Outcome measures and serious asthma exacerbation in clinical trials of asthma controller medications.

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.

Conclusion: 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.