Effects of Non-statin Lipid-Modifying Agents on Cardiovascular Morbidity and Mortality Among Statin-Treated Patients: A Systematic Review and Network Meta-Analysis

Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients.Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes.Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72–0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65–0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75–0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST.Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients

Does the use of efficacy or effectiveness evidence in cost-effectiveness analysis matter?

Objective: To test the association of clinical evidence type, efficacy-based or effectiveness-based (“E”), versus whether or not asthma interventions' cost-effectiveness findings are favorable. Data sources: We conducted a systematic review of PubMed, EMBASE, Tufts CEA registry, Cochrane CENTRAL, and the UK National Health Services Economic Evaluation Database from 2009 to 2014. Study Selection: All cost-effectiveness studies evaluating asthma medication(s) were included. Clinical evidence type, “E,” was classified as efficacy-based if the evidence was from an explanatory randomized controlled trial(s) or meta-analysis, while evidence from pragmatic trial(s) or observational study(s) was classified as effectiveness-based. We defined three times the World Health Organization cost-effectiveness willingness-to-pay (WTP) threshold or less as a favorable cost-effectiveness finding. Logistic regression tested the likelihood of favorable versus unfavorable cost-effectiveness findings against the type of “E.” Results and conclusions: 25 cost-effectiveness studies were included. Ten (40.0%) studies were effectiveness-based, yet 15 (60.0%) studies were efficacy-based. Of 17 studies using endpoints that could be compared to WTP threshold, 7 out of 8 (87.5%) effectiveness-based studies yielded favorable cost-effectiveness results, whereas 4 out of 9 (44.4%) efficacy-based studies yielded favorable cost-effectiveness results. The adjusted odds ratio was 15.12 (95% confidence interval; 0.59 to 388.75) for effectiveness-based versus efficacy-based achieving favorable cost-effectiveness findings. More asthma cost-effectiveness studies used efficacy-based evidence. Studies using effectiveness-based evidence trended toward being more likely to disseminate favorable cost-effective findings than those using efficacy. Health policy decision makers should pay attention to the type of clinical evidence used in cost-effectiveness studies for accurate interpretation and application

A cost-effectiveness study of intravenous immunoglobulin in childhood idiopathic thrombocytopenia purpura patients with life-threatening bleeding

Background: Although the international guideline recommends intravenous immunoglobulin (IVIG) as the first-line treatment for childhood idiopathic thrombocytopenia purpura (ITP) with life-threatening bleeding, ITP patients may not be able to access IVIG because of the limitation in health benefit packages especially in developing countries. There remains an important policy question as to whether IVIG used as a first-line treatment is worth the money spent. Thus, the objective of this study was to perform a cost-effectiveness analysis of adding IVIG to the standard treatment of platelet transfusion and corticosteroids, for the treatment of childhood ITP with life-threatening bleeding in the context of Thailand. Methods: A cost-effectiveness analysis using a hybrid model consisting of a decision tree and Markov models was conducted with a societal perspective. The effectiveness and utility parameters were determined by systematic reviews, while costs and mortality parameters were determined using a retrospective electronic hospital database analysis. All costs were presented in 2012 US$. The discount rate of 3$3,172 per quality-adjusted life-year gained ($/QALY) for the addition of IVIG versus standard treatment alone. The probability of response to corticosteroids was the most influential parameter on ICER. According to the willingness-to-pay of Thailand, of approximately$3,861/QALY, the probability of IVIG being cost effective was 33 %. Conclusions: The addition of IVIG to standard treatment in the treatment of childhood ITP with life-threatening bleeding is possibly a cost-effective intervention in Thailand. However, our findings were highly sensitive. Policy makers may consider our findings as part of the information for their decision making

The Association of Pre-operative Serum Albumin Levels and Post-operative In-Hospital Death in Patients Undergoing Gastrointestinal Surgeries in Thailand: A Retrospective Cohort Study

Abstract Background Pre-operative hypoalbuminemia is known to predict negative outcomes for patients undergoing major surgeries. However, various cut-off points for starting exogenous albumin have been recommended. Objective This study investigated the association between pre-operative severe hypoalbuminemia, in-hospital death, and length of hospital stay in patients undergoing gastrointestinal surgery. Methods A retrospective cohort study using a database analysis was undertaken on hospitalized patients who underwent major gastrointestinal surgery. The pre-operative serum albumin level was classified into three groups: severe hypoalbuminemia (< 2.0 mg/dL) and non-severe hypoalbuminemia (≥ 2.0–3.4 g/dL) and normal level (3.5–5.5 g/dL). To compare between different cut-offs, a sensitivity analysis using another albumin level classification as severe hypoalbuminemia (< 2.5 mg/dL) and non-severe hypoalbuminemia (≥ 2.5–3.4 g/dL) and normal level (3.5–5.5 g/dL) was applied. The primary outcome was post-operative in-hospital death. Propensity-score adjusted regression analyses were applied. Results A total of 670 patients were included. Their average age was 57.4 ± 16.3 years, and 56.1% were men. Only 59 patients (8.8%) had severe hypoalbuminemia. Overall, a total of 93 in-hospital deaths (13.9%) occurred among all included patients, but there were 24/59 (40.7%) deaths among patients with severe hypoalbuminemia, 59/302 (19.5%) deaths among patients with non-severe hypoalbuminemia, and 10/309 (3.2%) deaths among patients with normal albumin level. The adjusted odds ratio for post-operative in-hospital death comparing patients with severe hypoalbuminemia and patients with normal albumin level was 8.11 (3.31–19.87; p < 0.001), while the odds ratio for in-hospital death comparing patients with non-severe and patients with normal albumin level was 3.89 (1.87–8.10; p < 0.001). A sensitivity analysis showed similar findings, the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as < 2.5 g/dL) was 7.44 (3.38–16.36; p < 0.001), while the odds ratio for in-hospital death for severe hypoalbuminemia (cut-off as 2.5–3.4 g/dL) was 3.02 (1.40–6.52; p = 0.005). Conclusions Severe pre-operative hypoalbuminemia in patients undergoing gastrointestinal surgery was associated with an increased risk of in-hospital mortality. The risk of death for patients with severe hypoalbuminemia was relatively similar when using different cut-offs such as < 2.0 and <2.5 g/dL

