UCSF

OBJECTIVE: Researchers are often interested in assessing the causal effect of an exposure on an outcome when randomization is not ethical or feasible. Estimating causal effects by controlling for confounders can be unconvincing because important potential confounders remain unmeasured. Study designs leveraging instrumental variables (IVs) offer alternatives to confounder-control methods but are rarely used in stress and trauma research. METHOD: We review the conceptual foundations and implementation of IV methods. We discuss strengths and limitations of IV approaches, contrasting with confounder-control methods, and illustrate the relevance of IVs for stress and trauma research. RESULTS: IV approaches leverage an external or exogenous source of variation in the exposure. Instruments are variables that meet three conditions: relevance (variation in the IV is associated with variation in the chance of exposure), exclusion (the IV only affects the outcome through the exposure), and exchangeability (no unmeasured confounding of the IV-outcome relationship). Interpreting estimates from IV analyses requires an additional assumption, such as monotonicity (the instrument does not change the chance of exposure in different directions for any two individuals). Valid IVs circumvent the need to correctly identify, measure, and control for all confounders of the exposure-outcome relationship. The primary challenge is identifying a valid instrument. CONCLUSIONS: IV approaches have strengths and weaknesses compared with confounder-control approaches. IVs offers a promising complementary study design to improve evidence about the causal effects of exposures on outcomes relevant to stress and trauma. Collaboration with scientists who are experienced with identifying and analyzing IVs will support this work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).