Tools for the assessment of quality and risk of bias in Mendelian randomization studies: a systematic review

Background. The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for risk of bias and/or quality of evidence assessment in (MR) studies, and a review of systematic reviews of MR studies. Methods. We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment. Results. Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates. Conclusions. We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. As none of these methods has been tested and validated for general use, we do not provide recommendations on their use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.