Impact of parameter settings on the estimation of drug exposure with the individualized dispensing patterns method

To assess the impact of parameter settings when using the individualized dispensing patterns (IDP) method to estimate exposure duration from dispensing data.

We conducted a cohort study using a 2% representative sample of the French healthcare insurance database from 2013 to 2022. The IDP method derives drug exposure distribution in a population sample, applies a selected percentile of this distribution to each individual's initial dispensing and then adjusts subsequent exposures at the individual level, incorporating a possible grace period to link consecutive dispensings into continuous exposure episodes. We studied two drugs with contrasting prescribing patterns: tramadol and rivaroxaban. We varied four parameters independently, compared median episode duration estimates and assessed consistency of exposed days estimates using kappa coefficients.

With the original IDP parameters, median continuous exposure episodes were 47 days for tramadol and 79 days for rivaroxaban. The impact of parameter choice was drug-specific: Percentile selection affected both drugs (kappa 0.58-0.65 for tramadol; 0.89-0.93 for rivaroxaban), sample population definition affected tramadol only (kappa 0.76), and grace period affected rivaroxaban (kappa 0.74-0.87). Heterogeneity across individual-level kappa values was always high (I² > 80%). These results informed the selection of drug-specific parameters, yielding clinically more plausible median episode durations: 15 days for tramadol and 96 days for rivaroxaban.

Consumption patterns in the study population should guide percentile and grace period selection. Tailored accordingly, the IDP method provides an adaptable framework for estimating drug exposure from databases. Transparent reporting of parameter selection is essential to ensure reproducibility and interpretability.