Comparison of Patient Reported Outcome Measures in Patients Undergoing Pre Versus Sub-pectoral Implant Based Breast Reconstruction
Conditions: Breast Disease, Breast Cancer, Patient Satisfaction, Surgery
Sponsor: The Leeds Teaching Hospitals NHS Trust

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Comparison of patient reported outcome measures 
in patients undergoing pre versus sub-pectoral 
implant based reconstruction 
 
 
 
 
IRAS Project ID: 283017 
 
 
Non-CTIMP trial 
 
Date and Version No: Version 1.0, 12th May 2020 
 
 
 
 
 
Chief Investigator: Mr Baek Kim, Consultant Oncoplastic Breast Surgeon, Leeds 
Breast and Reconstructive Unit, St James’s University Hospital, 
Leeds, UK.   
 
 
 
Co-Investigators: Ms Shireen McKenzie, Consultant Oncoplastic Breast Surgeon, 
Leeds Breast and Reconstructive Unit, St James’s University 
Hospital, Leeds, UK 
 
Mrs Sue Hartup, Breast Research Sister 
St. James’s University Hospital, Leeds, UK  
 
 
Ms Stacey Jones, Research Fellow, Leeds Breast and 
Reconstructive Unit, St James’s University Hospital, Leeds, UK 
 
  
 
 
Sponsor: 
 
Leeds Teaching Hospitals NHS Trust 
 
 
 
 

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Contents 
 
 
 
 
 
 
            
 
Pages 
 
1. Key Trial Contacts  
 
 
 
 
 
 
     4 
 
2. Abbreviations 
 
 
 
 
 
 
 
     5 
 
3. Background and Rationale 
 
 
 
 
 
     6 
 
4. Objectives and Outcome Measures 
 
 
 
 
     9 
 
5. Trial Design  
 
 
 
 
 
 
 
    10 
 
5.1 Research Design 
 
 
 
 
 
 
    10 
5.2 Study Measures 
 
 
 
 
 
 
    10 
5.3 Study Duration  
 
 
 
 
 
 
    11 
5.4 Findings  
 
 
 
 
 
 
 
    11 
 
6. Patient Identification 
 
 
 
 
 
 
    11 
 
6.1 Trial Participants 
 
 
 
 
 
 
    11 
6.2 Inclusion Criteria 
 
 
 
 
 
 
    11 
6.3 Exclusion Criteria 
 
 
 
 
 
 
    12 
6.4 Participants in the local service evaluation 
 
 
    12 
 
7. Trial Procedures 
 
 
 
 
 
 
 
    12 
 
7.1 Recruitment 
 
 
 
 
 
 
 
    12 
7.2 Informed Consent 
 
 
 
 
 
 
    13 
7.2.1 Patients who withdraw consent 
 
 
 
    13 
7.3 Baseline Assessments 
 
 
 
 
 
    13 
7.4 Subsequent Timepoints 
 
 
 
 
 
    14 
7.5 Patient Outcome Measures  
       
 
 
               14 
7.6 Discontinuation/Withdrawal of Participants 
 
 
    15 
 
8. Statistics 
 
 
 
 
 
 
 
 
    15 
 
8.1 Sample Size and Recruitment Rate 
 
 
 
    15 
8.2 General Considerations 
 
 
 
 
 
    15 
8.3 Recruitment, Follow up and Attrition 
 
 
 
    16 
8.4 Clinical Measure and Processes 
 
 
 
 
    16 
8.5 Patient Outcome Measures  
 
 
 
 
    16 
 
9. Data Management  
 
 
 
 
 
 
    16 
9.1 Source Data 
 
 
 
 
 
 
 
    16 
9.2 Access to Data  
 
 
 
 
 
 
    17 
9.3 Data Recording and Record Keeping 
 
 
 
    17 
 
10. Safety 
 
 
 
 
 
 
 
 
    18 
   

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11.  Ethical and Regulatory Considerations 
 
 
 
    19 
 
11.1 Approvals 
 
 
 
 
 
 
 
    19 
11.2 Reporting 
 
 
 
 
 
 
 
    19 
11.3 Patient Confidentiality 
 
 
 
 
 
    19 
 
12. Public and Patient Involvement  
 
 
 
 
    19 
 
13.  Archiving 
 
 
 
 
 
 
 
 
    20 
 
14. Insurance 
 
 
 
 
 
 
 
 
    20 
 
15. Publication Policy  
 
 
 
 
 
 
    20 
 
16. References  
 
 
 
 
 
 
 
    21 
 
 
 
 
 
 
 
 
 

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1. Key Trial Contacts 
 
Chief Investigator: 
 
 
 
