METHODS: A cost-utility analysis using a lifetime Markov model was conducted among Thai patients with NAFLD, from a societal perspective. Pioglitazone, vitamin E, a weight reduction program, and usual care were investigated, with the outcomes of interest being the number of cirrhosis and hepatocellular carcinoma (HCC) cases, life expectancy, quality-adjusted life-years (QALYs), lifetime costs, and the incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed.
RESULTS: When compared with usual care, a weight reduction program can prevent cirrhosis and HCC cases by 13.91% (95% credible interval [CrI] 0.97, 20.59) and 2.12% (95% CrI 0.43, 4.56), respectively; pioglitazone can prevent cirrhosis and HCC cases by 9.30% (95% CrI -2.52, 15.24) and 1.42% (95% CrI -0.18, 3.74), respectively; and vitamin E can prevent cirrhosis and HCC cases by 7.32% (95% CrI -4.64, 15.56) and 1.12% (95% CrI -0.81, 3.44), respectively. Estimated incremental life expectancy and incremental QALYs for all treatment options compared with usual care were approximately 0.06 years and 0.07 QALYs, respectively. The lifetime costs of both a weight reduction program and pioglitazone were less than usual care, while vitamin E was $3050 (95% CrI 2354, 3650). The weight reduction program dominated all other treatment options. The probability of being cost-effective in Thailand's willingness-to-pay threshold ($4546/QALY gained) was 76% for the weight reduction program, 22% for pioglitazone, 2% for usual care, and 0% for vitamin E.
CONCLUSIONS: A weight reduction program can prevent cirrhosis and HCC occurrences, and dominates all other treatment options. Pioglitazone and vitamin E demonstrated a trend towards decreasing the number of cirrhosis and HCC cases.
MATERIALS AND METHODS: International and Thai databases were searched from inception to February 2017. Clinical trials investigating effects of PM menopausal or postmenopausal women were included. Outcomes were self-reported menopausal symptoms, serum reproductive hormones, urino-genital tract function, and bone surrogates. Methodological quality was assessed by Cochrane risk-of-bias v2.0, and a 22-parameter quality score based on the CONSORT checklist for herbal medicines.
RESULTS: Eight studies (9 articles) used data from 309 menopausal patients. Five-studies demonstrated that PM was associated with climacteric scores reduced by ~50% compared to baseline. Other PM studies using limited numbers of placebo participants suggested improved vaginal and other urogenital tract symptoms. Bone alkaline phosphatase halved (suggesting lowered bone turnover). Variable serum reproductive hormone levels suggested menopausal status differed between studies. PM active ingredients and sources were not defined. Adverse event rates (mastodynia, vaginal spotting, dizziness) were similar in all groups (PM, conjugated equine estrogen, and placebos) but serum C-reactive protein doubled. These studies had design and reporting deficiencies, high risks of biases, and low quality scores.
CONCLUSIONS: The efficacy of PM on menopausal symptoms remains inconclusive because of methodological short-comings especially placebo effects inherent in self-assessment/recall questionnaires and no PM standardization. PM efficacy and safety need a fundamental re-appraisal by: (i) cohort (retro- and prospective) studies on current users to define its traditional use for rejuvenation; (ii) tightly coupling long-term efficacy to safety of well-defined PM and multiple end-points; (iii) using study design related to current understanding of menopause progression and estrogen pharmacology (iv) robust pharmacovigilance.
METHODS: Long-term costs and outcomes were projected using a validated IMS CORE Diabetes Model, version 8.5. Cohort characteristics, baseline risk factors, and costs of diabetes complications were derived from Thai data sources. Relative risk was derived from a systematic review and meta-analysis study. Costs and outcomes were discounted at 3% per annum. Incremental cost-effectiveness ratio (ICER) was presented in 2015 US Dollars (USD). A series of one-way and probabilistic sensitivity analyses were performed.
RESULTS: IDet yielded slightly greater quality-adjusted life years (QALYs) (8.921 vs 8.908), but incurred higher costs than IGlar (90,417.63 USD vs 66,674.03 USD), resulting in an ICER of ∼1.7 million USD per QALY. The findings were very sensitive to the cost of IDet. With a 34% reduction in the IDet cost, treatment with IDet would become cost-effective according to the Thai threshold of 4,434.59 USD per QALY.
CONCLUSIONS: Treatment with IDet in patients with T2DM who had uncontrolled blood glucose with oral anti-diabetic agents was not a cost-effective strategy compared with IGlar treatment in the Thai context. These findings could be generalized to other countries with a similar socioeconomics level and healthcare systems.
