Comparing the Effectiveness of Computer-aided-design Computer-aided-manufacture (CAD/CAM) Insoles Manufactured From Foam-box Cast vs Direct Scan on Patient Reported Outcome Measures: A Double-blinded, Randomised Controlled Trial
Phase: NA
Conditions: Foot Injury, Foot Deformity, Foot Sprain, Feet, Flat, Foot Ankle Injuries
Sponsor: NHS Greater Glasgow and Clyde

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
Trial Title: Comparing the effectiveness of computer-aided-design computer-aided-
manufacture (CAD/CAM) insoles manufactured from foam-box cast vs direct scan on patient 
reported outcome measures: A double-blinded, randomised controlled trial 
Short title: Comparing clinical outcomes using two insole manufacture techniques 
London Stanmore REC Reference: 22/LO/0579 
NHS GGC R&I No: GN22OR165 
IRAS Project ID: 317502 
Date and Version No: 08/09/2022 V2.0 
Chief Investigator: 
Name: Dr Graham Chapman 
Employer: University of Central Lancashire 
Allied Health Research unit, University of Central Lancashire, 
Preston, Lancashire, PR1 2HE 
Email: gchapman2@uclan.ac.uk           Tel: +44 (0)1772 894949 
Principal Investigator: 
Name: Laura Barr MSc, BSc (hons), PGCert 
Employer: Orthotic Service, NHS Greater Glasgow and Clyde 
Work Address: Orthotic Department, Gartnavel General Hospital, 
Lower Ground Floor, Great Western Road, Glasgow, G12 0YN 
Email: laura.barr@ggc.scot.nhs.uk       Tel: +44 (0)7950 995191  
Co-Investigator:  
Name: Jillian Tawse, BSc (hons) 
Employer: Orthotic Service, NHS Greater Glasgow and Clyde 
Work Address: Orthotic Department, Gartnavel General Hospital, 
Lower Ground Floor, Great Western Road, Glasgow, G12 0YN 
Email: Jillian.Tawse@ggc.scot.nhs.uk      Tel: +44 (0)141 211 1459 
Co-Investigator:  
Name: Colette Dickson, MRes, BSc (hons) 
Employer: Orthotic Service, NHS Greater Glasgow and Clyde 
Work Address: Orthotic Department, Gartnavel General Hospital, 
Lower Ground Floor, Great Western Road, Glasgow, G12 0YN 
Email: Colette.Dickson@ggc.scot.nhs.uk Tel: +44 (0)141 211 1459 
Co-Investigator:  
Name: Hannah Scott, BSc (hons) 
Employer: Orthotic Service, NHS Greater Glasgow and Clyde 
Work Address: Orthotic Department, Gartnavel General Hospital, 
Lower Ground Floor, Great Western Road, Glasgow, G12 0YN 
Email: hannah.scott4@ggc.scot.nhs.uk   Tel: +44 (0)141 211 1459 
Sponsor: 
Greater Glasgow Health Board - commonly known as NHSGGC 
(hereafter ‘NHSGGC’) 
Funder: 
The study is not funded. Support in Kind from National Health 
Service, Greater Glasgow and Clyde, Orthotic Department 
Chief Investigator Signature:  
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
Conflicts of interest: The Sponsor and investigation team have no conflicts of interest in this 
study 
 
 
Confidentiality Statement: 
This document contains confidential information that must not be disclosed to anyone other 
than the Investigator Team, HRA, participating site, and members of the Research Ethics 
Committee and Regulatory Authorities unless authorised to do so. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
TABLE OF CONTENTS 
1. 
AMENDMENT HISTORY ...................................................................................................... 5 
2. 
SYNOPSIS ............................................................................................................................ 6 
3. 
ABBREVIATIONS .................................................................................................................. 8 
4. 
BACKGROUND AND RATIONALE ....................................................................................... 10 
5. 
OBJECTIVES AND OUTCOME MEASURES ......................................................................... 12 
6. 
TRIAL DESIGN .................................................................................................................... 14 
6.2.1 
Overall Description of Trial Participants ................................................................ 15 
6.2.2 
Inclusion Criteria .................................................................................................... 15 
6.5 
Definition of End of Trial ........................................................................................... 22 
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment ...................... 22 
6.7 
Source Data ............................................................................................................... 23 
7. 
TREATMENT OF TRIAL PARTICIPANTS .............................................................................. 24 
7.1 
Description of Study Intervention(s) ......................................................................... 24 
7.2 
Maintenance and storage of device ......................................................................... 24 
7.4  
Concomitant Medication .......................................................................................... 24 
8. 
SAFETY reporting .............................................................................................................. 26 
8.1 Definitions ...................................................................................................................... 26 
8.2 Recording and Reporting of Adverse Events ................................................................. 27 
8.3 Recording and Reporting of Serious Adverse Events ..................................................... 27 
8.4 Reporting to Sponsor ..................................................................................................... 27 
8.5 Reporting of USADEs to the REC .................................................................................... 28 
8.6 Reporting of SADEs and USADES to IRIC ........................................................................ 28 
8.7 Annual Reports ............................................................................................................... 28 
9. 
STATISTICS ........................................................................................................................ 29 
9.1 
Description of Statistical Methods ............................................................................ 29 
9.2 
The Number of Participants ...................................................................................... 29 
9.3 
The Level of Statistical Significance .......................................................................... 29 
9.4 
Criteria for the Termination of the Trial ................................................................... 29 
9.5 
Procedure for Accounting for Missing, Unused, and Spurious Data. ....................... 29 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan ......... 29 
9.7 
Inclusion in Analysis .................................................................................................. 30 
10. 
Direct Access to Source Data/Documents .................................................................... 31 
11. 
Quality Control and Quality Assurance Procedures ..................................................... 32 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
12. 
Ethics ............................................................................................................................. 33 
12.1 Declaration of Helsinki .............................................................................................. 33 
12.2 ICH Guidelines for Good Clinical Practice ................................................................. 33 
12.3 Approvals .................................................................................................................. 33 
12.4 Participant Confidentiality ........................................................................................ 33 
13. 
Data Handling and Record Keeping .............................................................................. 34 
14. 
Financing and Insurance ............................................................................................... 35 
15. 
Publication Policy .......................................................................................................... 36 
16. 
REFERENCES .................................................................................................................. 37 
17. 
Appendices ................................................................................................................... 40 
 
