From Rotator Cuff Repair to Reverse Shoulder Arthroplasty - Clinical and Radiological Results
Conditions: Rotator Cuff Tears, Rotator Cuff Tear Arthropathy, Rotator Cuff Injuries
Sponsor: Lovisenberg Diakonale Hospital

CONFIDENTIAL 
Protocol CARS 3. Version 2.0  
.  
 
Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
Only the electronic version is valid. 
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Title Page 
Protocol Title: CARS-3 
Brief title: From rotator cuff surgery to reverse shoulder arthroplasty – clinical 
outcomes and radiological results 10 years after surgery 
A prospective cohort study to investigate clinical and radiological outcome with patient reported 
outcome measurements (PROMs) and x-ray in patients 10 years after undergoing arthroscopic 
rotator cuff repair for acute or degenerative rotator cuff tear. 
Protocol Number: 2.0 
Amendment Number: 2.0 
Study Phase: Including 
Regulatory Agency Identifier Number(s): 
Clinicaltrials.gov: 
Regional Committees for Medical and Health Research Ethics (REK):   
Current Research Information System In Norway (CRISTIN): 
 
520047 
2559577 
 
 
 
 
 
 
Approval Date:  
 
Principal investigator Signatory: 
 
Kjersti Kaul Jenssen, MD, PhD 
 
 
Date 09.09.24 
 
Principal investigator functions including Medical Monitors, Coordinating Investigator, and 
Principal Investigator Names and Contact Information can be found in Appendix 10  

CONFIDENTIAL 
Protocol CARS 3. Version 2.0  
.  
 
Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
Only the electronic version is valid. 
Page 2 of 30 
 
www.norcrin.no 
 
 
 
 

CONFIDENTIAL 
Protocol CARS 3. Version 2.0  
.  
 
Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
Only the electronic version is valid. 
Page 3 of 30 
 
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Protocol Amendment Summary of Changes Table 
 
DOCUMENT HISTORY 
Document 
Date 
2.0 Full protocol norcrin template 
09.09.2024 
1.0 Original Protocol “Prosjektbeskrivelse” 
01.11.2022 
Amendment 2.0 (09.09.2024) 
This document is a synthesis of the project protocol submitted and approved by REK, along with local agreements 
and adjustments for the study. This document is therefore non substantial with regards to the trial, but relevant for 
the supervision of it (article 81.9)] based on the criteria set forth in Regulation 536/2014 of the European Parliament 
and the Council of the European Union. This is because it neither significantly impacts the safety or rights of the 
subjects or on the reliability and robustness of the data generated in the clinical trial. 
Overall Rationale for the Amendment: 
Minor changes to criteria. Constant Murley score and MRI results removed from secondary outcome as the results 
from patient reported outcome measurement and x-ray is sufficient to answer the research question. WORC Index 
set to primary outcome alone. More accurate description of statistical analysis. 
Removed non-important/not applicable text from chapter 9 and 11. Updated index.  
 
Section # and 
Name 
Description of Change 
Brief Rationale 
3. Methods 
Removal of MRI and Constant 
Murley score. WORC Index set to 
primary outcome alone. 
Not necessary 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
Protocol CARS 3. Version 2.0  
.  
 
Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
Only the electronic version is valid. 
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Table of Contents  
 
