A Prospective Cross-sectional Study to Determine the Reliability and Validity of Inline 'Pull' Dynamometry for Measuring Peak Knee Extensor Torque in Patients Following Anterior Cruciate Ligament (ACL) Reconstruction: HRA & HCRW Approval Issued.
Phase: NA
Conditions: Anterior Cruciate Ligament Injuries, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Tear
Sponsor: Liverpool University Hospitals NHS Foundation Trust

 
 
 
 
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Study Title: A prospective cross-sectional study to determine the reliability and validity of 
inline ‘pull’ dynamometry for measuring peak knee extensor torque in patients following 
anterior cruciate ligament (ACL) reconstruction. 
 Internal Reference No: R&D SP0558 
Ethics Ref: Insert 
EUDAMED (AVAILABLE FROM Dec 2020): Insert 
UDI (available from May 2021): Insert 
Date and Version No: 19 May 2021, version 1.1 
 
 
 
 
 
 
 
 
 
 
 
 
 
              
 
 
 
 
 
Style Definition: Central Title

 
 
 
 
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SIGNATURE PAGE 
The undersigned confirm that the following protocol has been agreed and accepted and that 
the Chief Investigator agrees to conduct the study in compliance with the approved protocol 
and will adhere to the principles outlined in the Declaration of Helsinki, the Liverpool 
University Hospitals NHS Foundation Trust SOPs, and other regulatory requirement. 
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 investigation without the 
prior written consent of the Sponsor 
I also confirm that I will make the findings of the study publically available through publication 
or other dissemination tools without any unnecessary delay and that an honest accurate and 
transparent account of the study will be given; and that any discrepancies from the study as 
planned in this protocol will be explained. 
 
For and on behalf of Liverpool University Hospitals NHS Foundation Trust 
 
Signature:  
...................................................................................................... 
 
Date: 
....../....../...... 
Name (please print): 
...................................................................................................... 
 
 
Position: 
...................................................................................................... 
 
 
 
 
 
Chief Investigator: 
Signature: 
  
 
Date: 
01/02/2021 
Name: Paul Carter 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Key Study Contacts 
Chief Investigator 
Mr Paul Carter 
07801949337 
Paul.Carter2@liverpoolft.nhs.uk 
Study Co-ordinator 
Mr Richard Norris 
07766718618 
Richard.Norris2@liverpoolft.nhs.uk 
Sponsor 
Heather Rogers   
RD&I Governance Manager 
Research Governance Committee Chair 
Liverpool University Hospitals NHS Foundation Trust 
Prescot St  
Liverpool  
Tel: 0151 706 3702 
Email: RGT@RLBUHT.nhs.uk  
 
Joint-sponsor(s)/co-sponsor(s)  
N/A 
Funder(s) 
N/A 
Key Protocol Contributors 
Eric Meira  
Huw Williams 
Rachel Oldershaw 
Scot Morrison 
Seth O’Neill 
Committees 
 
 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other 
than the Sponsor, the Investigator Team, host(s), regulatory authorities, and members of the 
Research Ethics Committee.   
Deleted: Malcolm Peoples¶

 
 
 
 
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TABLE OF CONTENTS 
1. 
AMENDMENT HISTORY ................................................................................................. 6 
2. 
SYNOPSIS ....................................................................................................................... 7 
3. 
ABBREVIATIONS ............................................................................................................ 9 
4. 
BACKGROUND AND RATIONALE ............................................................................... 10 
5. 
OBJECTIVES ................................................................................................................. 11 
5.1 
Primary Objective ................................................................................................... 11 
5.2 
Secondary Objectives ............................................................................................ 11 
6. 
TRIAL DESIGN .............................................................................................................. 11 
6.1 
Summary of Trial Design ........................................................................................ 11 
6.2 
Primary and Secondary Endpoints/Outcome Measures ........................................ 12 
6.3 
Trial Participants .................................................................................................... 12 
6.4 Study Procedures ......................................................................................................... 13 
6.5 
Definition of End of Trial ......................................................................................... 15 
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment ....................... 15 
6.7 
Source Data ........................................................................................................... 16 
7. 
TREATMENT OF TRIAL PARTICIPANTS ..................................................................... 16 
7.1 
Description of Study Intervention(s) ....................................................................... 16 
7.2 
Maintenance and storage of device ....................................................................... 17 
8. 
SAFETY reporting .......................................................................................................... 17 
8.1 Reporting of AE ............................................................................................................ 17 
8.2 Reporting Procedures for All SAEs/ SADEs/ UADEs ................................................... 17 
8.3 Annual Reports ............................................................................................................ 18 
9. 
STATISTICS .................................................................................................................. 18 
9.1 
Description of Statistical Methods .......................................................................... 18 
9.2 
The Number of Participants ................................................................................... 18 
9.3 
The Level of Statistical Significance ....................................................................... 18 

