Cost-effectiveness Evaluations Among the Direct Oral Anticoagulants for the Prevention and Treatment of Venous Thromboembolism: Systematic Review

Venous thromboembolism (VTE) is associated with high recurrence, mortality, and cost burden. Direct oral anticoagulants (DOACs) are currently used for VTE treatment, and they offer more benefits over warfarin, despite being more expensive. There is no consensus on the most cost-effective DOAC agent, especially in VTE. This systematic review aims to summarize the comparative cost-effectiveness studies and their impact among DOACs in the treatment of VTE. Literature systematic review of PubMed, Embase, and EconLit was conducted in February 2018 to identify all cost-effectiveness studies of DOAC for the treatment and prevention of VTE. Two independent investigators systematically collected search results and assessed the quality of the studies. The search identified 7 articles, all of which had dabigatran and rivaroxaban as comparators, 6 of which also included apixaban, and 2 of which also had edoxaban. Results of 3 articles concluded that apixaban is a dominant strategy compared to other DOACs in terms of Incremental Cost-Effectiveness Ratio (ICER) in the treatment and prevention of recurrent VTE. One article compared rivaroxaban and dabigatran, with the latter dominating rivaroxaban in terms of ICER. Compared to other DOACs, 2 articles reported apixaban being associated with highest annual total medical cost avoidance of US$4244 and US$4440 per patient-year (ppy), respectively. One article reported that apixaban had the highest annual total medical cost differences of US$918 ppy compared to other DOACs. This systematic review demonstrates that apixaban is considered a cost-effective strategy for VTE treatment and prevention of recurrent VTE.This report was made possible by Qatar University grant # (QUST-1-CPH-2019-3). The statements made herein are solely the responsibility of the authors.Scopu

Clinical and Pharmacokinetic Outcomes of Peak–Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial

Background Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration–time curve to minimum inhibitory concentration cure breakpoints (AUC24/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date. Objectives We aimed to compare clinical and pharmacokinetic outcomes between peak–trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC24/MIC and cure rates. Methods A multicentered pragmatic parallel-group RCT was conducted in Hamad Medical Corporation hospitals in Qatar. Adult non-dialysis patients initiated on vancomycin were randomized to peak–trough-based or trough-only-based vancomycin TDM. Primary endpoints included vancomycin AUC24/MIC ratio breakpoint for cure and clinical effectiveness (therapeutic cure vs therapeutic failure). Descriptive, inferential, and classification and regression tree (CART) statistical analyses were applied. NONMEM.v.7.3 was used to conduct population pharmacokinetic analyses and AUC24 calculations. Results Sixty-five patients were enrolled [trough-only-based-TDM (n = 35) and peak–trough-based-TDM (n = 30)]. Peak–trough-based TDM was significantly associated with higher therapeutic cure rates compared to trough-only-based TDM [76.7% vs 48.6%; p value = 0.02]. No statistically significant differences were observed for all-cause mortality, neutropenia, or nephrotoxicity between the two groups. Compared to trough-only-based TDM, peak–trough-based TDM was associated with less vancomycin total daily doses by 12.05 mg/kg/day (p value = 0.027). CART identified creatinine clearance (CLCR), AUC24/MIC, and TDM approach as significant determinants of therapeutic outcomes. All patients [n = 19,100%] with CLCR ≤ 7.85 L/h, AUC24/MIC ≤ 1256, who received peak–trough-based TDM achieved therapeutic cure. AUC24/MIC > 565 was identified to be correlated with cure in trough-only-based TDM recipients [n = 11,84.6%]. No minimum AUC24/MIC breakpoint was detected by CART in the peak–trough-based group. Conclusion Maintenance of target vancomycin exposures and implementation of peak–trough-based vancomycin TDM may improve vancomycin-associated cure rates. Larger scale RCTs are warranted to confirm these findings.Open Access funding provided by the Qatar National Library. We would like to thank Dr. Hani Abdelaziz and Dr. Eman El-Mekaty for their efforts and contributions in the design and implementation of this study. We would also like to thank all staff at HMC who helped to conduct the study

Pharmacoeconomics Evaluations of Oral Anticancer Agents: Systematic Review of Characteristics, Methodological Trends, and Reporting Quality

Objectives: To review literature characteristics, describe methodological trends, and assess the reporting quality of the economic evaluations of oral anticancer drugs (OACDs). Methods: The review included comparative economic evaluations of OACDs. The search was conducted via PubMed, Embase, EconLit, and Economic Evaluation Database, and studies till December 2017 were included. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, literature inclusion and data extraction were performed in duplicate by separate investigators. Outcome measures were literature characteristics, gaps and methodological trends, and reporting quality using the Consolidated Health Economic Evaluation Reporting Standards checklist. Data were summarized on the basis of methodological themes of interest. Descriptive statistics and tabulations were used for result presentation. Results: Out of 241 found articles, 21 were included. There is a recent increasing interest in the economics of OACDs, whereby the cost per quality-adjusted life-year, via cost-utility analysis, is the most used for decision making. Most of the studies were from the payer perspective, and the primary sources of data were clinical trials, expert panels, and medical charts. The dominance status (higher effect, lower cost) was a commonly reported outcome. Decision-analytic modeling was used in most of the studies, mostly including Markov modeling. Studies were highly heterogeneous in methodological aspects, and the included studies did not meet most of the reporting quality criteria. Conclusions: High heterogeneity in methods in studies may limit the robustness and transferability of results, potentially misleading decision makers toward wrong decisions on OACDs. The transferability and generalizability of results are further limited by a" less than ideal " adherence to current reporting standards.Source of financial support: No funding was received for the purpose of this study