Title Page ........................................................................................................................................1 
Protocol Amendment Summary of Changes Table .........................................................................3 
Table of Contents ...........................................................................................................................4 
List of Abbreviations .....................................................................................................................6 
1. 
Protocol Summary ..........................................................................................................7 
1.1. 
Synopsis ............................................................................................................................7 
1.2. 
Schedule of Activities (SoA) ............................................................................................9 
2. 
Introduction ...................................................................................................................10 
2.1. 
Study Rationale ...............................................................................................................10 
2.2. 
Background .....................................................................................................................10 
2.3. 
Benefit/Risk Assessment ................................................................................................11 
2.3.1. 
Risk Assessment .............................................................................................................11 
The planned x-ray will not give any significant radiation dose and 
therefore we expect no risk of development of cancer, as 
described for large radiation doses. ................................................................................11 
2.3.2. 
Benefit Assessment .........................................................................................................11 
We expect that the benefit of the data and knowledge collected will be 
superior to the cost for the patients coming to a ten-year follow-
up appointment................................................................................................................11 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................11 
3. 
Objectives, Endpoints, and Estimands .......................................................................12 
4. 
Study Design ..................................................................................................................13 
4.1. 
Overall Design ................................................................................................................13 
4.2. 
Scientific Rationale for Study Design ............................................................................13 
4.3. 
End-of-Study Definition .................................................................................................13 
5. 
Study Population ...........................................................................................................14 
5.1. 
Inclusion Criteria ............................................................................................................14 
5.2. 
Exclusion Criteria ...........................................................................................................14 
5.3. 
Screen Failures ................................................................................................................15 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................16 
6.1. 
Study Intervention Administered ....................................................................................16 
6.2. 
Assignment to Study Intervention ..................................................................................16 
7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................17 
7.1. 
Participant Discontinuation/Withdrawal from the Study ................................................17 
7.1.1. 
Discontinuation of radiological examinations ................................................................17 
7.1.2. 
Discontinuation of questionnaire ....................................................................................17 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
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7.2. 
Lost to Follow up ............................................................................................................18 
8. 
Study Assessments and Procedures.............................................................................19 
8.1. 
Administrative Procedures ..............................................................................................19 
8.2. 
Safety Assessments .........................................................................................................19 
8.2.1. 
Physical Examinations ....................................................................................................19 
8.2.2. 
Radiological Examinations .............................................................................................19 
8.2.3. 
Patient reported outcome measurements (PROMs) ........................................................20 
8.3. 
Adverse Events (AEs) Serious Adverse Events (SAEs), and 
Other Safety Reporting ...................................................................................................20 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information .....................................................................................................................20 
8.3.2. 
Method of Detecting AEs and SAEs ..............................................................................21 
8.3.3. 
Follow-up of AEs and SAEs ...........................................................................................21 
8.3.4. 
Regulatory Reporting Requirements for SAEs ...............................................................21 
9. 
Statistical Considerations .............................................................................................22 
9.1. 
Statistical hypothesis.......................................................................................................22 
9.2. 
Statistical Analyses .........................................................................................................22 
9.2.1. 
General Considerations ...................................................................................................22 
9.2.2. 
Primary Endpoint Analysis .............................................................................................22 
9.2.3. 
Secondary Endpoint Analysis .........................................................................................23 
9.2.4. 
Other Analyses ................................................................................................................23 
9.3. 
Sample Size Determination ............................................................................................23 
9.4. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................24 
9.4.1. 
Regulatory and Ethical Considerations ...........................................................................24 
9.4.2. 
Informed Consent Process ..............................................................................................24 
9.4.3. 
Data Protection................................................................................................................24 
9.4.4. 
Study and Site Start and Closure ....................................................................................25 
9.4.5. 
Publication Policy ...........................................................................................................26 
9.5. 
Appendix 10: Contact details ..........................................................................................28 
10. 
References ......................................................................................................................30 
 
 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
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List of Abbreviations  
 
AE 
SAE 
 
 
SA   
Adverse Event 
Serious Adverse Event] 
 
Shoulder arthroplasty  
RC 
Rotator Cuff 
aRCR 
CA 
RSA 
Arthroscopic rotator cuff repair 
Cuff arthropathy 
Reverse shoulder arthroplasty 
 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
© 2015-2021 TransCelerate BioPharma 
Doc. No. CT 2.01.01. Valid from 16 Aug 2022.  
Only the electronic version is valid. 
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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title:  
CARS-3 
Brief Title: 
From rotator cuff surgery to reverse shoulder arthroplasty – clinical outcomes and radiological 
results 10 years after surgery  
 
Objectives, Endpoints, and Estimands: 
 
Objectives 
Endpoints 
Primary 
 
 WORC Index 
 
 
 Change baseline to 10 years 
postoperatively 
 
Secondary 
 
 Cuff arthropathy 
 
 
 EuroQol-5 (EQ-5D-5L) 
 
 Subjective Shoulder Value 
 Rotator Cuff Survival 
 Cuff arthropathy on x-ray according to 
Hamada-Fukuda and Seebauer 
Classification at 10 years 
postoperatively 
 Change in EQ-5D-5L from baseline to 
10 years postoperatively. 
 SSV score 10 years postoperatively 
 Survival of RC repair in terms of 
number of RSA performed in the 
study group within 10 years 
postoperatively 
 
Overall Design Synopsis: 
This study is a cohort study design. All patients have already been operated. 
Brief Summary: 
The purpose of this study is to measure clinical and radiological results in participants with 
arthroscopic rotator cuff repair 10 years after surgery.   

