Optimum Radiographic Assessment of the Medial and Lateral Tibiofemoral Compartments Within the Arthritic Knee
Phase: NA
Conditions: Osteoarthritis, Knee
Sponsor: Oxford University Hospitals NHS Trust

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Study Title:  Optimum radiographic assessment of the medial and lateral tibiofemoral compartments 
within the arthritic knee 
Ethics Ref: South Central – Oxford B REC (15/SC/0476)  
Date and Version No: Version 1.1 
 
Chief Investigator: 
Mr Thomas Hamilton 
The Botnar Research Centre Institute of Musculoskeletal Science, 
Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD 
Tel: 01865 227696 
Email: Thomas.Hamilton@ndorms.ox.ac.uk 
Investigators:  
Mr Hemant Pandit, Oxford University Hospitals Trust 
Dr Stephen Mellon, University of Oxford 
Professor David Murray,  Oxford University Hospitals Trust 
Sponsor:  
Oxford University Hospitals NHS Trust  
Funder: 
Departmental Funding, Oxford Orthopaedic Engineering Centre 
Chief Investigator Signature:  Thomas Hamilton 
 
One or more of the investigators has received support from a commercial partner related to 
unicompartmental knee replacement. This funding is not related to this study. 
  
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, host organisation, and members of the Research Ethics Committee, unless 
authorised to do so. 
 

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TABLE OF CONTENTS 
 
1. 
SYNOPSIS ............................................................................................................................................... 4 
2. 
ABBREVIATIONS ..................................................................................................................................... 5 
3. 
BACKGROUND AND RATIONALE ............................................................................................................ 5 
4. 
OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS .......................................................................... 7 
5. 
STUDY DESIGN ....................................................................................................................................... 8 
6. 
PARTICIPANT IDENTIFICATION .............................................................................................................. 8 
6.1. 
Study Participants .......................................................................................................................... 8 
6.2. 
Inclusion Criteria ............................................................................................................................ 8 
6.3. 
Exclusion Criteria ........................................................................................................................... 9 
7. 
STUDY PROCEDURES ............................................................................................................................. 9 
7.1. 
Recruitment ................................................................................................................................... 9 
7.2. 
Informed Consent .......................................................................................................................... 9 
7.3. 
Screening and Eligibility Assessment ........................................................................................... 10 
7.4. 
Baseline Assessments .................................................................................................................. 10 
7.5. 
Subsequent Visits ........................................................................................................................ 10 
7.6. 
Discontinuation/Withdrawal of Participants from Study ............................................................ 10 
7.7. 
Definition of End of Study ........................................................................................................... 11 
8. 
INTERVENTIONS ................................................................................................................................... 11 
9. 
SAFETY REPORTING ............................................................................................................................. 11 
10. 
STATISTICS AND ANALYSIS ............................................................................................................... 11 
10.1. 
Description of Statistical Methods .......................................................................................... 11 
10.2. 
The Number of Participants .................................................................................................... 12 
10.3. 
Analysis of Outcome Measures/Endpoints ............................................................................. 12 
11. 
DATA MANAGEMENT ...................................................................................................................... 12 
11.1. 
Access to Data ......................................................................................................................... 12 
11.2. 
Data Recording and Record Keeping ....................................................................................... 12 
12. 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 13 
13. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................... 13 
13.1. 
Declaration of Helsinki............................................................................................................. 13 
13.2. 
ICH Guidelines for Good Clinical Practice ................................................................................ 13 
13.3. 
Approvals ................................................................................................................................. 13 
13.4. 
Reporting ................................................................................................................................. 13 

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13.5. 
Participant Confidentiality ....................................................................................................... 13 
13.6. 
Expenses and Benefits ............................................................................................................. 13 
14. 
FINANCE AND INSURANCE .............................................................................................................. 14 
14.1. 
Funding .................................................................................................................................... 14 
14.2. 
Insurance ................................................................................................................................. 14 
15. 
PUBLICATION POLICY ....................................................................................................................... 14 
16. 
REFERENCES .................................................................................................................................... 15 
17. 
APPENDIX A:  STUDY FLOW CHART ................................................................................................. 16 
18. 
APPENDIX C:  AMENDMENT HISTORY ............................................................................................. 17 
 
