Effects of a national policy advocating rational drug use on decreases in outpatient antibiotic prescribing rates in Thailand

OBJECTIVE: This study examined the effects of a national policy advocating rational drug use (RDU), namely, the 'RDU Service Plan', starting in fiscal year 2017 and implemented by the Thai Ministry of Public Health (MOPH), on trends in antibiotic prescribing rates for outpatients. The policy was implemented subsequent to a voluntary campaign involving 136 hospitals, namely, the 'RDU Hospital Project', which was implemented during fiscal years 2014-2016. METHODS: Hospital-level antibiotic prescribing rates in fiscal years 2014-2019 for respiratory infections, acute diarrhea, and fresh wounds were aggregated for two hospital groups using equally weighted averages: early adopters of RDU activities through the RDU Hospital Project and late adopters under the RDU Service Plan. Pre-/post-policy annual changes in the prescribing levels and trends were compared between the two groups using an interrupted time-series analysis. RESULTS: In fiscal years 2014-2016, decreases in antibiotic prescribing rates for respiratory infections and acute diarrhea in both groups reflected a trend that existed before the RDU Service Plan was implemented. The immediate effect of the RDU Service Plan policy occurred in fiscal year 2017, when the prescribing level among the late adopters dropped abruptly for all three conditions with a greater magnitude than in the decrease among the early adopters, despite nonsignificant differences. The medium-term effect of the RDU Service Plan was identified through a further decreasing trend during fiscal years 2017-2019 for all conditions in both groups, except for acute diarrhea among the early adopters. CONCLUSIONS: The national policy on rational drug use effectively reduced antibiotic prescribing for common but questionable outpatient conditions

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Effects of a national policy advocating rational drug use on decreases in outpatient antibiotic prescribing rates in Thailand.

OBJECTIVE: This study examined the effects of a national policy advocating rational drug use (RDU), namely, the 'RDU Service Plan', starting in fiscal year 2017 and implemented by the Thai Ministry of Public Health (MOPH), on trends in antibiotic prescribing rates for outpatients. The policy was implemented subsequent to a voluntary campaign involving 136 hospitals, namely, the 'RDU Hospital Project', which was implemented during fiscal years 2014-2016. METHODS: Hospital-level antibiotic prescribing rates in fiscal years 2014-2019 for respiratory infections, acute diarrhea, and fresh wounds were aggregated for two hospital groups using equally weighted averages: early adopters of RDU activities through the RDU Hospital Project and late adopters under the RDU Service Plan. Pre-/post-policy annual changes in the prescribing levels and trends were compared between the two groups using an interrupted time-series analysis. RESULTS: In fiscal years 2014-2016, decreases in antibiotic prescribing rates for respiratory infections and acute diarrhea in both groups reflected a trend that existed before the RDU Service Plan was implemented. The immediate effect of the RDU Service Plan policy occurred in fiscal year 2017, when the prescribing level among the late adopters dropped abruptly for all three conditions with a greater magnitude than in the decrease among the early adopters, despite nonsignificant differences. The medium-term effect of the RDU Service Plan was identified through a further decreasing trend during fiscal years 2017-2019 for all conditions in both groups, except for acute diarrhea among the early adopters. CONCLUSIONS: The national policy on rational drug use effectively reduced antibiotic prescribing for common but questionable outpatient conditions.

Self-administration of medications for chronic diseases and drug-related hospital admissions in elderly patients at a Thai hospital.

Background Studies of self-administered medications associated with hospital admissions are limited. Objective This study aimed to identify drug-related hospital admissions among elderly patients with diabetes, hypertension and chronic obstructive pulmonary disease and its association with self-administered medications. Method This was a prospective study of 335 patients admitted to a district hospital in Thailand from October 2018 to April 2019. The patients were divided into two groups: one with self-administered medication and the other with caregiver-administered medication. Pharmaceutical Care Network Europe V8.02-defined drug-related problems were identified. Those that conformed to the Hallas contribution and causality criteria were deemed drug-related hospital admissions and causes of the problems were examined. Main outcome measure An association between self-administration of medications and hospital admission was determined using a multivariable logistic regression analysis. Results The prevalence of drug-related hospital admissions was 20.6% (95% confidence interval, CI 16.4-25.3%) as an overall and was significantly higher in the self-administration group (25.4%) than in the caregiver administration group (12.7%). Among the drug-related hospital admissions in the self-administration and caregiver administration groups respectively, 71.7 and 62.5% were preventable, 63.2 and 37.7% were caused by patient themselves, and 26.3 and 37.5% were from adverse drug reactions. Medical conditions frequently caused by the patients included the exacerbation of chronic obstructive pulmonary disease due to using inhalers less than prescribed or administering drugs in the wrong manner in the self-administration group and hypoglycemia due to a long interval between insulin injection and meal consumption in the caregiver administration group. Compared to caregiver-administered medications, self-administration of medications increased the odds of hospital admission by approximately two-fold (adjusted odds ratio, OR 2.24, 95% CI 1.13-4.43). Other independent risk factors included the use of five or more medications a day (OR 2.65, 95% CI 1.16-6.07), the presence of underlying chronic obstructive pulmonary disease (OR 2.11, 95% CI 1.05-4.23) and self-medication (OR 2.59, 95% CI 1.12-5.99). Conclusion Self-administered medication was associated with hospital admissions in elderly patients with chronic diseases. To prevent problems, priority should be given to interventions to ensure the appropriate administration of inhaled medications for chronic obstructive pulmonary disease and antihyperglycemic agents.

