TheraSphere Post-approval Study to Calculate the Radiation-absorbed Dose of Technetium-99m Macroaggregated Albumin (Tc-99m MAA) to the Whole Body and Non-liver Critical Organs.
Conditions: Hepatocellular Carcinoma
Sponsor: Boston Scientific Corporation

 
                                                                                 
     
 
 
 
 
 
NCT05233098 
Document Date: October 31, 2022 
 
 
 
 

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TheraSphere Post-Approval Study 
 
Study Reference Number: S2494 
 
 
CLINICAL INVESTIGATION PLAN 
 
 
 
 
 
Sponsored By: 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752, United States 
 
 
 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Contact Information 
Role 
Contact  
Clinical Contact 
Michelle Wells 
Sr. Manager, Clinical Trials  
Peripheral Interventions 
One Scimed Place 
Maple Grove, MN 55311 
United States 
1-763-494-1883 
michelle.wells@bsci.com 
Coordinating Principal 
Investigator(s) 
Riad Salem, MD, MBA 
Professor of Radiology, Medicine and Surgery 
Chief, Section of Vascular and Interventional Radiology 
Vice-Chair, Image-Guided Therapy 
Department of Radiology 
Northwestern University 
676 N. St Clair, Suite 800 
Chicago, IL 60611, USA  
1-312-695-6371 office phone 
rsalem1@nm.org 
Vendors/Labs/External 
Organizations 
A list of vendors/laboratories/external organizations involved in 
the trial is maintained by the sponsor. A complete listing of 
applicable vendors will be provided to clinical study sites. 
 
 
 
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Form/Template 92120219_Rev/Ver F 
Confidential  
 
                                                                           TheraSphere Post-Approval Study, 92762413, Rev/Ver B                         
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Original Release: August 17, 2021 
Current Version: October 27, 2022 
Revision Version 
Protocol Date 
Template 
number and 
version 
Protocol Section 
Modified 
Summary of Changes 
 
Justification for 
Modification 
A 
17 AUG 2021 
92120219, 
Rev F 
N/A 
Initial Release 
N/A 
B 
27 OCT 2022 
92120219, 
Rev F 
• 
2. Protocol synopsis 
• 
4. Introduction 
• 
6. Study Objective 
• 
7. Study Design 
• 
8. Subject Selection 
• 
10. Study Methods 
• 
14. Compliance 
• 
23. Abbreviations 
and Definitions 
• 
Removed reference to the TheraSphere 
IFU 
• 
Removed reference to uploading images to 
Imaging Portal 
• 
Corrected 21 CRF 50 and 56 to 21 CFR 50 
and 56 
• 
Removed abbreviations and definitions 
that do not appear in the text 
• 
Updates to support study 
enrollment by allowing 
inclusion of all patients 
receiving Tc-99m MAA 
infusion to determine 
eligibility for 
TheraSphere treatment. 
No impact on study 
results is expected from 
this update.  
• 
Updates to reflect change 
in image processing: 
analysis is being 
performed at study site 
instead of at a core lab, 
no upload of images 
required. 
• 
Administrative 
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2. Protocol Synopsis 
Patient Exposure Study 
 
Study 
Objective(s) 
Primary Objective: to calculate the radiation-absorbed dose of 
Technetium-99m macroaggregated albumin (Tc-99m MAA) to the 
whole body and to potential irradiated non-liver critical organs. 
Patient 
Population  
Patients who are being evaluated for TheraSphere administration.  
Study Product 
Tc-99m macroaggregated albumin 
Study Design 
Post-market prospective, single-arm, open-label, observational study.  
Patients will be required to provide written informed consent prior to 
any study procedures being conducted. Patients who provide written 
informed consent, fulfill all the inclusion criteria and meet none of the 
exclusion criteria will be considered enrolled in the study.  
Patients who are enrolled in the study will have 3 images taken after Tc-
99m MAA injection, with the final image occurring between 18 and 24 
hours after Tc-99m MAA injection.  
Planned 
Number of 
Patients 
A total of five patients will be enrolled in the study.  
Planned 
Number of 
Sites / 
Countries 
The study will be conducted at up to three clinical study sites in the US.  
Study Visit 1:
Written 
Informed 
Consent, I/E 
assessment, 
Subject 
enrollment 
Y-90 
mapping 
with Tc-99m 
MAA
Study Visit 2:
SPECT-CT 
immediately 
after Tc-99m 
MAA 
injection
Study Visit 3:
SPECT 4 
hours + 2 
hours after 
Tc-99m MAA 
injection
Study Visit 4:
SPECT > 18 
hours but <
24 hours 
after Tc-99m 
MAA 
injection
Study End
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Patient Exposure Study 
 
Primary 
Endpoints 
Mean absorbed dose (Gy) and activity (Bq) will be summarized for the 
whole body and for critical non-liver organs (including whole body 
effective dose). 
Follow-up 
Schedule 
At a minimum, all patients will be evaluated at the following 
timepoints: 
• Immediately following Tc-99m MAA injection 
• 4 hours ± 2 hours after Tc-99m MAA injection 
• > 18 hours after Tc-99m MAA injection but < 24 hours after Tc-
99m MAA injection 
 
At each evaluation timepoint, the following images will be performed: 
• Immediately following Tc-99m MAA injection: Single Photon 
Emission Computed Tomography in conjunction with Computed 
Tomography (SPECT-CT) 
• All other images: Single Photon Emission Computed 
Tomography (SPECT) 
 
The start of the study for each eligible patient will be immediately after 
signed written informed consent. The study will be considered complete 
after five patients have completed three post-Tc-99m MAA imaging 
assessments. 
Study Duration Enrollment is expected to be completed within 24 months; therefore, the 
total study duration is estimated to be 24 months. 
Participant 
Duration 
The study duration for each subject is expected to be up to 24 hours. 
Inclusion 
Criteria 
1. Patients 21 years and older 
2. Patient written informed consent 
3. Patients who receive Tc-99m MAA while being evaluated for 
TheraSphere treatment  
Exclusion 
Criteria 
1. Patients who are contraindicated for TheraSphere treatment 
2. Patients who are contraindicated for Tc-99m MAA per the 
applicable Package Insert 
3. Patients who do not receive Tc-99m MAA during pre-treatment 
Y-90 mapping 
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Patient Exposure Study 
 
Statistical Methods  
Statistical Test 
Method 
No formal hypothesis testing is proposed for the study assessment. 
Analyses and summaries will be descriptive. 
 
