Cost-effectiveness analysis of endovascular coiling and neurosurgical clipping for aneurysmal subarachnoid hemorrhage in Thailand.

BACKGROUND: For patients with aneurysmal subarachnoid hemorrhage (aSAH), the Universal Coverage Scheme in Thailand covers the full costs of surgical and endovascular procedures except for those of embolization coils and assisting devices. Costs and effectiveness were compared between endovascular coiling and neurosurgical clipping to inform reimbursement policy decisions. METHODS: Costs and quality-adjusted life years (QALYs) were compared between coiling and clipping using the decision tree and Markov models. Mortality and functional outcomes of clipping were derived from national and hospital databases, and relative efficacies of coiling were obtained from meta-analyses of randomized controlled trials. Risks of rebleeding were abstracted from the International Subarachnoid Aneurysm Trial. Costs of the primary treatments, retreatments and follow-up care as well as utilities were obtained from hospital-based data. Non-health and indirect costs were abstracted from standard cost lists. RESULTS: Coiling and clipping contributed 10.59 and 9.28 QALYs to patients aged in their 50s. Under the societal and healthcare perspectives, the incremental costs incurred by coiling compared with clipping were US$1923 and $4343, respectively, which were equal to the incremental cost-effectiveness ratio of US$1470 and $3321 per QALY gained, respectively. Coiling became a cost-saving option when the costs of coil devices were reduced by 65.7%. At the country's cost-effectiveness threshold of US$5156, the probability of coiling being cost-effective was 71.3% and 65.6%, under the societal and healthcare perspectives, respectively. CONCLUSION: Endovascular treatment for aSAH is cost-effective and this evidence supports coverage by national insurance.

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.

Effect of a Rational Drug Use Policy on the prescribing safety in outpatient settings in Thailand.

OBJECTIVE: In Thailand, the 'Rational Drug Use (RDU) policy' has been implemented in the Ministry of Public Health (MOPH) hospitals since October 2016. This study aimed to explore the effects of the RDU policy on prescribing safety indicators for elderly patients and those with common chronic diseases. METHOD: Electronic outpatient databases were obtained from 15 MOPH hospitals. The selected indicators were the (1) glibenclamide prescribing in patients with diabetes mellitus who were elderly or had renal impairment; (2) duplicate prescribing of renin angiotensin system (RAS) blockers in patients with hypertension; (3) non-steroidal anti-inflammatory drugs (NSAIDs) prescribing in patients with chronic kidney disease stages 3-5; and (4) long-acting benzodiazepines prescribing in patients ≥65 years. The policy effects in terms of changes in prescribing trends were estimated using interrupted time-series analysis based on quarterly (Q) data. The postpolicy trends (2016, Q4-2017, Q4) were compared with the prepolicy trend (2014, Q1-2016, Q3). KEY FINDINGS: The unsafe prescribing of glibenclamide in patients with diabetes mellitus was 19.2% in Q1, 2014 and decreased significantly due to the RDU policy to 11.0% in Q4, 2017 (-4.23 percentage points quarterly, P < 0.001). The unsafe prescribing of RAS blockers and long-acting benzodiazepines was relatively low in Q1, 2014 (1.0% and 1.1%, respectively) and did not decrease further after the RDU policy. The unsafe prescribing of NSAIDs was 4.2% in Q1, 2014, increased abruptly one quarter after the policy and decreased afterwards. CONCLUSION: The RDU policy seemed to be a contributing factor that decreased the unsafe prescribing of glibenclamide, while the policy effect was minimal for the other indicators.

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.

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.

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.

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.

Assessing the efficiency of hospital pharmacy services in Thai public district hospitals.

The purpose of this study was to assess the efficiency of hospital pharmacy services and to determine the environmental factors affecting pharmacy service efficiency. The technical efficiency of a hospital pharmacy was assessed to evaluate the hospital's ability to use pharmacy manpower in order to produce the maximum output of the pharmacy service. Data Envelopment Analysis (DEA) was used as an efficiency measurement. The two labor inputs were pharmacists and support personnel and the ten outputs were from four pharmacy activities: drug dispensing, drug purchasing and inventory control, patient-oriented activities, and health consumer protection services. This was used to estimate technical efficiency. A Tobit regression model was used to determine the effect of the hospital size, location, input mix of pharmacy staff, working experience of pharmacists at the study hospitals, and use of technology on the pharmacy service efficiency. Data for pharmacy service input and output quantities were obtained from 155 respondents. Nineteen percent were found to have full efficiency with a technical efficiency score of 1.00. Thirty-six percent had a technical efficiency score of 0.80 or above and 27% had a low technical efficiency score (< 0.60). The average TE score increased in respect to the hospital size (0.60, 0.71, 0.75, and 0.83 in 10, 30, 60, and 90-120 bed hospitals, respectively). Hospital size and geographic location were significantly associated with pharmacy service efficiency.