Study design and population
This 12-week, pragmatic, open-labelled, randomized controlled study was conducted in the outpatient unit, Department of Medicine, Siriraj Hospital, Bangkok, Thailand. The study population consisted of 18-year-old or older individuals who met the 2015 American College of Rheumatology-European Ledge Against Rheumatism Gout Classification Criteria(5) or Rome Criteria (20) with SUA of more than 6 mg/d despite ULT treatment and having poor adherence to ULT based on the Medication Taking Behavior measure for Thai patients (MTB-T) questionnaire(21). Patients must have sufficient ability to use Thai language and have access to an Android or iOS smartphone device. Patients were excluded if they could not complete the questionnaires or were diagnosed with dementia or a psychiatric, visual, auditory, or neurological disorder, which interfered with smartphone use. Written informed consents were obtained from all patients prior to enrollment. Eligible patients were randomly assigned in a 1:1 ratio using a computer generated sequence with a block of four randomization to use the reminder "Drug Diary" app, or the patient education “Roo-Rak-Koh” app. Research nurse (PT) generated the random allocation sequence and assigned participants to interventions. This study was approved by the Scientific Ethics Committee of the Siriraj Institutional Review Board (COA Si no. 015/2020). The study was prospectively registered as a clinical trial with the Thai Clinical Trial Registry (TCTR20200123002). All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study adheres to CONSORT guidelines for reporting clinical trials.
Study Procedures
Baseline visit
The patients were instructed to download the app "Drug Diary" or the app"Roo-Rak-Koh". The researchers assisted patients to set up their medication schedule and reminder on the app and demonstrated how to use the app. For patients in the patient education group, researchers demonstrated functions in the application. All patients were asked to use the apps for 12 weeks and reminded by telephone on days 3, 30, and 60. For ULT, the stable dose of ULT was maintained throughout the study. The exact number of pills that should be taken per 12-week prescription of each medication was prescribed. The patients were instructed to take only the pills that were prescribed at the initial visit.
The following data were collected: demographic data (age, sex, educational level, occupation, body mass index, and comorbidities); history of alcohol use; characteristics of gout (diagnosis, duration of the disease, and number of gout flare); laboratory data (SUA level and glomerular filtration rate [GFR]); gout treatments (ULT dose and gout prophylaxis therapy), and other medications. Medication adherence was assessed using the Medication Taking Behavior measure for Thai patients (MTB-T) questionnaire, a medication taking behavior scale developed in the Thai language. The MTB-T score consists of six questions that are analyzed using a 4-point Likert scale. The total score is 24 points. A score of 24 indicates 'high adherence', scores of 22–23 suggest 'moderate adherence', and a score less than 22 is considered 'low adherence'. The scale showed good psychometric properties for medication adherence in Thai patients with various chronic diseases, including rheumatic diseases and musculoskeletal disorders (21).
Follow-up visit
All patients were instructed to bring all their leftover pills when they came to the clinic at 12 weeks of follow-up. SUA, GFR, and the frequency of gout attacks were collected. The adherence to medication and the satisfaction with the apps were assessed. Adherence was assessed using MTB-T and the pill count rate (%). Pill count rate is a simple objective indirect measurement of patient adherence to medication intake(22). The adherence rate was calculated using the following equation:
Medication adherence was defined as followed, the MTB-T questionnaire score of 24 or the pill count rate > 80% indicated 'high adherence', the MTB-T questionnaire score of 22-23 or the pill count rate range between 60-80% 'moderate adherence' and 'low adherence' if both previous conditions are not met. Patient satisfaction in both applications was measured using a visual analog scale (VAS) of 0-10, which evaluated satisfaction from 0 (terrible) to 10 (delighted).
Outcomes
The co-primary outcomes were the proportion of patients with high adherence, according to the MTB-T score, the percentage of pill count adherence and the proportion of patients with SUA <6 mg / dL at 12 weeks. Secondary outcomes consisted of the proportion of patients with high adherence, based on pill count, changes in SUA level, GFR, and frequency of flare-up of gout, as well as patient satisfaction with both applications.
Data collection
Study data were collected and managed using REDCap (Research Electronic Data Capture) electronic data capture tools hosted at Siriraj Center of Excellence in Bioinformatics and Data Management, Faculty of Medicine Siriraj Hospital, Mahidol University.(23) REDCap is a secure web-based application designed to support data capture for research studies. It provides 1) an intuitive interface for validated data entry; 2) audit trails to monitor data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for the importing of data from external sources.
Statistical Analysis
Assuming that the proportion of participants with high adherence at 12 weeks after using “Drug diary” app and “Roo-rak-koh” app was 67.8% and 50%(24), respectively, a sample size of 119 in each group was needed to yield a power of 80% to detect a difference between two groups with a 0.05 two-sided significance level. To compensate for 10% dropout rate during the study period, a total of 130 participants in each group was required.
Descriptive statistics were presented for the baseline data. For all results, categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate, while continuous data were compared using the independent T-test or the Mann-Whitney U test for data that were not normally distributed. The analysis was carried out using the intention-to-treat (ITT) method. Nonresponder imputation was used for models examining achievement of SUA when follow-up values were missing. A p-value of less than 0.05 was considered statistically significant. All analyses were performed using the Statistical Package for the Social Science (SPSS) 20.0.