 
 
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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .........................................................................................................7 
3.1. Table of Figures .......................................................................................................9 
3.2. Table of Tables ......................................................................................................10 
4. 
INTRODUCTION .................................................................................................................11 
4.1. Background and Study Rationale ........................................................................11 
5. 
STUDY PRODUCT DESCRIPTION .......................................................................................11 
6. 
STUDY OBJECTIVE ...........................................................................................................12 
7. 
STUDY DESIGN .................................................................................................................12 
7.1. Scale and Duration ................................................................................................12 
7.2. Justification for the Study Design ........................................................................13 
8. 
SUBJECT SELECTION ........................................................................................................13 
8.1. Study Population and Eligibility ..........................................................................13 
8.2. Inclusion Criteria ..................................................................................................13 
8.3. Exclusion Criteria .................................................................................................14 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................14 
9.1. Point of Enrollment ...............................................................................................14 
9.2. Withdrawal ............................................................................................................14 
9.3. End-of-Study Definition........................................................................................14 
10. STUDY METHODS .............................................................................................................14 
10.1. Data Collection ......................................................................................................14 
10.2. Study Candidate Screening ..................................................................................16 
10.2.1. Strategies for Recruitment and Retention .................................................16 
10.3. Informed Consent ..................................................................................................16 
10.4. Study Visit 1: Screening Visit ...............................................................................16 
10.5. Study Visit 2: Immediately following Tc-99m MAA Injection .........................16 
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10.6. Study Visit 3: 4 hours (+ 2 hours) following Tc-99m MAA Injection ..............17 
10.7. Study Visit 4: > 18 hours but < 24 hours following Tc-99m MAA Injection ...17 
10.8. Study Completion ..................................................................................................17 
10.9. Source Documents .................................................................................................17 
11. STATISTICAL CONSIDERATIONS ......................................................................................17 
11.1. Primary Endpoints ................................................................................................18 
11.2. Sample Size ............................................................................................................18 
11.3. General Statistical Methods .................................................................................18 
11.3.1. Analysis Sets .............................................................................................18 
11.3.2. Control of Systematic Error/Bias ..............................................................18 
11.4. Data Analyses ........................................................................................................18 
11.4.1. Other Endpoints/Measurements ................................................................18 
11.4.2. Changes to Planned Analyses ...................................................................18 
12. DATA MANAGEMENT .......................................................................................................18 
12.1. Data Collection, Processing, and Review ............................................................18 
12.2. Data Retention .......................................................................................................19 
13. DEVIATIONS ......................................................................................................................19 
14. COMPLIANCE ....................................................................................................................20 
14.1. Statement of Compliance ......................................................................................20 
14.2. Investigator Responsibilities ................................................................................20 
14.2.1. Delegation of Responsibility ....................................................................22 
14.3. Institutional Review Board ...................................................................................22 
14.4. Sponsor Responsibilities .......................................................................................23 
14.5. Insurance ................................................................................................................23 
15. MONITORING ....................................................................................................................23 
16. POTENTIAL RISKS AND BENEFITS ...................................................................................23 
16.1. Package Insert .......................................................................................................23 
16.2. Risks associated with Participation in the Clinical Study .................................24 
16.3. Possible Interactions with Concomitant Medical Treatments, if applicable ...24 
16.4. Risk Minimization Actions ...................................................................................24 
16.5. Anticipated Benefits ..............................................................................................24 
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17. SAFETY REPORTING .........................................................................................................24 
17.1. Reportable Events by investigational site to Boston Scientific .........................24 
17.2. Definitions and Classification ...............................................................................25 
17.3. Relationship to Procedure ....................................................................................26 
17.4. Investigator Reporting Requirements .................................................................28 
17.5. Reporting to Regulatory Authorities / IRBs / Investigators ..............................29 
18. INFORMED CONSENT ........................................................................................................29 
19. COMMITTEES ...................................................................................................................30 
19.1. Safety Monitoring Process ....................................................................................30 
20. SUSPENSION OR TERMINATION ........................................................................................31 
20.1. Premature Termination of the Study ..................................................................31 
20.1.1. Criteria for Premature Termination of the Study ......................................31 
20.2. Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval .................................................................................................................31 
20.3. Requirements for Documentation and Subject Follow-up ................................31 
20.4. Criteria for Suspending/Terminating a Study Site ............................................32 
21. STUDY REGISTRATION AND RESULTS .............................................................................32 
21.1. Study Registration .................................................................................................32 
21.2. Clinical Investigation Report ...............................................................................32 
21.3. Publication Policy ..................................................................................................32 
22. BIBLIOGRAPHY .................................................................................................................33 
23. ABBREVIATIONS AND DEFINITIONS .................................................................................33 
23.1. Abbreviations .........................................................................................................33 
23.2. Definitions ..............................................................................................................34 
 
 
3.1. Table of Figures 
Figure 7.1-1: TheraSphere Post-Approval Study Design ....................................................... 13 
 
