If a formal approach is desired, I think state-space modeling is ideal. Note in particular that your problem (irregular timing of measurements) arises only from the customary statistician’s habit of treating the data as the ding an sich, rather than a mere phenomenon. The state-space approach, by contrast, posits an underlying state process (generally, multivariate) that evolves (generally) in continuous time, and gives rise to the data via a measurement process that is distinct from the underlying state process.
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