Pilot Robotic Mastectomy in Singapore (PRoMiSing I) Study: First Safety and Feasibility Prospective Cohort Study in South East Asia
Phase: NA
Conditions: Breast Cancer
Sponsor: Changi General Hospital

 
Version <5>, Dated <5 Jul 2023> 
Page 1 of 15 
Restricted, Sensitive (Normal) 
STUDY PROTOCOL 
 
PROTOCOL TITLE: 
Pilot Robotic Mastectomy in Singapore (PRoMiSing I) Study: First Safety and Feasibility Prospective Cohort Study in 
South East Asia 
 
PROTOCOL VERSION: 5.0  
 
 
PROTOCOL DATE: 05 Jul 23 
 
 
PRINCIPAL INVESTIGATOR:  
Dr Mok Chi Wei, Consultant, Changi General Hospital 
 
CO-INVESTIGATORS: 
Dr Tan Su-Ming, Senior Consultant and Head, Division of Breast Surgery,  
Department of Surgery, Changi General Hospital 
 
Dr Hing Jun Xian. Associate Consultant, Changi General Hospital 
 
Dr Melissa Seet Yert Li, Associate Consultant, Changi General Hospital 
 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 2 of 15 
Restricted, Sensitive (Normal) 
Table of Contents 
1. 
BACKGROUND AND RATIONALE................................................................................................. 4 
2. 
HYPOTHESIS AND OBJECTIVES ................................................................................................. 4 
3. 
EXPECTED RISKS AND BENEFITS ............................................................................................... 6 
4. 
STUDY POPULATION .................................................................................................................. 6 
4.1. 
LIST THE NUMBER AND NATURE OF SUBJECTS TO BE ENROLLED. ................................................................................ 6 
4.2. 
CRITERIA FOR RECRUITMENT AND RECRUITMENT PROCESS ...................................................................................... 6 
4.3. 
INCLUSION CRITERIA .............................................................................................................................................. 6 
4.4. 
EXCLUSION CRITERIA .............................................................................................................................................. 7 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY ................................................................. 7 
6. 
SAFETY MEASUREMENTS.......................................................................................................... 10 
6.1. 
DEFINITIONS ................................................................................................................................ 10 
6.2. 
COLLECTING, RECORDING AND REPORTING OF SERIOUS ADVERSE EVENTS (SAES) TO CIRB ............................ 11 
6.3. 
SAFETY MONITORING PLAN .............................................................................................................. 11 
6.4. 
COLLECTING, RECORDING AND REPORTING OF REPORTABLE ADVERSE EVENTS RELATING TO MEDICAL DEVICE TO THE 
HEALTH SCIENCES AUTHORITY (HSA) ............................................................................................................ 11 
7. 
DATA ANALYSIS........................................................................................................................ 11 
7.1. 
DATA QUALITY ASSURANCE ................................................................................................................................... 11 
7.2. 
DATA ENTRY AND STORAGE .................................................................................................................................. 12 
8. 
SAMPLE SIZE AND STATISTICAL METHODS ............................................................................. 12 
8.1. 
DETERMINATION OF SAMPLE SIZE ......................................................................................................................... 12 
8.2. 
STATISTICAL AND ANALYTICAL PLANS .................................................................................................................... 12 
9. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .................................................................... 12 
10. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................................... 12 
11. ETHICAL CONSIDERATIONS ..................................................................................................... 13 
11.1. 
INFORMED CONSENT ............................................................................................................................................. 13 
11.2. 
CONFIDENTIALITY OF DATA AND PATIENT RECORDS .............................................................................................. 13 
12. PUBLICATIONS ......................................................................................................................... 13 
13. RETENTION OF STUDY DOCUMENTS ........................................................................................ 14 
14.   REFERENCES……………………………………………………………………………………………………….10 
 
 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 3 of 15 
Restricted, Sensitive (Normal) 
 
 
 
 
PROTOCOL SIGNATURE PAGE 
 
 
 
Protocol Title: Surgical and Patient Reported Outcomes in Robotic Mastectomy – A Pilot Study 
 
 
Protocol Number: NA 
 
 
Protocol Version/ Date: 5 dated 05 July 2023 
 
 
Sponsor Name: NA 
 
 
 
Declaration of Investigator 
 
I confirm that I have read the above-mentioned protocol and its attachments. I agree to conduct the 
described trial in compliance with all stipulations of the protocol, regulations and ICH E6 Guideline for 
Good Clinical Practice (GCP). 
 
