Exploring the Benefits of a 3D Patient-specific Alignment in Total Knee Arthroplasty
Phase: NA
Conditions: TKA Outcomes
Sponsor: KU Leuven

AZ Delta – KU Leuven  
                                                  protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
Confidential 
 
                                 Protocol: RATKA_CBO 
 
   
 
 
 
  
 
 
 
Exploring the Benefits of a 3D Patient-specific 
Alignment in Total Knee Arthroplasty 
 
 
 
 
 
NCT number:  
Not yet assigned 
Document Title:  Study Protocol and Statistical Analysis Plan 
Document Date: 12/27/2025 
 
 
 
 
 
 
 
 
 
Sponsor / Organization: 
KU Leuven 
Herestraat 49, B-3000 Leuven 
Phone: +32 50 66 48 00 
Email:  info.brugge@kuleuven.be 
 
 
 
 
 
 
 
 
 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
2
Cover letter 
Application Ethical Approval S67874 (RATKA CBO v1) 
April 2023 
 
 
 
 
 
 
 
 
 
 
 
 
Dear members of the PRS Review, 
We would to present to you for approval our study titled ‘Clinical and Biomechanical 
Outcome after Robotically-Assisted Total Knee Arthroplasty by Comparing Three Alignment 
Strategies’ (S67874). 
This study aims to compare the clinical, functional and biomechanical outcomes after the 
rehabilitation period following Total Knee Arthroplasty (TKA) of patients with either a Tibial 
Anatomic Alignment (TA TKA), Mechanical Alignment (MA TKA) strategy, or a new, updated 
3D patient-specific alignment TA TKA strategy by controlling the orientation and position of 
the prosthesis for 3D patient-specific alignment to further optimize post-operative outcomes. 
Participant recruitment of this study takes place at the AZ Delta Hospital facility and the 
measurements after the rehabilitation period to evaluate the clinical and biomechanical 
outcomes take place at the Human Movement Laboratory, KU Leuven Campus Brugge.  
The undersigned declares (1) to have taken note of the submitted documents and 
amendments, (2) to have no scientific or ethical objections, (3) there are no charges to the 
patient, health insurance, or hospital for participating to the study. Quality and safety 
standards for patient care in clinical research are not changed from those generally adopted 
by sponsors in their routine activities, consistent with Joint Commission International 
standards. 
 
Yours sincerely, 
Zhijun li 
 
 
 
 
 
 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
3
 
CLINICAL TRIAL PROTOCOL 
 
Exploring the Benefits of a 3D Patient-specific 
Alignment in Total Knee Arthroplasty 
 
 
RATKA_CBO 
 
Version number: v 6 –  Date 12/27/2025 
 
EudraCT Nr:  Not yet assigned 
  ‘clinical trial’ (EudraCT nr applicable): any investigation in human subjects intended to discover or verify 
the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal 
product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or 
to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) 
with the object of ascertaining its (their) safety and/or efficacy. This includes clinical trials carried out in either 
one site or multiple sites, whether in one or more than one Member State   -   https://eudract.ema.europa.eu  
 
Sponsor 
KU Leuven 
Herestraat 49, B-3000 Leuven 
 
Coordinating Investigator 
Prof. Kurt Claeys, PhD, PT, MT(Dept. Rehabilitation Sciences) 
 
 
Confidentiality Statement 
The information in this document is strictly confidential and is available for review to Investigators, 
potential Investigators and appropriate Ethics Committees, Institutional Review Boards or Competent 
Authorities.  No disclosure should take place without written authorization from the Sponsor. 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
4
CLINICAL TRIAL PROTOCOL HISTORY 
 
CTP / Amendment # 
Date 
Reason for amendment 
Clinical Trial Protocol v1 
31/10/2023 
NA 
Clinical Trial Protocol v2 
Clinical Trial Protocol v3   
Clinical Trial Protocol v4    
Clinical Trial Protocol v5        
11/06/2023 
14/11/2023 
15/11/2023 
27/11/2023 
NA 
NA 
NA 
NA 
 
 
 
 
 
 
 
 
LIST OF PARTICIPATING SITES 
(if applicable) 
List Of Participating Sites 
Principal Investigator 
Contact details 
 
 
 
Dept. Rehabilitation Sciences 
 
AZ Delta Roeselare 
 
Dept. Rehabilitation Sciences 
 
 
 
Kurt Claeys 
 
Luyckx Thomas 
 
Zhijun li 
 
Kurt.Claeys@kuleuven.be 
 
 
thomas.luyckx@azdelta.be 
 
zhijun.li@kuleuven.be 
 
 
 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
5
SIGNATURES 
  Form to be repeated for every Participating Site and signature of Prinicple Investigator.   
There can only be one (1) single Coordinating Investigator, while multiple Principal Investigator can be 
applicable (one (1) Principal Investigator per Participating Site) depending on the amount of Participating Sites. 
 
Title:  Exploring the Benefits of a 3D Patient-specific Alignment in Total Knee Arthroplasty 
Protocol: RATKA_CBO 
 
The undersigned confirm that the following protocol has been acknowledged and accepted and that they 
agree to conduct the Trial in compliance with the approved protocol and will adhere to the principles 
outlined in the requirements for the conduct of clinical trials in the EU as provided for in Directive 
2001/20/EC or the Regulation 536/2014 as soon as applicable and any subsequent amendments, the 
ICH-GCP guidelines, the most recent version of the Declaration of Helsinki,  the Belgian law of May 
7th 2004 regarding experiments on the human person (as amended) or the Belgian law of May 7th 2017 
on clinical trials on medicinal products for human use as soon as applicable, the EU General Data 
Protection Regulation 2016/679 (GDPR), the relevant Belgian laws implementing the GDPR, the 
Belgian Law of August 22nd 2002 on patient rights and the Sponsor’s SOPs, and other regulatory 
requirements as amended. 
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the Trial without the prior written consent of the 
Sponsor. 
I also confirm that I will make the findings of the Trial publicly available through publication or other 
dissemination tools, in accordance with this protocol without any unnecessary delay and that an honest 
accurate and transparent account of the Trial will be given; and that any discrepancies from the Trial as 
planned in this protocol will be explained. 
 
Coordinating Investigator 
 
Prof. Kurt Claeys, PhD, PT, MT 
 
 
 
 
Name & Title 
Signature 
Date 
 
Principal Investigator (Participating Site) (Principal Investigator is the same as 
Coordinating investigator in case of a monocentric trial) 
 
 
Prof. Prof. Luyckx Thomas  PhD, MD  
 
 
Name & Title 
Signature 
Date 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
6
TABLE OF CONTENTS 
 
