Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Background and Aim: Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods: A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014-2017, and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs. Results: Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra-therapeutic] vs S$4970.80 [sub-therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592). Conclusion: MM guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

A cultural adaptation and validation study of a self-report measure of the extent of and reasons for medication nonadherence among patients with diabetes in Singapore.

BACKGROUND: This self-report measure is a new instrument to measure the extent of and reasons for medication adherence separately. However, few studies have assessed its psychometric properties in diabetic patients and also in Asian populations. OBJECTIVES: To validate this self-report measure in diabetic patients in Singapore. METHODS: We collected data prospectively using a questionnaire among 393 diabetic patients from hospitals in Singapore from July 2018 to January 2019. Using the COnsensus-based Standards for the selection of health Measurement INstruments framework, we assessed face validity, internal consistency, test-retest reliability, structural validity, and measurement error. We tested four a priori hypotheses on correlation of extent score with patient-reported outcome measures to assess construct validity. We examined cross-cultural validity via measurement invariance across gender, age groups, and languages. RESULTS: We performed cognitive interviews with 30 consenting English-literate, Chinese-literate, and Malay-literate (10 patients per language) diabetic patients (age range 48-76 years, 53% male, disease duration range 1-30 years) and face validity was supported. Among 393 patients (mean age: 59.4±12.2 years, 50.9% female, 52.4% Chinese), we showed moderate internal consistency (Cronbach's alpha =0.67) and test-retest reliability (intra-class coefficient=0.56 [95% CI 0.37-0.70]). We calculated smallest detectable change as 0.80. We established construct validity by meeting all four hypotheses. We showed structural validity as confirmatory factor analysis confirmed a one-factor model, with excellent fit statistics (Comparative Fit Index=1.0; Tucker-Lewis Index=1.0; Root Mean Square Error of Approximation<0.001; Standardized Root Mean Residuals<0.001). Analysis of cross-cultural validity supported configural invariance model but not metric invariance and scalar invariance model. Caution must be taken against directly comparing extent scores across gender, age groups, and languages. CONCLUSION: This self-report measure is valid and reliable in measuring medication adherence in diabetic patients in Singapore.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

Adherence to premixed insulin in a prefilled pen compared with a vial/syringe in people with diabetes in Singapore.

BACKGROUND: The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singapore and most of Asia has not been studied. OBJECTIVES: This study aimed to compare adherence to premixed insulin formulated in a prefilled pen versus a vial/syringe and to identify predictors of adherence in 955 patients managed at the outpatient clinics of the largest acute care hospital in Singapore. METHODS: In this retrospective longitudinal study, electronic medical and pharmacy refill records were used to determine adherence to insulin over 24 months, measured in terms of compliance and persistence. Compliance is expressed as the medication possession ratio (used as continuous and categorical variables), and persistence is reported as a dichotomous variable with a permissible refill gap of 30 days before discontinuation of therapy is considered. Multivariate linear or logistic regression analysis was used to identify predictors of adherence. RESULTS: Compared with prefilled pen users, vial/syringe users were older (mean [SD] age, 64.1 [10.6] vs 62.4 [11.9] years; P = 0.032), and more were undergoing polypharmacy (69.6% vs 54.1%; P < 0.001). The mean (SD) medication possession ratio was comparable in vial/syringe versus prefilled pen users (83.8% [26.9%] vs 86.0% [23.2%]; P = 0.266). Prefilled pen users were more persistent with therapy compared with vial/syringe users (odds ratio = 1.36; 95% CI, 1.01-1.86) after adjusting for sociodemographic and clinical covariates. Median time to discontinuation of therapy was comparable (vial/syringe vs prefilled pen: 409 vs 532 days; P = 0.076). Being managed by an endocrinologist and not receiving government subsidies were significant predictors of persistence. CONCLUSIONS: Compared with other studies that found strong associations between adherence and insulin devices, the findings of this study suggest that persistence but not compliance varies by insulin device. The willingness to pay for health care, in addition to affordability, may affect insulin therapy adherence. Patients with uncontrolled diabetes due to suspected nonadherence may benefit from referral to a multidisciplinary care team comprising endocrinologists, diabetes nurse educators, dietitians, and allied health professionals. These findings are applicable to outpatients with similar demographic features managed at other acute care hospitals in Singapore. The impact of insulin devices on glycemic control needs to be investigated in future larger studies.