Impact of Bilingual Prescription Medication Labels on Medication Adherence and Medication Management Self-Efficacy Among Elderly Singaporeans: A Pilot Study
Phase: NA
Conditions: Diabetes Mellitus, Type 2, Hypertension
Sponsor: Singapore General Hospital

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STUDY PROTOCOL 
 
PROTOCOL TITLE: 
The Impact of Bilingual Prescription Medication Labels on Medication Adherence and Medication 
Management Self-Efficacy Among Elderly Singaporeans: A Pilot Study 
 
PROTOCOL NUMBER:  
1 
 
PROTOCOL VERSION:  
3  
PROTOCOL DATE:  
10 September 2021 
 
PRINCIPAL INVESTIGATOR:  
Dr Khee Giat Yeng, Principal Clinical Pharmacist, Singapore General Hospital 
 
CO-INVESTIGATORS: 
Mr Hwang Yi Kun, Pharmacist, Singapore General Hospital  
Ms Rachel Gan Ee Ling, Pharmacist, Singapore General Hospital 
Ms Sumithra Suppiah, Research Associate, Duke-NUS Medical School 
Dr Rahul Malhotra, Assistant Professor, Duke-NUS Medical School 
 
 

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Table of Contents 
1. 
BACKGROUND AND RATIONALE................................................................................................. 4 
2. 
HYPOTHESIS AND OBJECTIVES.................................................................................................. 5 
3. 
EXPECTED RIKS 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 ......................................................................................................................................... 7 
4.4. 
EXCLUSION CRITERIA ........................................................................................................................................ 7 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY ................................................................. 7 
6. 
SAFETY MEASUREMENTS.......................................................................................................... 11 
6.1. 
DEFINITIONS .................................................................................................................................................. 11 
6.2. 
COLLECTING, RECORDING AND REPORTING OF SERIOUS ADVERSE EVENTS (SAES) TO CIRB ................................. 11 
6.3. 
SAFETY MONITORING PLAN .............................................................................................................................. 11 
6.4. 
COMPLAINT HANDLING .................................................................................................................................... 11 
7. 
DATA ANALYSIS........................................................................................................................ 12 
7.1. 
DATA QUALITY ASSURANCE.............................................................................................................................. 12 
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 .................................................................... 13 
10. QUALITY CONTROL AND QUALITY ASSURANCE ...................................................................... 13 
11. ETHICAL CONSIDERATIONS ..................................................................................................... 13 
11.1. 
INFORMED CONSENT ....................................................................................................................................... 13 
11.2. 
CONFIDENTIALITY OF DATA AND PATIENT RECORDS ........................................................................................... 14 
12. PUBLICATIONS ......................................................................................................................... 14 
13. RETENTION OF STUDY DOCUMENTS ........................................................................................ 14 
14. FUNDING AND INSURANCE ...................................................................................................... 14 
LIST OF ATTACHMENTS .................................................................................................................... 15 
 
 
 
 

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PROTOCOL SIGNATURE PAGE 
 
 
 
Protocol Title: 
The Impact of Bilingual Prescription Medication Labels on Medication Adherence and Medication 
Management Self-Efficacy Among Elderly Singaporeans: A Pilot Study 
 
 
Protocol Number: 
1 
 
 
Protocol Version/ Date: 
3/1 September 2021 
 
 
Sponsor Name: 
Population-based, Unified, Learning System for Enhanced and Sustainable Health Centre Grant (PULSES 
CG) 
 
 
 
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:  _Khee Giat Yeng___________________________ 
                                                            
 
Principal Investigator Signature: 
 
                                                            
 
Date:   10 September 2021_ 
                                                            
 
 
 
 

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1. 
BACKGROUND AND RATIONALE 
 
