Perception, Adherence, Clinical, Economical and Health-Related Quality of Life Outcomes of CareAide® App Usage in Chronic Diseases
Phase: NA
Conditions: Adherence, Medication, Chronic Disease, Quality of Life, Economic Burden, Asthma, Hypertension, Heart Failure, Diabetes
Sponsor: University of Malaya

1 
Version 9 Date: 30.7.2022 
Study Protocol 
Perception, Adherence, Clinical, Economical and Health-Related Quality of Life Outcomes of 
CareAide® App usage in Chronic Diseases 
Protocol number, version number and date: 
Protocol number, Version 9.0, 30 July 2022  
Name and Institution of Principal/Coordinating investigator: 
Dr Ong Siew Chin, School of Pharmaceutical Sciences Universiti Sains Malaysia (USM), Penang  Dr. 
Baharudin Ibrahim, Faculty of Pharmacy, Universiti Malaya, Malaysia                                                    
Professor Dr. Hasniza Binti Zaman Huri, Faculty of Pharmacy, Universiti Malaya, Malaysia       
Name and Institution of Principal investigator at the Site: 
Dr. Baharudin Ibrahim, Faculty of Pharmacy, Universiti Malaya, Malaysia                                                      
Dr. Navin Kumar A/L Loganadan, Hospital Putrajaya 
Dr. Jaya Muneswarao A/L Ramadoo@Devudu, Hospital Pulau Pinang                                          
 
Dr. Izyan Binti A Wahab, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia                          
Dr. Kayatri A/P Govindaraju, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia                    
Dr. Rajat Rana, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia        
 
Ng Chow Kyn, Universiti Sains Malaysia, Malaysia                                                               
 
Mohamed Syamir, Faculty of Pharmacy, University of Malaya, 50603 Kuala Lumpur, Malaysia 
Name and Institution of Sub/Co investigator at the Site:  
 
 
 
 
 
Dato’ Dr. Mohamed Jahangir bin Abdul Wahab, Hospital Pulau Pinang, Malaysia                                               
Ho Shien Chee, Hospital Pulau Pinang, Malaysia
Name and address of Sponsor: 
CaringUp Malaysia Sdn Bhd  
8-1, Level 8, Menara CIMB. No.1, Jalan Stesen Sentral 2 Kuala Lumpur, Sentral 50470 Kuala Lumpur. 
Malaysia
Study site/s: 
University Malaya Medical Centre, Kuala Lumpur 
Hospital Putrajaya, Putrajaya 
Hospital Pulau Pinang, Pulau Pinang 

Version 9 Date: 30.7.2022 
2 
1.0 Introduction/Background 
The prevalence of non-communicable diseases (NCDs) including diabetes, hypertension, 
heart failure and asthma is higher especially in the bottom income group. According to WHO and 
Ministry of Health (MOH) Malaysia 2020 report, expenditure for chronic diseases estimated 
involved around 0.65% of Malaysia’s gross domestic product (GDP) which is about RM8.91 
billion (Ministry of Health Malaysia, 2020).  This showed that chronic diseases imposed a 
significant health burden to our country. Therefore, stakeholders and public should work together 
to identify the sources and curb the prevalence of chronic diseases from continuing to rise in 
Malaysia. Despite free access to essential medicines and health services in the public sector, health 
literacy remains poor, service uptake remains low, and medication non-adherence persists.  
Adherence to therapies is a primary determinant of treatment success and is associated with 
improved clinical outcomes in the management of chronic diseases. Generally, the medication 
adherence rates are lower in chronic disease patients than in those with acute disease. Failure to 
adherence negatively affects the efficacy, safety and costs of therapies. According to the World 
Health Organization’s (WHO’s) 2003 report, 50% of patients with chronic diseases do not adhere 
to their prescribed treatment and identified non-compliance as global health crisis. Similarly, in 
Malaysia, despite the Malaysian population having good and easy access to effective medical 
therapy under the public healthcare system, approximately 46% to 56% of patients with 
hypertension were non-adherent in terms of their medications. Increasing medical adherence is, 
therefore, a public health priority. 
The health ministry has tried various interventions aiming to improve medication 
adherence, including technical, behavioural, educational, social support and structural 
interventions. However, changing people’s behaviours toward medication adherence can be 
challenging. To compound this problem, long-term care requires the active involvement of 
healthcare resources and is usually costly and labour-intensive. Thus, new and innovative 
approaches to changing the attitudes and behaviours regarding adherence are needed. 
In Asia-Pacific countries, usually it is the families who are primarily and personally 
responsible for the healthcare of the patients due to the culture. Thus, it is crucial to include them 
as part of the solutions to the adherence issues. In the age of fourth industrial revolutions and the 
advancements of digital technologies, digital solutions such as applications (‘apps’) on 

Version 9 Date: 30.7.2022 
 
3 
 
smartphones, are increasingly used in healthcare. Further, the extensive development of 
information and communication technologies characteristic of modern society enables 
interventions to reach large populations. CareAide® is a digital app that may help to manage 
complex medicine schedules and improve adherence thus help manage complex medicine 
schedules with minimal involvement of healthcare resources. The app can include both the patients 
and the caregivers to monitor the medication taking behavior.  
Previous studies have shown the association of adherence and clinical outcomes in 
diabetes, hypertension, asthma and heart failure patients (Asche et. al. 2011; Chia et. al. 2021; 
Shang et. al. 2019; Vahatalo et. al. 2021). These studies have shown the improvement of glycaemic 
control, blood pressure, health care utilization, quality of life, mortality, cardiovascular events and 
asthma control with higher adherence. Therefore, by using the CareAide® app, we hypothesized 
that these important clinical and health-related quality of life outcomes will also be indirectly 
improved when the adherence increases. 
Mobile health interventions have been proved to be cost-effective in the management of 
diabetes and hypertension in overseas studies (Li et al., 2021; Tsuji et. al., 2020; Purcell et al., 
2014). However, a few systematic reviews found that the outcome for economic evaluation were 
inconsistent, and most studies reported applied simple platforms such as text messages or phone 
reminder (Beratarrechea et al., 2014, Iribarren et al., 2017; Li et al., 2020; Sanyal et al., 2018).  
Furthermore, there is little evidence regarding the economic evaluation of mobile health apps for 
improving chronic disease management in developing country such as Malaysia. Therefore, this 
study will also explore the economic impact of mHealth app (CareAide ®) in the management of 
chronic diseases among adults in Malaysia.  
Despite the launch and its utility, it is important to understand how people perceive and use 
the digital app. The user satisfaction survey can provide a better understanding of users’ perception 
of the CareAide® app. Through assessing users’ perception and satisfaction with the app, it is 
possible to improve the design of future CareAide® app that is more effective and can tailor the 
features according to their needs. Therefore, this study also aims to gauge the perception and 
satisfaction of the CareAide® app. Findings from this study will be helpful for the app developers 
for revisiting their app features and services that can lead to continued use of the app.  
2.0 Research Questions 
1. Can CareAide® improve the medication adherence? 

Version 9 Date: 30.7.2022 
 
4 
 
2. What is the clinical impact of CareAide® on chronic diseases? 
3. What is the economical and HRQOL impact of CareAide®? 
4. What is the users’ perception on the CareAide® application? 
 
3.0 Research Objective:  
3.1 Primary Objective 
1. To evaluate the effect of CareAide® intervention on adherence to medications in patients 
with chronic diseases. 
 
