An approach to quantifying the potential importance of residual confounding in systematic reviews of observational studies: a GRADE concept paper

Verbeek, J. H. et al. (2021) An approach to quantifying the potential importance of residual confounding in systematic reviews of observational studies: a GRADE concept paper. Environment International, 157, 106868. (doi: 10.1016/j.envint.2021.106868) (PMID:34530289)

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Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Katikireddi, Professor Vittal
Creator Roles:
Katikireddi, S. V.Conceptualization, Writing – review and editing
Authors: Verbeek, J. H., Whaley, P., Morgan, R. L., Taylor, K. W., Rooney, A. A., Schwingshackl, L., Hoving, J. L., Katikireddi, S. V., Shea, B., Mustafa, R. A., Murad, M. H., and Schünemann, H. J.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > MRC/CSO SPHSU
Journal Name:Environment International
ISSN (Online):1873-6750
Published Online:13 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Environment International 157: 106868
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Inequalities in healthMedical Research Council (MRC)MC_UU_00022/2HW - MRC/CSO Social and Public Health Sciences Unit
172690Understanding the impacts of welfare policy on health: A novel data linkage studySrinivasa KatikireddiOffice of the Chief Scientific Adviser (CSO)SCAF/15/02HW - Public Health
Chief Scientist Office (CSO)SPHSU17