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
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Study details include: 
 The study duration will be up to 15 years postoperative (>10 years follow up in some 
patients as the study starts in 2024 and the patients are operated in the time period 2010-
2014).  
 The participants will be examined 10 years postoperatively and were examined 
preoperatively at the time of surgery in 2010-2014.  
Number of Participants: 733 
733 participants will be invited to participate in the 10-year follow up examination.  
 
Data Monitoring/Other Committee: No 
A data monitoring committee has not been appointed for this study.  
 
 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
 
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Only the electronic version is 
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1.2. 
Schedule of Activities (SoA) 
 
 September 2024: Inclusion of patients starts 
 2024-2025: Data collection. 
 2026-2027: Statistical analyses and submission of manuscript to relevant journals. 
 2027-2028: Presentation of results from study 2 at relevant conferences. 
 
 
 
 

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Last version 09.09.24 (original 01.11.2022) 
 
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2. 
Introduction 
Shoulder pain is a common problem in the Norwegian population. Up to 34% of women and 
28% of men on extended sick leave (>8 weeks) suffer from disorders of the shoulder, neck and 
upper extremity. Rotator cuff (RC) tear is a major cause of shoulder pain (1-3). RC lesions cause 
symptoms such as muscle weakness, pain and loss of shoulder range of motion. Arthroscopic RC 
repair is performed in an increasing proportion of these patients with increased results in 
shoulder function, but there is a lack in long term follow up (4-7). In this study we aim to 
evaluate pre- and perioperative prognostic factors for favorable outcome.  
2.1. 
Study Rationale 
 
2.2. 
Background 
The incidence of RC tears is increasing, and so is the amount of arthroscopic RC repairs 
performed. Despite the reported good results, there is a large number of repairs that do not heal or 
re-tear. The high re-tear rate (10-25%) is a challenge and although several risk factors of re-tear 
have been suggested, more studies are required to identify the patients with risk of re-tear after 
surgery (4-10).  
 
Patients with non-healed RC repairs or re-tears are at risk of developing osteoarthritis (OA) or a 
progressive massive tear leading to pain and dysfunction. There are few long-term follow up 
studies after RC repair. Development of OA to some degree is reported in as many as 55% of 
patients, some of whom need further surgery with a shoulder replacement (11-13). At the end 
stage of a RC tear, with muscle atrophy and fatty infiltration of the RC, joint replacement surgery 
with reversed shoulder arthroplasty (RSA) is a good treatment solution.  
 
In this project, we address these critical gaps in knowledge and aim to investigate the factors 
influencing the clinical outcome after rotator cuff surgery and re-tear in a large prospective cohort 
study. We will study how many patients suffering from poor outcome and develop cuff 
arthropathy in need of RSA.  
 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
 
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Only the electronic version is valid. 
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2.3. 
Benefit/Risk Assessment 
We foresee no risks associated with completing this study, as there is no planned new 
intervention. We expect a high rate of patients who want to participate, as they were asked to do 
so when first joining the registry at the time of surgery. Complications will be registered.  
2.3.1. 
Risk Assessment 
The planned x-ray will not give any significant radiation dose and therefore we expect no risk of 
development of cancer, as described for large radiation doses. 
 
2.3.2. 
Benefit Assessment 
We expect that the benefit of the data and knowledge collected will be superior to the cost for the 
patients coming to a ten-year follow-up appointment  
 
2.3.3. 
Overall Benefit Risk Conclusion 
Considering the measures taken to minimize risk to participants participating in this study, the 
potential risks identified in association with this cohort study, where the intervention has taken 
place ten years ago, are justified by the anticipated benefits that may be afforded to participants 
with arthroscopic rotator cuff repair. 