 
 

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1. SYNOPSIS 
 
Study Title 
Optimum radiographic assessment of the medial and lateral tibiofemoral 
compartments within the arthritic knee 
Short title 
Optimum radiographic assessment of the knee 
Study Design 
Clinical Investigation 
Study Participants 
Patients aged over 50 years with knee osteoarthritis, any grade, affecting the 
tibiofemoral joint. 
Planned Sample Size 
225 
Planned Study Period 
August 2015 to January 2017 (18 months) 
 
Objectives 
Primary 
 
To assess the accuracy of different xray views of measuring joint space width 
within each compartment within the knee. 
Secondary 
 
To define the sensitivity and specificity of four different xray views at 
predicting bone on bone arthritis and joint space narrowing within each of 
the knee compartments and suitability for unicompartmental knee 
replacement. 
To define the sensitivity and specificity of MRI at predicting suitability for 
unicompartmental knee replacement. 
To assess the sensitivity and specificity of different xray techniques at 
inferring the status of soft tissue structures (anterior cruciate ligament and 
medial collateral ligament) within the arthritic knee. 
To develop a decision aid to help clinicians decide between likelihood of a 
patient being a candidate for unicompartmental knee replacement based on 
pre-operative xray and MRI findings. 
 
 
 

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2. ABBREVIATIONS 
CI 
Chief Investigator 
CRF 
Case Report Form 
CTRG 
Clinical Trials & Research Governance, University of Oxford 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
MRI 
Magnetic Resonance Imaging 
ICF 
Informed Consent Form 
NHS 
National Health Service 
NRES 
National Research Ethics Service 
OA 
Osteoarthritis 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
SOP 
Standard Operating Procedure 
TKR 
Total Knee Replacement 
UKR 
Unicompartmental Knee Replacement 
 
3. BACKGROUND AND RATIONALE 
Xrays are the most frequently used imaging test when evaluating the knee for joint replacement. They are 
non-invasive, safe and cost effective. They allow assessment of: progression of disease, appropriateness 
for joint replacement (in particular UKR) as well as likely prognosis following replacement. Despite a 
multitude of standardised views there is a lack of consensus regarding the optimum views to evaluate joint 
space narrowing within each compartment (lateral, medial and patellofemoral). 
The optimum imaging protocol is one that is acceptable to patients, involves the fewest xrays to obtain 
the most clinically relevant information and one that utilises the least resources in terms of staff and 
equipment. Currently standard assessment involves: standing anteroposterior, lateral and skyline views. 
In addition in patients being considered for joint replacement valgus/varsus stress xrays are used to 
evaluate the lateral compartment (as well as medial collateral ligament) and medial compartment 
respectively to assess the status of the cartilage. In patients with loss of cartilage on one side, typically 
medial, but preserved cartilage on the other a UKR, as opposed to TKR, may be indicated.  
Currently there is a lack of consensus amongst orthopaedic surgeons in the UK as to the best way to image 
the knee joint to establish degree and pattern of arthritis [1, 2]. For a long time it has been known that 
weight bearing views are a better method at establishing the true joint space compared to non-weight 
bearing views width due to the increased forces across the joint [3-5]. In addition it is known that full 
extension views, despite being the most commonly used view, may also underestimate joint space 

