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 controlled trials (RCTs) have never been published, and trials with statistically-significant findings are more likely to be published than those without (Dwan et al 201311ya). Importantly, negative trials face additional hurdles beyond study publication bias that can result in the disappearance of non-statistically-significant results (Boutron et al 201014ya;Dwan et al 201311ya;Duyxet al2017). 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.
Figure 1: The cumulative impact of reporting and citation biases on the evidence base for antidepressants. (a) displays the initial, complete cohort of trials, while (b) through (e) show the cumulative effect of biases. Each circle indicates a trial, while the color indicates the results or the presence of spin. Circles connected by a grey line indicate trials that were published together in a pooled publication. In (e), the size of the circle indicates the (relative) number of citations received by that category of studies.