Elderly, an at-risk group: Life expectancy among the elderly is rising globally, including 
Singapore.1 A longer life places the elderly at risk of chronic diseases, which often entail long term 
drug therapy.2 The elderly, thus, with their co-morbidities, have a higher risk of polypharmacy, 
which in turn is associated with a greater likelihood of medication non-adherence.3 Further, given 
their exposure to polypharmacy, the elderly often have to navigate through multiple PMLs on 
a daily basis.     
Prescription Medication labels (PMLs): PMLs, affixed on packets/bottles of prescription 
medications, are the patients’ main source of medication-related instructions in Singapore. 
Many patients in Singapore receive no information from healthcare providers except the 
instructions on PMLs, further highlighting their relevance.4 Correct understanding of PMLs is key 
to medication safety and adherence,5-7 esp. for the elderly.8 Difficulty in finding and comprehending 
information on PMLs can adversely affect patient safety and adherence to instructions.9 Although 
local data on medication errors attributed to PML misunderstanding are lacking, a study elsewhere 
reported that majority of outpatient medication errors are due to patients’ inability to take their 
own medications as intended10. And, poor medication safety and adherence result in poor clinical 
outcomes and unnecessary healthcare costs.11 Thus, ensuring that patients, esp. the elderly, 
correctly understand their PMLs is vital.  
 
A key barrier faced by elderly Singaporeans in reading and understanding their PMLs is 
the language commonly used on them, English. A study of a national sample of elderly 
Singaporeans found that despite 69% being unable to read English, their PMLs were mostly only in 
English (81%).12 This discrepancy places the elderly at risk of medication errors, non-adherence, 
and side effects. At the same time, many elderly Singaporeans who cannot read English can read 
another official language (Mandarin Chinese/Malay/Tamil).13 This highlights a direct and 
innovative approach to make existing PMLs patient-centric, i.e., add another preferred 
language – bilingual PMLs. A study led by the project mentor showed that bilingual PMLs lead to 
a substantial increase in understanding of PML content among the elderly, supporting its real-world 
utility.12,14 And, patient feedback collated by the project Co-Is (SGH pharmacists) strongly suggests 
the need for bilingual PMLs. However, adoption of bilingual PMLs in Singapore has been slow. 
One reason is the lack of evidence for their positive impact on important medication-related 
outcomes, i.e., medication management self-efficacy and medication adherence. The proposed 
study will provide rich preliminary data that will enable the conduct of a larger RCT on the 
impact of bilingual PMLs on these very medication-related outcomes.  
 
Conceptual Framework: Our framework focuses on the relationship 
between attainment of knowledge (medication knowledge via PMLs), 
medication management self-efficacy and engagement in self-care 
behaviours (i.e. medication taking behaviour) as a process that ultimately 
affects our key outcome, medication adherence. (Figure 1)  
Attainment of knowledge: Cognitive processes (i.e., perception, 
memory, problem solving, etc.) generally subsume the concept of 
understanding.15 In investigating PML understandability, understanding 
has been defined as the capacity to describe – using one’s own words 
(i.e., more than simply reading) – how a medication should be taken.16 In 
context of our study, bilingual PMLs will facilitate understanding among 
the elderly, resulting in attainment of medication knowledge. Research 
shows that lack of knowledge is likely to affect individual’s self-
Figure 1: Conceptual framework 

