Observational data have become a popular source of evidence for causal effects when no randomized controlled trial exists, or to supplement information provided by those. In practice, a wide range of designs and analytical choices exist, and one recent approach relies on the target trial emulation framework. This framework is particularly well suited to mimic what could be obtained in a specific randomized controlled trial, while avoiding time-related selection biases. In this abstract, we present how this framework could be useful to emulate trials in malignant melanoma, and the challenges faced when planning such a study using longitudinal observational data from a cohort study. More specifically, two questions are envisaged: duration of immune checkpoint inhibitors, and trials comparing treatment strategies for BRAF V600-mutant patients (targeted therapy as 1st line, followed by immunotherapy as 2nd line, vs. immunotherapy as 2nd line followed by targeted therapy as 1st line). Using data from 1027 participants to the MELBASE cohort, we detail the results for the emulation of a trial where immune checkpoint inhibitor would be stopped at 6 months vs. continued, in patients in response or with stable disease.

Complex systems can be modeled at various levels of granularity, e.g., we can model a person at the cognitive level, on the neuronal level, or down to the biochemical level. When multiple models represent the same system at different scales, we would like to be able to reason about the causal effects of interventions on each level in such a way that the models remain consistent across levels. In the first part of this talk, I consider which conditions must be fulfilled for two structural equation models (SEMs) to stand in such a causally consistent relation. In the second part of the talk, I present recent work on learning causally consistent SEMs across multiple levels, distinguishing between bottom-up (micro- to macro-level) and top-down (macro- to micro-level) approaches.