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Background  While the population attributable fraction (PAF) provides potentially valuable information regarding the community-level effect of risk factors, significant limitations exist with current strategies for estimating a PAF in multiple risk factor models. These strategies can result in paradoxical or ambiguous measures of effect, or require unrealistic assumptions regarding variables in the model. A method is proposed in which an overall or total PAF across multiple risk factors is partitioned into components based upon a sequential ordering of effects. This method is applied to several hypothetical data sets in order to demonstrate its application and interpretation in diverse analytic situations.    Results  The proposed method is demonstrated to provide clear and interpretable measures of effect, even when risk factors are related/correlated and/or when risk factors interact. Furthermore, this strategy not only addresses, but also quantifies issues raised by other researchers who have noted the potential impact of population-shifts on population-level effects in multiple risk factor models.    Conclusion  Combined with simple, unadjusted PAF estimates and an aggregate PAF based on all risk factors under consideration, the sequentially partitioned PAF provides valuable additional information regarding the   process   through which population rates of a disorder may be impacted. In addition, the approach can also be used to statistically control for confounding by other variables, while avoiding the potential pitfalls of attempting to separately differentiate direct and indirect effects.

Partitioning the population attributable fraction for a sequential chain of effects