Visualizing the evolution of evidence: Cumulative network meta-analyses of new generation antidepressants in the last 40 years.

It is often challenging to present the available evidence in a timely and comprehensible manner. We aimed to visualize the evolution of evidence about antidepressants for depression by conducting cumulative network meta-analyses (NMAs) and to examine whether it could have helped the selection of optimal drugs. We built a Shiny web application that performs and presents cumulative NMAs based on R netmeta. We used a comprehensive dataset of double-blind randomized controlled trials of 21 antidepressants in the acute treatment of major depression. The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation), and treatment effects were summarized via odds ratios. We evaluated the confidence in evidence using the CINeMA (Confidence in Network Meta-Analysis) framework for a series of consecutive NMAs. Users can change several conditions for the analysis, such as the period of synthesis, among the others. We present the league tables and two-dimensional plots that combine efficacy, acceptability and level of confidence in the evidence together, for NMAs conducted in 1990, 1995, 2000, 2005, 2010, and 2016. They reveal that through the past four decades, newly approved drugs often showed initially exaggerated results, which tended to diminish and stabilize after approximately a decade. Over the years, the drugs with relative superiority changed dramatically; but as the evidence network grew larger and better connected, the overall confidence improved. The Shiny app visualizes how evidence evolved over years, emphasizing the need for a careful interpretation of relative effects between drugs, especially for the potentially amplified performance of newly approved drugs. HIGHLIGHTS: Network meta-analysis is considered to be a proper way of demonstrating the available evidence, since it allows comparisons between multiple interventions, and has been proved to be statistically powerful. It is challenging to present the voluminous results of NMA in an efficient and comprehendible manner. Evidence evolution based on the relatively new method NMA has not been investigated yet. The results of NMA should not only include the effects but also the confidence in the evidence, which can help interpret the findings appropriately. Effective use of rapidly developing statistical analysis and presentation tools such as Shiny package in R, may facilitate and simplify the visualization of NMA output. We should stay conservative towards new drugs, as their performance was often shown to be exaggerated initially, and it took time to become stable.