Developing A Gout Action Plan in Primary Care Setting in Singapore
Phase: NA
Conditions: Gout; Hyperuricemia, Gout Flare, Gout Chronic
Sponsor: SingHealth Polyclinics

 
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RESEACH STUDY PROTOCOL 
 
 
PROTOCOL TITLE:  
DEVELOPING A GOUT ACTION PLAN IN PRIMARY CARE SETTING IN SINGAPORE 
 
 
 
 
 
 
 
 
 
 
 
PROTOCOL NUMBER: 
 
 
 
 
 
 
 
 
 
 
VERSION NUMBER: 2 
 
 
 
 
 
 
 
 
 
 
VERSION DATE: 24 MAR 2025 
 
 
 
 
 
 
 
 
 
 
PRINCIPAL INVESTIGATOR:  
Liew Siew Lee, Family Physician, SingHealth Polyclinic  
 
 
 
 
 
 
 
 

 
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PROTOCOL SIGNATURE PAGE 
 
 
PROTOCOL TITLE:  
DEVELOPING A GOUT ACTION PLAN IN PRIMARY CARE SETTING IN SINGAPORE 
 
 
 
 
 
 
 
 
PROTOCOL NUMBER: 
 
 
 
 
 
 
 
 
 
 
VERSION NUMBER: 2 
 
 
 
 
 
 
 
 
 
 
VERSION DATE: 24 MAR 2025 
 
 
 
 
 
 
 
 
 
 
 
 
Declaration of Investigator 
 
I confirm that I have read the above-mentioned protocol and its attachments. I agree to conduct the 
described study in compliance with all stipulations of the protocol, regulations and ICH E6 Guideline for 
Good Clinical Practice (GCP).  
 
 
LIEW SIEW LEE 
___________________________________________________________________________________ 
Name of Principal Investigator: 
 
 
___________________________________________________________________________________ 
Signature of Principal Investigator: 
 
 
___________________________________________________________________________________ 
Date: 
 
 
PASIR RIS POLYCLINIC 
___________________________________________________________________________________ 
Name of Study Site:  
Note: 
- This page should be signed with wet-ink signature or digital signature. Do not paste digital image of a wet-
ink signature.  
 
- Signed copies of this signature page should be stored in the study file and in the respective study site’s 
investigator file. 

 
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Table of Contents 
1. 
BACKGROUND AND RATIONALE................................................................................................. 4 
2. 
HYPOTHESIS AND OBJECTIVES.................................................................................................. 5 
3. 
EXPECTED RISKS AND BENEFITS ............................................................................................... 5 
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.......................................................................................................... 10 
6.1. 
DEFINITIONS .................................................................................................................................................. 10 
6.2. 
COLLECTING, RECORDING AND REPORTING OF SERIOUS ADVERSE EVENTS (SAES) TO CIRB ................................. 11 
6.3. 
SAFETY MONITORING PLAN .............................................................................................................................. 11 
6.4. 
COMPLAINT HANDLING .................................................................................................................................... 11 
6.5. 
COLLECTING, RECORDING AND REPORTING OF REPORTABLE ADVERSE EVENTS RELATING TO MEDICAL DEVICE TO THE 
HEALTH SCIENCES AUTHORITY (HSA) ........................................................................ ERROR! BOOKMARK NOT DEFINED. 
7. 
DATA ANALYSIS........................................................................................................................ 11 
7.1. 
DATA QUALITY ASSURANCE.............................................................................................................................. 11 
7.2. 
DATA ENTRY AND STORAGE ............................................................................................................................. 11 
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 ........................................................................................... 13 
12. PUBLICATIONS ......................................................................................................................... 14 
13. RETENTION OF STUDY DOCUMENTS ........................................................................................ 14 
14. FUNDING AND INSURANCE ...................................................................................................... 14 
LIST OF ATTACHMENTS .................................................................................................................... 15 
APPENDIX 1 – REFERENCES ........................................................................................................................................... 15 