CKDNET, a quality improvement project for prevention and reduction of chronic kidney disease in the Northeast Thailand.

BACKGROUND: The incidence of chronic kidney disease (CKD) is high in the Northeast Thailand compared to other parts of the country. Therefore, a broad program applying all levels of care is inevitable. This paper describes the results of the first year trial of the Chronic Kidney Disease Prevention in the Northeast Thailand (CKDNET), a quality improvement project collaboratively established to curb CKD. METHODS: We have covered general population, high risk persons and all stages of CKD patients with expansive strategies such as early screening, effective CKD registry, prevention and CKD comprehensive care models including cost effectiveness analysis. RESULTS: The preliminary results from CKD screening in general population of two rural sub-districts show that 26.8% of the screened population has CKD and 28.9% of CKD patients are of unknown etiology. We have established the CKD registry that has enlisted a total of 10.4 million individuals till date, of which 0.13 million are confirmed to have CKD. Pamphlets, posters, brochures and other media of 94 different types in the total number of 478,450 has been distributed for CKD education and awareness at the community level. A CKD guideline that suits for local situation has been formulated to deal the problem effectively and improve care. Moreover, our multidisciplinary intervention and self-management supports were effective in improving glomerular filtration rate (49.57 versus 46.23 ml/min/1.73 m2; p < 0.05), blood pressure (129.6/76.1 versus 135.8/83.6 mmHg) and quality of life of CKD patients included in the program compared to those of the patients under conventional care. The cost effectiveness analysis revealed that lifetime cost for the comprehensive health services under the CKDNET program was 486,898 Baht compared to that of the usual care of 479,386 Baht, resulting in an incremental-cost effectiveness ratio of 18,702 Baht per quality-adjusted life years gained. CONCLUSION: CKDNET, a quality improvement project of the holistic approach is currently applying to the population in the Northeast Thailand which will facilitate curtailing of CKD burden in the region.

Access to reperfusion therapy and mortality outcomes in patients with ST-segment elevation myocardial infarction under universal health coverage in Thailand.

BACKGROUND: Evidence on access to reperfusion therapy for patients with ST-segment elevation myocardial infarction (STEMI) and associated mortality in developing countries is scarce. This study determined time trends in the nationally aggregated reperfusion and mortality, examined distribution of percutaneous coronary intervention (PCI) utilization across provinces, and assessed the reperfusion-mortality association in Thailand that achieved universal health coverage in 2002. METHODS: Data on hospitalization with STEMI in 2011-2017 of 69,031 Universal Coverage Scheme (UCS) beneficiaries were used for estimating changes in the national aggregates of % reperfusion and mortality by a time-series analysis. Geographic distribution of PCI-capable hospitals and PCI recipients was illustrated per provinces. The reperfusion-mortality association was determined using the propensity-score matching of individual patients and panel data analysis at the hospital level. The exposure is a presence of PCI or thrombolysis. Outcomes are all-cause mortality within 30 and 180 days after an index hospitalization. RESULTS: In 2011-2017, the PCI recipients increased annually 5.7 percentage (%) points and thrombolysis-only recipients decreased 2.2% points. The 30-day and 180-day mortalities respectively decreased annually 0.20 and 0.27% points among the PCI recipients, and they increased 0.79 and 0.59% points among the patients receiving no reperfusion over the same period. Outside Bangkok, the provinces with more than half of the patients receiving PCI increased from 4 provinces of PCI-capable hospitals in 2011 to 37 provinces, which included the neighboring provinces of the PCI-capable hospitals in 2017. Patients undergoing reperfusion had lower 30-day and 180-day mortalities respectively by 19.6 and 21.1% points for PCI, and by 14.1 and 15.1% points for thrombolysis only as compared with no reperfusion. The use of PCI was associated with decreases in 30-day and 180-day mortalities similarly by 5.4-5.5% points as compared with thrombolysis only. A hospital with 1% higher in the recipients of PCI had lower mortalities within 30 and 180 days by approximately 0.21 and 0.20%, respectively. CONCLUSIONS: Patients with STEMI in Thailand experienced increasing PCI access and the use of PCI was associated with lower mortality compared with thrombolysis only. This is an evidence of progress toward a universal coverage of high-cost and effective health care.