CLINICAL TRIAL PROTOCOL ............................................................................................. 3 
CLINICAL TRIAL PROTOCOL HISTORY ........................................................................... 4 
LIST OF PARTICIPATING SITES .......................................................................................... 4 
SIGNATURES .......................................................................................................................... 5 
TABLE OF CONTENTS .......................................................................................................... 6 
LIST OF ABBREVIATIONS ................................................................................................... 9 
FUNDING AND SUPPORT ................................................................................................... 10 
ROLES AND RESPONSIBILITIES ....................................................................................... 10 
TRIAL SYNOPSIS ................................................................................................................. 12 
TRIAL FLOWCHART ........................................................................................................... 14 
1 
Background and Rationale ............................................................................................... 15 
2 
Trial Objectives and Design ............................................................................................. 15 
2.1 
Trial objectives ......................................................................................................... 15 
2.2 
Primary Endpoints .................................................................................................. 163 
2.3 
Secondary Endpoints ................................................................................................ 16 
2.4 
Trial Design .............................................................................................................. 16 
3 
Trial Population / Eligibility Criteria ............................................................................. 173 
3.1 
Inclusion criteria ..................................................................................................... 173 
3.2 
Exclusion criteria ...................................................................................................... 17 
3.3 
Expected Duration of the Trial ............................................................................... 174 
3.4 
Screening failures ................................................................................................... 174 
3.5 
Consent withdrawal ................................................................................................ 174 
4 
Trial Procedures ............................................................................................................. 184 
4.1 
Selection of Participants / Recruitment .................................................................. 184 
4.2 
Consent ................................................................................................................... 184 
4.3 
Randomization Procedure / Code Break (if applicable) ........................................... 18 
4.4 
Visit schedule and assessments ................................................................................ 19 
4.4.1 Screening / Baseline ............................................................................................ 195 
4.4.2 Treatment Visits .................................................. Error! Bookmark not defined.5 
4.4.3 Discontinuation of Treatment – End of Trial Visit – Withdrawal ................. Error! 
Bookmark not defined.5 
4.4.4 Follow-up Visits .................................................. Error! Bookmark not defined.5 
5 
Adverse Event Reporting  ................................................................................................ 19 
(see website CTC documenten/ISF/safety reporting) ........... Error! Bookmark not defined.6 
5.1 
Definitions .............................................................. Error! Bookmark not defined.6 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
7
5.1.1 Adverse Event (AE) ............................................ Error! Bookmark not defined.6 
5.1.2 Adverse Reaction (AR) ....................................... Error! Bookmark not defined.6 
5.1.3 Serious Adverse Event (SAE) ............................. Error! Bookmark not defined.6 
5.1.4 Suspected Unexpected Serious Adverse Reaction (SUSAR) ..... Error! Bookmark 
not defined. 
5.1.5 Adverse Events of Special Interest (AESI) ........... Error! Bookmark not defined. 
5.2 
Adverse Events that do not require Reporting .......... Error! Bookmark not defined. 
5.3 
Recording and Reporting of Averse Events ........... Error! Bookmark not defined.7 
5.3.1 Assessment ............................................................ Error! Bookmark not defined. 
5.3.2 Timelines for reporting ......................................... Error! Bookmark not defined. 
5.3.3 Follow-up .............................................................................................................. 19 
5.3.4 Pregnancy .............................................................................................................. 19 
5.3.5 Technical Complaints ........................................... Error! Bookmark not defined. 
5.3.6 Death ..................................................................... Error! Bookmark not defined. 
5.4 
Reporting requirements to Ethics Committee’s (EC’s) and Competent Authorities 
(CA’s) Error! Bookmark not defined. 
5.4.1 Sponsor’s reporting of Suspected Unexpected Serious Adverse Reactions 
(=SUSARs) ....................................................................... Error! Bookmark not defined. 
5.4.2 Annual reporting (see website CTC documenten/ISF: annual safety report) Error! 
Bookmark not defined. 
5.4.3 Overview reporting requirements ......................... Error! Bookmark not defined. 
6 
Statistics and Data Analysis ............................................................................................. 20 
6.1 
Sample Size Determination ...................................................................................... 21 
6.2 
Statistical Analysis .................................................................................................... 21 
6.2.1 Efficacy Analysis .................................................................................................. 21 
7 
Data handling ................................................................................................................... 21 
7.1 
Data Collection Tools and Source Document Identification .................................... 23 
7.1.1 Operational aspects ............................................................................................... 24 
7.1.2 Legal requirements ................................................................................................ 24 
7.2 
Access to Data, Audit and Inspection ....................................................................... 25 
7.3 
Monitoring ................................................................................................................ 25 
7.4 
Archiving .................................................................................................................. 25 
8 
Ethical and Regulatory Considerations ............................................................................ 26 
8.1 
Ethics Committee (EC) review & reports ............................................................... 267 
8.2 
Peer review ............................................................................................................... 26 
8.3 
Regulatory Compliance ............................................................................................ 26 
8.4 
Protocol / GCP compliance ...................................................................................... 27 
8.5 
Data protection and participant confidentiality ........................................................ 27 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
8
8.6 
Insurance ................................................................................................................... 27 
8.7 
Amendments ............................................................................................................. 27 
9 
Publication Policy ............................................................................................................. 28 
10 Intellectual Property ......................................................................................................... 28 
11 JCI .................................................................................................................................... 29 
12 References ........................................................................................................................ 29 
Appendices .............................................................................................................................. 30 
    Appendix 1: Forgotten Joint Score ...................................................................................... 30 
    Appendix 2: Oxford Knee Score ......................................................................................... 31 
    Appendix 3: VAS Satisfaction .......................................................................................... 355 
    Appendix 4: VAS Pijn ....................................................................................................... 355 
    Appendix 5: Pain Catastrophizing Scale  .......................................................................... 356 
    Appendix 6: Tinetti Test .................................................................................................... 357 
    Appendix 7: Data Processing Annex ................................................................................. 358 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
9
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
(e)CRF 
(electronic) Case Report Form 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
APR 
Annual Progress Report 
AR 
Adverse Reaction 
CA 
Competent Authority 
CI 
Coordinating Investigator 
CM 
Concomitant Medication 
CTP 
Clinical Trial Protocol 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
FAMHP 
FJS 
Federal Agency for Medicines and Health Products 
Forgotton Joint Score 
FPFV 
First Patient First Visit 
GCP 
Good Clinical Practice (latest version of ICH E6) 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IMP 
Investigational Medicinal Product 
ISF 
Investigator Site File 
LPLV 
MA 
OKS 
PCS 
Last Patient Last Visit 
Mechanical Alignment 
Oxford Knee Score 
Pain Catastrophizing Scale 
PI 
Principal Investigator (Participating Site) 
PRO 
Patient Reported Outcome 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SUSAR 
TA 
Suspected Unexpected Serious Adverse Reaction 
Tibial Anatomic Alignment 
TKA 
TMF 
Total Knee Arthroplasty 
Trial Master File 
TSC 
Trial Steering Committee 
UAR 
VAS 
Unexpected Adverse Reaction 
Visual Analogue Scale 
 
 
PI and CI shall each be referred to as « Investigator(s) » 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
10
 
FUNDING AND SUPPORT 
Funder 
Kind of Financial or Non-Financial Support 
NA 
 
 
 
 
  The protocol should include information regarding funding, institutional affiliations, , incentives for Trial 
participantss and information regarding provisions for treating and/or compensating Trial participants who are 
harmed as a consequence of participation in the Trial. 
 
 
 
 
 
 
 
 
ROLES AND RESPONSIBILITIES 
This was a multicenter study that included two centers, one is KU Leuven and the other is AZ 
Roeselare Hospital. All study terms were approved and adopted by both committees. The 
UZ/KU Leuven Ethics Committee has the authority to interpret all experimental terminology 
and contractual terms and is directly responsible to the research team. The AZ Roeselare Ethics 
Committee assisted the research team in collaborating on this study. The research team 
conducted the research in strict compliance with the ethics committee approval requirements. 
The AZ Roeselare Ethics Committee can feedback suggestions and requirements during the 
experiment to the UZ/KU Leuven Ethics Committee, and feedback the results to the research 
team through the recommendations after the UZ/KU Leuven Ethics Committee research 
discussion. The AZ Roeselare Ethics Committee shall not interfere directly with the research 
process of the research team. 
 
The PI is responsible for the conduct of the Trial at his/her Participating Site, must protect the 
rights, safety and well-being of the participants and ensure adequate supervision of the conduct 
of the Trial at the Participating Site. If any tasks are delegated, the PI must maintain a log (see 
CTC website documenten/ISF: delegation of responsibilities log and training log) of 
appropriately qualified persons to whom he/she has delegated specified Trial-related duties. 
The PI must ensure that there is adequate and documented training for all Trial staff 
participating in the conduct of the Trial.  
 
Kurt Claeys and Zhijun li is responsible for laboratory testing of patients as KU Leuven  PI. 
Luyckx Thomas as the PI of AZ Delta Roeselare Hospital, who is responsible for introducing 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
11
patients to the laboratory of KU Leuven for testing and conducting questionnaire surveys in 
the outpatient clinic according to the patients' special requirements. Otherwise, all 
questionnaires will be followed up via phone call by Kurt Claeys or Luyckx Thomas. 
 