OBJECTIVES: To assess the comparative efficacy and safety of different types of systemic immunosuppressive treatments for moderate to severe eczema using NMA and to generate rankings of available systemic immunosuppressive treatments for eczema according to their efficacy and safety.
SEARCH METHODS: We searched the following databases up to August 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase.
SELECTION CRITERIA: All randomised controlled trials (RCTs) of systemic immunosuppressive agents for moderate to severe atopic eczema when compared against placebo or any other eligible eczema treatment.
DATA COLLECTION AND ANALYSIS: We synthesised data using pair-wise analysis and NMA to compare treatments and rank them according to their effectiveness. Effectiveness was assessed primarily by determining the proportion of participants who achieved at least 75% improvement in the Eczema Area and Severity Index (EASI75) and improvement in the Patient-Oriented Eczema Measure (POEM). Safety was evaluated primarily by considering the proportion of participants with serious adverse events (SAEs) and infection. We deemed short-term follow-up as ≤ 16 weeks and long-term follow-up as > 16 weeks. We assessed the certainty of the body of evidence from the NMA for these primary outcomes using six domains of CiNEMA grading.
MAIN RESULTS: We included a total of 74 studies, with 8177 randomised participants. Approximately 55% of participants were male, with average age of 32 years (range 2 to 84 years), although age and gender were unreported for 419 and 902 participants, respectively. Most of the included trials were placebo controlled (65%), 34% were head-to-head studies (15% assessed the effects of different doses of the same drug), and 1% were multi-armed studies with both an active comparator and a placebo. All trials included participants with moderate to severe eczema, but 62% of studies did not separate data by severity; 38% of studies assessed only severe eczema. The total duration of included trials ranged from 2 weeks to 60 months, whereas treatment duration varied from a single dose (CIM331, KPL-716) to 60 months (methotrexate (MTX)). Seventy studies were available for quantitative synthesis; this review assessed 29 immunosuppressive agents from three classes of interventions. These included (1) conventional treatments, with ciclosporin assessed most commonly; (2) small molecule treatments, including phosphodiesterase (PDE)-4 inhibitors, tyrosine kinase inhibitors, and Janus kinase (JAK) inhibitors; and (3) biological treatments, including anti-CD31 receptors, anti-interleukin (IL)-22, anti-IL-31, anti-IL-13, anti-IL-12/23p40, anti-OX40, anti-TSLP, anti-CRTH2, and anti-immunoglobulin E (IgE) monoclonal antibodies, but most commonly dupilumab. Most trials (73) assessed outcomes at a short-term duration ranging from 2 to 16 weeks, whereas 33 trials assessed long-term outcomes, with duration ranging from 5 to 60 months. All participants were from a hospital setting. Fifty-two studies declared a source of funding, and of these, pharmaceutical companies funded 88%. We rated 37 studies as high risk; 21, unclear risk, and 16, low risk of bias, with studies most commonly at high risk of attrition bias. Network meta-analysis suggests that dupilumab ranks first for effectiveness when compared with other biological treatments. Dupilumab is more effective than placebo in achieving EASI75 (risk ratio (RR) 3.04, 95% confidence interval (CI) 2.51 to 3.69) and improvement in POEM score (mean difference 7.30, 95% CI 6.61 to 8.00) at short-term follow-up (high-certainty evidence). Very low-certainty evidence means we are uncertain of the effects of dupilumab when compared with placebo, in terms of the proportion of participants who achieve EASI75 (RR 2.59, 95% CI 1.87 to 3.60) at longer-term follow-up. Low-certainty evidence indicates that tralokinumab may be more effective than placebo in achieving short-term EASI75 (RR 2.54, 95% CI 1.21 to 5.34), but there was no evidence for tralokinumab to allow us to assess short-term follow-up of POEM or long-term follow-up of EASI75. We are uncertain of the effect of ustekinumab compared with placebo in achieving EASI75 (long-term follow-up: RR 1.17, 95% CI 0.40 to 3.45; short-term follow-up: RR 0.91, 95% CI 0.28 to 2.97; both very low certainty). We found no evidence on ustekinumab for the POEM outcome. We are uncertain whether other immunosuppressive agents that targeted our key outcomes influence the achievement of short-term EASI75 compared with placebo due to low- or very low-certainty evidence. Dupilumab and ustekinumab were the only immunosuppressive agents evaluated for longer-term EASI75. Dupilumab was the only agent evaluated for improvement in POEM during short-term follow-up. Low- to moderate-certainty evidence indicates a lower proportion of participants with SAEs after treatment with QAW039 and dupilumab compared to placebo during short-term follow-up, but low- to very low-certainty evidence suggests no difference in SAEs during short-term follow-up of other immunosuppressive agents compared to placebo. Evidence for effects of immunosuppressive agents on risk of any infection during short-term follow-up and SAEs during long-term follow-up compared with placebo was of low or very low certainty but did not indicate a difference. We did not identify differences in other adverse events (AEs), but dupilumab is associated with specific AEs, including eye inflammation and eosinophilia.