CONFIDENTIAL 
Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
 
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Only the electronic version is valid. 
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3. 
Objectives, Endpoints, and Estimands 
 
 
Objectives 
Endpoints 
Primary 
 
 WORC Index 
 
 Change from baseline to 10 years 
postoperatively 
Secondary 
 
 Cuff arthropathy 
 
 
 EuroQol-5 (EQ-5D-5L) 
 
 Subjective Shoulder Value 
 Rotator Cuff Survival 
 Cuff arthropathy on x-ray according to 
Hamada-Fukuda and Seebauer 
Classification at 10 years 
postoperatively 
 Change in EQ-5D-5L from baseline to 
10 years postoperatively. 
 SSV score 10 years postoperatively 
 Survival of RC repair in terms of 
number of RSA performed in the 
study group within 10 years 
postoperatively 
 
Primary estimand  
The primary clinical question of interest is:  
Is it possible to develop a prognostic prediction model for favorable outcome 10 years after 
arthroscopic rotator cuff repair?  
The estimand is described by the following attributes: 
 Population:  
Patients with rotator cuff tear 
 Endpoint:  
Change from baseline to 10 years in WORC Index and development of cuff arthropathy 
 

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Protocol CARS 3. Version 2.0  
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Last version 09.09.24 (original 01.11.2022) 
 
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4. 
Study Design 
 
4.1. 
Overall Design 
Prospective cohort design of 733 participants. 
4.2. 
Scientific Rationale for Study Design 
The study design is well suited to follow many patients over time. They will be asked to submit 
their patient reported outcome measures digitally and they will be evaluated on x-ray. The 
validated chosen PROM (WORC Index) is reported to be correlated with clinical function 
evaluated by a physiotherapist (Constant Murley Score). With this design and choice of 
outcomes, we will be able to answer our research question.  
4.3. 
End-of-Study Definition 
The end of the study is defined as the date of the last x-ray or submission of PROMs of the last 
participant in the study.  
A participant is considered to have completed the study if the participant has completed all 
periods of the study including the last x-ray and all of the PROMs. 
 

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Last version 09.09.24 (original 01.11.2022) 
 
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5. 
Study Population 
733 patients operated at Lovisenberg Diaconal Hospital for an arthroscopic rotator cuff repair in 
the period 2010-2014. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 to 95 years of age inclusive, at the time of signing the informed 
consent. 
Type of Participant and Disease Characteristics 
2. Participants who have been operated with an arthroscopic rotator cuff repair and 
included in the rotator cuff registry at Lovisenberg Diaconal Hospital 2010-2014. 
3. Participants who are able to read and write Norwegian 
 
Sex and Contraceptive/Barrier Requirements 
4. All 
 
Informed Consent 
5. Capable of giving signed informed consent  
 
 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Lack of competence to consent 
Other Exclusion Criteria 
2. Patient is unwilling or unable to participate 
3. Not able to submit patient reported outcome measurements in any format and x-ray 
4.  
 
 
 

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Last version 09.09.24 (original 01.11.2022) 
 
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5.3. 
Screen Failures 
A screen failure occurs when a participant who has consented to participate in the clinical study 
is not subsequently entered in the study. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the CONSORT publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any severe adverse events 
(SAE). 
Individuals who do not meet the criteria for participation in this study screen failure will not be 
rescreened.  
 

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Last version 09.09.24 (original 01.11.2022) 
 
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6. 
Study Intervention(s) and Concomitant Therapy 
Study interventions are all pre-specified, investigational and non-investigational medicinal 
products, medical devices and other interventions (e.g., surgical and behavioral) intended to be 
administered to the study participants during the study conduct. The surgical intervention was 
performed in 2010-2014 and there is no planned new intervention. 
6.1. 
Study Intervention Administered 
Table 1.  Study Intervention Administered 
Intervention Label 
 
Intervention Name 
Arthroscopic rotator cuff repair 
Type  
Surgical procedure 
Use 
The standard arthroscopic rotator cuff repair was performed by a 
trained orthopedic surgeon. The number of involved and sutured 
tendons, surgery on the biceps tendon, supplemental resection of 
acromion and acromioclavicular joint was reported with other 
concomitant procedures as well. 
 