 It is the CI's responsibility to supervise the conduct of the Trial. 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
12
TRIAL SYNOPSIS 
 
Title of clinical Trial 
(«Trial») 
Exploring the Benefits of a 3D Patient-specific Alignment in 
Total Knee Arthroplasty 
Protocol Short Title 
Acronym 
RATKA_CBO 
Trial Phase (I, II, III, IV) 
NA 
Sponsor name 
KU Leuven 
Coordinating Investigator Prof. Kurt Claeys, PhD, PT, MT(Dept. Rehabilitation Sciences) 
           Contact Adress CI 
Spoorwegstraat 12, 8200 Brugge 
           Contact Email CI 
Kurt.Claeys@kuleuven.be 
           Contact Phone CI 
+ 32 16 37 65 62 
EudraCT number 
Not yet assigned 
Other public database nr  
 
Principal Investigators 
and Participating Sites 
Prof. Kurt Claeys, PhD, PT, MT(Dept. Rehabilitation Sciences) 
Prof. Luyckx Thomas,  MD, PhD(AZ Delta Roeselare) 
Medical 
condition 
or 
disease 
under 
investigation 
knee osteoarthritis 
Trial rationale  
Implant positioning and component alignment in TKA is one 
of the determining factors in patient outcome. Currently, 
different alignment strategies in TKA surgery are used. Current 
literature does not show clear superiority. Recently, a new and 
individualized alignment strategy, Tibial Anatomic Alignment 
(TA), was introduced.  
Primary objective 
Clincal and biomechanical outcome in TA TKA versus MA 
TKA versus 3D patient-specific alignment TA TKA versus HC 
Secondary objective(s) 
Patient Satisfaction in TA TKA versus MA TKA versus 3D 
patient-specific alignment TA TKA versus HC 
Trial Design 
Cohort Study/Longitudinal Study 
Endpoints 
Clincal and Biomechanical Outcome, Satisfaction 
Sample Size 
3x15 = 45, HC=15 
IMP, dosage and route of 
administration 
NA 
Active comparator 
product(s) 
NA 
Maximum duration of 
treatment of a Participant 
One single visit with clinical and biomechanical testing within 
2 years postsurgery 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
13
Maximum duration of 
Trial 
4 year 
Anticipate First Patient 
First Visit (FPFV) 
1st February 2024 
Anticipate Last Patient 
Last Visit (LPLV) 
1st September 2027 
 
 

AZ Delta – KU Leuven  
                                                  protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
Confidential 
 
                                 Protocol: RATKA_CBO 
 
TRIAL FLOWCHART 
Schedule of Events – Trial specific Procedures / Assesments 
 
Procedure/Assesment 
Contact 1/ IC 
Data Collection 
Contact 2 
Prospective Testing 
Contacts 
1 
 
2 
3 
Informed consent 
X 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
Demographics 
 
X 
 
 
Medical, Surgical history 
 
X 
 
 
 
Collecting Data 
 
 
 
 
preop x-rays 
 
X 
 
 
perop alignment & positioning 
 
X 
 
 
surgical technique: cement, patella 
 
X 
 
 
 
Appointment for testing 
 
 
X 
 
Clinical Testing 
 
OKS-12 
 
 
 
X 
FJS-12 
 
 
 
X 
VAS Satisfaction 
 
 
 
X 
PCS 
 
 
 
X 
Tinetti 
 
 
 
X 
VAS Pain 
 
 
 
X 
Biomechanical Testing 
 
Gait and functional movement (forward 
lunge, squat) analysis: kinetic, kinematic, 
EMG 
 
 
 
X 

AZ Delta – KU Leuven  
                                                  protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
Confidential 
 
                                 Protocol: RATKA_CBO 
 
1 Background and Rationale 
  Briefly explain the background and issues/medical need of the Trial. Make a convincing case as to why the 
Trial would create valuable and useful scientific knowledge.  What will be the expected benefits, risks and 
rationale why it is expected this Trial will have a positive benefit/risk balance. 
- 
Postoperative function and patient satisfaction are becoming increasingly relevant in 
patients after knee arthroplasty surgery. Despite adequate pre- operative planning, 
improved surgical techniques and rehabilitation protocols, only 75%-85% of patients 
seems satisfied after TKA procedurs. 
- 
Implant positioning and component alignment are determining factors in patient outcome. 
Currently, different alignment strategies in TKA surgery are used such as Mechanical 
Alignment (MA) and Kinematical Alignment (KA). MA is is still seen as the gold-standard 
alignment technique in TKA. However, recently KA is introduced because it restores more 
the patients individual joint orientation what is considered to be beneficial for soft tissue 
balance in the knee.  In literature no clear superiority of one alignment technique is shown 
concerning clinical and functional outcome after knee arthroplasty procedures. 
- 
A few years ago, an individualized alignment strategy, Tibial Anatomic Alignment (TA), 
was introduced and is supposed to be beneficial for soft tissue balance postoperative in 
knee arthroplasty patients. However, the benefits of TA in TKA on clinical and functional 
outcome remains up to date unclear prior to this study.  
- 
New clinical insights following the implementation of this TA TKA strategy led very 
recently to a new, updated 3D patient-specific alignment TA TKA strategy by controlling 
the orientation and position of the prosthesis for 3D patient-specific alignment to further 
optimize post-operative outcomes. 
- 
This project aims to compare the clinical, functional and biomechanical outcomes one-year 
post-surgery of patients with 3D patient-specific alignment TKA, TA TKA, healthy 
controls (HC) and MA TKA. 
2 Trial Objectives and Design 
2.1 
Trial objectives 
  Formulate specific statements of the purpose of the Trial (i.e. aims and objectives). Define the primary 
research question, and address a specific hypothesis. 
See 
also: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002877.pdf  
- 
General objective: to have more insights in the clinical en biomechnical outcome in 
patients with 3D patient-specific alignment TA TKA vs. TA TKA vs. MA TKA and vs. HC 
o Specific Aim 1: to have more insights into clinical outcome in patients with 3D 
patient-specific alignment TA TKA vs. TA TKA vs. MA TKA vs. HC 
o Specific Aim 2:  to have more insights into biomechanical outcome in patients with 
3D patient-specific alignment TA TKA vs. TA TKA vs. MA TKA vs. HC during 
gait and functional movements  
- 
Hypothesis: a TA TKA strategy is expected to provide better clinical and functional 
outcomes for the patient at the end of the rehabilitation period (1 year post-surgery) 
compared to MA TKA. 3D patient-specific aligned TA TKA is expected to provide better 
clinical and functional outcomes for the patient at the end of the rehabilitation period 
compared to TA TKA or MA TKA, and closer to HC. 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
16
2.2 
Primary Endpoints 
- 
Clincal and functional outcome: VAS Satisfaction, VAS Pain, PCS, OKS, FJS 
- 
Fall risk: Tinetti test  
- 
Biomechanical outcome during gait and functional movements 
 
2.3 
Secondary Endpoints 
- 
Significan differences will be set below the 0.05 (P-value=0.05).  
- 
Compare a single task, calculate the mean and standard deviation, SPM (Statistical 
Parametric Mapping) filter out the places and periods of difference through one-way 
ANOA( analysis of variance), Paired t-test to determine if there is a difference between 
two groups.  
- 
Independent t-test to identify other items that are independent between each two groups (P-
value= 0.05). 
- 
Compare multiple tasks. SPM (Statistical Parametric Mapping) two-way ANOA will used 
to do the test (P-value= 0.05).  
 
2.4 
Trial Design 
  Describe the design of the Trial to be conducted (eg double-blind, single-blind, open label, cross-over, 
parallel group,….).  Describe also the scientific rationale for the Trial design.  The use of figures or charts is 
recommended.  
See 
also: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002877.pdf 
Cohort Study/longitudinal Study 
45 patients that will be undergo a total knee replacement procedure, robotically-assisted. The 
participants will assigned to one of the three experimental groups: the MA TKA technique  
group (n=15), the TA TKA technique group (n=15), and the 3D patient-specific aligned TA 
TKA technique  group (n=15) 3D patient-specific aligned technique will be used Patients 
were divided into three groups according to the definition of three alignments, which were 
determined by the surgeon responsible for the operation based on the surgeon's experience 
and adjusted based on the robot's detection of the patient's soft tissue condition. The final 
tibia osteotomy plan will ultimately determine which group the patient falls into and will be 
documented in the patient's case file. During tibial osteotomy, perpendicular to the 
mechanical axis was divided into MA group. When it is parallel to the tibial joint line, it is 
classified as TA TKA. When the tibial osteotomy is parallel to the joint line and tilted 
posteriorly, and when the femoral osteotomy copies the rotation axis of the femoral condyle 
axis, the direction of the femoral prosthesis copies the direction of the femoral condyle 
alignment, which belongs to 3D patient-specific aligned TA TKA. The specific osteotomy 
method will be recorded in the documented of surgical procedure and in the patient's medical 
record the patient's case by the surgeon. HC (n = 15), 15 healthy participants, matched for age 
and gender, were included in the study ( Healthy participants, mainly grandparents of 
students at the Bruges Campus or parents of employees, eligible healthy controls can be 
matched and extracted on specific request in the Bruges Campus Gait Laboratory database). 
At one year of follow-up testing, clinical and biomechanical results will be evaluated in a 
movement analysis laboratory. Those responsible for follow-up studies will not be told which 
group the patients belong to ( Investigators of testing and follow-up studies are blinded to 
which group the patients being tested or followed belong to.) Only after all tests are 
completed can researchers review the patient's case file. The researchers classified the 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
17
specific osteotomy methods recorded in the patient case files and then performed statistical 
comparative analyses. The criterion for judging and quantifying which of the three groups 
has better results is to test and compare which group obtains results that are closer to the 
healthy control group (P value = 0.05). 
  
