Post-operative Emesis and Pain Outcomes After Cesarean Delivery (EPOC)
Conditions: Pain, Postoperative, Cesarean Section, Nausea, Postoperative, Vomiting, Postoperative
Sponsor: KK Women's and Children's Hospital

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STUDY PROTOCOL 
 
 
 
 
 
Post-operative Emesis and Pain Outcomes after Cesarean 
delivery (EPOC) 
 
 
 
UNIQUE PROTOCOL ID: EPOC01 
 
CIRB NUMBER:  
2017/2381 
 
PROTOCOLVERSION:  1.0 
 
PROTOCOL DATE:  
1 Aug 2018 
 
PRINCIPAL INVESTIGATORS:  
Dr Farida Ithnin, Senior Consultant, KK Women's and Children's 
Hospital (KKH) 
 
 
 
 
 
 
 
 
*Also refer to Section F9 on the sample size details. 
 
 
 
 

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Table of Contents 
A. 
PROTOCOL TITLE & PROTOCOL ADMINISTRATORS .................................................................. 3 
B. 
STUDY SITES, STUDY TEAM & SUBMISSION BOARD ................................................................. 4 
C. 
CONFLICT OF INTEREST ............................................................................................................. 5 
D. 
NATURE OF RESEARCH ............................................................................................................... 6 
E. 
STUDY FUNDING INFORMATION ............................................................................................... 6 
F. 
RESEARCH METHODOLOGY ........................................................................................................ 7 
G. 
RECRUITMENT DETAILS ........................................................................................................... 15 
H. 
STUDY SITES & RECRUITMENT TARGETS ................................................................................ 17 
I. 
RESEARCH PARTICIPANT CHARACTERISTICS ......................................................................... 17 
J. 
CONSENT PROCESS – CONSENT REQUIRED ............................................................................ 19 
K. 
RESEARCH DATA CONFIDENTIALITY ....................................................................................... 21 
L. 
DATA & SAFETY MONITORING ................................................................................................. 23 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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A1. Please enter the Full Protocol Title and Protocol Number (if available) for this Study 
A2. You may assign Protocol Administrators for this study below 
Section A: Protocol Title & Protocol Administrators 
Protocol Title 
: Post-operative Emesis and Pain Outcomes after Cesarean delivery 
(EPOC) 
Protocol Number 
( Optional) 
: EPOC01 
No. Name 
Institution/Organization 
Department 
Office 
No. 
Email 
1 
Dr Han Nian Lin 
Reena 
KK Women's and Children's 
Hospital (KKH) 
Division of Clinical Support 
Services 
Han.NianLin@kkh.com 
.sg 
2 
Ms Teo Pei Chih 
Agnes 
KK Women's and Children's 
Hospital (KKH) 
Department of Women's 
Anaesthesiology 
Agnes.Teo.PC@kkh.c 
om.sg 
3 
Dr Tan Chin Wen KK Women's and Children's 
Hospital (KKH) 
Department of Women's 
Anaesthesiology 
Tan.Chin.Wen@kkh.co 
m.sg 

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B3. Submission Board and other IRB 
(i) Which CIRB is this application being submitted to? 
 
CIRB D Anaesthesia (including acupuncture) 
(ii) Has the study been submitted to another IRB? No 
(iii) Has the application been previously rejected by any IRB? (Including 
SingHealth CIRB) No 
Section C: Conflict of Interest 
Does the Principal Investigator or any Study Team Member have any potential conflict of 
interest? The Declaration is also for the immediate family members of the Principal 
Investigator and Study Team Members listed below. 
 
Name 
Study 
Role 
Department 
Institution 
Yes/No 
 
Dr 
Ithnin 
Farida Binte 
PI 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Chan Ju In 
Jason 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr 
Cheng 
ShangMing 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr 
Dabas 
Rajive 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Goy Wee 
Lip 
Raymond 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Lee Song 
En John 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Leong Wan 
Ling 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Lew Eileen 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Lim Ming 
Jian 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr 
Mathur 
Deepak 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr 
Nagarajan 
Singaraselvan 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
 
 
 
 
 
 
 
Dr 
Oh 
Ting 
Ting 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Sng Ban 
Leong 
Co-I 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
Dr Tan Hon 
Sen 
Co-I 
Department of Anaesthesiology Singapore General Hospital (SGH) 
No 
Ms Liu Juan 
Study 
Team 
Member 
Department 
of 
Women's 
Anaesthesiology 
KK Women's and Children's Hospital 
(KKH) 
No 
 
 
 
 

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Section D: Nature of Research 
D1. Please select one category that best describes your research 
activities. Clinical Research 
NOTES: 
Submission to HSA might be required if you are conducting clinical trials. You should 
check with HSA if you are unsure. 
D2. Is this a US FDA IND/IDE study or data is intended to be reported to FDA in support 
of an IND/IDE Application? 
No 
Section E: Study Funding Information 
E1. Please give information regarding the study's funding source or sponsor 
information. 
Grant 
i. Name of Grant Agency: 
Others, please specify 
ANAESTHESIOLOGY & PERIOPERATIVE SCIENCES ACP 
ii. Grant Name: Anaesthesiology ACP Pilot Research Grant iii. 
Amount: 10000 
iv. Deadline of Grant Application: 31 Jan 
2018 v. Has the grant been approved? Yes 
 
 
Reference Number ANAESPRG18/02 
NOTES: 
If you choose this option, the CIRB may only start reviewing the study when 
preliminary result for the Grant Application is available. Please contact the CIRB 
once you have received information on the grant results to start the CIRB review 
process. If your grant application was not successful, please advise the CIRB on 
your next course of action (e.g. withdrawal of the study, look for alternative funding 
etc.). 
E3. Who will be responsible for the payment and compensation of injury or illness 
to participants arising from participation in the study? 
The Hospital does not make any provisions to compensate study participants for research 
related injury. However, compensation may be considered on a case-by-case basis for 
unexpected injuries due to nonnegligent causes. 
E4. Who will be responsible for research-related costs? For sponsored studies, 
please list the costs that will be borne by the sponsor. 
Anaesthesiology ACP Pilot Research Grant 
 
 
 
 
 
 

