The threat of serious outcome reporting bias in randomized controlled trials on acute ischemic stroke - to evidence synthesis: a meta-epidemiological study

Sep 30, 2026

Serious outcome reporting bias (ORB) in randomized controlled trials (RCTs) can distort the findings of systematic reviews and lead to inferior clinical and policy decisions. This meta-epidemiological study assesses the prevalence and potential predictors of ORB across RCTs included in acute ischemic stroke (AIS) systematic reviews and evaluates correction at the systematic-review evidence synthesis level. Results include 33 systematic reviews and 287 RCTs, with ORB suspected in 48.08% and reversal-based over/underestimation affecting efficacy and adverse reactions.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Methods

Results

Conclusions

The threat of serious outcome reporting bias in randomized controlled trials on acute ischemic stroke to evidence synthesis: a meta-epidemiological study Na Zhang1,2,3\#, Youlin Long2,3\#, Xinyao Wang2,3, Xinyi Wang3, Qiong Guo3,4, Zhengchi Li3, Liang Du2,3 1General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, China; 2Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu, China; 3Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, Chengdu, China; 4West China Medical Publishers, West China Hospital, Sichuan University, Chengdu, China Contributions: (I) Conception and design: N Zhang, Y Long, L Du, Z Li; (II) Administrative support: L Du, Z Li; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: N Zhang, Y Long, Xinyao Wang, Xinyi Wang, Q Guo; (V) Data analysis and interpretation: N Zhang, Y Long, Xinyao Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. \#These authors contributed equally to this work as co-first authors. Correspondence to: Liang Du, MD. Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, No. 37 Guoxuexiang Road, Chengdu 610041, China; Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, No. 37 Guoxuexiang Road, Chengdu 610041, China. Email: [duliang@scu.edu.cn](duliang@scu.edu.cn); Zhengchi Li, MD. Innovation Institute for Integration of Medicine and Engineering, West China Hospital, Sichuan University, No. 37 Guoxuexiang Road, Chengdu 610041, China. Email: [603172078@qq.com](603172078@qq.com). Background: Stroke is the second-leading cause of death and the third-leading cause of disability, with acute ischemic stroke (AIS) being the most serious subtype. Systematic reviews of randomized controlled trials (RCTs) for AIS play a crucial role in formulating clinical guidelines and health policies. However, potential outcome reporting bias (ORB) in RCTs may skew the analytical results of systematic reviews and ultimately lead to suboptimal medical decisions. This study was conducted to investigate the prevalence and possible influencing factors of ORB in RCTs included in systematic reviews of AIS and to correct ORB at the level of systematic reviews. Methods: A systematic literature search was conducted across three databases to retrieve subject headingsand text terms related to AIS, RCTs, and systematic reviews, with the aim of identifying AIS-related systematic reviews published in 2022. ORB in trials was employed to assess the risk of ORB in RCTs, and multivariate logistic regression was used to identify the possible ORB-related factors, including registration, country, quality of journal, funding, sample size, and type of control. The correcting for ORB model was used to correct ORB evidence synthesis results. Results: A total of 33 systematic reviews and 287 nonduplicate RCTs were included in this study. ORB was suspected in 138 (48.08%) of these RCTs. Statistically significant outcomes were more likely to be reported than were nonsignificant ones [relative risk (RR) =3.18; 95% confidence interval (CI): 2.77–3.64] . The potential factors associated with ORB were unregistered status [odds ratio (OR) =4.87; 95% CI: 1.93–12.28] and sample sizes smaller than 100 (OR =2.57; 95% CI: 1.30–5.10) . The corrected results indicated that 31.58% of the therapeutic effects were overestimated due to reversal and that 16.67% of adverse reactions were underestimated due to reversal. Among outcomes without reversal, 56.52% of the effect sizes and 60.87% of the P values exceeded the clinically acceptable range. Conclusions: The presence of ORB within the field of AIS poses a serious threat to the reliability of evidence synthesized in systematic reviews. In the future, healthcare practitioners and decision-makers should

FAQs

What is the main objective of this study on acute ischemic stroke RCTs?

To determine how common outcome reporting bias (ORB) is in RCTs included in AIS systematic reviews, identify influencing factors, and apply correction at the evidence-synthesis level.

How was ORB assessed and what factors were examined?

ORB in trials was used to evaluate the risk of ORB in RCTs, and multivariate logistic regression tested candidate factors including registration, country, journal quality, funding, sample size, and control type.

Which factors were associated with a higher likelihood of ORB?

Unregistered status and smaller sample sizes (under 100) were associated with ORB, with statistically supported odds ratios.

Sep 30, 2026

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