3 Trial Population / Eligibility Criteria 
3.1 
Inclusion criteria 
  List details such as age, sex, disease, characteristics, baseline values, etc., under which a trial participant is 
deemed to be suitable (eligible) to participate in the Trial. Informed consent to participate must be stated as an 
inclusion criterion. It should be stated if women of child bearing age will be included and which suitable methods 
of contraception will be used to enable inclusion into the Trial. A simple list format is the preferred style. 
Patients eligible for inclusion in this Trial have to meet all of the following criteria: 
1. Written informed consent must be obtained prior to any screening procedures 
2. Received a primary total knee replacement (incl. patella) robotically-assisted 
3. Male or female 
4. Age between 50 and 80 
5. Able to walk independently 
 
3.2 
Exclusion criteria 
  List details such as prior/concomitant therapy, concomitant disease/disorders, diagnostics assessments, 
medical/lifestyle conditions, prior/concurrent clinical Trial, etc., under which a participant is considered to be 
unsuitable for inclusion into the Trial. It should be stated if women of child bearing age will be excluded. A simple 
list format is the preferred style. 
Patients eligible for this Trial must not meet any of the following criteria: 
1. Revision surgery 
2. Patient with a history of neurological, psychiatric or neurodegenerative disease 
3. Any disorder, which in the investigator’s opinion might jeopardise participant’s safety 
or compliance with the protocol. 
4. Other musculoskeletal lesions that may affect the gait pattern 
3.3 
Expected Duration of the Trial 
  Specify the expected duration and define the end of the Trial for the Trial participant. This can be the full 
Trial duration e.g. first patient first visit to last patient last visit including follow up. Alternatively, for long 
running trials (e.g; oncology), the end of Trial can be defined at a specific time point at which the Trial will be 
regarded as completed even if patients are still in follow up. A simple table format is the preferred style. Make 
the distinction between the expected Trial duration at the site and the expected Trial duration for a single patient. 
Trial duration at the site:  
- 
4 years 
 
Trial duration for a single patient:  
- 
One single visit with clinical and biomechanical testing within 2 years postsurgery 
 
3.4 
Screening failures 
  Describe the process when a participant will be considered as screen failure.  (see CTC website 
documenten/ISF: screening log)   
All participants that are considered for Trial participation and meet all of the inclusion criteria 
will be documented on the Screening Log, including Screen Failures. Participants who meet 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
18
one or more of the exclusion criteria must not proceed to be enrolled in the Trial and will be 
identified on the Screening Log as Screen Failure.   
 
3.5 
Consent withdrawal  
Participants may voluntarily withdraw consent to participate in the Trial for any reason at any 
time. The participant’s request to withdraw from the Trial must always be respected without 
prejudice to further treatment. This will be documented by the PI in the patient’s medical 
record. The PI must take into account the consequences of such withdrawal: (1) use of personal 
data / study data, (2) use of human biological material already collected 
4 Trial Procedures 
4.1 
Selection of Participants / Recruitment 
  Specify which department or Institution will recruit the participants and how the participants will be 
approached for inclusion and obtainment of such informed consent. 
See also link: Adverteren / Rekruteren Richtlijnen    
 
 
 
 
. 
Patients of the orthopedic unit of AZ Delta Roeselare (Prof. Dr. T. Luyckx, Prof. Dr. P 
Winnock de Grave) will be recruited. Patients are contacted by phone and trial setup will be 
explained. If patient is willing to contribute, informed consent is sent by post to the patient. 
Once informed consent is completed and signed by the patient and sent back, patient will be 
invited for a test-moment at the movement analysis laboratory in KU Leuven Campus Bruges. 
4.2 
Consent  
  See also: Informed consent formulier (ICF)  
 
 
 
 
 
 
The Trial can and will be conducted only on the basis of prior informed consent by the Trial 
participants. All participants will be informed about the aim of the study, possible adverse 
events, procedures and possible hazards to which the participant will be exposed, mechanism 
of treatment allocation (if applicable), strict confidentiality of any patient data, respective 
insurance coverages as required by local law and medical records possibly being reviewed for 
trial purposes by authorized individuals other than their treating physician.  
The Investigator shall obtain a signed and personally dated informed consent form from 
participants or their legal representative(s) prior to their enrollment at their Participating Site. 
This means that informed consent must be obtained prior any procedure specifically conducted 
for the purposes of the Trial. It is emphasized in the information sheet that participation is 
voluntary and that the participant is free to refuse further participation in the Trial whenever 
he/she wants to. This will not have any impact on the participants subsequent care.   
All originally signed obtained ICFs must be retained/archived in the ISF at the Participating 
Site and cannot be destroyed (even when a scanned copy is available) before expiration of legal 
archiving term (defined in section “Archiving”). Adequate information regarding a point of 
contact where the participant may obtain further information about the Trial will be provided 
in the ICF.  
All of the above must be done in accordance with the applicable national legislation and local 
regulatory requirements. 
4.3 
Randomization Procedure / Code Break (if applicable) 
  Provide details of the randomization procedure to be used for each subject (e.g. central randomization 
procedures), the method used to generate the randomization schedule (e.g. computer generated), the source of 
the randomization schedule (e.g. sponsor, investigator, or other), and whether or not an Interactive Voice/Web 
Response System (IVRS/IWRS) will be used. Provide a description of the specific blinding procedures, if any, to 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
19
be used and where/how code break will be achieved if necessary. If blinding will not be used, include a statement 
to that effect. 
 
No randomization procedure applicable. Researchers will use a blind method when conducting 
clinical and biomechanical testing on these 3 groups (researchers do not know which group the 
patients to be tested belong to). When all patients have completed all testing. During the data 
analysis process, the researchers learned which group the patients belonged to, as documented 
in the patient case file.Visit schedule and assessments 
  Describe the sequence of visits and applicable procedures/investigations in more detail to be performed as 
stipulated in the Trial flowchart.  Also take possible re-screening and re-consenting procedures in mind.  
Applicable and allowed visit-windows can be added. 
See Trial Flowchart 
Procedure/Assesment 
Contact 1/ IC 
Data Collection 
Contact 2 
Prospective Testing 
Contacts 
1 
 
2 
3 
Informed consent 
X 
 
 
 
Inclusion/Exclusion criteria 
X 
 
 
 
Demographics 
 
X 
 
 
Medical, Surgical history 
 
X 
 
 
 
Collecting Data 
 
 
 
 
preop x-rays 
 
X 
 
 
perop alignment & positioning 
 
X 
 
 
surgical technique: cement, patella 
 
X 
 
 
 
Appointment for testing 
 
 
X 
 
Clinical Testing 
 
OKS-12 
 
 
 
X 
FJS-12 
 
 
 
X 
VAS Satisfaction 
 
 
 
X 
PCS 
 
 
 
X 
Tinetti 
 
 
 
X 
VAS Pain 
 
 
 
X 
Biomechanical Testing 
 
Gait and functional movement 
(forward lunge, squat) analysis: 
kinetic, kinematic, EMG 
 
 
 
