VR as a Distraction Technique for Management of Acute Anxiety and Pain During Outpatient Colposcopy Procedures - a Single Centre Randomised Control Trial
Phase: NA
Conditions: Anxiety, Colposcopy
Sponsor: University of Ulster

COVER PAGE 
 
Mind over Cervix: Using Virtual Reality to reduce 
Colposcopy Anxiety 
VR as a distraction technique for management of 
acute anxiety and pain during outpatient colposcopy 
procedures – a single centre randomised control 
trial 
 
 
 
 
Clincal Trials ID  :  FCNUR-23-098 
 
NCT : Not yet assigned 
 
IRAS ID : 335105 
 
Document date and version : v5 18.04.24 
 
 
 
 
 

 
Mind over Cervix: Using Virtual Reality to reduce Colposcopy Anxiety 
VR as a distraction technique for management of acute anxiety and pain 
during outpatient colposcopy procedures – a single centre randomised control 
trial  
 
Data Category 
Information 
Sources of monetary or material 
support 
Ulster University  
Queen Elizabeth Hospital, Gateshead 
Primary Sponsor 
Ulster University 
Contact for public queries 
Dr Victoria Braden Mb Bao BCh MRCOG 
(Clinical research fellow) 
victoria.braden@nhs.net 
Contact for scientific queries 
Dr Victoria Braden Mb Bao BCh MRCOG 
(Clinical research fellow) 
victoria.braden@nhs.net 
Public title 
Mind over Cervix: Using Virtual Reality to 
reduce Colposcopy Anxiety 
Scientific title 
Virtual Reality as a distraction technique for 
management of acute anxiety and pain during 
outpatient colposcopy procedures – a single 
centre randomised control trial  
 
Countries of recruitment 
England 
Health condition(s) or problem(s) 
studied 
Anxiety, pain reduction, colposcopy  
Intervention 
Virtual reality headsets to reduce anxiety. 
Comparator – standard care in colposcopy  
Key inclusion and exclusion criteria 
Inclusion Criteria (Patients) 
- 
Patients: biological females of >18 
years of age who attend for outpatient 
colposcopy and provide informed 
written consent 
Exclusion criteria (Patients)  
- 
Significant hearing or visual 
impairments that would impair 
communication during the procedure 

- 
Any known characteristics that may 
make the office procedure more 
difficult (>1previous LLETZ, previous 
cervical conisation, uterine didelphis)  
- 
Inability to provide consent. 
- 
Denial or withdrawal of informed oral 
consent 
Inclusion Criteria (Staff)  
− Have completed colposcopy training and 
be a registered member of the British 
Society of Colposcopy and Cervical 
Pathology (BSCCP) 
− Informed written consent to take part in 
the trial.  
Exclusion criteria (Staff)  
− The denial or withdrawal of informed 
consent.  
− Trainee colposcopist performing clinic. 
 
 
 
Study type 
Interventional 
Allocation: randomized 
Intervention model: parallel assignment 
Masking: non blinded 
Primary purpose: anxiety reduction 
Phase I 
Date of first enrolment 
TBC 
Target sample size 
141  
Recruitment status 
Awaiting ethical approval  
Primary outcome(s) 
Reduction in anxiety experienced by biological 
females attending for outpatient colposcopy as 
measured by STAI (state trait anxiety index) 

Key secondary outcomes  
Reduction in pain experienced by biological 
females attending for outpatient colposcopy as 
measured by numerical rating scores (NRS) 
Understanding the acceptability and 
effectiveness in terms of reducing anxiety of VR 
interventions within the procedural groups and 
how these might vary as a function of different 
patient demographics.  
Feasibility and acceptance of intervention from 
clinicians’ perspective 
Does the introduction of VR have an impact on 
patients’ attendance to follow up appointments  
 
 
 
Names protocol contributors 
 
Main Sponsor: University of Ulster 
Funders: N/A 
Study Coordination Centre: Queen Elizabeth Hospital, Queen Elizabeth Avenue, 
Gateshead, NE9 6SX 
 
IRAS 
 
Study Management Group 
 
Chief Investigator: Dr Claire McFeeters  
 
Primary Investigator: Dr Victoria Braden  
 
Study Supervisor: Dr Nithya Ratnavelu  
 
Co-Investigators: Wendy McCormack, Lorraine Pearce,  
 
Statisticians: Dr Hannah Mitchell, Dr Lisa McFetridge (Queens University, Belfast)  
 
  
Study Management: Ulster University  
 
Study Coordination Centre:  Queen Elizabeth Hospital, Gateshead.  
 

Funding: This study is part of a research fellowship. The medical devices company 
Rescape have provided the headsets for use in research free of charge but have had 
no role in the design of the study and will not have a role during its execution, 
analyses, interpretation of data or decision to submit results. It will have no access to 
or ownership over any patient data collected during this study.  
 
 
General and clinical queries, supply of study documents and collection of data 
please contact Dr Victoria Braden (Clinical Research Fellow, Chief Investigator) 
(Victoria.braden@nhs.net) or Ms Nithya Ratnavelu (Consultant Gynaeoncologist, 
Study Supervisor) (Nithya.ratnavelu@nhs.net)  
 
