Instruments assessing risk of bias of randomized trials frequently included items that are not addressing risk of bias issues.

OBJECTIVES: To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias. STUDY DESIGN AND SETTING: We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two reviewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above. RESULTS: Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items. CONCLUSION: Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias.

Use of antioxidants supplementation on developmental outcomes in children with Down syndrome-A systematic review and meta-analyses.

BACKGROUND: The background of this study is to evaluate the published literature on the use of antioxidants in improving developmental outcomes in children with DS. METHODS: The systematic review included interventional studies (randomized controlled trials [RCTs] and quasi-RCTs [q-RCTs]) of children aged 0 to 18 years diagnosed with DS who received antioxidants to improve developmental outcomes. Studies were excluded if they were interventional studies with non-random allocation or lack of control group or non-interventional studies including observational studies, systematic and narrative review articles, editorials and commentaries. Studies were also excluded if data from participants with DS were included as part of a larger group of participants (e.g., children with intellectual disability) and the data could not be separated for subgroup analysis, or if outcomes did not assess developmental domains (e.g., reported biochemical markers only). The review included children with other conditions associated with developmental disability, only when data for children with DS were separately reported. RESULTS: Eleven RCTs and q-RCTs fulfilled the eligibility criteria with 683 participants with Down syndrome ranging in age from newborns to 17 years. Nine studies did not show any statistically significant clinical benefit of using antioxidants. Three studies were included in a meta-analysis comparing changes in the effect sizes (post and pre-intervention) in Global Developmental Quotient (GDQ) between the intervention and control groups. CONCLUSION: This review concludes that it is likely that the results are valid and suggest that the use of Antioxidant has no improvement in GDQ for children with DS. It is also unclear if any benefit exists for other developmental domains.