title: Premarket safety and efficacy studies for ADHD medications in children.
abstract: BACKGROUND
  Attention-deficit hyperactivity disorder (ADHD) is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing.
  
  
  METHODS
  We identified all ADHD medications approved by the Food and Drug Administration (FDA) and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials.
  
  
  RESULTS
  A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419). Eleven drugs (55%) were approved after <100 participants were studied and 14 (70%) after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9), with 5 (38%) drugs approved after participants were studied <4 weeks and 10 (77%) after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed.
  
  
  CONCLUSIONS
  Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.
authors.affiliation: Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Pediatrics, Harvard Medical School, Boston, Boston, Massachusetts, United States of America; Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Florence T
authors.initials: FT
authors.lastname: Bourgeois
authors.affiliation: Faculty of Arts and Sciences, Wellesley College, Wellesley, Massachusetts, United States of America.
authors.forename: Jeong Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America; Department of Pediatrics, Harvard Medical School, Boston, Boston, Massachusetts, United States of America; Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, Boston Children's Hospital, Boston, Massachusetts, United States of America; Harvard Medical School Center for Biomedical Informatics, Boston, Massachusetts, United States of America.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Mandl
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002986:Clinical Trials as Topic; D017277:Drug Approval / Q000379:methods* / Q000458:organization & administration; D006801:Humans; D040541:Marketing; D018401:Sample Size; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000697:Central Nervous System Stimulants