Issue Date: 18.04.24 
Protocol Amendment Number: 05 
Author(s): V.B, C.M, N.R  
 
Abstract 
• 
Background: Colposcopy is an important aspect of biological females's 
health. Due to cervical screening and early treatment of abnormal results with 
colposcopy, the incidence of cervical cancer has greatly reduced. However, 
due to its intimate nature and association with cancer, colposcopy has been 
shown to be a time of very high anxiety for patients. As healthcare gets more 
patient centred it becomes imperative that we try to improve the patient 
experience. Virtual reality (VR) is increasingly used throughout healthcare as 
a method of reducing anxiety and pain for patients. We believe this could be 
of great benefit to patients attending for outpatient colposcopy as a form of 
non-pharmacological digital distraction.  
• 
Methods: We will perform a single centre, non-blinded, parallel, randomised 
control trial to measure the reduction in state trait anxiety (STAI) scores and 
numerical rating scores (NRS) for pain in participants allocated to the 
intervention arm (addition of VR headsets during their colposcopy 
appointment) compared to the control arm (standard colposcopy care). All 
biological females attending Queen Elizabeth Hospital, Gateshead, for their 
colposcopy appointment will be offered enrolment to the trial dependant on 
inclusion/exclusion criteria.  
• 
Discussion: We believe the addition of the VR headsets will have a 
significant impact in reducing patients's anxiety and pain and improving their 
overall satisfaction scores. This has potential to translate to other outpatient 
procedures within the hospital.  
• 
Trial registration:  
Keywords 

Colposcopy 
Cervical Screening 
Virtual Reality 
Anxiety reduction 
Pain reduction 
 
 
Introduction 
Background and rationale  
 
Colposcopy 
 
There are approximately 3200 new cases of cervical cancer diagnosed annually in 
the UK, with around 690 biological females dying from the disease. However, 99.8% 
of these cases are preventable. The numbers of cancer are consistently dropping, 
largely due to the advances in cervical screening and colposcopy, however 
screening attendance is at a 20 year low with one in four people with a cervix not 
participating. (1) More than 95% of cervical cancers are due to the human papilloma 
virus (HPV), particularly type 16 and 18. HPV is a common viral infection of the 
reproductive tract that most sexually active men and women will be infected by at 
some point of their lives. 90% of people will clear the infection themselves without 
any symptoms or treatment required, however HPV infection is a well-known risk 
factor for many types of cancer. If HPV does infect cervical epithelial cells, it changes 
the way cells interact with one another, causing the infected cells to multiply in an 
uncontrolled manner. (2) These can form the precancerous cells known as cervical 
intra-epithelial neoplasia (CIN). These changes, especially in young biological 
females, often revert to normal cells due to an appropriate immune response and the 
rapid proliferation of cells of the cervix. 60% of CIN-1 will regress to normal after 1 
year. People with CIN-2 and CIN-3 are at higher risk for developing cervical cancer 
and so should receive treatment. Regular cervical smears enable early detection of 
cervical changes to CIN cascade and prompt referral to colposcopy for further 
investigation. (2,3) 
 

 
 
 
Colposcopy is the process of visualizing the cervix, specifically the transformation 
zone, using a binocular microscope called a colposcope. The transformation zone is 
where the ectocervical columnar cells are continuously converting into squamous 
cells in the endocervix. This is the most common site for cervical cancer to arise.  
235,223 biological females are year are referred to colposcopy following an 
abnormal smear. (1) After inserting a speculum, acetic acid or schillers iodine is 
applied to the cervix by the clinician. Normal cervical tissue appears pale after 
application of acetic acid, while areas of abnormal tissue, such as those with 
dysplasia or precancerous changes, turn white due to increased protein coagulation 
- known as the "acetowhite" effect. Iodine works by staining glycogen-rich cells 
brown, which helps in differentiating between normal and abnormal tissue. 
Normal cervical squamous epithelium is rich in glycogen and stains dark brown, 
while areas lacking glycogen, such as those with dysplasia or abnormal changes, 
remain unstained. If these show concerns about the cells in the cervix, they can 
either be biopsied if unsure of the diagnosis or treated in the form of a large loop 
excision of the transformation zone (LLETZ).  A LLETZ is when the colposcopist 
uses a thin looped wire with electrical current passing through it is used to take a 
biopsy of the cervix, including the transformation zone. This can be painful for 
patients, so local anesthetic is used to provide some pain relief. The cervix is 
innervated with parasympathetic nerve fibers from S2-S4 which travel through the 
broad ligament to enter the cervix at 3o’clock and 9 o’clock. This is where the 
clinician will inject local anesthetic to minimize pain for the patient. Despite the use of 
local anesthetic, there can still be an element of discomfort for the patients. (4) The 
specimen is then sent to the histopathology lab for examination to investigate the 
extent of any abnormalities. The aim is that any precancerous changes are excised 

with clear margins. Various outcomes from the examination and procedure can 
mean many patients are invited to reattend for a further colposcopy in a few weeks 
or months – such as follow up following a biopsy, unclear margins, mismatch 
between clinical findings and histopathological findings or the specimen being 
upgraded to a cancer. (5) Hence, colposcopy is often not a one stop clinic for service 
users so anxiety may be increasingly heightened as time progresses.  
 
Despite colposcopy having undeniable significance in biological female’s healthcare, 
the entire process is associated with high levels of stress and anxiety for patients.  
Colposcopy is a unique circumstance due to the intimate nature of the examination 
and the association with cancer. It is associated with fear, stress and loss of control. 
Many studies show that patients experience a “very high” level of anxiety when 
attending for colposcopy. (6) In comparison to other medical procedures, biological 
female patients experience a higher level of anxiety when attending colposcopy than 
when they are attending for cardiac surgery. (6,7) Anxiety can negatively impact a 
person’s cognitive abilities and decreases the ability to recall and act on advice, 
leading to patients being less likely to comply with any information given. (8) Higher 
pre-procedural anxiety is predictive of post operative pain reported by patients in 
gynecological settings. Thus, by addressing these feelings, clinicians can reduce 
pain perception, however reducing this during a procedure without pharmacological 
agents remains a difficult task. (9) 
Research has shown that heightened anxiety and pain during colposcopy can also 
negatively impact patients willingness to comply with recommended follow up 
appointments and screening procedures. (10) Although the absolute value varies 
widely from region to region, it shown that people with a cervix who do not attend for 
regular cervical screening have a higher risk of developing cervical cancer compared 
to people who do not attend for screening. (11) Additionally, the discomfort 
associated with the procedure can lead to increased muscle tension and resistance, 
activating the cycle of pain, and potentially affecting the accuracy and ability to 
complete the investigation. (12) If an examination or treatment is unable to be 
completed, these patients are often added to a theatre list for a general anesthetic to 
allow the clinician the ability to complete the process. Although this will always be a 
necessity for some patients, it puts them at risk of a general anesthetic, as well as 
taking valuable theatre time that could be used for other cases, so it is preferable to 
do as many patients as possible in the outpatient setting 
As healthcare is becoming more holistic and patient centered, it is imperative that we 
aim to create as positive an experience as possible for both patients and healthcare 
providers.  
 
