The instrumental variable method has been employed within economics to infer causality in the presence of unmeasured confounding. Emphasising the parallels to randomisation may increase understanding of the underlying assumptions within epidemiology. An instrument is a variable that predicts exposure, but conditional on exposure shows no independent association with the outcome. The random assignment in trials is an example of what would be expected to be an ideal instrument, but instruments can also be found in observational settings with a naturally varying phenomenon e.g. geographical variation, physical distance to facility or physician's preference. The fourth identifying assumption has received less attention, but is essential for the generalisability of estimated effects. The instrument identifies the group of compliers in which exposure is pseudo-randomly assigned leading to exchangeability with regard to unmeasured confounders. Underlying assumptions can only partially be tested empirically and require subject-matter knowledge. Future studies employing instruments should carefully seek to validate all four assumptions, possibly drawing on parallels to randomisation.
Keywords: Causal inference; Exchangeability; Instrumental variable; Monotonicity; Randomization; Unmeasured confounding.