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efficacy to adhere to complex regimens.17,18 Further, it has been suggested that interventions aimed 
at improving medication adherence should design interventions targeted at increasing knowledge 
and self-efficacy.19 
Medication management self-efficacy: Self-efficacy, drawing on the social-cognitive theory, is 
defined as “the individual’s belief in their capabilities to implement a specific/a set of 
behaviour(s)”.20 More specifically, in context of medication management, self-efficacy refers to a 
belief in the patient’s capacity to follow a prescribed medical regimen when faced with challenging 
situations.21 Several studies have found a positive link between medication management self-
efficacy and medication adherence.22 Self-efficacy directly affects health behaviours.23 Patients with 
higher self-efficacy are more likely to have better adherence to self-care tasks, such as medication 
taking.24,25  
Medication adherence: Adherence to medications is critical to ensuring optimal health outcomes, 
yet around 50% of patients do not do so.26 In the United States, up to two-thirds of all medication-
related hospitalizations result from poor medication adherence. Singaporean data also portrays low 
medication adherence rates.27,28 Medication adherence is influenced by patient, physician, 
medication and health-system factors.29 Our study, by initiating evidence gathering for the 
impact of bilingual PMLs on medication adherence, concurrently addresses two such 
factors, a patient factor, i.e., language reading ability, and a health-system factor, 
particularly important in Singapore, i.e., PMLs.    
Overall, we conceptualise that by facilitating attainment of medication knowledge (better 
understanding via bilingual PMLs), patients will advance their medication management self-efficacy, 
leading to engagement in medication taking behaviour, ultimately resulting in medication 
adherence.  
Need for rigorous PML intervention studies: A recent review on the impact of improved PMLs 
concluded that intervention studies that test PML improvements in a rigorous manner are 
lacking.30 It also recommended that future studies should extend research to outcomes more 
proximal to medication taking – medication adherence and medication management self-
efficacy. In Singapore, the only published PML intervention did show bilingual PMLs (vs English 
PMLs) to increase PML understanding.12 However, it, again, did not assess medication adherence 
and medication management self-efficacy. Thus, rigorous intervention studies that assess the 
impact of improved PMLs on a range of medication-related outcomes are needed.  
Our proposal is the first step towards a well-informed, rigorous intervention study or RCT 
that will provide concrete evidence on the impact of the provision of bilingual PMLs on key 
medication-related outcomes – medication adherence, medication management self-
efficacy, and PML understanding. The experience gained, and data collected, through the 
conduct of the 2 pilot trials, funded through the current proposal, will allow us to choose the 
optimal trial design, and refine protocols for recruitment, engagement and retention of study 
participants for the larger RCT as well as determine variability in outcomes so that the larger RCT 
is appropriately powered to detect meaningful differences in the outcomes – an immediate output 
of our proposed project will be a grant proposal to a national level grant mechanism for the 
conduct of the larger RCT. Eventually, the 2 pilot trials, and the subsequent larger RCT, will 
contribute to implementing patient-centered PMLs.  
 
 
2. 
HYPOTHESIS AND OBJECTIVES 
 
Since the proposed study will collect preliminary data for informing the larger RCT, it does not aim 
to detect a significant difference in the trial outcomes in either pilot trial. Rather, its specific aims 
are:  

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AIM 1. To assess the feasibility of administering the intervention in the 2 “pilot” RCT versions. 
The proposed formative study will inform which of the 2 pilot trials will be scaled up and tested in 
the larger RCT. It will also result in finalization of the intervention and measurement material. 
AIM 2. To refine protocols for study participant recruitment, engagement and retention.  
AIM 3. To gain experience with and refine measurement of the medication-related outcomes. 
 
A key outcome, medication adherence, will be measured using several approaches – self-report 
(ARMS31,32; MedTake Assessment33), which is easier and cheaper34, and objective (pill count35; 
electronic medication packaging [EMP]36), which is tedious and expensive – during the 2 pilot trials. 
Comparison of the various approaches against the EMP (the most objective approach) will inform 
the choice of the measurement approach to be used for medication adherence in the larger RCT.  
 
 
3. 
EXPECTED RIKS AND BENEFITS 
 
Risks to participants are expected to be minimal in the study: 
 
(1) Potential risk from breach of confidentiality: Exposure of patient-related information such their 
personal details and medical information (including medication they are taking, medication-
adherence scores) 
 
Expected benefits are as follows: 
 
(1) Improved medication-related outcomes: Provision of bilingual PMLs through the study is 
expected to improve the following 3 areas for participants- medication adherence, medication 
management self-efficacy, and PML understanding. Improvements in these 3 areas will enhance the 
benefits patients will receive from their medication therapy, resulting in greater medication-related 
outcomes. 
 
 
4. 
STUDY POPULATION 
 
4.1. 
List the number and nature of subjects to be enrolled.  
 
A total of 40 patients will be recruited from Singapore General Hospital’s outpatient clinics, which 
is the only study site involved. There will be no subject restrictions based on race of the subject, but 
as per the inclusion criteria set out in section 4.3 below, they should be able to speak English 
and/or Mandarin, and unable to read in English but able to read Mandarin (as they will benefit the 
most from bilingual PMLs). 
 
4.2. 
Criteria for Recruitment and Recruitment Process 
 
Patients who meet all the inclusion criteria set out in section 4.3 below and do not meet any of the 
exclusion criteria set out in section 4.4 below are eligible to be recruited into the study. Suitable 
patients will be identified by either the patient’s primary physician or by a pharmacist at Diabetes 
and Metabolism Centre (DMC) pharmacy. These suitable patients will be introduced to the study 
and if they express interest, they will be referred to the research assistant for consent taking, 
administration of the baseline covariate questionnaire and randomisation to study group. 