 
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1. 
BACKGROUND AND RATIONALE 
Gout is a common inflammatory arthritis often seen in primary care. Worldwide prevalence ranges from under 
1% to 6.8%.1 The prevalence of gout has risen over the past three decades, accompanied by an increase in 
morbidity. 2 In Singapore, prevalence of gout is 4.1% amongst the Singapore Chinese population.3 Gout is 
associated with significant morbidity and mortality due to coronary heart disease and kidney disease3, and has 
substantial burden and impact in quality of life, with higher healthcare utilization and high unemployment rate 
observed in middle aged men with gout. 4 
 
Patients with poorly controlled gout suffer from frequent gout flares, with acute onset of joint pain and swelling, 
affecting health-related quality of life.5 A meta-synthesis showed that gout flares impact on patients’ lives, 
including physical, psychological, social and family life. 6  In a primary care institution in Singapore, 28.2% of 
patients with gout had poorly controlled disease.7  In a rheumatology clinic in Singapore, 33% of patients with 
gout visited emergency department at least once for gout flare, while 19.5% had at least one hospitalization for 
gout.4  
 
Acute gout flares can be mitigated by pharmacotherapy. Timely administration of acute medications is important 
to alleviate the pain leading to early resolution of symptoms. American College of Rheumatology (ACR) 
Guideline 20208 and European League Against Rheumatism (EULAR) 2016 9 recommend colchicine, non-
steroidal anti-inflammatory drugs (NSAIDs) or corticosteroid for treatment of acute gout flare. In primary care 
clinics in Singapore, colchicine was often prescribed for an acute gout flare.7 However, colchicine has 
gastrointestinal side effects such as vomiting and diarrhoea10, and some patients are not aware of its side effects 
and exceeded prescribed dose. 10 NSAIDs might improve the pain if given within 24 hours. 11 However, NSAIDs 
are associated with gastrointestinal, renal and cardiovascular adverse effects, thus they may not be the suitable 
pharmacotherapy for those with renal, gastrointestinal or cardiovascular comorbidities. 12 NSAIDs also cause 
hypersensitivity reactions with estimated prevalence of hypersensitivity to NSAIDs to be 0.5 to 1.9% of the 
general population. 13 For patients who are unable to tolerate NSAIDs or colchicine, or have chronic renal 
disease, systemic corticosteroid such as oral prednisolone might be a good alternative as it provides similar 
improvement in pain relief. 11 14 
 
Aside to pharmacotherapy, dietary control is important to prevent gout flares. ACG guideline 2020 8 includes 
conditional recommendations to reduce alcohol intake, adopt a low-purine diet, and prioritize weight loss. A 
meta-analysis showed that red meat, seafood, alcohol, fructose or sweetened soft drinks increase risk of gout and 
hyperuricaemia, while consumption of soy foods, dairy products and vegetables reduce risk of gout. 15 However, 
there is lack of awareness in dietary triggers especially in those with active gout. 16 A recent study in Australia 
found that patients with gout lack knowledge about the risk and protective factors of gout. 17 Patients resisted 
dietary changes due to the restrictive nature of the diet, lack of resources for information, and perceived it as 
unrealistic and unmanageable. 18  
 
Gout control remains suboptimal despite established guideline. Urate lowering therapy (ULT) remains the key in 
gout management and its initiation is recommended for patients with recurrent gout flares with treat-to-target 
strategy. 8 However, in primary care institution in Singapore, it was found that half of the patients with poorly 
controlled gout were not prescribed urate lowering therapy.7 In patients with gout, the overall adherence rate to 
ULT is as low as 47%.19 Patients with gout demonstrate poor adherence to urate lowering therapy as they have 
limited knowledge of gout and its treatment, their attitude and perception towards taking long term medications. 
Some patients avoid ULT due to fear of side effects or flares during initiation, leading to nonadherence. 20 
Self-management is important in the management of chronic diseases. 21 Interventions of self-management have 
been shown to improve self-efficacy, health behavior, subsequently improving health status and quality of life 

 
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and reducing healthcare utilization. 22   Self-efficacy refers to an individual’s belief in their capacity to execute 
behaviours necessary to produce specific performance attainments, and it is correlated with self-care. Raising 
self-efficacy is important to change behavior in self-care. 23  
 