 
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
1. 
AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date issued 
Author(s) of changes 
Details of Changes 
made 
1 
V2.0 
08/09/2022 
Laura Barr 
Per recommendation 
from London-
Stanmore REC: The 
term “Feasibility” 
removed from all trial 
documentation, in 
acknowledgement that 
this is a full clinical 
trial. The term 
“feasibility outcomes” 
changed to “tertiary 
outcomes”. 
2 
V2.0 
08/09/2022 
Laura Barr 
Page 1:  REC reference 
added. 
3 
V2.0 
08/09/2022 
Laura Barr 
Section 2:  Start date, 
recruitment end date 
and trial end date 
updated to reflect 
approval dates from 
REC. 
Protocol amendments will be listed here whenever a new version of the protocol is 
produced. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
2. 
SYNOPSIS 
Study Title 
Comparing the effectiveness of computer-aided-design computer-aided-manufacture 
(CAD/CAM) insoles manufactured from foam-box cast vs direct scan on patient reported 
outcome measures: A double-blinded, randomised controlled trial 
Internal ref. 
no. 
R&I no GN22OR165 
Type of study 
A single centre, double blinded, randomised controlled trial  
Trial Design 
Interventional, equivalence Trial design. 
Trial 
Participants 
Participants with a medical condition or lower limb biomechanical deficit which would 
commonly be treated with the use of insoles, as per the NHS Greater Glasgow and Clyde MSK 
Foot and Ankle Pathway: 
http://www.clinicalknowledgepublisher.scot.nhs.uk/Published/PathwayViewer.aspx?fileId=119 
Planned 
Sample Size 
114 (57 per group) 
Follow-up 
duration 
Total duration of individual participant involvement: 14-16 weeks total. Including initial 
assessment and fitting 2-4 weeks, and 12-week follow-up. 
Planned Trial 
Period 
Total Project length: 12 Months 
Expected Recruitment Start date: 29/09/2022 
Expected Recruitment End date: 29/06/2023 
Anticipated Trial End Date (all participants completed recruitment, completed intervention, 
completed all follow up, all data collected and all issues resolved): 29/09/2023 
Primary 
Objective 
To compare the changes in pain in two groups of participants fitted with custom CAD/CAM 
insoles manufactured using different foot shape capture methods  
Secondary 
Objectives 
1. To compare the changes in foot function in two groups of participants fitted with 
custom CAD/CAM insoles manufactured using different foot shape capture methods 
2. To compare the changes in foot health in two groups of participants fitted with custom 
CAD/CAM insoles manufactured using different foot shape capture methods  
3. To compare the participant satisfaction in two groups of participants fitted with custom 
CAD/CAM insoles manufactured using different foot shape capture methods  
4. To compare the time-in-transit and cost-time analysis of the custom CAD/CAM insoles 
manufactured using different foot shape capture methods 
5. To compare the environmental impact of custom CAD/CAM insoles manufactured using 
different foot shape capture methods 
Tertiary 
Objectives 
1. Recruitment rate 
2. Participant compliance with the study protocol / Adherence 
3. Adverse events 
4. Drop-out rate 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
Device Type  
Custom, Computer aided design (CAD) Computer aided manufacture (CAM), Ethylene-vinyl 
acetate (EVA) Foot Orthoses (insoles) 
Manufacturer 
Name  
Manufactured in the NHS Greater Glasgow and Clyde Orthotic Department, at Gartnavel 
General Hospital. Manufactured using the Paromed Paromanager CAD/CAM system 
Principle 
intended use  
For the use of any persons with a medical condition or lower limb biomechanical deficit which 
would commonly be treated with the use of insoles, as per the NHS GGC MSK Foot and Ankle 
Pathway: 
http://www.clinicalknowledgepublisher.scot.nhs.uk/Published/PathwayViewer.aspx?fileId=119 
Length of 
time the 
device has 
been in use.  
These devices are currently used as a standard care across NHS services in the UK, and have 
been for many years. Both methods of shape-capture are standard clinical practice across the 
UK. No novel techniques or devices are under investigation within this trial. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
3. 
ABBREVIATIONS 
ACRT 
Advanced Clinical Referral Triage 
AE 
Adverse event 
AR 
Adverse reaction 
CAD 
Computer aided design 
CAM 
Computer aided manufacture 
CI 
Chief Investigator 
Co-I 
Co-Investigator 
CTA 
Clinical Trials Authorisation 
CTRG 
Clinical Trials and Research Governance 
EVA 
Ethylene-vinyl acetate  
FHSQ 
Foot Health Status Questionnaire  
GDPR 
General Data Protection Regulation 
GGC 
Greater Glasgow and Clyde 
GGH 
Gartnavel General Hospital 
GRI 
Glasgow Royal Infirmary 
MHRA 
Medicines and Healthcare products Regulatory Agency 
MSK 
Musculoskeletal 
NHS 
National Health Service 
OPUS CSD 
Orthotic and Prosthetic User Survey Client Satisfaction with Device 
Module 
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
R&D 
NHS Greater Glasgow and Clyde Research & Development Department 
REC 
Research Ethics Committee 
RES 
Research Ethics Service 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
SAE 
Serious Adverse Event 
SDV 
Source Data Verification 
SOP 
Standard Operating Procedure 
 
 
 
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
4. 
BACKGROUND AND RATIONALE 
Computer aided design (CAD) with computer aided manufacture (CAM) foot orthoses 
(insoles) represent 14% (n=2739, per annum 2020) of all Orthotic Department provision in 
NHS Greater Glasgow and Clyde (GGC), representing a significant proportion of Orthotic 
service users, and financial burden to the National Health Service (NHS). The production of 
CAD/CAM insoles relies on acquiring a digital model of the patient’s foot from which the 
final insole can be produced.  This digital model is created either by directly scanning the 
patient’s foot in to the CAD/CAM system to produce a 3D model, or by taking a physical cast 
of the foot which is then scanned. These two methods of shape-capture are used 
interchangeably throughout NHS Orthotics services. 
In the NHS GGC Musculoskeletal (MSK) Foot and Ankle pathway1, patients receive insoles via 
fully digital design and manufacture, utilising direct foot scanning. Other NHS health-boards 
and Trusts across the UK have adopted a partially digitised approach, whereby shape-
capture is achieved with a traditional foam-box casting method. To date, no work has been 
undertaken to determine the clinical outcomes and economic impact relating to these 
different treatment approaches.  
 