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3.2. Table of Tables 
Table 8.2-1: Inclusion Criteria ................................................................................................ 13 
Table 8.3-1: Exclusion Criteria ............................................................................................... 14 
Table 10.1-1: Schedule of Assessments .................................................................................. 15 
Table 17.2-1: Safety Definitions ............................................................................................. 25 
Table 17.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 27 
Table 17.4-1: Investigator Reporting Requirements ............................................................... 28 
Table 23.1-1: Abbreviations ................................................................................................. 33 
Table 23.2-1: Definitions ...................................................................................................... 34 
 
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4. Introduction 
4.1. Background and Study Rationale 
TheraSphere is a Y-90 glass microsphere therapy for Selective Internal Radiation Therapy 
(SIRT) in hepatocellular carcinoma (HCC). The treatment goal of SIRT is to selectively target 
and deliver a tumoricidal radiation dose to tumors within the liver, while maintaining an 
acceptable radiation dose to the normal liver tissue. 
TheraSphere is administered through the hepatic artery which supplies blood to the hepatic 
tumors. The mean tissue penetration of the beta energy from the Y-90 in the microspheres is 
approximately 2.5 mm, with a maximum range up to 11 mm. Cancer cells adjacent to the 
embedded microspheres are killed while the nearby hepatic parenchyma and tissues in 
adjacent organs are generally spared the destructive effects of the beta radiation.  
The United States Food and Drug Administration (FDA) approved the use of TheraSphere to 
treat unresectable HCC on March 17, 2021.  
Prior to administration of TheraSphere, hepatic arteriography and Technetium-99m 
macroaggregated albumin (Tc-99m MAA) scanning are performed to detect extrahepatic 
shunting to the lung or the gastrointestinal tract. 
This study is being conducted, at the request of the FDA, to provide data to calculate the 
radiation-absorbed dose of Tc-99m MAA to the whole body and to potential irradiated non-
liver critical organs. 
5. Study Product Description 
Lung perfusion scintigraphy with Tc-99m MAA is an important diagnostic tool in SIRT 
planning. Tc-99m MAA is utilized as a TheraSphere surrogate.  
There are several Tc-99m MAA imaging agents that have been approved by the FDA that can 
be used for TheraSphere pre-treatment mapping. The specific brand of Tc-99m MAA imaging 
agent that is used is at the discretion of the physician. 
Several studies have examined the biodistribution of Tc-99m MAA as used in TheraSphere 
pre-treatment planning procedures. Bailey et al published a retrospective case series review 
of 70 HCC patients and examined extrahepatic uptake using combined planar and SPECT/CT 
imaging (1).  Results showed the largest uptake was seen in the renal cortex, salivary glands, 
thyroid gland and gastric mucosa amongst 70 patients (100%), 23 patients (33%), 23 patients 
(33%) and 32 patients (46%), respectively. Lesser uptake was noted in other organs in fewer 
patients. This extrahepatic deposition is thought to be a result of deposition of  Tc-99m MAA 
breakdown products such as free Tc-99m-pertechnetate which is released over time (1) (2) 
(3).  In the gastric mucosa and thyroid gland, free 99mTc-pertechnetate deposition is visualized 
as a diffuse pattern and in the stomach is distinguishable from non-target Tc-99m MAA 
delivery and does not represent non-target administration or a pathologic concern (3) (4). Uliel 
et al suggested that using a high labelling efficiency Tc-99m-pertechnetate and minimizing 
the time interval between radiotracer injection and imaging time reduces the amount of 
nonspecific background activity (3).  
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In clinical practice, there is typically a delay between Tc-99m MAA injection and imaging 
during which dissociation of the Tc-99m MAA occurs. Grosser et al found that there was a 
time-dependent significant release of free 99mTc from the liver over a 24-hour time period 
after examining scans taken at 1, 5 and 24 hours after intraarterial Tc-99m MAA injection (5). 
The biexponential decay curve can be best described as: T half-life, fast = 7.9 hours, T half-
life, slow =22.4 hours; adjusted R2=0.77.  The authors therefore recommended that liver 
perfusion scintigraphy with Tc-99m MAA be performed no later than four hours after 
injection. De Gersem et al did a similar study performing whole body scans at < 1 hour, 
between 1 and 4 hours, and > 4 hours post Tc-99m MAA injection (2). They found higher 
levels of radioactivity in the lung (extrahepatic deposition) in the > 4 hour scans than in the < 
1 hour scans.   This overestimation has clinical relevance as the authors conclude that based 
on > 4 hour scan results, several patients would have been excluded from receiving 
radioembolization. The longer imaging is delayed post radiotracer injection, the more free Tc-
99m is released. The same logic can be applied to extrahepatic activity seen on imaging post 
Tc-99m MAA injection.  Indeed, Bailey et al did not note any correlation between 
extrahepatic uptake and time to imaging however their mean interval was only 92 minutes 
(1).   
In summary, several authors have described the reasons for extrahepatic organ uptake of Tc-
99m MAA degradation products as visualized on imaging. Presence of radiotracer in these 
organs originates from Tc-99m MAA degradation products and does not pose a clinical 
concern (3). Keeping the time interval between radiotracer injection and imaging as short as 
possible limits the distribution of radiotracer degradation products to extrahepatic tissue (1).  
6. Study Objective 
The objective of this study is to provide data to calculate the radiation-absorbed dose of  
Tc-99m MAA to the whole body and to potential irradiated non-liver critical organs. 
7. Study Design 
The TheraSphere Post-Approval Study is a post-market, prospective, single-arm, open-label, 
observational study to support the use of TheraSphere for the treatment of hepatocellular 
carcinoma. 
7.1. Scale and Duration 
This study is planned to be conducted at up to 3 clinical study sites in the United States. Five 
patients will be enrolled in the study. 
A patient is considered enrolled once an informed consent form has been signed, and all 
inclusion and no exclusion criteria have been met.  
If the patient is found to not meet the inclusion criteria, the patient should not be included in 
the study. 
Patients enrolled in the study will have 3 images taken after Tc-99m MAA injection. The final 
image will occur between 18 and 24 hours after Tc-99m MAA injection.   
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Enrollment is expected to be completed within 24 months; therefore, the total study duration 
is estimated to be 24 months. 
  
