Date of Award


Document Type


Degree Name

Medical Doctor (MD)

First Advisor

Andres Martin


To determine if there is evidence of a time-lag bias in the publication of pediatric antidepressant trials. We conducted a meta-analysis of published and unpublished randomized, placebo-controlled trials of serotonin reuptake inhibitors (SRIs) in subjects less than 18 years old with major depressive disorder.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. 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 = 4.17 }1.85) than trials with positive findings (2.17 ±0.88; log-rank χ2 = 4.35, p = 0.037). The estimated efficacy in trials with standard publication time (number needed to treat = 7.1, 95%CI: 5.3 - 11.1) was significantly greater than those with delayed publication (16.7, 95%CI: 9.1 - ∞; χ2 = 4.98, p = 0.025). 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 = 0.17). 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 on a larger problem in scientific publishing.


This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.