Optoacoustic Images Versus Imagio® Ultrasound

Not Applicable

Completed

Interventions: Device: Reader Study - Imagio Ultrasound
Device: Reader Study Imagio Ultrasound + Optoacoustic Imaging
Device: Mammography

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Imagio IUS	Mammography	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.
Imagio IUS	Reader Study - Imagio Ultrasound	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.
Imagio (IUS+OA)	Reader Study Imagio Ultrasound + Optoacoustic Imaging	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.
Imagio (IUS+OA)	Mammography	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.

Primary Outcome Measures

Name	Time	Method
Gain in Specificity at Fixed 98% Sensitivity (fSp)	Baseline to 12 months +/- 30 days follow-up	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.

Secondary Outcome Measures

Name	Time	Method
Negative Likelihood Ratio (NLR)	Baseline to 12 months +/- 30 days follow-up	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 = \[(1-sensitivity) / specificity\].
Positive Likelihood Ratio (PLR)	Baseline to 12 months +/- 30 days follow-up	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 = \[sensitivity / (1-specificity)\].
Partial Area Under the Curve (pAUC)	Baseline to 12 months +/- 30 days follow-up	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.