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Section F: Research Methodology 
F1. Please provide an abstract of your proposed research (Up to 300 words). 
Approximately 1 in 5 women who undergo cesarean delivery would suffer from severe post-
operative pain, which may further increase their risks from developing postpartum depression. 
Predictive factors such as pre-operative pain, age and anxiety could significantly contribute to 
post-operative nausea and vomiting (PONV) and pain in general surgery, however little 
information is available with regards to cesarean delivery. Previous studies demonstrated that 
pain scores upon local anesthetic injection is positively correlated to post-cesarean pain scores. 
Additionally, anxiety, anticipated post-operative pain score and anticipated medication need are 
also found to be promising risk factors to postcesarean pain management. 
We aim to investigate the risk factors of causing post-operative emesis after cesarean delivery, 
and to reaffirm that there is a positive correlation between pain on local anesthetic injection, 
presence of mechanical temporal summation (MTS) and post-Cesarean pain scores. We will 
recruit 200 parturients undergoing cesarean delivery at KK Women’s and Children’s Hospital and 
requiring regional anesthesia. Pain and anxiety assessment will be conducted via visual 
analogue scoring (VAS), MTS assessment and a series of questionnaires. After the delivery, all 
patients will be given appropriate analgesia, and the pain score at movement will be recorded. 
Secondary outcomes include pain scores at rest, analgesia consumption, time-to-first-rescue 
analgesia, opioid-related side effects, patient satisfaction and postpartum depression. 
This proposal will determine the clinical relevance of pre-operative determinants for post-
cesarean pain management in local context. This would help us discover new risk management 
strategies and identify modifiable treatment. We hope that this will serve as a guideline for 
consistent and reliable delivery of care while enhancing the effectiveness and patient satisfaction 
in obstetrics pain management. 
F2. What are the specific aims and hypothesis of this study? 
Primary hypothesis: Women that undergo cesarean delivery at KK Women’s and 
Children’s Hospital, Singapore, who has higher pain score upon local anesthetic injection, 
will have higher risk of getting postcesarean pain. 
Primary aim: To determine whether there is a positive correlation between pain on local 
anesthetic injection and post-Cesarean pain scores in women that undergo cesarean 
delivery at KK Women’s and Children’s Hospital, Singapore. 
Secondary hypothesis (1): Women that undergo cesarean delivery at KK Women’s and 
Children’s Hospital, Singapore, who has mechanical temporal summation (MTS>0), will 
have higher risk of getting post-cesarean pain. 
Secondary aim (1): To determine whether there is a positive correlation between 
mechanical temporal summation and post-Cesarean pain scores in women that undergo 
cesarean delivery at KK Women’s and Children’s Hospital, Singapore. 
Secondary hypothesis (2): Women that undergo cesarean delivery at KK Women’s and 
Children’s Hospital, Singapore, who has higher anxiety score, anticipated pain score and/or 
anticipated medication need, will have higher risk of getting post-cesarean pain. 
Secondary aim (2): To determine whether there is a positive correlation between higher 
anxiety score, anticipated pain score and/or anticipated medication need and post-
Cesarean pain scores in women that undergo cesarean delivery at KK Women’s and 
Children’s Hospital, Singapore. 
Exploratory Aim: To examine the correlation between medical history (presence of 
hyperemesis gravidarum, motion sickness, PONV etc.), demographical data and the incidence 
of post-operative emesis.  
 

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F3. Please briefly describe the background to the current study proposal. Critically 
evaluate the existing knowledge and specifically identify the gap that the proposed 
study is intended to fill. 
Cesarean delivery is one of the most common surgical procedures performed in the United 
States, making up over 32% of all live births – about 1.3 million per year [1]. Similarly, 
cesarean delivery constitutes about 30% total delivery in our institution, contributing to 3000-
4000 cases annually. Approximately 1 in 5 women who undergo Cesarean delivery will 
experience acute, severe postoperative pain[2]. This is important because the most significant 
predictive factor for the development of chronic pain after Cesarean delivery appears to be the 
severity of acute pain in the post-operative period [2, 3].  Thus, it is imperative to optimize pain 
management strategies during this time. The challenge for physicians is that inter-individual 
pain experience is highly variable, such that a “one-size-fits-all” approach is often inadequate 
for a large portion of patients with greater pain needs. 
Many methods have been put forth to try to utilize preoperative measures to predict which 
patients will have greater post-operative pain needs, with varying levels of success. A 
systematic review of general surgery procedures found that preoperative pain, anxiety, age, 
and type of surgery were the most common variables consistently found to be significant 
predictors of postoperative pain, and that type of surgery, age, and psychological distress 
were the most commonly found significant predictors of analgesic consumption [4]. Although 
research has been done on this subject in the general surgical population, there is less 
information available with regards to Cesarean delivery. 
Patients undergoing Cesarean delivery are unique in that in addition to their own recovery, 
they also must begin bonding with and caring for their newborns after delivery. The need for 
early mobilization and avoidance of over-sedation is also important in this population due to an 
increased risk for thromboembolic complications in the postpartum period [5]. It is also 
important to avoid under-treating this population, as acute, severe post-Cesarean pain triples a 
woman’s chances of developing postpartum depression [2]. Additionally, severe acute post-
Cesarean pain greatly increases the risk of developing chronic pain [2], which occurs in 9.2% - 
18% of women who undergo Cesarean delivery [6-8]. 
With the unique needs of this population in mind, prior research has focused on seeking out 
factors that may help identify patients who will have greater pain needs after Cesarean 
delivery. Previous studies have compared preoperative quantitative sensory testing (QST) and 
postoperative pain, with some encouraging results. Studies on preoperative pressure pain 
thresholds and pressure pain tolerance have shown modest correlation between these factors 
and postoperative pain and analgesic need [9-11]. Testing of preoperative pain using electrical 
stimulation has also yielded modest correlations with postoperative pain and analgesic 
consumption [9, 10, 12, 13]. Preoperative heat pain and sensitivity have likewise demonstrated 
correlations of varying strength with postoperative pain [14-16]. Finally, one recent study has 
found a significant correlation between patients’ pain scores in response to preoperative local 
anesthetic injection and post-Cesarean pain scores [17]. 
Other studies have been performed that utilize preoperative questionnaires in an attempt to 
predict postCesarean pain, again with encouraging results. One study used preoperative 
State-Trait Anxiety Inventory (STAI) scores and found that patient’s responses correlated with 
their total analgesic needs[15]. Another study employed a preoperative “Pain Catastrophizing 
Scale,” and found that patient’s responses were correlated with their post-operative pain 
scores [16]. Finally, a more recent attempt has used a simple, three question preoperative 
assessment and found that patient’s responses were correlated with postoperative pain on 
mobilization in both derivation and validation cohorts, accounting for up to 20% of the variance 
in post-Cesarean pain [18]. Following up these findings, the same group found that within a 
cohort of patients identified as having higher pain needs with the “three simple questions,” 
those who were randomized to receive higher doses of pain medication reported better 
postoperative pain management compared to a control group that received standard doses of 
pain medication [19]. 
Of the physical factors that have been studied, pain scores upon injection of local anesthetic 
seem to be the most promising in regards to clinical application, as the testing involved in the 
other methods (pressure, heat, and electric stimulation) are likely too time-intensive to be 