Surfactant therapy for meconium aspiration syndrome in neonates: A systematic overview of systematic reviews and recent clinical trials

Aim: To conduct a systematic overview of systematic reviews (SRs) and randomized clinical trials (RCTs) on surfactant therapy in neonatal meconium aspiration syndrome. Methods: We searched EMBASE, PROQUEST and PubMed to summarize the different effects of surfactant lung lavage and bolus surfactant therapies in neonates with meconium aspiration syndrome. Results: With a total of 1377 patients, three SRs and two RCTs were included in analysis. Surfactant effectiveness was concluded by low-quality SRs, with high risk of bias, which was contradicted by high-quality SRs, with low risk of bias. In SRs, the surfactant lung lavage reduced mortality, need for extracorporeal membrane oxygenation and hospitalization, while the bolus surfactant did not. In recent high-quality RCTs, however, the two modalities did not significantly differ. Conclusion: The evidence on surfactant effectiveness and its method of administration is sparse and inconsistent.This research was funded by a Qatar University grant number: QUST-1-CPH-2019-15.Scopu

Evaluations of Morphine and Fentanyl for Mechanically Ventilated Patients With Respiratory Disorders in Intensive Care: A Systematic Review of Methodological Trends and Reporting Quality

Background: Mechanically ventilated patients with respiratory disorders may require sedatives, such as opioids. Objectives: To define methodological trends, gaps, and the reporting quality of the comparative clinical and economic evaluations of fentanyl and morphine in ventilated patients in the intensive care unit. Methods: We conducted a literature review of the MEDLINE, Embase, OVID, ScienceDirect, Springer Link, and EconLit databases, comparing studies in the management of ventilated patients with respiratory disorders in the intensive care unit using either fentanyl or morphine, or both. We assessed the methodological aspects of the literature characteristics and trends of, for example, modeling, data sources, cost calculation, and data analysis, appraising the quality of reporting via the CONsolidated Standards Of Reporting Trials, STrengthening the Reporting of OBservational studies in Epidemiology, and the Consolidated Health Economic Evaluation Reporting Standards checklists. Results: Among 1327 articles, 33 (comprising 22 in adults, 8 in neonates, and 3 in pediatrics) met the inclusion criteria. No head-to-head morphine versus fentanyl evaluations explicitly confined to subjects with respiratory conditions were undertaken. Studies relied on various scales to measure the sedation level as a primary study outcome, limiting the comparability of study conclusions. Seven articles of adults were identified to be economic studies from the hospital perspective. On the basis of different endpoints, the same sedation regimen performed differently in various studies. None of the randomized controlled trials, observational cohorts, or pharmacoeconomics studies met most of the assessed reporting quality criteria. Conclusions: Our review identified poor reporting quality and high heterogeneity of methods used, potentially limiting the degree to which studies could be interpreted, decisions could be influenced, and findings could be generalized.Scopu

Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting

Purpose: Morphine and fentanyl opioids are common analgesic agents for consideration in the neonatal intensive care unit (NICU) for neonates with respiratory distress syndrome (RDS) and undergoing mechanical ventilation (MV). The aim of this study was to evaluate the clinical and economic impact of morphine versus fentanyl in neonates with RDS undergoing MV. Methods: Retrospective cost-effectiveness analysis of critically ill neonates with RDS receiving standard doses of morphine versus fentanyl at Women's Wellness and Research Center, Qatar. Clinical data of neonates were extracted from medical records of patients from 2014 to 2016. A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration. Primary end points were successful pain relief rate based on the Premature Infant Pain Profile scale and overall direct medical cost of therapy. Study population of 126 neonates was used to achieve results with 80% power and 0.05 significance. Sensitivity analysis was conducted to enhance robustness of conclusions against input uncertainties and to increase generalizability of results. Findings: Morphine achieved a success of 68% versus 43% with fentanyl (risk ratio = 1.72; 95% CI, 1.16 2.56; P = 0.0075). Morphine was associated with a minimal incremental cost-effectiveness ratio of USD 135 per additional case of successful pain relief over fentanyl. Higher morphine cost was reported in 2% of cases. Sensitivity analysis found model insensitivity to input uncertainties except NICU stay and cost of MV. Implications: This is the first cost-effectiveness evaluation of morphine versus fentanyl in the NICU. Morphine significantly improved the relieve of pain over fentanyl. It had 98% probability of dominance over fentanyl. Results in this study support the use of morphine over fentanyl as first-line monotherapy with MV in NICU settings.Qatar UniversityScopu