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4.3. 
Inclusion Criteria 
 
(1) Singapore Chinese citizen/permanent resident; (2) age ≥50 years; (3) just received a new (i.e., 
not received before) oral medication for a chronic disease from DMC pharmacy; (4) no 
moderate/severe cognitive impairment (≥5 correct responses on the Abbreviated Mental Test, 
AMT); (5) not deaf (self-reported); (6) no binocular presenting near vision impairment (near visual 
acuity, with routinely used spectacles/lenses: at least 6/15 (0.40 logMAR) on the Landolt’s C 
chart); (7) able to speak English and/or Mandarin; (8) unable to read in English but able to read 
Mandarin (as they will benefit the most from bilingual PMLs); (9) assessed as non-adherent as per 2 
questions - “ In the last one month, how often did you take your medications as prescribed by the 
doctor?” and “At times do you forget to take your prescription medications?” (as they will benefit 
the most from an intervention aimed at improving medication adherence). 
 
4.4. 
Exclusion Criteria 
 
(1) Patients who received, from the prescribing physician, a set of instructions for their new oral 
medication that does not match standard instructions (as the bilingual instructions for non-standard 
instructions would not be prepared for beforehand) 
 
 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY 
 
This is a 2-arm open-label parallel-group RCT with 2 versions (Pilot Trial A, and Pilot Trial B). A 
total of 40 eligible patients, after informed consent, will be randomized (1:1; block randomization, 
block of 4) in the DMC pharmacy to either Pilot Trial A or Pilot Trial B (Figure 2). 
 
 
 
 
 
 
 
 
 
 
 
 
 

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5.1 
Study Design 
Briefly, in Pilot Trial A, all will be first given the usual English PML for their new medication. 
There may be non-standardized, ad-hoc noting on the PML by the pharmacy staff when participant 
is deemed not able to understand the English PML. All content of the non-standardized, ad-hoc 
noting including pictures drawn will be recorded. Then, at 2 weeks post-recruitment, their 
baseline level of the 3 medication-related outcomes (w.r.t. the new medication) will be gauged, after 
which they will be randomized (1:1; block randomization, block of 4) to one of 2 PMLs (Bilingual 
[intervention] or English [usual care]) at their home. Follow-up assessment of the 3 medication-
related outcomes will be also be done at 2 weeks post-randomization at their home. 
 
In Pilot Trial B, participants will be randomized (1:1; block randomization, block of 4) just after 
recruitment to one of 2 PMLs (Bilingual [intervention] or English [usual care]) in the DMC 
pharmacy. There may be non-standardized,ad-hoc noting on the PML by the pharmacy staff when 
participant is deemed not able to understand the English PML. All content of the non-
standardized, ad-hoc noting including pictures drawn will be recorded. The 3 medication-related 
outcomes will be assessed at 2 weeks post-randomization at their home. 
 
All participants will receive their usual medical care, and usual medication counselling at the DMC 
pharmacy for all their medications. All medications, other than the new oral medication (which 
made them eligible, and whose PML will be intervened upon), will be dispensed with usual English 
PMLs. 
 
5.1.1   Modified Study Design In View Of COVID-19  
In view of COVID-19 restrictions imposed as of 16 August 2021, a portion of the Main 
Questionnaire will be done via phone call instead of fully relying on home visits. The study staff 

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will conduct a home visit to complete the remaining questions from the Main Questionnaire and 
collect data from the Rx CapTM bottles, with a time limit of 20 minutes to keep participants and 
staff safe.  
 
Additionally, should any participants be subjected to COVID-19 Stay Home Notices or Quarantine 
Orders, participation will immediately be forfeited for the safety of participants and study staff. 
Retrieval of the Rx CapTM bottle and delivery of remaining medicines will be arranged in a proper 
manner in accordance to any guidelines set by the SGH Research Office and MOH.  
 