Mr Baek Kim, FRCS MD MA 
Consultant Oncoplastic Breast Surgeon 
Leeds Breast and Reconstructive Unit  
St James’s University Hospital  
Leeds, UK. 
0113 20 68724      
b.kim@nhs.net 
Sponsor 
Leeds Teaching Hospitals NHS Trust 
Co-Investigator 
Ms Shireen McKenzie, MBChB MD FRCS(Ed) 
PGCert(ClinEd) FHEA 
 
Consultant Oncoplastic Breast Surgeon 
Leeds Breast and Reconstructive Unit  
St James’s University Hospital  
Leeds, UK. 
0113 20 68460      
shireen.mckenzie@nhs.net 
Clinical 
Collaborators: 
Ms Stacey Jones 
Breast Research Fellow 
Leeds Breast and Reconstructive Unit  
St James’s University Hospital  
Leeds, UK. 
0113 20 68724 
staceyjessica.jones@nhs.net 
 
Sue Hartup, RGN, BSc, PGC 
Breast Care Research Sister 
Level 4 Bexley Wing 
St James’s University Hospital 
Leeds  
0113 2068628 
s.hartup@nhs.net 
 
 
 

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2. Abbreviations 
 
AE 
Adverse Event 
ABS 
Association of Breast Surgery 
BRCA 
Breast Cancer Gene  
BREAST-Q 
BREAST-Q questionnaire 
CI 
Chief Investigator 
CNST 
Clinical Negligence Scheme for Trusts 
CRF 
Case Report Form 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GP 
General Practitioner 
IBR 
Immediate Breast Reconstruction 
ICF 
Informed Consent Form 
LTHT 
Leeds Teaching Hospitals NHS Trust 
MDT 
Multi-Disciplinary Team 
NACT 
Neo-adjuvant chemotherapy 
NMBRA 
The National Mastectomy and Breast Reconstruction Audit 
NHS 
National Health Service 
NIHR 
National Institute of Health Research 
NRES 
National Research Ethics Service  
PI 
Principal Investigator 
PIS 
Participant/ Patient Information Sheet 
ppm 
Patient Pathway Manger (electronic patient record system - Leeds Teaching 
Hospitals) 
PRO 
Patient Reported Outcomes 
PROMs 
Patient Reported Outcome Measures 
QoL 
Quality of Life 
R&I 
NHS Trust Research and Innovation Department 
REC 
Research Ethics Committee 
RGF 
Research Governance Framework 
SOP 
Standard Operating Procedure 
SPSS 
Statistical Package for the Social Sciences (statistical package) 
TMF 
Trial Master File 
 
 

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3. Background and Rationale 
 
 
Breast cancer affects around 55000 women per year in the UK (2015-2017; Cancer 
Research UK) and 5 year survival for all breast cancer is favourable at 86.6% in the UK as a 
result of advances in locoregional and systemic treatment. Nationally approximately 40% of 
women undergo mastectomy to treat breast cancer[1]. All eligible women are offered 
immediate breast reconstruction (IBR), with the UK National Mastectomy and Breast 
Reconstruction Audit (NMBRA) showing that up to 43% of women opted for immediate 
breast reconstruction[1], and that the rate of IBR is increasing in UK over time[2]. There is 
also an increasing number of patients who opt to undergo risk reducing mastectomies and 
reconstruction due to high family history risk or germline genetic mutations[3] (e.g. BRCA). 
 
Given this increased uptake of IBR, it is important to study the patient’s quality of life after 
mastectomy and reconstruction. When compared to mastectomy alone, current research 
shows improved quality of life in patients who opt to receive reconstruction[4]. Women opting 
for reconstruction reported positive effects on their self-esteem, body image, sexuality and 
psychological health.  
 
Currently there are two well established methods of breast reconstruction after mastectomy: 
autologous ‘flap’ reconstruction or implant reconstruction. Whilst autologous reconstruction 
utilises tissue transfer from the patient themselves, implant reconstruction uses a silicone 
implant device or a saline tissue expander to re-create the breast mound. Implant 
reconstruction is the commonest form of breast reconstruction and in Leeds Teaching 
Hospitals NHS Trust (LTHT), 60% of patients receiving IBR opt for implant based 
reconstruction. The breast surgery unit at LTHT is a national oncoplastic fellowship centre 
and perform around 100 IBR of all types per year (personal communication and analysis; 
author BK). 
 
Traditionally immediate implant based reconstructions were not technically possible as 
implant size required to recreate breast shape was usually too large and raising pectoralis 
major and serratus anterior muscle was insufficient to cover and stabilise the implant 
position[5]. Therefore, smaller expanders were commonly placed under both muscles and 
gradually inflated. This was then later exchanged to an implant. The aesthetic outcome from 
such procedures was sub-optimal with increased risk of pain and implant malposition. 
 