Cognitive impairment, quality of life and healthcare utilization in patients with chronic kidney disease stages 3 to 5.

AIM: This study aimed to examine associations between cognitive impairment and quality of life and healthcare utilization in patients with chronic kidney disease (CKD) stages 3 to 5. METHODS: A cross-sectional study was conducted in 379 outpatients with a mean age of 65.7 years at tertiary care hospitals in Thailand. Cognitive function was measured using the Mini-Mental State Examination, and quality of life was measured using the five-dimension European quality of life (EQ-5D-5L) multi-attribute utility instrument. The effects of cognitive impairment on the likelihood of reporting 'no problems' for each EQ-5D dimension, the quality of life scores and healthcare utilization were determined using an appropriate multivariate analysis. RESULTS: The prevalence of cognitive impairment in patients with CKD stages 3 to 5 was 15.8% (95% confidence interval [CI], 12.3, 19.9). Patients with cognitive impairment had a significantly lower likelihood of achieving good outcomes in the mobility, self-care, usual activities and anxiety/depression dimensions of the EQ-5D-5L than those with normal cognition. Patients with cognitive impairment had a significantly lower quality of life score than those with normal cognition by 0.06 points (95% CI, 0.01, 0.10). Cognitive impairment increased the number of emergency visits (rate ratio, RR, 3.47; 95% CI, 1.45, 8.29). Compared to CKD stage 3, CKD stage 5 decreased the quality of life score by 0.06 points (95% CI, 0.01, 0.10) and increased the rate of hospitalization (RR, 2.29; 95% CI, 1.27, 4.12). CONCLUSION: Cognitive impairment in patients with CKD was associated with lower quality of life scores and increased healthcare utilization.

Effects of restrictive reimbursement on the prescribing and expenditures on non-essential lipid-lowering drugs.

BACKGROUND: The rapid cost escalation of the government employee scheme in Thailand was driven by the overprescription of non-essential drugs (NEDs), which were not listed in the National Lists of Essential Medicines. A restrictive reimbursement policy implemented in October 2012 required prescribers to base the prescription of NEDs on six criteria, including A and B for safety, C for effectiveness, D for availability, and E and F for costs, hence known as the A-F policy. OBJECTIVE: The A-F policy was examined in terms of its outcomes regarding the prescription volume and reimbursement expenditure for lipid-lowering drugs (LLDs). METHODS: Data on LLD prescription in 2012-2015 from outpatient settings in 29 public hospitals were standardized using quantities based on the World Health Organization's Anatomical, Therapeutic and Chemical (ATC) classification and the defined daily dose (DDD) system. The policy effects were estimated using an interrupted time-series analysis. RESULTS: The restrictive reimbursement policy decreased both the prescription volume and the reimbursement value of non-essential LLDs. Within the first month of policy implementation, the percentage of NEDs, as defined by DDDs and reimbursement expenditure, immediately decreased by 15.1 and 15.2% points in provincial hospitals and by 8.3 and 4.4% points in military hospitals, respectively. The prescription of NEDs continued to decrease thereafter, despite there being no statistically significant changes in the trend of decreased prescribing compared with the prepolicy period. The decrease in the prescription of NEDs resulted in the declining reimbursed amount per day and stable expenditure of LLDs as a whole. CONCLUSION: The effectiveness on the A-F restrictive reimbursement on NED prescribing helped stabilize the expenditure on LLDs.

Coprescription of QT interval-prolonging antipsychotics with potentially interacting medications in Thailand.