Digitisation of medical devices in the orthotics industry conceptualised gains in production 
speed and reduction in waste materials when compared to traditional manufacture utilising 
physical shape capture2. Yet the continued interim stages of foam cast moulds and physical 
transportation of casts to manufacturers sacrifices these benefits. As services began 
adopting CAD systems in place of traditional manufacture, the standard service model for 
shape-capture has remained in place on some sites, despite the increased accessibility to 
mobile direct scanners over the past 10 years3. In NHS Scotland, the evolution of insole 
production with the introduction of CADCAM, has therefore lead to the creation of two 
industry standards; whereby a recent consultation with NHS Health boards across Scotland 
have shown some services continuing to use traditional foam-box casts, where others have 
chosen to utilise direct digital scanning on site.  
Motivation and hesitation in transitioning to a fully digital work stream have been assumed, 
but are currently unsupported by research. A common reluctance to adopt direct scanning is 
based on the assumption that digital shape capture and foam-box casts do not produce like-
for-like models, and therefore cannot result in the production of equally effective insoles. 
Although differences in volume have been shown4, the effect on the final device production 
and ultimately the treatment efficacy and resulting effectiveness have not been evaluated.  
Other concerns centralise on costs associated with the acquisition of direct scanning 
equipment. Although prior cost analyses have shown a fully digital supply chain to be more 
expensive than a fully traditional supply chain2, this does not reflect the practices associated 
with a partially digital workflow as seen across NHS Scotland. Nor does this consider a cost 
comparison over the life span of a digital scanner, or the environmental impact of the 
manufacture and transportation of traditional cast materials.  
Overall, the evidence base relating to CAD/CAM insoles, demonstrates little consistency or 
rationale behind the mode of shape-capture used during the process of manufacture. Often 
the shape-capture method is undocumented or unclear5-7, or documented without any 
attributed clinical reasoning8-16. In 2019, Parker et al investigated the differences in a fully 
digital workflow compared with fully traditional manufacturing techniques, but did not 
investigate the specific impact of shape-capture in isolation. Furthermore, these studies 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
report no consideration as to the environmental impact of phenolic foam production and 
disposal required for traditional foot shape-capture17-18, or the carbon footprint of 
transportation from manufacturer to digital upload of the foot shape from the foam-box 
cast, a step which is not required when utilising direct digital scan techniques. In line with 
NHS Net Zero targets 202019, and the recognition of Orthotic Services throughout the UK 
that largescale change is required to achieve this20, the practice of single-use traditional 
shape capture techniques requires immediate scrutiny. 
It is clear from the literature and current widespread indiscriminate practices across NHS 
Orthotic Services, that more research is required to assist with best practice in the 
manufacture of CAD/CAM insoles. Given the proportion of Orthotic Service users who 
receive insoles from the NHS, this trial has the potential to guide practice toward beneficial 
changes in patient outcomes, as well as providing NHS Orthotic departments with 
information to assist in the development of long-term service models in line with NHS and 
Government targets. 
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
5. 
OBJECTIVES AND OUTCOME MEASURES 
 
Objectives 
Outcome Measures  
Timepoints of 
evaluation of this 
outcome measure (as 
applicable) 
 Primary Objective 
 
To compare the changes in pain 
in two groups of participants 
fitted with custom CAD/CAM 
insoles manufactured using 
different foot shape capture 
methods   
 
 
Foot Health Status Questionnaire 
(Appendix 1) (FHSQ)21-23 – Pain sub-
domain. The minimal important difference 
has a threshold of a 12.5 point change for 
pain 24   
  
 
 
Completed at the 
Second Appointment, 
Third Appointment, 
Fourth Appointment 
and Fifth 
Appointment 
 
Secondary Objectives 
 
1. To compare the changes in 
foot function in two groups 
of participants fitted with 
custom CAD/CAM insoles 
manufactured using different 
foot shape capture methods 
 
 
 
2. To compare the changes in 
foot health in two groups of 
participants fitted with 
custom CAD/CAM insoles 
manufactured using different 
foot shape capture methods  
 
 
3. To compare the participant 
satisfaction in two groups of 
participants fitted with 
custom CAD/CAM insoles 
manufactured using different 
foot shape capture methods  
 
4. To compare the time-in-
transit and cost-time analysis 
 
 
1. Foot Health Status Questionnaire – 
Function sub-domain. The minimal 
important difference has a threshold of 
a 7.1 point change for foot function 24 
 
 
 
 
2. Foot Health Status Questionnaire – 
foot health sub-domain. The minimal 
important difference has a threshold of 
a -0.4 point change for foot health 24 
 
 
 
3. Orthotic and Prosthetic User Survey 
(OPUS) 25-28 Satisfaction with device 
survey (Appendix 2) 
 
 
 
 
4. Time-in-transit – Measurement of 
 
 
1. Completed at the 
Second 
Appointment, 
Third 
Appointment, 
Fourth 
Appointment and 
Fifth appointment 
2. Completed at the 
Second 
Appointment, 
Third 
Appointment, 
Fourth 
Appointment and 
Fifth appointment 
3. Completed at the 
fifth appointment 
 
 
 
 
4. Throughout 
duration of trial 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
of the custom CAD/CAM 
insoles manufactured using 
different foot shape capture 
methods 
 
 
 
5. To compare the 
environmental impact of 
custom CAD/CAM insoles 
manufactured using different 
foot shape capture methods 
 
transit and delivery times associated 
with each arm of the trial will be 
compared. 
Cost analysis – Costs relating to time-
in-transit for each arm of the trial will 
be compared 
5. Analysis of annual custom insole 
production in NHSGGC in relation to 
the environmental impact of the 
required phenolic foam production29 
and carbon footprint of transportation 
from manufacturer to digital upload of 
foam-box cast using carbon foot print 
calculations30.   
 
 
 
 
 
 
5. Calculated 
retrospectively 
from April 2021 – 
April 2022 
Tertiary Objectives 
 
Assessment of factors over a 
defined 9-month recruitment 
period including: 
1. Recruitment rate 
 
 
 
 
2. Participant compliance with 
the study protocol / 
Adherence 
 
 
 
3. Adverse events 
 
 
 
 
4. Drop-out rate 
 
 
 
 
1. Recruitment rate = n/recruitment 
period 
 
 
 
2. Participants will keep a diary of daily 
wear time, in accordance with prior 
publications on measuring Orthotic 
Adherence31.  The minimum threshold 
for adherence is >21 hours per week32 
 
3. Adverse events 
 
 
 
 
4. Dropout rate = n dropout/duration of 
trial 
 
 
 
 
1. Throughout 
recruitment period 
and calculated at 
the trial conclusion 
 
 
2. Data collected from 
participants at the 
third appointment, 
fourth appointment 
and fifth 
appointment 
3. Self-reported by 
participants at any 
time throughout the 
trial period 
 
 
4. Collected 
throughout trial and 
calculated at trial 
conclusion 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
6. 
TRIAL DESIGN 
6.1 
Summary of Trial Design 
Type of Trial summary: 
A single centre, double blinded, randomised controlled trial comparing the effectiveness of 
two methods of foot shape capture currently used in NHS Orthotic services in Scotland. This 
is an Interventional, equivalence trial using medical devices (insoles). 
 
Trial Setting summary: 
Participant assessment and treatment will be provided in a hospital setting, within the NHS 
GGC Orthotic Department. There will be one trial site, located at the Glasgow Royal 
Infirmary (GRI). This trial will minimise participant on-site visits by utilising telephone 
contacts throughout the participation period to collect relevant participant reported 
outcome measures (outlined in more detail below). At the conclusion of the participant 
involvement in the trial, they will transition back to usual care within the NHS GGC Orthotic 
Department. 
 
Duration of participant involvement and visit summary: 
From enrolment to exiting the trial, participants will be involved in the trial for 14-16 weeks.  
During the study there will be 5 appointments.  Participants will visit the Orthotic 
Department at GRI for the first appointment and second appointment as per standard 
practice in the NHS GGC Orthotic Department, and will receive telephone follow-up contact 
at the third, fourth and fifth appointments: 
First appointment: Face-to-Face Hospital visit for screening, consenting, foot/clinical 
assessment and randomisation. Duration of appointment - 40 minutes.  
Second appointment at week 2-4: Face-to-Face Hospital Visit for insole fitting and 
completion of baseline participant reported outcome measures. Duration of appointment - 
40 minutes. 
Third appointment at week 6-8: Telephone follow-up appointment to complete participant 
reported outcome measures and participant self-reporting of insole usage hours/day. 
Duration of appointment - 15 minutes. 
Fourth Appointment at week 10-12: Telephone follow-up appointment to complete 
participant reported outcome measures and participant self-reporting of insole usage 
hours/day. Duration of appointment - 15 minutes. 
Fifth Appointment at week 14-16: Telephone follow-up appointment to complete participant 
reported outcome measures and participant self-reporting of insole usage hours/day. 
Duration of appointment - 15 minutes. 
 