X 
 
5 Adverse Event Reporting 
5.1 
Definitions 
5.1.1 Adverse Event (AE) 
An AE is any untoward medical occurrence in a patient or subject during an experiment, and 
which does not necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the use of a product, 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
20
whether or not considered related to the product. Any worsening (i.e., any clinically significant 
adverse change in the frequency or intensity of a pre-existing condition) should be considered 
an AE. 
5.1.2 Adverse Reaction (AR) 
An AR is any untoward and unintended responses to an investigational medicinal product or 
to an experiment and, when an investigational product is concerned, related to any dose 
administered. 
5.1.3 Serious Adverse Event (SAE) 
An SAE is any untoward medical occurrence that results in any of the following: 
• Death 
• A life-threateninga experience 
• In-patient hospitalisation or prolongation of existing hospitalisation 
• A persistent or significant disability or incapacity 
• A congenital anomaly or birth defect 
• Important medical events that may be considered an SAE when - based on appropriate 
medical judgement - they may jeopardise the subject and may require medical or 
surgical intervention to prevent one of the above outcomes 
 
a The term “life threatening” in the definition of SAE refers to an event in which the subject was at risk of 
death at the time of the event. It does not refer to an event which hypothetically might have caused death if it 
was more severe. 
5.2 
Recording of adverse events (AEs) 
The risk associated with the study-specific intervention is  falling. The risk of subjects falling 
will be assessed and subjects will be assisted by handrails to minimize this risk. If the subject 
still has a tendency to fall, the experimental task will be stopped or the difficulty of the 
experimental task will be reduced. 
The participant will be asked to report any adverse event related to the study-specific 
intervention to the study team. These reported events will be documented by the Investigator 
in the source documents and reported to the Sponsor through the (e)CRF. 
The following minimum information should be recorded for each adverse reaction (AR): 
- AE description 
- start and stop date of the AR 
- severity 
- seriousness 
- causality assessment to the study interventions 
- outcome 
5.3 
Reporting to the Ethics Committee 
The sponsor will assess whether any relevant safety information that becomes available during 
the study should be reported ad hoc to the EC. 
The sponsor has the obligation to, once a year throughout the clinical trial (or on request), 
submit a progress report to the EC containing an overview of all SARs (Serious Adverse 
Reactions) occurred during the reporting period and taking into account all new available safety 
information received during the reporting period.  
6 Statistics and Data Analysis 
  Describe the measures taken to avoid, or at least minimize, biases. Clearly define the study hypotheses which 
will be the object of statistical testing. 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
21
Hypothesis:  TA TKA strategy is expected to provide better clinical and functional outcomes 
for the patient at the end of the rehabilitation period (1 year post-surgery) compared to MA 
TKA. 3D patient-specific aligned TA TKA is expected to provide better clinical and functional 
outcomes for the patient at the end of the rehabilitation period compared to TA TKA. 
Three groups of patients after a TKA with a different alignment streategy are compared. To 
minimize biases all patients were operated with a same implant, same surgical approach and at 
the same hospital. Researchers will be blinded during clinical and biomechanical testing of the 
3 groups. 
6.1 
Sample Size Determination 
  Give the number of participants to be enrolled, together with the rationale for the sample size (the “power 
calculation”). 
6.2 
Power analysis showed that 45 participating patients would need to be recruited, 15 
participants per treatment group. An additional 15 healthy participants are needed 
to compare which treatment regimen has results closer to those of healthy 
volunteers (Healthy participants, mainly grandparents of students at the Bruges 
Campus or parents of employees, eligible healthy controls can be matched and 
extracted on specific request in the Bruges Campus Gait Laboratory 
database).Statistical Analysis  
  The statistical analysis plan will be developed and finalized before database lock and will describe the 
participant populations to be included in the analysis, and procedures for accounting for missing, unused, and 
spurious data. This section is a summary of the planned statistical analysis of the primary and secondary 
endpoints. 
Describe the statistical methods to be employed, including timing of any planned interim analysis. Stipulate the 
level of significance that is to be used in each Trial analysis, together with the procedure(s) for accounting for 
any missing, unused, and spurious data. Procedures for reporting any deviation from the original statistical plan 
should be described and justified. 
6.2.1 
Efficacy Analysis 
Endpoint 
Statistical Analysis Methods 
Primary 
Normality testing (Shapiro Wilk or Kolmogorov Smirnof test) 
Secondary 
Based on normality testing: unpaired T-test or Mann Whitney test 
Exploratory 
Regression or multivariate analysis 
7 Data handling  
  Give details of whether paper or electronic CRF will be used, describe the proposed database etc.     See 
website CTC: e-CRF). 
Paper CRF, stored by Dr. Philip Winnock de Grave 
 
Specify what kind of data will be collected (see definitions and links below):  
http://wiki/display/public/muzlidoc/Gezondheidsgegevens+en+onderzoek   
  
Data collection, management, storage, and backup will be performed by the doctoral 
researchers associated with this project (Zhijun Li), under the supervision of the PI (Kurt 
Claeys). The doctoral researcher associated with this project will be responsible for data 
documentation & metadata, under the supervision of the PI.  
Participant identities will be linked to data using an alphanumeric code. The separate and 
uniquely double pass-word coded "Subject Identification Code List", which matches 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
22
identifying codes with the subjects' names, will be managed by the principle investigator (EM) 
and stored separately, using the Digital vault for private data service of the ICTS, KU Leuven. 
This system involves a secure and operating system in ICTS's special, secure environment for 
private data. The research record will be confidential, to the extent provided by federal, state, 
and local law. No one will see the record except people who have a right to see it. The 
participant will not be identified by name in any reports on this study.  
Digital, pseudonymized data (i.e. coded and containing no personal information) will be stored 
on a Large Volume Storage (L-drive) of the KU Leuven, specifically developed to store large 
amounts of data for long periods of time. Only the investigators will have access to these files. 
The PI of this project (KC) will be the only one who can grant access to this network drive. 
Additionally, copies can be made on the individual work pc of the researchers involved in the 
project.  Paper copies of the descriptive data and questionnaires will be stored in a secured 
locker at the Department of Rehabilitation Sciences, Campus Bruges of the KU Leuven. Only 
authorized personnel will have access to this locked storage room as they will need to be 
granted access by the PI (KC). Audio, video, kinematic data will be automatically encrypted 
and saved to a study dedicated laptop/tablet and to the secured KU Leuven’s secure internal 
servers.  
Back-up of the data will be provided via the university's secure network drive with automatic 
daily backup procedures. Additionally, a mirror of the data is provided in a second ICTS data 
centre for business continuity or disaster recovery purposes. The paper copies will be digitized 
and together with the digital data stored on the university's secure network drive with automatic 
daily backup procedures. Sufficient storage and backup capacity for the data is provided on the 
KU Leuven servers and networks.   
At the end of the project, the files will be delivered to the principal investigator, who will 
continue to ensure their safekeeping. In accordance with the policy of KU Leuven, these files 
will be kept for at least another ten years after project completion. Data will be archived on the 
secured university’s network drive (K-drive), which is specifically developed to archive data 
for long periods of time.  
All data will be treated with strict confidentiality during the project. In order to guarantee the 
confidentiality of the information (including potentially personal data, whether or not from 
patients) and the privacy of those involved, the investigators will always handle Information 
with the utmost care and discretion within the framework of this study. The investigators will 
observe complete confidentiality at all times with regard to the information of which he/she 
has gained knowledge during the performance of this study.   
In carrying out this research, the investigators commit themselves to the following duty of 
confidentiality:   
- during and after completion of the study, the investigator accepts to strictly observe the duty 
of discretion with regard to the information that has been collected and the activities the 
investigator has participated in, and with regard to the patients, healthy volunteers, and staff 
members with whom the investigator comes into contact;   
- the investigator will only process and collect data that are relevant and necessary for the 
study;   
- the investigator will not share data with anyone not directly involved in this research;   
- the investigator will take all necessary measures to protect the confidentiality of information 
and the privacy of data subjects;  

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
23
- the investigator will handle the information carefully and responsibly and the access granted 
to information systems and digital data carriers.   
The research data files will be strictly confidential, to the extent provided by federal, state, and 
local law. No one will see the research data except people who have a right to see it. In addition, 
participants will not be identified in any way at an individual level in any reports on this study.   
The collection, processing, and disclosure of personal data, such as patient health and medical 
information are subject to compliance with the GDPR legislation (General Data Protection 
Regulation) and with the General Data Protection Regulation (EU Regulation 2016/679).  
 
 
 
 Anonymous data are data that cannot be related to an identified or identifiable person and such data are 
consequently not personal data. Anonymous data can be collected (no identified or identifiable data are 
mentioned on questionnaire) or data can be anonymized after collection (once received and before analysis, all 
data which are related to an identified or identifiable data, are deleted). In case data are anonymized, no one 
(not even the Investigator / CI / Trial staff) can link the data to an identifiable person. The principles of data 
protection do not apply to “anonymous data”, namely data which do not relate to an identified or identifiable 
natural person or to personal data rendered anonymous in such a manner that the data subject is not or no longer 
identifiable (by any person or by any means). When assessing anonymity you should take into account that GDPR 
applies to directly identifiable data (the data subject can be identified because of a name or another specific 
identifier) and to indirectly identifiable data (the data subject can be identified because in their combination the 
collected data allow to single out an individual). As such account should for example also be taken of the size of 
the population of which the individual is part. For example aggregated data, where information about many 
individuals are combined into broad classes, groups or categories, so that it is no longer possible to distinguish 
information relating to those individuals will most likely be considered as anonymous. Additionally, you should 
be aware that data can only be considered anonymized when it is not possible to re-identify the data subject. This 
means that no key is held to re-convert key-coded data. This also means that data cannot be anonymous to you, 
while they are not anonymous to the holder of the original source data. 
 