6.2. 
Assignment to Study Intervention 
The participants who meet the eligibility criteria and are willing to participate will give consent 
and submit the patient reported outcome measurements electronically. They have already been 
operated and there is no new intervention planned. Hence this is a 10-year follow-up of already 
included patients treated with rotator cuff repair. 

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Last version 09.09.24 (original 01.11.2022) 
 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal 
 
7.1. 
Participant Discontinuation/Withdrawal from the Study 
 A participant may withdraw from the study at any time at the participant’s own request 
for any reason (or without providing any reason). 
 A participant may be withdrawn at any time at the discretion of the investigator for safety 
and behavioral reasons.  
 At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted, as shown in the SoA. See SoA for data to be collected at the time of 
study discontinuation and follow-up and for any further evaluations that need to be 
completed. 
 The participant will be permanently discontinued from the study intervention and the 
study at that time. 
 If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
7.1.1. 
Discontinuation of radiological examinations 
 If the participant is not able or willing to conduct the planned x-ray examination, he/she 
will be asked to partly participate in the study. He/she will be asked to submit PROMs 
questionnaires.  
7.1.2. 
Discontinuation of questionnaire  
 If the participant is not able or willing to submit PROMs electronically, he/she will be 
asked to submit by paper.  
 If the participant is not able or willing to submit PROMs neither electronically nor by 
paper, he/she will be asked to submit by phone call. 
 If the participant is not able or willing to submit PROMs in general, he/she will be asked 
to partly participate in the study. He/she will be invited to conduct the x-ray examination. 
 

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7.2. 
Lost to Follow up 
A participant will be considered lost to follow-up if the participant repeatedly fails to return for 
x-ray examination and submitting the patient reported outcome measurements and is unable to be 
contacted by the study site. 
The following actions must be taken if a participant fails to submit the patient reported outcome 
measurements or the x-ray examination: 
 The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible, counsel the participant on the importance of maintaining the assigned visit 
schedule, and ascertain whether the participant wishes to and/or should continue in the 
study. 
 If the participant cannot get the x-ray at the local hospital, he/she will be invited to 
participate only with patient reported outcome measurements. 
 If the participant cannot submit the patient reported outcome measurements 
electronically, he/she will be invited to answer the scheme on paper and will receive the 
paper by mail.  
 Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, telephone calls, and if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
 Should the participant continue to be unreachable, the participant will be considered to 
have withdrawn from the study.  
 If vital status is determined as deceased, this will be documented, and the participant will 
not be considered lost to follow-up.  

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8. 
Study Assessments and Procedures 
 Study procedures and their timing are summarized in the SoA. Protocol waivers or 
exemptions are not allowed. 
 Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
 All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
 Procedures conducted as part of the participant’s routine clinical management and 
obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within 
the timeframe defined in the SoA. 
 In the event of a significant study-continuity issue (eg, caused by a pandemic), alternate 
strategies for participant visits, assessments, medication distribution and monitoring may 
be implemented by the sponsor or the investigator, as per local health authority/ethics 
requirements.   
8.1. 
Administrative Procedures 
 
8.2. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations 
 Preoperative physical examination was performed before the participant received the 
arthroscopic rotator cuff repair 2010-2014.  
 No new physical examination is planned in this study. 
8.2.2. 
Radiological Examinations 
 Participants will be examined by x-ray of the shoulder in standard projections: 
o One scapular Y-view 
o Three in anteroposterior view with arm in neutral, 30° external rotation and 
60° internal rotation  

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 Degree of cuff arthropathy will be described according to Hamada classification, 
grade 1-5. 
8.2.3. 
Patient reported outcome measurements (PROMs) 
Participants will be asked to submit PROMs.  
 PROMs questionnaire will be sent out electronically and participants will be asked to 
submit electronically in the “Nettskjema” portal.  
 PROMs planned for this study 
o Western Ontario Rotator Cuff Index (WORC). Disease specific questionnaire to 
measure health-related quality of life, validated in patients with rotator cuff 
disease. Original A. Kirkley, S. Griffin, CCD, C. Alvarez 1998. Norwegian 
version is cross-culturally adapted according to the guidelines for translation of 
outcome measures, by Ekeberg et al. 2008.  
o EQ-5D-5L. Generic quality of life questionnaire measuring health in five 
dimensions. Original fra EuroQol Group. Norwegian version 2011.  
o Subjective Shoulder Value (SSV). Participant’s subjective shoulder assessment 
expressed as a percentage of an entirely normal shoulder, which would score 
100%. Norwegian version.  
o Additional questions regarding reoperation, patients satisfaction and if they would 
have been willing to undergo the procedure again will be asked 
 
