A Proof-of-technology, Pilot, Prospective Clinical Study to Investigate the Feasibility and Performance of PROVIZ-a Radiomics-based Machine Learning Software, to Support Targeting of Prostate Biopsies on MRI Images in Biopsy-naive Patients
Phase: NA
Conditions: Prostate Cancer Diagnosis
Sponsor: Norwegian University of Science and Technology

PROVIZ proof-of-technology Study Protocol 
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Study Protocol 
      
 
A proof-of-technology, pilot, single-site, open-label, prospective clinical study to 
investigate the feasibility and performance of PROVIZ – a radiomics-based machine 
learning software, to support targeting of prostate biopsies on magnetic resonance images 
in biopsy-naive patients. 
 
This document represents a direct extraction of pertinent sections from the approved 
Clinical Investigation Plan (CIP) Version 1.5, dated 22nd January 2024, tailored to 
outline the study protocol. 
 
 
 
 
 
 
 
 
 
 
 
 

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1.1.1 List of abbreviations: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
s 
Abbreviation Term 
ADC 
Apparent diffusion coefficient maps  
ADE 
Adverse device effect 
AE 
Adverse event  
AI 
Artificial intelligence  
ASADE 
Anticipated serious adverse device effect 
AUC 
Area under the receiver operating characteristic curve 
bpMRI 
bi-parametric MRI  
CAD 
Computer-aided detection and diagnosis  
CIP 
Clinical investigation plan 
CRF 
Case report form  
csPCa 
Clinically significant prostate cancer  
DD 
Device deficiency  
DRE 
Digital rectal examination  
DWI 
Diffusion-weighted imaging  
eCRF 
Electronic Case report form  
EU 
European union 
FROC 
Free-response receiver operating characteristic curve 
GUI 
Graphical user interface  
Hemit 
Central Norway regional health IT 
IB 
Investigator’s brochure 
ICD 
Informed consent document  
ID 
Identity document 
ISO 
International organization for standardization 
mpMRI 
multi-parametric MRI  
MRI 
Magnetic resonance imaging  
NTNU 
Norwegian university of science and technology 
PACS 
Picture archiving and communication system 
PI 
Principal investigator  
PI-RADS 
Prostate imaging-reporting and data system 
PSA 
Prostate-specific antigen  
REC 
Regional committee for medical and healthcare research ethics  
SADE 
Serious adverse device effect  
SAE 
Serious adverse event  
SaMD 
Software as a medical device  
SIL 
Subject identification log 
SLV 
The Norwegian medicines agency 
SOP 
Standard operating procedure  
T2W 
T2-weighted imaging  
UADE 
Unanticipated adverse device effect 
USADE 
Unanticipated serious Adverse device effect  

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6.4 Procedures 
6.4.1 Clinical investigation procedure 
The clinical investigation procedure is summarized in Figure 6.4.1 and the decision to send 
patients for biopsy sampling summarized in Figure 6.4.2. 
 
Figure 6.4.1: Summary of the clinical investigation workflow. 

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Figure 6.4.2: Simplified explanation on how lesions are selected for biopsy during the 
prospective study. 
The patient meets for an invited MRI scan due to a suspected prostate cancer according to 
current clinical practice. A research coordinator checks to see if the patient meets the 
inclusion criteria for the investigation. This is done by asking the patient and checking the 
patient records. If the patient meets the criteria, then he is eligible for enrollment. He is 
then given an informed consent to participate that explains the purpose of the study, the 
risks and benefits, and the participant's rights in layman’s terms. Oral and written 
information will be given to the patient prior to scanning, and any questions will be 
answered. Patients accepting to take part will sign the informed consent after the scanning.  
The clinical investigation step by step as follows: 
1. Patient scanned using MRI with bpMRI protocol.  
2. The patient scan is stored in the production PACS (i.e., the hospital PACS) system. 
3. The images will be deidentified and the patient will get a pseudonym, before they 
sent to the local PACS (i.e., the study server PACS). All the of the sensitive, 
identifiable, and locatable information by means of a standard identification 
mechanism within the metadata for the patients and the physicians will be 
anonymized.  

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4. A password-protected Subject Identification Log (SIL) linking subject names to 
newly assigned IDs will be created and updated for each newly enrolled subject. 
The spreadsheet is stored in the hospital system and the password is only accessible 
to authorized individuals. 
5. The images will be sent to the local PACS on the sever via teleradiology. 
6. The radiologist will open the patient scan using the production PACS, as usual, 
check the images, and identify the suspicious areas, which need to be biopsied, 
according to PI-RADS. 
7. The radiologist will open the GUI desktop application from his/her workstation and 
check the software outputs (i.e., tumor probability map, the detection map, and 
gland segmentation). Here the pseudonym will be used from the SIL to enquire the 
subject in the local PACS. 
8. The radiologist compares his/her findings with the results of the investigational 
software. If there are areas detected by the software (detection map) that were not 
detected by the radiologist, the radiologist selects these areas (up to 3 areas). 
9. The radiologist will fill a report in the eCRF to be used by researchers only, flagging 
the detected areas for biopsy sampling into: 
a. Defined solely by the radiologist, with PI-RADS score + location. 
b. Overlap between the radiologist and the investigational software, with PI-
RADS score + location. 
c. Defined solely by the investigational software, with location. 
The location should be according to the areas identified by PI-RADS (Figure 6.4.3). 
Table 6.4.1 gives an example on the report. 
 