  
 
 
 
 
Principal Investigator Name:  __________________________________________ 
                                                            
 
Principal Investigator Signature:  _______________________________________ 
                                                            
 
Date:  __________________________________________ 
                                                            
 
 
 
 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 4 of 15 
Restricted, Sensitive (Normal) 
 
 
1. 
BACKGROUND AND RATIONALE 
 
 
Conventional nipple and/or skin-sparing mastectomy (NSM/SSM) with or without immediate 
reconstruction is becoming one of the mainstream surgical treatment for breast cancer and risk 
reducing mastectomy in recent years. While this technique provides satisfactory oncologic and aesthetic 
outcomes, its disadvantages include skin flap and/or nipple-areolar complex (NAC) necrosis, NAC 
malposition/distortion as well as visible scar(s) on the breast.  
 
In terms of technical aspects, NSM/SSM has its inherent challenges in view of limited incisions and 
thereby difficulties in dissection. Since 2015, a number of institutions worldwide had adopted a new 
technique of NSM/SSM using robotic surgical system. Institutional experiences worldwide 
demonstrated feasibility and safety of this technique coupled with improved patients’ satisfactions.  
 
To date, there is no center in Singapore or the region offering Robotic NSM/SSM (R-NSM/R-SSM). 
The authors believe that robotic mastectomy is a feasible and safe technique that can be utilized in our 
institution and it provides superior aesthetic outcomes with less morbidity and higher patient 
satisfaction if compared to conventional NSM/SSM.  
 
The aim of this study is to conduct a single-arm prospective pilot study to investigate the safety and 
feasibility, as well as aesthetic outcomes, surgical complications and patients’ satisfactions of R-NSM/R-
SSM. 
 
 
2. 
HYPOTHESIS AND OBJECTIVES 
 
Hypothesis  
 
Based on institutional cohort studies to date, we believe that robotic mastectomy is a safe surgical 
alternative to conventional surgery in terms of surgical outcomes while offering comparable if not 
superior aesthetic outcomes and improved patients’ satisfactions.  
 
Objectives 
 
The proposed study aims to report to ascertain on the surgical outcomes, aesthetic and health related 
quality of life outcomes as well as satisfaction in patients undergoing robotic mastectomy. 
 
Primary Outcomes: 
1. 
Surgical Outcomes  
- Operative parameters - docking time, console time, reconstruction time, total operative time 
- Length of stay – defined as the length of hospitalization from admission till discharge 
- 30-days morbidity/complications 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 5 of 15 
Restricted, Sensitive (Normal) 
Secondary Outcomes: 
1. 
Oncologic outcomes 
- Positivity of margins as a surrogate for short term oncologic safety 
2. 
Health-Related Quality of Life (QOL) and Patient Satisfaction using validated Breast-Q  
            questionnaire at 1 and 6 months after operation 
 
Surgical Outcomes  
- 
Operative parameters  
• Docking time – defined as time taken to dock the robot before robotic mastectomy 
• Console time – defined as time taken for robotic mastectomy robot docking time, 
conversion) 
• Reconstruction time – defined as time taken for breast reconstruction, if applicable 
• Total operative time – defined as time taken from axilla staging procedure, robot 
docking time, console time, closure and time taken for reconstruction, if applicable. 
• Length of stay – defined as the length of hospitalization from admission till discharge 
 
- 
30-days morbidity/complication 
• Wound infection requiring intervention – defined as wound infection where 
conservative treatment fails and requires surgical debridement 
• Flap and nipple areolar complex (NAC) necrosis – defined as ischaemia of mastectomy 
skin flap or nipple areolar complex necrosis 
• Postoperative hematoma/bleeding requiring intervention – defined as immediate post-
operative bleeding or haematoma requiring emergent exploration and haemostasis 
• Anesthesia related complications – defined as complications related to anaesthesia 
conduct  
Oncologic outcomes 
- 
Positivity of margins – defined as margins involved or uninvolved. Margins involvement is 
defined as tumor-on-ink for invasive carcinoma and 2 mm margin or less for ductal 
carcinoma-in-situ 
 
