DARWIN EU® - Incidence, period prevalence, and characterisation of individuals with paediatric pulmonary arterial hypertension

Study type

• Study topic:
  Disease /health condition
• Study topic, other:
  paediatric pulmonary arterial hypertension
• 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

Population studied

• Short description of the study population:
  For objective 1 (incidence of individuals with PAH):; Inclusion criteria; • Aged <18 years at index date; • Observation in the data source of 365 days prior to the index date (except for those aged less than one year old and individuals in hospital settings, CDWBordeaux); Exclusion criteria; • Prior occurrence of pulmonary arterial hypertension; ; For objective 1 (period prevalence of individuals with PAH):; Inclusion criteria; • Aged <18 years at index date; • Observation in the data source of 365 days prior to the index date (except for those aged less than one year old and individuals in hospital settings, CDWBordeaux); For objective 2 (characterisation of individuals with PAH); Inclusion criteria; • Recorded diagnosis of pulmonary arterial hypertension; • Aged <18 years at index date; • Observation in the data source of 365 days prior to the index date (except for those aged less than one year old and individuals in hospital settings, CDWBordeaux); Exclusion criteria; • Occurrence of pulmonary arterial hypertension prior to index date; • Occurrence of right sided heart failure any time prior to index date (for characterisation of individuals in terms of right sided heart failure incidence);
• Age groups:
  • 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)

Study design details

• Study design:
  For the first objective, we will perform a disease epidemiology study ; For the second objective, we will perform a characterisation study ;
• Main study objective:
  1. Estimate the yearly incidence and period prevalence of pulmonary arterial hypertension (PAH) in the paediatric population, stratified by age group (0 to 1 year, 1 to 2-years, 2 to 5-years, 5 to 12-years, and 12 to 17-years); 2. Characterise paediatric patients newly diagnosed with PAH:; a) Describe the number and proportions of individuals by sex and age at index date; b) Within 180-days prior to index date and then within the first five years after index date, within sequential 90-day periods, potential etiology (congenital heart disease, bronchopulmonary dysplasia, congenital diaphragmatic hernia, persistent pulmonary hypertension of the newborn) and comorbidities (right heart failure, ascites, arrythmia, hemoptysis, lung-heart transplant, atrial septostomy or Potts shunt, syncope); c) Within the first five-years after index date, within sequential 90-day periods, describe the number and proportion of individuals treated with monotherapy of the following treatments, including endothelin receptor antagonists (ERAs, bosentan, ambrisentan, macitentan), phosphodiesterase type 5 inhibitors (PDE5-is, sildenafil, tadalafil), soluble guanylate cyclase stimulators (sGC, riociguat), prostacyclin receptor agonists (treprostinil, epoprostenol, iloprost, selexipag, ralinepag) or combination therapy of these classes, including ERAs + PDE5-I, ERAs + sGC, PDE5-i + prostacyclin receptor agonists, and ERA + PDE5-I + prostacyclin receptor agonists; d) Describe the number and proportion of individuals treated with monotherapy of the following treatments, including endothelin receptor antagonists (ERAs, bosentan, ambrisentan, macitentan), phosphodiesterase type 5 inhibitors (PDE5-is, sildenafil, tadalafil), soluble guanylate cyclase stimulators (sGC, riociguat), prostacyclin receptor agonists (treprostinil, epoprostenol, iloprost, selexipag, ralinepag) or combination therapy of these classes, including ERAs + PDE5-I, ERAs + sGC, PDE5-i + Prostacyclin receptor agonists, and ERA + PDE5-I + prostacyclin receptor agonists by age group (0 to 1 year, 1 to 2-years, 2 to 5-years, 5 to 12-years, and 12 to 17-years) at time of prescription/dispensing; e) Within 180-days prior to index date and then within the first five-years after index date, within sequential 90-day periods, describe the number and proportion of individuals with at least one record for each of the following measures: 6-minute walk distance (6MWD) test, echocardiography, NT-proBNP, WHO functional class, right heart catheterisation, and cardiovascular MRI (Magnetic resonance imaging; f) Within the first five-years after index date in sequential 90-day periods, describe the number of and proportion of individuals who were admitted to hospital or died.;
• Outcomes:
  The outcome for objective 1 is PAH diagnosis. For objective 2, covariates will be used to characterise the ; included individuals with PAH: Demographic factors include sex, age and age group; conditions include right ; heart failure, ascites, arrythmia, haemoptysis, and syncope, congenital heart disease, bronchopulmonary ; dysplasia, congenital diaphragmatic hernia, persistent pulmonary hypertension of the newborn; procedures; or measurements include lung-heart transplant, atrial septostomy or Pott shunt, 6 minute walking test, ; echocardiography, NT-proBNP test, WHO functional class, right heart catheterisation, cardiovascular MRI;; and drug treatments, including mono- and combination therapies of endothelin receptor antagonists, ; phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin receptor ; agonists.
• Data analysis plan:
  The calculation of PAH incidence rates with 95% confidence intervals per data source will be stratified by ; year and age group (0 to 1 year, 1 to 2-years, 2 to 5-years, 5 to 12-years, and 12 to 17-years). Period ; prevalence will be reported as the percentage of patients with new or ongoing PAH of the total population; at risk in each data source, stratified by year and age group. We will characterise individuals with PAH in ; terms of demographics at index date, as well as the number and proportion of records of comorbidities, ; procedures, treatments, hospitalisation in sequential 90-day windows after index date, and at baseline [-; 180,0] for procedures, measurements, and acute conditions. Chronic conditions will be measured at index ; date and any time prior [-inf,0]. Characterisation by number and proportion of treatment records will also ; be stratified by age group at time of prescribing/dispensing.