“pseudonymisation” means the processing of personal data in such a manner that the personal data can no 
longer be attributed to a specific data subject without the use of additional information, provided that such 
additional information is kept separately and is subject to technical and organisational measures to ensure that 
the personal data are not attributed to an identified or identifiable natural person; 
E.g. The participant’s name or other identifiers should be stored separately from the Trial data and replaced with 
a unique code to create a new identity for the participant. In such a case data are encoded (pseudonymised) and 
solely the Investigator and his/her Trial staff shall be able to link the data to an identifiable person; the codelist 
must be retained in a secured place on site and can under no circumstances leave the site or be accessed by 
unauthorized persons. 
Personal data means any information about an identified or identifiable natural person (“data subject”); an 
identifiable person is one who can be identified, directly or indirectly, in particular by reference to an identifier 
such as a name, a picture, an identification number (such as a phone number, even a professional phone number, 
a code, a bank account number), an online identifier (such as location data or an e-mail address, even a 
professional email address) or to on or more factors specific to the physical (such as a fingerprint), psychological, 
genetic, mental, economic, cultural, social identity of that natural person. They do not only include data having 
to do with individuals' privacy, but also data having to do with an individual's professional or public life. 
 
7.1 
Data Collection Tools and Source Document Identification 
 Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded 
data from automated instruments, copies or transcriptions certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the 
pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial). (ICH-GCP 
E6(R2) Documentation of source data is necessary for the evaluation and validation of clinical findings, 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
24
observations and other activities during the Trial. Source documentation serves to substantiate the integrity 
of Trial data, confirms observations that are recorded in the eCRF and confirms the existence of Trial 
participants. 
Certified Copy: 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. (ICH-GCP E6(R2) 
Case Report Forms (CRF): A printed, optical, or electronic document designed to record all of the protocol 
required information to be reported to the sponsor on each trial subject. (ICH-GCP E6(R2) 
 
7.1.1 Operational aspects  
7.1.1.1 Data collection  
Source Data will be collected and recorded in the Trial participants files/medical records. 
If applicable, worksheets may be used for the capture of some data to facilitate completion of 
the (e)CRF. Any such worksheets will become part of the Trial participant's source 
documentation. 
It remains the responsibility of the Investigator to check that all data relating to the Trial, as 
specified in the Trial protocol, are entered into the (e)CRF in accordance with the instructions 
provided and that the forms are filled out accurately and complete. 
(e)CRFs are provided by the sponsor for each subject. The Trial data will be transcribed by 
Trial Staff, as soon as possible after a subject visit, from the source documents into an (e)CRF 
in an pseudonymized manner using a unique identifier assigned by the Sponsor.  
The eCRFs should be available for review at the next scheduled monitoring visit (if applicable).  
7.1.1.2 Data Validation  
All data relating to the Trial must be prepared and validated by the Investigator. All (e)CRF 
entries, corrections and alterations must be made by the Investigator or other authorized Trial 
staff.  
Proper audit trails are available to demonstrate the validity of the Trial data.  
7.1.1.3 Data Management 
The trial Data Manager will perform extensive consistency checks on the received data. 
Queries will be issued in case of inconsistencies.  
7.1.1.4 Data Transfer 
Any participant record or datasets that are transferred to the Sponsor will contain the identifier 
only; participant names or any information which would make the participant identifiable will 
not be transferred. All pseudonymized data relating to the Trial must be transmitted in a secure 
manner to the Sponsor (see 8.1.2. legal requirements). 
7.1.2 Legal requirements 
All Source data will be kept on a secured location at all times. These data must be collected 
and processed with adequate precautions to ensure confidentiality and compliance with 
applicable data protection laws and regulations and more in particular the EU General Data 
Protection Regulation 2016/679 (GDPR), the relevant Belgian laws implementing the GDPR. 
Appropriate technical and organizational measures to protect the data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must 
be put in place. Trial staff whose responsibilities require access to personal data agree to keep 
the data confidential. 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
25
The Investigator and the Participating Site shall treat all information and data relating to the 
Trial disclosed to them in this Trial as confidential and shall not disclose such information to 
any third parties or use such information for any purpose other than the performance of the 
Trial. The collection, processing and disclosure of personal data, such as patient health and 
medical information is subject to compliance with applicable laws and regulations regarding 
personal data protection and the processing of personal data. 
The Investigator will maintain all source documents and completed (e)CRFs that support the 
data collected from each Trial participant, as well as all Trial documents as specified in ICH-
GCP Chapter 8, Essential Documents for the Conduct of a Clinical Trial, and all Trial 
documents as specified by the applicable regulatory requirement(s) in the TMF / ISF.  
The Investigator will take measures to prevent accidental or premature destruction of these 
documents. 
Transfer of the pseudonymized data will be performed via a secured method of transfer 
taking into account all applicable security arrangements and regulations (such as the the 
European General Data Protection Regulation regarding data protection). The receiving party 
will agree to keep the transferred data confidential at all times.  
7.2 
Access to Data, Audit and Inspection 
 
  The Investigator will permit Trial-related monitoring, audits and competent authorities or other health 
authorities inspections, providing direct access to all relevant Source Data / Documents. 
In addition (e)CRFs must be made available at all times for monitor, audit by the Sponsor’s 
Trial auditor and for inspection by the competent authorities and other health authorities. The 
accuracy of the data will be verified by review of the Source Documents (if applicable and 
depending on the audit / inspection purposes). 
 
7.3 
Monitoring 
  Monitoring section only to be incorporated in the protocol if monitoring (by CTC or another CRO) is 
applicable.  Please always check with CTC.) 
Monitoring of the Trial will be conducted periodically by Trial monitors (independent from 
Trial staff).  The Sponsor and Investigator/Participating Site will permit direct access to the 
Trial data and to the corresponding Source Data and documents to verify the accuracy of these 
data. The Trial will be monitored to ensure that the Trial is being conducted in compliance with 
GCP and current legislation, verify, among other procedures, that written informed consent has 
been obtained correctly, that the Trial procedures have been followed as shown in this protocol, 
and that the data have been recorded, for which the Source Data will be compared with the data 
recorded in the (e)CRF. More details about the monitoring strategy for this Trial are described 
in the Trial specific Monitoring Plan. 
 
7.4 
Archiving  
As specified in ICH-GCP section 8.1 Addendum the Sponsor and Investigator/Participating 
Site should maintain a record of the location(s) of their respective Essential Documents 
(including but not limited to Source Documents, completed and final CRF and ISF / TMF). 
The Sponsor should ensure that the Investigator has control of and continuous access to the 
(e)CRF data reported to the Sponsor during the Trial.  
The Investigator / Participating Site should have control of all Essential Documents and records 
generated by the Investigator / Participating Site before, during and after the Trial. 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
26
The Sponsor is responsible for archiving trial specific documentation (such as but not limited 
to protocol, potential amendments, final report and database)according to ICH-GCP. Source 
data and site-specific study documents (such as but not limited to the originally signed ICFs) 
will be archived locally on site according to local practice, guidelines for at least 20 years. 
Archived data may be held on electronic record, provided that a back-up exists and that hard 
copies can be obtained, if required. Destruction of Essential Documents will require 
authorisation from the Sponsor. 
 