BACKGROUND: The US FDA has designated pimozide, thioridazine, and ziprasidone as contraindicated for patients at risk of QT interval prolongation, and assigned haloperidol, olanzapine, paliperidone, quetiapine, and risperidone as associated with a significant risk of QT prolongation. This study aimed to examine trends and hospital variations in concomitant prescribing among these eight selected antipsychotics, and coprescription with interacting drugs known to increase QT prolongation risk. METHODS: Data on outpatient antipsychotic prescriptions during 2012-2015 were obtained from 16 general hospitals and 10 university hospitals nationwide. A time-series analysis was used for estimating trends in coprescription that led to drug interactions. RESULTS: Coprescribing among the eight antipsychotics ranged from 7.5% for quetiapine to 33.1% for thioridazine. The rate of coprescription with contraindicated interacting drugs was 9.7% for thioridazine and 21.9% for pimozide, and increased by 1.1 and 1.4 percentage points (% pt.) yearly for thioridazine in general and university hospitals, respectively. Coprescribing with interacting drugs with precautions was 2.8% for quetiapine, 7.4% for ziprasidone, and 27.9% for risperidone; these percentages increased yearly by 1.7% pt. for ziprasidone and 2.6% pt. for risperidone in general hospitals, as well as by 1.0% pt. for risperidone in university hospitals. The median proportion of patients exposed to a QT-prolonging interaction was 12.3% across hospitals (interquartile range, 9.9-19.5%). Wide interhospital variation was found in percentages of drug interactions among patients receiving thioridazine, ziprasidone, paliperidone, or olanzapine in general hospitals, and among patients receiving paliperidone or pimozide in university hospitals. CONCLUSIONS: Coprescription of antipsychotics with interacting drugs that could increase the risk of QT prolongation was common in Thailand, and thioridazine, ziprasidone, and risperidone showed increasing trends. We urge the incorporation of a unified list of QT-prolonging antipsychotics and interacting drugs into a computerized drug interaction warning system, and existing national rational drug use campaigns should cover this important issue.

Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 genotype-guided doses in renal transplantation patients.

AIMS: Although cytochromeP450(CYP)3A5 gene polymorphism affects personalized tacrolimus doses, there is no consensus as to whether CYP3A5 genotypes should be determined to adjust the doses. The aims were to compare the therapeutic ranges and clinical outcomes between the conventional and genotype-guided tacrolimus doses. METHODS: This randomized controlled study compared 63 cases of the conventional tacrolimus dose group (0.1 mg/kg/day) with 62 cases of the genotype-guided doses group of 0.125, 0.1 and 0.08 mg/kg for CYP3A5*1/*1, *1/*3, and *3/*3 genotypes for the initial 3 days of kidney transplantation. After day 3, dose adjustment occurred in both groups to achieve therapeutic concentrations. RESULTS: The genotype-guided group had an increased proportion of patients with tacrolimus concentrations in the therapeutic range at the steady state on day 3 (40.3 vs 23.8%, P = .048). A lower proportion of over-therapeutic concentration patients was noted in the genotype-guided group in the CYP3A5*3/*3 genotype (9.7 vs 27%, P = .013). Unexpectedly, more delayed graft functions (DGFs) were in the genotype-guided group (41.9 vs 22.2%, P = .018) especially in the CYP3A5*1/*1 participants who might have had an aggravated DGF by a longer ischaemic time and higher serum donor creatinine levels than in the control group. There were no significant differences of glomerular filtration rates or graft or patient survivals over a median 37-month follow-up period. CONCLUSIONS: Determination of the CYP3A5 genotype improved therapeutic range achievement. CYP3A5*1/*1 patients who have high risks of DGF should be closely monitored because of an increased risk of DGF and reduced glomerular filtration rate with high tacrolimus doses.

Ginkgo biloba Extract (EGb761), Cholinesterase Inhibitors, and Memantine for the Treatment of Mild-to-Moderate Alzheimer's Disease: A Network Meta-Analysis.

