Drug Utilization Patterns in Rare Diseases

Drugs were coded using Anatomical Therapeutic Chemical (ATC) classification and therefore divided into fourteen anatomical or pharmacological groups (1st level) (Table 1).
Considering all RDs, the population study was stratified into two age groups: adult (age ≥ 18 years) and pediatric (age < 18 years). The prevalent cases on 1 January of each year of the study period were calculated. All RD patients were pseudonymized by a unique identification number and then linked to the regional pharmaceutical databases.
For pediatric and adult patients, the drug-use profile was assessed through three indicators: (1) the prevalence of use, a measure of exposure, was evaluated per calendar year and calculated as the ratio between the number of cases with at least one pharmaceutical prescription and the number of prevalent cases in the same year. The prevalence rates were expressed as percentage and stratified by year, age group, therapeutic category and sex; (2) the prescriptions/users (Pr/Us) ratio, a measure of intensity of use, was calculated by dividing the total number of prescriptions of drugs belonging to each therapeutic category by the number of users (cases with at least one prescription) in the same therapeutic category and in the same year [16 ,17 (link)]; (3) the total defined daily dose (DDD, the assumed average maintenance dose per day for a drug used as per its main indication in adults) utilized, on average, on any given day of the year and analyzed in a group of 1000 cases (DDD/1000 cases per day) [18 ]. The DDDs were not calculated for the following categories/subgroups, according to the guidelines (https://www.whocc.no/atc_ddd_index/, accessed on 15 October 2022): A15—appetite stimulants; B05—blood substitutes and perfusion solutions; C05—vasoprotectives; D—dermatologicals; J06—immune sera and immunoglobulins (except for nebacumab in J06BC01); J07—vaccines; L01—antineoplastic agents (except for the protein kinase inhibitors in L01E only); P03—ectoparasiticides, incl. scabicides, insecticides and repellents; S02—otologicals; S03—ophthalmological and otological preparations; V09—diagnostic radiopharmaceuticals; V10—therapeutic radiopharmaceuticals. Furthermore, since the population analyzed comprised patients with RDs, the subgroup N07B—drugs used in addictive disorders—was also not included in the estimate of DDD. The indicator DDD/1000 cases per day was stratified by age class, sex and calendar year.
The proportion test was used to explore differences by gender about percentages in the study cohort, and a p-value < 0.05 was considered statistically significant. The data were analyzed with Stata, version 16 [19 ].