Design, conduct, and analysis of safety among drug-related systematic reviews: A cross-sectional survey

Article type
Authors
Li L1, Deng K1, Busse J2, Zhou X3, Xu C1, Liu Z1, Ren Y1, Zou K1, Sun X1
1Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University
2Department of Health Research Methods, Evidence and Impact, McMaster University
3Evidence-Based Medicine Research Center, School of Basic Science, Jiangxi University of Traditional Chinese Medicine
Abstract
Background: Well planned and rigorously conducted systematic reviews and meta-analyses provide the best evidence to inform drug safety, however, no surveys comprehensively examined the methodological issues regarding drug safety.

Objectives: To examine the design, conduct, and analysis of systematic reviews assessing drug safety through a cross-sectional survey.

Methods: We searched PubMed to identity systematic reviews published in the Cochrane Database of Systematic Reviews and Core Clinical Journals indexed in 2015, and randomly sampled systematic reviews assessing drug effects at a 1:1 ratio of Cochrane and non-Cochrane reviews. Teams of two investigators independently conducted study screening and collected data, using pre-specified, standardized questionnaires. In addition to general information, we collected details about the planning and analyses of safety outcomes.

Results: We included 120 systematic reviews, including 60 Cochrane and 60 non-Cochrane ones. Most reviews searched PubMed/MEDLINE (n=117, 97.5%), EMBASE (n=105, 87.5%) and Cochrane CENTRAL (n=110, 91.7%), and conducted independent and duplicate study selection (n=98, 81.7%), risk of bias assessment (n=105, 87.5%), and data collection (n=105, 87.5%). Only nine (7.5%) reviews clearly defined safety outcomes, and seven (5.8%) defined a primary safety outcome; none stated whether the primary safety outcome was pre-defined. Among the 80 reviews that pooled the primary dichotomous safety data across studies, less than half (41%; n=33) conducted subgroup analysis to explore for sources of heterogeneity or reported a GRADE assessment for the overall quality of evidence. Cochrane reviews were more likely to provide a study protocol (100% vs. 23.3%, P