Health-Related Quality of Life (QOL) and Patient Satisfaction using validated Breast-Q questionnaire at 
1 and 6 months after operation 
 
- 
Health-Related QOL- defined as QOL from psychosocial, physical and sexual well-being 
perpectives 
- 
Patient satisfaction – defined as satisfaction with breasts, satisfaction with outcome and 
satisfaction with care 
 
 
 
 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 6 of 15 
Restricted, Sensitive (Normal) 
3. 
EXPECTED RISKS AND BENEFITS 
 
Risks associated with robotic mastectomy are similar to conventional surgical options which are as 
below: 
 
 
Post-surgical Pain 
 
Post-surgical Bleeding / Haematoma 
 
Wound Infection / Abscess 
 
Wound Breakdown and /or Necrosis 
 
Scar and Keloid formation. 
 
Shoulder Stiffness 
 
Numbness 
 
Seroma 
 
Benefits include, but not limited to: 
 
 
Smaller incision which may translate to lesser pain and faster recovery 
 
Improved patients’ satisfaction 
 
  
4. 
STUDY POPULATION 
 
4.1. 
List the number and nature of subjects to be enrolled.  
Patients who fit the inclusion and exclusion criteria detailed below will be enrolled. Each breast 
operated on will be consider as 1 case eg, if a patient is scheduled for bilateral mastectomy it will be 
considered as 2 cases. Study may recruit up to 20 patients to achieve the target of 20 cases. 
 
4.2. 
Criteria for Recruitment and Recruitment Process 
 
Patient selection for robotic mastectomy are similar to conventional mastectomy. 
 
4.3. 
Inclusion Criteria 
 
Women aged 21-70, with invasive breast cancer, ductal carcinoma in situ (DCIS), BRCA or other breast 
cancer genetic mutation carriers or high risk female patients who are otherwise candidates for 
conventional NSM/SSM will be eligible for the study. All suitable patients will be offered the option of 
R-NSM/ R-SSM.  
 
 
For patients with breast cancer (invasive or DCIS), selection criteria include but not limited to: 
 
1. 
Early breast cancer 
2. 
Tumor size less than 5 cm 
3. 
No evidence of lymph node metastases 
4. 
No evidence of skin or chest wall invasion.  
 

 
Version <5>, Dated <5 Jul 2023> 
Page 7 of 15 
Restricted, Sensitive (Normal) 
4.4. 
Exclusion Criteria 
 
1. Extensive axillary lymph node metastasis (Stage IIIB or later) 
2. Heavy smokers (>20 cigarettes a day) 
3. High risk patient with severe and poorly controlled co-morbid conditions (include but not 
limited to diabetes, heart disease, renal failure or liver dysfunction) 
4. Poor performance status or high risk for anaesthesia (ASA 3 and above) 
5. Inflammatory or Locally Advanced Breast Cancer (with or without chest wall or skin invasion) 
6. Previous thoracic radiation therapy for any reason 
7. Pregnancy 
8. Psychiatric, addictive, or any disorders which compromises the ability to give informed consent 
for participation in this study 
 
 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY 
 
This study is a prospective pilot study which aims to recruit 20 patients for robotic mastectomy. 
 
Patient selection 
 
Patients who fulfil the inclusion and exclusion criteria will be enrolled in this study. Written informed 
consent pertaining to the use of clinical records or perioperative pictures will be obtained from each 
participant. 
 
Pre-operative breast ultrasound, mammography and/or MRI are used to determine the eligibility of 
patients for robotic mastectomy. Computed tomography (CT) scan of the thorax,abdomen and pelvis as 
well as whole-body bone scan may be used to exclude the possibility of distant metastases in indicated 
cases.  
 
Indications for robotic mastectomy include breast cancer (early stage breast cancer, tumor size of less 
than 5 cm, no evidence of lymph node metastases and no evidence of skin or chest wall invasion) and 
high risk ladies indicated for risk reducing mastectomy.  
 