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clinically feasible, while local anesthetic injection is already part of the standard protocol for 
initiating spinal or epidural anesthesia. And although all of the questionnaires appear to have 
some potential for clinical use, the three simple questions appears to be the most useful due to 
its brevity while maintaining acceptable sensitivity and specificity for identifying patients who 
will fall in the upper 20th percentile of pain needs [18]. Local anesthetic injection and the “three 
simple questions” are both promising techniques that could lead to greater post-Cesarean pain 
management, but neither has yet to be validated outside of their respective institution of origin. 
Therefore, the purpose of this study is to evaluate the effectiveness of these two measures for 
the prediction of postoperative pain in women undergoing Cesarean delivery at KKH. 
While numerous studies have investigated risk factors for postoperative nausea and vomiting 
in the general surgical population, there are relatively little data in the obstetric patient 
population. We will collect information about potential risk factors for post-operative nausea 
and vomiting (PONV), and assess for association with the occurrence of PONV. We will 
collect information about the following factors: history of PONV after CD, history of PONV after 
non obstetric surgery, history of morning sickness, history of hyperemesis gravidarum, history 
of motion sickness, smoking history, occurrence of intraoperative nausea and vomiting, and 
exteriorization of the uterus. 
F4. Please provide a list of relevant references. 
1. Hamilton, B.E., et al., Births: Final Data for 2014. Natl Vital Stat Rep, 2015. 64(12): p. 1-64. 
2. Eisenach, J.C., et al., Severity of acute pain after childbirth, but not type of delivery, predicts 
persistent pain and postpartum depression. Pain, 2008. 140(1): p. 87-94. 
3. Niklasson, B., et al., Risk factors for persistent pain and its influence on maternal wellbeing 
after cesarean section. Acta Obstet Gynecol Scand, 2015. 94(6): p. 622-8. 
4. Ip, H.Y., et al., Predictors of postoperative pain and analgesic consumption: a qualitative 
systematic review. Anesthesiology, 2009. 111(3): p. 657-77. 
5. James, A.H., et al., Venous thromboembolism during pregnancy and the postpartum period: 
incidence, risk factors, and mortality. Am J Obstet Gynecol, 2006. 194(5): p. 1311-5. 
6. Kainu, J.P., et al., Persistent pain after caesarean section and vaginal birth: a cohort study. Int 
J Obstet Anesth, 2010. 19(1): p. 4-9. 
7. Nikolajsen, L., et al., Chronic pain following Caesarean section. Acta Anaesthesiol Scand, 2004. 
48(1): p. 111-6. 
8. Sng, B.L., et al., Incidence and risk factors for chronic pain after caesarean section under 
spinal anaesthesia. Anaesth Intensive Care, 2009. 37(5): p. 748-52. 
9. Buhagiar, L., et al., Predictors of post-caesarean section pain and analgesic consumption. J 
Anaesthesiol Clin Pharmacol, 2011. 27(2): p. 185-91. 
10. Buhagiar, L.M., et al., Pre-operative pain sensitivity: A prediction of post-operative outcome in 
theobstetric population. J Anaesthesiol Clin Pharmacol, 2013. 29(4): p. 465-71. 
11. Ortner, C.M., et al., Preoperative scar hyperalgesia is associated with post-operative pain in 
womenundergoing a repeat Caesarean delivery. Eur J Pain, 2013. 17(1): p. 111-23. 
12. Nielsen, P.R., et al., Prediction of post-operative pain by an electrical pain stimulus. Acta 
AnaesthesiolScand, 2007. 51(5): p. 582-6. 
13. Wilder-Smith, C.H., et al., Postoperative sensitization and pain after cesarean delivery and the 
effects ofsingle im doses of tramadol and diclofenac alone and in combination. Anesth Analg, 
2003. 97(2): p. 52633, table of contents. 

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14. Granot, M., et al., Postcesarean section pain prediction by preoperative experimental pain 
assessment.Anesthesiology, 2003. 98(6): p. 1422-6. 
15. Pan, P.H., et al., Multifactorial preoperative predictors for postcesarean section pain and 
analgesicrequirement. Anesthesiology, 2006. 104(3): p. 417-25. 
16. Strulov, L., et al., Pain catastrophizing, response to experimental heat stimuli, and post-
cesarean sectionpain. J Pain, 2007. 8(3): p. 273-9. 
17. Orbach-Zinger, S., et al., Severe pain during local infiltration for spinal anaesthesia predicts 
postcaesarean pain. Eur J Pain, 2015. 19(9): p. 1382-8. 
18. Pan, P.H., et al., Predicting acute pain after cesarean delivery using three simple 
questions.Anesthesiology, 2013. 118(5): p. 1170-9. 
19. Booth, J.L., et al., A Randomized Controlled Trial Comparing Two Multimodal Analgesic 
Techniques inPatients Predicted to Have Severe Pain After Cesarean Delivery. Anesth Analg, 
2016. 122(4): p. 1114-9. 
20. Gureje O, Simon GE, Von Korff M. A cross-national study of the course of persistent pain in 
primary care. Pain. 2001 May;92(1-2):195-200. 
21. Carroll LJ, Cassidy JD, Cote P. Depression as a risk factor for onset of an episode of 
troublesome neck and low back pain. Pain. 2004 Jan;107(1-2):134-9. 
22. Doan L, Manders T, Wang J. Neuroplasticity Underlying the Comorbidity of Pain and 
Depression. Neural plasticity. 2015;2015. 
F5. Please provide an account of the Principal Investigator's preliminary studies 
and progress reports (if any) pertinent to this application. 
We have an extensive research network collaboration with national and cluster funding, 
together with publications and conference presentations to illustrate collaboration, 
productivity and capability to execute large clinical trials. We have expertise in studies 
related to PND, persistent pain and childbirth pain, expertise in large clinical trials and 
focused pain publications.  
Studies Related to Postnatal Depression 
At KK Hospital, we have developed a strong collaborative multidisciplinary research team, 
with the principal investigator who has childbirth pain and PP management skills, co-
investigators (Dr Helen Chen, Dr Chua Tze Ern) with expertise in PND and (Assoc Prof Tan 
Ene Choo) genetics, extending the work funded by the NMRC Exploratory Development 
Grant (NMRCEDG1006). The abstract was presented for the oral competition at the 
recently concluded Association of Anaesthetists in Great Britain and Ireland meeting in 
Edinburgh September 2015 and has been accepted for publication by the journal 
Neuropsychiatric Disease and Treatment (impact factor 1.8). 
We conducted a pilot cohort study involving 479 women who delivered at KK Hospital from 
November 2010 to October 2013 who had psychological assessment. The analgesic 
outcomes were analysed retrospectively. PND diagnosis was made using psychiatrist 
diagnosis. PND was present in 12.9% (62/479). The incidence of PND was 10.0% (33/329) 
of women who received epidural analgesia and 19.3% (29/150) of those who choose non-
epidural analgesia (p=0.0149). The independent risk factors included the absence of 
epidural analgesia being associated with increased risk of PND (OR 1.95,95%CI 1.04-
3.66,p=0.0367). Increasing age was associated higher risk of PND (OR 1.56,95%CI 1.15- 
2.14,p=0.005, every 5 years increase). Psychological factors associated with PND were 
family history of depression (OR 11.1, 95%CI 4.23-29.75,p<0.0001), history of depression 
(OR 10.61,95%CI 2.34- 
58.15,p=0.003) and previous history of PND (OR 9.42,95%CI 3.7-24.54,p< 0.0001). Though 
the findings of this observational study is intriguing, a more definitive trial is required to 
provide strong evidence for this observation. Furthermore, the outcomes for PP after 
childbirth were not available. 

