Structured tools for assessing quality and risk of bias in Mendelian randomization studies: an updated systematic review
Clinical Snapshot
PICO Framework
| P — Population | Mendelian randomization studies and their quality assessment tools |
| I — Intervention | Structured quality and bias assessment tools for MR studies |
| C — Comparator | Previous systematic review findings (studies up to July 2021) |
| O — Outcomes | Number, characteristics, and comprehensiveness of available MR quality assessment tools |
Bottom Line
This systematic review update identifies a rapid expansion in Mendelian randomization quality assessment tools, with 15 new instruments developed since 2021. While this growth reflects the field's maturation, substantial heterogeneity in tool structure and content creates challenges for standardized quality evaluation. The review highlights persistent gaps in assessing linkage disequilibrium, missing data, and dynastic effects. For Australian clinicians and researchers, this work underscores the need for careful tool selection when evaluating MR evidence for clinical decision-making. The lack of standardization means systematic reviews of MR studies may reach different quality conclusions depending on which assessment tool is used. Priority should be given to developing consensus-based, validated quality assessment frameworks to ensure reliable evaluation of MR evidence informing clinical practice.
Key Findings
Effect Size: Total of 29 tools identified (19 providing structured evaluation)
Primary Outcome: Identification of 15 additional MR quality assessment tools since 2021
Nnt Or Sensitivity: 12 of 19 evaluation tools were newly identified in this update
Confidence Interval: Not applicable for this methodological review
Clinical Application
Tools are available but lack of standardization creates implementation challenges Highly relevant to Australian genetic epidemiology research groups and NHMRC-funded MR studies; supports evidence-based medicine initiatives Researchers conducting Mendelian randomization studies, systematic reviewers evaluating MR evidence, journal editors and peer reviewers
Abstract
BACKGROUND: The growing use of Mendelian randomization (MR) has heightened the need for rigorous quality and bias assessment tools. A previous systematic review included studies published up to July 2021 identified 14 structured instruments for conducting, evaluating, and reporting MR studies. However, methodological developments have accelerated in the years since. METHODS: We updated the previous systematic review to include tools published between July 2021 and January 2025, applying the same search strategy and eligibility criteria. Two reviewers independently screened articles, extracted data, and mapped tool content to bias domains. RESULTS: We identified 15 additional articles, bringing the total to 29 tools. Of these 29, 19 provided structured evaluation tools. Twelve of the 19 evaluation tools were newly added in the present review, which addressed broader methodological domains beyond core instrumental variable assumptions, including genetic instrument selection, population stratification, sensitivity analyses, and dataset considerations. However, substantial variation in bias domains, structure, and scoring methods across tools persists. Key gaps remain in the assessment of linkage disequilibrium, missing data, and dynastic effects. CONCLUSIONS: While the number of structured tools has increased in recent years, the lack of standardization across tools makes it difficult to compare across systematic reviews of MR studies. Developing more complete and standardized evaluation frameworks and properly testing these tools in practice are important next steps to improve the overall quality of MR research.
References
- 1.Yu, J., Zou, M., Spiga, F., Dawson, S., Davey Smith, G., & Higgins, J. P. T. (2026). Structured tools for assessing quality and risk of bias in Mendelian randomization studies: an updated systematic review. International Journal of Epidemiology, dyag052. https://doi.org/10.1093/ije/dyag052
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