Virtual Reality 
 
A 2007 Cochrane review looked at the various randomized controlled trials that 
investigated ways to reduce anxiety levels during colposcopy. (13) Of the 

randomized controlled trials included, playing music or video colposcopy as 
distraction techniques appeared to have good effect. (13,14) 
Advanced technologies are increasingly being used throughout health care to 
alleviate the feelings of anxiety and stress felt by many patients. Virtual Reality (VR) 
is an immersive technology that transports users to computer generated 
environments. It is increasingly being used as an alternative form of analgesia in 
medical procedures as well as being effective in managing phobias, PTSD and other 
behavioral healthcare. (15 – 18) It works by combining clinical hypnotherapy and 
integrative therapeutic techniques, delivered via a virtual reality headset with 
accompanied sound modules to distract patients. By providing a controlled and 
engaging sensory experience, it diverts patients’ attention aware from the procedure 
itself, reducing anticipatory anxiety and enhancing overall relaxation. (15, 19, 25) 
 
There are multifaceted benefits from using VR as a form of digital distraction. Firstly, 
it is nonpharmacological. This circumvents potential side effects associated with 
sedatives or anxiolytic medications. (20) Secondly, its versatility allows tailoring of 
experiences to individual preferences, accommodating various ages groups and 
clinical scenarios. Moreover, the interactive and customisable nature of VR allows 
healthcare workers to engage patients in the decision-making process, fostering a 
collaborative approach. (21)  Ambulatory procedures should use multimodal forms of 
pain relief including pharmacological as well as non-pharmacological. By giving the 
patient options, this will increase the number of successful procedures. (22) 
 
A 2023 systematic review looking at the use of VR in pain management shows it as 
a feasible option, with a reduction in pain perceived and anxiety levels in surgical 
patients. (23) Other recent studies in gynecological outpatient settings such as 
brachytherapy rod removal have shown it to be an effective adjunct to improve pain 
and anxiety score with a similar efficacy to nitrous oxide. (20) Moreover, it has also 
been shown to increase emotional detachment from the procedure in patients, aiding 
relaxation, reducing unnecessary movement and allowing the healthcare 
professionals to focus on the treatment. (24) This dual effect should both increase 
clinic efficiency as well as decrease the frequency of procedure abandonment.  
The use of virtual reality during colposcopy procedures has not yet been published, 
therefore, it is important to establish if this improves patient anxiety, pain and overall 
satisfaction.   
 
Patient and Public Involvement 
 
A scoping exercise was carried out in the outpatient colposcopy clinic prior to 
initiation of the intervention to assess the people attending attitudes in relation to 
colposcopy and the introduction of VR headsets. Biological females attending clinic 
were interviewed by the lead researcher and given questionnaires to assess their 
attitudes to colposcopy and acceptability of using the headset. Most participants 
reported feeling “nervous” and “jittery” as “very much so,” on the modified STAI 

score. 87% of participants interviewed (N=15) stated they would be accepting to use 
the VR headset during their consultation and thought it would be of benefit.  
Biological females attending colposcopy will be invited to take part a focus group to 
review our patient information leaflets, questionnaires and consent forms to ensure 
they are easily understandable by service users. We will use the focus groups to 
ensure the study runs in a way that the local patient population feel is beneficial to 
them.   
The study has been presented at the regional colposcopy business meeting with a 
very strong consensus from clinical staff that this will be a worthwhile study to 
perform for patients attending colposcopy.  
The research proposal was presented to the colposcopy staff at the monthly 
business meeting and to the gynaecological oncology team at an inaugurate annual 
research meeting. The proposal was met with enthusiasm from the team and 
everyone presented to was willing to take part. Feedback regarding logistics was 
given and incorporated into the proposal.   
The study is aligned to current government aims of transforming the NHS for the 
future. We are living in an increasingly digitalised environment and further research 
and investment is needed in these advancing technologies. Use of VR is highly 
transferrable into other outpatient procedural settings which could improve patient 
experience globally. NICE guidance in 2018 has recommended that further studies 
be performed to investigate methods to reduce anxiety in biological females 
undergoing colposcopy in order to improve patient experience and reduce the 
number of patients lost to follow up.  
 
Aim 
The aim of this study is to assess the effectiveness of utilising Virtual Reality 
technology as a non-pharmacological intervention to alleviate anxiety, reduce pain 
perception, and enhance overall satisfaction for people with a cervix undergoing 
colposcopy procedures. 
 
Nul hypothesis  
The addition of virtual reality headsets to outpatient colposcopy as a form of digital 
digital has no effect on biological females measured anxiety or pain scores.  
 
Objectives 
Primary objective 
- 
To determine if the addition of virtual reality headsets during outpatient 
colposcopy appointments has an impact on patients’ anxiety perception 
compared to standard management.  
 