8.3. 
Adverse Events (AEs) Serious Adverse Events (SAEs), and Other 
Safety Reporting 
 
We foresee no adverse events or serious adverse events in completion of our study as there is no 
planned new intervention. We foresee no AE or SAE in relation to the PROMs being submitted. 
If any AE or SAE occur in relation to the planned x-ray examination, this will be reported in a 
separate form and in the electronic patient journal.  
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up. This includes events reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
All SAEs will be collected from the start of study intervention (start of inclusion for the 10-year 
follow up) until the last follow-up visit.  

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All AEs will be collected from the start of study intervention (start of inclusion for the 10-year 
follow up) until the last follow-up visit. 
Medical occurrences that begin before the start of study intervention (start of inclusion for the 
10- year follow up) but after obtaining informed consent will be recorded as medical 
history/current medical conditions, not as AEs. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. The investigator will submit any updated SAE data to 
the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and the investigator considers the 
event to be reasonably related to the study intervention or study participation, the investigator 
must promptly notify the sponsor. 
8.3.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3).  
8.3.4. 
Regulatory Reporting Requirements for SAEs 
 Prompt notification by the investigator to the sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
 The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, institutional review boards 
(IRBs)/independent ethics committees (IECs), and investigators. 
 
 
 

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9. 
Statistical Considerations 
The statistical analysis plan will be finalized prior to inclusion of first participant. This section is 
a summary of the planned statistical analyses of the most important endpoints including primary 
and key secondary endpoints. 
9.1. 
Statistical hypothesis 
The main objective is to develop a prognostic prediction model for clinical outcome 10 years 
after arthroscopic rotator cuff repair. To quantify the relative importance of preoperative and 
perioperative prognostic factors on functional outcomes ten years after rotator cuff repair and to 
identify and quantify patients who need shoulder replacement surgery ten years after rotator cuff 
repair as a measure of failure. 
 
9.2. 
Statistical Analyses 
9.2.1. 
General Considerations 
 Descriptive statistics will be provided as means with standard deviation (SD) and mean 
differences as two-sided 95% confidence intervals (CI). 
 Significance level is set to 5%. 
 
9.2.2. 
Primary Endpoint Analysis 
9.2.2.1. 
WORC Index 
 The analysis will be performed to develop a prognostic prediction model for favorable 
outcome after 10 years 
 Minimal important change (MIC) is set to -275 points (of a total score of 2100). If 
calculated as prosentage MIC is set to 13 ((275/2100)*100). 
 WORC Index at baseline, 1, 2 and at 10 years will be reported as total raw score (SD). 
Mean difference will be presented as whole number with 95% CI. Decrease or increase in 
WORC Index score will also be presented as percent. 
 Prognostic factors will be used in a multivariable linear regression model with 
appropriate methods for variable selection. WORC Index at 10 years as dependent 
variable. Results will be provided as coefficients with 95% CI and P-value. 
 

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9.2.3. 
Secondary Endpoint Analysis 
9.2.3.1. 
Cuff arthropathy on x-ray 
 Descriptive statistics will be provided as means with standard deviation (SD). 
 A suitable inter/intrarater reliability test (Gwets AC or Cohen’s Kappa) will be performed 
on agreement of arthropathy degree in 50 x-ray images. This will be performed at time 0 
and after 3 weeks.  
 
9.2.3.2. 
EQ-5D-5L 
 EQ-5D-5L at baseline and at 1, 2 and 10 years will be reported as a total score (SD). 
Mean difference will be presented as whole number with 95% CI. 
 A paired sample t-test or statistical models for repeated measurements may be performed 
to evaluate change in continuous outcome across time. 
 