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More recently, acellular dermal matrices [6] has led to an improvement in implant based 
breast reconstruction. Acellular dermal matrix is sutured to the lower part of pectoralis 
muscle that is raised. This enables full coverage and stabilises the implant and therefore 
avoids the need for raising the serratus anterior muscle or routine use of expanders. As a 
result, this reduces the number of surgeries the patient requires, as well as improve 
aesthetic outcome. This technique is defined as sub-pectoral implant based breast 
reconstruction. It has been adopted widely [7] and has become established as standard 
practice. 
 
In the last 5 years, surgical techniques and technologies have advanced further to enable 
the implant to be placed above the pectoral muscle. This avoids the need to raise the 
pectoral muscle and therefore has advantages in reducing post-operative pain and length of 
the operating time. This has been made possible with larger acellular dermal matrices that 
are able to stabilise implant position without needing to raise the pectoral muscle to cover 
the implant device. This technique is defined as pre-pectoral implant based breast 
reconstruction[8] and has been adopted widely in UK given the perceived advantages for the 
patient. There is currently a national study [9] that is examining patient outcome in pre-
pectoral implant based breast reconstruction. Figure 1 clearly demonstrates the difference 
between pre- and sub-pectoral implant reconstruction. 
 
  
 
Figure 1. Pre- versus sub-pectoral breast reconstruction [10] 
 
Both surgical techniques have proven safety for the patient in demonstrating low 
complication rates such as implant loss rate due to infection. There are potential advantages 
as well as disadvantages for each surgical technique as demonstrated by the table 1. 

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Sub-pectoral 
Pre-pectoral 
Raising the pectoral muscle can result in 
excess upper pole fullness of the 
reconstructed breast. 
More predictable aesthetic result as the 
pectoral muscle is not raised.  
Animation deformity, which is defined as 
visible twitching of the pectoral muscle 
(under the skin) with certain arm or shoulder 
movements. Patients may find this unsightly. 
No animation deformity.  
Potentially greater pain due to partial division 
of the pectoral muscle resulting in slower 
recovery to normal function. 
Potentially less pain and therefore shorter 
hospital stay and quicker recovery to normal 
function. 
Additional tissue coverage over the implant 
resulting in less likelihood of implant 
palpability, rippling, or capsular contracture. 
 
Thin tissue coverage over the implant. This 
may increase the risk of rippling which may 
be treated with further revisional surgery 
(e.g. lipomodelling to improve tissue 
coverage over the implant). 
 
Table 1. Potential advantages and disadvantages of pre- vs. sub-pectoral implant based 
breast reconstruction. 
 
Given the equipoise and proven safety of both surgical techniques, eligible patients are 
counselled about their surgical options when opting for implant based breast reconstruction. 
Implant based reconstruction includes a fixed volume silicone implant device as well as an 
expander device which has an outer silicone shell with an internal saline chamber which can 
be inflated gradually once the surgical wound has healed. Expanders can be used for both 
pre- and sub-pectoral reconstruction and is used in cases where there are potentially higher 
wound healing risks (e.g. patients with smoking history). This is fully discussed between the 
surgeon and the patient as part of a standard informed consent.  
 
At LTHT, we are able to offer patients both pre- and sub-pectoral implant based 
reconstruction. The current practice shows that equal proportion of patients opt for pre- 
versus sub-pectoral implant based IBR (BK: personal communication and preliminary data). 
However, it is unclear how much of this decision making is influenced by the patient or the 
surgeon. There is no current research of national guideline suggesting recommendation of 
one surgical technique versus the other.  

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Therefore, it becomes even more important to examine and compare patient reported 
outcome measures (PROMs) in both patient groups. This is an important research question 
as if PROMs are significantly higher in one patient group versus the other, this has 
significant implications for future patients when counselled with regards to their surgical 
options. Decision making for breast reconstruction is complex for the patient and the 
healthcare professionals involved. Therefore, further research such as this study is required 
to aid this process. 
 
BREAST-Q is a validated questionnaire specific for breast patients undergoing 
reconstruction [11-13]. It is able to assess multiple pertinent PROMs including the patient’s 
expectation of breast reconstruction, the level of pain, physical function after surgery, 
satisfaction with shape of the reconstruction, and satisfaction with the treating medical team 
and the level of information provided. Importantly, it has questions specific to implant based 
breast reconstruction and has specific questions relating to the potential issue of animation 
deformity [14]. It is also validated for use at multiple time points after surgery (including 
longer term PROMs at 12 months). Therefore, assessing PROMs using the BREAST-Q in 
patients undergoing pre- or sub-pectoral implant based IBR at the Leeds Breast Unit, a high 
volume reconstructive surgery centre, provides an ideal setting to answer this important 
research question.  
 
 
4. Objectives and Outcome Measures 
 
Does the difference in the surgical technique for immediate implant breast reconstruction 
(pre- versus sub-pectoral) influence patient perceived outcomes? 
 
Aims: 
The current lack of research evidence and guidelines on the topic signifies that the type of 
operation undertaken usually comes down to surgeon or patient preference. By completing 
this project we aim to provide better: 
 
Patients with curated information regarding short and longer term post-surgical 
patient reported outcomes. 
 