5.2      Study Methodology 
Bilingual PMLs (Intervention): Bilingual PMLs, for common medications at the DMC pharmacy, 
which “mirror” medication instructions on the corresponding English PMLs, will be developed by 
the investigator team. While the Health Products (Therapeutic Products) Regulations 2016 
mandate English PML provision, there is no restriction to adding another language.37 In fact, some 
polyclinics already print PMLs in their patients’ preferred language, upon request, to supplement 
English PMLs.38  
Randomization: All 3 block randomization sequences (Pilot Trial A or B, then, study arm within 
each Pilot Trial) will be generated a priori. After a participant gives consent, project staff will be 
informed of his/her allocation to Pilot Trial A or B. For those in Pilot Trial A, further assignment 
to study arm will be disclosed only after the baseline level of the 3 medication-related outcomes is 
assessed at 2 weeks post-recruitment. For those in Pilot Trial B, assignment to study arm will be 
disclosed immediately, as there is no baseline assessment of the 3 medication-related outcomes.      
 
Covariates: A range of socio-demographic and medication-related (e.g. no. of medications, help 
received in medication management) variables will be collected, using a questionnaire, at 
recruitment.   
 
Medication-related outcomes: They will be gauged at 2 weeks post-recruitment and 2 weeks post-
randomization for those in Pilot Trial A, and at 2 weeks post-randomization for those in Pilot Trial 
B.  
 
5.2.1   Measurements 
Medication adherence: It will be measured in 4 different ways: 
1. Adherence to Refills and Medications Scale (ARMS)31,32: A validated self-reported 
medication-adherence scale intended for patients with chronic diseases. The 12-item 
questionnaire consists of 2 sub scales - adherence to refilling prescriptions and adherence 
with taking medications. Each item is structured using the Likert scale, with the following 
response options and corresponding scores: “none” (score of 1), “some” (score of 2), 
“most” (score of 3 ), or “all of the time” (score of 4).  The range of possible total scores is 
12 to 48. Lower scores indicate better adherence. 
2. MedTake Assessment33: A self-reported measure, recommended by Ministry of Health, 
Singapore for pharmacy staff when they provide pharmaceutical care services,39 that 
assesses patient adherence and knowledge to dose, dosage, indication, food or water co-
ingestion, and regimen. A composite score (0–100%; higher ~ better) summarizes patient’s 
ability to take medication safely. 
3. Pill count40: A pill count, in context of the new oral medication, will be done.  
% adherence=  ((quantity dispensed)-(quantity remaining))/((prescribed number of pills per 
day)×(no.of days between dispensing date and interview)) 
 
Electronic medication packaging [EMP]: All participants will be dispensed their new oral 

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medication in a Rx CapTM medication bottle (www.rxcap.com), whose Rx CapTM Bluetooth smart 
cap will automatically track medication usage every time it is opened. Project staff will sync 
participants’ data, collected and stored within the Smart Cap, at each home visit, and import it to 
the Rx CapTM Engage platform for analysis. Continuous (% adherence to prescribed regimen; 0-
100%) and categorical variables (not at all; partially; fully) for medication adherence will be 
derived.  Rx CapTM medication bottle is not being used in standard clinical practice yet and it is 
used for this proposed research only. To our best knowledge, Rx CapTM medication bottle is not 
validated for use clinically yet. 
 
Medication management self-efficacy: The 8-item Medication Understanding and Use Self-Efficacy 
Scale (MUSE), comprising 2 subscales – (1) taking medication (4 items), and (2) learning about 
medication (4 items), will be used. Item scores (four-point Likert scale; strongly disagree (score=1), 
to, strongly agree(score=4)) will be summed for subscale (range: 4-16) and total (range: 8-32) 
scores.41 
 
PML understanding: It will be assessed by asking questions adapted from a local study12 (led by the 
mentor) assessing this construct among elderly Singaporeans. Respondents will be asked tailored 
questions (in their preferred language) specific to the instructions presented on their PML for the 
new oral medication, for instance “How many times a day do you have to take this medication?”. 
Each question will be marked as “correct” or “incorrect”. Continuous (% correct responses; 0-
100%) and categorical variables (none; partial; complete) for PML understanding will be derived. 
 