An action plan is a patient-held guide to support self-management with educational value. In chronic diseases 
such as asthma, the action plan provides information on how to manage the disease on a day-to-day basis and has 
proven to encourage self-management, improve health outcomes and quality of life, and reduce unscheduled 
visits to physicians. 24 25 Likewise, gout is a chronic condition with acute gout flares intermittently, that will 
benefit from self-management. In a study in Malaysia, patients were capable in self-management of gout but to 
variable extent, some practice diet control, some use painkillers during acute gout attacks, some use traditional 
medicine rather than taking allopurinol, some use exercise or stress-reducing activities, and the type of self-
management might be influenced by cultural and social factors. 26   
 
To our knowledge, there is no well recognised gout action plan. A gout action plan has not been subjected to 
prior development in terms of content, design and acceptability. We hope that by developing a gout action plan, 
it will give information to patients about the disease to raise knowledge on gout, to reduce frequency of 
exacerbation via dietary control and lifestyle measures, to provide information on pain relief medications and the 
risks of taking painkiller, and urate lowering therapy for those with recurrent gout flares, and safety-netting 
advice on when to seek help. The study thus aims to develop a prototype of gout action plan by incorporating 
patients’ and primary care physicians’ perspectives, hoping to improve quality of life and healthcare utilization 
among patients with gout.  
 
 
 
2. 
HYPOTHESIS AND OBJECTIVES 
Aims 
Primary aims  
1. Explore primary care professionals’ (PCPs) perspectives and challenges in management of gout and 
assess whether novel gout action plan addresses the challenges. 
2. Explore patients’ understanding of gout, experiences and challenges of managing gout and medications, 
and assess whether they are willing to use novel gout action plan. 
 
Secondary aims: 
1. Assess the feasibility and acceptability of gout action plan in a pilot open label randomized 
controlled trial (RCT). 
2. Assess preliminary effectiveness of gout action plan in reducing frequency of gout exacerbation, 
improving gout control and quality of life.  
Hypothesis  
1. A prototype gout action plan can be developed to aid in management of gout.  
2. In primary care professionals who manage patients with gout, there are variable views and perspectives 
towards gout action plan.  
3. Patients have variable understanding and challenges of managing gout and different opinions in using gout 
action plan.  
4. Gout action plan is an effective tool in reducing gout flares, improving gout control and quality of life.  
 
3. 
EXPECTED RISKS AND BENEFITS 
Expected risks 
1. Data privacy 

 
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As this study involved audio-recording of the interview for transcribing of information and collection of basic 
demographic information using data collection form, there is a potential risk of data breach affecting 
participant’s confidentiality. 
 
2. Emotional risk  
Emotional risk from an adverse emotional response to a sensitive topic breached during the interview process. 
The interviewer will explain to participants that they may refuse to answer any of the questions if they feel 
uncomfortable to answer the questions, may take a break at any time during the interview or choose to 
discontinue the study at any time.  
 
3. Discomfort during blood taking  
Patient might experience pain and minimal bleeding during the blood taking.  
 
Benefits 
Patients might benefit from the gout action plan and learn to self-manage gout in their daily life.   
 
4. 
STUDY POPULATION 
 
4.1. 
List the number and nature of subjects to be enrolled.  
The study will be conducted at Pasir Ris Polyclinic, one of the Singhealth Polyclinics. For first part of the study, 
due to its qualitative nature, we aim to recruit approximately 10-15 patients with gout and 10-15 healthcare 
professionals until data saturation is reached. For second part of the study on open label randomized controlled 
trial, we aim to recruit 72 participants.  
 
Adult patients aged 21 and above with the clinical diagnosis of gout who are being followed up at Pasir Ris 
Polyclinic will be randomly recruited into the study. Healthcare professionals who involve in the care of gout 
will also be recruited into the first part of the study. Children or minorities will be excluded from the study.  
 