3.2 Secondary Objectives 
1. To determine the clinical outcomes of CareAide® usage in patients with chronic diseases. 
2. To evaluate and determine the cost-effectiveness of CareAide® in the management of 
chronic diseases in Malaysia.  
3. To study and assess the burden and health-related quality of life (HRQoL) of chronic 
diseases for estimation of the quality adjusted life years (QALY). 
4. To gauge the users’ perception and satisfaction of the CareAide® application.  
 
4.0 Methodology 
4.1 Study Design 
A 3- and 6- month open-label multicentre randomized controlled trial with two parallel groups will 
be conducted. This study will take place in the outpatient setting of the three hospitals [i.e., 
Hospital Putrajaya, Hospital Pulau Pinang and Universiti Malaya Medical Center (UMMC)) in 
Malaysia]. Standard chronic disease treatments will be given to both groups of participants, but 
the CareAide ® app will be provided for the experimental group during the trial. Both groups will 
be allocated to 1:1 ratio. Randomization number will be generated by using online number 
generated programme. Consultants reviewing patients at medical, cardiology, diabetes mellitus 
and asthma clinics will provide referral and notify independent researchers for eligibility and group 
assignments. Eligible patients will then be instructed to see pharmacists/researchers at outpatient 
pharmacies to refill their prescriptions and subsequently enrol in the assigned study group either 
to receive an intervention with CareAide® or to receive normal clinical care. Information and 
training on the app will be provided by these researchers to the participants. 

Version 9 Date: 30.7.2022 
 
5 
 
 
4.2 Participant Recruitment, Eligibility Criteria and Study Procedures 
Patients will be recruited at the respective outpatient clinics. At the usual care clinic appointments, 
patients have their demographics and baseline data of blood pressure, blood sugar, basic blood 
profiles, 
asthma 
control 
and 
review 
of 
their 
disease 
management 
collected 
by 
consultants/researchers. Patients who meet the study criteria will then be instructed to see 
pharmacists/researchers 
at 
outpatient 
pharmacy 
to 
refill 
their 
medications. 
The 
pharmacists/researchers will screen patients’ inclusion and exclusion criteria for this study and 
will explain that they may or may not be selected for the study and if they agree, proceed to provide 
written informed consent. The adherence data from the screening will be collected to gauge the 
general adherence rate in these group of patients. An independent researcher, who is not involved 
in the intervention and control groups, will use the random number function in Excel to generate 
randomisation sequences. The random numbers will be placed in opaque envelopes, which 
subsequently will be opened by pharmacists/researchers at the outpatient pharmacies. Participants 
and pharmacists/researchers are unblinded to group assignment and are aware of the intervention, 
but the study hypotheses are not disclosed to the participants. The assessor and statisticians are 
blinded to participant allocation. The study will be evaluating usual care compared with usual care 
plus pharmacist-driven patient-specific adherence interventions - CareAide® medication 
adherence digital application. Usual care provided by these hospitals comprises clinic 
appointments every 3 to 6 months.  
 
4.2.1 Intervention group 
- 
Intervention group will be asked to download and use the CareAide® app to help manage 
medications for 12 to 24 weeks. CareAide® is a free digital application designed to manage 
complex medicines schedules and improve adherence. 
 
4.2.2 Control group 
- 
Control group will not be asked to download any digital applications but only receive the 
usual care by the hospitals. 
 
4.3 Patients’ inclusion and exclusion criteria are as follow: 

Version 9 Date: 30.7.2022 
 
6 
 
 
 
4.3.1 Inclusion criteria: 
o Age: 18 years and above 
o Diagnosed with selected non-communicable diseases (NCDs): hypertension, 
diabetes mellitus, heart failure or asthma for at least 6 months 
o Prescription generated from one of the following specialty clinics: Medical, 
Cardiology, Diabetes Mellitus or Asthma clinics 
o Medications are prescribed in previous 3 months and refill at the point of 
recruitment 
o Morisky Medication Adherence Scale (MMAS) score < 6 
o More than three medications daily or two medications with multiple dosing 
intervals. 
o One or more hospital admissions in the prior 24 months 
o Understand and able to command in English and own a smartphone 
 
4.3.2 Exclusion criteria: 
o Medications prescribed from other institution providers 
o Existing mobile health app or medication reminder app user 
o Pregnant 
o Cognitively impaired 
o Prisoners 
o Bed-bound 
o Severe diseases/comorbidities – terminal cancer, psychiatry, etc 
 
4.3.3 Withdrawal criteria: 
Participants can choose to withdraw at any time for any reason, specified or unspecified, and 
without prejudice to their care. Participants may be withdrawn if the investigator feels that it is not 
for the participants’ best interest to continue. The following is a list of possible reasons for study 
intervention discontinuation:  
o Screening failure 

Version 9 Date: 30.7.2022 
 
7 
 
o Participant withdrawal of consent 
o Participant is not compliant with study procedures 
o Protocol violation requiring discontinuation 
o Lost to follow-up 
o Request from sponsor for early termination of study 
o Participant death 
Withdrawn participants will not be replaced. It will be documented whether or not each subject 
completes the clinical study. If the Investigator becomes aware of any serious, related adverse 
events after the subject completes or withdraws from the study, they will be recorded in the source 
documents and on the Case Report Form (CRF). The Investigator will contact participants who are 
lost to follow-up. Contacts attempts with such subjects will be documented in the participant’s 
records (e.g., times and dates of attempted phone contact, receipt for mailing a registered letter, 
etc.). 
 
4.4 Outcome measurements 
4.4.1 Phase 1 
4.4.1.1 Primary outcome  
Medication adherence: CareAide® effectiveness is measured with a medication adherence tool at 
baseline and follow-up time periods at 3 months and 6 months using Morisky Medication 
Adherence Scale-8 (MMAS-8) and proportion of days covered (PDC). The primary outcome of 
the study is medication adherence, which is assessed using the 8-item Morisky Medication 
Adherence Scale (MMAS-8) and the Proportion of Days Covered (PDC) method. Measurements 
are taken at baseline and at two additional time points, with a 3-month interval following the 
intervention. MMAS-8 is a licensed validated questionnaire to assess medication adherence, where 
a higher score represents higher medication adherence and vice versa. Comprising of 8 items, the 
score ranges from 0 to 8, where a higher score represents a higher medication adherence. The 
internal consistency (Cronbach’s alpha) of MMAS-8 is 0.83 along with a sensitivity of 93% and a 
specificity of 57%. The PDC method utilises pharmacy refill records (Raebel et al., 2013). The 
PDC can be calculated as below (Hess et al., 2006; Raebel et al., 2013; Pednekar et al., 2019): 
Nm/Nd x 100% 

Version 9 Date: 30.7.2022 
 
8 
 
Where Nm denotes the number of days covered by the medication while Nd meant the number of 
days in the study period. The patients are considered to be adherent if their PDC scores are ≥0.8 
or 80% (Karve et al., 2009). The prescription refill data was extracted from outpatient/hospital 
database. 
 