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narrowing as in full extension the femur and tibia articulate across an area of the joint that is not typically 
not involved during activity, and hence can have relatively well preserved cartilage, giving a false 
impression of the joints disease state[6]. These findings have been adopted, and continue to be adopted, 
into routine clinical practice and there continues to be an increase in the proportion of surgeons 
performing standing and semi-flexed views [2]. However the best method of evaluating the disease state 
in each compartment has yet to be defined. 
When deciding between UKR and TKR the detection of the degree and pattern of arthritis is of critical 
importance. UKR are known to perform poorly in partial thickness disease and require full thickness 
cartilage in the retained tibiofemoral compartment[7, 8]. To establish whether a patient meets the 
indications for UKR xrays are used with stress views being the gold standard, as well as the standard 
assessment that the studies of long term outcomes on UKR are based. Gibson and Goodfellow, who were 
first to describe stress xrays in the workup of a patient for UKR, reported that those patients with a joint 
space width of more than 5mm in the lateral compartment had intact lateral cartilage during surgery 
making them appropriate for UKR [9]. More recently Waldstein et al. reported that patients with a lateral 
joint space width of more than 4mm may be appropriate for UKR however overall they noted poor 
correlation between joint space width measured on valgus stress views and intra-operative Outerbridge 
grade[10]. 
In addition to the low quantity of evidence regarding the relationship between stress views and intra-
operative status of the joint the feasibility of performing stress xrays also limits their use. Stress xrays are 
resource dependent, can be uncomfortable for patients and require an additional practitioner. As such 
they are often not performed with many clinicians adopting alternative xray views, MRI or direct 
observation via arthroscopy [11]. It has been proposed that standing views with the knee in 15 degrees 
then 45 degrees flexion may load the medial and lateral compartments respectively and that these views 
may be an alternative to stress views without the requirement for an additional practitioner. However the 
outcomes based on these forms of assessment, and the relationship between the joint space width 
measured using these contemporary techniques has not been reported. An alternative would include a 
stress device that allows a stress xray to be performed without the requirement of the clinician. 
This study will evaluate the status of knee cartilage in 225 patients with varying degrees, and patterns, of 
knee OA using standing extension anteroposterior, 15 degrees flexion posteroanterior, 45 degrees flexion 
posteroanterior and valgus and varus stress views as well as MRI. These results will be compared to the 
gold standard imaging technique of stress views as well as to direct measurements of retrieved tissue in 
those patients who undergo knee replacement surgery. The sensitivity and specificity of each of the 
imaging techniques at predicting suitability for UKR will be calculated, the optimum imaging views 
proposed, and ultimately the results of this study will be used to develop a decision aid, based on optimum 
views, to help clinicians decide between likelihood of a patient being a candidate for UKR based on pre-
operative xray and MRI findings. 
 
 

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4. OBJECTIVES AND OUTCOME MEASURES/ENDPOINTS 
Objectives 
Outcome Measures  
Primary Objective 
• 
To assess the accuracy of different xray 
views of measuring joint space width 
within each compartment within the knee. 
 
Joint space width in the medial and lateral 
tibiofemoral  compartments of the knee 
measured in mm. 
 Secondary Objectives 
• 
To define the sensitivity and specificity of  
four different xray views at predicting bone 
on bone arthritis and joint space narrowing 
within each of the knee compartments and 
suitability for UKR. 
• 
To define the sensitivity and specificity of 
MRI at predicting suitability for UKR. 
• 
To assess the sensitivity and specificity of 
different xray techniques at inferring the 
status of soft tissue structures (anterior 
cruciate ligament and medial collateral 
ligament) within the arthritic knee. 
 
A joint space width of 0mm will be classified as 
bone on bone arthritis, >0mm to <5mm will be 
classified as joint space narrowing and >= 5mm 
will be classified as full thickness cartilage. The 
sensitivity and specificity of each technique, at 
detecting 
each 
disease 
state 
in 
each 
compartment, compared to the gold standard of 
stress views will be recorded. 
 
The sensitivity and specificity of MRI, compared to 
the gold standard of stress views, at predicting the 
status of each compartment will be recorded. 
 
In patients proceeding to joint replacement as 
part of their standard clinical pathway the 
sensitivity and specificity of different xray 
techniques at inferring the status of soft tissue 
structures (anterior cruciate ligament and medial 
collateral ligament) within the arthritic knee will 
be compared to operative findings. 
 
