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EFSPI/PSI Causal Inference SIG Webinar: Instrumental Variable Methods

30 September 2025

A natural experiment is an observational study that enables causal conclusions to be drawn. In a natural experiment, individuals are divided either at random or in a way that mimics randomization (known as quasi-randomization), but this division is performed by a natural process or an artificial distinction rather than by an investigator. The variable that divides individuals is known as an instrumental variable.  In this talk, I will provide an introduction to instrumental variables: what they are, and how they can be used to make causal claims. I will then present Mendelian randomization, the use of genetic variants as instrumental variables. Due to inherent randomness in the process of genetic inheritance, genetic variants act somewhat like randomization. As the majority of drugs influence proteins and genes encode proteins, there is a specific relevance for Mendelian randomization to the drug development pipeline. Mendelian randomization can provide evidence on target validation, re-purposing, safety signals, mechanistic relevance, and effect heterogeneity: are pathways worth drugging, what outcomes do they affect, how do they affect them, and who would most benefit from intervention? The talk will be illustrated with examples of targets for existing and emerging drugs.

Speakers: Jack Bowden, Novo Nordisk and University of Exeter and Stephen Burgess, University of Cambridge

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