 
4.2. 
Criteria for Recruitment and Recruitment Process 
Recruitment of patients: 
Eligible patients will be identified through either screening from electronic medical records (EMR) using 
SingHealth Outpatient Appointment System (OAS) and Sunrise Clinical Manager (SCM) or referred by 
attending physicians to the study team. National Electronic Health Record (NEHR) will not be assessed for 
research purpose. The study team will obtain prior knowledge of a potential participant’s medical appointment 
from the SingHealth OAS and SCM so that the physician can be reminded about the arrival of potential 
participant.  
If potential patient participants show interest in the study, they will be directed to the study team. The study team 
will verify the eligibility, and after an initial explanation of the study, participant will be provided a copy of 
participant information sheet and consent forms to bring home and to think about their participation before the 
signing of the consent form on the day of interview or focus group discussion. Adequate time will be given to 
read the documents and questions, emphasizing the voluntary nature of participation and its independence from 
routine clinical care. Written informed consent will be obtained in-person at the study site, in a quiet and 
separate room or space, ensuring privacy. The study team member taking the consent will not be the treating 
physician of the patient. The participant will sign hard copies of the consent form, and the copies will be kept by 
participant and study team.  
Recruitment of healthcare professionals: 
Primary care healthcare professionals in Pasir Ris Polyclinic, and other clinics will be invited to participate in the 
in-depth interview. The study team will conduct a briefing about the study in clinic meeting and invite potential 
participants to take part. Potential participants who are not present at the clinic meeting will also be contacted by 

 
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study team in-person. The study team will ensure that there is no dependent or hierarchical relationship between 
the team and the potential HCP participants. 
 
 
4.3. 
Inclusion Criteria 
Inclusion Criteria  
Inclusion Criteria (for patients):  
- 
Adults who are 21 years old and above 
- 
Clinical diagnosis of gout as per ACE-EULAR 2015 criteria  
- 
Had at least an episode of gout exacerbation within the last 1 year 
- 
Able to speak and read English  
- 
Singapore citizens or permanent residents  
- 
Able to provide informed consent  
Inclusion Criteria (for healthcare professionals): 
- 
Currently still in clinical practice 
- 
Manage gout in their clinical practice 
 
4.4. 
Exclusion Criteria 
Exclusion Criteria 
Exclusion Criteria (for patients) 
• 
Mental disorders 
• 
Cognitive impairment  
• 
Hearing and/ or speech impairments 
• 
Pregnant  
• 
Known terminal illness 
• 
Unable to provide informed consent  
Exclusion Criteria (for healthcare professionals): 
• 
Not involved in gout management in the practice 
• 
No longer in clinical practice 
 
5. 
STUDY DESIGN AND PROCEDURES/METHODOLOGY 
The study will employ a sequential mixed-method design, which comprises of:  
1. Qualitative research to develop and refine prototype of gout action plan by gathering perspectives from 
both patients and healthcare providers.  
2. An open label pilot RCT to assess feasibility and acceptability of gout action plan, and preliminary 
outcome on effectiveness of gout action plan in reducing gout flares, improvement in uric acid and 
quality of life.  
 
Part 1- Qualitative phase: Creation of a prototype gout action plan  
Using written asthma action plan as a guide, a prototype gout action plan will be drafted based on the latest 
evidence.  The gout action plan outlines how to manage gout, identifying triggers, recognizing when symptoms 
worsen, appropriate medication usage, and when to seek medical attention. It is categorized into zone system, 
which consists of green zone (well controlled), yellow zone (mild symptoms), red zone (severe symptoms).  
 
Qualitative phase: In-depth interviews and focus group discussions will be conducted with primary care 
healthcare professionals (physicians, nurse, pharmacist, and dietician) who are involved in patient care, as well 
as patients with gout. The interviews and discussions will explore on their understanding of gout and its 
management, experiences of managing gout, perceptions of self-management, and opinions on the prototype of 
gout action plan. This will provide insights into iterative refinement of the gout action plan. Prototype will thus 
be refined down the multiple interactions of interview or discussions till data saturation is reached. For 

 
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healthcare professionals, maximum variation sampling will be employed based on their age and years of clinical 
experience. For patient, maximum variation sampling will be employed based on their age, ethnicity and 
socioeconomic status.  The session will be audio-recorded.  
 