   
Tertiary Objectives 
• 
To develop a decision aid to help clinicians 
decide between likelihood of a patient 
being a candidate for UKR based on pre-
operative xray and MRI findings. 
 
The findings from this study will be used to 
develop a decision aid. The sensitivity and 
specificity of this decision aid will be calculated 
in the cohort of patients undergoing surgery 
using intra-operative audit findings as the gold 
standard.  
 

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5. STUDY DESIGN 
The study is a clinical investigation to determine the optimum xray technique for each compartment of 
the knee in patients aged over 50 years with knee arthritis.  
All patients attending knee clinic will be informed about the study in advance. Those patients who meet 
the inclusion criteria will be referred to the research team in clinic. Screening would be performed in clinic 
and in those patients that do not have exclusion criteria further information about the study will be given 
and if the patients agree to participation valid informed consent will be taken. Screening and consent 
would take around 10 minutes. Two additional xray views will be taken alongside routine clinical views and 
would be expected to take a maximum of 10 additional minutes. An MRI scan would also be arranged, and 
this would take place at a separate time arranged at the patients convenience and would take around 30 
minutes. No further research appointments would be performed. In patients who, as part of their clinical 
care, undergo knee replacement the excised joint surfaces, which are normally disposed of, would be 
retained and the degree and pattern of articular cartilage wear would be quantitatively evaluated before 
disposal.  In addition an audit of the intra-operative findings would be performed. 
Evaluation for inclusion and exclusion criteria would be via pre-tested standardised pro forma. A pain visual 
analogue scale would be used to assess for the presence and degree of pain during stress views. Xray 
images would be measured using custom measuring software (Matlab, Massachusetts , USA), MRI images 
would be measured using a segmentation method that has previously been described (Solidworks, 
Massachusetts , USA). Intra-operative audit of joint surfaces and soft tissue structures would be recorded 
on a standardised, pre-tested pro forma. Retrieved intra-operative samples of the joint surface would be 
scored using a validated technique, digitally photographed and surface geometry measured using a 3D 
laser scanner.  
A flow chart of the study can be seen in Appendix A.  
6. PARTICIPANT IDENTIFICATION 
6.1. Study Participants 
Patients aged over 50 years referred to knee clinic with radiographic evidence of knee osteoarthritis, any 
grade, affecting the tibiofemoral joint 
6.2. Inclusion Criteria 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 50 years or above. 
• 
Knee osteoarthritis any grade, affecting the tibiofemoraljoint 
• 
In the Investigator’s opinion, is able and willing to comply with all trial requirements. 
• 
Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of 
participation in the trial. 
 
 
 

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6.3. Exclusion Criteria 
The participant may not enter the study if ANY of the following apply: 
• 
Previous joint replacement on ipsilateral knee 
• 
Previous anterior cruciate ligament reconstruction or injury 
• 
Previous high tibial osteotomy 
• 
Previous intraarticular 
• 
fracture 
• 
History of Inflammatory arthritis 
• 
Unable to stand with assistance for two minutes 
7. STUDY PROCEDURES 
• 
Screening and consent (performed at clinic appointment) - 10 minutes 
• 
Standard Clinical Xrays 
o Standing anteroposterior view 
o Lateral view 
o Patelofemoral view 
o Valgus stress view (clinician performed or using validated device) 
o Varus stress view (clinician performed or using validated device) 
• 
Research xrays (performed at the same time as routine clinical xrays) – 10 minutes 
o Standing posteroanterior (PA) view 15 degrees flexion 
o Standing posteroanterior (PA) view 45 degrees flexion 
• 
MRI (performed during a separate appointment at the patients convenience) – 30 minutes 
• 
Measuring of routinely retrieved joint surface cartilage (performed in research laboratory) 
7.1. Recruitment 
All patients attending knee clinic will be provided with an information leaflet via the post 2 weeks before 
their appointment about the study. Patients will be identified as eligible by the clinical team and will be 
referred to the research team who will be based in clinic. The research team will screen patients using a 
standardised, pre-tested, pro forma. Further information about the trial will be provided.  Patients who 
meet inclusion, but not exclusion criteria, and who are willing to participate in the study will be consented 
for the study. 
7.2. Informed Consent 
Consent will be performed by a member of the research team who is suitably qualified and experienced, 
and has been authorised to do so by the Chief Investigator. 
Written and verbal versions of the Participant Information and Informed Consent will be presented to the 
participants detailing no less than: the exact nature of the study; what it will involve for the participant; 
the implications and constraints of the protocol; the known side effects and any risks involved in taking 
part. It will be clearly stated that the participant is free to withdraw from the study at any time for any 
reason without prejudice to future care, and with no obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will participate 