 
 
 
 
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9.4 
Criteria for the Termination of the Trial. ................................................................. 18 
9.5 
Procedure for Accounting for Missing, Unused, and Spurious Data. ..................... 19 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ........ 19 
9.7 
Inclusion in Analysis ............................................................................................... 19 
10. 
Direct Access to Source Data/Documents ................................................................. 19 
11. 
Quality Control and Quality Assurance Procedures ................................................... 19 
12. 
Ethics ......................................................................................................................... 19 
12.1 
Declaration of Helsinki ........................................................................................... 19 
12.2 
ICH Guidelines for Good Clinical Practice ............................................................. 19 
12.3 
Approvals ............................................................................................................... 20 
12.4 
Participant Confidentiality ....................................................................................... 20 
13. 
Data Handling and Record Keeping .......................................................................... 20 
14. 
Financing and Insurance ............................................................................................ 20 
15. 
End of study definition ................................................................................................ 20 
16. 
Publication Policy ....................................................................................................... 21 
17. 
Archiving .................................................................................................................... 21 
18. 
REFERENCES .......................................................................................................... 21 
 
 
 

 
 
 
 
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1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes 
made 
1 
1.1 
19/05/21 
Richard Norris 
Change of device 

 
 
 
 
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2. 
SYNOPSIS 
Measurement of peak knee extensor torque is important following anterior cruciate ligament 
(ACL) reconstruction. Isometric electromechanical dynamometry (Iso-ED) is the gold 
standard method of measuring peak knee extensor torque, but access to this equipment is 
limited due to the associated expense and lack of portability. Inline ‘pull-type’ dynamometry 
is an alternative measure that is more affordable, portable and less time consuming, but this 
device has not been adequately investigated for reliability or validity. This study will 
investigate the reliability and validity of an inline ‘pull-type’ dynamometer for measuring peak 
knee extensor torque in patients following ACL reconstruction. For the reliability study, 
healthy volunteers will be assessed by two assessors (inter-rater) at the index testing 
session, with testing repeated by one assessor one week later (test-retest). Validity will be 
investigated against Iso-ED as the gold standard. The results of this study will help to 
determine whether inline dynamometry can be recommended as a reliable and valid means 
of measuring knee extensor torque in clinical practice. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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Study Title 
Reliability and validity of inline ‘pull-type’ dynamometry for measuring 
peak knee extensor torque in patients following anterior cruciate 
ligament (ACL) reconstruction. 
Internal ref. no. 
R&D SP0558 
Type of study 
Clinical investigation of a medical device 
Trial Design 
Prospective, cross sectional study using a within-participant, repeated 
measures design. 
Trial Participants 
Healthy participants recruited from staff at LUH for reliability study 
Patients who have had ACL reconstruction at LUH for validity study 
Planned Sample Size 
20 participants for reliability study 
44 participants for validity study 
Follow-up duration 
One week for reliability study 
No follow up required for validity study 
Planned Trial Period 
6 months 
Primary Objective 
To determine the reliability and validity of inline ‘pull-type’ dynamometry 
for measuring peak knee extensor torque 
Secondary 
Objectives 
To determine comfort levels when testing using different devices 
Primary Endpoint 
Peak knee extensor torque, recorded in Newton-metres, measured with 
inline dynamometry and isometric electromechanical dynamometry 
Secondary 
Endpoints 
Pain during testing measured with a numerical rating scale 
 
Device Name  
KForce Link 
Cybex HUMAC Norm (CSMI Medical Solutions, Stoughton, MA, USA) 
dynamometer, using software version Humac 2009. 
Manufacturer Name  
K-invent 
Principle intended 
use  
Force measurement 
Length of time use 
the device has been 
in use.  
Inline dynamometer: 3 years  

 
 
 
 