 
Figure 7.1-1: TheraSphere Post-Approval Study Design 
 
7.2. Justification for the Study Design 
This post-market study is being conducted at the direction of the FDA. Eligible study patients, 
after discussion and agreement with their treating physician, will be undergoing evaluation 
for the delivery of TheraSphere for the treatment of HCC. This study will provide data on the 
pre-Y-90 radiation-absorbed dose risk of Tc-99m MAA to the whole body and to potential 
irradiated non-liver critical organs.  
8. Subject Selection  
8.1. Study Population and Eligibility  
The intended population for the TheraSphere Post-Approval study is patients with HCC who 
are undergoing evaluation to assess eligibility for TheraSphere treatment. 
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.3) is 
met.  
Table 8.2-1: Inclusion Criteria 
Inclusion 
Criteria 
1. Patients 21 years and older 
2. Written informed consent 
3. Patients who receive Tc-99m MAA while being evaluated for TheraSphere treatment  
 
Study Visit 1:
Written 
Informed 
Consent, I/E 
assessment, 
Subject 
enrollment 
Y-90 mapping 
with Tc-99m 
MAA
Study Visit 2:
SPECT-CT 
immediately 
after Tc-99m 
MAA injection
Study Visit 3:
SPECT 4 hours 
+ 2 hours 
after Tc-99m 
MAA injection
Study Visit 4:
SPECT > 18 
hours but < 24 
hours after 
Tc-99m MAA 
injection
Study End
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8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8.3-1) will be excluded from this 
clinical study. 
Table 8.3-1: Exclusion Criteria 
Exclusion 
Criteria 
1. Patients who are contraindicated for TheraSphere treatment  
2. Patients who are contraindicated for Tc-99m MAA per the applicable Package 
Insert   
3. Patients who do not receive Tc-99m MAA during pre-treatment Y-90 mapping 
 
9. Subject Accountability 
9.1. Point of Enrollment 
Patients who provided written informed consent, meet all inclusion criteria and meet no 
exclusion criteria are considered enrolled in the study. 
9.2. Withdrawal 
Patients may leave the study at any time for any reason and without any consequences. The 
Investigator or designee will try to obtain the reason for study withdrawal and document this 
in the source data. An Investigator may discontinue a patient from the study, with or without 
the patient’s consent, for any reason that may, in the Investigator’s opinion, negatively affect 
the well-being of the patient. If a patient is withdrawn from the study, the Investigator will 
promptly inform the patient and sponsor. Data already collected will be retained and reported; 
however, no new data will be collected after the withdrawal. 
Patients withdrawn from the study for any reason will be asked to participate in a limited 
capacity by allowing their medical status to be followed by telephone contact, medical chart 
review, or other agreed upon method. If a patient decides not to continue participation in a 
limited capacity, the Investigator will not access their medical record or other confidential 
records for new purposes related to the study; however, study data collected prior to their 
withdrawal may be reviewed and publicly available records may be consulted prior to or after 
their withdrawal. 
9.3. End-of-Study Definition  
The study will be considered complete after five patients have three post-Tc-99m MAA 
imaging assessments. 
10. Study Methods 
10.1. Data Collection 
The data collection schedule is shown in Table 10.1-1. 
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Table 10.1-1: Schedule of Assessments 
Procedure/Assessment 
Study Visit 1: 
Screening and 
Enrollment 
Study Visit 2: 
Immediately 
following Tc-
99m MAA 
injection 
Follow-up Visits 
Study Visit 3: 
4 hours (+ 2 
hours) following 
Tc-99m MAA 
injection 
Study Visit 4: 
> 18 hours but < 24 
hours following Tc-
99m MAA 
injection 
Informed consent process, including informed consent signature date 
X 
 
 
 
Inclusion/Exclusion Criteria Assessment 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
SPECT-CT 
 
X 
 
 
SPECT 
 
 
X 
X 
Procedure-related Serious Adverse Events assessment 
 
X 
X 
X 
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10.2. Study Candidate Screening 
A patient is considered enrolled once an informed consent form has been signed, and all 
inclusion and no exclusion criteria have been met. 
If the patient is found to not meet the inclusion criteria, the patient should not be included in 
the study, nor should the patient be followed post-procedure per protocol. 
10.2.1. 
Strategies for Recruitment and Retention 
The intended population for the this study are patients who are undergoing evaluation for the 
use of TheraSphere to treat HCC. Patients may be recruited through the Investigator’s practice 
or referring physicians. Any information disseminated to potential patients (e.g. 
advertisements, pamphlets, posters) must be approved by the investigational center’s IRB 
prior to use.  
Every effort must be made by the site to collect patient data per the Data Collection Schedule 
in Section 10.1. 
10.3. Informed Consent 
Before any study-specific tests or procedures are performed, patients will be asked to read 
and sign the IRB-approved study Informed Consent Form (ICF). Patients must be given ample 
time to review the ICF and have questions answered before signing. 
Refer to section 9.1 for definition of point of enrollment. 
10.4. Study Visit 1: Screening Visit 
After a patient has given written informed consent, the following data should be collected. 
Data may be collected within 30 days prior to the Tc-99m MAA injection. 
• Inclusion/Exclusion criteria assessment 
• Demographics 
• Medical history 
10.5. Study Visit 2: Immediately following Tc-99m MAA Injection 
Immediately following the injection of Tc-99m MAA during Y-90 mapping, the following 
data should be collected:  
• Procedural and study product data 
• Tc-99m MAA SPECT-CT 
• Procedure-related serious adverse events 
 
NOTE: all adverse events related to Tc-99m MAA should be reported to the applicable 
manufacturer through their defined Post-Market Surveillance procedure. 
 