BACKGROUND: Cholinesterase inhibitors (ChEIs) and memantine have been reported to provide modest benefits for cognition and aspects of functioning in Alzheimer's disease (AD). Ginkgo biloba extract (EGb761), a phytomedicine, is widely used and expected to be well-tolerated. A few trials have compared EGb761 with ChEIs, and the results were inconclusive. OBJECTIVE: A network meta-analysis was conducted to evaluate the therapeutic benefits and tolerability of EGb761, three ChEIs (donepezil, galantamine, and rivastigmine), and memantine in mild-to-moderate AD patients. METHODS: Electronic databases were searched through 30 June 2017. We included randomized double-blinded trials with a minimum treatment duration of 22 weeks for EGb761 240 mg/day and 12 weeks for ChEIs or memantine. The study patients included AD or probable AD patients without other types of dementia or neurological disorders. Cognition, function, and behavior symptoms were compared between treatments using the standardized mean difference (SMD). Clinical global impression, treatment discontinuation, and adverse events were compared between treatments using the relative risk (RR). Statistical pooling of the individual trial results was conducted using a frequentist approach. The probability of being the best for a treatment was estimated using surface under the cumulative ranking. RESULTS: EGb761 and memantine showed no therapeutic benefits in all study outcomes. For cognition, all ChEIs were significantly better than placebo (SMD from - 0.52 to - 0.26), and galantamine was better than rivastigmine in the oral and patch forms, EGb761, and memantine (SMD [95% confidence interval (CI)]: - 0.22 [- 0.40 to - 0.05]; - 0.26 [- 0.45 to - 0.07]; - 0.34 [- 0.56 to - 0.12]; and - 0.42 [- 0.71 to - 0.13], respectively). Compared to placebo, galantamine, the rivastigmine patch, and oral rivastigmine provided modest functional benefits (SMD, from 0.21 to 0.24), and galantamine provided behavioral benefits (SMD [95% CI]: - 0.15 [- 0.26 to - 0.04]). All ChEIs provided a better improvement in clinical global impression than placebo (RR from 1.20 to 1.69). The global impression ratings were more improved with donepezil than with galantamine (RR [95% CI]: 1.40 [1.09-1.80]) or with EGb761 (RR [95% CI]: 1.40 [1.06-1.85]), with a 96% probability of donepezil being more effective than the other study agents. Rivastigmine in oral and patch forms, galantamine, and donepezil had a higher risk of being discontinued than placebo (RR [95% CI]: 2.14 [1.49-3.06]; 2.04 [1.30-3.20]; 1.79 [1.28-2.49]; 1.49 [1.03-2.17], respectively). Discontinuation of EGb761 was not statistically lower than that of the ChEIs, in which donepezil had the lowest probability (38%) of being discontinued. CONCLUSION: EGb761 and memantine showed no treatment benefits compared to placebo and ChEIs. Galantamine provided the highest beneficial effect on cognition and behavioral symptoms. Donepezil provided a better clinical global impression and tolerability than the other ChEIs and EGb761, with a similar benefit for cognition as galantamine.

Budget impact analysis of the new reimbursement policy for day surgery in Thailand.

INTRODUCTION: In 2017 the Thai Ministry of Public Health proposed a new financing mechanism to promote day surgery under the Universal Coverage Scheme - the main public insurance arrangement for Thais. The key feature of the policy is health facilities performing day surgery can claim the treatment expense based on relative weight (RW) instead of adjusted RW (adjRW). Procedures for 12 diseases (so-called "candidate procedures") are eligible for the new reimbursement. The objective of this study was to assess the current day surgery situation in Thailand and analyze potential budget impact from the new policy. METHODS: A quantitative cross-section design was employed. Individual inpatient records of the Universal Coverage Scheme during 2014-2016 were analyzed. Descriptive statistics and simulation analyses were applied. The analyses were divided into three subtopics: 1) case volume and expense claim, 2) utilization across facilities, and 3) case mix index and budget impact. RESULTS: Overall, day surgery accounted for 4.8% of admissions with candidate procedures. Inguinal hernias, hemorrhoids, and common bile duct stones caused the largest sum of admission numbers and admission days. Currently, the annual reimbursement for candidate procedures treated as inpatient cases is around 290.8 million Baht (US$ 8.8 million), with about 12.4 million Baht (US$ 0.38 million) for day surgery cases. If all candidate procedures were performed as day surgery and diagnostic-related groups (DRG) version 6 was applied, the incremental budget would amount to 1.9 million Baht (US$ 58,903). CONCLUSIONS: The new reimbursement policy will likely lead to minimal budget burden. Even in the case of maximal uptake of the policy, the needed budget would increase by just 15%. The marginal budget increment was explained by the infinitesimal RW-adjRW difference. Apart from the financial measure, other qualitative aspects of the policy, such as infrastructure and health staff readiness, should be explored.

Access to and price trends of antidiabetic, antihypertensive, and antilipidemic drugs in outpatient settings of the Universal Coverage Scheme in Thailand.