Part 1A 
In-depth interviews with patients and focus group discussions with patients will be conducted with patients with 
gout. The interviews and discussions will explore their understanding of disease and treatment, experience of 
patient-physician consult, perceptions of self-management, and opinions on prototype gout action plan.  
Interview guide is developed based on theoretical domain framework.   
 
Basic patient demographics and data on their gout duration, comorbidities and medications will be collected 
using the attached data collection form.  
 
Research questions to be explored with patients with gout:  
1. To understand patients' knowledge, skills, and behaviours related to gout management. 
2. To identify factors that influence adherence to treatment and lifestyle modifications. 
3. To explore emotional, social, and environmental factors impacting gout management. 
4. What is their experience of physician consultation for gout management?  
5. What are their barriers and facilitators to gout self-management?  
6. What is their opinion on the prototype gout action plan? Is it easily understandable? Is it informative enough? 
What are the barriers of using gout action plan? When will they use the gout action plan?   
 
Topic guide is as attached in attachment section.  
Subjects: primary care patients with gout exacerbation within 1 year   
Sampling method: Convenience sampling. Maximum variation sampling will be employed based on their age, 
ethnicity and socioeconomic status.   
Outcome: identification of themes, needs and information that will help in the creation of prototype gout action 
plan.  
Expected participant participation time: 60 minutes  
 
Part 1B  
In-depth interviews with patients and focus group discussions with primary care providers, nurses, pharmacist, 
dietician. The interviews and discussion will explore their understanding of gout and experiences of managing 
gout, their views on self-management of gout, and views on gout action plan.  
 
Research questions to be explored: 
1. What is their understanding of gout and its management?  
2. What are their experiences of treating gout patients? Do they know about treatment goals and urate-
lowering therapy?  
3. What is their perception about self-management?  
4. What are their opinions on the prototype of gout action plan? What are the barriers and enablers of 
action plan? Do they think need any training or resources to support use of gout action plan?  
 
Topic guide is as attached in attachment section.  
 
Subjects: primary care healthcare professionals (physicians, nurses, pharmacist, dietician) who manage patients 
with gout   
Sampling method: Convenience sampling and purposive sampling. Maximum variation sampling will be 
employed based on their age and years of clinical experience.  

 
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Outcome: identification of themes, needs and information that will help in the creation of prototype gout action 
plan.  
 
Expected participant participation time: 60 minutes  
 
The interviews and discussions will provide insights into iterative refinement of the gout action plan. Prototype 
will thus be refined down the multiple interactions of interview or discussions till data saturation is reached.  
 
The session will be audio-recorded using audio recorder. After each interview, the interviewer will transfer the 
audio-recording to a password-protected corporate laptop and erase it from the audio-recorder. The audio 
recording will be transcribed verbatim using the research department’s transcribing software or transcription 
platforms (such as transcribe.gov.sg or Note Buddy) or engagement of transcriptionist. All participant identifiers 
will be removed from the transcript to ensure confidentiality. All transcripts will be checked by interviewer for 
accuracy. De-identified data will be used for analysis. Analysis of data will be performed using a thematic 
approach. All the audio files and transcriptions of the recordings will have password encryption and stored in the 
same password-protected corporate laptop in workplace. Only study members will have access to the password. 
The electronic data will be kept for 6 years post completion of the study.   
 
Participants who consented will be informed on the date and time of the in-depth interviews or focus group 
discussions. Participants who come for the in-depth interviews and focus group discussions will sign the written 
consent form before participation. After written consent is obtained, participants will be asked to fill up the data 
collection form which contains their basic demographics information and health status information. Participants 
will be de-identified. Participants will be briefed on the purpose of the study, their roles and rights. They will be 
informed that the interview or discussion will be audio recorded. Field notes will be taken to record non-verbal 
cues. Interviewer will use topic guide for the interview or discussion.  
 
At the end of the interview or discussion, participant will be given token of appreciation.  
 
