Time-lag bias in trials of pediatric antidepressants: a systematic review and meta-analysis

Objective: To determine whether there is evidence of a time-lag bias in the publication of pediatric antidepressant trials.

Method: We conducted a meta-analysis of published and unpublished randomized placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years of age with major depressive disorder. Our main outcomes were (1) time to publication of positive versus negative trials, and (2) proportion of treatment responders in trials with standard (<3 years after study completion) versus delayed publication.

Results: We identified 15 randomized, placebo-controlled trials of SRIs for pediatric depression. Trials with negative findings had a significantly longer time to publication (median years ± standard deviation = 4.2 ± 1.9) than trials with positive findings (2.2 ± 0.9; log-rank χ(2) = 4.35, p = .037). The estimated efficacy in trials with standard publication time (number needed to treat = 7, 95% CI = 5-11) was significantly greater than those with delayed publication (17, 95% CI = 9-∞; χ(2) = 4.98, p = .025). The inflation-adjusted impact factor of journals for published trials with positive (15.33 ± 11.01) and negative results (7.54 ± 7.90) did not statistically differ (t = 1.4, df = 10, p = .17).

Conclusions: Despite a small number of trials of SRIs for pediatric antidepressants, we found a significant evidence of time-lag bias in the publication of findings. This time-lag bias altered the perceived efficacy of pediatric antidepressants in the medical literature. Time-lag bias is not unique to child psychiatry and reflects a larger problem in scientific publishing.