Under the Universal Coverage Scheme (UCS) with payment per capita for outpatient (OP) services, hospitals' financial risks will rise if access to essential drugs increases. This study examined trends in access to and price of essential drugs for noncommunicable diseases (NCDs) and an overall purchasing price index (PPI) for an OP drug basket from public hospitals. To examine drug access, OP prescription data from 2010-2012 were obtained from the UCS. Access to thirteen drugs for diabetes, hypertension, and dyslipidemia was examined for trend using a time-series analysis. To calculate the PPI, drugs in the same dataset in 2010 that each contributed at least 0.2% of the total OP drug expenditure (N = 118 items) were selected together with drugs expected for near future growth (N = 48 items). The PPI was constructed from purchasing prices in 16 hospitals using a standard method developed by the International Labour Organization. Based on 166 drug items accounting for 75% of OP drug expenditures, the overall PPI continually declined by 6.8% from 2010 to 2012. Access to the 13 selected NCD drugs, accounting for 22% of the total OP drug expenditure increased from 22 to 30 per 1,000 population for antidiabetics, 27 to 47 for antihypertensive agents, and 32 to 53 for antilipidemics from 2010-2012. Growth in the study drug recipients was relatively higher than that in the population and diagnosed patients. Due to generic market competition, metformin, glipizide, amlodipine, losartan, simvastatin, atorvastatin, and fenofibrate prices decreased by 6-22%. Antiretrovirals and risperidone prices decreased by more than 10% due to price negotiation by the UCS. Access to essential drugs for diabetes, hypertension and dyslipidemia has increased. A decline in the PPI could contain essential drug expenditure when the demand for the drugs increased. Generic market competition and price negotiation by the UCS led to price reduction.

Trends and variations in outpatient coprescribing of simvastatin or atorvastatin with potentially interacting drugs in Thailand.

BACKGROUND: The aim of this study was to assess trends and variations in coprescribing of simvastatin or atorvastatin with interacting drugs in Thailand. METHODS: Outpatient prescriptions between 2013 and 2015 in 26 tertiary care hospitals were analyzed for statin coprescribing. The proportion of patients exposed to coprescribing was estimated for semi-annual changes, using a time-series analysis and for hospital variations, using an interquartile range (IQR). RESULTS: The coprescribing of simvastatin with all contraindicated drugs in 10 university and 16 general hospitals, respectively, was 3.6 and 3.1% in 2013, then decreased to 3.2 and 2.6% in 2014 and to 2.6 and 2.0% in 2015. The drug most frequently coprescribed with simvastatin, on a decreasing trend (by 0.19 percentage points) was gemfibrozil (in 2013, 2014 and 2015, respectively; 2.9, 2.3 and 2.0% in university hospitals, and 2.5, 2.0 and 1.6% in general hospitals). A similar trend was found in atorvastatin-gemfibrozil coprescribing. Patients coprescribed simvastatin with the rest of the contraindicated drugs were relatively stable at 0.6-0.8%. No protease inhibitors were coprescribed with simvastatin and atorvastatin. The IQR of simvastatin coprescribing in the university hospitals was smaller than that in the general hospitals and decreased over time. CONCLUSIONS: Coprescriptions potentially leading to drug interactions with simvastatin in Thailand were observed although the contraindicated drugs were acknowledged. Mutual awareness among health professionals and the implementation of electronic prescribing should be strengthened as zero drug interaction was possible as in the case of protease inhibitors in the present study.

Cost-Effectiveness Analysis of Direct-Acting Oral Anticoagulants for Stroke Prevention in Thai Patients with Non-Valvular Atrial Fibrillation and a High Risk of Bleeding.

OBJECTIVE: The objective of this study was to assess the cost effectiveness of direct-acting oral anticoagulants for stroke prevention in Thai patients with non-valvular atrial fibrillation and a HAS-BLED score of 3. METHODS: Total costs (US$) in 2017 and quality-adjusted life-years were estimated over 20 years using a Markov model. A base-case analysis was conducted under a societal perspective, which included direct healthcare, non-healthcare and indirect costs in Thailand. Clinical events for warfarin and utilities were obtained from Thai patients whenever possible. The efficacy of direct-acting oral anticoagulants was derived from trial-based East Asian subgroups and adjusted for time in the target international normalized ratio range of warfarin. RESULTS: In the base case, use of apixaban instead of warfarin incurred an additional cost of US$20,763 per quality-adjusted life-year gained. Substituting apixaban with rivaroxaban and rivaroxaban with high-dose edoxaban would incur an additional cost per quality-adjusted life-year by US$507 and US$434, respectively. Compared with warfarin, high-dose edoxaban had the lowest incremental cost-effectiveness ratio of US$9704/quality-adjusted life-year, followed by high-dose dabigatran (incremental cost-effectiveness ratio US$11,155/quality-adjusted life-year). The incremental cost-effectiveness ratios based on a payer perspective were similar. The incremental cost-effectiveness ratio was below Thailand's cost-effectiveness threshold when high-dose dabigatran and edoxaban prices were reduced by 50%. Changes in key parameters had a minimal impact on incremental cost-effectiveness ratios. CONCLUSIONS: For both societal and payer perspectives, high-dose edoxaban with a price below the country cost-effectiveness threshold should be the first anticoagulant option for Thai patients with non-valvular atrial fibrillation and a high risk of bleeding.