Secondary objectives 
- 
To determine if the addition of virtual reality headsets during outpatient 
colposcopy appointments has an impact on patients’ pain perception 
compared to standard management 

- 
Understanding the acceptability and effectiveness regarding anxiety 
reduction of VR interventions within the procedural groups and how these 
might vary as a function of different patient demographics.  
- 
Feasibility and acceptance of intervention from clinicians’ perspective 
- 
To investigate if the introduction of VR have an impact on patients’ 
attendance to follow up appointments  
 
 
Study Design 
 
Trial design  
The “Mind over Cervix” trial is designed as a single centre, prospective, non-blinded, 
randomised control trial with two parallel groups to determine the superiority of VR 
headsets in patients’ anxiety reduction and pain reduction during outpatient 
colposcopy compared to standard care. 
 
Study setting  
The study will be carried out in the colposcopy outpatient clinic in Queen Elizabeth 
Hospital (QEH), Gateshead, Gateshead Health Trust.  
QEH is a large tertiary referral centre for gynaeoncology and colposcopy in the 
north-east of England. Over 1700 patients attend the department for colposcopy 
annually. (24) Colposcopy is provided by consultant gynaeoncologists, consultant 
gynaecologists and nurse colposcopists.  
 
Withdrawal Criteria  
Patients can withdraw from the study at any time and without giving a reason. 
Deciding to withdraw or not take partake in the study will not have any effect on the 
standard of care they receive. In addition, any staff member may withdraw their 
consent at any time without giving a reason.  
 
Recruitment  
Queen Elizabeth Hospital in Gateshead is a large tertiary referral centre for 
Gynaeoncology and colposcopy in the northeast of England. Over 1700 patients 
attend the department for colposcopy annually. (24) 
Following prospective ethical and trust approval via IRAS, all patients who attend for 
outpatient colposcopy will be informed of the study prior to their arrival to the 
department. They will be sent a patient invitation leaflet (Appendix 1) to their home 
through the post 2-4 weeks prior to their appointment to inform them of the study and 
the fact they may be approached. On arrival to the department, a poster will be 
displayed in the department to remind attendees of the study and the potential for 
their participation (Appendix 1a). They will be given information again via the PIL 
(Appendix 1b) which will be provided by the clerical staff when they attend reception 
to check in for their appointment.  

A member of the research team comprising of the PI (V.B) and other research and 
colposcopy staff (L.P) will approach the patients once they have arrived at their 
colposcopy appointment. Patients will be asked if they have had a chance to read 
the PIL, explain the process further and if they have any initial questions.  Each 
patient will then be asked if they would be interested in taking part in the study. If the 
service user declines, colposcopy care will proceed as normal. If the patient agrees 
to take part, they will be taken to a free clinic room to allow the consent process to 
be completed confidentially. (Appendix 2a) The right of the patient to withdraw 
consent at any time without reason will be respected. Following consent, the form 
will be copied in triplicate with one copy added to the clinical research file, one to the 
patients’ notes and one to the patient. The patients’ colposcopist will be notified of 
the involvement in the study. Patients will be identified by their unique study number 
only. Number of cases which declined and number not suitable for inclusion will be 
noted prospectively and anonymously in a screening log of patient age and ethnicity. 
 Previous PPI work performed in the department indicated that the majority (87%, 
n=15) patients approached would be accepting to take part in the study. Virtual 
reality has been studied extensively in clinical trials with high uptakes in patient 
populations reported. (6,15,17,18,19,20) 
All colposcopy staff who work in the clinic will be invited to take part in the study. The 
trial has already been presented and proposed to the team at a unit monthly 
business meeting. It was met with enthusiasm and all trained colposcopists present 
where agreeable to participation. They will be enrolled by a staff participant 
information leaflet (Appendix 1c) and consented by a member of the research team 
(Appendix 2b) 
 
Eligibility criteria  
Inclusion Criteria (Patients) 
- 
Patients: biological females of over 18 years of age who attend for 
outpatient colposcopy  
- 
Be able to complete informed consent.  
Exclusion criteria (Patients) 
- 
Significant hearing or visual impairments that would interfere with 
communication during the procedure. 
- 
Any known characteristics that may make the office procedure more 
difficult (>1previous LLETZ, previous cervical conisation, uterine didelphis)  
- 
Inability to provide consent. 
- 
Denial or withdrawal of informed oral consent 
- 
There are no addition exclusion criteria as per the manufacturers 
instructions  
 
Inclusion Criteria (Staff) 
- 
Have completed colposcopy training and be a registered member of the 
British Society of Colposcopy and Cervical Pathology (BSCCP) 
- 
Have completed informed consent. 

Exclusion Criteria (Staff) 
- 
The denial or withdrawal of informed consent.  
- 
Trainee colposcopist performing clinic. 
 
 
 
Interventions 
 
 
Explanation for the choice of comparators  
Biological females are offered a colposcopy appointment depending on the results of 
their routine cervical screening. Screening occurs every 3 years from age 25 until 49, 
and then 5 yearly from age 50 to 64. Cervical screening looks for HPV initially, and if 
this is found then cytology is performed on the specimen. If abnormal cells are found, 
patients are referred to colposcopy for further investigation. Here, the cervix is 
examined in great detail for any concerning changes. If there are areas of concern, it 
may require a LLETZ treatment to remove part of the cervix to prevent it from 
developing into cancer.  
Despite the undeniable importance of colposcopy in women’s’ health, it is known to 
be a time of very high anxiety. In line with NHS values, we need to try to improve 
patients experience of colposcopy and try novel methods of reducing their anxiety. 
VR has been shown to be an effective and safe intervention in other outpatient 
procedures to reduce anxiety, it has not yet been investigated during outpatient 
colposcopy procedures. (15,18,19,20) 
 
  
Intervention description  
Once consented and enrolled in the trial, participants will then be asked to complete 
the study questionnaire (Appendix 4) which will be a paper-based format. This will 
allow measurement of baseline and state anxiety and anticipated pain. We will 
collect this data prior to randomisation of the participant into either arm of the trial. 
Patients will then be randomly allocated to either the VR intervention arm or the 
standard procedure arm. The clinician taking consent will ask the service to choose 
from two opaque, blank envelopes that will contain inside if they are to be enrolled in 
the intervention or control arm. The envelopes will be blinded to both the clinician 
and the patient prior to selection.  
 