4.4.1.2 Secondary outcomes 
Fasting blood sugar, HbA1C, cardiovascular events (heart failure admission, mortality), asthma 
control and blood pressure, hospitalizations and emergency visits measurements will be based on 
the clinics attended by the participants. Health care utilization, quality of life and health care 
expenditures will be measured for all the participants. 
 
i. Data Collection 
Data on patients’ sociodemographic, resources consumptions such as direct and indirect medical 
costs and health quality of life (HRQoL) will be collected.  
 
ii.  Sociodemographic  
Data such as socio-demographics (age, sex, education level, occupation, income, and religion), 
will be collected via face-to-face interview or phone interview via a structured and validated 
questionnaire.  
 
iii.  Direct Medical Cost 
This study will apply a bottom-up micro costing approach for direct cost estimation. Healthcare 
costs such as outpatient visits, medicine use, hospitalization, diagnostic and laboratory test costs 
will be gathered in this study for direct cost estimation of chronic diseases. Costs for outpatient 
visits, hospitalization, diagnostic and laboratory tests will be valued based on the MOH Full Paying 
Patient Tariff Schedule of fees for a foreigner patient scheme provided by the Financial 
Department for Ministry of Health Hospitals. Medication utilization costs will be estimated from 
the National Price List of Medicines provided by the Procurement Unit of the Pharmacy 
Department. Costs of medicine per patient will be calculated by total drugs supplied for a patient 
multiplied by the average acquisition cost price obtained of the hospital. All costs will be valued 
in Malaysia Ringgit (MYR).   

Version 9 Date: 30.7.2022 
 
9 
 
 
iv.  Indirect Medical Cost 
Indirect medical or patient out-of-pocket cost such as transportation costs, productivity losses, 
caregiver costs and waiting time in outpatient visit will be collected with the used of cost 
questionnaires to the participants. Patients will be requested to report the resource utilization over 
the past 3 months during the first time after recruitment(baseline) and after every 3 months (at 3 
and 6 months). Transportation costs included parking fees. Patient time costs will be calculated 
based on waiting time in outpatient visit with the wages per hour of patient. Rate of wages per 
hour will be estimated based on patient’s reported income per hour. Productivity losses will not be 
accounted for patients who are retired and jobless. This economic cost will help to evaluate the 
economic impact of CareAide from patients’ perspective. All costs will be valued in Malaysia 
Ringgit (MYR).   
 
v.  Health-related quality of life (HRQoL) of patients  
The overall health state and quality of life will be collected with the EuroQol-5D (EQ-5D-5L) and 
Short Form 36 Health Survey (SF-36) questionnaires to determine quality-adjusted life years 
(QALYS) over 3- and 6- months follow-up time. This study will use the EQ-5D-5L and SF-36 
surveys to assess the HRQoL of chronic disease patients. The EQ-5D-5L instrument of the 
EuroQol is a validated tool to measure the health status of various groups in various diseases. This 
tool composed of five dimensions: mobility, self-care, usual activities, pain/discomfort and 
anxiety/ depression (Lins et. al., 2016). Another questionnaire SF-36 is a self-reported measure of 
health with 36 items which cover eight domains of health. The eight domains including vitality, 
mental health, physical functioning, bodily pain, general health perceptions, physical role 
functioning, emotional role functioning and social role functioning (Lins et al., 2016).  Both tools 
consist of questionnaires whereas EQ-5D-5L consists of additional visual analogue scale. These 
tools will be conducted via face-to face or phone interview to assess the health status of 
respondents.  
Trained research personnel will explain the purpose of the study and obtain consent of the 
participants before distributing or administering the questionnaires. Participants will then be 
distributed with questionnaires. EQ-5D-5L and SF-36 have different languages versions of the 
validated phone interview or face-to face questionnaires included English, Malay, Tamil and 

Version 9 Date: 30.7.2022 
 
10 
 
Chinese languages for Malaysians. Research personnel will provide or use the patients’ preferred 
version of language for conducting the survey. 
 
Figure 1: Consolidated Standards of Reporting (CONSORT) flow chart (Consort, 2021; 
Evsenbach et. al., 2011). 
 
4.4.2 Phase 2 
Only the participants using the CareAide® app will be given the questionnaires at the end of 6 
months follow up to understand the participant's perception of the perceived usefulness of the app 
and rate their satisfaction with the app. A structured questionnaire will be developed from existing 
literature (Kim et al., 2016; Eveleth & Robert, 2020) to facilitate data collection. It will be designed 
to be self-administered. The questionnaire will be divided into three sections to specify the type of 
questions to be asked. The first section consists of basic demographics, including age, gender, 
ethnicity, personal health status, and the number of medications taken. Section two includes the 
questions to explore the perception of the users towards the app. The responses will be measured 
using a 5-point Likert scale.  Section three consists of a questionnaire to rate their satisfaction with 
the app. 
Assessed for Eligibility
Baseline Measure
Randomization
Intervention Group 
(with CareAide App)
Control Group (without 
CareAide App)
Follow-up at 3 month 
and 6 month
Analysis

Version 9 Date: 30.7.2022 
 
11 
 
For perception, the perceived usefulness questions were developed from the work of Kim et al., 
2016), and the self-efficacy questions will be developed from Eveleth & Robert, (2020). The 
ratings will be given on a 5-point Likert scale. A higher rating corresponds to the higher agreement 
(e.g., 1=strongly disagree, 5=strongly agree). 
For satisfaction, the satisfaction questionnaire will be an adaptation of the user satisfaction survey 
used in the mobile health (mHealth) apps by Melin et al. (2020). The questionnaire consists of 11 
questions, 10 items where the respondent will be asked to rate to what extent they agree on each 
item on a 5-point Likert scale and concluded with an open question on the recommendation of any 
suggestions to customise the experience to the patient's needs. 
Data will be collected via a self-administered questionnaire to explore the study participants´ 
perceptions and satisfaction with the CareAide® app. The self-administered questionnaires will 
either be mailed or given in person to the respondents, and their participation is entirely voluntary. 
The content validity of the questionnaire will be assessed by a panel of experts based on their 
evaluation analysis through comments and feedback submitted. The questionnaire will be pilot 
tested on 20 patients to check the feasibility and validity of the questionnaire. Results from the 
pilot study will not be included in the final analysis. Should the respondents fail to understand and 
answer the questionnaire, modifications will be done to obtain accurate data. Cronbach’s alpha test 
will be used to assess the internal consistency of the questionnaire. 
 
Section 1: Participant demographics 
Age group, gender, ethnicity, phone type, health status, education level, and number of 
medications taken 
 
Section 2: Perception of perceived usefulness of the CareAide® app 
       i.         Improves medication adherence 
     ii.         Makes remote patient monitoring possible and easy 
    iii.      Improves the chance patients take their medications properly and on time - 
Excellent reminder to take or refill patient prescriptions and track pills remaining. 
    iv.         Improves social performance - Patients interaction with mobile apps (whether 
is clear and understandable) 

Version 9 Date: 30.7.2022 
 
12 
 
     v.         Practicality of technology for elderly (technology laggards, novice users or lack 
of comfort and familiarity with smartphones). 
  