Effect of CYP3A5 genotype on hospitalization cost for kidney transplantation.

Background Dosage quantities of tacrolimus (TAC) vary according to cytochrome P450 3A5 (CYP3A5) genotype. Genotyping is expected to optimize the response to TAC response and to minimize adverse effects. In Thailand, kidney transplantation is reimbursable with the same diagnosis-related group payment regardless of patient's CYP3A5 genotype. Objective This study aimed to determine the costs of TAC administration, therapeutic drug monitoring (TDM), and hospitalization for kidney transplantation across CYP3A5*1/*1, *1/*3, and *3/*3 genotypes. Setting A single transplant center in a university hospital. Method This is an observational study that collected data from patients pooled from both arms of a randomized controlled trial that tested initial doses of TAC. Main outcome measure TAC and TDM cost and hospitalization cost for transplantation were compared between genotypes. Results The CYP3A5*1/*1 patients had the highest median combined TAC-TDM cost and hospitalization cost ($1062 and $9097), followed by CYP3A5*1/*3 ($859 and $6467) and CYP3A5*3/*3 patients ($761 and $5604). The CYP3A5*1/*1 patients had a higher hospitalization cost by $2787 over the CYP3A5*1/*3 patients, despite marginal significance. The CYP3A5*1/*1 patients had a significantly higher cost of TAC plus TDM (by $309) and hospitalization cost (by $3275) than the CYP3A5*3/*3 patients. Both study costs were significantly higher in patients with delayed graft functioning than in patients with instant or slow graft functioning. Conclusion The benefits of genotype detection in patients with CYP3A5*1/*1 should be considered for a higher reimbursement rate because of the substantial differences in total hospitalization cost for kidney transplantation among patients with different CYP3A5 genotypes.

Cost-effectiveness analysis of policy options on first-line treatments for advanced, non-small cell lung cancer in Thailand.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have shown to be better for progression-free survival than chemotherapy as the first-line treatment for advanced, non-small cell lung cancer (NSCLC), especially in patients with epidermal growth factor receptor mutation (EGFR M+). This study evaluates under the Thai health system context, cost-effectiveness of (A) the use of platinum doublets for all without EGFR testing, and (B) an EGFR test followed by TKIs or platinum doublets conditional on test results. MATERIALS AND METHODS: A decision analysis model was constructed to estimate quality-adjusted life years (QALYs) and total cost for each option. Cancer progression and death were pooled from randomized, controlled trials. Quality of life was obtained from patient interview, using the European Quality-of-Life, 5-Dimension questionnaire. Costs associated with treatment outcomes were derived from patient chart reviews. RESULTS: Combining the EGFR test with each TKI, gefitinib, erlotinib and afatinib if M+ or otherwise platinum doublets, resulted in higher effectiveness than the use of platinum doublets for all by 0.15, 0.19 and 0.21 QALYs, respectively. Among the three TKIs, gefitinib was dominated economically by erlotinib, which incurred an incremental cost-effectiveness ratio (ICER) of $46,783/QALY over the platinum doublets for all. Moving to the next best, afatinib resulted in the ICER of $198,961/QALY over erlotinib. Probabilities for any TKIs being cost-effective when compared with platinum doublets over a wide range of willingness to pay were modest. CONCLUSION: In Thailand, the first-line treatment for advanced NSCLC with TKIs conditional on EGFR test results was not cost-effective as compared with platinum doublets for all.

Association Between a Centrally Reimbursed Fee Schedule Policy and Access to Cataract Surgery in the Universal Coverage Scheme in Thailand.

Importance: Uptake of cataract surgery in developing countries is much lower than that in developed countries. Cataract unawareness and financial barriers have been cited as the main causes. Under the Universal Coverage Scheme (UCS), Thailand introduced a central reimbursement (CR) system for cataract surgery. It is unknown if this financial arrangement could incentivize service provision (private or public) in areas that are hard to reach. Objective: To examine the association between the CR policy and access to cataract surgery in Thailand. Design, Setting, and Participants: Using time series analysis, hospitalization data during 2005 to 2015 for UCS members were analyzed for time trends and subnational variations in the cataract surgery rate (CSR) before and after the CR implementation. Main Outcomes and Measures: The annual growth in access was estimated using segmented regression. The CSR gap across regions was determined by the slope index of inequality (SII). Unequal access across districts was represented by the gap between the top and bottom quintiles. Results: During 2005 to 2015, a total of 0.98 million UCS members (mean [SD] age, 67.4 [11.2] years; 58.7% female) received cataract surgery. The number of cases increased from 77 897 in 2005 to 192 290 in 2015. At the national level, the CSR per 100 000 population increased from 352.0 to 378.7 cases in 2005 to 2008, to 716.3 cases in 2013, and then to 765.3 cases in 2015. With the use of mobile services through an exclusive CR, 3 private hospitals took the lead in service growth, sharing 79.2% of cases in the private sector in 2009. From 2010, the number of cases in public hospitals grew yearly by 12.6% to 13.6% until 2012, rose 21.7% in 2013, and then the rate of increase declined to that of 8.2% to 8.3% in 2014-2015. During the periods of an increase in overall access, the CSR gap across regions widened as indicated by the SII of 755.4 cases per 100 000 population in 2010 because of rapid uptake in areas with mobile services. When the national CSR became adequately large and mobile services were discouraged in 2013, the gap in 2014-2015 narrowed. Conclusions and Relevance: This study found that the appropriate payment and service designs helped reduce the cataract surgery backlog. With an adequately high CSR, Thailand is on track to reach the VISION 2020 goal, aiming for blindness elimination by the year 2020, which has been achieved by most developed countries.

