Table 2.

Components of a causal question and estimand per ICH E9(R1) [41] and target trial emulation [17]

ICH E9(R1) attribute	Target trial emulation protocol component	Explanation	Related notation in this paper
Population	Eligibility criteria	Inclusion and exclusion criteria, including dates of eligibility, for the potential study population	Measured baseline characteristics†: W
Treatment	Treatment strategies	The ideal hypothetical intervention(s) of interest in each arm of the target trial, including what treatment or exposure or intervention individuals would experience at study baseline and any postbaseline interventions, such as preventing censoring or requiring adherence for a specified duration. It is also important to consider whether there are different versions of treatment (e.g., different versions of the same surgery performed by different surgeons), and which versions would be included in the treatment strategy [107].	Baseline treatment: A, Censoring††: C
	Follow-up period	The events that define the starting (e.g., randomization, prescription) and stopping (e.g., outcome, death) points for the observation period
Variable or end point	Outcome	Outcome of interest, including the time point(s) at which the outcome will be evaluated	Outcome: Y
Population summary	Causal contrasts of interest	Causal estimand†††: e.g., average treatment effect, causal relative risk, and average treatment effect within prespecified subgroups	See above

^†Baseline participant characteristics can include additional variables not used to define eligibility criteria. Baseline variables do not completely characterize the population, but for simplicity, we only consider measured baseline characteristics in the notation below.

^††In the current paper, we focus on interventions on baseline treatment and postbaseline censoring. However, the approach represented extends naturally to treatment strategies that incorporate additional postbaseline interventions (see e.g., Robins and Hernán (2009) [108], Petersen (2014) [28]).

^†††A mathematical quantity that is a function of potential outcomes (see above).