Data collection summary: 
Participant reported outcome measures:- 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
Eligible participants will complete the Foot Health Satisfaction Questionnaire (FHSQ) at their 
second appointment, third appointment, fourth appointment and fifth appointment.  The 
Orthotic and Prosthetic User Survey (OPUS) questionnaire will be collected at the fifth 
appointment.  
 
Tertiary outcomes:- 
Participant self-reported insole usage will be collected by the PI at the third appointment, 
fourth appointment and fifth appointment to monitor compliance with insole use. 
Outcomes relating to time in transit, cost-analysis, recruitment rate and dropout rate will be 
reported by the PI at the timescales as indicated in section 6. Objectives and Outcome 
Measures.  
 
Assessment findings:- 
Findings from the assessment as outlined in section 6.4.2 of this protocol will be collected at 
the first appointment. Any changes to medication throughout the trial will be collected 
during third appointment, fourth appointment, and fifth appointment.   
 
Adverse events:- 
Adverse events reported by participants at any time during the trial will be addressed as 
outlined in section 8 of this protocol. 
 
6.2 
Trial Participants  
6.2.1 Overall Description of Trial Participants 
Participants with a medical condition or lower limb biomechanical deficit which would 
commonly be treated with the use of insoles as a first or second line intervention, as per the 
NHS GGC MSK Foot and Ankle Pathway: 
http://www.clinicalknowledgepublisher.scot.nhs.uk/Published/PathwayViewer.aspx?fileId=1
199 
6.2.2 Inclusion Criteria 
All participants: 
 Are aged 18 years or above 
 Are referred to the NHS GGC Orthotic service requiring a new assessment for insoles 
 are deemed suitable for CAD/CAM insoles as assessed by the PI or Co-I on clinical 
assessment 
 Are able to commit to five appointments over a 16-week period (two Face-to-Face 
appointments, three Telephone Appointments) 
 Have suitable own footwear that can accommodate a CAD/CAM insole as assessed 
by the PI or Co-I, and as per standard practice can wear these for 12-weeks 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
 An adequate understanding of written and verbal information in English in order to 
provide informed consent and answer the study questionnaires 
 
6.3.3 Exclusion Criteria 
 
Potential participants will not enter the trial if any of the following apply: 
 
 Scheduled elective surgery or other procedures which is likely to affect mobility 
during the trial. 
 Scheduled steroid injection to the foot or ankle up to 3 months prior to joining the 
trial, or during participation in the trial 
 Age <18 years 
 Adult with Incapacity, under The Adults with Incapacity (Scotland) Act 2000 
 Participant unable or unwilling to consent 
 Medial longitudinal arch height of the foot exceeds depth of EVA blank (35mm) 
 Clinical assessment concludes that the participant requires an insole material other 
than EVA 
 Clinical assessment concludes that the participant does not require or will be unlikely 
to benefit from CAD/CAM insoles.  
 The participant is unable to commit to the trial conditions. 
 Peripheral Neuropathy present 
 Active foot ulceration present 
 Participant with life expectancy of less than 6 months. 
 Any other significant disease or disorder which, in the opinion of the PI or Co-I, may 
either put the participants at risk because of participation in the trial, or may 
influence the result of the trial, or the participant’s ability to participate in the trial. 
 Participants who have participated in another research trial involving an 
investigational foot orthosis in the past 12 weeks. 
 
6.4 
Study Procedures 
 
6.4.1.1 Recruitment 
 
Potential participants will be made aware of the trial and will receive a Participant  
Information Sheet (PIS) in the following way: 
 
During the Advanced Clinical Referral Triage (ACRT) process, which is standard practice 
in the NHS GGC Orthotic service, all new patient referrals are reviewed by an Orthotist 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
and patients are contacted by telephone prior to being added to the waiting list.  During 
the ACRT process Orthotists may mention the trial to potential participants, and 
post/email the PIS if requested. The PIS will invite potential participants to make contact 
with the research team for further information or to discuss eligibility or any questions 
that the potential participant may have. The PIS assures the potential participants that 
participation or otherwise in the research will not affect their care in any way.  
 
For potential participants that respond indicating a willingness to be contacted, they will 
be contacted by the PI by telephone to provide more information about the study and if 
the potential participant(s) is still interested in the study, the PI will screen for eligibility. 
The research team will provide opportunities to answer any questions regarding the 
study, and the potential participant will be offered the choices of i) declining further 
participation, ii) arrange a date/time for the First Appointment at the time of the 
telephone contact or iii) to receive a follow-up telephone contact approximately one 
week later after initial contact has been made.  
 
For those potential participants that do not respond to the invitation letter, after two 
weeks the PI, who is a member of the direct care team at the Orthotic Department in 
NHS GGC, will make one telephone call to the potential participant to see whether they 
have received the PIS and have any questions related to the study. The potential 
participant will be offered the choices of i) declining further participation, ii) a date/time 
for the First Appointment at the time of the telephone contact or iii) receiving a follow-
up telephone contact approximately one week later, by a member of the research team, 
if the potential participant consents for their details to be shared with the PI. 
 
6.4.1.2 
Informed Consent 
 
At the First Appointment, participants who wish to participate in the trial will be invited 
to provide informed, written consent, by personally signing and dating the latest 
approved version of the informed consent form before any study specific procedures 
are performed. Consent will be taken by the PI with a witness if required by the 
participant and recorded on a pre-printed consent form.  The right of the participant to 
refuse consent without giving reason will be respected. Further, the participant will 
remain free to withdraw from the study at any time without giving reason and without 
prejudicing any further treatment. The participant will be allowed as much time as they 
wish 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. A 
copy of the consent form will be given to the participant, one filed in the CRF, and one 
filed in the hospital notes. The written consent will be obtained by the PI, who is fully 
trained in Good Clinical Practice. The process of obtaining written consent will be clearly 
documented in the participant’s medical notes. 
6.4.2 Screening and Eligibility Assessment 
Screening and Eligibility assessment will all take place at the First Appointment.  
Protocol waivers are not permitted in this trial.  

