Sepsis is the immune system’s overwhelming reaction to an infection. It is the cause of one in five deaths worldwide, which is more than the total combined number of deaths due to breast, bowel, and prostate cancer. However, according to GlobalData’s Trials Intelligence platform, there are 12 times fewer sepsis clinical trials than the mentioned cancers (Figure 1). This is not for a lack of translational research; for the last 30 years, thousands of genetically engineered animals’ lives’ have been saved in pre-clinical studies that demonstrated specific antibodies, and drugs neutralised molecular players and pathways involved in sepsis. However, this has not resulted in a new, effective drug that improved the rate of survival. In fact, the World Health Organization (WHO) projects that at current rates, sepsis will be the top cause of death worldwide by 2050.
Sepsis can be difficult to recognise due to the generic nature of many symptoms such as increased perspiration, difficulty breathing, and dizziness, which are all associated with a litany of ailments. When it is not managed promptly, it can progress to septic shock, tissue damage, organ failure, and often death. The mortality rate of patients with severe sepsis is over 30%. Unfortunately, only half of patients who survive will completely recover. Others will die within one year and for those that live beyond this, up to 50% will have considerable cognitive impairments, as well as possible physical and psychological disabilities. Understanding the disturbing consequences associated with sepsis makes the lack of therapies, or innovative studies, incomprehensible.
Sepsis clinical trials are undeniably challenging and complex. However, promising modifications extensively outlined in the literature have yet to be incorporated into modern trials. Despite the argument that adaptive clinical trial designs are more suitable for sepsis studies, as they allow emerging discoveries to be incorporated into participants treatments, GlobalData’s Trials Intelligence platform indicates that most trials continue to follow a traditional design.
Additionally, the disparity between successful pre-clinical studies compared to the immense failure of clinical trials, indicates inappropriate and irrelevant animal models are being used. Instead, many demonstrate that human cells and tissues would improve translational research, but the same mistakes continue to be made. An overhaul to the sepsis research paradigm is long overdue. Time will determine if efforts to improve data regarding sepsis will step up, and if so, be enough to prevent its current trajectory.