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The principal investigator has recently published an invited review article as the senior 
author in a peer reviewed journal: Trends in Anaesthesia and Critical Care on ‘Childbirth 
pain and Postpartum Depression’. The article illustrates the expanded role of the 
anaesthetists beyond pain relief and provides an argument for the discipline to take a 
greater role in patient care during childbirth. The accompanying commentary by Vuilleumier 
et al titled ‘Is Birthing pain the trigger of postpartum depression? A commentary on 
Childbirth pain and Postpartum Depression’ is evidence of the overwhelming interest in this 
topic. The authors suggested that further work is needed in order to understand how pain 
and depression relate to each other and that improved attention to helping women achieve 
desired pain control during and after childbirth may have far reaching benefits.   
Studies Related to Persistent Pain and Childbirth Pain 
The principal investigator was awarded the NMRC Transition Award (NMRC/TA/0017/2013) 
together with co-investigator (Assoc Prof Tan Ene Choo) and mentor (Prof Alex Sia). This 
ongoing study utilizes a comprehensive programme to investigate persistent pain after 
hysterectomy. Based on a preliminary study of the first 100 subjects, pain catastrophizing 
is a univariate analysis significant factor in chronic posthysterectomy, in particular women 
with increased rumination and helplessness. The independent risk factors were increased 
pain scores in the recovery room and lower risk in the Chinese race suggesting ethnic 
differences. The results were presented for oral presentation competition at the recently 
concluded Australian Pain Society Meeting at Brisbane March 2015. 
Our pilot data using arterial spin labelling, a new MRI sequence allows objective 
quantification of relative cerebral blood flow. There is increased perfusion in the thalamus 
during heat stimulation (rising to 90mL/100g/min) that returns to baseline (60mL/100g/min) 
after stimulus is removed. Initial group analysis shows increased relative cerebral blood 
flow in multiple regions (frontal lobe, insula, temporal lobe, caudate) for those who develop 
chronic pain compared to those who are pain free.  
We have also found that chronic or persistent pain after Caesarean section is associated 
with acute pain recalled in the immediate postoperative period after Caesarean section. The 
principal investigator presented the results as part of an invited speaker presentation at the 
Australian and New Zealand College of Anaesthetists Meeting at Singapore May 2014 on 
chronic pain in obstetrics. 
The principal investigator and mentor specializes in obstetric anaesthesia and analgesia 
with productivity in publications on labour epidural analgesia and childbirth pain. The recent 
paper specifically addressed the role of breakthrough pain (unscheduled epidural 
supplementation by anaesthetist to treat pain whilst being on labour epidural analgesia due 
to inadequate pain relief) being associated with dysfunctional labour, reduced patient 
satisfaction and reduced successful patient bolus during epidural analgesia.  
COLEUS: Clinical Trial Network Collaboration with PND and PP 
COLEUS Clinical Trials Grant framework (NMRC/CTGIITL/0001/2014) investigates 
psychological and pain development associated with labour epidural analgesia as 
secondary outcomes in the setting of a randomized controlled trial of innovative epidural 
delivery systems developed between KK Hospital and industry. This research network 
establishes the close scientific collaboration between anaesthesia (Dr Sng Ban Leong, Dr 
Leong Wan Ling, Prof Alex Sia) and Women’s Mental Wellness Service (Dr Helen Chen, Dr 
Chua Tze Ern). The trial is focuses on nulliparous women who requested epidural 
analgesia during labour only and aims to identify outcomes of PND, PP after childbirth and 
breastfeeding outcomes within women who receive epidural analgesia. The principal 
investigator is experienced in leading a large research trial with scientific rigor in innovative 
medical technology. The administrative and statistical setup includes electronic online 
randomization and data management through REDCAP electronic database.  
From the COLEUS trial screening log (as of 18 November 2015), 814 women were 
screened. 667 women (81.9%, 667 out of 814) expressed that they were uncertain of their 
choice of pain relief during the screening phase. 98 women refused epidural analgesia and 
49 women were certain of receiving epidural analgesia. The trial epidural regimens were 
administered to 199 women, 218 women received epidural analgesia but not part of the trial 

