Target Trial Emulation Framework as a Tool of Causal Inference

Target trial emulation (TTE)-oriented study designs can improve real world evidence (RWE) acceptability, mitigate bias, evaluate clinically relevant treatment strategy, and overcome temporal challenges.

Observational studies in pharmacoepidemiology play a pivotal role in assessing evidence for clinical decision makers when randomized controlled trials would be practically or ethically infeasible to conduct. For instance, long-term effects of drug use, drug-drug interactions, or treatments in vulnerable subpopulations such as pregnant women, cannot be estimated in randomized controlled trials. However, analyses using observational data can result in misleading findings when the basic principles of a study design are breached. Conceptualizing an observational study as an attempt to emulate a hypothetical randomized trial offers a structured approach to overcome several avoidable biases, leveraging the so-called target trial emulation (TTE) framework. This framework is used to design the protocol of an ideal hypothetical randomized trial, which includes the eligibility criteria, treatment strategies, treatment assignment procedure, outcomes, follow-up, causal contrasts, and statistical analysis. The principles of TTE are increasingly being adopted by researchers using observational data to address causal related questions.