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10.6. Study Visit 3: 4 hours (+ 2 hours) following Tc-99m MAA Injection 
At 4 hours (+2 hours) following the injection of Tc-99m MAA during Y-90 mapping, the 
following data should be collected:  
• Tc-99m MAA SPECT 
• Procedure-related serious adverse events 
 
NOTE: all adverse events related to Tc-99m MAA should be reported to the applicable 
manufacturer through their defined Post-Market Surveillance procedure. 
10.7. Study Visit 4: > 18 hours but < 24 hours following Tc-99m MAA Injection 
At least 18 hours, but no more than 24 hours, following the injection of Tc-99m MAA during 
Y-90 mapping, the following data should be collected:  
• Tc-99m MAA SPECT 
• Procedure-related serious adverse events 
 
NOTE: all adverse events related to Tc-99m MAA should be reported to the applicable 
manufacturer through their defined Post-Market Surveillance procedure. 
10.8. Study Completion 
A patient’s participation in the study will be complete after the final data point in Study Visit 
4 has been collected. Serious procedure-related adverse events that are still ongoing at the end 
of the subject’s participation in the trial will be followed up for resolution status and this 
information will be provided to BSC for the purpose of regulatory agency reporting for the 
trial. 
10.9. Source Documents 
It is preferable that original source documents are maintained, when available. In lieu of 
original source documents, certified copies are required to be maintained.  A certified copy is 
a copy (irrespective of the type of media used) of the original record that has been verified 
(i.e., by a dated signature or by generation through a validated process) to have the same 
information, including data that describe the context, content, and structure, as the original.  
11. Statistical Considerations 
The details of all statistical analyses will be described in the Statistical Analysis Plan.  
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11.1. Primary Endpoints 
The endpoints of the study are the mean absorbed doses and delivered activity for whole body 
and for critical organs (including whole body effective dose). The mean and standard 
deviation will be summarized for each of these. 
11.2. Sample Size 
A formal sample size was not conducted for this study; however, five patients with three 
images each are required. 
11.3. General Statistical Methods 
11.3.1. 
Analysis Sets 
The Intent to Treat (ITT) population will comprise of all patients enrolled in the study that 
meet eligibility criteria. All analyses will be performed on the ITT population. 
11.3.2. 
Control of Systematic Error/Bias 
To minimize patient selection bias, all consecutively eligible patients, who provide written 
informed consent, will be included in the study. 
11.4. Data Analyses 
Analyses and summaries will be descriptive. For continuous and/or ordinal variables, the 
descriptive statistics will include number evaluated, mean, standard deviation, median, 
quartiles, minimum and maximum. Categorical data will be summarized with observed counts 
and percentages for each category. 
11.4.1. 
Other Endpoints/Measurements 
Demographics data and medical history will also be summarized. Additionally, SAEs related 
to the procedure will be summarized. SAEs will be coded according to MedDRA. 
11.4.2. 
Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the analyses will be 
documented in an amended Statistical Analysis Plan approved prior to performing the 
analyses. Changes from the planned statistical methods after performing the analyses will be 
documented in the clinical study report along with a reason. 
12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system.  
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The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case report 
forms (eCRFs) in compliance with local regulations. A written signature on printouts of the 
eCRFs must also be provided if required by local regulation. Changes to data previously 
submitted to the sponsor require a new electronic signature by the Investigator acknowledging 
and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. 
Manual and/or automatic queries will be created in the Medidata EDC system and will be 
issued to the site for appropriate response. Site staff will be responsible for resolving all 
queries in the database. 
All access to the clinical database will be changed to “Read only” after all data is either “Hard 
Locked” or “Entry Locked”. Once acceptance of the final report or finalization of publications 
(as applicable) is received, final database storage and archiving activities can begin. Once all 
of the closeout activities are completed a request to IT is submitted to have the “Database 
Locked” or Decommissioned and all database access revoked. 
12.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all essential 
study documents and source documentation that support the data collected on the study 
subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform BSC in writing where 
paper or electronic files are maintained in case files are stored off site and are not readily 
available. 
13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB, and the regulatory authority if applicable of any deviation 
from the investigational plan to protect the life or physical well-being of a subject in an 
emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 working days 
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after the emergency occurred, or per prevailing local requirements, if sooner than 5 working 
days.  
Protocol deviations related to informed consent, inclusion/exclusion criteria and safety 
reporting, with the reason for the deviation and the date of occurrence, must be documented 
and reported to the sponsor within the EDC. Sites may also be required to report deviations 
to the IRB, and the regulatory authority, per local guidelines and national/government 
regulations.  
Protocol deviations not related to the informed consent process, eligibility, or safety reporting 
are not required to be reported to the sponsor for this study. Every attempt should be made to 
perform procedures and collect data according to this protocol. 
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/FDA notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
The sponsor will not approve protocol waivers.  
14. Compliance 
14.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site can 
be “Authorized to Enroll,” the investigational site must enter into a Clinical Study Agreement 
with the sponsor that details the financing of the study as well as the rights and obligations of 
the investigational site and the investigator. This study will be conducted in accordance with 
21 CFR 50 and 56, ethical principles that have their origins in the Declaration of Helsinki, 
and applicable individual country laws and regulations. The study shall not begin until the 
required approval/favorable opinion from the IRB and/or regulatory authority has been 
obtained, if appropriate. Also, the study shall not begin prior to issuance of the site 
Authorization to Enroll, as provided by the sponsor. Any additional requirements imposed by 
the IRB/ or regulatory authority shall be followed, if appropriate.  
14.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation plan,  
ethical principles that have their origins in the Declaration of Helsinki, any conditions of 
approval imposed by the reviewing IRB, and prevailing local and/or country laws and/or 
regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement.   
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