9.2.3.3. 
Reverse shoulder arthroplasty and RC survival 
 Survival of RC repair in terms of number of RSA performed in the study group within 10 
years postoperatively 
 Descriptive statistics will be provided as means with standard deviation (SD) 
9.2.4. 
Other Analyses 
 
9.3. 
Sample Size Determination 
733 participants will be invited to participate. We do not expect 733 to be included as some of 
them is now old, some are not alive and some will not be willing, or able, to consent. The sample 
size calculation is done in STATA 18.0 and based on calculation of a sample size required for 
developing a clinical prediction model as described by Riley et al.  
Adjusted R2=0.36 as described by Jenssen et al. at the two year follow up of the same cohort. 25 
variables are included. The mean preoperative WORC at inclusion is set as the intercept (44) and 
standard deviation is based on the intercept (18,3).   
This gives us a sample size of 458 participants. The cohort is set from the start of the project in 
2010, but we hope to include a minimum of 458 participants in this round and find the expected 
samples size adequate.  
 
 

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Supporting Documentation and Operational Considerations 
9.4. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
9.4.1. 
Regulatory and Ethical Considerations 
 This study will be conducted in accordance with the protocol and with the following: 
o Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and  
 The study will utilize data from a prospective registry of all arthroscopic repaired RC 
tears performed at Lovisenberg 2010-2014.  
 All patients included in the registry have received written and oral information and 
signed an informed consent for their registry data to be used for research.  
 Qualitative data registries of treated patients do not require approval from the national or 
regional committees in Norway, and therefore MD, PhD Kaul-Jenssen received an 
exemption from the Regional Committee for Medical and Health Research Ethics, section 
South-East C, Norway (IRB00001870), allowing her project to be implemented without 
further approval. Results from the prospective registry of all arthroscopically repaired 
RCs with 2-year follow-up data were published in 2018 (46).  
 We will now use these data and ask the same patients to join the ten-year follow-up. We 
received new approval from the Regional Committee for Medical and Health Research 
Ethics to implement this in December 2022 (ID: 520047).  
9.4.2. 
Informed Consent Process 
 The investigator or the investigator’s representative will explain the nature of the study, 
including the risks and benefits, to the potential participant and answer all questions 
regarding the study. 
 Potential participants must be informed that their participation is voluntary. They will be 
required to sign a statement of informed consent as approved by the Regional Committee 
for Medical and Health Research Ethics. 
 The participant will sign the consent form electronically by using their personal Bank-ID 
for secure two-step verification. 
9.4.3. 
Data Protection 
 Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 

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names or any information which would make the participant identifiable will not be 
transferred. 
 The participant must be informed that their personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant who will be required to give consent for their data to 
be used as described in the informed consent  
 The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
 Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
9.4.4. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the study will start to invite participants to the 10-year 
follow up. 
The first act of recruitment is the date of first invitation and will be the study start date. 
Study/Site Termination 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
For study termination: 
 Discontinuation of further study intervention development 
For site termination: 
 Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor’s procedures, or GCP guidelines 
 Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the investigator 

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 Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The investigator shall promptly inform the participant and should assure 
appropriate participant therapy and/or follow-up. 
9.4.5. 
Publication Policy 
 The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor 
before submission. This allows the sponsor to protect proprietary information and to 
provide comments. 
 The sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the sponsor will generally support 
publication of multicenter studies only in their entirety and not as individual site data. In 
this case, a coordinating investigator will be designated by mutual agreement. 
 Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
 
 

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9.5. 
Appendix 10: Contact details 
 
 
Principal invastigator : 
Name and title: Dr. Kjersti Kaul Jenssen, PhD, MD 
Address: Lovisenberggata 17, 0456 Oslo 
Tel: 913 92 624 
E-mail: kjkj@lds.no 
Co-Investigator : 
Name and title: Dr. Sigbjørn Dimmen, Prof., MD 
Address: Lovisenberggata 17, 0456 Oslo 
Tel: 902 44 894 
E-mail: disi@lds.no 
Co-Investigator/Postdoc 
Name and title: Dr. Christian Owesen, PhD, MD 
Address: Lovisenberggata 17, 0456 Oslo 
Tel: 905 15 843 
E-mail: cow@lds.no 
PhD-candidate 
Name and title: Dr. Birthe Marie Roang-Winjum, MD 
Address: Sykehuset Telemark, Pb 2900 Kjørbekk, 3710 Skien 
Tel: 906 65 939 
E-mail: birroa@sthf.no 
Research coordinator 
Name and title: Julianne H. Lillegård, physiotherapist LDS 
Address: Lovisenberggata 17, 0456 Oslo 
Tel:  
E-mail: juliannehelenefroyen.lillegard@lds.no 