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
Rescreening will not be permitted, as it is unlikely that a participant who does not meet the 
inclusion criteria on first screening, will be able to meet this at a later date within the trial 
period. 
Participants will be assessed and screened according to the inclusion and exclusion criteria 
in sections 6.2.2 and 6.3.3 of this protocol. This will involve: 
 Review and recording of relevant medical history from the participant’s medical 
record, which is standard practice in the NHS GGC Orthotic department.  
 Review and recording of the following groups of medications routinely taken by the 
participant:  Biologics, DMARDs, NSAIDs, oral steroids, or analgesics.  
 Diagnosis of foot and ankle pathology i.e. Plantar fasciopathy, tendinopathy, 
arthropathy etc. 
 Physical examination of the foot and ankle, including recording the outcomes of the 
following standard biomechanical tests –  
1. Foot Posture Index 33 
2. Jacks test for Functional Hallux Limitus 34 
3. Palpation technique for Subtalar Joint Axis Location 35 
4. Passive assessment of ankle dorsiflexion stiffness by ‘position of first detectable 
resistance 36 
5. Supination resistance test 37 
6. Visual gait analysis 
 
6.4.3 Baseline Assessments 
First Appointment – face-to-face visit at the NHS GGC GRI Orthotic clinic, as per standard 
practice 
1. Participant physically attends the clinic 
2. Participant is assessed by the PI and Co-I, using the assessment methods outlined 
above in section 6.4.2 
3. Insole specification agreed between the PI, Co-I and participant 
4. Participant is assigned a unique participant number. 
5. ALL participants receive a direct scan and a foam-box cast, using the methods 
outlined above in section 9.2 
6. PI exits – blinded to the randomisation group 
7. Co-I randomises the participant to the treatment arm by opening one of the sealed 
envelopes: The treatment arm will indicate if the insoles will be manufactured using 
the direct scan or the foam-box cast.  
8. Participant is not informed of the randomisation outcome – blinded to treatment 
arm 
9. Participant is invited to a fitting appointment with the PI in 2-4 weeks and leaves the 
clinic 
10. Co-I creates an insole order on the standard Orthotic department ordering system 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
11. Co-I sends ALL foam-box casts to Gartnavel General Hospital to be scanned into the 
CAD/CAM system.  The CAD/CAM system records the time and date of each scan, 
which will be used to inform the time-in-transit aspect of the trial. 
12. PI undertakes modelling of both the direct scan and the scanned foam-box cast. 
13. Co-I documents the specific functional elements of the insole on the excel data 
spreadsheet against the unique participant number 
14. Co-I documents the assessment findings for each of the biomechanical assessment 
methods (outlined in section 9.2 of the protocol) on the excel data spreadsheet 
against the unique participant number 
 
6.4.4 Randomisation and Codebreaking  
The trial has been registered on the web based registration system 
http://www.Clinicaltrials.Gov, and assigned trial number NCT05444192. 
 
Randomisation:  
All eligible participants will receive their randomised treatment/insole at the First 
Appointment, after they have been screened, assessed, and consented to join the trial. 
Randomisation will be conducted according to a random number algorithm, contained in 
pre-sealed envelopes, by the CI. The sealed envelopes will be sent to the Co-I and stored 
securely in a locked filing cabinet in the Glasgow Royal Infirmary Orthotic Department. The 
envelopes will be opened on a 1:1 basis by the Co-I during the assessment appointment. The 
PI and the participants will be blinded to the treatment arm.   
 
Blinding: 
The PI will be blinded to the allocation group for the duration of the trial. This will be 
achieved by the PI not being present during the randomisation process at the First 
Appointment, when the participant will be randomised into one of two treatment arms 
which will be allocated by the Co-I.  Subsequently the PI will not have any access to the 
insole paperwork which will be removed by administration staff at Gartnavel General 
Hospital following insole manufacture.  The insoles for each participant will be placed in 
clear plastic bags containing only the participants name and appointment time. The insoles 
will then be sent to Glasgow Royal Infirmary for the participant fitting appointment, as per 
standard practice.  On arrival at the Glasgow Royal Infirmary, the Co-I will double check that 
the paperwork has been removed, and the bag contains only the insoles, participant name 
and appointment time. It is standard practice for the administration staff and the on-site 
orthotist to double check clinical goods in this way.   
 
There will be no visible difference in the insoles for each treatment arm.  CAD/CAM insoles 
manufactured from direct foot scans and foam-box casts are modelled and milled in the 
same way and have the same outward appearance. 
 
The participants will be blinded to the allocation group for the duration of the trial. This will 
be achieved by the Co-I taking both a direct scan and a foam-box cast for each participant. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
The participant will not be aware of which scan/cast has been used for the final manufacture 
of the insoles. 
Code-Breaking: 
If the clinical condition of a participant necessitates breaking the allocation code, the Co-I 
(not blinded) will access the CAD/CAM insole ordering system to confirm the treatment-arm. 
This process will not unbind the whole trial, nor will it disclose the randomisation schedule.  
Out of hours code-breaking will not be required due to the low risk level of the intervention.  
At the end of the study the data from the two groups will be analysed independently, after 
which the groups will be releveled. 
 
6.4.5 Subsequent assessments 
Second appointment – Fitting of insoles face-to-face visit at NHS GGC GRI Orthotic clinic, as 
per standard practice 
1. Participant receives a reminder call from the PI the day before appointment to 
confirm attendance 
2. PI fits the insoles  
3. Participant is advised to wear the insoles for 10 minutes before leaving the clinic 
4. If any issues arise during the 10 minutes, PI adjusts the insoles (repeat until no issues 
when leaving the clinic) 
5. PI documents adjustments made against the unique participant number on the excel 
data sheet. 
6. If the participant is unable to wear the insoles for any reason they will exit the trial at 
this stage which will be documented as “unable to proceed”. In these instances the 
participant will be transferred back to the standard orthotic clinic for ongoing 
treatment as appropriate, and an appointment will be offered within the standard 
waiting time of 12 weeks at the NHSGGC Orthotic Clinic unless unsuitable for the 
participant. 
7. If continuing within the trial, the participant will be invited to attend a telephone 
appointment in 4 weeks with the PI 
8. Participant completes the FHSQ and the PI calculates the FHSQ scores using the 
validated FHSQ calculation, and documents these against the unique participant 
number on the excel data sheet.  
9. Participant is asked if there has been any change to their use any of the following 
groups of medications:  Biologics, DMARDs, NSAIDs, oral steroids, or analgesics. This 
is documented by the PI on the CRF. 
10. Participant is asked to keep a daily diary documenting the total number of hours per 
day that the insoles were worn for. 
 
Third Appointment – 4 Week Review 
1. Participant receives a reminder call from the PI the day before appointment to 
confirm attendance. 
2. Participant attends the telephone clinic 
3. If the participant is unable to wear the insoles for any reason they will exit the trial at 
this stage which will be documented as “unable to proceed”, in these instances the 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
participant will be transferred back to standard orthotic clinic for ongoing treatment 
as appropriate, and an appointment will be offered within the standard waiting time 
of 12 weeks at the NHSGGC Orthotic Clinic unless unsuitable for the participant. 
4. If continuing with the trial the participant completes the FHSQ 
5. Participant reports the daily wear-time of the insoles according to their diary over 
the past 4 weeks. 
6. Participant is asked if there has been any change to their use any of the following 
groups of medications:  Biologics, DMARDs, NSAIDs, oral steroids, or analgesics. This 
is documented by the PI on the CRF. 
7. Participant invited to attend a telephone appointment in 4 weeks with PI 
8. PI calculates the FHSQ scores using the validated FHSQ calculation, and documents 
these against the unique participant number on the excel data sheet 
9. PI records the daily wear-time, documenting these against the unique participant 
number on the excel data sheet. 
 