 
8 Ethical and Regulatory Considerations 
8.1 
Ethics Committee (EC) review & reports  
  See also link: https://www.uzleuven.be/nl/ethische-commissie/onderzoek  
 
 
 
The Trial will be conducted in compliance with the principles outlined in the requirements for 
the conduct of clinical trials in the EU as provided for in Directive 2001/20/EC or the 
Regulation 536/2014 as soon as applicable and any subsequent amendments, the ICH-GCP 
guidelines, the most recent version of the Declaration of Helsinki,  the Belgian law of May 7th 
2004 regarding experiments on the human person (as amended) or the Belgian law of May 7th 
2017 on clinical trials on medicinal products for human use as soon as applicable, the EU 
General Data Protection Regulation 2016/679 (GDPR), the relevant Belgian laws 
implementing the GDPR, the Belgian Law of August 22nd 2002 on patient rights and all other 
applicable legal and regulatory requirements. 
Before the start of the Trial, this protocol, the ICFs and other related documents e.g. 
advertisements and general practisioners information letters, will be submitted for review to 
the EC and to the relevant CA for Trial authorization (the below mentioned obligations shall 
only apply to the extent applicable). The Trial shall not commence until such approvals have 
been obtained. 
The CI acknowledges that it is his responsibility to produce APR and he will do so by 
submitting to the EC/CA within 30 days of the anniversary date on which the favorable opinion 
was given, and annually until the Trial is declared ended. 
The Investigator shall notify the EC/CA of the end of the Trial. Should the Trial be ended 
prematurely, the Investigator will notify the EC/CA and include the reasons for the premature 
termination within 15 days of the descision. The Investigator will submit a final report with the 
results, including any publications/abstracts, to the EC/CA within 1 year. 
8.2 
Peer review  
 Example: This Trial protocol was peer reviewed by certain independent experts. Peer review was conducted 
by expert referees to the professional and scientific standards expected for clinical studies. 
This Trial protocol was peer reviewed by certain independent experts. Peer review was 
conducted by expert referees to the professional and scientific standards expected for clinical 
studies. 
8.3 
Regulatory Compliance 
This Trial protocol and the conduct of the Trial in general is in compliance with applicable 
law, including but not limited to the Belgian law of May 7th 2004 regarding experiments on the 
human person and any relevant amendments. 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
27
8.4 
Protocol / GCP compliance 
  See website CTC documenten/ISF: protocol deviation log and corrective action plan) 
The Trial must be performed in accordance with the protocol, current ICH-GCP, and applicable 
regulatory and country-specific requirements. GCP is an international ethical and scientific 
quality standard for designing, conducting, recording, and reporting studies that involve the 
participation of human subjects. Compliance with this standard provides public assurance that 
the rights, safety, and well-being of Trial participants are protected, consistent with the 
principles that originated in the most recent version of the Declaration of Helsinki, and that the 
Trial data are credible. 
It is acknowledged and agreed that prospective, planned deviations or waivers to the protocol 
are not allowed under applicable regulations on clinical studies and must not be used. However, 
should there be an accidental protocol deviation, such deviation shall be adequately 
documented in the source documents and on the relevant forms and reported to the CI and 
Sponsor. Protocol deviations which are found to frequently recur, will require (immediate) 
action. CI acknowledges that such recurring protocol deviations could be potentially classified 
as a serious violation. 
It is understood that “a serious violation” is likely to effect to a significant degree: 
- 
the safety or physical or mental integrity of the participants of the Trial; or 
- 
the scientific validity of the Trial 
8.5 
Data protection and participant confidentiality 
The Trial will be conducted in compliance with the requirements of the Belgian Privacy Act 
of 8 December 1992 on the protection of privacy in relation to the processing of personal data 
and the applicable European Directives and Regulations regarding data protection. Any 
collection, processing and disclosure of personal data, such as patient health and medical 
information is subject to compliance with the aforementioned personal data protection laws 
(Cfr. DPA in Annex). 
Any personal data shall be treated as confidential at all times including during collection, 
handling and use, and that the personal data (including in any electronic format) shall be stored 
securely at all times and with all technical and organizational security measures that would be 
necessary for compliance with data protection legislation. The Sponsor shall take appropriate 
measures to ensure the security of all personal data and guard against unauthorized access 
thereto or disclosure thereof or loss or destruction while in its custody. 
8.6 
Insurance 
Art 29 of the Belgian Law relating to experiments on human persons dated May 7th, 2004 
applies. In accordance with this Belgian law, the sponsor is unfailingly liable for any damage 
suffered by the participating patient and/or his beneficiaries that is directly or indirectly related 
to the trial. The sponsor of this study (KU Leuven) has taken out insurance to cover this 
liability.   
8.7 
Participants must pay for their own transportation to and from the laboratory. If a 
participant's participation in the study requires additional travel, that is, travel 
beyond routine care, travel expenses for these additional trips will be 
reimbursed.Amendments 
  See alsolink: https://www.uzleuven.be/nl/ethische-commissie/onderzoek 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
28
In accordance with the Belgian law of May 7th 2004 regarding experiments on the human 
person, the Sponsor may make a non-substantial amendment at any time during a Trial. If the 
Sponsor wishes to make a substantial amendment to the clinical Trial agreement or the 
documents that supported the original application for the clinical Trial authorisation, the 
Sponsor must submit a valid substantial amendment to the Competent authority (CA) for 
consideration. If the Sponsor wishes to make a substantial amendment to the EC application or 
the supporting documents, the CI must submit a valid substantial amendment to the EC for 
approval. The CA and/or the EC will provide a response regarding the amendment within 28 
days of receipt of the notice. It is the Sponsor’s responsibility to decide whether an amendment 
is substantial or non-substantial for the purposes of submission to the CA and/or EC. 
Any subsequent protocol amendments will be submitted to the EC and regulatory authorities 
for approval. No substantial amendment that require review by EC will be implemented until 
the EC grants a favorable opinion for the Trial. The CI acknowledges that amendments may 
also need to be reviewed and accepted by the Competent Authority before they can be 
implemented in practice at Participating Sites. 
9 Publication Policy 
  Can be revised in compliance with the ethical aspects 
Publications will be coordinated by the CI. Authorship to publications will be determined in 
accordance with the requirements published by the International Committee of Medical Journal 
Editors and in accordance with the requirements of the respective medical journal.  
For multi-centric Trials, it is anticipated that the primary results of the overall Trial shall be 
published in a multi-centre publication. 
Participating Site is not allowed to publish any subset data or results from the Trial prior to 
such multicentre publication.  
Any publication by Participating Site will be submitted to the Sponsor for review at least thirty 
(30) days prior to submission or disclosure. Sponsor shall have the right to delay the projected 
publication for a period of up to three (3) months from the date of first submission to the 
Sponsor in order to enable the Sponsor to take steps to protect its intellectual property rights 
and know-how.  
10 Intellectual Property 
  Only to insert if no participating site agreement is signed and the protocol serves as contract 
between the parties 
Any know how, inventions, methods, developments, innovations and discoveries, whether 
patentable or not, arising from the Trial or made in the performance of the Trial protocol  
(“Inventions”) shall vest in the Sponsor. The Participating Site, its employees and 
Investigator(s) shall promptly disclose to Sponsor any such Inventions. Parties have expressly 
agreed that any and all Trial data as collected and prepared in the performance of the Trial 
protocol shall be the sole property of Sponsor. 
11 JCI 
 
In order to ensure the same quality and safety standards in patient care for clinical research as 
commonly applied by Sponsor in its regular activities, also in accordance with Joint 
Commission International standards, the Sponsor shall comply with the following 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
29
obligations:  (a) the Sponsor will use trained and qualified employees or contractors to 
manage and coordinate the Trial; (b) the Sponsor will ensure that multi-center Trial reporting 
is reliable and valid,  statistically accurate, ethical, and unbiased. The same requirements are 
applicable if multi-center Trial data and multi-center Trial results are provided to the 
INSTITUTION; (c) the Sponsor will not grant incentives, other than standard compensations 
and reimbursement of costs, to Trial participants or to participating site’s staff that would 
compromise the integrity of the research; (d) the Sponsor is responsible for monitoring and 
evaluating the quality, safety, and ethics of the Trial and will respect the participating site’s 
policies and processes when performing such monitoring and evaluation activities; (e) the 
Sponsor will protect the privacy and confidentiality of the Trial participants in accordance 
with all applicable laws. 
 
12 References 
 
1) Bourne R.B., Chesworth B.M., Davis A.M., Mahomed N.N., Charron K.D. Patient 
satisfaction after total knee arthroplasty: who is satisfied and who is not?. Clin 
Orthop Relat Res. 2010; 468: 57-63 
 
2) Eckhoff D.G., Bach J.M., Spitzer V.M., Reinig K.D., Bagur M.M., Baldini T.H., et al. 
Three-dimensional mechanics, kinematics, and morphology of the knee viewed 
in virtual reality. J Bone Joint Surg Am. 2005; 87: 71-80 
 
3) Insall J.N., Binazzi R., Soudry M., Mestriner L.A. Total knee arthroplasty. Clin 
Orthop Relat Res. 1985; 192: 13-22 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
30
Appendices 
  Additional documents can be included as Appendix, such as ICF, PRO’s, questionaires, scores, specific Trial 
information, additional guidelines (coding, classification, …) and scoring information, etc… 
Appendix 1: The Forgotten Joint Score 
 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
31
Appendix 2: Oxford Knee Score 
 
 
 
 
 
 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
32
Appendix 3: VAS Satisfaction 
 
How satisfied are you with the result of your knee replacement surgery? 
 