 
 
 
 
 
 
 
 
 

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Table 6.4.1: Example of radiological report of findings, for research purposes only. 
Pseudonym 
POT0001 
Finding 
number 
Human 
Investigational 
software 
Finding 
Location 
PI-RADS 
score 
1 
x 
 
Mid-PZpm-R 
3 
2 
x 
 
Apex-PZa-L 
4 
3 
x 
x 
Base-PZpl-R 
4 
4 
 
x 
Mid-PZa-L 
N/A 
 
 
 
Figure 6.4.3: The prostate regions according to PI-RADS. 
10. The radiologist fills out the report as usual without identifying whether a finding is 
identified by the investigational software or human, keeping the lesion number. The 
radiologist will add a sentence to his report indicating that some of these lesions 
may have been identified by investigational software. 

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11. The radiologist then opens Eigen Artemis Profuse software (Eigen Health, CL, 
USA) to delineate the prostate and suspicious lesions as usual. The radiologist 
semi-automatically delineates and adjusts the entire prostate after reviewing the 
automatic segmentation on the GUI screen. This is followed by delineation of the 
suspicious findings by the radiologist and the AI (up to 3 solely AI findings). Note 
that radiologists begin delineation in order (i.e., lesion 1, then 2, then 3, then 4, as 
indicated in the report in order). 
12. The radiologist will export the delineations file to the Eigen ARTEMIS - Prostate 
Fusion Biopsy System (Eigen Health, CL, USA). 
13. The urologist will review the radiologist's report and unless the patient has 
contraindications to prostate biopsy (due to comorbidity or remaining life 
expectancy) the patient will be registered for biopsy sampling procedure.  
14. When the patient arrives for the biopsy, he is prepared as usual.  
15. Prior to biopsy, the operating room nurse will import the radiologist's 
segmentations into the Eigen ARTEMIS - Prostate Fusion Biopsy System (Eigen 
Health, CL, USA). 
16. The urologist will perform an ultrasound scan for fusion with the MRI scan. 
17. The urologist will then obtain biopsies according to the standard clinical procedure. 
This includes targeting the delineated suspicious areas at least once. In some cases, 
the urologist may perform a systematic biopsy in addition to the targeted biopsy. 
The urologist will ask the nurse to place each biopsied specimen in a plastic tube 
immediately after collection and to immediately label the tube with Lesion 1, 2, 3 
... etc. (corresponding to the lesion number assigned by the radiologist for the 
targeted biopsies) in addition to labelling the biopsy location according to PI-RADS 
(Figure 6.4.3). 
18. The tubes are sent to pathology department for histopathological evaluation. Each 
lesion is evaluated separately. Some suspicious areas may have more than one 
biopsy taken from them. Then they are pooled and evaluated together to determine 
the overall Gleason score for each lesion separately.  
19. The data will be collected by the researchers, once every week, where the patient 
pseudonym (e.g., POT0001) will be used to name folders and deidentify scans upon 
exporting. The subject's scan images are pseudonymized and exported to an 
encrypted external hard drive and then uploaded to the lab at HUNT cloud. The 
graphical report of the biopsy procedure might be exported from the ARTEMIS 

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system to an encrypted external hard drive and then uploaded to the laboratory at 
HUNT cloud. The radiologist's report on the patient is exported to the Digital Life 
lab at HUNT cloud. The patient's clinical information is collected and exported to 
the lab at HUNT cloud. The lesion-based histopathology assessment report is 
exported to the lab at HUNT cloud. 
20. The data collected will finally be used for analyses according to primary and 
secondary objectives of the study. 
Overall, the deviation from normal clinical practice is very small. Deviations mainly relate 
to subject enrollment, the inclusion of test software in image analysis, and the storage and 
export of data for research. Specifically, the deviation is in steps 3, 5, 7, 8, 9, 19, and 20. 
Steps 3, 4, and 5 will be performed by HEMIT; steps 7, 8, and 9 will be performed by the 
radiologist; and steps 4, 19, and 20 will be performed by the sponsor’s representatives 
(research coordinators), see Section 6.4.2. 
Additional activities to the above procedure include user reporting of safety-related 
concerns or adverse events, or software-related bugs or errors to the PI and communication 
between the clinic and the PI to determine if it is necessary to suspend or terminate the 
study early. In addition, software users will be trained in the proper use of the software 
prior to the start of the investigation. 
14. 5 Procedures for recording and reporting Adverse Events and Device 
Deficiencies 
All adverse events, effects, device deficiencies, and related information will be recorded 
in detail in the medical records and the eCRF by the investigator or one of his/her delegate. 
The investigator will report all of these to the sponsor as it is specified in Table 14.4.1. The 
Sponsor will report all reportable events to the SLV in accordance with the SLV reporting 
procedure within the timeframes specified in Section 14.4.