Reader-02: Optoacoustic Images Versus Imagio® Ultrasound
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Imagio IUS 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
Imagio ultrasound images to be reviewed as part of Reader study
Device: Mammography
Mammography as available per standard of care
Other Names:
|
| Experimental: Imagio (IUS+OA) 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
Imagio Ultrasound + Optoacoustic images to be reviewed as part of Reader study
Device: Mammography
Mammography as available per standard of care
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | American College of Radiology Center for Research and Innovation | Philadelphia | Pennsylvania | United States | 19103 |
Sponsors and Collaborators
- Seno Medical Instruments Inc.
Investigators
- Study Director: Shaan Schaeffer, Seno Medical
Study Documents (Full-Text)
More Information
Publications
None provided.- Reader-02 Study
Study Results
Participant Flow
| Recruitment Details | New Independent Reader Study (new readers re-reading a sub-set of randomly selected images acquired during PIONEER-01 Study- (NCT01943916)). Reader-02 study execution dates: 30 Jul 2019 to 3 Nov 2019 |
|---|---|
| Pre-assignment Detail | Imagio Ultrasound (IUS) and Imagio optoacoustic/ultrasound (IUS+OA) images of breast masses previously acquired from the PIONEER-01 study (NCT01943916) referenced above were used for this study. Reader-02 was a single-arm sequentially read multi reader/case (MRMC) study comparing IUS vs Imagio (IUS+OA). New readers were recruited-NO new subjects/masses. Results were based on biopsy diagnosis or truth panel decision as ground truth obtained during PIONEER-01. |
| Arm/Group Title | Overall (Subjects Randomly Selected From PIONEER-01 Study) |
|---|---|
| Arm/Group Description | Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, baseline data are for overall population only. |
| Period Title: Overall Study | |
| STARTED | 480 |
| COMPLETED | 480 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Overall (Subjects Randomly Selected From PIONEER-01 Study) |
|---|---|
| Arm/Group Description | Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, baseline data derived from PIONEER-01 for sub set of 480 cases read during Reader-02 Study. |
| Overall Participants | 480 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
49.9
(14.4)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
480
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
87
18.1%
|
| Not Hispanic or Latino |
387
80.6%
|
| Unknown or Not Reported |
6
1.3%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
14
2.9%
|
| Native Hawaiian or Other Pacific Islander |
1
0.2%
|
| Black or African American |
54
11.3%
|
| White |
389
81%
|
| More than one race |
2
0.4%
|
| Unknown or Not Reported |
20
4.2%
|
| Region of Enrollment (Count of Participants) | |
| United States |
480
100%
|
| Mass Diagnosis (Count of Participants) | |
| Subjects (Benign+TPB+HR) |
300
62.5%
|
| Subjects (Cancer) |
180
37.5%
|
Outcome Measures
| Title | Gain in Specificity at Fixed 98% Sensitivity (fSp) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 12 months +/- 30 days follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-diagnose (ITD) |
| Arm/Group Title | IUS Alone | Imagio (IUS+OA) |
|---|---|---|
| Arm/Group Description | IUS alone imaging | IUS+OA imaging |
| Measure Participants | 480 | 480 |
| Mean (95% Confidence Interval) [% benign+TPB masses correctly identified] |
38.22
|
47.20
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IUS Alone, Imagio (IUS+OA) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0268 |
| Comments | Threshold for statistical significance <0.05 | |
| Method | Random Reader, Random Mass | |
| Comments | Curve Fitting Method: Empirical | |
| Title | Negative Likelihood Ratio (NLR) |
|---|---|
| Description | 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]. |
| Time Frame | Baseline to 12 months +/- 30 days follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-diagnose (ITD) |
| Arm/Group Title | Imagio Alone | Imagio (IUS+OA) |
|---|---|---|
| Arm/Group Description | IUS alone imaging | IUS+OA imaging |
| Measure Participants | 480 | 480 |
| Mean (95% Confidence Interval) [Ratio] |
0.053
|
0.047
|
| Title | Positive Likelihood Ratio (PLR) |
|---|---|
| Description | 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)]. |
| Time Frame | Baseline to 12 months +/- 30 days follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| Total population of subjects/masses |
| Arm/Group Title | IUS Alone | Imagio (IUS+OA) |
|---|---|---|
| Arm/Group Description | IUS alone imaging | IUS+OA imaging |
| Measure Participants | 480 | 480 |
| Mean (95% Confidence Interval) [Ratio] |
1.548
|
1.959
|
| Title | Partial Area Under the Curve (pAUC) |
|---|---|
| Description | 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. |
| Time Frame | Baseline to 12 months +/- 30 days follow-up |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-diagnose (ITD) |
| Arm/Group Title | IUS Alone | Imagio (IUS+OA) |
|---|---|---|
| Arm/Group Description | IUS Alone Imaging | IUS+OA imaging |
| Measure Participants | 480 | 480 |
| Mean (95% Confidence Interval) [Percentage of Probability] |
0.0205
|
0.0244
|
Adverse Events
| Time Frame | Baseline to 12 months +/- 30 days follow-up | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Overall (Subjects Randomly Selected From PIONEER-01 Study) | |
| Arm/Group Description | Each subject had one mass that was read by all readers. Each subject served as her own control, with imaging of each mass by both IUS and IUS+OA modalities. Therefore, safety data are for overall population only. | |
All Cause Mortality |
||
| Overall (Subjects Randomly Selected From PIONEER-01 Study) | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/480 (0%) | |
Serious Adverse Events |
||
| Overall (Subjects Randomly Selected From PIONEER-01 Study) | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/480 (0.4%) | |
| General disorders | ||
| Device breakage | 1/480 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Lung cancer | 1/480 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Overall (Subjects Randomly Selected From PIONEER-01 Study) | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/480 (2.9%) | |
| Cardiac disorders | ||
| Tachycardia | 1/480 (0.2%) | 1 |
| Hepatobiliary disorders | ||
| Gallbladder disorder | 1/480 (0.2%) | 1 |
| Infections and infestations | ||
| Postoperative wound infection | 1/480 (0.2%) | 2 |
| Injury, poisoning and procedural complications | ||
| Contusion | 1/480 (0.2%) | 1 |
| Post-procedural haematoma | 1/480 (0.2%) | 1 |
| Procedural dizziness | 1/480 (0.2%) | 1 |
| Upper limb fracture | 1/480 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Muscle spasms | 1/480 (0.2%) | 1 |
| Nervous system disorders | ||
| Paraesthesia | 5/480 (1%) | 5 |
| Skin and subcutaneous tissue disorders | ||
| Dermatitis contact | 1/480 (0.2%) | 1 |
| Skin warm | 1/480 (0.2%) | 1 |
| Vascular disorders | ||
| Hypertension | 1/480 (0.2%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The results of the study are the property of Seno Medical Instruments, Inc. All publications (manuscripts, abstracts or other modes of presentation) must be submitted and reviewed and approved in writing by Seno Medical Instruments, Inc., in advance of submission. The over all study results will first be submitted as a primary paper.
Results Point of Contact
| Name/Title | Vice President of Clinical Operations |
|---|---|
| Organization | Seno Medical Instruments, Inc. |
| Phone | 210-615-6501 |
| sschaeffer@senomedical.com |
- Reader-02 Study