Sex as a prognostic factor in systematic reviews: challenges and lessons learned

Sex is a common baseline factor collected in studies that has the potential to be a prognostic factor (PF) in several clinical areas. In recent years, research on sex as a PF has increased; however, this influx of new studies frequently shows conflicting results across the same treatment or disease state. Thus, systematic reviews (SRs) addressing sex as a PF may help us to better understand diseases and further personalize healthcare. We wrote this article to offer insights into the challenges we encountered when conducting SRs on sex as a PF and suggestions on how to overcome these obstacles, regardless of the clinical domain. When carrying out a PF SR with sex as the index factor, it is important to keep in mind the modifications that must be made in various SR stages, such as modifying the PF section of CHARMS-PF, adjusting certain sections of QUIPS and extracting data on the sex and gender terms used throughout the studies. In this paper, we provide an overview of the lessons learned from carrying out our reviews on sex as a PF in different disciplines and now call on researchers, funding agencies and journals to realize the importance of studying sex as a PF.