Section 3: Participant Satisfaction with the CareAide® app 
a) What did you think about using the health app? (5-point Likert scale) 
·       It was easy to use 
·       It was good to use 
·       The time spent using it has been acceptable 
·       The introduction of how to use it was sufficient 
·       It was too time-consuming 
·       It was boring to use 
·       It was a disturbance/ distraction 
·       I will recommend it to others  
b) Do you have any suggestions about how the app could do better and customise the 
experience for your needs? 
___________ 
 
4.5 Sample Size 
The primary outcome for this study is to assess medication adherence of patient after using mobile 
health application. Therefore, sample size for this randomized controlled trial is calculated using 
the continuous outcome formula below (Charan & Biswas, 2013; Wittes, 2002): 
n! =
2(Z" #
$  + Z&)#P (1 −P)
(P'  − P# )#
 
n!(    sample size required for each group (i = 1,2) 
Z" #
$ = Assumed type I error: α equal to 5%, then Z).)+ #
$ = Z).)#+  =  1.96 (From Z table) 
Z&= Assumed power of 80% Z&=0.84 
P'  − P#= Effect Size= Difference in the proportion of events in two groups 
P= Total prevalence 
Total Sample size needed: 388 per group 
Note: Based on few past studies reported for non-adherence rate for patients in Malaysia is within 
46.6% to 56% (Ting et al., 2019). Therefore, assumption of prevalence of chronic disease is 70% 

Version 9 Date: 30.7.2022 
 
13 
 
of the adult and adherence rate of 50% is made. A systematic review showed that mobile app able 
to improve adherence by 7% to 40% (Pérez-Jover et al., 2019). Medication non-adherence rate of 
50% is expected in control group and 40% is expected in intervention group. For a 10% absolute 
difference in medication non-adherence rate between control and intervention group, 388 patients 
per arm should be recruited in the study assuming a type I error of 5% and power of 80%.  
N (number to enrol) * (1-% drop out) = desired sample size 
Therefore N (number to enrol) = desired sample size / (1- % drop out) 
N= 388/0.80= 485 per group 
Based on a systemic review published by Wood and colleagues found out there is a possibility of 
20% loss of follow-up, drop out and those who are unable to meet the inclusion criteria (Wood et 
al., 2004). Therefore, a minimum sample size of 970 is needed in this study, with the number of 
485 in each arm. 
The sample size obtained from the primary outcome is too large and which might need to spend 
more time and manpower. Hence, the sample size calculation is repeated with the use of secondary 
outcome which is cost-effectiveness economic evaluation of the study. Glick (2011) formula is 
applied for the calculation of sample size as it incorporates all important economic evaluation 
informations such as difference in treatment costs and effects and willingness to pay threshold in 
a single formula.  
n! =
2 DZ" #
$  + Z&E
#
(𝑆𝑑,
# + H𝑊#𝑆𝑑-
#J −H2 𝑊 𝑝 𝑆𝑑, 𝑆𝑑-J ) 
(W∆Q − ∆C)#
 
 
n!(    sample size required for each group (i = 1,2) 
Z" #
$ = Assumed type I error: α equal to 5%, then Z).)+ #
$ = Z).)#+  =  1.96 (From Z table) 
Z& = Assumed power of 80% Z&=0.84 
W = Willingness to pay threshold 
p = Expected correlation between difference in costs (∆C) and effects (∆Q) 
∆Q = Expected difference in mean effects 
∆C = Expected difference in mean costs 
𝑆𝑑- = Expected standard deviation for the effects 
𝑆𝑑, = Expected standard deviation for the costs 

Version 9 Date: 30.7.2022 
 
14 
 
To our knowledge, there is no published study has evaluated the direct and indirect costs and 
quality of life associated with mobile health app for the management of non-communicable 
diseases. Therefore, the calculation is based on the assumption and few literature results. 
According to a study published in Malaysia, RM 2499.15 is required for the managing of patient 
complicated with diabetes and heart failure after the first event (Shafie & Ng, 2020). The cost from 
the study is adjusted according to Consumer Price Index 2022. The cost difference between 
treatment group is considered as around 30% as reported by the use of mobile app in the 
management of heart failure study (Cano Martín et al., 2014). A minimum difference of 0.01 is 
estimated in term of QALY in favour of mobile health app user.  𝑆𝑑, and 𝑆𝑑- are assumed as 
RM1000 and 0.01 respectively. The willingness to pay threshold is set at RM 28,470 per QALY 
as reported by Lim et al. (2017). The correlation coefficient is set at minimum 0.1 as estimated 
from cost-effectiveness analysis of a mobile-based intervention for patients with type 2 diabetes 
mellitus conducted by Li et al. (2021). A number of 150 patients (75 per study group) is required 
to detect at least 80% power assuming a two-tailed test and alpha of 5% between treatment group. 
The sample size will be rounded up to 200 patients to account for a possibility of 20% attrition. 
The sample size obtained is corresponding to the sample size applied in Li et al. (2021) cost-
effectiveness analysis study. 
4.6 Data Analyses 
Intention to treat (ITT) analysis will be applied to evaluate the results to avoid any bias. 
The data analysis will be using the SPSS version 27. Data will be coded and analysed. Descriptive 
or categorical data will be expressed as mean ± standard deviation (SD) unless otherwise stated. 
Student t-test will be used for analysis of normally distributed or continuous variables. Mann-
Whitney test will be used for non-normally distributed data. Categorical data will be analysed 
using Chi-square or Fischer’s exact test. A value of P < 0.05 is considered statistically significant.  
The prevalence of medication compliant is quantified at 3 months and 6 months follow-up. 
Independent t-test or Mann-Whitney test will be used to compare MMAS score rankings between 
the intervention and control groups. Chi-Square test of independence will be used to determine the 
difference in number of patients with medication adherence between the intervention and control 
groups at 3 months and 6 months follow-up. Ordinal logistic regression, with the MMAS 
adherence score ranking, will be used to examine the association between intervention and control 
groups.  

Version 9 Date: 30.7.2022 
 
15 
 
For the perception and satisfaction towards the app, the frequency and percentage of 
respondents in each category (strongly disagree to strongly agree) will be calculated. The median 
of each statement will then be calculated to give an overview of perception and satisfaction towards 
the CareAide® app. Chi-square, Mann-Whitney U, Kriskall Wallis, Chi-square tests and logistic 
regression will be used where appropriate. The open-ended question will be analysed using 
thematic analysis as proposed by Braun and Clarke (2012). Codes will be assigned to the data to 
describe the content. After the coding is completed, themes will be generated, reviewed, and 
named. Linear regression analysis will be conducted to determine the independent predictors of 
HRQoL.  
An economic evaluation will be conducted from a payer and societal perspective. Costs 
and outcomes will be discounted at 3% per year (Shafie et al., 2019) as the results will be 
extrapolated to examine costs and outcome over a year.. Cost effectiveness analysis will be 
estimated based on the results of cost data and EQ-5D-5L to calculate the incremental cost per 
quality adjusted life year (QALY) gained. Total incremental cost effectiveness ratio (ICER) will 
be calculated by dividing the difference between the cost of CareAide intervention group and 
control group by the difference between the QALYs of CareAide intervention group and control 
group. Sensitivity analysis will be performed by bootstrapping technique to ensure or examine the 
robustness of ICER. Then, cost effectiveness acceptability curve (CEAC) will be created to 
estimate the proportion of the result being cost-effective in relation to the Willingness-to-Pay 
(WTP) threshold. 
 
4.7 Risk and Benefit to study participants 
The study contributes minimal or no risk to the participants. This study may improve the 
medication adherence for participants. 
4.8 Risk Benefit Assessment 
As stated above, this study contributes minimal or no risk to the participants. As this study involves 
questionnaire survey, participants are requested to spend 15 to 30 minutes to complete 
questionnaires carefully and truthfully. 
4.9 Ethical Consideration 

Version 9 Date: 30.7.2022 
 
16 
 
For government hospitals, ethical approval will be sought from the Medical Research Ethics 
Committee (MREC), meanwhile PPUM-MREC will be sought for PPUM research site.  
 
