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Estimating the effect of a change in a particular risk factor and a chronicdisease requires information on the risk factor from two time points; theenrolment and the first follow-up. When using observational data to study theeffect of such an exposure (change in risk factor) extra complications arise,namely (i) when is time zero? and (ii) which information on confounders shouldwe 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 verychallenging. Researchers have applied different methodologies with mixedsuccess, because the different choices made when answering these questionsinduce systematic bias. Here we review these methodologies and highlight thesources of bias in each type of analysis. We discuss the advantages and thelimitations of each method ending by making our recommendations on the analysisplan.

How to estimate the association between change in a risk factor and a health outcome?