Hypertonic Saline in Bronchiolitis and Type I Error: A Trial Sequential Analysis.

Unlabelled: : media-1vid110.1542/5799873875001PEDS-VA_2018-1144 BACKGROUND AND OBJECTIVES: Meta-analyses of nebulized hypertonic saline (HS) for acute viral bronchiolitis have yielded disparate conclusions. Trial sequential analysis (TSA) is a novel method designed to account for potential sources of error in conventional meta-analysis. We sought to use TSA to determine if the existing literature base is sufficient to draw firm conclusions about the effectiveness of HS in bronchiolitis.

Methods: We used the cohort of studies identified in previously published conventional meta-analyses. Included studies were those in which authors compared treatment with HS versus normal saline (or supportive care) in children with bronchiolitis to reduce hospital length of stay (LOS) or hospitalizations. TSA results are used to provide a required information size and monitoring boundaries for statistical significance.

Results: For the LOS outcome, 17 studies including 1866 patients analyzed in which authors used conventional meta-analysis reveal a statistically significant benefit (mean difference = -0.41 days; 95% confidence interval = -0.07 to -0.75); however, TSA suggests that those conclusions are premature because of failure to reach the adequate information size of 2665 individuals. For the risk of hospitalization outcome, 8 studies including 1728 patients analyzed in which authors used conventional meta-analysis reveal a reduction in the relative risk of hospitalization (relative risk = 0.86; 95% confidence interval = 0.76 to 0.98); however, TSA suggests these conclusions are premature because of failure to reach the adequate information size of 4770. Both LOS and hospitalization results from conventional meta-analysis would be considered potentially false-positives by TSA.

Conclusions: TSA reveals that concluding benefit from HS for children with bronchiolitis potentially represents type I error.