5.0 Conflict of Interest  
There is no conflict of interest to declare.  
5.1 Privacy and Confidentiality 
Data will be kept at Universiti of Malaya (UM). Primarily only investigators in the study will have 
access to the research data. However, individuals involved in this sub-study, qualified monitors 
and auditors, the sponsor or its affiliates and governmental or regulatory authorities may inspect 
and copy research, where appropriate and necessary. Any unused sample that has not been 
processed in research will be destroyed. Information that was extracted from medical records will 
not be destroyed until 7 years after the last publication. Results that will be obtained from this 
study will be published, presented, and shared with other researcher, scientist and community. In 
Caringup system, the user (patient/family) data is owned by the user. The user can delete their data 
at any time. The data from all the repositories can be erased as bounded by the General Data 
Protection Regulation (GDPR). The personal data will be encrypted and stored in Microsoft Azure 
cloud. A user (patient or family members) will get Data Privacy Policy in English and Malay when 
signing up to use CareAide app. No data will be transmitted from hospitals such as UMMC, 
Hospital Putrajaya and Hospital Pulau Pinang to CaringUp company. The data of the patients who 
participate in the study will be provided by CaringUp to research team. Patient data is owned by 
patient. They can delete at any time according to the regulation.   
5.2 Publication Policy 
No personnel information will be revealed, and subjects will not be identified when the findings 
of the results are published. Permission from the Director General of Health, Malaysia will be 
obtained prior to publication. 
5.3 Termination of Study 
The sponsor may decide to terminate the study at any time if there is sufficient reasonable cause. 
Circumstances that may warrant termination or suspension such as lack of recruitment, inability 

Version 9 Date: 30.7.2022 
 
17 
 
to sustain or further manage the study or due to safety concerns. Participants will be informed if 
the study is terminated and follow-up visits will be arranged if needed. 
 
 
 
 
 
References 
Asche, C., LaFleur, J., & Conner, C. (2011). A review of diabetes treatment adherence and the 
association 
with 
clinical 
and 
economic 
outcomes. 
Clin 
Ther, 
33(1), 
74-109. 
https://doi.org/10.1016/j.clinthera.2011.01.019 
 
Baker-Eveleth, L., & Stone, R. W. (2020). User's perceptions of perceived usefulness, satisfaction, 
and intentions of mobile application. International Journal of Mobile Communications, 18(1), 1-
18. 
 
Beratarrechea, A., Lee, A. G., Willner, J. M., Jahangir, E., Ciapponi, A., & Rubinstein, A. (2014). 
The impact of mobile health interventions on chronic disease outcomes in developing countries: a 
systematic 
review. 
Telemed 
J 
E 
Health, 
20(1), 
75-82. 
https://doi.org/10.1089/tmj.2012.0328Charan, J., & Biswas, T. (2013). How to Calculate Sample 
Size for Different Study Designs in Medical Research. Indian Journal of Psychological Medicine, 
35(2), 121-126.  
 
Cano Martín, J. A., Martínez-Pérez, B., de la Torre-Díez, I., & López-Coronado, M. (2014). 
Economic impact assessment from the use of a mobile app for the self-management of heart 
diseases by patients with heart failure in a Spanish region. Journal of medical systems, 38(9), 1-7. 
 
Chia, Y. C., Devaraj, N. K., Ching, S. M., Ooi, P. B., Chew, M. T., Chew, B. N., Mohamed, M., 
Lim, H. M., Beh, H. C., & Othman, A. S. (2021). Relationship of an adherence score with blood 
pressure control status among patients with hypertension and their determinants: Findings from a 
nationwide blood pressure screening program. The Journal of Clinical Hypertension, 23(3), 638–
645. 
 
Consort - The CONSORT Flow Diagram. (2021). Retrieved 11 December 2021, from 
http://www.consort-statement.org/consort-statement/flow-diagram. 
 
Eysenbach, G. (2011). CONSORT-EHEALTH: Improving and Standardizing Evaluation Reports 
of Web-based and Mobile Health Interventions. Journal Of Medical Internet Research, 13(4), 
e126. doi: 10.2196/jmir.1923. 
 
Glick, H. A. (2011). Sample size and power for cost-effectiveness analysis (part 1). 
Pharmacoeconomics, 29(3), 189-198. https://doi.org/10.2165/11585070-000000000-00000  

Version 9 Date: 30.7.2022 
 
18 
 
Iribarren, S. J., Cato, K., Falzon, L., & Stone, P. W. (2017). What is the economic evidence for 
mHealth? A systematic review of economic evaluations of mHealth solutions. PloS one, 12(2), 
e0170581. 
 
Islam, S., Peiffer, R., Chow, C., Maddison, R., Lechner, A., & Holle, R. et al. (2020). Cost-
effectiveness of a mobile-phone text messaging intervention on type 2 diabetes—A randomized-
controlled trial. Health Policy and Technology, 9(1), 79-85. 
 
Kim, S. C., Yoon, D., & Han, E. K. (2016). Antecedents of mobile app usage among smartphone 
users. Journal of marketing communications, 22(6), 653-670. 
 
Li, J., Sun, L., Hou, Y., & Chen, L. (2021). Cost-Effectiveness Analysis of a Mobile-Based 
Intervention for Patients with Type 2 Diabetes Mellitus. Int J Endocrinol, 2021, 8827629. 
https://doi.org/10.1155/2021/8827629 
 
Li, R., Liang, N., Bu, F., & Hesketh, T. (2020). The Effectiveness of Self-Management of 
Hypertension in Adults Using Mobile Health: Systematic Review and Meta-Analysis. JMIR 
Mhealth Uhealth, 8(3), e17776. 
 
Lim YW, Shafie AA, Chua GN, Hassali MAA (2017). Determination of CostEffectiveness 
Threshold for Health Care Interventions in Malaysia. Value in Health, 20(8), 1131-1138. 
 
Lins, L., & Carvalho, F. M. (2016). SF-36 total score as a single measure of health-related quality 
of life: Scoping review. SAGE open medicine, 4, 2050312116671725.  
 
Melin, J., Bonn, S. E., Pendrill, L., & Trolle Lagerros, Y. (2020). A Questionnaire for Assessing 
User Satisfaction with Mobile Health Apps: Development Using Rasch Measurement Theory. 
JMIR mHealth and uHealth, 8(5), e15909.  
 
Ministry of Health Malaysia. (2020). The impact of noncommunicable diseases and their risk 
factors on Malaysia’s gross domestic product. Retrieved 9 December 2011, from 
https://www.moh.gov.my/index.php/database_stores/attach_download/554/64 
 
Pérez-Jover, V., Sala-González, M., Guilabert, M., & Mira, J. J. (2019). Mobile Apps for 
Increasing Treatment Adherence: Systematic Review. Journal of medical Internet research, 21(6), 
e12505.  
 
Purcell, R., McInnes, S., & Halcomb, E. J. (2014). Telemonitoring can assist in managing 
cardiovascular disease in primary care: A systematic review of systematic reviews. BMC Family 
Practice, 15(1), 43. https://doi.org/10.1186/1471-2296-15-43 
 
Sanyal, C., Stolee, P., Juzwishin, D., & Husereau, D. (2018). Economic evaluations of eHealth 
technologies: A systematic review. PLoS One, 13(6), e0198112. 
 
Shafie, A. A., Fen, N. C., Shabaruddin, F. H., Din, R. M., Yen, L. S., & Lajis, R. et al. (2019). 
Pharmacoeconomic Guidelines Malaysia Second Edition 2019.  

Version 9 Date: 30.7.2022 
 
19 
 
Shafie, A. A., & Ng, C. H. (2020). Estimating the costs of managing complications of type 2 
diabetes mellitus in Malaysia. Malaysian Journal of Pharmaceutical Sciences, 18(2), 15-32. 
Shang, P., Liu, G. G., Zheng, X., Ho, P. M., Hu, S., Li, J., Jiang, Z., Li, X., Bai, X., & Gao, Y. 
(2019). Association between medication adherence and 1‐year major cardiovascular adverse 
events after acute myocardial infarction in China. Journal of the American Heart Association, 8(9), 
e011793. 
 
