Rubor, calor, tumor, dolor: objective assessments of inflammation

Abstract

Well-informed decisions are needed in the earliest phase of dermatological drug development. Only 6.3% of the drugs targeting immunosuppressive and anti-inflammatory processes reaches market registration. Knowledge about the pharmacodynamic properties of a dermatological agent is essential to increase the probability of success from early-phase clinical trials to market registration in dermatology. Despite the increasing amount of early-stage drug trials incorporating pharmacodynamic endpoints, there seems to be a lack of understanding how to integrate pharmacodynamic outcomes into early-stage dermatological drug trials. There are success stories from investigations employing objective pharmacodynamic endpoints in both disease and challenge models, showing that integrating such endpoints during the initial clinical stages of drug development is feasible. This thesis investigates and advocates a more objective methodology, suggesting the integration of imaging techniques and precise biomarkers as pharmacodynamic endpoints in early-stage dermatology trials. However, this advocacy for pharmacodynamic endpoints in early-stage dermatology trials raised two main questions: how to evaluate pharmacodynamic endpoints in early-stage dermatology trials and which specific pharmacodynamic endpoints should be considered for evaluation.