Ana Penedones

A systematic review of observational studies evaluating costs of adverse drug reactions

Introduction The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient’s health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs. Objective To identify and characterize the best available evidence on ADE-associated costs. Methods MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in “ambulatory”, “hospital”, or both. Costs were classified as “direct” and “indirect”. Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated. Results Twenty-nine (94%) longitudinal observational studies and two (7%) cross-sectional studies were included. Twenty-three (74%) studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%). Twenty (65%) studies evaluated any therapeutic group. Twenty (65%) studies estimated costs of ADEs leading to or prolonging hospitalization. The “direct costs” were evaluated in all studies, whereas only two (7%) also estimated the “indirect costs”. The “direct costs” in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7,192.36. Discussion Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings, validated methods to measure ADE-associated costs need future research efforts.

A systematic review and meta-analysis of the association between systemic fluoroquinolones and retinal detachment

Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta‐analysis aims to investigate such association, in the light of the best scientific evidence available.

Risk of Ophthalmic Adverse Effects in Patients Treated with MEK Inhibitors: A Systematic Review and Meta-Analysis

Objectives: This meta-analysis aims to evaluate the risk of ophthalmic adverse effects associated with MEK inhibitors. Methods: A literature search was conducted in PubMed and the Cochrane Library to identify randomized clinical trials (RCTs) which have been designed to evaluate the efficacy and safety of MEK inhibitors. Overall risk of ophthalmic adverse effects, chorioretinopathy, retinal detachment, blurred vision, uveitis, and eye haemorrhage were the assessed outcomes. Peto odds ratios (ORs) with their 95% confidence intervals (CIs) were pooled. Between-study heterogeneity was assessed using I2 statistics. Results: Thirteen RCTs were included in this meta-analysis. Overall, MEK inhibitors were associated with an increased risk of ophthalmic adverse effects (OR 2.24; 95% CI 1.75-2.87; p < 0.0001; I2 = 86.5%). An increased risk was also estimated for chorioretinopathy (OR 5.44; 95% CI 2.89-10.23; p < 0.0001; I2 = 0%), retinal detachment (OR 6.54; 95% CI 3.28-13.03; p < 0.0001; I2 = 0%), and blurred vision (OR 2.30; 95% CI 1.50-3.54; p < 0.0001; I2 = 60.1%), but not for uveitis (OR 0.99; 95% CI 0.14-7.03; p = 0.991; I2 = 2.9%) or eye haemorrhage (OR 0.72; 95% CI 0.04-12.39; p = 0.824; I2 = 29.8%). Conclusions: Treatment with MEK inhibitors seems to increase the risk of ophthalmic adverse effects. A need for monitoring the safety of this class of drugs exists. Regulators, clinicians, and other health care professionals must, together, be involved in this process.

Methodologic Assessment of the Systematic Reviews of Ophthalmic Adverse Drug Reactions Published in Ophthalmology Journals: A Systematic Review

Purpose: This systematic review aims to characterize and review the methodology of the systematic reviews reporting ophthalmic adverse drug reactions. Methods: This systematic review followed the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-analyses guide. MEDLINE and EMBASE databases were searched, by all Ophthalmology journals. All systematic reviews reporting ophthalmic adverse drug reactions in the last decade were included. Data on methodology were extracted. Methodological quality was assessed through A MeaSurement Tool to Assess systematic Reviews 2 scale. Descriptive analysis was performed. Results: Twenty-one systematic reviews were identified. Almost 60% of the systematic reviews reported non-ophthalmic drugs. Nine (43%) systematic reviews did not follow any recommendation. A search filter was not applied in 48% systematic reviews. Observational data was the source of information most included. The methodological quality was assessed in 57% systematic reviews. A meta-analysis was performed in 57% systematic reviews. The protocol’s elaboration, the explanation of the sources of information and the list of excluded articles were the domains less performed in the systematic reviews. Conclusion: The systematic reviews reporting ophthalmic adverse drug reactions diverged in some methodological aspects. Such an issue deserves further investigation, since discrepancies may lead to biased conclusions and, consequently, impact clinical and/or regulatory decisions.