Ting, C., Adruce, S., Loo, S., Ting, H., & Tnay, J. (2019). Interventions on Improving Medication 
Adherence in Malaysia: A Mini Review. Journal Of Young Pharmacists, 11(2), 122-125.  
 
Tsuji, S., Ishikawa, T., Morii, Y., Zhang, H., Suzuki, T., Tanikawa, T., Nakaya, J., & Ogasawara, 
K. (2020). Cost-Effectiveness of a Continuous Glucose Monitoring Mobile App for Patients with 
Type 2 Diabetes Mellitus: Analysis Simulation. J Med Internet Res, 22(9), e16053. 
https://doi.org/10.2196/16053 
 
Vahatalo, I., Kankaanranta, H., Tuomisto, L. E., Niemela, O., Lehtimaki, L., & Ilmarinen, P. 
(2021). Long-term adherence to inhaled corticosteroids and asthma control in adult-onset asthma. 
ERJ Open Res, 7(1). https://doi.org/10.1183/23120541.00715-2020 
 
Wittes, J. (2002). Sample Size Calculations for Randomized Controlled Trials. Epidemiologic 
Reviews, 24(1), 39-53.  
 
Wood, A. M., White, I. R., & Thompson, S. G. (2004). Are missing outcome data adequately 
handled? A review of published randomized controlled trials in major medical journals. Clinical 
trials, 1(4), 368-3.

Page 1 of 7
 
 
Version 5.0, dated 15 July 2022     
 
PATIENT INFORMATION SHEET AND INFORMED CONSENT FORM 
(for adult subjects and interventional studies) 
 
1. Title of study: Perception, Adherence, Clinical, Economical and Health-Related Quality of 
Life Outcomes of CareAide® App usage in Chronic Diseases 
 
2. Name of investigator and institution:   
 
a. Dr. Ong Siew Chin (Pincipal/Coordinating Investigator) 
b. Associate Professor Dr. Baharudin Ibrahim (Pincipal Investigator at University Malaya 
Medical Centre, Kuala Lumpur) 
c. Associate Professor Dr. Hasniza Binti Zaman Huri (Co/Sub Investigator at University 
Malaya Medical Centre, Kuala Lumpur) 
d. Dr. Navin Kumar A/L Loganadan (Principle Investigator at Hospital Putrajaya, Putrajaya) 
e. Dr. Jaya Muneswarao A/L Ramadoo@Devudu (Principle Investigator at Hospital Pulau 
Pinang, Pulau Pinang) 
 
 
3. Name of sponsor:  CaringUp Malaysia Sdn Bhd 
 
4.   Introduction: 
 
You  are  invited  to  participate  in  a  research  study  because  you  have chronic disease 
that requires on long term medication treatment. CareAide® is a digital app that may help to 
manage complex medicine schedules and improve adherence thus help manage complex 
medicine schedules with minimal involvement of healthcare resources. The app can include 
both the patients and the caregivers to monitor the medication taking behavior. The details of 
the research trial are described in this document. It is important that you understand why the 
research is being done and what it will involve. Please take your time to read through and 
consider this information carefully before you decide if you are willing to participate. Ask the 
study staff if anything is unclear or if you like more information. After you are properly 
satisfied that you understand this study, and that you wish to participate, you must sign this 
informed consent form.  To  participate  in  this  study,  you  may  be  required  to  provide  
you  doctor  with information on your health history; you may harm yourself if you are not 
truthful with the information provided. 
 
Your participation in this study is voluntary. You do not have to be in this study if you do not 
want to. You may also refuse to answer any questions you do not want to answer.  If you 
volunteer to be in this study, you may withdraw from it at any time. If you withdraw, any 
data collected from you up to your withdrawal will still be used for the study. Your refusal to 
participate or withdrawal will not affect any medical or health benefits to which you are 
otherwise entitled. 
 
This study has been approved by the Medical Research and Ethics Committee, Ministry of 
Health Malaysia. 
 
5.   What is the purpose of the study? 

Page 2 of 7
 
 
Version 5.0, dated 15 July 2022     
 
 
The purpose of this study is to evaluate and determine the effect and clinical outcome of 
CareAide® intervention on adherence to medications in patients with chronic diseases. 
Besides, this study is also designed to evaluate cost-effectiveness of this intervention by 
assessing the burden and health related quality of life of the patient with chronic disease. Last 
but not least, the users’ perception and satisfaction of the CareAide® application will also be 
gauged and reviewed in this study. This research is necessary because chronic diseases 
imposed a significant health burden to our country. Many studies found that the medication 
adherence rates are lower in chronic disease patients than in those with acute disease. Failure 
to adherence negatively affects the efficacy, safety and costs of therapies. New and innovative 
technology such as mobile health application, CareAide® should be applied to improve 
medication adherence of patient in managing their chronic diseases which in turn to improve 
patient health status. 
 
This research will be conducted for the duration of 3 years (Jan 2022 until Dec 2024) and 
your participation will be around 6 months. The expected number of participants is 970 
individuals from Malaysia. 
 
6.   What kind of study products will I receive? 
 
If you agree to participate in the study, you will be instructed to see pharmacists/researchers 
at outpatient pharmacies to refill their prescriptions. The pharmacists/researchers will screen 
for the inclusion and exclusion criteria for this study and will explain that the you may or may 
not be selected for the study and if you agree, proceed to provide written informed consent. 
You will be subsequently enrolled in the assigned study group either to receive an 
intervention with CareAide® or to receive normal clinical care. An independent researcher, 
who is not involved in the intervention and control groups, will use the random number 
function in Excel to generate randomisation sequences. The random numbers will be placed 
in opaque envelopes, which subsequently will be opened by pharmacists/researchers at the 
outpatient pharmacies. You have equal chance of being assigned to each of the groups.  
 
The study product is a mobile health application. You will be provided information and 
training about the app if you are in the group to receive and intervention with CareAide®. 
 
Group 1: Patient will be asked to download and use the CareAide® app to help manage 
medications for 12 to 24 weeks. CareAide® is a free digital application designed to manage 
complex medicines schedules and improve adherence. 
 
Group 2: Patient will not be asked to download any digital applications but only receive 
the usual care by the hospitals. 
 
7.   What will happen if I decide to take part? 
 
Study Procedures 
If you agree to be in this study, you will undergo some activities, test and evaluations to 
determine if you are eligible for this study. Such tests and evaluations are completed during a 
screening period that takes place before participation in the main part of the study. Please refer 
to the study activities table below. 

Page 3 of 7
 
 
Version 5.0, dated 15 July 2022     
 
 
Study Activity Table: 
 
Screening/ 
Assess 
for 
Eligibility 
Baseline 
Assessment 
and  
Randomiza
tion 
Follow Up 
at 3 Month 
Follow Up 
at 6 Month 
Visit
1
2
3
4
Timeline (at weeks)
-1
0
12
24
Procedures 
Screen Inclusion and Exclusion 
Criteria
X 
 
 
 
Informed Consent
X
Randomization
X
Subjects Demographics
X
Medical History
X
Medication History
X
X
X
Laboratory data
X
X
X
Vital Signs (Blood Pressure, 
Heart Rate etc.)
 
