Investigators from multiple institutions conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of oseltamivir in the treatment of uncomplicated influenza in children. Clinical trials that were conducted between 1997 and 2016, included children, were placebo-controlled, and evaluated several different influenza outcomes were eligible. Individual participant data from each trial were obtained and pooled.
The primary exposure was study arm (receipt of oseltamivir or placebo). The main outcome of interest was duration of acute respiratory illness in hours. All participants, regardless of influenza virus infection status, were analyzed. Subgroup analyses were also completed among those who received treatment early (<24 hours vs 24–48 hours from the onset of symptoms), by age group (<6 years, 6–11 years, 12–17 years), among individuals with and without asthma, and among those with and without laboratory-confirmed influenza virus infection.
Five RCTs were included that involved a total of 2,561 participants. Of these, 1,281 received oseltamivir and 1,280 received placebo. There was a significant reduction in the duration of illness among those who received oseltamivir (−17.6 hours; 95 % CI, −34.5, −0.7). In subgroup analyses, a significantly larger reduction in duration of illness was observed among those who received treatment in <24 hours than in those initiating treatment 24–48 hours after onset of symptoms (−22.8 vs −4.4 hours) and among those with laboratory-confirmed (vs uninfected) influenza illness (−17.5 vs 3.1 hours). Among the subgroup of children with asthma, no statistically significant effect of treatment was found.
The authors conclude that oseltamivir reduces the duration of influenza illness in children.
Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.
Controversy surrounding the efficacy of oseltamivir for the treatment of influenza in children provided the impetus for the current study.1 Four critical issues need to be addressed in this meta-analysis.
First, the investigators searched multiple databases to identify all relevant studies that included children. Of the 68 unique records from the search, only 5 (4 published and 1 unpublished) trials met their strict criteria. This observation is not unique for oseltamivir. The National Institutes of Health estimates that 70% of medications used in children have not been evaluated in clinical trials in pediatric participants.2
The second issue is heterogeneity or the degree of dissimilarity in the results of individual studies. The main outcome was duration of illness in hours, which was defined as the absence of fever in all trials, but other criteria varied. Some trials used resolution of major signs and symptoms (eg, fever, tachypnea, difficult breathing, and cough). Other trials required that cough or rhinitis were mild or absent and that the child had...