Part 2: Open label pilot RCT 
Quantitative phase – two-arm pilot randomized controlled trial (RCT) 
- 
Arm 1: usual care + gout action plan for 24 weeks 
- 
Arm 2: usual care  
Randomization 
Patients will be randomly assigned in a 1:1 ratio to either control or intervention arm in an open-label fashion, 
using computer-generated random numbers for randomization of subjects. The randomized sequence will be 
written and kept in an opaque sealed envelope and labelled with a serial number. When patients consent to 
participate in the study, the team will open the opaque sealed envelope and allocated them to the study arms 
accordingly. It is impossible to blind the patients and research team members to the patient allocation in view of 
the nature of the intervention.   
 
Upon recruitment and after patient consented, basic patient demographics and data on their gout duration, 
comorbidities and medications will be collected using the attached data collection form. They will be asked to 
recall and self-report frequency of gout flares for the past 6 months prior to recruitment. They will also need to 
fill up an EQ-5D-5L questionnaire on health-related quality of life which takes approximately 5 minutes to fill it 
up. They will also be sent for laboratory for blood test to test for uric acid level. Blood will be taken from arm 
using a syringe and needle, during recruitment and at a 6-month visit, for participants in both intervention and 
control groups. About 3ml of blood will be taken each time. In total, there will be about 6ml taken over a period 
of 6 months. The Institutional Review Board waiver under Section 37(3) of the Human Biomedical Research Act 

 
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2015 (“HBRA”) for the removal of human biological materials is not required. This is because we will collect 
samples from adults with mental capacity to personally give consent for this research study. 
 
For those patients who are assigned into the intervention arm, they will be sent to care manager to explain on the 
gout action plan and its details.  
 
Study participants will be followed up for 24 weeks after enrolment. At 24 weeks, they will be asked on their 
frequency on gout flares after the recruitment and to fill up the EQ-5D-5L questionnaire together. They will also 
be sent to laboratory for blood test on uric acid level. The follow up survey will be conducted by phone call or 
questionnaire at a convenient time for them or during the clinic visit.  
 
Participant withdrawal 
Participants may choose to withdraw from the study at any time without providing an explanation and this will 
not result in any punitive consequences.  
 
Potential difficulties and limitations and alternative approaches to achieve the aim 
1) Recruitment 
- In the event of difficulty recruiting adequate number of patients, proposed measures will include  
1. Email reminders and message reminders to staffs in clinic to look for patients with gout 
2. Obtaining prior knowledge of a potential participant’s medical appointment so that the physician of 
that day can be reminded about the potential participant’s arrival.  
- In the event of difficulty recruiting adequate number of physicians 
1. Making use of primary care message groups and networks to reach out to potential HCPs participants 
2. Speaking to family medicine department heads or private general practice group heads to help 
disseminate the need for participants 
 
2) Difficulties during interviews  
- As patient participants are recruited on the day of their visit to the clinic, not all will be free for face-to-face 
interview on the same day. Similarly, not all HCPs will be free for face-to-face interview on the same day as 
recruitment. Some participants may prefer to have interview done on a different day.  
Alternative approach: the research team may offer the option of a face-to-face interview to the participants 
depending on his or her availability.  
 
3) Lost to follow up  
- In open label RCT for 24 weeks, patients might not return for follow up during the subsequent visit. Proposed 
measures will include message reminders to patients on their follow up visit.  
 
 
 
 
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 

 
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• 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 
The reporting requirements will be in accordance to the reporting requirements published on CIRB website at the 
time when the event took place. 
 
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.   
 
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 
After each interview, the interviewer will transfer the audio-recording to a password-protected corporate laptop 
and erase it from the audio-recorder. The soft copy research data will be stored in institution issued PC and hard 
copy will be kept under lock and key for 6 years before they are deleted. They will always be password protected, 
and data will not be transferred using thumb drive of other unsecured means.  
 
6.4. 
Complaint Handling  
All complaints will be reviewed by the study team and escalate to clinic director/ supervisor of Research 
department.  
 