Contraindications include those with locally advanced breast cancer (with or without chest wall or skin 
invasion) or inflammatory breast cancer, extensive axillary lymph node metastasis (stage IIIB or later) or  
high risk patients with severe and poorly controlled co-morbid conditions (include but not limited to 
diabetes, heart disease, renal failure, liver dysfunction), pregnant ladies, patients with previous thoracic 
radiation as well as patients with any psychiatric, addictive, or any disorders which compromises the 
ability to give informed consent for participation in this study. 
 
The inclusion and exclusion criteria are based on current evidence derived from exisiting literature on 
robotic mastectomy. 
 
Data collection include clinicopathologic characteristics of patients, type of mastectomy, method of 
breast reconstruction (if any), operative time, intra-operative blood loss, length of hospital stay, 
complications and margin involvement. Patients’ satisfaction and quality of life (QOL) will also be 
assessed using Breast-Q and QoR-15 questionnaire at screening and post operation. 
 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 8 of 15 
Restricted, Sensitive (Normal) 
 
Conduct of Robotic Mastectomy  
 
Pre-operative marking and positioning 
Pre-operative marking will be done with the patient in standing and supine position. After induction of 
general anaesthesia, patient will then be placed in a supine position with ipsilateral arm abducted to 90° 
to avoid conflict with the operative procedure.  
 
 
Axillary staging procedure 
In patients for whom sentinel lymph node biopsy (SLNB) is indicated, 3 to 5ml of 1% methylene blue 
(Merck, Darmstadt, Germany) will be injected into the breast parenchyma facing the ipsilateral axilla 
after induction of general anaesthesia. The breast tissue around the injection site will be gently massaged 
for 5 to 10 minutes. SLNB will be performed according to standard practice. Fresh frozen section will 
be sent for intra-operative analysis as indicated. If SLN is positive for metastases, a complete axillary 
lymph node dissection (ALND) up to level II will be performed. 
 
 
Robotic Docking and Mastectomy 
To create working space for placement of the single port (Glove Port; Nelis Corporation, Gyeonggi-do, 
Korea), a 3–4 cm subcutaneous flap will be dissected with electro cautery under direct vision. The 
tunneling technique is then used to facilitate skin flap dissection and create space between the skin flap 
and the breast parenchyma. Once adequate dissection is achieved, the single port is then inserted 
through the axilla incision and carbon dioxide (CO2) insufflation with air pressure kept at 8 mmHg will 
be used to create space for mastectomy. The ipsilateral shoulder will be elevated to 30 degrees to 
prevent conflict between the operating table and docking of the robotic surgery system. The robotic 
side cart (da Vinci; Intuitive Surgical, Sunnyvale, CA, USA) is then positioned from the contralateral 
side or over the patient’s head, with the two robotic arms endoscope extending over the patient in 
proximity to the ports before the ports are then docked to the robotic arms. Subsequently, the conduct 
of the operation is then shifted to the da Vinci Xi (Intuitive Surgical, Sunnyvale, CA, USA) robotic 
platform controlled by the operating surgeon at the console. A 30 degree 12 mm diameter camera 
(Intuitive Surgical, Denzlingen, Germany) in the upper port will be used to prevent collisions with other 
instruments. Dissection is carried out using a 8 mm monopolar scissors (Intuitive Surgical, Sunnyvale, 
CA, USA). Traction and counter-traction, along with maintaining exposure will be carried out using a 8 
mm ProGrasp forceps (Intuitive Surgical, Sunnyvale, CA, USA). The location of the scissors and the 
ProGrasp forceps could be changed inter-variably during the operation. Dissection is first initiated from 
the superficial skin flaps by dissecting the septa between the skin flap and parenchyma created by the 
tunneling technique with monopolar scissors. A sub-areolar biopsy and fresh frozen section analysis will 
be performed in a nipple sparing mastectomy. If cancer cell invasion is then found in the sub-areolar 
area, the entire NAC will be removed and conversion to a skin sparing mastectomy will be performed. 
After completion of the superficial skin flap dissection, dissection of the peripheral portion of the 
breast parenchyma is carried out subsequently. Posterior dissection is then performed by detaching the 
breast tissue from the pectoralis major muscle fascia with the perforator vessels clearly identified and 
secured. After completion of dissection, the entire breast specimen will be removed intact through the 
incision. 
 