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10. 
References 
 
1. 
Foss L, Gravseth HM, Kristensen P, Claussen B, Mehlum IS, Knardahl S, et al. The impact of workplace risk factors 
on long-term musculoskeletal sickness absence: a registry-based 5-year follow-up from the Oslo health study. J Occup Environ 
Med. 2011;53(12):1478-82. 
2. 
van der Zwaal P, Pekelharing JF, Thomassen BJ, Swen JW, van Arkel ER. [Diagnosis and treatment of rotator cuff 
tears]. Ned Tijdschr Geneeskd. 2011;155(34):A3163. 
3. 
Tempelhof S, Rupp S, Seil R. Age-related prevalence of rotator cuff tears in asymptomatic shoulders. J Shoulder 
Elbow Surg. 1999;8(4):296-9. 
4. 
Moosmayer S, Lund G, Seljom US, Haldorsen B, Svege IC, Hennig T, et al. At a 10-Year Follow-up, Tendon Repair Is 
Superior to Physiotherapy in the Treatment of Small and Medium-Sized Rotator Cuff Tears. J Bone Joint Surg Am. 
2019;101(12):1050-60. 
5. 
Agout C, Berhouet J, Bouju Y, Godenèche A, Collin P, Kempf JF, et al. Clinical and anatomic results of rotator cuff 
repair at 10 years depend on tear type. Knee Surg Sports Traumatol Arthrosc. 2018;26(8):2490-7. 
6. 
Kim YK, Jung KH, Kim JW, Kim US, Hwang DH. Factors affecting rotator cuff integrity after arthroscopic repair for 
medium-sized or larger cuff tears: a retrospective cohort study. J Shoulder Elbow Surg. 2018;27(6):1012-20. 
7. 
Tanaka S, Gotoh M, Tanaka K, Mitsui Y, Nakamura H, Ozono H, et al. Functional and Structural Outcomes After 
Retears of Arthroscopically Repaired Large and Massive Rotator Cuff Tears. Orthop J Sports Med. 
2021;9(10):23259671211035752. 
8. 
Rashid MS, Cooper C, Cook J, Cooper D, Dakin SG, Snelling S, et al. Increasing age and tear size reduce rotator cuff 
repair healing rate at 1 year. Acta Orthop. 2017;88(6):606-11. 
9.  
Vastamäki M, Lohman M, Borgmästars N. Rotator cuff integrity correlates with clinical and functional results at a 
minimum 16 years after open repair. Clin Orthop Relat Res. 2013;471(2):554-61. 
10. 
Jenssen KK, Lundgreen K, Madsen JE, Kvakestad R, Dimmen S. Prognostic Factors for Functional Outcome After 
Rotator Cuff Repair: A Prospective Cohort Study With 2-Year Follow-up. Am J Sports Med. 2018;46(14):3463-70. 
11. 
Flurin PH, Hardy P, Valenti P, Meyer N, Collin P, Kempf JF. Osteoarthritis after rotator cuff repair: A 10-year follow-
up study. Orthop Traumatol Surg Res. 2017;103(4):477-81. 
12. 
Herve A, Thomazeau H, Favard L, Colmar M, Mansat P, Walch G, et al. Clinical and radiological outcomes of 
osteoarthritis twenty years after rotator cuff repair. Orthop Traumatol Surg Res. 2019;105(5):813-8. 
13. 
Johannsen AM, Arner JW, Elrick BP, Nolte PC, Rakowski DR, Horan MP, et al. Minimum 10-Year Outcomes of 
Primary Arthroscopic Transosseous-Equivalent Double-Row Rotator Cuff Repair. Am J Sports Med. 2021;49(8):2035-41.