The patient will be brought into the colposcopy consultation room, where the clinic 
will proceed as normal. The doctor/nurse providing the treatment will explain the 
process of colposcopy to the patient so that they know what to expect from the 
procedure as per standard practice. This involves undressing, sitting on the 
colposcopy couch, insertion of a speculum, application of acetic acid/iodine, 
inspection of the cervix using a colposcopy and treatment or biopsy if indicated.  

Once the patient has been informed about both the colposcopy procedure and the 
VR intervention, they will be invited to prepare for their examination. There is always 
one assistant present in the room during any routine colposcopy appointment. The 
main role of the assistant is to provide support to the patient. If in the intervention 
arm, once the patient is prepared and seated in the colposcopy chair, the assistant 
will place the VR headset on the patient and begin the immersive therapy. The 
participant will be shown an immersive video specifically designed by Rescape 
Innovation Ltd, Cardiff, UK to reduce anxiety that will encourage them to focus on 
their breathing throughout.  Rescape have been delivering VR therapies for over 3 
years. DR.VR™ a pain and anxiety product, has been licensed and deployed into 
over 100 healthcare environments across the UK. The device and software are CE 
marked and is a class one medical device with content informed by cognitive 
behavioural therapy and dialectical behavioural therapy. The system which consists 
of a headset, earphones and tablet smart device is designed to work from its 
container without the need for local internet connection. It has a rigorous 
decontamination protocol between patients.  DR.VR™ has been used successfully in 
the NHS in a range of specialisms such as A&E (32), phlebotomy (33), burns (34), 
and paediatrics (33).  
A routine colposcopy appointment will normally take on average 5 minutes, or 
if treatment is being performed may take 10-15minutes. The VR videos developed by 
Rescape last approximately 7 minutes each. There are 3 videos available that we 
can play back-to-back to ensure immersion in the VR intervention with no break. The 
videos have been specifically chosen to aid feelings of relaxation and include, 
walking through a forest while David Attenborough narrates and an under the sea 
diving experience through a shipwreck. Participants will still be able to hear the 
clinician throughout the colposcopy to allow them to stay informed of any procedural 
elements taking place. No other aspects of the participants care in colposcopy will be 
changed apart from the addition of the headset. All other forms of pain relief will be 
provided as required in normal colposcopy. This includes local anaesthetic to provide 
a cervical block and nitrous oxide for inhalation. The participant will be free at her 
own will to remove the headset at any stage, and this will be recorded as part of the 
assessment.  
Once the colposcopy treatment is complete the participant will be assisted to remove 
the headset and informed the results of the colposcopy the routine manner. 
Participants who are part of the control arm of the study will have colposcopy 
performed as per standard practice with no VR headset application at the time.  
 
Following the completion of the colposcopy, participants will then be asked by the 
research team to complete another short paper questionnaire (Appendix 5) to 
quantify their perceived pain and actual anxiety score during the procedure. This will 
be kept anonymised and blinded from the clinician who has carried out consultation.  
 
Participants who were allocated to be in the control arm of the study will be offered 
the opportunity to trial a headset following completion of their enrolment in the study.  

 
Following completion of patient interaction, the clinician who has carried out the 
procedure will be asked to fill out a paper questionnaire (Appendix 6) provided by the 
PI/CRN regarding the ease and timing of the procedure, and if any difficulties were 
encountered with the equipment or communication with the patient.  
 
Staff Training 
 
All clinicians and clinic staff who will be involved in application of the headset to 
participants have had training from Rescape or PI on how to use to the system. The 
training video is available to all staff if they feel they need to renew their training. The 
training log has been recorded and will be added to the standard operating 
procedure file. (SOP). 
 
 
Criteria for discontinuing or modifying allocated interventions  
 
Participants are free to remove the VR headset at any point in the intervention. They 
will be informed of this prior to its application. Participants will be free withdraw 
consent and leave the trial at any point during the process. They do not have to give 
prior warning or any explanation. This will not change the clinical procedure being 
conducted. If participant becomes upset or display signs of anxiety during the 
procedure the distress protocol will be followed (Appendix 3)  
There is a risk of cybersickness during the application of the headset. Patients will be 
informed of this during the consent process and informed to remove the headset 
should this occur. This is included in the distress protocol and the deviation log 
(Appendix 7).  
 
Strategies to improve adherence to interventions  
 
Potential participants will be shown photographs of the VR headset prior to 
enrolment in the trial via the PIL provided to ensure understanding of its involvement. 
If they are in the VR intervention arm, they will be given the opportunity to see the 
VR device prior to beginning the therapy. They will be given the opportunity to try the 
headset on prior to beginning the colposcopy consultation to ensure they are 
amenable to having it placed prior to the procedure.  
  
Relevant concomitant care permitted or prohibited during the trial  
Some patients attending colposcopy will only have an inspection performed of the 
cervix, other patients will have a biopsy or a LLETZ procedure performed. If a biopsy 
or LLETZ procedure is performed, the entire colposcopy experience will take longer 
and may be more painful than if only inspection is performed. If a patient needs a 
biopsy or LLETZ performed, this will not be known until the colposcopy inspection 

has taken place, so it is not possible to stratify the study group arms prior to 
enrolment in the trial.   
  