5.2.2   Other Factors 
Potential Difficulties/Alternative Approaches: ((1) Each respondent will be compensated with $20 
worth of shopping vouchers as fair reimbursement for incidental expenses incurred for 
participating. The reimbursement can indirectly address potential recruitment issues by helping 
assuage any logistic issues the potential participants may have. (2) While we aim to recruit elderly 
who can read Mandarin, we may be limited by the language competency of the project staff. 
Nevertheless, we will try and arrange for conversant staff from other studies to supplement data 
collection. (3) The potential improvements to PMLs to be drawn from the expected findings may 
not directly address the needs of the elderly who are completely illiterate or have severe 
visual/cognitive impairment. Nonetheless, the pilot trials and subsequent RCT will benefit a large 
proportion of Singaporean elderly. 
 
Withdrawals: Participants are free to withdraw their consent and discontinue their participation at 
any time without prejudice to him/her or effect on his/her medical care. However, the data that 
have been collected until the time of participant’s withdrawal will be kept and analysed, to enable a 
complete and comprehensive evaluation of the study. 
 
The study team may stop a participant’s participation in the study at any time for one or more of 
the following reasons: 
− Failure to follow the instructions of the Principal Investigator and/or study staff. 
− The Principal Investigator decides that continuing the participant’s participation could be 
harmful. 
− The study is cancelled. 
 
When a participant’s participation in the study is withdrawn or stopped, their medications will be 
switched out from the Rx CapTM bottle to the usual twist-cap amber bottles or ziplock bags that is 
provided by SGH Pharmacy. For those randomized to receive bilingual PMLs, their bilingual 

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PMLs will be switched out to the usual English PMLs that are provided by SGH Pharmacy. 
 
 
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. 
 
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 PI, Co-Is, and study team will monitor and report any serious adverse events to the CIRB. As 
the study is expected to pose less than minimal risk to participants, the research team, overseen by 
the Principal Investigator, will perform data and safety monitoring. Research staff will ask 
participants about potential serious adverse events and more commonly known adverse events of 
their newly prescribed oral medication during their follow-up home visits. 
 
6.4. 
Complaint Handling  
 
Any complaints will be directed to the research team for investigation, and overseen by the 
Principal Investigator. 

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We will adhere to prevailing COVID-19 control measures as recommended by the SGH Research Office 
 
7. 
DATA ANALYSIS 
7.1. 
Data Quality Assurance 
 
All data collected on hardcopy survey forms will be transcribed into electronic data using double 
data entry by two different individuals and verified for consistency. Any discrepancies will be 
resolved by referring to source documents. Only study team members will handle and access these 
data. 
 
7.2. 
Data Entry and Storage 
 
All data with personal identifiers will be encrypted with password-protection. All physical research 
data including consent forms, data entry forms will be stored in locked cabinets at SGH. All soft 
copy research data will be coded, with participants' identifiers stored separately from research data, 
and only available on computers within the institution. Only de-identified data will be shared with 
study team members for data analysis and only the investigators and authorized personnel 
(principal investigator, co-investigators and research assistant) directly involved with the study will 
have access to the data. After study completion, research data will be stored on institution 
computers and remain password-protected, for a minimum of 7 years after completion of research 
study or date of publication of the research using the research data, whichever is later. 
 
The Rx CapTM bottle measures patients medication adherence (Adherence is considered “met” 
when the new oral medication is taken based on both prescribed number of times per day and 
prescribed time of the day), each participant will be given 1-2 Rx CapTM pill tracker bottles. The 
electronic cap of the pill tracker records the date and time when the patient opens the vial to take 
his/her medication. This bottle does not collect any personal identifiers. A Rx CapTM account 
would be created for each participant.  However, these accounts will be created by the study team 
using non-identifiable user information (i.e., “dummy” email addresses/usernames). As such, no 
personal identifiers will be stored in third-party databases. 
 
 
8. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
8.1. 
Determination of Sample Size  
 
Sample size/ power calculation is an important component for a RCT. However, as the proposed 
study is to conduct two pilot versions of a RCT, aiming to obtain preliminary data that will inform 
the sample size/ power calculation of a following, larger RCT, no sample size estimation has been 
done for the proposed study. 
 