Healthcare professionals with a more extensive understanding of the advantages and 
limitations of both types of surgery from the patient’s perspective. 
 

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This will equip the patient and the healthcare professional to make more informed decisions 
regarding the optimal surgical technique. 
 
 
Objectives: 
 
Compare aesthetic outcome of pre- and sub-pectoral reconstructions using Patient 
Reported Outcome Measures (PROMs) 
 
Compare potential difference in pain between pre- and sub-pectoral reconstructions 
as reported by PROMs 
 
Compare potential difference in functionality between pre- and sub-pectoral 
reconstructions using PROMs 
 
Outcome Measures: 
We will collect PROMS on a prospective cohort of patients undergoing immediate implant 
based reconstruction after mastectomy for cancer or for risk reduction. The Association of 
Breast Surgery (ABS) guidelines for oncoplastic breast surgery [15] states that patients 
undergoing breast reconstruction should have PROMs data collected on a routine basis. We 
will utilise the BREAST-Q questionnaire (BREAST-Q, 2017), which is a validated PROMs 
survey that has been published widely. 
 
 
5. Trial Design 
 
5.1 
Research Design 
A prospective non-randomised longitudinal cohort study with data collection for patients 
undergoing mastectomy with immediate implant based reconstruction surgery for early 
breast cancer or risk reduction using repeated measures and mixed methods. 
 
5.2 
Study Measures 
a) Clinical Outcomes and process of care measures 
e.g. anaesthetic blocks used, number of hospital contacts, unplanned admissions, clinic 
appointments, phone calls with hospital staff, medications prescribed and taken, any 
changes to treatment plan. Details will be obtained via the individual electronic patient 
records. 
b) Patient Reported outcomes 
PROs using validated questionnaires 

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The BREAST-Q utilises PROMs to evaluate outcomes for various types of breast surgeries. 
Two of its ‘modules’ are relevant to this study; ‘Reconstruction’ and ‘Reconstruction 
Expectations’. Each module contains multiple independently scored ‘scales’ with overarching 
themes of psychosocial and physical quality of life. To establish a baseline pre-operatively, 
we will use the ‘Reconstruction Expectations’ module. To explore the change in PROMs over 
time, the ‘Reconstruction’ module will be given to patients post-operatively (BREAST-Q, 
2017). The main strength of using BREAST-Q is that it allows for comparison to other work 
in the same field of research. Furthermore, the outcome of the study could aid in designing 
and setting up of future multi-centre studies. 
 
The questionnaires will be collected at four time points; pre-surgery, 2 weeks post-surgery 
and at 3 and 12 months post-surgery. This is in line with current clinical follow up for patients 
undergoing implant based reconstruction in Leeds. Therefore, patients will not require any 
additional clinical visits. The PROM scores may also be influenced by their surgical outcome 
(e.g. complication after reconstructive surgery). Therefore, routine clinical data regarding the 
patient’s treatment outcome (e.g. any return to theatre or re-admission) will be collected 
alongside sociodemographic, relevant medical history data and the questionnaire. 
 
5.3 
Study Duration 
Patients will be a participant in the study for approximately thirteen months. Thirteen months 
following surgery is completion of the patient’s involvement in the study.  
 
5.4 
Findings 
The overall findings will determine the feasibility of using this approach to support the care of 
patients undergoing immediate implant based reconstructive surgery for breast cancer or 
risk reduction. All data and opinions will inform the future development of information which 
aims to improve patient choice, experience and outcomes. 
 
 
6.0       Participant Identification 
6.1 Trial Participants 
The sample of patients will include all prospective patients who undergo immediate implant 
based breast reconstruction in the Leeds Breast Unit between August 2020 and September 
2021. 
 
 

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     6.2 Inclusion criteria 
 
Female age ≥ 18 years 
 
Skin or nipple sparing mastectomy with immediate implant based reconstruction for 
cancer or for risk reduction (e.g. BRCA mutation) 
 
Unilateral or bilateral mastectomy  
 
Implant or expander based immediate reconstruction 
 
Able to read and understand questionnaire in English 
 
    6.3 Exclusion criteria 
 
Male or transgender 
 
Skin or nipple sparing mastectomy alone with no reconstruction 
 
Delayed reconstruction 
 
Autologous reconstruction 
 
Cognitive impairment or inability to provide informed consent 
 
    6.4 Participants in the local service evaluation 
Patients who have already completed the questionnaires through their participation in a 
local service evaluation, will also be approached to ask to participate. They will be 
provided with a separate patient information sheet which explains the difference between 
the service evaluation and the study.  Retrospective consent will be sought to use this 
information as part of this study.  
 
