  Estimating the effect of a change in a particular risk factor and a chronic
disease requires information on the risk factor from two time points; the
enrolment and the first follow-up. When using observational data to study the
effect of such an exposure (change in risk factor) extra complications arise,
namely (i) when is time zero? and (ii) which information on confounders should
we account for in this type of analysis? From enrolment or the 1st follow-up?
Or from both?. The combination of these questions has proven to be very
challenging. Researchers have applied different methodologies with mixed
success, because the different choices made when answering these questions
induce systematic bias. Here we review these methodologies and highlight the
sources of bias in each type of analysis. We discuss the advantages and the
limitations of each method ending by making our recommendations on the analysis
plan.