X 
X 
X 
Physical Exam (ECG etc.)
X
X
X
Direct and indirect cost
X
X
X
Medication 
Adherence 
Asssessment 
(Morisky 
Medication 
Adherence 
Scale, 
Proportion of Days Covered)
 
X 
X 
X 
Health Related Quality of Life 
(HRQoL)
 
X 
X 
X 
Perception 
of 
the 
perceived 
usefulness of the app and rate 
your satisfaction of the app
 
 
 
X 
 
Screening Visit / Assess for Eligibility  
You will be referred by consultants at the respective outpatient clinics if you meet our study 
criteria during consultation period. You will then be instructed to see pharmacists/researchers 
at outpatient pharmacies to refill their prescriptions and will be screened for inclusion and 
exclusion criteria for this study. You will be provided a written informed consent if you are 
selected and agreed to participate in this study. 
 
Baseline Visit and Randomization 
If you pass Screening, your demographics and baseline data of blood pressure, blood sugar, 
basic blood profiles, asthma control and review of your disease management will be collected 
by consultants/researchers.  
Following that you will be randomly assigned by chance. An independent researcher, who is 
not involved in the intervention and control groups, will use the random number function in 
Excel to generate randomisation sequences. The random numbers will be placed in opaque 
envelopes, which subsequently will be opened by pharmacists/researchers at the outpatient 

Page 4 of 7
 
 
Version 5.0, dated 15 July 2022     
 
pharmacies. You will be subsequently enroll in the assigned study group either to receive an 
intervention with CareAide® or to receive normal clinical care. Information and training on 
the app will be provided by these researchers to the participants. 
Besides, you will be given a questionnaire form to be answered. This form contains few 
sections which will enquire and assess about your direct and indirect cost estimation, 
medication adherence and Health Related Quality of Life (HRQoL). These few sections are to 
assess for the 3 months prior to randomization or this study. For direct medical cost, you will 
be requested to report the cost of visiting and medication obtained from facility other than 
your current recruited facility. You will be required to declare the indirect cost such as cost of 
transportation, productivity losses, caregiver costs and waiting time in outpatient visit. 
Morisky Medication Adherence Scale (8-Item) questionnaire will be used to assess your 
medication adherence. Moreover, you will be requested to fill up EQ-5D-5L and SF-36 
surveys to assess your HRQoL. 
 
Follow Up Visit At 3 Months 
This is the first follow up visit of the study, which is 3 months after the intervention allocation. 
You will be assessed for fasting blood sugar, HbA1C, cardiovascular events (heart failure 
admission, mortality), asthma control and blood pressure.  
Besides, you will be given a questionnaire form to be answered. This form contains few 
sections which will enquire and assess about your direct and indirect cost estimation, 
medication adherence and Health Related Quality of Life (HRQoL) over the last 3 months. 
 
Follow Up Visit At 6 Months 
This is the last follow up visit of the study, which is 6 months after the intervention allocation. 
You will be assessed for fasting blood sugar, HbA1C, cardiovascular events (heart failure 
admission, mortality), asthma control and blood pressure.  
Besides, you will be given a questionnaire form to be answered. This form contains few 
sections which will enquire and assess about your direct and indirect cost estimation, 
medication adherence and Health Related Quality of Life (HRQoL) over the last 3 months. 
You will be given the questionnaires at the end of 6 months follow up to assess your 
perception of the perceived usefulness of the app and rate your satisfaction with the app if you 
are allocated to Group and using the CareAide® app. 
 
8.   When will I receive the trial product and how should it be kept? 
 
You will be asked to download and use the CareAide® app throughout the 6 months period 
of the study if you are assigned to Group 1. The study staff will instruct you on how to 
download and manage the app. In contrast, you will not be asked to download any digital 
applications but only receive the usual care by the hospitals if you are assigned to Group 2. 
 
9.   What are my responsibilities when taking part in this study? 
 
It is important that you answer all of the questions asked by the study staff honestly and 
completely which will take about 30 minutes of your time. Study team will also access your 
medical records for the following information: 
1. Patient’s Data 

Page 5 of 7
 
 
Version 5.0, dated 15 July 2022     
 
2. Direct Healthcare Cost Estimation (Outpatient follow up visits, Inpatient admission, Intensive 
care unit admission, Emergency admission, others community care services, laboratory 
investigation test, medications history) 
3. Pharmacy Refill Record 
 
You will be given a questionnaire form to be answered. This form contains 6 sections which will 
enquire about your demographic data, disease state, direct and indirect cost estimation, Morisky 
Medication Adherence Scale (8-Item), perceptions of the use of CareAide® App and Health 
Related Quality of Life (HRQoL). 
10. What kind of treatment will I receive after my participation in the trial? 
 
No study product will be given to you at the end of your participation in the study. Whether 
you complete the study or withdraw early, your usual care and treatment for chronic 
disease still received from hospital.  
 
11. What are the potential risks and side effects of being in this study? 
 
Participation to this study will not affect your treatment, and the risk is minimal. You are free 
to decline to answer any of the questions that you feel uncomfortable with. 
 
12. What are the benefits of being in this study? 
 
There may or may not be any benefits to you. You will not be reimbursed or paid for 
participation in this study. Information obtained from this study will help to evaluate and 
determine the effect and clinical outcome of CareAide® intervention on adherence to 
medications in patients with chronic diseases. This study also helps to estimate the direct and 
indirect cost of managing chronic diseases in Malaysia and how this app able to reduce the 
economic burden from payer and societal perspective. Furthermore, it is able to understand the 
health-related quality of life of patients in management of chronic diseases. 
 
13. What if I am injured during this study? 
 
If you are injured as a result of being in this study, you should contact your study 
investigator. In the event of a bodily injury or illness directly resulting from the study 
product or a medical procedure required for this study, the sponsor will pay for reasonable 
and necessary treatment. The sponsor is not responsible for medical expenses due to pre-
existing medical conditions, any underlying diseases,  any ongoing treatment  process,  
your negligence or willful misconduct, the negligence or willful misconduct of your study 
doctor or the study site or any third parties. You do not lose any of your legal rights to seek 
compensation by signing this form.  
 
14. What are my alternatives if I do not participate in this study? 
 
You do not have to participate in this study to get treatment for your disease or condition. 
This study will not affect your treatment options. 
 
15. Who is funding the research? 
 

Page 6 of 7
 
 
Version 5.0, dated 15 July 2022     
 
This study is sponsored by CaringUp Malaysia Sdn Bhd who will pay for study product 
(mobile health application) and data collection procedure. All other drugs and procedures 
that are not required by the study but are part of your routine medical care will have to be 
paid by you or your insurance.  
 
16. Can the research or my participation be terminated early? 
 
The study doctor or the sponsor may due to concerns for your safety, stop the study or your 
participation at any time. If the study is stopped early for any reason you will be informed 
and arrangements made for your future care. You may be asked to attend a final follow-up 
visit.  
17. Will my medical information be kept private? 
 
All your information obtained in this study will be kept and handled in a confidential manner, 
in accordance with applicable laws and/or regulations. Permission from the Director General 
of Health, Malaysia will be obtained prior to publication. When publishing or presenting the 
study results, your identity will not be revealed without your expressed consent. Primarily only 
investigators in the study will have access to the research data. However, Individuals involved 
in this sub-study, qualified monitors and auditors, the sponsor or its affiliates and 
governmental or regulatory authorities may inspect and copy research, where appropriate and 
necessary. Any unused sample that has not been processed in research will be destroyed. Any 
information that was extracted from medical records will not be destroyed until 7 years after 
the last publication of findings using your information. Moreover, the staffs will inform you in 
a timely manner about any new findings or changes about the study product which may affect 
your health or willingness to continue in this study. Where necessary, you may be asked to 
reconsent to participate. 
 
