(069) Conceptual bases for the standardization of calculation approaches for establishing exposure duration of single drug utilization records in multi-database studies

Publication Number: 732

Background: In observational studies based on routinely collected healtcare data, prescription, dispensation or administration records are usually leveraged for exposure assessment. The number of days of treatment (DOT) associated with each drug utilization record (DUR) of interest can be calculated in several ways depending on data source-specific available information and investigator's choiches. Therefore, standardization of calculation approaches is paramount to facilitate methods' documentation and result comparisons.

Objectives: To define a set of calculation choices (recipes) for standardizing DOT calculation for single DURs.

Methods: A list of recipes to calculate DOT from electronic DURs was created based on literature search and researchers’ experience. Concepts needed to implement the recipes were defined using the standard terms of the European Directorate for the Quality of Medicine.

Results: Five recipes were defined based on 5 concepts. Concepts: 1)unit of presentations (i.e. unit in which the strength(s) of the manufactured item or pharmaceutical product is presented and described, e.g. tablet, bottle); 2)active substance amount (e.g. mass or volume), 3)pharmaceutical product amount (e.g. mass of cream, volume of oral solution), 4)medicinal product (identified by the marketing authorization number) and DUR (i.e. a record record ≥1 medicinal product unit). Recipes were classified as Daily Dose(DD)-based (n=3) and Fixed duration-based (n=2). DD-based recipes, for which a prescribed/assumed DD is required, were further categorized based on the nature of the chosen DD: units of presentations/day (recipe 1: DOT=number of medicinal products*number of units of presentation per medicinal product÷DD); active substance/day (recipe 2: DOT=number of medicinal products*active substance amount per medicinal product÷DD); pharmaceutical product amount/day (recipe 3: DOT=number of medicinal products*pharmaceutical product amount per medicinal product÷DD). E.g. applying recipe 1 to a DUR containing 2 units of “Atorvastatin 40mg 30 tablets”, assuming a DD of 1 tablet/day, DOT=60 days. Fixed-duration recipes, instead, allow calculating DOT assuming a fixed duration of the DUR (recipe 4: DOT=fixed-duration) or assuming a fixed duration for each unit of medicinal product in the DUR (recipe 5: DOT= number of medicinal products*fixed-duration). E.g. applying recipe 4 to either a DUR containing 3 units of “Acitretin 30mg 30 tablets” or a DUR containing 2 units of “Acitretin 25mg 20 tablets”, assuming a fixed DUR duration of 30 days based on prescribing recommendations, DOT=30 days for both DUR.

Conclusions: We provided comprehensive conceptual bases for the standardization of calculation approaches for assigning exposure duration to any DUR.