Structured tools for assessing quality and risk of bias in Mendelian randomization studies: an updated systematic review

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.