7.0  Trial Procedures 
7.1 Recruitment 
All eligible patients will be identified at the Leeds Breast diagnostic MDT meetings and 
through clinics. Those planned for a mastectomy and implant based reconstruction are 
offered the option of completing the BREAST-Q as part of routine care. The direct clinical 
team will discuss this with the patient and this will not impact on routine care of decision 
making for either pre- or sub-pectoral implant based reconstruction (i.e. non-randomised). All 
patients deemed eligible will be offered the study patient information sheet and given a 
minimum of 24 hours to consider the study. As common practice is for surgery to be 2-3 
weeks after the clinic appointment, there will be sufficient time for the patient to consider the 
information and ask any questions they may have about participation.  
 
 
 

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    7.2 Informed Consent 
The participant must personally sign and date the latest approved version of the Informed 
Consent form before any study specific procedures are performed. It is the responsibility of 
the Chief Investigator (or designee as listed on the Site Responsibilities Form) to obtain 
written informed consent in compliance with national requirements from each patient prior to 
entry into the study. On the day of surgery, the clinical team will confirm if the patient wishes 
to participate and if yes, will arrange for consent to be taken. Written informed consent will 
be taken by an appropriately trained member of the team and may include experienced 
research nurses or trials assistants, as per the delegation log. This is in accordance with 
Good Clinical Practice (GCP) guidelines and will have been documented and approved by 
the Chief Investigator on the delegation log.  Patients will be reminded that participation is 
voluntary and that they can withdraw at any time point without this affecting their care. This 
process will be clearly documented in the patients’ medical notes.  
A copy of the signed Informed Consent will be given to the participant. The original signed 
form will be retained in the trial site file and a copy will be placed in the patient’s notes. 
There will be two study PIS’s; one for prospective patients and one for retrospective patients 
who participated in the local service evaluation and have already completed BREAST-Q 
questionnaires. There will be two ICFs for the study, one for those entering as prospective 
patients who have not yet had their surgery and a separate ICF for those who participated in 
the local service evaluation. 
On consent, all participants will be allocated an anonymised sequential trial identification 
number which will be used on all trial data collection. 
 
    7.2.1 Patients who withdraw consent 
Patients are free to withdraw from the study at any time.  
 
    7.3 Baseline Assessments 
Once written informed consent is obtained, participants will be asked to complete the 
baseline questionnaire. Clinical data will be obtained from medical notes by the clinician 
and/or research team and will include (but not limited to) gender, age, diagnostic details, co-
morbidities, smoking status, previous surgical and planned treatments. 
 
Timepoint 0  
After consent but prior to surgery 
Following written informed consent and prior to the planned surgery, the baseline BREAST-
Q questionnaire will be completed by every patient.  
 

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The following data items will be collected during the study: 
 
Reason for surgery (cancer or risk reduction) 
 
Uni or Bilateral surgery 
 
Type of mastectomy (skin and nipple preserving or nipple sacrificing, skin reducing) 
 
Pre- or sub-pectoral reconstruction 
 
Any axillary surgery 
 
Breast implant size 
 
Details of any anaesthetic block used (to reduce post-operative pain) 
 
Any additional cancer treatments (e.g. chemotherapy, radiotherapy) 
 
Any complications (e.g. haematoma, infection) 
 
Unplanned hospital re-admission 
 
Unplanned further surgery 
 
Implant loss at 3 months due to infection 
 
Expectation of pain after surgery 
 
Expectation of appearance after surgery 
 
Expectation of breast symmetry 
 
Expectation of change in sensation 
 
Satisfaction of breast shape and implant 
 
Psychosocial well-being 
 
Physical well-being related to chest 
 
Satisfaction with the information and care provided by the clinical team 
 
Sociodemographic information  
 
    7.4 Subsequent Timepoints 
 
Timepoint 1  
On completion of surgery and discharge from hospital  
All study participants will be asked to complete the BREAST-Q questionnaire 2 weeks (+1 
week) after having surgery. Patients will be due to be seen at a routine outpatient 
appointment and will be offered the opportunity to complete the questionnaires whilst in 
clinic. Due to COVID-19, the clinician and the patient may decide that a telephone clinic 
consultation is more appropriate rather than a face-to-face consultation. Participating in this 
study will not influence this decision making. For these cases where the follow up 
consultation is not face-to-face, a letter will be sent asking them to complete the 
questionnaire along with a pre-paid envelope to return the questionnaire. 
 

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Timepoint 2  
All participants will be asked to complete the BREAST-Q questionnaire 3 months post-
surgery (+ 6 weeks). Patients are routinely seen in a follow up clinic, so they will be offered 
the opportunity to complete the questionnaires whilst in clinic. If they are missed or if the 
clinic consultations are via telephone (as explained above), a letter will be sent to the 
participant asking them to complete the questionnaire booklet along with a pre-paid 
envelope to return the questionnaires.  
 