 
7. 
DATA ANALYSIS 
 
7.1. 
Data Quality Assurance 
Study data will be checked and validated by data management executive in Department of Research to ensure that 
the data obtained from this research is accurate, complete and reliable.  
 
7.2. 
Data Entry and Storage 
Information from the hard copy (data collection forms, questionnaires and consent forms) will be transcribed to a 
Microsoft Excel document with password protection. The hard copy documents will be kept in a research folder, 
stored under lock and key in the polyclinic research room at Pasir Ris polyclinic. The folder will not be taken out 
of the clinic. 
 
After each interview, the interviewer will transfer the audio-recording to a password-protected corporate laptop 
and erase it from the audio-recorder. The audio recording will be transcribed verbatim using the research 
department’s transcribing software or transcription platforms (such as transcribe.gov.sg or Note Buddy) or 
engagement of transcriptionist. All participant identifiers will be removed from the transcript to ensure 
confidentiality. All transcripts will be checked by interviewer for accuracy. De-identified data will be used for 
analysis. All the audio files and transcriptions of the recordings will have password encryption and stored in the 
same password-protected corporate laptop in workplace. Only study members will have access to the password. 

 
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Information from the data collection form will be transcribed to excel document (with password encryption) in a 
password-protected corporate laptop in workplace. There will be no USB or removal device used for data 
storage. The physical consent forms and the electronic data will be kept for 6 years post completion of study. 
The physical consent forms will be stored in a secure physical archive and the electronic data in an electronic 
archive. Only the principal investigator and co-investigators will have access to the archives.  
 
8. 
SAMPLE SIZE AND STATISTICAL METHODS 
 
8.1. 
Determination of Sample Size  
For qualitative part, sample size calculation is not applicable. Prototype of gout action plan will be refined until 
saturation is reached. Hennink 27 showed that 9-17 interviews or 4-8 focus group discussion reached saturation 
for studies with relatively homogenous study populations and narrowly defined objectives. Therefore, for this 
study, we aim to recruit 10-15 participants from each group.  
For pilot RCT, based on sample size rule of thumb for pilot study, Browne 28 cites to ‘use at least 30 subjects or 
greater to estimate a parameter’, whereas Whitehead 29 suggests that pilot trial sample size to be 25 per treatment 
arm for small effect size of 0.2 for a main trial designed with 90% power and two-sided 5% significance. With a 
6-months follow up visit, assuming a potential 30% attrition rate, the final sample size after buffering for drop 
out will be 36 per arm (n=72). The sampling method will be convenience sampling.  
 
8.2. 
Statistical and Analytical Plans 
Qualitative and quantitative data will be analyzed separately.  
 
Qualitative data:  
Audio recordings of the interviews will be transcribed using the research department’s transcribing software or 
transcription platforms (such as transcribe.gov.sg or Note Buddy) or engagement of transcriptionist. All personal 
identifiable information will be removed. The transcripts will be sent to the study team through secured email 
and reviewed for accuracy and completeness prior to data analysis. In the event of significant errors being found, 
they will be sent back to transcribers or transcribing platforms or transcribing software for amendments. The 
transcripts will be analyzed to understand the views of healthcare providers and patients on gout action plan.  
Thematic analysis will be performed by at least 2 study team members after familiarizing with the data. Using 
grounded theory approach, codes and the respective data extracts will be categorized into broader themes and 
subthemes to form a coding framework which will be refined iteratively as data from the first 2-3 participants are 
analyzed. Identification of themes, needs and information will help in creation of prototype of gout action plan. 
In the event of discrepancies in the coding framework among the study team members, this will be resolved 
through consensus and if necessary, by engaging another study team member to analyze the data to reach an 
eventual coding framework.  
Computer-assisted qualitative data analysis software Nvivo will be used to help with management and analysis 
of data.  
 
