Optoacoustic Images Versus Imagio® Ultrasound

Study Overview
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Brief Summary
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The Imagio® Pivotal Study is intended to evaluate if the results observed in the previous Feasibility Study can be confirmed for pre-specified effectiveness endpoints. Using Intention-to-Diagnose (ITD) masses from the PIONEER Pivotal study, 480 to 840 masses are to be used for the Pivotal Study, the remaining masses will be reserved for training the SenoGram® model.

Detailed Description
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This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 15 readers with an additional 5 as back-up readers depending on qualifications and availability. Readers that participated in the Seno PIONEER Study (NCT01943916) or the Reader-01 Feasibility Study (NCT03708393) are not eligible to participate as readers in this Pivotal Study. Imagio® [Ultrasound (IUS) + Optoacoustic (OA)] (IUS)(IUS+OA) training will be completed prior to any reads taking place. Read 1 will be immediately followed by Read 2 within the same read session.

Official Title
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Imagio® Pivotal Multi-Reader, Multi-Case Study of Optoacoustic Images Versus Imagio® Ultrasound to Guide Decision to Biopsy

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Reader Study - Imagio Ultrasound
* Device: Reader Study Imagio Ultrasound + Optoacoustic Imaging
* Device: Mammography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One analyzable mass per patient: BI-RADS 3 and 4a, 4b, 4c and 5 masses as declared by clinical site investigator via PIONEER study inclusion criteria and categorized as BIRADS 3, 4a, 4b 4c and 5 by conventional diagnostic ultrasound (CDU) Masses declared to be in the PIONEER Intention to Diagnose (ITD)/analysis population, including high risk cases per original PIONEER protocol Patient age, indication for study entry and available medical history Evaluable mammograms and OA and IUS video loops and stills for each mass Exclusion Criteria: Critical missing IUS or OA still image and/or video loop views or incorrect IUS or OA stills and video loops that would preclude a case from being evaluated by readers Reader-02 Proficiency Test and training cases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This will be a controlled, blinded, multi-reader, multi-case (MRMC) study using a sequential design. The study will include 15 readers with an additional 5 as back-up readers depending on qualifications and availability. Readers that participated in the Seno PIONEER Study or the Reader-01 Feasibility Study are not eligible to participate as readers in this Pivotal Study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imagio IUS<br>Read 1 (Control): History + Mammogram (if available) + IUS (Imagio Ultrasound) stills and videos provided), IUS Probability of Malignancy (POM) and Breast Imaging Reporting and Data System (BI-RADS) scored and the data form then locked. | Device: Reader Study - Imagio Ultrasound<br>* Imagio ultrasound images to be reviewed as part of Reader study<br>Device: Mammography<br>* Mammography as available per standard of care<br>* Other names: Mammo;|
| Experimental: Imagio (IUS+OA)<br>Read 2 (Test): History + Mammogram (if available) + IUS (stills and videos provided), and Imagio (IUS+OA) (stills and videos provided). Imagio (IUS+OA) POM and Breast Imaging Reporting and Data System (BI-RADS) assigned after viewing the SenoGram® output. The dataform is locked. | Device: Reader Study Imagio Ultrasound + Optoacoustic Imaging<br>* Imagio Ultrasound + Optoacoustic images to be reviewed as part of Reader study<br>Device: Mammography<br>* Mammography as available per standard of care<br>* Other names: Mammo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gain in Specificity at Fixed 98% Sensitivity (fSp) | Primary effectiveness endpoint was the difference (gain) in specificity (fSp) at fixed 98% sensitivity for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in each subject (subject as own control); results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth). fSp derived from empirical receiver operating characteristic (ROC) using endpoint interpolation. | Baseline to 12 months +/- 30 days follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative Likelihood Ratio (NLR) | NLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in each subject (subject as own control); results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth). NLR = [(1-sensitivity) / specificity]. | Baseline to 12 months +/- 30 days follow-up | 
| Positive Likelihood Ratio (PLR) | PLR for the Imagio IUS+OA relative to IUS alone, across all 15 independent readers; both imaging modalities used in each subject (subject as own control); results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth). PLR = [sensitivity / (1-specificity)]. | Baseline to 12 months +/- 30 days follow-up | 
| Partial Area Under the Curve (pAUC) | pAUC considers only the region of the area under the ROC curve that corresponds to clinically relevant values of sensitivity, defined as 95% to 100%, for Imagio IUS+OA vs. IUS alone, averaged across 15 readers. Both imaging modalities used in each subject (subject as own control); results for each imaging modality compared to biopsy diagnosis or 12-month follow-up ruling of benign as determined by truth panel (ground truth). A higher pAUC indicates better diagnostic accuracy. | Baseline to 12 months +/- 30 days follow-up |