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3. 
ABBREVIATIONS 
AE 
Adverse event 
ADE  
Adverse Device Effect  
CI 
Chief Investigator 
CRF 
 
Case Report Form 
CRO  
Contract Research Organisation 
CT 
 
Clinical Trials 
CTA 
 
Clinical Trials Authorisation 
                   GCP 
 
 Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
ICH 
International Conference of Harmonisation 
LUHft 
Liverpool University Hospitals NHS Foundation Trust 
MHRA 
Medicines and Healthcare products Regulatory Agency 
NHS 
National Health Service 
NRES 
National Research Ethics Service (previously known as COREC) 
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&I 
 R&I Department 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event  
SADE 
Serious Adverse Device Effect  
SIL 
Subject Information Leaflet (see PIL) 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 
UADE 
Unanticipated Adverse Device Effect  
 
 
 
 

 
 
 
 
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4. 
BACKGROUND AND RATIONALE 
Lower limb strength testing is utilised in various settings including surveillance of uninjured 
athletes (1), patient monitoring during rehabilitation and determining readiness to return-to-
play (RTP) following anterior cruciate ligament reconstruction (ACLR) (2). Knee extensor 
muscle weakness is associated with an increased risk of re-injury and reduced functional 
performance following ACLR (3-5) and is a modifiable risk factor for knee osteoarthritis (6). 
Knee extensor strength deficits may be present in those that pass functional RTP tests (e.g., 
hop for distance) (5, 7, 8), highlighting the importance of quantifying knee extensor strength 
specifically.  
Isometric electromechanical dynamometry (Iso-ED) is the gold standard method for 
quantifying knee extensor strength (indicated by peak isometric torque) (9), with hand-held 
dynamometry (HHD) considered an alternative measure that is more affordable, portable and 
less time consuming (10). ‘Push-type’ HHD requires belt stabilisation for stronger subjects 
(10-13) and demonstrates similar peak isometric torque generating capacity to Iso-ED when 
performed at approximately 90° knee flexion in healthy volunteers (14). However, peak knee 
extensor torque occurs at 60-70° knee flexion (15), which is difficult to measure using belt-
stabilised ‘push-type’ HHD due to slippage of the device or a non-perpendicular force being 
applied to the gauge (16). When compared directly, ‘push-type’ HHD performed at 
approximately 90° knee flexion overestimated limb symmetry in subjects with various knee 
joint impairments and could not be recommended as a direct substitute for Iso-ED at 60° 
knee flexion (16). 
To date, only one study has investigated the reliability and validity of HHD for measuring 
peak knee extensor torque in patients following ACLR (17). ‘Push-type’ HHD performed 
isometrically at 90° knee flexion was shown to have excellent test-retest reliability (ICC: 0.98) 
and 100% specificity for detecting a limb symmetry index (LSI) >10%, but only moderate to 
good validity (r=0.62) versus isokinetic dynamometry. Although LSI is recommended as an 
objective, criterion-based guideline for return to running (18) or RTP (2) following ACLR, leg 
dominance or dysfunction of the reference limb may overestimate the capacity of the side 
being measured, potentially leading to a premature return to high-risk activities and 
subsequent re-injury (19). Peak isometric knee extensor torque normalised to body weight is 
an alternative means of determining whether an individual has achieved target values 
associated with positive knee-joint function following ACLR (³3.0-3.1 Nm/kg) (20, 21). Mean 
peak torque values in the aforementioned study were 1.67 (±7.4) Nm/kg and 2.03 (±7.9) 
Nm/kg for isometric HHD and isokinetic testing respectively, indicating a lower force 
generating capacity for ‘push-type’ HHD. In addition, since the reference values were 

 
 
 
 
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obtained isokinetically (60º/sec), it is likely that the validity of ‘push-type’ HHD would be lower 
if Iso-ED was used as the reference standard. 
Inline dynamometers allow isometric knee extensor torque to be measured at peak angles 
(i.e., 60-70°), but the reliability and validity of this ‘pull-type’ dynamometry has not been 
adequately evaluated (10, 22). The objective of this study therefore is to determine the 
reliability and validity of inline ‘pull-type’ dynamometry for measuring peak isometric knee 
extensor torque in patients following ACLR. We hypothesise that inline dynamometry is a 
reliable and valid measure of peak isometric knee extensor torque when performed at 60-70° 
knee flexion, using Iso-ED as the gold-standard reference. 
5. 
OBJECTIVES 
5.1 
Primary Objective 
To determine the reliability (inter and test-retest) and validity of the KForce Link inline 
dynamometer for measuring peak isometric knee extensor torque in patients following ACLR. 
5.2 
Secondary Objectives 
To determine comfort levels for each device during testing, as measured with a numerical 
rating scale of pain (0-10). 
6. 
TRIAL DESIGN 
6.1 
Summary of Trial Design 
This is a prospective, cross sectional study using a within-participant, repeated measures 
design. 
 