Quantitative data: 
Descriptive statistics will be generated for the baseline characteristics of the study participants, and frequencies 
and percentages will be presented for categorical variables while mean and standard deviation will be presented 
for continuous variables.  
To assess effectiveness of gout action plan, the continuous outcome between the two groups will be compared 
using independent t-test. When outcomes are categorized into binary outcomes, Chi-square test will be 
performed. The baseline outcomes will also be assessed with demographic using either Chi-square test or 
Fisher’s Exact test for categorical variables, and independent t-test or ANOVA for continuous variables to 
ensure both groups are comparable. Multivariate linear regression model will be performed with each outcome 
below and the following covariates to determine effectiveness of the intervention: intervention (gout action 
plan), baseline outcome and any demographic factors with a p-value of less than 0.1 in the bivariate analysis. All 

 
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analyses will be performed using SPSS software version 29.0. A p-value of less than 0.05 is considered to be 
statistically significant.  
 
9. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
The study team 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 study team will perform data and safety monitoring to ensure adherence with the protocol. The study team 
will be responsible for the evaluation of data quality and monthly review of the collected data.  
 
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 
After an initial verbal explanation, potential participants will be given patient information sheet and consent 
forms to bring home and to think about their participation before the signing of the consent form on the day of 
the interview or focus group discussion. The initial place for verbal consent will be in the consultation room in 
the clinic, where privacy of patients and quiet environment is assured. The written consent will be taken in a 
quiet room on the day of the interview or focus group discussion to ensure privacy. Adequate time will be given 
to the participants to think through their decision and clarify accordingly. The person taking the consent of a 
patient will not be the treating physician or the treating healthcare worker of the patient. The person taking the 
consent of a physician will not be the direct superior of the physician.  
 
11.2. Confidentiality of Data and Patient Records 
The study will collect 2 types of research data in both hard and soft copy.  
Information from the hard copy (data collection forms, questionnaires and consent forms) will be transcribed to a 
Microsoft Excel document with password protection. The hard copy documents will be kept in a research folder, 
stored under lock and key in the polyclinic research room at Pasir Ris polyclinic. The folder will not be taken out 
of the clinic. 
After each interview, the interviewer will transfer the audio-recording to a password-protected corporate laptop 
and erase it from the audio-recorder. The audio recording will be transcribed verbatim using the research 
department’s transcribing software or transcription platforms (such as transcribe.gov.sg or Note Buddy) or 
engagement of transcriptionist. All participant identifiers will be removed from the transcript to ensure 
confidentiality. All transcripts will be checked by interviewer for accuracy. De-identified data will be used for 
analysis. All the audio files and transcriptions of the recordings will have password encryption and stored in the 
same password-protected corporate laptop in workplace. Only study members will have access to the password. 
Information from the data collection form will be transcribed to excel document (with password encryption) in a 
password-protected corporate laptop in workplace. There will be no USB or removal device used for data 
storage. The physical consent forms and the electronic data will be kept for 6 years post completion of study. 
The physical consent forms will be stored in a secure physical archive and the electronic data in an electronic 
archive. Only the principal investigator and co-investigators will have access to the archives.  

 
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12. PUBLICATIONS 
The investigators adhere to the ICMJE guidelines for authorship, acknowledgements and review procedures for 
scientific publications.  
The primary author will be the person who drafts the manuscript for publication, and the corresponding author 
will be the individual who takes primary responsibility for communication with the journal during manuscript 
submission, peer review, and publication process, and ensures that all the journal’s administrative requirements, 
such as providing details of authorship, ethics committee approval, and gathering conflict of interest forms and 
statements, are properly completed, although these duties may be delegated to one or more co-authors.  
 
13. RETENTION OF STUDY DOCUMENTS 
Records for all participants, including CRFs, all source documentation (containing evidence to study eligibility, 
history and physical findings, laboratory data, results of consultations, etc.) as well as IRB records and other 
regulatory documentation will be retained by the PI in a secure storage area in the clinic with lock and key access. 
The records should be accessible for inspection and copying by authorized authorities. Research data will be stored 
in institution issues PC or drive for 6 years before they are deleted when the study is completed.  
 
14. FUNDING AND INSURANCE 
SingHealth Polyclinics Research Seed Fund is applied and pending approval. PI will look for other sources of fund 
if the SHP Seed Fund is not approved.  
 

 
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List of Attachments 
 
Appendix 1 – References 
 
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