Fourth Appointment – 8 Week Review 
1. Participant receives a reminder call from the PI the day before appointment to 
confirm attendance. 
2. Participant attends the telephone clinic 
3. If the participant is unable to wear the insoles for any reason they will exit the trial at 
this stage which will be documented as “unable to proceed”. In these instances 
participant will be transferred back to standard orthotic clinic for ongoing treatment 
as appropriate, and an appointment will be offered within the standard waiting time 
of 12 weeks at the NHSGGC Orthotic Clinic unless unsuitable for the participant. 
4. If continuing with the trial Participant completes the FHSQ 
5. Participant reports the daily wear-time of the insoles according to their diary over 
the past 4 weeks. 
6. Participant is asked if there has been any change to their use any of the following 
groups of medications:  Biologics, DMARDs, NSAIDs, oral steroids, or analgesics. This 
is documented by the PI on the CRF. 
7. Participant is invited to attend a telephone appointment in 4 weeks with the PI 
8. PI calculates the FHSQ scores using the validated FHSQ calculation, and documents 
these against the unique participant number on the excel data sheet. 
9. PI records the daily wear-time, documenting these against the unique participant 
number on the excel data sheet. 
 
Fifth Appointment – 12 Week Review 
1. Participant receives a reminder call from the PI the day before appointment to 
confirm attendance. 
2. Participant attends the telephone clinic 
3. If participant unable to wear the insoles for any reason they will exit the trial at this 
stage documented as unable to proceed. In these instances participant will be 
transferred back to standard orthotic clinic for ongoing treatment as appropriate, 
and an appointment will be offered within the standard waiting time of 12 weeks at 
the NHSGGC Orthotic Clinic unless unsuitable for the participant. 
4. If continuing with the trial Participant completes the FHSQ and OPUS  

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
5. Participant reports the daily wear-time of the insoles according to their diary over 
the past 4 weeks. 
6. Participant is asked if there has been any change to their use any of the following 
groups of medications:  Biologics, DMARDs, NSAIDs, oral steroids, or analgesics. This 
is documented by the PI on the CRF. 
7. The participant is thanked for their involved in the trial, and provided with contact 
details and self-referral information for the NHS GGC Orthotic Department so that 
they can continue to access standard care from the department in future on request. 
8. PI calculates the FHSQ and OPUS scores using the validated FHSQ and OPUS 
calculation, and documents these against the unique participant number on the 
excel data sheet 
9. PI records the daily wear-time, documenting these against the unique participant 
number on the excel data sheet. 
6.5 
Definition of End of Trial  
The trial will conclude when either of the two conditions: 
1. The recruitment phase has run for 9-months (plus 12-week follow up of all 
participants)  
2. Participant recruitment = 114 (plus final 12-week follow up of all participants)  
AND 
 
All the enrolled participants have concluded all 5 appointments, and all the data has 
been entered into the excel data sheet.  
   
6.6 
Discontinuation/ Withdrawal of Participants from Study Treatment 
During the course of the trial a participant may choose to withdraw early from the trial 
at any time. This may happen for a number of reasons, including but not limited to:  
 
   The occurrence of what the participant perceives as an intolerable AE.  
   Inability to comply with trial procedures  
   Participant decision  
 
The following options for withdrawal from the trial are included on the PIS: 
 
1.   Participants can withdraw from the study but permit data obtained up until the point 
of withdrawal to be retained for use in the study analysis. No further data would be 
collected after withdrawal.  
2.   Participants can withdraw completely from the study and withdraw the data collected 
up until the point of withdrawal. The data already collected would not be used in the 
final study analysis.  
 
In addition, the PI may discontinue a participant from the trial treatment at any time if 
the Investigator considers it necessary for any reason including, but not limited to: 
 
   Ineligibility arising during the trial – i.e. development of a medical condition as outlined 
in the exclusion criteria.  

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
   Significant non-compliance with treatment regimen or trial requirements – i.e. 
participant has not worn or unable to wear the insoles between appointments 
   An adverse event which requires discontinuation of the CAD/CAM insoles or results in 
inability to continue to comply with trial procedures 
   Disease progression which requires discontinuation of the CAD/CAM insoles – i.e. 
medically too unwell to continue participation, or disease progression as outlined in 
the exclusion criteria 
 
The type of withdrawal and 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.  
 
All participants withdrawn from the trial for any reason, will be offered an appointment 
at the general NHS GGC Orthotic service to resume their standard care. Contact 
information for the NHS GGC Orthotic Department is included within the PIS. 
6.7 
Source Data 
Source documents are original documents, data, and records from which participants’ 
Case Report Form (CRF) data are obtained. These include, but are not limited to, 
hospital records (from which medical history and previous and concurrent medication as 
specified at each of the participant appointments in section 6 of this protocol, may be 
summarised into the CRF), diaries, medical imaging reports for relevant radiographs of 
the foot, MRI of the foot and CT of the foot, and correspondence from the participant. 
CRF entries will be considered source data if the CRF is the site of the original recording 
(e.g., there is no other written or electronic record of data). In this study the CRF will be 
used as the source document for FSHQ data, OPUS data, physical assessment data, and 
diary of insole wear time data. All other participant information will be sourced from 
verifiable from source documents (e.g. hospital records, diaries, medical imaging reports 
for relevant radiographs of the foot, MRI of the foot and CT of the foot, and 
correspondence from the participant).  
All CRF documents will be stored safely in a locked filing cabinet in the Glasgow Royal 
Infirmary. On all study-specific documents, other than the signed consent form, the 
participant will be referred to by the unique participant number, not by name. 
Source data verification ensures accuracy and credibility of the data obtained. The PI will 
review the reported data to ensure they are accurate, complete, and verifiable from 
source documents. All data reported on the CRF will be supported by source documents. 
Data Verification will be carried out by the PI who will check the CRF for completeness 
and clarity, and crosscheck them with source documents 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
7. 
TREATMENT OF TRIAL PARTICIPANTS 
7.1 
Description of Study Intervention(s) 
The treatment which will be supplied to all participants is a pair of custom, CAD/CAM 
ethylene vinyl acetate (EVA) foot orthoses (insoles). The insoles are manufactured either 
from a direct digital scan of the participants feet, or from a foam-box cast of the participants 
feet which will then be scanned into the CAD/CAM system. This is a standard treatment 
widely used across Orthotic Services in the UK.  
7.2 
Maintenance and storage of device 
 All Direct Foot scans will be saved by the Co-I in the CAD/CAM insole system at the 
time of their first appointment, per standard clinical practice.  
 All Foam-box casts will be sent by the secure internal NHS mail system to Gartnavel 
General Hospital to the Orthotic Technician, as per standard clinical practice. The 
foam-box cast will be scanned and saved by the Orthotic Technician in the CAD/CAM 
insole system, per standard clinical practice.  
 All digital models will also be available for repeat prescriptions for participants 
attending the NHS GGC Orthotic department again in future once they return to 
standard care. 
 Following manufacture, all physical insoles will be delivered to GGH Orthotic 
Administrators, as per standard NHS GGC Orthotic Department process. 
 All insoles will be placed into clear plastic bags with the participant name and date of 
appointment attached.  No other paperwork will be send to GRI with the insoles. 
 Insoles will be sent to the GRI Orthotic Department using a secure internal courier, as 
per standard clinical practice.   
 The Co-I will double check the insoles on arrival at GRI to ensure that only the 
participant name and date of appointment is contained in the bag with the insoles. It 
is standard practice for the Orthotist on site at GRI to double check the incoming 
goods for appointments.  
 As per standard practice in the NHS GGC Orthotic Service, the insoles will be stored 
in the locked in an Orthotic Appointments Cupboard in Glasgow Royal Infirmary until 
the time of the participant fitting appointment. 
 
