Objectives Due to their interrelatedness, modelling independent effects of intensity, duration, and time since exposure on disease risk is complex. The indiscriminate use of the cumulative exposure metric (product of intensity and duration of exposure) might bias reported associations between exposure to hazardous agents and disease risk. We explored the use of a general framework to flexibly model the effects of intensity, duration, and time since exposure on chronic disease.

Method We will provide examples of models falling within the flexible framework. One of such models is an excess relative risk model that is linear in cumulative exposure and exponential in the intensity (or duration) of exposure and time since cessation. This model has been applied successfully to explore effect modification of cumulative exposure by intensity (or duration) of exposure for a number of exposures. We will demonstrate the application of this model in two studies of smoking and chronic disease.

Results In our example the excess relative risk model generally fits the data best. In both studies we observed a strong effect of time since cessation. We observed effect modification by intensity of smoking in one study.

Conclusions Application of flexible models will provide insight into whether the use of cumulative exposure in an epidemiological analysis is justified or whether reducing complex exposure history to a metric such as cumulative exposure is overly restrictive. Combining information on observed patterns of effect modification with mechanistic insights might contribute to the incorporation of biological hypotheses in the development of more biologically relevant exposure metrics.