EQ-5D-based utilities and healthcare utilization in Thai adults with chronic epilepsy.

Quality of life and resource use are key parameters that justify economic values in treatments for epilepsy. Health profiles and service utilization were assessed in 224 adults with 15.7years of epilepsy in two super-tertiary care facilities in Thailand. The European Quality of Life, 5-Dimension (EQ-5D)-based utilities and subsequent outpatient (OP) visits and hospitalizations were determined with respect to seizure control outcomes that were assessed by neurologists. Mean utility and visual analogue scale (VAS) scores were respectively higher in 67 patients who are seizure-free (0.82 and 78.9) than in 157 patients who had uncontrolled or persistent seizures, which were divided into seizure reduction (0.79 and 75.5) and no improvement in seizure frequency (0.72 and 73.5). Controlling for patient characteristics, those who are seizure-free had significantly higher utility and VAS scores than those with no improvement by 0.10 (95% confidence interval (CI): 0.03-0.17) and 6.25 (95% CI: 0.09-12.41), respectively. Seizure-free patients were less likely to report pain or discomfort, as compared with patients with seizure reduction (odds ratio (OR): 0.41, 95% CI: 0.19-0.90) and patients with no improvement (OR: 0.32, 95% CI: 0.13-0.75). Over a six-month period, mean OP visits were significantly lower in seizure-free patients (2.27 times) than in those with seizure reduction (3.00 times) and those with no improvement (4.08 times). Mean hospitalizations over 12months among the three groups were 0.03, 0.24, and 0.14 times, respectively. For persistent seizures, 50% received only conventional antiepileptic drugs (AEDs). When epilepsy treatments are considered for their costs and effectiveness, utilities and healthcare use, conditional on seizure control status, can be applied for further analyses.

Cost-Utility of Video-Electroencephalography Monitoring Followed by Surgery in Adults with Drug-Resistant Focal Epilepsy in Thailand.

OBJECTIVES: This study assessed whether video-electroencephalography (VEEG) monitoring followed by surgery was cost-effective in adult patients with drug-resistant focal epilepsy under Thai health care context, as compared with continued medical treatment without VEEG. METHODS: The total cost (in Thai Baht, THB) and effectiveness (in quality-adjusted life years, QALYs) were estimated over a lifetime horizon, using a decision tree and a Markov model. Data on short-term surgical outcomes, direct health care costs, and utilities were collected from Thai patients in a specialized hospital. Long-term outcomes and relative effectiveness of the surgery over medical treatment were derived, using systematic reviews of published literature. RESULTS: Seizure-free rates at years 1 and 2 after surgery were 79.4% and 77.8%, respectively. Costs of VEEG and surgery plus 1-year follow-up care were 216,782 THB, of which the VEEG and other necessary investigations were the main cost drivers (42.8%). On the basis of societal perspective, the total cost over a 40-year horizon accrued to 1,168,679 THB for the VEEG option, 64,939 THB higher than that for no VEEG. The VEEG option contributed to an additional 1.50 QALYs over no VEEG, resulting in an incremental cost-effectiveness ratio of 43,251 THB (USD 1236) per 1 QALY gained. Changes in key parameters had a minimal impact on the incremental cost-effectiveness ratio. Accounting for uncertainty, there was an 84% probability that the VEEG option was cost-effective on the basis of Thailand's cost-effective threshold of 160,000 THB/QALY. CONCLUSIONS: For patients with drug-resistant epilepsy, VEEG monitoring followed by epilepsy surgery was cost-effective in Thailand. Therefore it should be recommended for health insurance coverage.