Reliability: 
A convenience sample of 20 healthy subjects (10 legs) will be recruited from Liverpool 
University Hospital to determine the inter- and test-retest reliability of the inline 
dynamometer. The testing procedure will be standardised between assessors. Subjects and 
assessors will be blinded to the results until all testing is completed. 
Subjects will be tested by assessors A and B at the first assessment to determine inter-rater 
reliability. Assessor A is a physiotherapy knee specialist with 17 years clinical experience 
and three years clinical experience using HHD. Assessor B is a specialist physiotherapist 
with 8 years clinical experience but no previous experience using HHD. The order of testing 
will be randomised to account for fatigue and learning effect using the random.org website 
(https://www.random.org/). 

 
 
 
 
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To determine test-retest reliability, measurements will be repeated by assessor A seven days 
after the index testing. All tests will be performed at the same time of the day, with subjects 
encouraged to continue their usual weekly exercise between testing sessions, but to avoid 
significant changes in training loads, which may affect fatigue levels and their ability to 
generate force. 
Validity: 
A convenience sample of 44 patients that have undergone ACL reconstruction will be 
recruited from Liverpool University Hospitals NHS Foundation Trust to determine the validity 
of the inline dynamometer versus Iso-ED. Inline dynamometry will be performed by Assessor 
A and Iso-ED performed by Assessor C (15 years’ experience). The order of testing will be 
randomised to account for fatigue and learning effect. Subjects and assessors will be blinded 
to the results until all testing is completed. 
6.2 
Primary and Secondary Endpoints/Outcome Measures 
The peak torque for each leg (Force [Newtons] x lever length [metres]) recorded at 60° knee 
flexion will be used as the primary outcome measure. Pain during testing on a numerical 
rating scale (NRS) will be used as a secondary outcome measure. 
6.3 
Trial Participants  
6.3.1 Overall Description of Trial Participants 
Reliability study: healthy subjects, as defined by the inclusion criteria below, recruited from 
NHS staff at Liverpool University Hospitals NHS Foundation Trust. 
Validity study: patients that have undergone ACL reconstruction surgery, with or without 
meniscal surgery, at Liverpool University Hospitals NHS Foundation Trust. 
6.3.2 Inclusion Criteria 
• 
Participant is willing and able to give informed consent for participation in the study. 
• 
Male or Female, aged 18 years or above. 
• 
No contraindications to maximal force testing (see exclusion criteria). 
• 
For the ACL reconstruction participant cohort: diagnosed with ACL injury that was 
managed with ACL reconstruction surgery, with or without additional meniscal 
surgery. If medicated, stable dose of current regular medication for at least 4 weeks 
prior to study entry. 
• 
For the healthy control participant cohort: no current or previous history of significant 
lower limb injury, or a history of previous minor injury that is symptomatic at the time 

 
 
 
 
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of recruitment. No previous lower limb surgery. No course of medication, whether 
prescribed or over the counter, other than vitamins and mineral supplements or, for 
females, oral contraceptives. 
 