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curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation related 
to informed consent, inclusion/exclusion criteria, and safety reporting from the 
approved protocol that occurred during the course of the clinical investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
• Record, report, and assess (seriousness and relationship to the procedure) every adverse 
event as applicable per the protocol. 
• Report to sponsor, per the protocol requirements, all reportable events. 
• Report to the IRB and regulatory authorities any adverse events as required by 
applicable laws or regulations or this protocol or by the IRB, and supply BSC with any 
additional requested information related to the safety reporting of a particular event. 
• Allow the sponsor to perform monitoring and auditing activities, and be accessible to 
the clinical research monitor or auditor and respond to questions during monitoring 
visits or audit(s). 
• Allow and support regulatory authorities and the IRB when performing auditing 
activities. 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in 
a clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, 
as needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
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with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks through up-to-date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that may interfere with the conduct 
of the clinical study or interpretation of results. 
14.2.1. 
Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, are competent to perform the tasks they have been delegated and 
adequate supervision of those to whom tasks are delegated. Where there is a sub investigator 
at a site, the sub investigator should not be delegated the primary supervisory responsibility 
for the site. The investigator is accountable for regulatory violations resulting from failure to 
adequately supervise the conduct of the clinical study.  
14.3. Institutional Review Board 
The investigational site will obtain the written and dated approval/favorable opinion of the 
IRB for the clinical investigation before recruiting subjects and implementing all subsequent 
amendments, if required. 
A copy of the written IRB and ICF, must be received by the sponsor before recruitment of 
subjects into the study. Prior approval must also be obtained for other materials related to 
subject recruitment or which will be provided to the subject. 
Any amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study.  All changes to the ICF will be IRB approved; a 
determination will be made regarding whether a new ICF needs to be obtained from 
participants who provided consent, using a previously approved ICF.  
Annual IRB approval and renewals will be obtained throughout the duration of the study as 
required by applicable local/country laws or regulations or IRB requirements. Copies of the 
study reports and the IRB continuance of approval must be provided to the sponsor.  
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14.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to Contract Research Organization (CRO), will have access to this 
information. Authorized regulatory personnel have the right to inspect and copy all records 
pertinent to this study. Study data collected during this study may be used by BSC for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, new medical research and proposals for developing new medical products and 
procedures. All data used in the analysis and reporting of this study or shared with a third-
party researcher will be without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
14.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC 
for subjects in the study will be obtained. 
15. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements.  
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
16. Potential Risks and Benefits 
16.1. Package Insert 
Please refer to the applicable Manufacturer’s Package Insert for the Tc-99m MAA for an 
overview of anticipated adverse events and risks associated to the product.   
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16.2. Risks associated with Participation in the Clinical Study 
As this study is a post-market observational study, the additional risk associated with 
participating in this study is related to the collection of patient data and confidentiality thereof.  
There may be additional risks linked to the procedure, and follow-up testing which are 
unforeseen at this time.  
16.3. Possible Interactions with Concomitant Medical Treatments, if applicable 
Refer to the Tc-99m MAA-specific Package Insert for recommendations and for further 
information on interactions and side effects associated with concomitant medical treatments 
following the procedure.  
16.4. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject selection 
criteria, close monitoring of the subject's physiologic status during procedures and/or follow-
ups and by promptly supplying BSC with all pertinent information required by this protocol. 
16.5. Anticipated Benefits 
Patients may or may not receive benefits from participating in this study. Medical science and 
future patients may benefit from the results of this study.   
17. Safety Reporting 
17.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of the following categories: 
• All procedure related serious adverse events 
• New findings/updates in relation to already reported events 
• All adverse events related to Tc-99m MAA should be reported to the applicable 
manufacturer through their defined Post-Market Surveillance procedure. 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the Tc-99m MAA or procedure, it should be submitted to BSC as a 
procedure-related adverse event. 
Any reportable event, experienced by the study subject after informed consent, whether prior 
to, during or subsequent to the procedure, must be recorded in the eCRF. 
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Underlying diseases and chronic conditions are not reported unless there is an increase in 
severity or frequency during the course of the investigation. Death should not be recorded as 
an SAE, but should only be reflected as an outcome of one (1) specific SAE (see Table 17.2-1 
for AE definitions). 
Refer to the applicable Package Insert for the known risks associated with Tc-99m MAA.  
17.2. Definitions and Classification 
Adverse event definitions are provided in Table 17.2-1. Administrative edits were made on 
the safety definitions from ISO 14155 and EU 2017/745 for clarification purposes. 
Table 17.2-1: Safety Definitions 
Term 
Definition 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MEDDEV 2.7/3  
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event.  
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient admission  
Note: although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria 
(e.g. medical or surgical intervention to prevent permanent 
impairment or damage) 
• 
elective and pre-planned treatment/surgery for a pre-existing 
condition that is documented in the subject’s record at the time of 
consent/enrollment 
• 
admission for social reasons and/or respite care in the absence of 
any deterioration in the subject’s general condition (e.g. subject is 
homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to the clinical 
study (e.g. procedure required by protocol) 
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Table 17.2-1: Safety Definitions 
Term 
Definition 
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization are 
evaluated to determine if they prolonged hospitalization or meet another 
SAE criteria. 
 