Provisions for post-trial care Patients that are enrolled into the study are covered 
by indemnity for negligent harm through the standard NHS Indemnity arrangements 
from Gateshead health trust.  Following the procedure participants will be offered the 
opportunity to ask the team any questions. They will be provided with contact details 
for the study team if they have any concerns when they have left following the 
procedure.  
Additional patient follow up will not routinely be performed as part of the study. Any 
follow up will be as per standard colposcopy practice.  
 
Outcomes  
 
Primary outcome 
 
- 
To determine any change in anxiety experienced by people with a cervix 
attending for outpatient colposcopy as measured by STAI (state trait 
anxiety index) in both the intervention arm and the control arm. Pre 
procedure paper questionnaires will be conducted to establish a baseline 
anxiety measure for patients. The comparison will be performed from the 
post procedure paper questionnaires from both arms of the study.  
 
Secondary outcomes 
- 
To determine any change in pain experience by people with a cervix 
attending for outpatient colposcopy as measured by a numerical rating 
scale (NRS) in both the intervention arm and control arm via paper 
questionnaires. 
- 
Understanding the acceptability and effectiveness of VR interventions 
within the procedural groups and how these might vary as a function of 
different patient demographics.  
- 
Feasibility and acceptance of intervention from clinicians' perspective 
- 
Does the introduction of VR have an impact on patients' attendance to 
follow up appointments?  
 
Participant timeline  

 
Sample size 
The sample size calculation was run using the packages pwr and pwrss within R. For 
the calculation the significance level of 0.05 and power of 0.8 where used along with 
a Cohen’s d of 0.5. Two different types of outcome variables will be used so the 
calculations used are based on ANCOVA (continuous) and the Mann-Whitney test 
(ordinal). Both results suggest a sample size of 64 participants in each group (128 in 
total) We have added on a 10% drop out rate which brings the total sample size to 
141.   
Assignment of interventions 
Sequence generation and concealment mechanism 
Patients invitation letter and 
PIL to study sent with 
colposcopy appointment letter 
to inform of study
Colposcopy arrival
- further patient information 
leaflet
Approached by research team 
-meets inclusion criteria
- consent for study
-allocation of unique study number
Pre procedural questionaire
Random allocation to VR 
intervention or control arm
Confirm willingness to proceed 
VR control  arm
Patient post procedure 
questionaire
Clinicians  questionnaire
Standard practice no 
intervention arm 
Patient Post procedure 
questionaire
Exclusion criteria
Hearing or visual impairments 
Any known characteristics that may make 
the office procedure more difficult 
(>1previous LLETZ, previous cervical 
conisation, uterine didelphis) 
Inability to provide consent
Denial or withdrawl of informed oral 
consent
Staff : the denial or withdrawl of informed 
consent. Trainee colposcopists. 

Participants will be randomly assigned to either control or VR intervention group by 
patient selection of a choice of two opaque envelopes. One envelope will instruct 
participant to be part of the control arm, one envelope will instruct the participant to 
be part of the intervention arm. The envelopes will be blinded to the researcher who 
provides the envelopes for the patient to choose.  
  
Concealment mechanism Potential patients will be invited to take part in the trial 
prior to knowledge of what arm they will be involved in. They will be asked to 
complete the initial questionnaire to get a baseline STAI score before randomisation. 
They will be randomly allocated by patient choice of an opaque sealed envelope that 
will contain if they are to join the intervention or control arm. These envelopes will be 
blinded to the research team until after the patient selection.  
  
Implementation All patients who consent for participation and meet the inclusion 
criteria will be randomized. Randomization will occur following the consent process 
and initial questionnaire. A member of the research team will be responsible for 
providing the sealed opaque envelopes for randomisation. Sealed identical opaque 
envelopes will be made ahead of time by the research team on a 1:1 ratio.  
Assignment of interventions: Blinding 
Who will be blinded?  
Due to the nature of the intervention, the study team felt it is not possible to blind 
participants or assessors once the study arm has been allocated. Participant 
questionnaire results will be concealed from the assessor at point of contact.  
  
Data collection and management 
Plans for assessment and collection of outcomes  
Primary outcome  
 
Anxiety reduction: Anxiety will be measured using the state trait anxiety index (STAI) 
STAI was chosen as it is a well-known measure of trait and state anxiety. It is 
considered the “gold standard” of measuring preoperative anxiety and its reliability 
and validity have been well reported in literature. (33,34) State items include “I feel 
upset,” “I feel frightened, “I feel nervous,” “I am jittery” and I feel confused.” Patients 
respond with a numerical value of 1 to 4 with 1 meaning “not at all” and 4 meaning 
“very much so”. (27,28)  
Participants will complete a questionnaire (Appendix 6a) with STAI questions prior to 
randomisation to get a baseline anxiety level. This will be compared to the post 
procedural questionnaire (Appendix 6b) with the same questions to compare the 
actual anxiety levels during the procedure. Comparison will be made between the 
two arms.  
 

 
Secondary Outcome  
 
Pain reduction: Pain scores will be measured by a Numeric Rating Scale (NRS) from 
0 through to 10. 0 represents “no pain” and 10 represents “worst pain imaginable”. 
This will be shown alongside a visual analogue scale (VAS) of pain on animated 
faces. This is a validated measure for pain, is easy to use, has high compliance rates 
and detects meaningful change.  (29,30,31) Participants will be asked to state the 
“maximum pain felt, if only for one moment,” and also state the “average pain 
experienced,” throughout the procedure. Respondents will select the single number 
that best represents their pain intensity. Results from participants in the intervention 
arm will be compared to participants in the control arm.  
 