6.3.3  Exclusion Criteria 
The participant may not enter the study if they are unable to provide written consent to study 
participation, or there are contraindications to maximal force testing, including the following: 
• 
History of chronic disease or disorder that may put the participants at risk because of 
participation in the study including non-united fractures, epilepsy, cardiac 
insufficiency, severe peripheral vascular disease, aneurysms, anticoagulant therapy, 
recent (<3 months) radiotherapy or chemotherapy, long term steroid use (>3 months), 
pregnancy, neurological disorders (e.g., Parkinson’s disease), skin conditions at point 
of force testing, severe osteoporosis, malignancy, rheumatoid arthritis. 
• 
Conditions or symptoms that may influence the result of the study, or the participant’s 
ability to participate in the study including pain, limited range of motion, knee effusion, 
or anaemia. 
6.4 Study Procedures 
Before testing, all subjects will complete a 10-minute warm up on a stationary bike followed 
by three trials (50%, 75% and 100% maximal effort) to familiarise themselves with each 
device and to screen for pain. If pain during testing is deemed intolerable by the subject, no 
further testing will be performed, and the subject will be excluded from the study. A 10-
minute recovery period will be used between testing on devices to avoid fatigue.  
Inline dynamometer – KForce Link (capacity 300kg): 
The subject will be sat on the end of a sturdy plinth with a small foam pad placed under the 
distal thigh for comfort. Ankle straps with double D-rings (Vorcool) will be securely attached 
directly above the malleoli, with one end of the dynamometer connected to the D-rings via a 
snap hook. Using a goniometer, the knee will be positioned in 60° knee flexion and the inline 
dynamometer aligned perpendicular to the leg by adjusting the height of the plinth and the 
inelastic strap, which anchors the dynamometer to the plinth. The subject will be instructed to 
maintain the trunk in an upright position, using their hands on the side of the plinth for 
stability. The dynamometer will be ‘zeroed’ with the knees relaxed at right angles before 
each trial. Lever length will be recorded in metres with a tape measure, using the lateral 
epicondyle of the femur and middle of the ankle strap as reference points. 

 
 
 
 
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Cybex isokinetic dynamometer: 
The testing procedure will be conducted at 60° knee flexion in accordance with the device 
instructions. Humantrak software will be used to determine peak knee extensor torque. 
For both devices, three maximal efforts will be performed on each leg with verbal 
encouragement to ‘push as hard as possible’ for five seconds, which is sufficient time to 
generate peak torque. Subjects will rest for 60-seconds between attempts, monitored with a 
timer (18). The highest value from the three efforts for each device will be used as the 
primary outcome for each subject. 
 
6.4.1 Informed Consent 
Informed consent will be gained by the principal investigator (Richard Norris) and co-
investigators (Malcolm Peoples and Huw Williams), as authorised by the Chief Investigator 
and Principal Investigator. 
 
The participant must personally sign and date the latest approved version of the informed 
consent form before any study specific procedures are performed. 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 
• 
the implications and constraints of the protocol 
• 
the potential 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 or impact on future care, and with no obligation to give the 
reason for withdrawal. The participant will be allowed as much time as required to consider 
the information, and the opportunity to question the Investigator, their GP or other 
independent parties to decide whether they will participate in the study.  
 
Written informed consent will then be obtained by means of participant dated signature and 
dated signature of the person who presented and obtained the informed consent. The person 
who obtained the consent must be suitably qualified and experienced and have been 
authorised to do so by the Chief/Principal Investigator. A copy of the signed Informed Consent 
will be given to the participants.  The original signed form will be retained at the study site.  

 
 
 
 
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6.4.2 Screening and Eligibility Assessment 
Hospital staff and patients (18 years or older) will be recruited by direct invitation or word of 
mouth. Patients that have undergone ACL reconstruction, who are already scheduled for 
force testing on the isokinetic dynamometer will be invited to have additional testing using 
inline dynamometry. Potential participants will be initially screened via telephone or face to 
face interview to confirm eligibility. Once signed consent is obtained, participants will be 
invited to attend testing sessions in a physiotherapy department at Liverpool University 
Hospitals.  
6.4.3 Baseline Assessments 
The following demographics will be recorded routinely at baseline: 
Gender, age, weight, height, leg dominance, Tegner activity score (TAS). 
 
Pain at rest, measured by a 0-10 numerical rating scale (NRS), will be recorded before 
initiation of testing. Lever length and force measurements will be recorded during testing. 
6.4.4 Randomisation and Codebreaking 
For both the reliability and validity studies, the order of testing will be randomised to account 
for fatigue and learning effect using the random.org website (https://www.random.org/). 
Subject numbers will be assigned sequentially as each subject enters the study.  Subjects 
and assessors will be blinded to the force measurement results until testing is complete on 
each device. Lever length will be measured and recorded by each individual assessor. 
6.4.5 Subsequent assessments 
Torque measurements for the participants in the test-retest reliability study will be repeated 
one week after index testing. At each visit, an eligibility check will be conducted (i.e., change 
to circumstances). 
6.5 
Definition of End of Trial  
The end of trial is defined as the point when all subject data has been collected for the 
reliability and validity studies and analysis of this data has been completed. 
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment 
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 it is considered 
necessary for any reason including:  

