The Paul Martini research group Clinical Septomics forms a bridge between the research groups Fungal Septomics und Host Septomics, which carry out basic research, and clinical applications of this research.
Sepsis infections and the resulting direct and indirect treatment costs are on the increase. In spite of this, there is a lack of pathophysiologically well-founded plans for tackling this problem or evidence-based diagnostic and therapeutic measures. As a result, new approaches to treating severe sepsis have so far failed. The transition from a localised infection to a systemic infection is fluid and cannot be reliably determined using clinical parameters alone. However, the speed of the diagnosis and thus the time that elapses before treatment begins is the decisive factor affecting survival. It is often the case that many hours pass, both before hospitalisation and as the disease progresses in hospital, before a diagnosis is made and appropriate treatment begins in the intensive care unit. An earlier diagnosis with the help of sensitive and specific molecular biomarkers would make a substantial contribution towards reducing the high morbidity and mortality rates.
Despite important gains in scientific and technical knowledge in modern molecular medicine, we have not yet been able to establish an effective method for molecular sepsis diagnosis as part of routine hospital procedure. In other branches of medicine, biomarkers have long been used in pre-clinical research. This includes therapeutic trials to test the effectiveness of a drug in animal models or in phase I trials on humans. In phase II and phase III clinical trials, biomarkers are frequently used as surrogate endpoints instead of a ‘firm’ clinical endpoint. Clinical Septomics is pursuing the goal of developing new disease-related biomarkers such as risk indicators and predictive biomarkers. These would be used for primary sepsis diagnosis and the prognostic estimate of the course of a sepsis infection. Clinical Septomics also wants to identify what are called drug-related biomarkers. These indicate whether a specific drug will be effective in an individual patient or whether it will be ineffective or even potentially harmful. This involves distinguishing between responders and nonresponders, and between high-risk and low-risk patients. In the long term, the aim of Clinical Septomics is to be able to carry out clinical trials using biomarkers on small groups of patients. This would speed up the approval of new sepsis therapeutics.
One of the significant shortcomings of sepsis research to date is related to the clinical validation of potential biomarkers. The overwhelming majority of such trials fail to meet the internationally binding ‘Standards for Reporting of Diagnostic Accuracy (STARD) Group’. Only when better links are made between the results from basic research and clinical findings obtained from comprehensively characterised patient cohorts, can the validation of new sepsis biomarkers be achieved more quickly. Basic research frequently produces publications of findings relating to potential new biomarkers and therapeutic targets. In contrast, the substantial costs in financial, methodological, logistical and medico-legal terms of preparing and carrying out diagnostic validation trials in line with STARD are underestimated.
The Clinical Septomics research group has years of experience in carrying out such trials. As early as the mid-1990s, the head of the group had significant responsibility for validation trials that led to the worldwide application of the sepsis marker Procalcitonin.