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(refusal, exclusion criteria) and 397 women (48.8%, 397 out of 814) chose non-epidural 
pain relief. Hence, there is clinical equipoise in randomizing the women who were uncertain 
of their choice of pain relief. Of the eligible 176 women with adequate follow up, 134 women 
(76.1%) responded to the postnatal survey at 6 to 10 weeks after delivery. 
F6. Short Term Implications of Research 
Our prospective group study will investigate the role of modifiable risk factors and develop a 
model that would take into account biological and psychological mechanisms to better 
understand PONV and pain after cesarean surgery.  We will identify modifiable risk factors 
and explore the interplay of psychological and pain pathways will be investigated through 
targeted selected serotonin, monoamine and oxytocin candidate gene polymorphism with 
post-operative pain, PONV and postnatal depression. Our study will broaden the current 
understanding and basic neurobiological mechanisms especially in central sensitisation and 
central nervous system dysregulation in PONV and post-operative pain. We will validate the 
role of analgesic interventions and needs in reducing the risk of PONV and post-cesarean 
pain and change the current clinical practice in the care during cesarean delivery 
management. The proposed study will guide us in future studies on potential novel risk 
stratification and identify modifiable risk factors as therapeutic targets. 
F7. Long Term Implications of Research 
The long term goal of our project is to establish a collaborative care model according to 
each individual’s risk factors and eventually to target specified interventions to minimize the 
risk of PONV and improve the pain experience after childbirth. The psychobiological model 
derived from this trial could be the basis of subsequent hypothesis testing in research into 
modifiable risk factors, as well as, validation of the model in a new population group such 
as other pain syndromes. This trial would aim to develop prediction and model validation in 
the long term. We plan to incorporate a longer term follow-up study (2 to 3 years) following 
this proposal to examine the sustained effect of these risk factors on post-operative pain 
and depression after childbirth including health sciences outcomes like cost-effectiveness 
analysis and longer term functional outcomes.  
Ultimately, this trial will lay a strong foundation for subsequent prospective randomized 
clinical trials to determine whether rigorous risk stratification, psychological treatment and 
analgesic interventions can prevent PONV and improva pain after childbirth. This proposal 
will also be the basis of framework for future research in pain and related psychological 
disorders. Foreseeable applications may include functional brain imaging extending the 
capabilities of the NMRC Transition Award which is still being developed. Future research 
studies, based on the model, drug interventions, targets and psychological interventions 
would lead to better healthcare and patient outcomes. 
F8. Discuss in detail the experimental design and procedures to be used to 
accomplish the specific aims of the study. If this study involves a retrospective 
medical record review, please specify the period of data collection. 
The proposed study is an observational study in 200 women who undergo cesarean delivery at 
KK Women’s and Children’s Hospital, Singapore. Informed consent will be obtained from all 
subjects. Singhealth Centralised Institutional Review Board approval and Clinical Trials 
Registration will be obtained. 
Before delivery 
Women scheduled to undergo a cesarean delivery under spinal or combined spinal epidural 
anesthesia will be approached to participate in the study. After obtaining informed consent, 
patients will be asked about any history of PONV after CD, history of PONV after non 
obstetric surgery, history of morning sickness, history of hyperemesis gravidarum, history of 

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motion sickness, smoking history, and occurrence of intraoperative nausea and vomiting. The 
obtained data will be documented in Data Collection Form. 
Patients will be asked to rate, using a 0-10mm visual analog scale (VAS), their surgical anxiety 
level (“On a scale of 0-100, with 0 being not anxious at all to 100 being extremely anxious, how 
anxious are you about your upcoming surgery?”), their anticipated pain (On a scale of 0-100, 
with 0 being no pain at all and 100 being pain as bad as you can imagine, how much pain do 
you anticipate experiencing after your upcoming surgery?”), and using a categorical scale, their 
anticipated pain medication need (“On a scale of 0 to 5, with 0 being none at all, 1 being much 
less than average, 2 being less than average, 3 being average, 4 being more than average, and 
5 being much more than average, how much pain medication do you anticipate needing after 
your upcoming surgery?”). 
Study survey will be administered upon recruitment in antenatal clinic or delivery suite or till 5-14 
days after discharge whenever patient is comfortable. It includes Edinburgh Postnatal 
Depression Scale (EPDS), Pain Catastrophizing Scale (PCS), Central Sensitisation Inventory 
(CSI), EQ-5D-3L and HADS. The estimated duration of the surveys is about 30 minutes.  
Mechanical temporal summation (MTS) assessment using a 180 gram von Frey filament applied 
to the patient’s arm, as demonstrated by Weissman-Fogel, et al.[20], will be done prior to 
surgery and results recorded. The anesthetic technique will be standardized using the current 
standards of care. All women will receive antacid prophylaxis with 30 ml sodium citrate. The 
spinal anesthesia administered will be standardized doses of intrathecal hyperbaric bupivacaine 
(10.5-12 mg), fentanyl (15 mcg), and preservative-free morphine (100 mcg). Before placing the 
spinal anesthetic, the skin at the site will be infiltrated with 2-5 ml 1.0% lidocaine as per standard 
practice.  It has been shown that the words used during local anesthetic injection can influence 
patient’s subjective experience of pain, so prior to local anesthetic injection we will use a 
standardized script to inform patients that local anesthetic is about to be given: “I am now giving 
you the numbing dose.” After the injection is completed and the needle is removed, the 
anesthesiologist will use a standardized script, “From 0 to 10, where 0 is no pain and 10 is the 
worst pain imaginable, how much did this procedure hurt?” Patient’s responses will be recorded. 
During cesarean delivery: Surgery, intraoperative and postoperative management will be 
performed according to standard practice. Data will be collected on heart rate, blood pressure, 
oxygen saturation, prescence of nausea and vomiting and use of wound infiltration. Acute pain 
in the postoperative care unit (PACU) will be treated at clinician's discretion. 
After delivery and before discharge from the hospital: The woman is interviewed at 0 to 48 
hours on the pain scores at rest and with movement (sitting up in bed from a supine position) 
and will be recorded in the nursing electronic records. Other data such as nausea scores, and 
occurrence of vomiting are also noted. Standard routine monitoring of haemodynamics 
parameters and pain relief will be done in the ward. Study surveys are continued while patient is 
comfortable before discharge or till 5-14 days after discharge. The survey for post-delivery 
health status (HADS, EQ-5D-3L) will take about 10 minutes to complete. 
Six - Ten weeks after delivery: The patient will have a phone survey/ online survey at 6 -10 
weeks post-delivery with: (1) EPDS (2) Pain Survey (3) Pain Vulnerability (PCS, CSI) (4) 
Breastfeeding Questionnaire (5) EQ-5D-3L and (6) HADS. Patients with scores on the 
depression scale consistent with postpartum depression will be referred to their obstetrician or 
primary care physician for further assessment and management. 
  
