The bigger, the better? When multicenter clinical trials and meta-analyses do not work

Courtesy of the development of the Internet, bursts of information technology, and globalization, huge multicenter studies along with meta-analyses have been introduced to the medical sciences society. Meta-analyses and multicenter studies revolutionized modern medicine and drug development, and empowered evidence based medicine by providing extremely high levels of evidence. Nevertheless, there are occasions that while results of local multi/single center studies showed efficacy of a new treatment, larger multicenter studies or meta-analyses failed to show efficacy, and vice versa. Generally, bigger studies are more powerful and we rely on their results in clinical decision making. Nevertheless, we should keep in mind that in certain circumstances, single center studies are of great importance, and are preferred to multicenter studies and meta-analyses. In order to have a better understanding of why and when multicenter studies along with meta-analyses might not be the best options, we have discussed three different scenarios.