Timepoint 3 
All participants will be asked to complete the BREAST-Q questionnaire 12 months post-
surgery (+ 6 weeks). Patients are routinely seen in a follow up clinic, so they will be offered 
the opportunity to complete the questionnaires whilst in clinic. If they are missed or if the 
clinic consultations are via telephone (as explained above), a letter will be sent to the 
participant asking them to complete the questionnaire booklet along with a pre-paid 
envelope to return the questionnaires.  
 
 
7.5 Patient Outcome Measures (see appendix) 
Participants in the study will complete the same measures on paper to ensure comparison 
between the timepoints. The questionnaire will be completed at baseline, 2 weeks and 3 and 
12 months post-surgery.  
7.6 Discontinuation/Withdrawal of Participants from Study 
Each participant has the right to withdraw from the study at any time.  In addition, the 
Investigator may discontinue a participant from the trial at any time if the Investigator 
considers it necessary for any reason including: 
 
Withdrawal of Consent 
 
If surgery not undertaken as planned at time of consent 
Any data acquired prior to withdrawal will be included in the final analysis (unless consent is 
withdrawn by the participant). The reason for withdrawal will be recorded. 
 
8 Statistics 
As we are exploring patient perceived outcomes and not evaluating a new intervention, a 
power calculation is not required to calculate sample size. Based on the rate of immediate 
implant based reconstructions performed in the Leeds Breast and Reconstructive unit, we 

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estimate that approximately 60 patients will be available to complete the questionnaire per 
year. We have set a pragmatic target of 60 patients to be recruited over the study period. 
This is especially relevant given the current coronavirus pandemic which has had an impact 
on routine patient care during 2020. 
 
    8.1 Sample size and recruitment rate 
This is a single centre study with a planned minimum sample size of 60 participants. We 
have allowed a 2 year period for recruitment. 
 
    8.2 General Considerations 
Statistical analysis of the recruitment and attrition rates, data collection, measures and 
outcome data is the responsibility of the Chief Investigator (assisted by the study team). 
The questionnaire score for each participant will be converted into a Rasch scale (scores 0-
100) as per BREAST-Q score conversion protocol. Simple comparative statistical analysis 
will be performed with the aid of SPSS to compare BREAST-Q scores between participants 
undergoing pre-pectoral implant reconstruction and sub-pectoral reconstruction. Each sub-
module PROMs category within the BREAST-Q will also be directly compared between the 
two groups. The matched BREAST-Q scores over the four time periods for each participant 
will also be analysed to explore the potential change in scores over the study follow-up 
period. Patient outcome (e.g. complication rates, re-admission, additional cancer treatment) 
will also be correlated with the BREAST-Q scores to examine their potential impact on 
PROMs.  
 
    8.3 Recruitment, Follow up and Attrition 
The feasibility of the recruitment process will be evaluated by using the screening logs, 
eligibility and consent processes. If reasons for ineligibility and non-participation have been 
provided, these will be summarised. Follow up retention, including the number of participants 
who withdraw and any reasons for withdrawal will be described.  
 
    8.4 Clinical Measure and Processes 
Telephone calls and contact with hospital staff to report problems such as pain or infection 
symptoms will be summarised.  
 
    8.5 Patient Outcome Measures 
Patient outcome measures will be summarised for each time point. Any differences between 
the two groups will be analysed where possible. All analyses will be used to help plan a 
future advice and information for patients undergoing implant based reconstruction. 

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9 Data Management 
Data collection will occur in accordance with GCP, Caldicott principles and the General Data 
Protection Regulation (GDPR) 2018, and will work in line with NHS confidentiality guidelines 
and codes of conduct. All questionnaires will be fully anonymised and contain no patient 
identifiable details. Anonymised data will be manually inputted into an excel spreadsheet 
which will be held on a password protected location within a secure NHS departmental drive. 
 
    9.1 Source Data 
Source documents are where data is first recorded, and from which participants’ data are 
obtained. These will include, but are not limited to, hospital records (from which medical 
history and previous and concurrent medication may be summarised into the CRF), clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, ppm 
(patient pathway manager - the Leeds electronic patient record) and correspondence. 
Source data verification will be monitored to confirm compliance with the protocol and the 
protection of patients’ rights as detailed in the Declaration of Helsinki 1964 as amended 
October 1996. Monitoring by the Chief Investigator or authorised authorities will be to ensure 
 
Sufficient data is recorded to enable accurate linkage between hospital records and 
CRFs 
 
Source data and all trial related documentation are accurate, complete, maintained 
and accessible for monitoring and audit 
 
Staff working on the trial will meet requirements of the EU Directive 
 
    9.2 Access to Data 
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. 
 
    9.3 Data Recording and Record Keeping 
General 
All information collected during the course of the trial will be kept strictly confidential.   
Information will be held securely on paper and electronically at the Leeds Teaching 
Hospitals NHS Trust. The Leeds Breast Unit will comply with all aspects of the Data 
Protection Act 1998 and operationally this will include: 
 
consent from patients to record personal details including name, date of birth, 
address and telephone number, email address, NHS ID and hospital ID  
 
appropriate storage, restricted access and disposal arrangements for patient 
personal and clinical details 

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 
consent from patients for access to their medical records by responsible 
individuals from the research staff, the sponsor or from regulatory authorities, 
where it is relevant to trial participation 
 
Consent from patients for the data collected for the trial to be used to evaluate 
safety and develop new research. 
 