Reconstruction 
In this study, suitable participants can opt for immediate reconstruction with implant or autologous 
tissue (latissimus dorsi flap) reconstruction 
 
 
Immediate Implant Reconstruction 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 9 of 15 
Restricted, Sensitive (Normal) 
Following removal of the specimen and adequate haemostasis, copious irrigation of the mastectomy 
pocket will be performed. Subsequently, the lateral border of the pectoralis major muscle is elevated to 
allow for submuscular pocket dissection. The working space is then developed under direct vision by 
electrocautery with assistance of a handle light retractor. The single port will then be re-inserted with 
CO2 insufflation for robotic sub-muscular pocket dissection using the da Vinci surgical platform. 
Dissection is performed medially towards the sternal border, taking care not to injure the perforator 
vessels. Inferiorly, the dissection is carried out beyond the inframammary fold over the lateral aspect, 
below which the muscle will be released to continue the dissection to the subcutaneous plane thus 
allowing for a more natural placement of the implant. In the lateral border, the superficial fascia of the 
serratus anterior muscle will be dissected posteriorly in a limited fashion so that it will just be enough to 
accommodate the lateral border of the implant. After initial dissection of the sub-muscular space with 
the da Vinci surgical platform, the robotic instruments and single port will then be removed. The 
operating table will be repositioned into the sitting position. The adequacy of the sub-muscular pocket 
dissection is checked and completed with the assistance of a light source retractor. After creation of the 
submuscular pocket, an implant (Mentor Worldwide LLC, Santa Barbara, CA) will then be placed 
followed by drains placement in both submuscular and subcutaneous planes. An acellular dermal matrix 
(ADM) or mesh might be used based on surgeon’s discretion.  
 
 
Immediate Pedicled Latissimus Dorsi (LD) Flap Reconstruction  
 
Following removal of the specimen and adequate haemostasis, copious irrigation of the mastectomy 
pocket is performed. Subsequently, the thoracodorsal pedicle is identified and marked with a vessel 
loop to prevent injury during the flap harvest. Patient is then shifted to the lateral decubitus position. 
Two 12 mm balloon trocars (Kii Balloon blunt tip system, Applied Medical, Rancho Santa Margarita, 
CA, USA) will be used as working ports. The ports are then docked to the robotic arms, and CO2 
insufflation is applied at 10–12 mmHg. Dissection will then start along the under surface of the 
latissimus dorsi muscle. Blood vessels encountered are carefully dissected, coagulated and cut with 
monopolar scissors. As the dissection through the under surface of the muscle to the borders is 
completed, further dissection over the superficial surface of the muscle ensued. The muscle is then 
disconnected from the infero-posterior and scapular border. Afterwards, the pedicled LD flap is 
exteriorized from the axilla wound and the robotic arms are then undocked. Reconstruction of the 
mastectomy defect will be performed with the patient turned back to a supine position. Fixation of the 
flap to all quadrants is performed with assistance from a handle light retractor to ensure full coverage of 
the defect. Care must be taken to ensure the correct axis of the vascular pedicle in order to prevent 
torsion of the blood supply. Drains will then placed both in the donor site as well as mastectomy cavity. 
 
Perioperative monitoring and discharge criteria 
Patients will be monitored in 23-hour ward as per current department protocol as conventional 
mastectomy and discharged on post-operative day 1 if discharge criteria fulfilled.  
 
Discharge criteria include ALL of the following: 
 
Patient MUST have ALL of the following: 
 Stable vital signs 
 Able to maintain pre-procedure mobility with minimal assistance as appropriate for the 
procedure 
 Able to retain feeds 
 Able to pass urine 
 Has a responsible adult to accompany him/her home 

 
Version <5>, Dated <5 Jul 2023> 
Page 10 of 15 
Restricted, Sensitive (Normal) 
 
Patient must NOT have ANY of the following: 
 Excessive pain not relieved by oral analgesics 
 Excessive nausea/ vomiting 
 Severe giddiness 
 Respiratory depression/ difficulty 
 Bleeding from surgical wound 
 
*Patient who doesn’t fulfil ALL of the above will be admitted for further observation 
 