Cultural beliefs, utility values, and health technology assessment

Abstract Background Health-care utilities differ considerably from country to country. Our objective was to examine the association of cultural values based on Hofstede’s cultural dimensions’ theory with utility values that were identified using the time trade off method. 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

Systematic review and network meta-analysis in health technology assessment

Conducting systematic review and meta-analysis (SR/MA) is a standard process for establishing evidences for health technology assessment. Quality assessment of studies included in SR/MA and SR/MA studies should be considered. This article provides recommendations on tools used for assessing the quality of studies included in each SR/MA and the quality of SR/MA. For assessing the quality of randomized controlled trial, we recommend a tool called "Risk of Bias", which focuses on random generation, allocation concealment, blinding and outcome reporting. For assessing the quality of observational study, the Newcastle Ottawa Scale (NOS) is recommended. The NOS consists of three different dimensionsselection, comparability, and outcomes or exposure. Another tool which is recommended is the Down and Black scale. It focuses on the quality of reporting, validity, bias and confounding, and power of study. For assessing the quality of SR/MA, we recommend to use a checklist developed by Klassen et al, covering well-defined question, inclusion criteria, comprehensiveness, quality of included studies, reproducibility, and external validity. This article also provides a fundamental of network metaanalysis that should be considered where no direct evidence exists or when there is a need to compare multiple interventions at the same time

Quality of reporting of randomised controlled trials of herbal interventions in ASEAN plus six countries: a systematic review

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Interpreting Pharmacoeconomic Findings

Important questions are \u27Is the drug worth paying for?\u27 and \u27Is the drug affordable within limited budgets?\u27 To answer these questions, decision-makers need to assess the clinical benefits and costs of newer and existing drugs. It is obvious that clinical benefits and costs of drugs should be assessed in an organized way rather than using an informal assessment, such as \u27educated guess\u27 or \u27what we did last time.\u27 Pharmacoeconomics provides systematic approaches to assess the clinical benefit and cost of drugs in a comparative manner.https://digitalcommons.chapman.edu/pharmacy_books/1022/thumbnail.jp

Economic Evaluation of Direct Oral Anticoagulants Compared to Warfarin for Venous Thromboembolism in Thailand: A Cost-Utility Analysis

Background: Direct oral anticoagulants (DOACs) have been used for venous thromboembolism (VTE) in Thailand. However, they have not been listed in the National List of Essential Medicines (NLEM). A cost-effectiveness analysis is needed to aid policymakers in deciding whether DOACs should be listed in the NLEM. This study aimed to assess the cost-effectiveness of DOACs for patients with VTE in Thailand. Methods: A cohort-based state transition model was constructed from a societal perspective with a lifetime horizon. All available DOACs, including apixaban, rivaroxaban, edoxaban, and dabigatran, were compared with warfarin. A 6-month cycle length was used to capture all costs and health outcomes. The model consisted of nine health states, including VTE on treatment, VTE off treatment, recurrent VTE, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial bleeding, post-intracranial bleeding, chronic thromboembolic pulmonary hypertension, and death. All inputs were based on a comprehensive literature review. The model outcomes included total cost and quality-adjusted life-years (QALYs) with a 3% annual discount rate. A fully incremental cost-effectiveness analysis and the incremental cost-effectiveness ratio (ICER) per QALY gained were calculated at a willingness-to-pay (WTP) of THB 160,000/QALY ($5003). The robustness of the findings was assessed using deterministic and probabilistic sensitivity analyses. Results: All DOACs were associated with a decreased risk of VTE recurrence and intracranial hemorrhage. In the base-case analysis, apixaban could increase 0.16 QALYs compared with warfarin. An ICER for apixaban was 269,809 Thai baht (THB)/QALY ($8437/QALY). Rivaroxaban had a better QALY than warfarin at 0.09 QALYs with an ICER of 757,363 THB/QALY ($23,682/QALY). Edoxaban and dabigatran could also increase by 0.10 QALYs with an ICER of 709,945 THB ($22,200) and 707,145 THB ($22,122)/QALY, respectively. Our probabilistic sensitivity analyses indicated that warfarin had a 99.8% possibility of being cost-effective, while apixaban had a 0.2% possibility of being cost-effective at the current WTP. Other DOACs had no possibility of being cost-effective. Conclusions: All DOACs were not cost-effective for VTE treatment at the current WTP in Thailand. Apixaban is likely to be the best option among DOACs