 
 

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F11. Please describe the participant’s visits (frequency and procedures involved). For 
studies with multiple visits, please attach study schedule. 
There will be 3 visits in total. The duration of study period for each participant can last about 
17 weeks. Below are the main time points for the study activities: 
Visit 1-Before surgery (duration: 4 weeks): 
- 
Patient screening and recruitment before the surgery: gestational age week 36 and above 
- 
Baseline Demographic data collection 
- 
Survey and data collection (EPDS, pain score, vital signs, HADS score, EQ-5D-3L, MTS, 
"three questions", pain vulnerability (PCS, CSI)) 
Visit 2-After surgery (duration of labour till 5-14 days after discharge: ~19 days): 
- 
Pain assessment, survey and data collection (pain score, vital signs, HADS score, EQ-
5D-3L, analgesia usage, occurrence of vomiting, and nausea scores) 
Visit 3-Follow up phone call survey at 6 - 10 weeks after delivery (duration: 10 
weeks):   

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- Phone survey/ Online survey and data collection (EPDS, breastfeeding, HADS score, EQ-
5D-3L, pain score, and pain vulnerability (PCS, CSI)) 
F12. Discuss the potential difficulties and limitations of the proposed procedures 
and alternative approaches to achieve the aims. 
There will be drop out in the follow up phone survey. However, the withdrawal rate has 
been accounted for. 
F13. What are the potential risks to participants? 
During the MTS pain assessment, a test would involve the repeated sensation of pinprick 
testing for increased sensitivity of pain to pinprick in some individuals. 
Analgesic choices will be made upon patient request and routine hospital protocol, 
monitoring and recording will apply. If subjects are screened to have high EPDS (13 or 
more) or persistent pain, they would be advised to seek clinical psychiatric or pain 
assessment at KK Hospital. The assessment would be done as clinical work and not 
research funded. 
No new research medications are involved by joining the study. The drugs being delivered 
are the same as what the patient shall receive as standard care. 
 
F14. What are the potential benefits (direct as well as indirect) to participants? 
Indirect benefit may refer to the medical knowledge gained in the future, from the 
research. 
As this will be an observational study, there will be no direct benefits or harms to patients who 
choose to participate in this study. On a population level, the data collected in this study may 
help to improve pain management for women undergoing cesarean delivery in the future.  
F15. What is the estimated timeline for this study? 
(i) Estimated start date  01-Jun-2017 
(ii) Estimated end date  01-Jun-2019 
Section G: Recruitment Details 
G1. How will potential participants be identified? Please tick all the applicable boxes. 
NOTES: 
If you have selected that participants are “Patients of study team”, please select 
“Yes” for K6. If healthy volunteers are recruited for the study, please select the 
option “Other methods of participant identification” and describe your method(s) 
of participant identification. 
[  ] Referral by attending healthcare professional 
[x] Patients of study team 
[  ] Databases 
[  ] Other methods of participant identification 
G2. Who will make the first contact with participant? 
Investigators and the clinical research coordinators in the study team will make the first 
contact with participant. 

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G3. How will the participant be contacted? 
This study will be advertised with brochures. These will be distributed through KKH, and given 
to all patients who meet the inclusion criteria during antenatal period. Potential study patients 
may be invited to participate by study team members in the antenatal clinics/wards and 
preoperative rooms/wards at KKH. On admission to preoperative rooms/wards, they will again 
be given a study brochure. The investigators and study team will be available to answer any 
queries on this trial in the antenatal clinics/wards and preoperative rooms/wards, through 
phone and email correspondence. 
Recruitment of patients from antenatal clinics/wards: 
All potential patients who are expected to meet the inclusion/exclusion criteria at term and are 
seen in the KKH antenatal clinics/wards will be invited to participate in the study.  
The informed consent process may be conducted at any time during prior to labour. 
Obstetricians and research team will approach the patients in the antenatal clinics/wards to 
provide information about the study. If a patient consents prior to labour, a copy of the 
consent form will be kept in the patient’s case notes. The study investigator will recheck the 
inclusion/exclusion criteria when the patient is at the preoperative rooms/wards prior to the 
initiation of the study activities. 
Recruitment of patients at preoperative rooms/wards: 
The patients will receive the study brochure when they arrive at the preoperative rooms/wards 
if the patients have pain score of 3 or less (out of 10 using numerical rating scale) and not in 
distress. Screening for inclusion/ exclusion criteria will be performed and discussion of the 
study will be done by the study investigators. 
G4. Will any advertising/recruitment materials be used to recruit research 
participants? 
Yes 
 [x] II Brochures 
Please state the location(s) where the brochures will be placed (e.g. in the general 
waiting area in Clinic X), and attach a copy of the brochure. 
Brochures will be placed and distributed in Antenatal clinics/wards and preoperative  
G5. Will any other recruitment strategies be used (e.g. talks in public places, 
societies etc.)? No 
G6. What is the Recruitment Period (if applicable)? Please provide us with the 
approximate recruitment period. 
 Start Date:  01-Jun-2017 
 End Date:  01-Jun-2019 
G7. How long will the participants be directly involved in the study (if applicable)? 
This includes the time from the screening procedures till completion of follow-up 
tests or examinations. 
If applicable, please elaborate. 
The duration of study period for each participant can last about 17 weeks. Below are the main 
time points for the study activities:  
- Screening and recruitment time point: gestational age week 36 and above (duration: 4 weeks)  
- Pain assessment and questionnaire completion time point (duration of labour till 5-14 days 
after discharge: ~19 days) 
- Follow up phone call survey time point: 6-10 weeks after delivery (duration: 10 weeks) 
 
 
 
 
 
 

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Section H: Study Sites & Recruitment Targets 
H1. Please state the target number of research participants to be recruited for each 
study site. 
No. 
Study Site 
Total Recruitment Target 
1 
KK Women's and Children's Hospital 
(KKH) 
200 
Section I: Research Participants Characteristics 
` 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I4. Are there any recruitment restrictions based on the gender of the research 
participants (e.g. only males will be included in this study)? 
Yes. Only female in labour and undergoing cesarean delivery will be included in this study. 
I5. Are there any recruitment restrictions based on the race of the research 
participants (e.g. only Chinese participants will be included in this study)?   No 
I6. Do the potential research participants have a dependent relationship with the 
study team (e.g. doctor-patient, employee-employer, head-subordinate, student-
teacher, departmental staff relationship)? 
Yes 
Describe how the study team will manage the dependent relationship to prevent 
coercion or undue influence. 
The study participants are receiving analgesia during cesarean delivery by which the 
analgesia is performed by the study team members. The study team will be engaging the 
study participants during antenatal period (antenatal clinics/wards) and prior to analgesia 
(preoperative wards/rooms). The partner of the study participant will be present at the visits. 
 