7.3 
Compliance with Trial treatment 
Participant compliance with the trial treatment will be assessed at the Third Appointment, 
Fourth Appointment and Fifth Appointment by means of discussion with the participant 
regarding their use of the insoles over the preceding 4-weeks, and by collection of their 
diary of daily wear time. 
7.4  
Concomitant Medication  
There are no contraindicated medications within the trial design. No medication 
changes are anticipated as a result of participating in this trial.  
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
7.5       Post-trial treatment 
 
All participants will be offered the opportunity to retain and continue use of the medical 
device (CAD/CAM insoles) after their participation in the trial has concluded.  
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
8. 
SAFETY REPORTING 
 
8.1 Definitions 
Adverse events (AE) 
An adverse event is any untoward medical 
occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other 
persons, whether or not related to the 
investigational medical device.  
   
Note 1 to entry: This definition includes events 
related to the investigational medical device or 
the comparator.  
Note 2 to entry: This definition includes events 
related to the procedures involved.  
Note 3 to entry: For users or other persons, this 
definition is restricted to events related to the use 
of investigational medical devices.  
   
Serious Adverse Event 
An adverse event that led to any of the following:  
a. death,  
b. serious deterioration in the health of the 
subject, users or other persons as defined by one 
or more of the following:  
1. a life-threatening illness or injury, or  
2. a permanent impairment of a body 
structure or a body function including chronic 
diseases, or  
3. in-patient or prolonged hospitalisation, or  
4. medical or surgical intervention to prevent 
life-threatening illness or injury or permanent 
impairment to a body structure or a body 
function,  
c. 
foetal distress, foetal death or a congenital 
abnormality or birth defect including physical or 
mental impairment  
   
Note 1 to entry: Planned hospitalisation for a pre-
existing condition, or a procedure required by the 
protocol, without serious deterioration in health, 
is not considered a serious adverse event.  
   
Serious adverse device event 
(SADE) 
A serious adverse device effect (SADE) is any 
adverse device effect that has resulted in any of 
the consequences characteristic of a serious 
adverse event. A SADE may be anticipated or 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
unanticipated.  
Unanticipated Serious Adverse 
Device Effect (USADE) 
Unanticipated serious adverse device effect 
(USADE) is a serious adverse device effect which 
by its nature, incidence, severity or outcome has 
not been identified in the current version of the 
risk analysis report.  
 
8.2 Recording and Reporting of Adverse Events 
AEs must be recorded, assessed, reported, analysed and managed in accordance with the 
Research Governance Framework for Health and Community Care and the study protocol. 
All AEs must be assessed for seriousness. AEs for this study will be recorded within the 
participant’s notes but are not considered reportable. 
8.3 Recording and Reporting of Serious Adverse Events   
Where an SAE requires recording; full details including the nature of the event, start and 
stop dates, severity, causal relationship to the device and/or trial procedures, and the 
outcome of the event will be recorded in the participant’s medical notes. These events will 
be monitored and followed up until satisfactory resolution and stabilisation. 
Assessment of causality  
I.e., does the event have a “reasonable causal relationship” with any trial specific procedures 
or the investigational device?  
The assessment of causality must be carried out by the PI or other medically qualified local 
investigator.  
 
Assessment of expectedness  
If the SAE is considered related to any trial specific procedures or the investigational medical 
device an assessment should be made of the expectedness i.e., is the SAE a recognised 
adverse effect of the investigational medical device or a trial procedure.   
8.4 Reporting to Sponsor   
The following events defined are considered reportable to the sponsor.  
 
 Any Serious Adverse Event that is considered related to the trial specific procedures, 
or the medical device(s) that is considered unexpected by the Chief Investigator or 
their delegate. (USADE) 
 
 Any device related serious adverse event that led or may have led to one of the 
following outcomes:  (SADES) 
o The death of a participant 
o A serious deterioration in the health of a participant.   
o A serious deterioration in health may include (non-exhaustive):  
o Life threatening illness  
o Permanent impairment of a body function or permanent damage to a body 
structure  
o A condition necessitating medical/surgical intervention to prevent a) or b)  
o Foetal distress or death, or any congenital anomalies or birth defects.  

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
 
SAEs meeting the above criteria must be reported to the Pharmacovigilance Office 
immediately (within 24 hours) using the SAE form for a non CTIMP found here: 
https://glasgowctu.org/Home/00-safety-reporting/. The SAE form should be completed and 
signed by appropriately delegated staff. The form should be e-mailed to the PV Office 
(pharmacovig@glasgowctu.org) and a copy placed in the Study Site File. 
 
If all the required information is not available at the time of initial reporting, the CI (or 
designee) must ensure that any missing information is forwarded to the PV Office as soon as 
this becomes available. The report should indicate that this information is follow-up 
information for a previously reported event. 
 
8.5 Reporting of USADEs to the REC  
 
The Sponsor will report all USADEs to the ethics committee within 15 days of the PV office 
becoming aware of the event, via the ‘report of serious adverse event form’ for non-CTIMPs 
published on the Health Research Authority web site. 
https://www.hra.nhs.uk/documents/2466/Non_CTIMP_Safety_Report_Form_Accessible_Se
ptember_2020_AA.odt 
 
The form should be completed in typescript and signed by the Chief Investigator.   
8.6 Reporting of SADEs and USADES to IRIC 
 
The CI or delegate must submit reports relating to the medical device that meet the above 
criteria to the Incident Reporting and Investigation Centre (IRIC – part of NHS National 
Services Scotland). Information about how to report an adverse incident can be found here:  
http://www.hfs.scot.nhs.uk/online-services/incident-reporting-and-investigation-centre-
iric/how-to-report-an-adverse-incident/  
8.7 Annual Reports 
 
In addition to the above reporting the CI will submit once a year, throughout the trial, or on 
request a progress/safety report to the Research Ethics Committee and R&D. 
 

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9. 
STATISTICS 
 
9.0.1  Responsibilities 
 
The research team consisting of the PI and research investigators will perform the data 
analysis and complete the write up. 
 