Understanding the acceptability and effectiveness of VR in variations of patient 
demographics: Participants will be asked to state the following demographics – age, 
ethnicity, parity, menopausal status, previous attendances to colposcopy and 
previous treatments in colposcopy. Acceptability will be monitored by participants 
ongoing consent of using the VR headset. If a patient removes the headset before 
the colposcopy assessment is completed, this will be noted in the post procedural 
questionnaire and be noted that the patient did not find it acceptable. The 
demographics of this patient cohort will be reviewed to see how VR effects different 
patient demographics.  
Feasibility and acceptance of intervention from clinicians’ perspective: Following 
completion of the colposcopy assessment, the clinician will be asked to complete a 
short survey of their experience using VR. (Appendix 6c) These will be questions on 
a Likert scale from “strongly disagree” to “strongly agree”. Clinicians will be asked did 
they find it easy to use the VR in their clinic, did they find it beneficial to the 
consultation, did they find it easy to communicate with the patient during the 
consultation.  
Does the introduction of VR have an impact on patients attendance to follow up 
appointments: Following completion of the trial intervention period, a retrospective 
analysis of patients who are enrolled in the trial and require a further attendance, 
adherence to their follow-up appointments will be monitored. This will be completed 
using the department’s electronic booking system to monitor attendance. This will be 
compared to the department’s previous 6-month non-attendance. Data will be 
compared to see if enrolment on the trial and the addition of VR had any benefit in 
patient compliance to follow-up.  
 
Plans to promote participant retention and complete follow-up  

Participants are free to withdraw from the trial at any stage without explanation. This 
will be explained to them. 
As participation in the trial is a relatively short amount of time, lasting only as long as 
their clinic appointment, we do not anticipate retention and follow-up being a 
significant factor in our study. 
 
Data management  
Research team members CMcF, NR, WM and LP have longstanding experience with 
data collection and storage. All study records and the Investigator Site File will be 
kept at site in a locked filing cabinet with restricted access.   The Trial Master File will 
be held at Queen Elizabeth Hospital, Gateshead NHS trust in a locked filing cabinet 
with restricted access. 
Data linkage will require use of NHS number which will be done securely with the IT 
network of Gateshead NHS Trust by a researcher with an NHS contract. The 
identifiable data will be stored with access restricted to the research team and will be 
protected by passwords. Computers will be protected by passwords and stored 
securely. The research team will follow guidance to ensure that personal data cannot 
be seen on screens or any other media by those outside the research team. 
Documentation including personal data will be minimal and if possible avoided and 
will be stored in locked cabinets in locked offices and destroyed in line with 
confidentiality requirements of the Trust as soon as it is no longer needed. 
A pseudo-anonymised database will be prepared for analysis within the Trust for 
transfer for analysis at Queens University Belfast. The data for use outside the NHS 
will be prepared in a manner that will not allow the potential identification of 
individuals by combinations of data, for example, by using appropriate and ethnic 
group grouping that do not risk identification of individuals and anonymising all but 
the highest-level geographical data. Team members carrying out test accuracy and 
analysis will have no access to personal identifiable data. 
Data generated from the research project will be stored for 10 years on NHS and/or 
University computers in an anonymised manner and after any patient identifiable 
information is removed. Access to these computers will be password protected and 
only by members of the research team.  
 
Confidentiality  
Confidentiality will be maintained at all times and be under the supervision of the 
primary investigator (VB). Members of the local site research team will have NHS 

contracts with the obligation to follow all relevant NHS codes of practice and 
guidance. They will maintain required relevant training including NHS information 
governance, data security and GCP.   
All participants will allocated a number from 1-141 on their enrolment into the trial. 
The PI will have a separate data log to enable correlation between clinical data and 
study data. No other members of the team will have access to it and it will be stored 
on a password protected trust computer.  
Questionnaires collected for analysis will be anonymous and results will be added to 
a password encrypted Excel, retaining the anonymity of the patients. This 
anonymous data will be sent via a secure link to the statisticians for analysis. No 
identifiable patient information will leave the hospital trust information system.  
  
 
Statistical methods 
Demographic characteristics will be explored for missing data and distribution 
abnormalities. Means and standard deviations will be used to characterise the 
sample. Analysis of covariance (ANCOVA) and non-parametric tests (Mann – 
Whitney) will be used to determine whether the VR intervention lead to a significant 
difference between baseline and follow up anxiety between control VR and control 
arm. Descriptive statistics (i.e. age, gender, ethnicity, previous attendance to 
colposcopy, menopausal status and parity) for the baseline values will be presented 
within each randomized controlled arm. P values will be used to estimate statistical 
significance for all analysis. 
 
End of Study Definition  
The end of study will be upon completion of the final visit of the last 
participant/volunteer enrolled in the trial.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Project Management Plan  
  
PROJECT MANAGEMENT PLAN (with project milestones) 
      
Action 
Timescal
e 
Responsibility 
Indicator / Outcome / 
Evidence 
  
Develop protocol Aug 23- 
Dec 23 
Fellow and 
Supervisors 
Creation of protocol to 
ensure robust methodology 
and outcome measures 
Scoping 
exercise 
amongst service 
users 
Oct 23- 
Dec 23 
Fellow 
Ensure in keeping with 
service users focus 
Train staff on VR 
equipment 
Oct 23 - 
ongoing 
Fellow, 
Rescape 
Train staff alongside 
Rescape to use equipment 
Recruitment PPI 
work for patient 
information 
leaflets, 
questionnaires 
Oct 23 - 
ongoing 
Fellow, 
Research 
nurses 
Approaching service users 
for feedback to ensure 
legibility 
Begin 
recruitment of 
service users 
March 24 
– August 
24 
Fellow, 
Research 
nurses 
Consenting and awareness 
Begin trial and 
data collection  
March 24 
– August 
24 
Fellow, 
Research 
team, 
supervisors 
Comparison of VR to 
standard care 
Completion of 
data collection 
and writing up  
Aug 24 – 
Dec 24 
Fellow, 
Supervisors  
Writing up analysis   
Dissemination of 
information  
Jan 25 – 
Aug 25 
Fellow, 
supervisors 
Conference presentations, 
publications 
 
