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Eur J Epidemiol. 2019 Oct 26. doi: 10.1007/s10654-019-00571-w. [Epub ahead of print]

Effect heterogeneity and variable selection for standardizing causal effects to a target population.

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Norwegian Institute of Public Health, Oslo, Norway.
PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.
Department of Biostatistics, University of Oslo, Oslo, Norway.
Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.


The participants in randomized trials and other studies used for causal inference are often not representative of the populations seen by clinical decision-makers. To account for differences between populations, researchers may consider standardizing results to a target population. We discuss several different types of homogeneity conditions that are relevant for standardization: Homogeneity of effect measures, homogeneity of counterfactual outcome state transition parameters, and homogeneity of counterfactual distributions. Each of these conditions can be used to show that a particular standardization procedure will result in an unbiased estimate of the effect in the target population, given assumptions about the relevant scientific context. We compare and contrast the homogeneity conditions, in particular their implications for selection of covariates for standardization and their implications for how to compute the standardized causal effect in the target population. While some of the recently developed counterfactual approaches to generalizability rely upon homogeneity conditions that avoid many of the problems associated with traditional approaches, they often require adjustment for a large (and possibly unfeasible) set of covariates.


Effect heterogeneity; Effect measures; External validity; Generalizability; Methodology; Standardization


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