9.0.2   Hypotheses 
 
We aim to evaluate the method of manufacturing CAD/CAM insoles from a direct-scan, 
compared to that of a foam-box cast. The null hypothesis is that the change in FHSQ 
Pain score pre and post-treatment will not differ between the treatment groups. The 
alternative hypothesis is that the change in FHSQ pain score will differ between groups. 
9.1 
Description of Statistical Methods 
The change in FHSQ scores for the sub-domains of Pain, Foot Function, Foot Health and 
Footwear, will be compared between groups at the specified data collection time points: 
baseline, 4-weeks, 8-weeks and 12-weeks, using mix methods Analysis of Variance or 
Friedman tests with post hoc Wilcoxon tests for within group analysis and Mann-
Whitney U tests for between group analysis if the data are not normally distributed.  
 
The change in OPUS scores for the sub domain of Satisfaction With Device, will be 
compared between groups at the specified data collection time point of 12-weeks, using 
unpaired t-tests or Mann-Whitney U tests if the data are not normally distributed.  
 
9.2 
The Number of Participants 
Power calculation for sample size: Based on data from Landorf et al.24 regarding FHSQ, a 
sample size was calculated to detect a clinically important difference between groups of 
13 (SD = 26.9) points in Foot Health Status Questionnaire scores using the pain sub-
domain as the primary outcome, giving a required minimum sample size of 54 
participants in each group plus 5% drop out rate = 57 per group. Total sample size 
n=114.  
9.3 
The Level of Statistical Significance 
Significance will be considered at P<0.5 
9.4 
Criteria for the Termination of the Trial 
If the medical devices (insoles) are found to cause serious adverse events 
9.5 
Procedure for Accounting for Missing, Unused, and Spurious Data. 
If the level of missing data exceeds 5%, multiple imputation will be used to address this. 
9.6 
Procedures for Reporting any Deviation(s) from the Original Statistical Plan 
Any deviation(s) from the original statistical plan will be described and justified in the 
final report. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
9.7 
Inclusion in Analysis 
All randomised participants, who have completed the trial and have not withdrawn their 
consent from their involvement in the trial, will be included in the analyses. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
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. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
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11. 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
 
11.1  Quality control and assurance 
The study will be conducted in accordance with the current approved protocol, and standard 
operating procedures within the NHS GGC Orthotic Department.  
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.  
 
11.2  Peer review 
This protocol has been peer reviewed by the supervisory team at the University of Central 
Lancashire.  

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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, with the ICH Guidelines for Good Clinical Practice (CPMP/ICH/135/95) July 
1996, and the UK policy Framework for Health and Social Care research. 
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) for written approval. No participants will be entered into the study until approvals 
have been received.  
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 a unique participant number on the CRF and the 
excel data sheet.  All electronic documents will be stored securely within a registered 
GDPR asset folder, and only accessible by trial staff and authorised personnel. The study 
will comply with the Data Protection Act 1998 which requires data to be anonymised as 
soon as it is practical to do so.  
 

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13. 
DATA HANDLING AND RECORD KEEPING 
All study data will be entered on a Microsoft excel spreadsheet, saved within a GDPR 
registered asset folder as per standard operating procedure in the NHS GGC Orthotics 
Department. Regular backups of the electronic data will be performed by the PI. 
The participants will be identified by a unique participant number only. The name and 
any other identifying detail will NOT be included in any study data electronic file.  
The Co-I will keep a list containing all subjects enrolled into the study. This list remains 
with the Co-I and is used for unambiguous identification of each subject. The list 
contains the unique participant number, full name, date informed consent signed, date 
of screening, the unique hospital number (CHI), and the randomisation group code. A 
copy of the participant’s consent and enrolment in the study will be recorded in the 
participant’s medical record. This data will identify the study and document the dates of 
the participant’s participation. 
 
Archiving: 
 
Although not required by law for non-CTIMPs, in line with the principles of ICH GCP 
essential study documents will be retained for up to a minimum of 5 years following the 
completion of the study. Arrangements for confidential destruction will then be made. If 
a participant withdraws consent for their data to be retained, it will be confidentially 
destroyed immediately. No records/study documentation/data may be destroyed 
without first obtaining written permission from the Sponsor. 
Essential documents could include (this list is not exhaustive): 
Signed informed consent documents for all participants. 
Participant identification code list, screening log and enrolment log. 
Record of all communications between the Investigator, the REC and the Sponsor. 
Composition of the REC, and the Sponsor  
List of sub-investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study and their signatures. 
Copies of case report forms and documentation of corrections for all participants. 
All other source documents (subject medical records, hospital records, etc.). 
All other documents as listed in section 8 of the ICH E6 Guideline for Good Clinical 
Practice (Essential Documents for the Conduct of a Clinical Trial). 
Normally, these records will be held in the Investigator's archives. If the Investigator is 
unable to meet this obligation, he or she must ask the Sponsor for permission to make 
alternative arrangements. Details of these arrangements should be documented. 
 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
14. 
FINANCING AND INSURANCE 
The time and cost associated with the study has been agreed in kind by the NHS GGC 
Orthotic Service.  
The PI has been funded for a 12-month Careers Fellowship by NHS Education Scotland, to 
support the PI’s research activities associated with this trial.  
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 NHS Greater Glasgow 
and Clyde Health Board, therefore, cannot agree in advance to pay compensation in these 
circumstances. In exceptional circumstances an ex-gratia payment may be offered.  

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
15. 
PUBLICATION POLICY 
All data and results will remain under the ownership of the research team and NHS GGC 
Orthotic Department. 

Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
16. 
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Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
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of two commonly used outcome measures for foot problems. Journal of foot and ankle 
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Environmental Impact of Additive Manufacturing for Individual Supplies. In Grabchenko’s 
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Cham. 
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Short title: Comparing clinical outcomes using two insole manufacture techniques 
IRAS Project ID: 317502  
Version Number: 2.0 
17. 
APPENDICES 
 
Appendix 1. Foot Health Status Questionnaire (FHSQ)  
Appendix 2. Orthotic and Prosthetic User Survey (OPUS) Satisfaction with device survey  
Appendix 3. Clinical CRF Template 
Appendix 4. Schedule of Procedures: 
Schedule of 
Procedures 
Visits 
First Appointment 
Screening and consent 
Second 
Appointment 
Fitting 
Third 
Appointment 
4-week 
review 
Fourth 
Appointment 
8-week 
review 
Fifth 
Appointment 
12-week 
review 
Informed consent 
x 
 
 
 
 
Demographics 
x 
 
 
 
 
Medical history 
including concurrent 
medications as 
outlined in section 6 
x 
 
 
 
 
Physical Assessment 
x 
 
 
 
 
Scan and cast of feet 
x 
 
 
 
 
Insoles fitted 
 
x 
 
 
 
FHSQ completion 
 
x 
x 
x 
x 
Self-reported diary 
 
 
x 
x 
x 
OPUS completion 
 
 
 
 
x 
Review any relevant 
medication changes 
as outlined in section 
6 
 
x 
x 
x 
 
x