Using fractional polynomials to model the effect of cumulative duration of exposure on outcomes: applications to cohort and nested case-control designs.
Bottom Line: Using a cohort design and a Cox proportional hazards model, we found a non-linear relationship between cumulative duration of use of the antiarrhythmic drug amiodarone and the risk of thyroid dysfunction.Using a nested case-control design and a conditional logistic regression model, we found evidence of a linear relationship between duration of use of bisphosphonate medication and risk of atypical femur fractures.Fractional polynomials allow one to model the relationship between cumulative duration of medication use and adverse outcomes.
Affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Management, Policy and Evaluation, University of Toronto, Toronto, Ontario, Canada; Schulich Heart Research Program, Sunnybrook Research Institute, Toronto, Canada.Show MeSH
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Mentions: The relationship between cumulative duration of bisphosphonate use and the log-odds ratio of atypical femur fracture (relative to a woman with a single day of bisphosphonate use) is described in the left panel of Figure 4 (a rug plot describing the distribution of cumulative duration of drug use is presented on the horizontal axis). We describe the relationship between cumulative duration of use and risk of atypical femur fracture for the best-fitting FP1 and FP2 transformations, the identity transformation (i.e. assuming a linear relationship), and the relationship described using restricted cubic regression splines. The vertical axis denotes the log-odds ratio comparing the odds of atypical femur fracture for a woman with a given cumulative duration of use of bisphosphonate relative to that of a woman whose cumulative duration of use was equal to one (i.e. with that of a woman who had used bisphosphonate for one single day).The FP2 (−0.5, 1) transformation described a clinical implausible relationship between duration of exposure and risk of atypical fracture. This transformation described a log-odds ratio that initially decreases with increasing duration of cumulative use. It then reaches a nadir. The log-odds ratio then increases with increasing duration of exposure.
Affiliation: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada; Institute of Health Management, Policy and Evaluation, University of Toronto, Toronto, Ontario, Canada; Schulich Heart Research Program, Sunnybrook Research Institute, Toronto, Canada.