In Europe, one in four road deaths occurred in an accident involving a goods vehicle in 2018 (ETSC 2020). Commercial drivers are at higher risk for suffering from physiological, psychological and prescribed medication and illicit drug use, including alcohol misuse. Fitness to drive or driver state monitoring systems integrate technologies able to detect altered driver states and provide them feedback. They constitute an emerging phenomenon, and their effects on changing people's behaviour to drive more safely, and in general, their impact on road safety should be better investigated.The scope of this paper is to present a methodology able to simulate different scenarios to understand how a driver state monitoring system can support improving road safety in the European Union. A conceptual framework is presented to support the definition of the impact assessment methodology and is applied to the PANACEA European research project. The project develops an integrated solution for driving ability assessment of commercial drivers, paired with a countermeasure and coaching solution. The PANACEA system uses algorithms and technologies for detecting, monitoring and assessing alcohol consumption, licit (barbituric) and illicit (methadone substitute) drugs, fatigue and cognitive load (Commercial Health Toolkits (CHTs)). It also provides strategic, tactical and operational countermeasures that will be tested and evaluated to assess their effectiveness and acceptance by the system's users.The methodology presented is able to assess both a single and multiple countermeasures among those developed within the project. Different scenarios have been considered by modifying the variables according to the screening prevalence, solution acceptance level, driving context and time. The methodology uses the results from the project pilot studies in terms of accuracy, sensitivity, and specificity of CHTs and countermeasures results in combination with evidence from the existing literature.