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G. Davey Smith

Publications and source records attributed to G. Davey Smith.

2 recordsLinked to original sources

Average causal effect estimation via instrumental variables: the no simultaneous heterogeneity assumption

Background: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment X has a causal effect on an outcome Y. Even if the instrument Z satisfies the three core IV assumptions of relevance, independence and the exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of X on Y. Sufficient assumptions for this include: homogeneity in the causal effect of X on Y; homogeneity in the association of Z with X; and no effect modification (NEM). Methods: We describe the NO Simultaneous Heterogeneity (NOSH) assumption, which requires the heterogeneity in the X-Y causal effect to be mean independent of (i.e., uncorrelated with) both Z and heterogeneity in the Z-X association. This happens, for example, if there are no common modifiers of the X-Y effect and the Z-X association, and the X-Y effect is additive linear. We illustrate NOSH using simulations and by re-examining selected published studies. Results: When NOSH holds, the Wald estimand equals the ACE even if both homogeneity assumptions and NEM (which we demonstrate to be special cases of - and therefore stronger than - NOSH) are violated. Conclusions: NOSH is sufficient for identifying the ACE using IVs. Since NOSH is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated.

stat.ME

Challenges in constructing genetic instruments for pharmacologic therapies

The genes that encode the targets of most therapies do not have rare variants with large-effect or common variants with moderate effects on the biomarker reflecting the pharmacologic action of the corresponding therapy. Therefore, providing genetic target validation for most therapies is challenging. Novel methods are being developed to combine multiple variants in the gene encoding the target of a therapy that are weakly associated with the biomarker reflecting the pharmacologic action of that therapy into a genetic score that can be used as an adequate instrumental variable. We describe one approach to solve this important problem.

q-bio.QM