Imagio Feasibility Multi-Reader, Multi-Case Study

Study Overview
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Brief Summary
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Controlled, blinded, multi-reader, multi-case study

Detailed Description
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The Imagio Feasibility Reader Study-01 Study is intended to evaluate if a subsequent pivotal study can be implemented to test prospective hypotheses for pre-specified effectiveness endpoints with an acceptable sample size. The Feasibility Study will be based on ITD masses from the PIONEER (NCT01943916) Pivotal study to simultaneously reflect the distributions with and without mammograms as well as site CDU BI-RADS scores within benign and malignant masses as strata. The study population will be split into 3 cohorts - Cohort 1, the 120 patient ITD Population used to run the primary/ secondary analyses. Cohort 2, 30 patients used to run exploratory analyses on false negative rate and Cohort 3, 5 patients used to run exploratory analyses on specific mass types

Official Title
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Imagio Feasibility 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: Imagio (IUS+OA)
* Device: Imagio Ultrasound
* Device: Mammography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Female subjects participating in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status Exclusion Criteria: - Female subjects who did not have known clinical status in the PIONEER-0 Study of the Imagio Breast Imaging System with known clinical status

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 5-12 independent readers depending on qualifications and availability. Imagio (IUS+OA) Training to be completed prior to any reads taking place. Read 1 is immediately followed by Read 2 within the same read session. Read 1 (Control): Mammogram (if available) + History + IUS (stills and videos provided), IUS Probability of Malignancy (POM) and BI-RADS scored and the data form locked. Read 2 (Test): Mammogram (if available) + History + IUS (stills and videos provided), and Imagio (IUS+OA) (stills and videos provided). An interim IUS POM and BI-RADS is recorded as well as a combined Imagio (IUS+OA) POM and BIRADS Pre and Post SenoGram on separate data forms.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imagio IUS<br>Read 1 - Mammo (as available) + Imagio Ultrasound | Device: Imagio Ultrasound<br>* Imagio ultrasound images to be reviewed as part of the reader study<br>Device: Mammography<br>* Mammography images as available per standard of care<br>* Other names: Mammo;|
| Experimental: Imagio (IUS+OA)<br>Read 2 - Mammo (as available) + (Imagio Ultrasound + OA) | Device: Imagio (IUS+OA)<br>* The Imagio ultrasound and opto-acoustic images to be reviewed as part of the reader study<br>Device: Mammography<br>* Mammography images 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 |
| --- | --- | --- |
| The Gain in Imagio IUS Alone Specificity vs Imagio (IUS+OA) Specificity at Fixed 95-99% Sensitivity (fSp), Cohort 1 | Primary effectiveness endpoint was the specificity of Imagio [IUS+OA] compared to IUS alone at fixed 95-99% sensitivity (fSp) interpolated from the area under the curve (AUC) of receiver operating characteristic (ROC) curves, averaged across all 10 independent readers. Both imaging modalities (IUS alone and IUS+OA) were read for 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). | Baseline to 12 month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Receiver Operating Characteristic (ROC) Area Under the Curve (pAUC), Cohort 1 | pAUC considers only the region of the ROC space that corresponds to clinically relevant values of sensitivity defined as 95% to 99% for Imagio [IUS+OA] vs. IUS alone; averaged across 10 readers. | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months) | 
| BiRads [Breast Imaging Reporting and Data System] Downgrades and Upgrades- Cohort 1 | The cumulative effect of downgrades and upgrades for benign masses expressed as the net gain of True Negative reads | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | 
| The Negative Likelihood Ratio (NLR) for IUS vs. Imagio® (IUS+OA), Cohort 1 | NLR (Imagio [IUS+OA] vs. IUS alone); averaged across 10 readers (all readers). | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months (≥11 months) | 
| SenoGram Usage Cohort 1 for Imagio (IUS+OA) Only | SenoGram Utilization by number of readers using the SenoGram reported by the readers. SenoGram is not used for Imagio IUS Arm only Imagio (IUS+OA) | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | 
| SenoGram Performance | Sensitivity of SenoGram estimated from cross-validation - Cohort 1 | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months | 
| SenoGram Performance | Specificity of SenoGram estimated from cross-validation | Imagio [IUS+OA] and IUS readings relative to biopsy results and TRUTH PANEL review of NDU cases with follow-up at 12 months |