 
Visit 1 
 
(Screening) 
Visit 2 
(Day of 
Surgery) 
Visit 3 (+/-2 
weeks)      
(30th POD) 
Visit 4 (+/-
2 Weeks) 
(6 months 
POD) 
Consent taking 
X 
 
 
 
Eligibility Check 
X 
 
 
 
Adverse Event Assessment 
 
X 
X 
X 
Clinical Assessment 
X 
 
X 
 
Collection of medical 
information 
X 
X 
X 
X 
 
As part of standard care, patients will be followed up as per conventional surgery. This 
includes twice weekly review of wound by the breast surgeon/ breast care nurses, with the 
earliest visit scheduled on post-operative day 4 and to continue until wound(s) have completely 
healed. 
 
 
6. 
SAFETY MEASUREMENTS 
6.1. 
Definitions 
 
 
Serious adverse event (SAE) in relation to human biomedical research, means any untoward 
medical occurrence as a result of any human biomedical research which: 
 results in or contributes to death 
 is life-threatening 
 requires in-patient hospitalisation or prolongation of existing hospitalisation 
 results in or contributes to persistent or significant disability/incapacity or 
 results in or contributes to a congenital anomaly/birth defect 
 results in such other events as may be prescribed  
 
Adverse event (AE) in relation to human biomedical research means any untoward medical 
occurrence as a result of any human biomedical research which is NOT serious.  Adverse event 
can be any unfavourable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease possibly/ probably/ definitely associated with the participant in the human 
biomedical research. 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 11 of 15 
Restricted, Sensitive (Normal) 
6.2. 
Collecting, Recording and Reporting of Serious Adverse Events (SAEs) to CIRB 
 
Only related SAEs (definitely/ probably/ possibly) will be reported to CIRB. Related means 
there is a reasonable possibility that the event may have been caused by participation in the 
research.  Please refer to the CIRB website for more information on Reporting Requirement 
and Timeline for Serious Adverse Events. 
 
The investigator is responsible for informing CIRB after first knowledge that the case qualifies 
for reporting. Follow-up information will be actively sought and submitted as it becomes 
available.  
 
Related AEs will not be reported to CIRB.  However, the investigator is responsible to keep 
record of such AEs cases at the Study Site File. 
 
6.3. 
Safety Monitoring Plan 
 
The principal investigator will be responsible for ensuring participants’ safety and for reporting Serious 
Adverse Events (SAE) and Unanticipated Problems (UP) to his Institutional Review Board (IRB) as 
required. The IRB will act in an advisory capacity to monitor participant safety, evaluate the progress of 
the study, to review procedures for maintaining the confidentiality of data, the quality of data collection, 
management, and analyses. 
 
6.4. 
Collecting, Recording and Reporting of Reportable Adverse Events relating to 
Medical Device to the Health Sciences Authority (HSA) 
 
The reporting requirements will be will be based on the reporting requirements published on 
HSA website at the time when the event took place. 
 
All adverse events relating to medical device which meets the three basic reporting criteria listed 
below, is considered as a reportable adverse event to HSA: 
 An AE (or potential AE) has occurred. 
 The medical device is associated with the AE. 
 The AE leads to one of the following outcomes: 
o It becomes a serious threat to public health. 
o The death of a patient, user or other person. 
o Serious deterioration in state of health of patient, user or other person. 
o There is no death or serious injury in the initial AE but it might lead to death 
or serious injury of a patient, user or other person if the AE recurs. 
 
 
7. 
DATA ANALYSIS 
7.1. 
Data Quality Assurance 
 
The principal investigator will institute a continual quality control and quality improvement programme 
to ensure the collection of high-quality data. These measures include a rigorous training and vetting 
programme for the research co-ordinator, a practice of zero-assumption for vague and conflicting 
information, clear and systematic data definition guidelines and an extensive set of inter- and intra- field 
edits that are used to identify and correct errors in the data. 