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in the study. The patient must personally sign and date the latest approved version of the Informed 
Consent form before any study specific procedures are performed. The written Informed Consent will then 
be dated and signature of the person who presented and obtained the Informed Consent. A copy of the 
signed Informed Consent will be given to the participant. The original signed form will be retained at the 
study site. One copy will be filed in the patient’s medical notes. 
7.3. Screening and Eligibility Assessment 
Screening will be performed via pre-tested, standardised, pro forma by a member of the research team. A 
maximum period of 2 months will be permitted between screening and MRI. Analysis of excised joint 
surfaces in those patients who undergo knee replacement as part of their clinical management will only 
be considered valid if the replacement is performed within 6 months of screening.  
7.4. Baseline Assessments 
At baseline a patient name, gender and date of birth will be recorded, together with hospital and NHS 
number will be recorded on the patient data sheet which will be linked to the CRF by way of a study 
number. 
Research xray views will also be performed during the baseline assessment. In addition to routine clinical 
xrays: standing anteroposterior, lateral, skyline views and valgus/varus stress xrays two research xray 
views will be performed. 
These two views are with the patient standing, hands resting on a frame for stability. The xrays are taken 
in the postero-anterior direction. The first of these standing views is taken with the knees flexed to 15 
degrees, the second with the knees flexed to 45 degrees. 
7.5. Subsequent Visits 
One further appointment would be required for this study. This appointment would be for MRI of the 
knee. The appointment would be performed at the patient’s convenience and would take 30 minutes in 
total. No further appointments would be required for the patient as part of this research project. 
7.6. Discontinuation/Withdrawal of Participants from Study 
Each participant has the right to withdraw from the study at any time.  In addition, the Investigator may 
discontinue a participant from the study at any time if the Investigator considers it necessary for any 
reason including: 
• 
Pregnancy 
• 
Ineligibility (either arising during the study or retrospectively having been overlooked at screening) 
• 
Significant protocol deviation 
• 
Withdrawal of Consent 
In the event of patient withdrawal from the study analysis of data obtained prior to withdrawl will be 
analysed as part of the study.  
Withdrawn participants will not be replaced. 

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The reason for withdrawal will be recorded in the CRF. 
7.7. Definition of End of Study 
The end of study is 6 months following recruitment of the last patient. 
8. INTERVENTIONS 
 
In addition to the standard clinical imaging protocol described above trial participants will undergo: 
- 
15 degrees flexion postero-anterior view 
- 
45 degrees flexion postero-anterior view  
- 
MRI knee without contrast 
In those patients undergoing surgery as part of their routine clinical management: 
- 
Intra-operative audit of joint surface and status of ligaments within the knee 
- 
Assessment of retrieved samples of joint surface that would otherwise be disposed of 
9. SAFETY REPORTING 
The study is low risk however in the event of an adverse event (AE) or serious adverse event (SAE) occurring 
to a participant this would be reported to the REC and R&D. 
10. STATISTICS AND ANALYSIS 
10.1. 
Description of Statistical Methods 
Joint space width of each of the compartments will be measured on each routine and research xray views 
taken using a standardised technique using custom software (Matlab, Massachusetts, USA).To compare 
the accuracy and agreement of different radiological views at measuring joint space width statistical 
methods for assessing agreement between two methods of clinical measurement as described by Bland 
and Altman will be used with stress views defined as the gold standard for comparison [12, 13].  
 