Data Collection  
Data collected on each patient must be recorded by the Chief Investigator, or his/her 
designee, as accurately and completely as possible. The Chief Investigator is responsible for 
the timing, completeness, legibility, accuracy and signing of the CRF and he will retain a 
copy of each completed form. The Clinical Investigators must allow study staff access to any 
required background data from hospital records (source data e.g. medical records) on 
request.  
All fields MUST be completed. If a test or measurement was not done, please indicate why 
that was omitted on the CRF. Entries must be made in black ballpoint pen. Errors must be 
crossed out with a single line leaving the original data un-obscured (i.e. without 
overwriting), the correction inserted and the change initialled and dated. An explanatory note 
should be added if necessary. Correction fluid/tape/labels must not be used. All data 
submitted on CRFs must be verifiable in the source documentation. These may include, but 
are not limited to, hospital records (from which medical history and previous and concurrent 
medication may be summarised into the CRF), clinical and office charts, laboratory and 
pharmacy records, diaries, radiographs and correspondence. All documents will be stored in 
confidential conditions.  Any deviation from this must be explained appropriately.  
Data Completeness 
Data completeness is an integral part of any trial.  A CONSORT style will be used to monitor 
data completeness from eligibility screening, approach, study acceptance through to the final 
follow-up visit.  This information will be made available to the TMG as regular reports.  The 
team will also report the number of: 
 
Patients screened per month 
 
Patients approached per month (and reasons why not approached) 
 
Patients recruited per month 
 
The number of patients who complete each follow up visit or are lost to follow-up 
 
The number of patients who complete the trial. 
The participants will be identified by a unique trial specific number and/or code in any 
database.  The name and any other identifying detail will NOT be included in any trial data 
electronic file. 

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10. 
Safety 
There are no pre-defined safety end-points for this study.  However, any adverse events 
which occur as a result of normal care will be reported to the study team. 
The majority of the research will involve completion of a simple and well validated 
questionnaire, so there will be no physical pain, discomfort or distress caused by these. 
However, questionnaires take time to complete and so can be seen as an inconvenience. 
Some of the questions refer to personal matters, so can be perceived as being intrusive. 
This study may add to the current knowledge of patient experience of implant based 
reconstruction techniques.  
 
 Burden will be minimised using the following approaches: 
 
The study pathway has been designed to avoid the need for extra visits as will be 
undertaken in conjunction with all standard of care appointments. 
 
The chosen assessment is widely used and is validated and has been found to be 
generally acceptable in use with patients.  
 
Experienced staff used to dealing with patients with cancer, will be involved. 
 
If a patient indicates that they wish to stop during the completion of the 
questionnaires this will be respected and they will be offered an opportunity to 
continue them later. 
 
11. 
 Ethical and Regulatory Considerations 
 
    11.1 Approvals 
This study is a single centre research study taking place at Leeds only. 
The protocol, informed consent forms and participant information sheets will be submitted to 
an appropriate Research Ethics Committee (REC), Health Research Authority (HRA) and 
host institution(s) for written approval. The Investigator will submit and, where necessary, 
obtain approval from the above parties for all substantial amendments to the original 
approved documents. 
 
    11.2 Reporting 

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The CI shall submit once a year throughout the clinical trial, or on request, an Annual 
Progress Report to the REC, host organisation and Sponsor.  In addition, an End of Trial 
notification and final report will be submitted to the REC, host organisation and Sponsor. 
 
    11.3 Patient Confidentiality 
The study staff will ensure that the participants’ anonymity is maintained.  The participants 
will be identified only by initials and a participants ID number on the CRF and any electronic 
database.  All documents will be stored securely and only accessible by authorised 
personnel. The trial will comply with the Data Protection Act, which requires data to be 
anonymised as soon as it is practical to do so. 
 
12. 
Public and Patient Involvement 
Discussions were had with local patients who have undergone breast reconstruction 
regarding their experiences of the procedure and how they made their choice of type of 
reconstruction. One patient has reviewed all the study paperwork including the protocol, 
information sheet and consent form. Patient involvement with this study is vital to its success 
and as such, their involvement has been key since inception. 
 