 
Version <5>, Dated <5 Jul 2023> 
Page 12 of 15 
Restricted, Sensitive (Normal) 
 
7.2. 
Data Entry and Storage 
 
Data entry will be done into an encrypted REDCAP database, as well as SPSS/STATA database. The 
files will be secured with an ID and password. The data is manually coded and stored digitally in 
secured institutional cloud storage  
 
8. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
8.1. 
Determination of Sample Size  
 
As this is a pilot study aimed to assess feasibility and safety of robotic mastectomy, sample size 
calculation is not necessary. However, the principal investigator will apply the current flat rules of 
thumb for overall pilot trial sample size of a subsequent two-armed trial in determining the current 
sample size. Using this rule, a minimum pilot sample size of 20 cases is recommended. 
 
For the sample size justification, confidence interval for one proportion approach with continuity 
correction method is used, which is able to identify a realistic uncertainty level about the safety endpoint 
based on binomial theory. A sample size of 20 cases will produce 80% confidence interval with a width 
equal to 28% (resulting in a 80% confidence interval of 6%-34%), when the sample proportion is 20%. 
Sample size calculation is performed using PASS software (PASS 14 Power Analysis and Sample Size 
Software (2015). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass.). 
 
In addition, based on a learning curve analysis on robotic mastectomy, a minimum of 12 cases are 
required to reduce the operative time and a pilot sample size of 20 will allow for meaningful 
interpretation and analysis of learning curve data in this pilot study. 
 
8.2. 
Statistical and Analytical Plans 
 
Patient characteristics and outcome variables will be reported via descriptive statistics. Continuous 
variables will be presented as mean, standard deviation, median, first- and third-quartile, minimum and 
maximum; while binary and categorical variables will be reported as frequency and percent. 95% 
confidence intervals will be generated for the primary and secondary endpoints. Statistical analyses will 
be performed using SAS software version 9.4 for Windows (Cary, NC: SAS Institute Inc.). 
 
9. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
 
The investigator(s)/institution(s) will permit study-related monitoring, audits and/or IRB review and 
regulatory inspection(s), providing direct access to source data/document. 
 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE 
 
Data entry are assessed by the PI against source documents for accuracy. Data definition are  
drawn up and codes listed in a Data dictionary. Internal cross checks are performed for   
conflicting, unlikely and out-lying information. PI will be responsible for data quality. 
 

 
Version <5>, Dated <5 Jul 2023> 
Page 13 of 15 
Restricted, Sensitive (Normal) 
 
11. 
ETHICAL CONSIDERATIONS 
 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and that are consistent with the Good Clinical Practice and the applicable 
regulatory requirements. 
 
This final study protocol, including the final version of the Patient Information and Informed Consent 
Form, must be approved in writing by the Centralised Institutional Review Board (CIRB), prior to 
enrolment of any patient into the study. 
 
The principle investigator is responsible for informing the CIRB of any amendments to the protocol or 
other study-related documents, as per local requirement. 
 
11.1. Informed Consent 
 
Written informed consent will be obtained from the patient by the principal investigator prior to any 
study procedures, and in a conducive environment without any coercion, duress or undue influence. 
 
The informed consent form will also be personally signed and dated by the investigator obtaining 
informed consent, the trial participant or legal representative, and HBRA prescribed witness or 
impartial witness (if the trial participant is unable to read or personally sign or date the informed 
consent form). 
 
The signature of the investigator obtaining informed consent should be consistent with the Signature 
Sheet. 
 
11.2. Confidentiality of Data and Patient Records 
 
The data in the database will be anonymised, and all patient identifiers will be coded. Patient’s name and 
NRIC number will be stored in a separate file, which will not contain any details of their medical 
history. All files will be secured with an ID and password. Duplication of data is disabled. 
 
Only the PI and research coordinator will have direct access to the research data and the rest of the 
study team members may request to have access via the PI.  All requests to view the data will have to 
made through the PI and the PI will control and monitor who and how the data is accessed. Access will 
be controlled by password and encryption of excel files and other various software used to collate data. 
 
12. 
PUBLICATIONS 
 
We follow guidelines for authorship, acknowledgement for authorship of publication based on 
recommendations 
of 
the 
International 
Committee 
of 
Medical 
Journal 
Editors 
(http://www.icmje.org/recommendations/browse/about-the-recommendations/purpose-of-the-
recommendations.html) 

 
Version <5>, Dated <5 Jul 2023> 
Page 14 of 15 
Restricted, Sensitive (Normal) 
 
13. 
RETENTION OF STUDY DOCUMENTS 
 
The electronic database will be retained for 7 years from the end of the study.  
 