 
 
 
 
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• 
The subject becomes pregnant 
• 
Ineligibility (either arising during the study or retrospectively having been overlooked 
at screening) 
• 
Significant protocol deviation 
• 
Significant non-compliance with study requirements 
• 
An adverse event which requires discontinuation of the testing procedure or results in 
an inability to continue to comply with study procedures 
• 
Disease progression which requires discontinuation of the study device or results in 
inability to continue to comply with study procedures 
• 
Consent withdrawn 
• 
Lost to follow up 
 
Withdrawal from the study will result in exclusion of the data for that participant from analysis. 
In the healthy participant cohort, withdrawn participants will be replaced unless the withdrawal 
was due to an adverse event that was directly associated with the testing procedure. The 
reason for withdrawal will be recorded in the CRF.   
 
If the participant is withdrawn due to an adverse event, the investigator will arrange for follow-
up visits or telephone calls until the adverse event has resolved or stabilised.   
 
6.7 
Source Data 
Source documents are original documents, data, and records from which participants’ CRF 
data are obtained.  These include, but are not limited to, hospital records containing medical 
history and surgical information. All documents will be stored safely in confidential conditions.  
On all study-specific documents, other than the signed consent, the participant will be referred 
to by their personal identification number (PIN), not by name. 
7. 
TREATMENT OF TRIAL PARTICIPANTS 
7.1 
Description of Study Intervention(s) 
For the reliability study, healthy subjects will be tested by two assessors at the index testing 
session, with three trials performed per assessor per leg. Testing will be repeated by one 
examiner, one week after index testing.  

 
 
 
 
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For the validity study, ACL subjects will be tested by two assessors with the two different 
devices, with three trials performed per assessor per leg. The highest score from the three 
trials per device will be used for analysis. 
 
7.2 
Maintenance and storage of device 
The inline dynamometer and accessories will be stored in a customised, protective case. 
Between testing sessions, this device will be stored in a locked room, accessible only to the 
Principal Investigator. The Cybex isokinetic dynamometer is a fixed device and remains in 
the physiotherapy department at Broadgreen hospital. 
8. 
SAFETY REPORTING 
8.1 Reporting of AE 
All AE’s occurring during the study observed by the investigator or reported by the 
participant, whether or not attributed to the device under investigation will be recorded on the 
CRF, as specified in the protocol.  All ADE’s will be recorded in the CRF.  
The following information will be recorded: description, date of onset and end date, severity, 
assessment of relatedness to device and action taken.  Follow-up information will be 
provided as necessary.  
The relationship of AEs to the device will be assessed by a medically qualified investigator or 
the sponsor/manufacturer and will be followed up until resolution or the event is considered 
stable.  
All ADEs that result in a participant’s withdrawal from the study or are present at the end of 
the study, will be followed up until a satisfactory resolution occurs. 
Where relevant, any pregnancy occurring during the clinical study and the outcome of the 
pregnancy, will be recorded and followed up for congenital abnormality or birth defect. 
8.2 Reporting Procedures for All SAEs/ SADEs/ UADEs 
As the devices are CE marked, all SAE/SADE/UADEs will be reported to the sponsor/legal 
representative and manufacture and LUHFT R&D within one working day of the 
investigator team becoming aware of them.  
Reports of related and unexpected SAEs will be submitted to ethics within 15 days of the 
Chief Investigator becoming aware of the event, using the SAE report form for non-CTIMPs 
published on the NRES website. 

