Comparative effectiveness and safety of direct-acting oral anticoagulants (DOACS) for the reduction of recurrent venous thromboembolism in cancer patients: A protocol for systematic review and network meta-analysis using a generalized pairwise modeling methodology.

BACKGROUND: There has been a significant improvement in both our understanding and therapeutic choices available to clinicians for the management of cancer associated thrombosis (CAT). Even with the recent publication of a systematic review and landmark trials demonstrating the non-inferiority of DOACS-based anticoagulation strategy compared to the standard of care in patients with CAT, there is unresolved uncertainty regarding the exact hierarchy of risks and effectiveness of various DOAC analogues in these cohorts of patients. METHOD: We will carry out a network meta-analyses, utilizing a novel generalized pairwise methodology to generate direct and indirect comparisons between the various DOAC analogues. We will search the following databases for studies that satisfies pre-specified inclusions criteria; these include PubMed, EMBASE, Cochrane library, Clinicaltrials.gov, conference abstracts among other sources. The primary efficacy and safety outcomes are recurrent VTE and major hemorrhagic events, respectively. Two reviewers will Search the databases independently with the view to identify studies that meet eligibility criteria. The methodological quality of the included studies will be determined using a recently validated risk of bias assessment tool. RESULTS: We expect that the result of this review will ascertain the hierarchy of risks and effectiveness of various DOAC analogues in patients with CAT. CONCLUSION: Results of this review will assist in informed decisions making regarding therapeutic guidelines of DOAC in CAT.

An investigation into the avoidability of adverse drug reactions using the LAAT and modified Hallas tools.

An adverse drug reactions avoidability tool called the Liverpool ADR avoidability assessment tool (LAAT) was recently developed (for research purposes), and subsequently validated with mixed interrater reliability (IRR). We investigated the comparative IRR of this tool in an inpatient cohort to ascertain its practical application in this setting.The patient population was comprised of 44 ADR drug pairs drawn from an observational prospective cohort of patents with ADR attending a Weill Cornell Medicine-affiliated tertiary medical Centre in Doha Qatar (Hamad General Hospital). Using the LAAT, and modified Hallas tools, 4 independent raters (2 Clinical Pharmacologists, and 2 General Physicians) assessed and scored the 44 ADR-drug pairs. Agreement proportions between the rating pairs were evaluated as well individual/overall kappa statistics and intraclass correlation coefficients. We evaluated the weight of each of the 7 questions on the LAAT tool to ascertain its determinative role.Across 44 ADR-drug pairs, the overall median Fleiss kappa using the LAAT, and modified Hallas tools were 0.67 (interquartile range (IQR) 0.55, 0.76), 0.36 (IQR, 0.23-0.71) respectively. The overall percentage pairwise agreement with the LAAT and modified Hallas tools were 78.5%, and 62.2% respectively. Exact pairwise agreement occurred in 37 out of 44 (range 0.71-1), and 27 of 44 (0.53-0.77) ADR-drug pairs using the LAAT and modified Hallas tools respectively. Using the LAAT tool, the overall intraclass correlation coefficient was 0.68 (CI 0.55, 0.79), and 0.37 (CI 0.22, 0.53) with the modified Hallas tool.We report a higher proportion of "possible" and "definite" avoidability outcomes of adverse drug reactions compared with the modified Hallas, or that reported by developers of the LAAT tool. Although initially developed for research purposes, our report has suggested for the first time a potential applicability of this tool in clinical environment as well.

Efficacy of sodium-glucose co-transporter 2 inhibitors in patients with type II diabetes: A protocol for systematic review of randomised controlled clinical trials utilising a generalised pairwise modelling methodology.

BACKGROUND: Recent systematic reviews have evaluated the efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2) inhibitors (SGLT2I) in improving glycaemic control and mortality in patients with type II diabetes mellitus. None have incorporated the most recent study or utilized the generalized pairwise modeling methodology network meta-analysis (NMA), as well as a novel bias risk assessment approach. METHODS: We propose to conduct literature search of all randomized controlled clinical trials published in English language evaluating the efficacy of (SGLT2I) versus placebo or usual standard of care from the inception of following databases to September 30, 2019: Controlled Clinical Trials Cochrane Controlled Trials Register (CCTR), Cochrane Database of Systematic Reviews (CDSR), EMBASE, Database of Abstracts of Reviews of Effectiveness (DARE), PubMed. Two reviewers will independently search these databases to identify studies that satisfy pre-specified eligibility criteria. Study bias risk assessment amongst other methodology quality evaluation of the studies will be carried out using a novel risk bias assessment tool. RESULTS: We anticipate that the result of this review will provide additional insight into the ranking of the efficacy of various (SGLT2I) in type II diabetic patients especially as it relates to mortality, glycemic control, and body weight reduction. CONCLUSION: The result of this review will be useful informing therapeutic decisions by policy makers with regards to commissioning of diabetic care.Prospero registration number: CRD42019139708.