For the secondary outcomes each of the compartments on each of the xray views will be classified as 
demonstrating bone on bone arthritis, full thickness cartilage or narrowing of joint space width. The 
sensitivity and specificity of each of the views at predicting each of these disease states will be compared 
with stress views which will be defined as the gold standard. The sensitivity and specificity of each of the 
views at predicting suitability for UKR will be calculated based on pre-defined indications of UKR. 
 
The sensitivity and specificity of MRI at predicting suitability for UKR, based on pre-defined xray derived 
indications as the gold standard will be calculated. 
The sensitivity and specificity of different xray techniques at inferring the status of soft tissue structures 
(anterior cruciate ligament and medial collateral ligament) within the arthritic knee will be evaluated 
against both MRI and intra-operative findings. 

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A decision aid will be developed based on the findings of this research and the sensitivity and specificity of 
this decision aid at predicting suitability for UKR will be calculated. Further work will then be performed to 
validate this scoring system. 
10.2. 
The Number of Participants 
From two previous studies evaluating the utility of PA views in 15 degrees flexion compared with AP 
standing for long term evaluation of progression of knee arthritis the difference in mean joint space width 
measured on Lyon Schuss and AP standing views is between 0.63mm with a population standard deviation 
of 1.1. This gives an effect size of 0.57. At a power of 0.8 and significance level of 0.05 using the Altman 
nomogram the required sample size would be 100 patients. From audit it has been identified that 50% of 
patient from clinic will be treated with surgery. In addition to allow for errors in xray alignment making 
interpretation not valid an additional 25 patients will be added giving a sample size of 225 patients. 
10.3. 
Analysis of Outcome Measures/Endpoints 
Each image will be measured independently and statistical analysis will be performed blinded to the 
treatment outcome. Should a patient withdraw consent prior to termination of the study data that has 
been collected will only be used for analysis where, for each endpoint, a complete set of data is present. 
11. DATA MANAGEMENT 
11.1. 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor or host institution for 
monitoring and/or audit of the study to ensure compliance with regulations. 
11.2. 
Data Recording and Record Keeping 
A password protected database containing patient identifiable information solely for identifying patients 
who have subsequently had surgery and for collecting the results of intraoperative findings will be kept 
on a secure university computer. This database will be securely destroyed six months following the end 
of the study. No other patient identifiable information will be kept. 
 
Xrays and MRI images will be measured in duplicate using pre tested software (Matlab, Massachusetts, 
USA) with the evaluator blinded to other images in that patients series as well as the final treatment 
outcome. 
The majority of data will be generated electronically and it will be stored and backed up securely within 
the research institute. Where data is required to be transcribed from a paper pro forma this information 
will be checked by an independent member of the research team. Data will be analysed using Stata version 
13 (Texas, USA). 
 
Data will be retained for 10 years in line with our organisations policy. 

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12. QUALITY ASSURANCE PROCEDURES 
The study may be monitored, or audited in accordance with the current approved protocol, ICH GCP, 
relevant regulations and standard operating procedures. 
13. ETHICAL AND REGULATORY CONSIDERATIONS 
13.1. 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki. 
13.2. 
ICH Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant regulations and 
with the ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July 1996. 
13.3. 
Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising material 
will be submitted to an appropriate Research Ethics Committee (REC), and host institution(s) for written 
approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
13.4. 
Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress report to the REC 
Committee, host organisation and Sponsor.  In addition, an End of Study notification and final report will 
be submitted to the same parties. 
13.5. 
Participant Confidentiality 
The study staff will ensure that the participants’ anonymity is maintained.  A password protected 
database containing patient identifiable information solely for identifying patients who have 
subsequently had surgery and for collecting the results of intraoperative findings will be kept on a secure 
university computer. This database will be securely destroyed six months following the end of the study. 
No other patient identifiable information will be kept.  All documents will be stored securely and only 
accessible by study staff and authorised personnel. The study will comply with the Data Protection Act, 
which requires data to be anonymised as soon as it is practical to do so. Patient identifiable information 
held on the secure database will be linked to the CRF and other study records by way of study number. 
13.6. 
Expenses and Benefits 
Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of 
receipts, or a mileage allowance provided as appropriate. 

