What phases of the drug development framework can epidemiological studies emulate?

Target trial emulation prompts investigators to frame their analysis question in terms of a hypothetical clinical trial. Although this does not solve the problem of confounding, the framework can protect against other sources of bias. A natural question is this: what kinds of trials can be emulated? In a late-phase trial (Phase 3 or 4), the goal is to obtain a well-defined causal estimate that closely approximates the impact of a proposed intervention. In an early-phase trial (Phase 2 or earlier), the estimate is a means to an end rather than an end in itself. An early-phase trial provides proof-of-concept evidence on the impact of an intervention in the exposure in terms of efficacy and safety, but the estimand may not correspond to the intervention to be implemented in practice. In a natural experiment where causal inferences rely on a plausibly random (or quasi-random) comparison, the estimand may not be directly translatable to applied practice. In this case, the analysis may be conceptualized as an early-phase target trial. This provides less specific evidence than a late-stage target trial, but in many cases, a more valid but less applicable comparison is preferable to a more applicable comparison that is more susceptible to bias.