I7. Does the study involve any vulnerable research participants? Please select 
'Yes' to view the options and select the applicable population(s). Yes 
[x] If Pregnant Women, Foetuses and Neonates is selected, please respond to Section L. 
[  ] If Children is selected, please respond to Section M. 
[  ] If Prisoners is selected, please respond to Section N. 
[  ] If a Cognitively Impaired Persons is selected, please respond to 
Section O. [  ] Others 

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I8. Does the study involve any of the following? 
[x] Inpatients. 
[  ] Outpatients. 
[  ] Healthy Volunteers. 
[  ] Not applicable. 
Research Participants – Pregnant Women, Foetuses & Neonates 
I9. Please indicate if your research involves: 
[x] Pregnant Women and Foetuses. 
[  ] Neonates of Uncertain Viability and/or Nonviable neonates. 
[  ] Nonviable neonates. 
 
 
I10. Describe if appropriate preclinical studies, including studies on pregnant 
animals and clinical studies including studies on non-pregnant women, have been 
conducted and data is available to assess risks to pregnant women and foetus. 
Not applicable. This is an observational study, and the labour analgesia shall be performed 
as per hospital routine practice. No research medications or procedures are involved in this 
study. The risk to the fetus is the least possible as labour analgesia options are established 
and routine procedures in pregnant women with minimal effects on the fetus. 
I11. Describe if the risk to the foetus is the least possible in order to achieve the 
research objectives. 
The risk to the fetus is the least possible as labour analgesia options are established and 
routine procedures in pregnant women with minimal effects on the fetus. 
I12. Describe the additional safeguards that will be provided to protect the rights, 
safety and welfare of these vulnerable participants. 
The informed consent process will be conducted during recruitment at the antenatal 
clinic/wards and preoperative room/wards before their labour pain onset. it will take place in 
a single private room. They will be given time and space to make an informed decision with 
their partner or husband present at all times. They will be given verbal as well as written 
information. 
I13. Special Informed Consent Requirements (Check all that apply). 
[x] I will obtain consent from the pregnant women because: 
[x] Research holds out the prospect of direct benefits to the pregnant women. 
[  ] Research holds out the prospect of direct benefits to both the pregnant women 
and the foetus. 
[  ] Risk to the foetus is not greater than minimal and the purpose of the research 
is the development of important biomedical knowledge that cannot be obtained 
by any other means. 
[  ] I will also obtain consent from the father because the research holds out the prospect 
of direct benefit solely to the foetus. 
[  ] The Informed Consent document(s) will provide information regarding the 
reasonably foreseeable impact of the research on the foetus or neonate. 

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I14. Assurances by Principal Investigator. 
• 
There will be no inducements, monetary or otherwise, offered to terminate a pregnancy. 
• 
Individuals engaged in the research will not have any part in any decisions as to the 
timing, method, orprocedures used to terminate a pregnancy. 
• 
Individuals engaged in the research will not have any part in determining the viability of 
a neonate. 
Section J: Consent Process – Consent Required 
J1. Describe when the consent process will take place with the potential participant. 
Participants should be approached prior to the initiation of any study procedures 
and should not be approached in a situation where they may feel compromised (e.g. 
while in labour, just prior to a surgical procedure or under sedation). 
This study will be advertised on study brochures placed in the antenatal clinics/wards and 
preoperative rooms/wards. They will be given to all parturients who meet the inclusion 
criteria during the antenatal period. On admission to preoperative rooms/wards, they will 
again be given a study brochure if the patients have pain score of 3 or less (out of 10 using 
numerical rating scale) and not in distress. The investigators and study team will be 
available to answer any queries on this trial in the antenatal clinics/wards and preoperative 
rooms/wards. With the activation of HBRA, informed consent will be obtained in the 
presence of a prescribed witness. 
Recruitment of patients from antenatal clinics/wards: 
All potential patients who are expected to meet the inclusion/exclusion criteria at term are 
seen in the KKH antenatal clinics/wards will be invited to participate in the study. The 
informed consent process may be conducted at any time during prior to labour. However, 
the patient will not be enrolled in the study until they have met all the inclusion criteria and 
exclusion criteria. If a patient consents prior to labour, a copy of the consent form will be 
kept in the patient’s case notes. The study investigator will recheck the inclusion/exclusion 
criteria when the patient is at the preoperative rooms/wards prior to the initiation of the 
study activities. Obstetricians and research team will approach the patients in the antenatal 
clinics/wards to provide information about the study. 
Recruitment of patients at preoperative rooms/wards: 
The patients will receive the study brochure when they arrive at the preoperative 
rooms/wards if the patients have pain score of 3 or less (out of 10 using numerical rating 
scale) and not in distress. 
Screening for inclusion/ exclusion criteria will be performed and discussion of the study will 
be done by the study investigators.  
All patients who choose to enrol in the study will be counselled by the investigators about 
the study protocol, both verbally and with the patient information sheet. Adequate time will 
be given for discussion and with the investigators to clarify any doubts. The risks and 
benefits in joining this study will be clarified at recruitment prior to written consent. 
 
 
 
 

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J2. Where will the consent process take place with the potential participant (e.g. in 
room ward, outpatient clinic etc.)? Please justify why the place chosen for the 
consent process is suitable. 
Informed consent will be taken place in the antental clinic/wards and preoperative 
rooms/wards in a private manner. 
J3. Please describe the consent process as follows: 
i. Explain if adequate time will be given to the participant to consider their 
participation. 
This study will be advertised on study brochures placed in the antenatal clinics/wards and 
preoperative wards/rooms. They will be given to all parturients who meet the inclusion 
criteria during the antenatal period. The patients will receive the study brochure again 
when they arrive at the preoperative wards/rooms if the patients have pain score of 3 or 
less (out of 10 using numerical rating scale) and not in distress. Investigators or Clinical 
Research Coordinators will explain to the patients about the study and patients will be 
given ample time to read the informed consent form about the study before obtaining their 
consent. 
ii. Please explain if the place where consent will be taken is suitable. This place 
should allow the participants to be comfortable and have the right frame of 
mind to consider participation. 
Participants will be approached in the antenatal clinic/wards and preoperative 
rooms/wards. The discussion will be conducted in private manner with the patient. 
iii. Please explain how the person taking consent would minimise the 
possibility of coercion or undue influence. 
Participants will receive a patient information sheet. This will be discussed with them in 
private manner in the antennal clinic/wards and preoperative rooms/wards. The subjects 
are able to withdraw from the study at any point. The contact details of the Principal 
Investigator will be provided in the information sheet. Patients are free to withdraw the 
study at any time (including timing after their delivery), should they decide not to 
participate. 
J4. Does your study involve potential vulnerable participants whereby obtaining 
informed consent from the participant is not possible and informed consent is 
required from a Legal Representative (LR)? No 
 
J5. Please describe the provisions to protect the "privacy interest" of the 
participants (e.g. consent will be obtained in a separate room, free from intrusion 
and participants are comfortable with the proposed settings). 
Research personnel will conduct all the discussions about the study and answer any question 
in private manner. 
 