18. Who should I call if I have questions? 
 
If you have any questions about the study or if you think you have a study related injury and 
you want information about treatment, please contact study investigator at site: 
Hospital Pulau Pinang: 012-2239848 (Dr. Jaya Muneswarao A/L Ramadoo@Devudu) 
Hospital Putrajaya: 012-6653893 (Dr. Navin Kumar A/L Loganadan) 
University Malaya Medical Centre:  010-3664181 (Associate Professor Dr. Baharudin 
Ibrahim) 
 
If you have any questions about your rights as a participant in this study, please contact: The 
Secretary, Medical Research & Ethics Committee, Ministry of Health Malaysia, at 
telephone 
number 
03-3362 
8407 
/ 
8205 
/ 
8888

Page 7 of 7
 
 
Version 5.0, dated 15 July 2022     
 
INFORMED CONSENT FORM 
 
Title of Study: Perception, Adherence, Clinical, Economical and Health-Related Quality of 
Life Outcomes of CareAide® App usage in Chronic Diseases 
 
By signing below I confirm the following: 
   I have been given oral and written information for the above study and have read 
and understood the information given. 
   I have had sufficient time to consider  participation  in  the  study  and  have  had  
the opportunity to ask questions and all my questions have been answered 
satisfactorily. 
   I understand that my participation is voluntary and I can at anytime free withdraw 
from the study without giving a reason and this will in no way affect my future 
treatment. I am not taking part in any other research study at this time. I understand 
the risks and benefits, and  I freely give  my informed  consent  to  participate  
under  the  conditions  stated.  I understand that I must follow the study doctor’s 
(investigator’s) instructions related to my participation in the study. 
   I understand that study staff, qualified monitors and auditors, the sponsor or its 
affiliates, and governmental or regulatory authorities, have direct access to my 
medical record in order to  make sure that the  study is  conducted  correctly and  
the data  are  recorded correctly. All personal details will be treated as STRICTLY 
CONFIDENTIAL 
   I will receive a copy of this subject information/informed consent form signed and 
dated to bring home. 
   I agree/disagree* for my family doctor to be informed of my participation in this 
study. (*delete which is not applicable) 
 
Subject: 
 
Signature:
I/C number:
Name: 
Date: 
 
Investigator conducting informed consent: 
 
Signature:
I/C number:
Name: 
Date: 
 
Impartial witness:  (Required if subject is illiterate and contents of patient information 
sheet is orally communicated to subject) 
 
 
Signature:
I/C number:
Name: 
Date: 

  JAWATANKUASA ETIKA & PENYELIDIKAN PERUBATAN 
 
 (MEDICAL RESEARCH & ETHICS COMMITTEE)  
 
 KEMENTERIAN KESIHATAN MALAYSIA 
 MINISTRY OF HEALTH MALAYSIA 
 Kompleks Institut Kesihatan Negara (NIH) 
        
 No.1, Jalan Setia Murni U13/52,                      
 Seksyen U13 Bandar Setia Alam, 
 40170 Shah Alam, Selangor. 
 
 
Tel: 03-3362 8398/8399/8404/8408                     
 
 
 

Ref : 22-01108-COI 
 
 
 Date : 29-August-2023 
 
_________________________________________________________________________ 
 

Ref : 22-01108-COI 
 
 
 Date : 29-August-2023 
 
_________________________________________________________________________ 
 
1
2
3
4
5
6
7
8
9
10
11
Health Research 
12
Emergency 

Ref : 22-01108-COI 
 
 
 Date : 29-August-2023 
 
_________________________________________________________________________ 
 
13
Developmental 
Paeds 
14
Pathology 
15
Pathology 
Haematology 
16
Legal 
17
Dr Mohammad Zabri 
Johari
Public Health 
Psychology, social 
research 
methodology, 
mixed methods 
research 
 
18
Ms Chun Geok Ying 
Pharmacy 
19
Dr Lean Qi Ying 
Pharmacy, 
Business 
Administration 
20
21
22

Ref : 22-01108-COI 
 
 
 Date : 29-August-2023 
 
_________________________________________________________________________ 
 
23
 
Malisanurhidayu 
Yaacob 
24
25
26
27
28
29
The Medical Research & Ethics Committee, Ministry of Health Malaysia operates in accordance to the 
International Council for Harmonization of Technical Requirement for Pharmaceutical for Human Use 
(ICH). 
 

07/11/2022, 3:45 PM
Approval Letter (Amendment)
Page 1 of 1
https://my.ummc.edu.my/iresearch/ApprovalLetterAmendment.asp?k…DDYetgsikhDKGTE9GLetgsikh&idamendment=21120&kategoriborang=v2
MEDICAL RESEARCH ETHICS COMMITTEE
(Formerly known as Medical Ethics Committee) 
UNIVERSITY OF MALAYA MEDICAL CENTRE
ADDRESS : LEMBAH PANTAI, 59100 KUALA LUMPUR, MALAYSIA
TELEPHONE : 03-79493209/2251 FAXIMILE : 03-79492030
NAME OF ETHICS COMMITTEE/IRB
Medical Research Ethics Committee, University Malaya Medical Centre
MREC ID NO: 2022311-11069
ADDRESS : LEMBAH PANTAI, 59100 KUALA LUMPUR, MALAYSIA
PROTOCOL NO(if applicable) :   1
TITLE: 
Perception, Adherence, Clinical, Economical And Health-Related Quality Of Life Outcomes Of Careaide® App Usage In
Chronic Diseases
PRINCIPAL INVESTIGATOR :    HASNIZA BINTI ZAMAN HURI
SPONSOR
Caring Up Malaysia Sdn Bhd
The following item [
] have been received and reviewed in connection with the above study to conducted by the above investigator.
[
] Application for Amendment/Notiﬁcation to Research Project (form) 
Ver.No :  -
Ver.Date :  15-09-2022
[     ] Annual Study Report/Study Closure Report
Ver.No :  -
Ver.Date :  -
[     ] Serious Adverse Event Report
Ver.No :  -
Ver.Date :  -
[
] Other documents
Ver.No :  -
Ver.Date :  27-09-2022
and the decision is [
]
[
 ] Approved (Expedited)
[     ] Approved (Full Board)
[     ] Rejected (reasons speciﬁed below or in accompanying letter)
[     ] Noted
Comments:
-
The investigators are required to:
1)
follow instructions, guidelines and requirements of the Medical Research Ethics Committee.
2)
report any protocol deviations/violations and any serious unexpected adverse events related to the conduct of the study or study product to Medical Research
Ethics Committee.
3)
provide annual and closure report to the Medical Research Ethics Committee.
4)
comply with International Conference on Harmonization – Guidelines for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki.
5)
obtain a permission from the Director of UMMC to start research that involves recruitment of UMMC patient.
6)
ensure that if the research is sponsored, the usage of consumable items and laboratory tests from UMMC services are not charged in the patient’s hospital bills
but are borne by research grant.
7)
note that he/she can appeal to the Chairman of Medical Research Ethics Committee for studies that are rejected.
8)
note that Medical Research Ethics Committee may audit the approved study.
9)
ensure that the study does not take precedence over the safety of subjects.
Date of expedited approval : 11-10-2022
Date of notiﬁcation : -
This is a computer generated letter. No signature required.