AUTHORS' CONCLUSIONS: Our findings indicate that dupilumab is the most effective biological treatment for eczema. Compared to placebo, dupilumab reduces eczema signs and symptoms in the short term for people with moderate to severe atopic eczema. Short-term safety outcomes from clinical trials did not reveal new safety concerns with dupilumab. Overall, evidence for the efficacy of most other immunosuppressive treatments for moderate to severe atopic eczema is of low or very low certainty. Given the lack of data comparing conventional with newer biological treatments for the primary outcomes, there remains high uncertainty for ranking the efficacy and safety of conventional treatments such as ciclosporin and biological treatments such as dupilumab. Most studies were placebo-controlled and assessed only short-term efficacy of immunosuppressive agents. Further adequately powered head-to-head RCTs should evaluate comparative long-term efficacy and safety of available treatments for moderate to severe eczema.
Methods: We performed a literature search to determine preference-based value algorithms in the general population of a given country. We then fitted a second-order quadratic function to assess the utility function curve that links health status with health-care utilities. We ranked the countries according to the concavity and convexity properties of their utility functions and compared this ranking with that of the Hofstede index to check if there were any similarities.
Results: We identified 10 countries with an EQ-5D-5L-based value set and 7 countries with an EQ-5D-3L-based value set. Japan's degree of concavity was highest, while Germany's was lowest, based on the EQ-5D-3L and EQ-5D-5L value sets. Japan also ranked first in the Hofstede long-term orientation index, and rankings related to the degree of concavity, indicating a low time preference rate.
Conclusions: This is the first evaluation to identify and report an association between different cultural beliefs and utility values. These findings underline the necessity to take local values into consideration when designing health technology assessment systems.
OBJECTIVE: To assess the effect of a service containing self-management support delivered by community pharmacists to patients with asthma.
METHODS: A systematic search was performed in the following databases from inception to January 2017: PubMed, Embase, Cochrane Library's Central Register of Controlled Trials, CINAHL (Cumulative Index to Nursing and Allied Health Literature) Plus, International Pharmaceutical Abstracts, and PsycInfo. Original studies were selected if they met the following criteria: (a) provided by community pharmacists; (b) the intervention service included the essential components of asthma self-management; (c) included a usual care group; and (d) measured control/severity of asthma symptoms, health-related quality of life (HRQOL), or medication adherence.
RESULTS: Of the 639 articles screened, 12 studies involving 2,121 asthma patients were included. Six studies were randomized trials, and the other 6 were nonrandomized trials. Patients with asthma who received a self-management support service by community pharmacists had better symptom control/lower severity compared with those receiving usual care (standardized mean difference [SMD] = 0.46; 95% CI = 0.09-0.82) with high heterogeneity (I2=82.6%; P = 0.000). The overall improvement in HRQOL and medication adherence among patients in the asthma self-management support group was greater than for those in the usual care group with SMD of 0.23 (95% CI = 0.12-0.34) and 0.44 (95% CI = 0.27-0.61), respectively. Evidence of heterogeneity was not observed in these 2 outcomes.
CONCLUSIONS: Self-management support service provided by community pharmacists can help improve symptom control, quality of life, and medication adherence in patients with asthma.
DISCLOSURES: This study received financial support from Naresuan University's Faculty of Pharmaceutical Sciences Research Fund. Two authors, Saini and Krass, have studies that were included in this review. However, they were not involved in the processes that could bias outcomes of the present study, that is, quality assessment and meta-analysis. The remaining authors have declared no conflicts of interest.
OBJECTIVE: This study aimed to determine the effects of telemedicine on asthma control and the quality of life in adults.
METHODS: An electronic search was performed from the inception to March 2018 on the following databases: Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, EMBASE, PubMed, and Scopus. Randomized controlled trials that assessed the effects of telemedicine in adults with asthma were included in this analysis, and the outcomes of interest were levels of asthma control and quality of life. Random-effects model meta-analyses were performed.