           0___________________________________________________10 
 
Very dissatisfied 
 
 
 
 
 
 
Very satisfied 
 
 
 
 
Appendix 4:  VAS Pijn 
 
How much pain have you experienced in the area of your operated knee during the last 4 
weeks? 
           0___________________________________________________10 
 
No pain 
 
 
 
 
  
                  Unbearable pain  
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
33
Appendix 5:  Pain Catastrophizing Scale 
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
34
Appendix 6:  Tinetti Test  
 
 
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
35
13 Appendix 7: Data Processing Annex (DPA) 
 
Definitions: 
• “Protocol” means the document entitled “Clinical and Biomechanical Outcome after 
Robotically-Assisted Total Knee Arthroplasty by Comparing Three Alignment 
Strategies ” containing the details of the academic study as developed by the Sponsor 
as approved by the relevant ethics committee. 
• “Sponsor” means  KU Leuven. 
• Participating site acts as a data processor as defined under article 4, 8) of the Regulation 
(EU) 2016/679 (“Data Processor”) for the Sponsor who acts as data controller as 
defined under article 4, 7) of the Regulation (EU) 2016/679 (“Data Controller”). 
• “Applicable Law”  means any applicable data protection or privacy laws, including:  
o the Regulation (EU) 2016/679 also referred as the General Data Protection 
Regulation ("GDPR");  
o other applicable laws that are similar or equivalent to or that are intended to or 
implement the laws that are identified in (a) of this definition;  
• "Personal Data" means any information relating to an identified or identifiable natural 
person (‘Data Subject’), including without limitation pseudonimized information, as 
defined in Applicable Law and described in the Protocol. 
Rights and obligations: 
1. The Data Processor is instructed to process the Personal Data for the term of the 
Protocol and only for the purposes of providing the data processing tasks set out in the 
Protocol. The Data Processor may not process or use Personal Data for any purpose 
other than a Data Subject’s medical records, or other than provided in the instructions, 
including with regard to transfers of personal data to a third country or an international 
organization, unless the Data Processor is required to do so according to Union or 
Member State law.  
 
2. Data Processor shall at all times maintain a record of processing of Personal Data in 
accordance with Applicable Law and if the Data Processor considers an instruction 
from the Data Controller to be in violation of the Applicable Law, the Data Processor 
shall promptly inform the Data Controller in writing about this 
 
3. The Data Processor must ensure that persons authorized to process the Personal Data 
have committed themselves to confidentiality or are under an appropriate statutory 
obligation of confidentiality. 
 
4. The Data Processor shall implement appropriate technical and organizational measures 
to prevent that the Personal Data processed is: 
(i) accidentally or unlawfully destroyed, lost or altered, 
(ii) disclosed or made available without authorization, or 
(iii)otherwise processed in violation of Applicable Law.  
 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
36
5. The appropriate technical and organizational security measures must be determined 
with due regard for: 
(i) the current state of the art, 
(ii) the cost of their implementation, and 
(iii)the nature, scope, context and purposes of processing as well as the risk of varying 
likelihood and severity for the rights and freedoms of natural persons. 
 
6. Taking into account the nature of the processing, the Data Processor shall assist the 
Data Controller, by means of appropriate technical and organizational measures, 
insofar as this is possible, in fulfilling its obligation to respond to requests from Data 
Subjects pursuant to laws and regulations in the area of privacy and data protection 
(such as, the right of access, the right to rectification, the right to erasure, the right to 
restrict the processing, the right to data portability and the right to object) 
 
7. The Data Processor shall upon request provide the Data Controller with sufficient 
information to enable the Data Controller to ensure that the Data Processor's obligations 
under this DPA are complied with, including ensuring that the appropriate technical 
and organizational security measures have been implemented. 
 
8. The Data Controller is entitled to appoint at its own cost an independent expert, 
reasonably acceptable to Data Processor, who shall have access to the Data Processor's 
data processing facilities and receive the necessary information for the sole purpose of 
auditing whether the Data Processor has implemented and maintained said technical 
and organizational security measures. The expert shall upon the Data Processor's 
request sign a non-disclosure agreement provided by the Data Processor, and treat all 
information obtained or received from the Data Processor confidentially, and may only 
pass on, after conferral with Data Processor, the findings as described under 8) (ii) 
below to the Data Controller. 
 
9. The Data Processor must give authorities who by Union or Member State law have a 
right to enter the Data Controller's or the Data Controller's processors’ facilities, or 
representatives of the authorities, access to the Data Processor's physical facilities 
against proper proof of identity and mandate, during normal business hours and upon 
reasonable prior written notice. 
 
10. The Data Processor must without undue delay in writing notify the Data Controller 
about: 
(i) any request for disclosure of Personal Data processed under the Protocol by 
authorities, unless expressly prohibited under Union or Member State law, 
(ii) any  finding of (a) breach of security that results in accidental or unlawful 
destruction, loss, alteration, unauthorized disclosure of, or access to, Personal Data 
transmitted, stored or otherwise processed by the Data Processor under the Protocol, 
or (b) other failure to comply with the Data Processor's obligations, or 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
37
(iii)any request for access to the Personal Data (with the exception of medical records 
for which the Data Processor is considered data controller) received directly from 
the Data Subjects or from third parties. 
 
11. Such a notification from the Data Processor to the Data Controller with regard to a 
breach of security as meant in 8) (ii)(a) above will contain at least the following 
information: 
(i) the nature of the Personal Data breach, stating the categories and (by 
approximation) the number of Data Subjects concerned, and stating the categories 
and (by approximation) the number of the personal data registers affected (datasets); 
(ii) the likely consequences of the Personal Data breach; 
(iii)a proposal for measures to be taken to address the Personal Data breach, including 
(where appropriate) measures to mitigate any possible adverse effects of such 
breach. 
 
12. The Data Processor shall document (and shall keep such documentation available for 
the Data Controller) any Personal Data breaches, including the facts related to the 
Personal Data breach, its effects and the corrective measures taken. After consulting 
with the Data Controller, the Data Processor shall take any measures needed to limit 
the (possible) adverse effects of Personal Data breaches (unless such consultation 
cannot be awaited due to the nature of the Personal Data breach). 
 
13. The Data Processor must promptly reasonably assist the Data Controller (with the 
handling of (a) responses to any breach of security as described in 10) (ii) above and 
(b) any requests from Data Subjects under Chapter III of the GDPR, including requests 
for access, rectification, blocking or deletion. The Data Processor must also reasonably 
assist the Data Controller by implementing appropriate technical and organizational 
measures for the fulfilment of the Data Controller's obligation to respond to such 
requests.  
 
14. The Data Processor must reasonably assist the Data Controller with meeting the other 
obligations that may be incumbent on the Data Controller according to Union or 
Member State law where the assistance of the Data Processor is implied, and where the 
assistance of the Data Processor is necessary for the Data Controller to comply with its 
obligations. This includes, but is not limited to, at the request to provide the Data 
Controller with all necessary information about an incident under 10) (ii), and all 
necessary information for an impact assessment in accordance with Article 35 and 
Article 36 of the GDPR.  
Subprocessor: 
15. The Data Processor may only engage a subprocessor, with prior specific or general 
written consent from the Data Controller. The Data Processor undertakes to inform the 
Data Controller of any intended changes concerning the addition or replacement of a 
subprocessor by providing a reasonable prior written notice to the Data Controller. The 
Data Controller may reasonably and in a duly substantiated manner object to the use of 

KU Leuven                                                                      protocol non-commercial interventional clinical trial (with IMP) v1 
Version 6 - 11-6-2023 
 
Confidential 
Protocol: RATKA_CBO 
 
38
a subprocessor. The Data Processor must inform the Data Controller in writing of the 
discontinued use of a subprocessor. 
 
16. Prior to the engagement of a subprocessor, the Data Processor shall conclude a written 
agreement with the subprocessor, in which at least the same data protection obligations 
as set out in this DPA shall be imposed on the subprocessor, including obligations to 
implement appropriate technical and organizational measures and to ensure that the 
transfer of Personal Data is done in such a manner that the processing will meet the 
requirements of the Applicable Law. 
 
17. The Data Controller has the right to receive a copy of the relevant provisions of Data 
Processor's agreement  with the subprocessor related to data protection obligations. The 
Data Processor shall remain fully liable to the Data Controller for the performance of 
the subprocessor obligations under this DPA. The fact that the Data Controller has 
given consent to the Data Processor's use of a subprocessor is without prejudice for the 
Data Processor's duty to comply   with this DPA     .