The Importance of Making Assumptions in Bias Analysis

Richard F. Maclehose, Thomas P. Ahern, Timothy L. Lash, Charles Poole, Sander Greenland

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Quantitative bias analyses allow researchers to adjust for uncontrolled confounding, given specification of certain bias parameters. When researchers are concerned about unknown confounders, plausible values for these bias parameters will be difficult to specify. Ding and VanderWeele developed bounding factor and E-value approaches that require the user to specify only some of the bias parameters. We describe the mathematical meaning of bounding factors and E-values and the plausibility of these methods in an applied context. We encourage researchers to pay particular attention to the assumption made, when using E-values, that the prevalence of the uncontrolled confounder among the exposed is 100% (or, equivalently, the prevalence of the exposure among those without the confounder is 0%). We contrast methods that attempt to bound biases or effects and alternative approaches such as quantitative bias analysis. We provide an example where failure to make this distinction led to erroneous statements. If the primary concern in an analysis is with known but unmeasured potential confounders, then E-values are not needed and may be misleading. In cases where the concern is with unknown confounders, the E-value assumption of an extreme possible prevalence of the confounder limits its practical utility.

Original languageEnglish (US)
Pages (from-to)617-624
Number of pages8
Issue number5
StatePublished - Sep 1 2021

Bibliographical note

Funding Information:
This work was supported by the US National Library of Medicine (R01LM013049).

Funding Information:
T.P.A. was also supported by National Institute of General Medical Sciences grant number P20GM103644. C.P. was supported by National Institute on Aging grant R01 AG056479. The other authors have no conflicts to report.

Publisher Copyright:
© 2021 Wolters Kluwer Health, Inc. All rights reserved.


  • E-value
  • Quantitative bias analysis
  • Uncontrolled confounding
  • Unmeasured confounding


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