Abstract

BackgroundIn 1995, Eide and Gefeller introduced the concepts of sequential and average attributable fractions as methods to partition the risk of disease among differing exposures. In particular, sequential attributable fractions are interpreted in terms of an incremental reduction in disease prevalence associated with removing a particular risk factor from the population, having removed other risk factors. Clearly, both concepts are causal entities, but are not usually estimated within a causal inference framework.MethodsWe propose causal definitions of sequential and average attributable fractions using the potential outcomes framework. To estimate these quantities in practice, we model exposure-exposure and exposure-disease interrelationships using a causal Bayesian network, assuming no unmeasured latent confounders. This allows us to model not only the direct impact of removing a risk factor on disease, but also the indirect impact through the effect on the prevalence of causally downstream risk factors that are typically ignored when calculating sequential and average attributable fractions. The procedure for calculating sequential attributable fractions involves repeated applications of Pearl’s do-operator over a fitted Bayesian network, and simulation from the resulting joint probability distributions.ResultsThe methods are applied to the INTERSTROKE study, which was designed to quantify disease burden attributable to the major risk factors for stroke. The resulting sequential and average attributable fractions are compared with results from a prior estimation approach which uses a single logistic model and which does not properly account for differing causal pathways.ConclusionsIn contrast to estimation using a single regression model, the proposed approaches allow consistent estimation of sequential, joint and average attributable fractions under general causal structures.

Highlights

  • In 1995, Eide and Gefeller introduced the concepts of sequential and average attributable fractions as methods to partition the risk of disease among differing exposures

  • Here we describe a Monte-Carlo approach based on a causal Bayesian network describing the inter-relationships between all risk factors and disease

  • It is possible that reverse causation might be at play; for instance, the negative. Our contributions in this manuscript are to first define sequential and average attributable fractions in a causal framework and second to describe a possible methodology to estimate these quantities based on simulation from causal Bayesian networks

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Summary

Introduction

In 1995, Eide and Gefeller introduced the concepts of sequential and average attributable fractions as methods to partition the risk of disease among differing exposures. As has been noted elsewhere, confusion abounds regarding the definition and interpretation of population attributable fractions (PAF) in epidemiology [1] In their seminal paper where Eide and Gefeller introduce average and sequential attributable fractions [2], they define the population attributable fraction as ‘the proportion by which a disease prevalence (or incidence) is reduced if the whole population is hypothesized to attain the same risk of disease as the individuals within the lowest exposure category.’. Ferguson et al Archives of Public Health (2020) 78:67 the exposure was totally eliminated from it’ (note that the use of the word eliminate is convenient but slightly misleading as it refers to a hypothetical population where the risk factor of interest was always absent rather than eliminated at a point in time) They define this second quantity as the ‘etiologic fraction’, introduced by Miettinen [3]. This seems sensible to us as it does have a direct causal implication (that is, it will only be non-zero if the exposure has some causal effect on disease), and can be estimated in real data, provided we can adequately adjust for confounding [7]

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