Safety outcomes of Selective Serotonin Reuptake Inhibitors in Adolescent Attention-Deficit/Hyperactivity Disorder (The ASSURE study)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  METHYLPHENIDATE

  ATOMOXETINE

  CLONIDINE

  BUPROPION
• Anatomical Therapeutic Chemical (ATC) code:
  (N06AB) Selective serotonin reuptake inhibitors

  Selective serotonin reuptake inhibitors
• Medical condition to be studied:
  Attention deficit hyperactivity disorder

Population studied

• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)
• Estimated number of subjects:
  20000

Study design details

• Main study objective:
  The primary objective is comparing the risk of safety outcomes which include neuropsychiatric events, cardiovascular events, and other events during concomitant use of methylphenidate and SSRI among adolescent ADHD patients.
• Outcomes:
  A primary outcome is a neuropsychiatric event that includes agitation, first-time psychosis, first-time tic disorder, mania, sleep disorder, suicidal event, and tremor. All conditions could be detected by diagnostic codes. Secondary outcomes are cardiovascular and other events. Cardiovascular events are including arrhythmia and hypertension. All conditions could be detected by diagnostic codes. Other events are including abdominal pain, constipation, headache, nausea/vomiting, seizure, and traumatic injury. All conditions could be detected by diagnostic codes.
• Data analysis plan:
  In this study, we compare the treatment cohort with the comparator cohort for the hazards of outcome during the time-at-risk by applying a Cox proportional hazards model. The time-to-event of outcome among patients in the treatment and comparator cohorts is determined by calculating the number of days from the start of the time-at-risk window (the cohort start date), until the earliest event among 1) the first occurrence of the outcome, 2) the end of the time-at-risk window and 3) the end of the observation period that spans the time-at-risk start. Propensity scores will be used as an analytic strategy to reduce potential confounding due to an imbalance between the target and comparator cohorts in baseline covariates. After estimating the PS, one-to-one matching will be performed.