Oversight and monitoring 
Composition of the coordinating centre   
 
Dr Victoria Braden (Principal investigator) Clinical Research Fellow 
Gynaecological Oncology  
- 
Design and conduct of “Mind over Cervix”.  
- 
Preparation of protocol and revisions  
- 
Chair of steering group 

- 
Overall responsibility for study milestones 
- 
Preparation of case report forms (CRFs) 
- 
Managing, monitoring and ensuring integrity of collaborative relationships 
- 
Direct and oversee day to day practicalities of study. 
- 
Consent patients for participation in trial 
- 
Intellectual contribution to preparation of reports, presentations and 
publications 
 
Ms Claire McFeeters (Chief Investigator)  
- 
Co – applicant 
- 
Expert in clinical trial research and virtual reality headsets  
- 
Advisor on preparation of protocol and revisions  
- 
Member of project management group 
- 
Intellectual contribution to preparation of reports, presentations and 
publications 
 
 
Ms Nithya Ratnavelu (Study Supervisor) Consultant Gynaecological 
Oncologist 
- 
Co – applicant 
- 
Member of project management group 
- 
Advisor on preparation of protocol and revisions  
- 
Intellectual contribution to preparation of reports, presentations and 
publications 
 
Ms Lorraine Pearce Clinical Research Nurse Gynaecological Oncology 
- 
Extensive experience in daily management of clinical trials 
- 
Recruitment and consent of patients 
- 
Distribution of patient information leaflets  
- 
Data collection and storage 
 
Ms Wendy McCormick Research Data Co-ordinator Gynaecological Oncology 
- 
Extensive experience in daily management of clinical trials 
- 
Recruitment and consent of patients 
- 
Distribution of patient information leaflets  
- 
Data collection and storage 
 
  
Dr Hannah Mitchell Statistician Member of project management group 
- 
Sample size calculation and analysis of data 
- 
Contribution to interpretation of results 
- 
Intellectual contribution to preparation of reports, presentations and 
publications 
 

 
Dr Lisa McFetridge Statistician 
- 
Member of project management group 
- 
Sample size calculation and analysis of data 
- 
Contribution to interpretation of results 
- 
Intellectual contribution to preparation of reports, presentations and 
publications 
 
 
Adverse event reporting and harms  
Definitions  
 
Adverse Event (AE): any untoward medical occurrence in a patient of clinical study 
subject 
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or 
effect that 
- 
Results in death 
- 
Is life threatening 
- 
Requires hospitalisation or prolongation of existing inpatients 
hospitalisation 
- 
Results in persistent or significant disability or incapacity 
- 
Is a congenital anomaly or birth defect 
 
Medical judgement may be exercised in deciding with an AE is serious in other 
situations. E.g., Patient distress, injury. 
 
All adverse events will be reported. Depending on the nature of the adverse event 
the reporting procedures below will be followed. Any questions concerning adverse 
event reporting will be directed to the Primary Investigator (VB) in the first instance.  
All SAEs will then be reported to Claire McFeeters (CI)where in the opinion of the 
Chief Investigator, the event was:  
• 
‘related’, i.e., resulted from the administration of any of the research 
procedures; and  
• 
‘unexpected’, i.e., an event that is not listed in the protocol as an expected 
occurrence  
Reports of related and unexpected SAEs should be submitted within 15 days of the 
Chief Investigator becoming aware of the event, using the NRES SAE form for non- 
IMP studies. The Chief Investigator must also notify the Sponsor of all SAEs.  
Local investigators will report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office.  

 
Plans for communicating important protocol amendments to relevant parties 
(e.g., trial participants, ethical committees)  
Any modifications to the protocol which may impact on the conduct of the study, 
potential benefit of the patient or may affect patient safety, including changes of 
study objectives, study design, patient population, sample sizes, study procedures, 
or significant administrative aspects will require a formal amendment to the protocol. 
Such amendments will be agreed by the steering group and be approved by the 
ethics committee. All changes will be disseminated to the necessary clinicians via 
the research team and emails. Patients will be informed of any chances upon their 
arrival.  
 
 
Dissemination plans  
We would intend to publish our research protocol and then subsequent findings will 
be disseminated by publication in a high impact peer reviewed scientific journal of a 
gynaecological nature. E.g., British Journal of Obstetrics and Gynaecology (BJOG). 
Our objective is to complete a high quality randomised controlled trial that will be 
informative to various healthcare professionals – primarily gynaecologists and nurse 
colposcopists. We believe that this has the potential to change and develop future 
guidelines for other areas of medicine that frequently use outpatient procedures, 
such as colonoscopy, ENT, tissue viability nurses.  
Results will also be disseminated via national and international presentations (e.g. 
British Gynaecological Cancer Society, for which Ms Ratnavelu, Co-PI is a 
committee member and British Society for Colposcopy and Cervical pathology 
meeting). This will ensure that data reaches the gynaecologists and policy makers 
who are responsible for these patients and have a direct impact on patient care.  
We will approach charities who are involved in women's health promotion such as 
“the Eve appeal” or “Well Being of Women” to aid us in publicising our results online 
to raise awareness amongst service users.  
 
  
Abbreviations 
VR  
Virtual Reality 
STAI  State Trait Anxiety Index 
NRS Numerical Rating Score 
PI 
Primary Investigator 
CI 
Chief Investigator 
HPV Human Papilloma Virus 
CIN 
Cervical Intraepithelial Neoplasia 
LLETZ 
Large loop excision of transformation zone 
QEH Queen Elizabeth Hospital 
BSCCP 
British Society for Colposcopy and Cervical Pathology 
CRF Case Report Form 

AE  
Adverse Event 
SAE  Serious adverse event 
SOP Standard operating procedure 
 
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