17.3. Relationship to Procedure 
The Investigator must assess the relationship of the reportable SAE to the study procedure. 
See criteria in Table 17.3-1:  
NOTE: Only procedure-related serious adverse events are required to be reported to BSC 
through the EDC. To avoid administrative errors, the table below has been left in its entirety. 
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Table 17.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Ref: MEDDEV 2.7/3 
Relationship to the device, comparator or procedures can be excluded when: 
- the event is not a known side effect of the product category the device belongs to 
or of similar devices and procedures; 
- the event has no temporal relationship with the use of the study device or the 
procedures; 
- the serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible; 
- the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event; 
- the event involves a body-site or an organ not expected to be affected by the 
device or procedure;  
- the serious event can be attributed to another cause (e.g. an underlying 
or concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors); 
- the event does not depend on a false result given by the study device used for 
diagnosis, when applicable; harms to the subject are not clearly due to use error; 
- In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device or comparator, or the relationship 
with procedures is weak but cannot be ruled out completely. Alternative causes are 
also possible (e.g. an underlying or concurrent illness/ clinical condition or/and an 
effect of another device, drug or treatment). Cases were relatedness cannot be 
assessed or no information has been obtained should also be classified as possible. 
Probably Related 
Ref: MEDDEV 2.7/3 
The relationship with the use of the study device, comparator, or the relationship 
with procedures seems relevant and/or the event cannot be reasonably explained by 
another cause, but additional information may be obtained. 
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Table 17.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Causal Relationship 
Ref: MEDDEV 2.7/3 
The serious event is associated with the study device or comparator or with 
procedures beyond reasonable doubt when: 
- the event is a known side effect of the product category the device belongs to or 
of similar devices and procedures; 
- the event has a temporal relationship with the study device use/application or 
procedures; 
- the event involves a body-site or organ that 
-the study device or procedures are applied to; 
-the study device or procedures have an effect on; 
- the serious event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
- the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when clinically feasible); 
- other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately ruled 
out; 
- harm to the subject is due to error in use; 
- the event depends on a false result given by the study device used for diagnosis, 
when applicable; 
- In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious event. 
 
17.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in  
Table 17.4-1. 
 
Table 17.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Serious Adverse Event  
Complete AE eCRF page 
with all available new and 
updated information.  
• 
Within 10 calendar days after becoming 
aware of the event or as per local/regional 
regulations.  
• 
Reporting required through end of study.  
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Event Classification 
Communication Method  
Communication Timeline post-market 
studies*  
(MEDDEV 2.12/1:  
GUIDELINES ON A MEDICAL DEVICE 
VIGILANCE SYSTEM) 
Provide all relevant source 
documentation (de-
identified/ pseudonymized) 
for reported event.  
• 
When documentation is available 
• 
Upon request of sponsor 
 
