title: Outcome measures and serious asthma exacerbation in clinical trials of asthma controller medications.
abstract: BACKGROUND
  With the introduction and approval of several new asthma controller medications for pediatric use, the risk-benefit ratio of these medications has not been fully evaluated.
  
  
  OBJECTIVE
  To determine whether physiologic pulmonary measurements are superior to other measures in evaluating outcomes and to determine whether asthmatic children have a higher risk of serious adverse events than adults.
  
  
  METHODS
  We obtained data on asthma controller medications approved between 1997 and 2010 from the US Food and Drug Administration archives. Six medications were approved for use in children and adults during this time. Of these, we were able to analyze 23 trials of 5 medications. Nine of the trials were conducted in pediatric patients and 14 in adults.
  
  
  RESULTS
  We determined whether the primary outcome measure was a physiologic pulmonary measure or another measure and compared trial outcomes. We also evaluated serious adverse events, including mortality rates for both adult and pediatric trials. The frequency of successfully demonstrating efficacy was far superior using physiologic pulmonary measures (13/14 [93%]) compared with other outcome measures (4/9 [44%]). The frequency of serious asthma exacerbations, although less than 1%, was higher in the pediatric group of patients (18/1,948 [0.9%]) compared with adults (4/2,460 [0.2%]), regardless of assignment to placebo or drug.
  
  
  CONCLUSIONS
  These results suggest that physiologic pulmonary function measures should be used in evaluating the efficacy of asthma controller medications. These data also indicate that pediatric patients may be more prone to serious asthma exacerbations during clinical trials.
authors.affiliation: Northwest Clinical Research Center, 1951 152nd Pl. N.E., Bellevue, WA 98007, USA. josh.schilling@gmail.com
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Schilling
authors.forename: Shirin R F
authors.initials: SR
authors.lastname: Khan
authors.forename: Arif
authors.initials: A
authors.lastname: Khan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004334:Drug Administration Schedule; D017277:Drug Approval; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D008297:Male; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents