Evidence-based medicine is the cornerstone of clinical practice, but it is dependent on the
quality of evidence upon which it is based. Unfortunately, up to half of all randomized con-
trolled trials (RCTs) have never been published, and trials with statistically significant findings
are more likely to be published than those without (Dwan et al., 2013). Importantly, negative
trials face additional hurdles beyond study publication bias that can result in the disappearance
of non-significant results (Boutron et al., 2010 ;Dwan et al ., 2013; Duyx et al., 2017). Here, we
analyze the cumulative impact of biases on apparent efficacy, and discuss possible remedies,
using the evidence base for two effective treatments for depression: antidepressants and
psychotherapy