13. 
 Archiving 
In line with the principles of GCP/UK Clinical trial Regulations guidelines, at the end of the 
trial, data will be securely archived at the centre for a minimum of 15 years.  Arrangements 
for confidential destruction will then be made. If a patient withdraws consent for their data to 
be used, it will be confidentially destroyed immediately. No records may be destroyed 
without first obtaining written permission from the Sponsor. 
 
14. 
Insurance 
NHS indemnity through the Clinical Negligence Scheme for Trusts (CNST). 
 
 
15. 
Publication Policy 
Credit for the main results will be given to all those who have collaborated in the trial, as its 
success depends on collaboration and participation.  Requirements for authorship for 
manuscripts submitted to medical journals will guide authorship decisions.  These state that 
authorship credit should be based only on substantial contribution to:  
 conception and design, or acquisition of data, or analysis and interpretation of data 
 drafting the article or revising it critically for important intellectual content 
 final approval of the version to be published 

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 and that all these conditions must be met (www.icmje.org ). 
 
The Chief Investigator will be named as main author in any publications.  In addition, all 
collaborators will be listed as contributors for the main trial publications, giving details of 
roles in planning, conducting and reporting the trial.  All publications will acknowledge 
gratitude to the women who have taken part in the study.   
 
 
 
 

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16. References 
 
1. 
Jeevan, R., et al., Findings of a national comparative audit of mastectomy and 
breast reconstruction surgery in England. J Plast Reconstr Aesthet Surg, 
2014. 67(10): p. 1333-44. 
2. 
Jeevan, R., et al., National trends and regional variation in immediate breast 
reconstruction rates. Br J Surg, 2016. 103(9): p. 1147-56. 
3. 
Manning, A.T., et al., Nipple-sparing mastectomy in patients with BRCA1/2 
mutations and variants of uncertain significance. Br J Surg, 2015. 102(11): p. 
1354-9. 
4. 
Zehra, S., et al., Health-related quality of life following breast reconstruction 
compared to total mastectomy and breast-conserving surgery among breast 
cancer survivors: a systematic review and meta-analysis. Breast Cancer, 
2020. 
5. 
Cordeiro, P.G. and C.M. McCarthy, A single surgeon's 12-year experience 
with tissue expander/implant breast reconstruction: part II. An analysis of 
long-term complications, aesthetic outcomes, and patient satisfaction. Plast 
Reconstr Surg, 2006. 118(4): p. 832-9. 
6. 
Loo, Y.L., et al., Comparing the Outcome of Different Biologically Derived 
Acellular Dermal Matrices in Implant-based Immediate Breast Reconstruction: 
A Meta-analysis of the Literatures. Plast Reconstr Surg Glob Open, 2018. 
6(3): p. e1701. 
7. 
Potter, S., et al., Short-term safety outcomes of mastectomy and immediate 
implant-based breast reconstruction with and without mesh (iBRA): a 
multicentre, prospective cohort study. Lancet Oncol, 2019. 20(2): p. 254-266. 
8. 
Wazir, U. and K. Mokbel, The Evolving Role of Pre-pectoral ADM-assisted 
Approach in Implant-based Immediate Breast Reconstruction Following 
Conservative Mastectomy: An Overview of the Literature and Description of 
Technique. In Vivo, 2018. 32(6): p. 1477-1480. 
9. 
Harvey, K.L., et al., The Pre-BRA (pre-pectoral Breast Reconstruction 
EvAluation) feasibility study: protocol for a mixed-methods IDEAL 2a/2b 
prospective cohort study to determine the safety and effectiveness of 
prepectoral implant-based breast reconstruction. BMJ Open, 2020. 10(1): p. 
e033641. 
10. 
https://www.breastflap.com/breast-reconstruction/options/implant-
reconstruction/. 
11. 
Kazzazi, F., et al., A comparison of patient satisfaction (using the BREAST-Q 
questionnaire) with bilateral breast reconstruction following risk-reducing or 
therapeutic mastectomy. J Plast Reconstr Aesthet Surg, 2018. 71(9): p. 1324-
1331. 
12. 
Thill, M., et al., Patient reported outcome and cosmetic evaluation following 
implant-based breast-reconstruction with a titanized polypropylene mesh 

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(TiLOOP(R) Bra): A prospective clinical study in 269 patients. Eur J Surg 
Oncol, 2020. 
13. 
Patel, A.U., et al., Functional return after implant-based breast reconstruction: 
A prospective study of objective and patient-reported outcomes. J Plast 
Reconstr Aesthet Surg, 2019. 
14. 
Fracol, M., et al., The Relationship between Animation Deformity and Patient-
Reported Outcomes: Application of the BREAST-Q to a Quantitative 
Stratification of Animation Severity. Plast Reconstr Surg, 2020. 145(1): p. 11-
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15. 
Cutress, R.I., C. Summerhayes, and R. Rainsbury, Guidelines for oncoplastic 
breast reconstruction. Ann R Coll Surg Engl, 2013. 95(3): p. 161-2.