.2 (93.4, 98.9) |

The results demonstrate the subject device establishes effective triage within a clinician's queue based on high sensitivity and specificity. Further, these results are substantially equivalent to those of the predicate device.

Triage effectiveness (turn-around time) was assessed as part of the standalone performance study. These cases were collected from multiple data sources spanning a variety of geographical locations, patient demographics and technical characteristics. The results demonstrated an average

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triage turn-around time under 30.0 seconds, which is substantially equivalent to the total performance time published for the predicate device.

Therefore, the subject device has been shown to satisfy the performance requirements per 21CFR892.2080, for radiological triage and notification software, by providing clinically effective triage for chest X-ray studies containing features suggestive of clinical findings of interest. This data demonstrates the subject device is safe and effective for its intended use, and thereby supports substantial equivalence.

## CONCLUSIONS IX.

The subject device and the predicate device are both software only packages, devices intended to assist with worklist triage by providing notification of findings in adults to trained clinicians. The subject and predicate devices utilize the same principles of operation and work in parallel to the current standard of care workflow.

Both the subject and predicate devices have the same software architecture, use the same deep learning AI principals to identify findings in images and require the same inputs and provide the equivalent outputs.

The minor differences between the subject and predicate devices do not raise new questions of safety and effectiveness.

Standalone performance testing and the comparison of technological characteristics with the predicate device shows that the subject device:

- . performs as intended,
- is safe and effective for its intended use, and ●
- . is therefore substantially equivalent to the predicate device.