17.5. Reporting to Regulatory Authorities / IRBs / Investigators 
BSC is responsible for reporting adverse event information to all participating Principal 
Investigators, IRBs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IRB, and regulatory authorities of 
SAEs as required by local/regional regulations. 
18. Informed Consent 
Subject participation in this clinical study is voluntary.  Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to any study-required procedures and/or 
testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, any applicable national regulations, and local Ethics 
Committee and/or Regulatory authority, as applicable. The ICF must be accepted by BSC or 
its delegate (e.g., CRO), and approved by the site’s IRB, or central IRB, if applicable. 
Boston Scientific will provide a study-specific template of the ICF to investigators 
participating in this study. The ICF template may be modified to meet the requirements of the 
investigative site’s IRB.  Any modification requires acceptance from BSC prior to use of the 
form.  The ICF must be in a language understandable to the subject and if needed, BSC will 
assist the site in obtaining a written consent translation. Translated consent forms must also 
have IRB approval prior to their use.  Privacy language shall be included in the body of the 
form or as a separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
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• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects 
throughout the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the site and a copy of the signed and dated document and any 
other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements (e.g., FDA requirement is within 5 working days of 
learning of such an event). Any violations of the informed consent process must be reported 
as deviations to the sponsor and local regulatory authorities (e.g. IRB), as appropriate. 
If new information becomes available that can significantly affect a subject's future health and 
medical care, that information shall be provided to the affected subject(s) in written form via 
a revised ICF or, in some situations, enrolled subjects may be requested to sign and date an 
addendum to the ICF. In addition to new significant information during the course of a study, 
other situations may necessitate revision of the ICF, such as if there are amendments to the 
applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB. The new version of the ICF must be approved by the 
IRB. Acceptance by Boston Scientific is required if changes to the revised ICF are requested 
by the site’s IRB. The IRB will determine the subject population to be re-consented. 
19. Committees 
19.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operation group review safety 
data as it is reported by the sites throughout the duration of the study. During scheduled 
monitoring activities, clinical research monitors further support this review through their 
review of source documents and other data information. The BSC Medical Safety and Safety 
Trial Operations team include health care providers with expertise in oncology and with the 
necessary therapeutic and subject matter expertise to evaluate and classify the events into the 
categories outlined above. 
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20. Suspension or Termination 
20.1. Premature Termination of the Study 
Boston Scientific, in collaboration with the FDA, reserves the right to terminate the study at 
any stage but intends to exercise this right only for valid scientific reasons and reasons related 
to protection of subjects.  Investigators, associated IRBs, and regulatory authorities, as 
applicable, will be notified in writing in the event of study termination. 
20.1.1. 
Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IRB or regulatory authorities to suspend or terminate the clinical 
investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
20.2. Termination of Study Participation by the Investigator or Withdrawal of IRB 
Approval 
Any investigator, or associated IRB or regulatory authority may discontinue participation in 
the study or withdraw approval of the study, respectively, with suitable written notice to 
Boston Scientific. Investigators, associated IRBs, and regulatory authorities, as applicable, 
will be notified in writing in the event of these occurrences. 
20.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB and regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled subjects will be managed thereafter will be provided.  
In the event an IRB terminates participation in the study, participating investigators, 
associated IRBs, and regulatory authorities, as applicable, will be notified in writing. Detailed 
information on how enrolled subjects will be managed thereafter will be provided by Boston 
Scientific. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility, detailed information on how enrolled subjects 
will be managed thereafter will be provided by Boston Scientific. 
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The Principal Investigator or his/her designee must return all study-related documents, unless 
this action would jeopardize the rights, safety, or welfare of the subjects. 
20.4. Criteria for Suspending/Terminating a Study Site 
Boston Scientific reserves the right to stop the inclusion of subjects at a study site at any time 
after the study initiation visit if no subjects have been enrolled for a period beyond one year 
after site initiation, or if the site has multiple or severe protocol violations/noncompliance 
without justification and/or fails to follow remedial actions. 
The IRB and regulatory authorities, as applicable, will be notified. Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule. 
21. Study Registration and Results 
21.1. Study Registration 
If required, to comply with applicable laws and regulations, the study will be registered on a 
publicly accessible database. 
21.2. Clinical Investigation Report 
Progress reports will be submitted to FDA every six months until enrollment is complete and 
annually thereafter until the study is complete. Complete study results will be made available 
in accordance with the legal requirements and the recognized ethical principles, in accordance 
with the Boston Scientific Policy. A Clinical Investigation Report will be made available to 
all investigators, IRB and regulatory authorities, as applicable in accordance with the Boston 
Scientific Policy and local requirements. As applicable an abbreviated Clinical Investigation 
Report will be made available on a publicly accessible database. 
21.3. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any 
publication or presentation relating to a BSC study or its results. BSC may submit study results 
for publication (regardless of study outcome) following the conclusion or termination of the 
study. Boston Scientific adheres to the Contributorship Criteria set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of study results in a timely 
manner, while maintaining an unbiased presentation of study outcomes, BSC personnel may 
assist authors and investigators in publication preparation provided the following guidelines 
are followed:  
• All authorship and contributorship requirements as described above must be 
followed. 
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• BSC involvement in the publication preparation and the BSC Publication Policy 
should be discussed with the Coordinating Principal Investigator(s) and/or 
Executive/Steering Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding 
publication content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/).  
22. Bibliography 
1. Bailey JS, Dewaraja Y, Hubers D, et al. Biodistribution of 99mTc-MAA on 
SPECT/CT performed for 90Y-radioembolization therapy planning: a pictorial 
review. Clin Transl Imaging. 2017; 5: p. 473-483. 
2. De Gersem R, Maleux G, Vanbilloen H, et al. Influence of time delay on the 
estimated lung shunt fraction on 99mTc-labelled MAA scintigraphy for 90Y 
microsphere treatment planning. Clin Nucl Med. 2013; 38: p. 940-942. 
3. Uliel L, Royal HD, Darcy MD, et al. From the Angio Suite to the gamma-camera: 
Vascular mapping and 99mTc-MAA hepatic perfusion imaging before liver 
radioembolization- A comprehensive pictorial review. J Nucl Med. 2012; 53: p. 
1736-1747. 
4. Ahmadzadehfar H, Sabet A, Biermann K, et al. The Significance of 99mTc-MAA 
SPECT/CT liver perfusion imaging in treatment planning for 90Y-microsphere 
selective internal radiation treatment. J Nucl Med. 2010; 51: p. 1206-1212. 
5. Grosser OS, Ruf J, Kupitz D et al.  Pharmacokinetics of 99mTc-MAA-and 99mTc-
HSA-microspheres used in preradioembolization dosimetry:  Influence on the 
liver-lung shunt. J Nucl Med. 2016; 57: p. 925-927. 
23. Abbreviations and Definitions  
23.1. Abbreviations 
Abbreviations are shown in Table 23.1-1.   
Table 23.1-1: Abbreviations 
Abbreviations 
Term 
AE 
Adverse Event 
Bq 
Becquerel 
BSC 
Boston Scientific Corporation 
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Abbreviations 
Term 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
Gy 
Gray 
HCC 
Hepatocellular Carcinoma 
ICF 
Informed Consent Form 
IRB 
Institutional Review Board 
SAE 
Serious Adverse Event 
SIRT 
Selective internal radiation therapy 
SPECT 
Single Photon Emission Computed Tomography 
SPECT-CT 
Single Photon Emission Computed Tomography in conjunction 
with Computed Tomography 
Tc-99m MAA 
Technetium-99m macroaggregated albumin 
Y-90 
yttrium-90 
23.2. Definitions 
Terms are defined in Table 23.2-1. 
Table 23.2-1: Definitions 
Term 
Definition 
Complication 
An undesirable clinical event that results in death, injury, or 
invasive intervention. Complications may include, but are not 
limited to perforation, occlusion, vessel spasm, etc. 
Complications may or may not be related to the procedure or 
commercial product.  
Source data 
Ref: ISO 14155 
All information in original records, certified copies of original 
records of clinical findings, observations, or other activities in a 
clinical investigation, necessary for the reconstruction and 
evaluation of the clinical investigation 
Note 1 to entry: This includes source data initially recorded in 
an electronic format. 
Source document 
Ref: ISO 14155 
Original or certified copy of printed, optical or electronic 
document conaining source data. 
 
 
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Boston Scientific
Report Generated: 29-Jul-2024 17:36:03  (GMT)
Criteria- Full Lifecycle (All Votes)
Project Document Signature Page
Object Number:
92762413
Name:
TheraSphere Post-Approval Study Protocol
Effective Date:
31-Oct-2022 02:30 GMT
State:
Released
Revision:
B
Sub Type:
null
CN Number:
2557997
Signatures:
Object Type
Number
Reviewer
Role
Vote
Vote Comments
Vote Date
Change Notice
2557997
Wells, Michelle
Clinical Project
Management -
Functional
Representative
Approve
28-Oct-2022
19:13 GMT
Change Notice
2557997
Jones, Lesley
Training
Approve
28-Oct-2022
19:29 GMT
Change Notice
2557997
Boucher, Eveline
Medical -
Functional
Representative
Approve
31-Oct-2022
10:31 GMT
Change Notice
2557997
Zhang, Lei
Biostatistics -
Functional
Representative
Approve
31-Oct-2022
14:30 GMT
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