 
Version <5>, Dated <5 Jul 2023> 
Page 15 of 15 
Restricted, Sensitive (Normal) 
 
 
14. 
REFERENCES  
1. LaiH-W, ChenC-Y, Mok CW, et al.Robotic nipple-sparing mastectomy: A preliminary report of a 
single institute and joint collective analysis of current reported series. Formos J Surg. 2019 
;52:175–182 
2. LaiH-W, MokCW, ToescaA, et al.Consensus Statement on Robotic Mastectomy: Expert Panel 
from International Endoscopic and Robotic Breast Surgery (IERBS) Symposium 2019. Ann 
Surg.;In press. Jan 2020 
3. Lai HW, Chen ST, Tai CM, Lin SL, Lin YJ, Huang RH, Mok CW, Chen DR, Kuo SJ. Robotic-
Versus Endoscopic-Assisted Nipple-Sparing Mastectomy with Immediate Prosthesis Breast 
Reconstruction in the Management of Breast Cancer: A Case–Control Comparison Study with 
Analysis of Clinical Outcomes, Learning Curve, Patient-Reported Aesthetic Results, and Medical 
Cost. Annals of Surgical Oncology. 2020 Feb 3:1-4. 
4. Lai HW, Chen ST, Mok CW, Lin YJ, Wu HK, Lin SL, Chen DR, Kuo SJ. Robotic versus 
conventional nipple sparing mastectomy and immediate gel implant breast reconstruction in the 
management of breast cancer-A case control comparison study with analysis of clinical outcome, 
medical cost, and patient-reported cosmetic results. Journal of Plastic, Reconstructive & Aesthetic 
Surgery. 2020 Feb 18. 
5. Toesca A, Peradze N, Galimberti V, Manconi A, Intra M, Gentilini O, et al. Robotic nipple-
sparing mastectomy and immediate breast reconstruction with implant:First report of surgical 
technique. Ann Surg 2017;266:e28-30. 
6. Toesca A, Peradze N, Manconi A, Galimberti V, Intra M, Colleoni M, et al. Robotic nipple-
sparing mastectomy for the treatment of breast cancer: Feasibility and safety study. Breast 
2017;31:51-6. 
7. Sarfati B, Struk S, Leymarie N, Honart JF, Alkhashnam H, Tran de Fremicourt K, et al. Robotic 
prophylactic nipple-sparing mastectomy with immediate prosthetic breast reconstruction: A 
prospective study. Ann Surg Oncol 2018;25:2579-86 
8. Lai HW, Chen ST, Lin SL, Chen CJ, Lin YL, Pai SH, et al. Robotic nipple-sparing mastectomy 
and immediate breast reconstruction with gel implant: Technique, preliminary results and patient-
reported cosmetic outcome. Ann Surg Oncol 2019;26:42-52. 
9. Sarfati B, Struk S, Leymarie N, Honart JF, Alkhashnam H, Kolb F, et al. Robotic nipple-sparing 
mastectomy with immediate prosthetic breast reconstruction: Surgical technique. Plast Reconstr 
Surg 2018;142:624-7. 
10. Lai HW, Lin SL, Chen ST, Chen SL, Lin YL, Chen DR, et al. Robotic nipple-sparing mastectomy 
and immediate breast reconstruction with gel implant. Plast Reconstr Surg Glob Open 
2018;6:e1828. 
11. Lai HW, Lin SL, Chen ST, Lin YL, Chen DR, Pai SS, et al. Robotic nipple sparing mastectomy 
and immediate breast reconstruction with robotic latissimus dorsi flap harvest – Technique and 
preliminary results. J Plast Reconstr Aesthet Surg 2018;71:e59-61. 
12. Lai HW, Wang CC, Lai YC, Chen CJ, Lin SL, Chen ST, et al. The learning curve of robotic 
nipple sparing mastectomy for breast cancer: An analysis of consecutive 39 procedures with 
cumulative sum plot. Eur J Surg Oncol 2019;45:125-33