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14. FINANCE AND INSURANCE 
14.1. 
Funding 
Insurance Mr Hamilton is funded for this work through and NIHR grant. Mr Pandit, Dr Mellon and Professor 
Murray are funded independently. Additional funding for this study is provided by departmental research 
funding to our research group. 
14.2. 
 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you are harmed 
whilst taking part in a clinical research study as a result of negligence on the part of a member of the study 
team this liability cover would apply. 
Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University NHS Trust, 
therefore, cannot agree in advance to pay compensation in these circumstances. 
In exceptional circumstances an ex-gratia payment may be offered. 
 
15. PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any 
other publications arising from the study. Authorship will be determined in accordance with the ICMJE 
guidelines and other contributors will be acknowledged. 
 
 

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16. REFERENCES 
 
1. 
Vince, A.S., A.K. Singhania, and M.M. Glasgow, What knee X-rays do we need? A survey of 
orthopaedic surgeons in the United Kingdom. Knee, 2000. 7(2): p. 101-104. 
2. 
Bhatnagar, S., et al., Evidence-based practice in the utilization of knee radiographs--a survey of all 
members of the British Orthopaedic Association. Int Orthop, 2006. 30(5): p. 409-11. 
3. 
Thomas, R.H., et al., Compartmental evaluation of osteoarthritis of the knee. A comparative study 
of available diagnostic modalities. Radiology, 1975. 116(3): p. 585-94. 
4. 
Leach, R.E., T. Gregg, and F.J. Siber, Weight-bearing radiography in osteoarthritis of the knee. 
Radiology, 1970. 97(2): p. 265-8. 
5. 
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17. APPENDIX A:  STUDY FLOW CHART 
 
 
 
 
 
 
 
Inclusion criteria: 
• 
All patients aged over 50 years old 
• 
Radiographic evidence of knee osteoarthritis, any grade, any compartment 
Exclusion criteria: 
• 
Inability to comprehend and/or consent for the study 
• 
Unable to stand with assistance for more than two minutes 
• 
Previous joint replacement on ipsilateral knee 
• 
Previous anterior cruciate ligament reconstruction/injury 
• 
Previous high tibial osteotomy 
• 
Previous intra-articular fracture 
• 
Inflammatory arthritis 
Additional research xrays: 
• 
Standing posteroanterior (PA) view 15 degrees flexion 
• 
Standing posteroanterior (PA) view 45 degrees flexion 
• 
Additional MRI of knee 
Current clinical xrays (standard of care): 
• 
Standing anteroposterior view 
• 
Lateral view 
• 
Skyline view (patellofemoral joint) 
• 
Valgus stress view (clinician performed or using validated device) 
• 
Varus stress view (clinician performed or using validated device) 
Sample Size: 
• 
225 patients 
• 
1 centre 
End of study 
In those patients who subsequently undergo surgery within 6 months: 
• 
Intra-operative audit of each compartment 
• 
Intra-operative audit of structures within the knee 
• 
Examination and laser scanning of excised joint surface 

Date and version No:     14 September 2015 Version 1.1 
 
 
Clinical Research Protocol Template version 8.0     
 
 
 
 
 
CONFIDENTIAL 
© Copyright: The University of Oxford and Oxford University Hospitals NHS Trust 2013  
Page 17 of 17 
18. APPENDIX C:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made