8.2. 
Statistical and Analytical Plans 
As we are conducting 2 “pilot” versions of a RCT, most analyses will be descriptive and 
exploratory. In both pilots, trial outcomes will be summarized using measures of central tendency 
and dispersion (e.g., mean and standard deviation). In Pilot Trial A, significant difference in change, 
from baseline to 2 weeks post-randomization, in the 3 medication-related outcomes between the 2 
arms will be assessed using t-test (for continuous variables, e.g. difference in change in ARMS 

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scores or MUSE scores) or chi-square test (for categorical variables, e.g. difference in change in % 
with complete PML understanding or % with complete adherence as per EMP). In Pilot Trial B, 
significant difference, at 2 weeks post-randomization, in the 3 medication-related outcomes 
between the 2 arms will be assessed using t-test (for continuous variables, e.g. difference in the 
ARMS scores or MUSE scores) or chi-square test (for categorical variables, e.g. difference in % 
with complete PML understanding or % with complete adherence as per EMP). For agreement 
between medication adherence assessed using EMP and that assessed using the 3 other approaches, 
Bland-Altman plots42 (adherence considered as continuous) and Cohen’s kappa43-45 (κ; adherence 
considered as categorical) will be used. While our findings will only provide a general sense of the 
intervention impact, they will primarily inform which measures to use for the subsequent RCT and 
for determining its optimal sample size. We will also tabulate participation rates and loss to follow-
up. 
 
 
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 
 
The research assistant engaged will be responsible for administering the study protocol. A clearly 
drafted protocol will be provided to the research assistant prior to initiation of the study, with 
members of the study team available throughout the study period for the research assistant to 
clarify at any point if unclear. Members of the study team from SGH Pharmacy Department, 
overseen by the Principal Investigator, will also be working closely with the research assistant 
throughout the study period at SGH DMC. 
 
 
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 Participant Information and Consent 
Form, must be approved in writing by the Centralised Institutional Review Board (CIRB), prior to 
enrolment of any patient into the study. 
 
The principal 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 
 
The consent process with the potential participant will take place at the outpatient clinic at SGH 
DMC level 3, which is a quiet and conducive environment that is usually familiar to patients. 
Otherwise, a separate room can be provided for potential participants who prefer a more private 
setting. Consent will be taken by the research assistant, who will provide necessary information in 

Version <3>, Dated <10/09/2021> 
Page 14 of 17 
accordance to the drafted Participant Information Sheet and Consent Form. As this study is likely 
to recruit a majority of non-English speakers, the Participant Information Sheet and Consent Form 
will be prepared in the 4 official languages (English, Mandarin, Malay and Tamil). 
 
The research assistant will provide potential participants with ample time to consider and consult 
their family members as necessary, and reinforce that they are free to refuse participation, which 
will in no way affect the medications they receive from the pharmacy usually. 
 
11.2. Confidentiality of Data and Patient Records 
 
All research data will be soft copy and stored on password-protected PC/laptops. Only the study 
team (principal investigator, co-investigators and research assistants) will have access to the 
research data, which will be password protected. All soft copy research data will be coded, with 
participants' identifiers stored separately from research data, and only available on computers 
within the institution. 
 
 
12. 
PUBLICATIONS 
 
The purpose of the 2 pilot trials conducted in this study is to gain experience and collect data to 
allow selection of an optimal trial design, and refine protocols for recruitment, engagement and 
retention of study participants for a larger RCT in future, as well as determine variability in 
outcomes so that the larger RCT is appropriately powered to detect meaningful differences in the 
outcomes. Should any findings from this study be published, source of funding of this study (as 
stated in section 14) will be acknowledged, together with any subsequent assistance that is received 
for the study from individuals not part of the study team. 
 
 
13. 
RETENTION OF STUDY DOCUMENTS 
 
After study completion, research data will be stored on institution computers and remain 
password-protected, for a minimum of 7 years after completion of research study or date of 
publication of the research using the research data, whichever is later. 
 
 
14. 
FUNDING and INSURANCE 
 
This study will be funded by the Population-based, Unified, Learning System for Enhanced and 
Sustainable Health Centre Grant (PULSES CG). 
 

Version <3>, Dated <10/09/2021> 
Page 15 of 17 
 
List of Attachments 
 
Appendix 1 
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Page 16 of 17 
Appendix 1 
 
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