DARWIN EU® - Clozapine and the incidence of agranulocytosis over time

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Clozapine
• Anatomical Therapeutic Chemical (ATC) code:
  (N05AH02) clozapine

  clozapine
• Medical condition to be studied:
  Agranulocytosis

Population studied

• Short description of the study population:
  The study population will include all new users of clozapine registered in the respective data sources between 1st of January 2010 and 31st of December 2024 (or latest date available). ; “New use” refers to a first prescription of clozapine within the study period with no clozapine prescription in the medical history. ; Eligibility Criteria: ; At least 1 year of data visibility before starting clozapine treatment.; Additional eligibility criteria:; To ensure sufficient follow-up, only individuals who initiated clozapine treatment at least one year before the end of the available data in the respective data source will be included.;
• Age groups:
  All

  In utero

  Paediatric Population (< 18 years)

  Neonate

  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adult and elderly population (≥18 years)

  Adults (18 to < 65 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Elderly (≥ 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)

Study design details

• Study design:
  A cohort study will be conducted using routinely collected health data from 5 data sources. The study will comprise three consecutive parts:; • Population-level cohort study (Objective 1, Population-level descriptive epidemiology of agranulocytosis and neutropenia in new users of clozapine).; • Cohort
• Main study objective:
  1. To estimate the incidence rates of agranulocytosis and neutropenia in consecutive weekly and monthly intervals following the initiation of clozapine treatment, overall and stratified by age and sex. ; 2. To characterise the timing of agranulocytosis and neutropenia events during clozapine treatment using Kaplan-Meier curves, overall and stratified by age and sex.; 3. To characterise individuals initiating clozapine treatment in terms of demographics and pre-specified conditions related to the indication for clozapine use.; 4. To determine the treatment duration for clozapine use. ;