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Assessing the impact of unmeasured confounders for credible and reliable real‐world evidence
Author(s) -
Zhang Xiang,
Stamey James D.,
Mathur Maya B.
Publication year - 2020
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.5117
Subject(s) - confounding , categorization , medicine , sensitivity (control systems) , causal inference , econometrics , computer science , data mining , statistics , artificial intelligence , mathematics , pathology , electronic engineering , engineering
Purpose We review statistical methods for assessing the possible impact of bias due to unmeasured confounding in real world data analysis and provide detailed recommendations for choosing among the methods. Methods By updating an earlier systematic review, we summarize modern statistical best practices for evaluating and correcting for potential bias due to unmeasured confounding in estimating causal treatment effect from non‐interventional studies. Results We suggest a hierarchical structure for assessing unmeasured confounding. First, for initial sensitivity analyses, we strongly recommend applying a recently developed method, the E‐value, that is straightforward to apply and does not require prior knowledge or assumptions about the unmeasured confounder(s). When some such knowledge is available, the E‐value could be supplemented by the rule‐out or array method at this step. If these initial analyses suggest results may not be robust to unmeasured confounding, subsequent analyses could be conducted using more specialized statistical methods, which we categorize based on whether they require access to external data on the suspected unmeasured confounder(s), internal data, or no data. Other factors for choosing the subsequent sensitivity analysis methods are also introduced and discussed, including the types of unmeasured confounders and whether the subsequent sensitivity analysis is intended to provide a corrected causal treatment effect. Conclusion Various analytical methods have been proposed to address unmeasured confounding, but little research has discussed a structured approach to select appropriate methods in practice. In providing practical suggestions for choosing appropriate initial and, potentially, more specialized subsequent sensitivity analyses, we hope to facilitate the widespread reporting of such sensitivity analyses in non‐interventional studies. The suggested approach also has the potential to inform pre‐specification of sensitivity analyses before executing the analysis, and therefore increase the transparency and limit selective study reporting.