RESULTS: A total of 22 studies (10,281 participants) were included. Each of 11 studies investigated the effects of single-telemedicine and combined-telemedicine (combinations of telemedicine approaches), and the meta-analyses showed that combined tele-case management could significantly improve asthma control compared with usual care (standardized mean difference [SMD] = 0.78; 95% confidence interval [CI]: 0.56, 1.01). Combined tele-case management and tele-consultation (SMD = 0.52 [95% CI: 0.13, 0.91]) and combined tele-consultation (SMD = 0.28 [95% CI: 0.13, 0.44]) also significantly improved asthma outcomes, but to a lesser degree. In addition, combined tele-case management (SMD = 0.59 [95% CI: 0.31, 0.88]) was the most effective telemedicine for improving quality of life, followed by combined tele-case management and tele-consultation (SMD = 0.31 [95% CI: 0.03, 0.59]), tele-case management (SMD = 0.30 [95% CI: 0.05, 0.55]), and combined tele-consultation (SMD = 0.27 [95% CI: 0.11, 0.43]), respectively.
CONCLUSIONS: Combined-telemedicine involving tele-case management or tele-consultation appear to be effective telemedicine interventions to improve asthma control and quality of life in adults. Our findings are expected to provide health care professionals with current evidence of the effects of telemedicine on asthma control and patients' quality of life.
METHODS: A retrospective database analysis at a university-affiliated hospital in Thailand was used. Diabetic patients receiving glucose-lowering medications from July 2008 to June 2011 were included. Patients were categorized into those exposed and not exposed to thiazolidinediones (TZDs). PSs were estimated by using conventional PS and CTS-PS. In the CTS-PS, PS was separately estimated for three specific calendar time periods. Patients were matched 1:1 using caliper matching. The outcomes were cardiovascular and all-cause hospitalizations. The TZD and non-TZD groups were compared with Cox proportional hazard models.
RESULTS: A total of 2165 patients were included. The average conventional PS was 0.198 (95% confidence interval [CI] 0.195-0.202), while the average PS in the CTS-PS approach was 0.212 (0.206-0.218), 0.180 (0.173-0.188), and 0.205 (0.197-0.213) for July 2008 to June 2009, July 2009 to June 2010, and July 2010 to June 2011, respectively. The average difference in PS was 0.012 (P < 0.001), -0.009 (P ≤ 0.002), and 0.000 (P = 0.950) in the three calendar time periods. The adjusted hazard ratios of the conventional PS-matched cohort were 0.97 (95% CI 0.39-2.45) and 0.97 (95% CI 0.78-1.20) for CVD-related and all-cause hospitalizations, while the adjusted hazard ratios of the CTS-PS-matched cohort were 1.11 (95% CI 0.43-2.88) and 1.12 (95% CI 0.91-1.39), respectively.
CONCLUSION: CTS-PS is different from PS estimated by using the conventional approach. CTS-PS should be considered when a pattern of medication use has changed over the study period.
METHODS: A validated computer simulation model (the IMS CORE Diabetes Model) was used to estimate the long-term projection of costs and clinical outcomes. The model was populated with published characteristics of Thai patients with type 2 diabetes. Baseline risk factors were obtained from Thai cohort studies, while relative risk reduction was derived from a meta-analysis study conducted by the Canadian Agency for Drugs and Technology in Health. Only direct costs were taken into account. Costs of diabetes management and complications were obtained from hospital databases in Thailand. Both costs and outcomes were discounted at 3 % per annum and presented in US dollars in terms of 2014 dollar value. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were also performed.
RESULTS: IGlar is associated with a slight gain in quality-adjusted life years (0.488 QALYs), an additional life expectancy (0.677 life years), and an incremental cost of THB119,543 (US$3522.19) compared with NPH insulin. The ICERs were THB244,915/QALY (US$7216.12/QALY) and THB176,525/life-year gained (LYG) (US$5201.09/LYG). The ICER was sensitive to discount rates and IGlar cost. At the acceptable willingness to pay of THB160,000/QALY (US$4714.20/QALY), the probability that IGlar was cost effective was less than 20 %.
CONCLUSIONS: Compared to treatment with NPH insulin, treatment with IGlar in type 2 diabetes patients who had uncontrolled blood glucose with oral anti-diabetic drugs did not represent good value for money at the acceptable threshold in Thailand.