 
 
 
 
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All reporting to LUHFT R&D will be signed by the PI or Co-investigator. 
8.3 Annual Reports 
In addition to the above reporting the Chief Investigator will submit once a year, throughout 
the trial, or on request a progress/safety report to the REC and R&D.  
9. 
STATISTICS 
9.1 
Description of Statistical Methods 
Inter and test-retest reliability will be calculated using intra-class correlation coefficients (ICC) 
with 95% confidence intervals (CI) and illustrated using a Bland & Altman plot. Standard 
error of measurement (SEM = [SD√(1-ICC)]) and the minimal detectable change (MDC) 
(1.96 x √2 x SEM) will be calculated to verify the absolute error of the instrument and the 
smallest change considered significant respectively. 
ICC values will be considered as follows: < 0.69: weak reliability, 0.70–0.79 reasonable 
reliability, 0.80–0.89 good reliability, and 0.90–1.0 excellent reliability 
Validity will be calculated using ICC (95% CI), Pearson product moment correlation 
(Pearson-r) and illustrated using Bland & Altman plot. 
Pearson values of coefficients will be established as follows: < 0.5 indicated weak validity, 
0.5–0.75 indicated moderate to good validity, and > 0.75 indicated excellent validity. 
9.2 
The Number of Participants 
Since this is a study looking at criterion validity using two repeated measures, the following 
formula is recommended: √3(SDdiff/N). Values from a similar study (Deones et al., 1994) 
were used to calculate an effect size of 0.506. After running a power calculation using 
G*Power, the sample size required for statistical significance was 40 subjects. A 10% larger 
sample size (n=44) will negate the attrition rate whilst maintaining statistical significance. 
9.3 
The Level of Statistical Significance 
An alpha level of P < 0.05 was considered statistically significant for all analyses  
9.4 
Criteria for the Termination of the Trial. 
The trial will be terminated after all data for the reliability and validity studies have been 
collected and the data analysed, as described in section 9.1. 

 
 
 
 
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9.5 
Procedure for Accounting for Missing, Unused, and Spurious Data. 
It is unlikely that we will not be able to collect data because of the single measures taken 
using a non-invasive orthopaedic device that is already in clinical use.  
All data, including instances where data was not able to be collected or the data was 
spurious, will be presented in the final report and acknowledged in published work with raw 
data included as supplementary material. 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
Power calculations have been performed using preliminary data and therefore we do not 
anticipate that we will deviate from the statistical plan.  
Any deviations will be described and justified in the final report, 
9.7 
Inclusion in Analysis 
Data included in the analysis is described in section 6.6 
 
10. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
Direct access will be granted to authorised representatives from the sponsor, host institution 
and the regulatory authorities to permit trial-related monitoring, audits and inspections. 
11. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
The study will be conducted in accordance with the current approved protocol, ICH GCP, 
relevant regulations and standard operating procedures.  
 
Regular monitoring will be performed according to ICH GCP. Data will be evaluated for 
compliance with the protocol and accuracy in relation to source documents. Following written 
standard operating procedures, the monitors will verify that the clinical trial is conducted and 
data are generated, documented and reported in compliance with the protocol, GCP and the 
applicable regulatory requirements.  
12. 
ETHICS 
12.1 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of 
the Declaration of Helsinki.  
12.2 
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 R2 

 
 
 
 
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12.3 
Approvals  
The protocol, informed consent form, participant information sheet and any proposed 
advertising material will be submitted to an appropriate Research Ethics Committee (REC), 
regulatory authorities (MHRA in the UK), Health Research Authority 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.    
12.4 
Participant Confidentiality 
The trial staff will ensure that the participants’ anonymity is maintained.  The participants will 
be identified only by initials and a PIN on the CRF and any electronic database.  All 
documents will be stored securely and only accessible by trial staff and authorised personnel. 
The study will comply with the Data Protection Act 2018 which requires data to be 
anonymised as soon as it is practical to do so.   
12.5  Other Ethical Considerations 
None identified 
13. 
DATA HANDLING AND RECORD KEEPING 
All study data will be stored on a password protected Microsoft Excel spreadsheet and 
entered on SPSS for data analysis. The participants will be identified by a study specific 
participants number and/or code in any database.  The name and any other identifying detail 
will NOT be included in any study data electronic file.  
14. 
FINANCING AND INSURANCE 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you 
are harmed whilst taking part in a clinical trial 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 LUHFTt , therefore, 
cannot agree in advance to pay compensation in these circumstances. In exceptional 
circumstances an ex-gratia payment may be offered.  
15. 
END OF STUDY DEFINITION 
End of study is defined as the point when all data has been collected for the reliability and 
validity studies and this data has been analysed. 

 
 
 
 
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16. 
PUBLICATION POLICY 
The end of study is defined as the point when all data sets for the reliability and validity 
studies have been collected and the data has been analysed. 
17. 
ARCHIVING 
Archiving for Device studies will be 15 years. 
18. 
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