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Section K: Research Data Confidentiality 
J6. Will consent be documented in the form of a written and signed Research Participant 
Information Sheet and Consent Form? 
J7. Will research participants receive any monetary payments (including transportation 
allowances) or gifts for their participation in the study? 
J8. Besides the Informed Consent Form, will any other materials or documents be used to 
explain the study to potential Research Participants (e.g. scripts, hand outs, brochures, 
videos, logs etc.)? 
J9. Will the study enrol non-English speaking participants? 
J10. Will the study be recruiting under emergency situations, when prior consent 
of participant is not possible, and the consent of the participant's legal representative, if 
present, should be requested? 
J11. Do you have any additional comments regarding the Informed Consent process? 
Yes 
File Name 
Description 
Version Number Version Date 
EPOC PIS Version 5 (tracked changes).doc EPOC PIS (tracked changes) 5 
24- 
-2018 
May 
EPOC PIS Version 5 (clean copy).doc 
EPOC PIS (clean copy) 
5 
-2018 
24- May 
Yes 
Participants will be reimbursed SGD20 for their time, inconvenience & transportation. 
No 
No 
No 
No 

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K1. Will coded/anonymous research data be sent to the study sponsor (e.g. 
pharmaceutical sponsored studies)? 
No, the study team would store all research data within the institution. 
i. Please state where the research data (soft copy and/or hardcopy) will be stored 
and indicate if the location storage is secured (i.e Password Protected PC or Laptop, 
data stored in physical location with lock and key access.) 
The soft copy of research data will be stored in a password protected PC. Hard copies 
of data collection forms are kept by the Principal Investigator under lock and key. The 
data is accessible only by Investigators for analysis purposes only. 
Our recruited subjects/ participants can also do online survey (on Survey Monkey 
platform)  6-10 weeks follow up instead of only phone survey. The online survey data 
will be stored in Survey 
Monkey's data center with reliable power sources and backup systems. Physical 
security controls are also ensured in their data center. The data will be encrypted using 
secure TLS cryptographic protocols. Participants' confidentiality will be protected as the 
online survey link will be sent to their email address only. No names or identification 
number that will identify subjects will be available on the online surveys and in the 
system.The survey data will then be extracted from the online system as password 
protected excel file. The soft copy of research data will be stored in a password 
protected 
PC. The data is accessible only by Investigators for analysis purposes only. 
 
ii. Who will have access to the research data, and how will access to the research 
data be controlled and monitored? (Please state the personnel who will have access 
to the study data eg. 
Principal Investigator, Co-Investigator, study coordinator.) 
An electronic database REDCap will be used for data entry into case report form (CRF). 
Password protected accounts will be created for relevant study personnel and the 
degree of database access granted to the each relevant study personnel (Principal 
Investigator,Co-Investigator and Clinical Research Coordinator) account will correspond 
to their trial responsibilities.The research data will be locked and soft copy will be under 
the computer security of Singhealth. 
For the 6-10 weeks online survey, participants' confidentiality will be protected as the 
online survey link will be sent to their email address only. No names or identification 
number that will identify subjects will be available on the online surveys and in the 
system. Only the Principal Investigator and designated Clinical Research Coordinator 
will have the access to the online surveys by using the designated secured password 
protected survey monkey login account. 
iii. Are there any other measures in place to protect the confidentiality of the 
research data? 
For electronic database REDCap, No names or identification number that will identify 
subjects will be ensured. The subjects are only identified by study number. 
For online survey, No names or identification number that will identify subjects will be 
available on the online survey and in the system. 
iv. Are there any research data sharing agreements with individuals or entities 
outside the Institution, to release and share research data collected? 
No 
v. Describe what will happen to the research data when the study is completed. 
The research data will be kept under lock and key and using computer security of 
Singhealth. The data will be destroyed after keeping for 6 years upon completion of the 
study. 
K2. Will any part of the study procedures be recorded on audiotape, film/video, or 
other electronic medium? 
No 
 
 

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Section L: Data & Safety Monitoring 
L1. The purpose of the Data and Safety Monitoring Plan is to ensure the safety and 
well-being of participants, and the integrity of the data collected for the study. 
Depending on the type and risk level of the study, this may include the Principal 
Investigator, experts within the department or institution, independent consultants or a 
combination of the said persons. 
Who will perform the data and safety monitoring? 
The data is kept by the principal investigator under lock and key and using computer 
security of SingHealth. The data is accessible only by the investigators for analysis 
purposes only. The plan for adverse effect monitoring would include reporting to Health 
Science Authority and CIRB. 
L2. Please describe the frequency of review (e.g. daily, weekly, quarterly) and what 
data (e.g. adverse events/serious adverse events) will be monitored for safety. 
Safety data is monitored at all times by the investigators. There will be monthly meeting to 
review the trial. 
Adverse events and serious adverse events will be reported to CIRB accordingly. 
 
L3. How is data integrity monitored to ensure that study data is authentic, accurate 
and complete, and if the data correlates with the case report forms? 
Data is extracted from data collection forms and random audits will be performed to make 
sure it is authentic, accurate and complete. 
L4. Please describe the stopping criteria for the research study based on efficacy, 
futility and safety criteria. 
The stopping criteria for the research study will be based on safety criteria. The review of 
serious adverse effects will be performed. 
L5. Please state the route of dissemination of any data and safety information to 
the study sites, as well as the person/team responsible for doing so. 
Face-to-face communication and email correspondence. 
 
Other Attachments 
Note: Please attach only documents that are not relevant to the above sections. 
File Name 
Description 
Version Number 
Version Date 
EPOC PDPA.pdf 
EPOC PDPA 
1 
-